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Caregiver satisfaction with paediatric HIV treatment and care in Nigeria and equity implications for children living with HIV Caregiver satisfaction has the potential to promote equity for children living with HIV, by influencing health-seeking behaviour. We measured dimensions of caregiver satisfaction with paediatric HIV treatment in Nigeria, and discuss its implications for equity by conducting facility-based exit interviews for caregivers of children receiving antiretroviral therapy in 20 purposively selected facilities within 5 geopolitical zones. Descriptive analysis and factor analysis were performed. Due to the hierarchical nature of the data, multilevel regression modelling was performed to investigate relationships between satisfaction factors and socio-demographic variables. Of 1550 caregivers interviewed, 63% (95% CI: 60.6-65.4) reported being very satisfied overall; however, satisfaction varied in some dimensions: only 55.6% (53.1-58.1) of caregivers could talk privately with health workers, 56.9% (54.4-59.3) reported that queues to see health workers were too long, and 89.9% (88.4-91.4) said that some health workers did not treat patients living with HIV with sufficient respect. Based on factor analysis, two underlying factors, labelled Availability and Attitude, were identified. In multilevel regression, the satisfaction with availability of services correlated with formal employment status (p < .01), whereas caregivers receiving care in private facilities were less likely satisfied with both availability (p < .01) and attitude of health workers (p < .05). State and facility levels influenced attitudes of the health workers (p < .01), but not availability of services. We conclude that high levels of overall satisfaction among caregivers masked dissatisfaction with some aspects of services. The two underlying satisfaction factors are part of access typology critical for closing equity gaps in access to HIV treatment between adults and children, and across socio-economic groups.
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Energy Expenditure and Intensity of Classroom Physical Activity in Elementary School Children There is limited data regarding objectively measured energy cost and intensity of classroom instruction. Therefore, the purpose of current study was to objectively measure energy cost and subsequently calculate MET values using a portable indirect calorimeter (IC) for both normal classroom instruction (NCI) and active classroom instruction (ACI). We assessed energy expenditure (EE) and intensity levels (METs) in elementary school children (17 boys and 15 girls) using an IC (COSMED K4b2). Independent t-tests were used to evaluate potential sex and grade level differences for age, BMI, VO2, EE, and METs. The average EE for NCI and ACI were 1.8 ± 0.4 and 3.9 ± 1.0, respectively. The average intensity level for NCI and ACI were 1.9 ± 0.4 and 4.2 ± 0.9 METs, respectively. PA delivered through ACI can elicit EE at a moderate intensity level. These results provide evidence for ACI as a convenient/feasible avenue for increasing PA in youth without decreasing instruction time.
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Liver - specific mono-unsaturated fatty acid synthase-1 inhibitor for anti-hepatitis C treatment Recently, direct antiviral agents against hepatitis C virus (HCV) infection have been developed as highly effective anti-HCV drugs. However, the appearance of resistant viruses against direct anti-viral agents is an unsolved problem. One of the strategies considered to suppress the emergence of the drug-resistant viruses is to use drugs inhibiting the host factor, which contributes to HCV proliferation, in combination with direct anti-viral agents. The replication complex was reported to be present in the membranous compartment in the cells. Thus, lipid metabolism modulators are good candidates to regulate virus assembly and HCV replication. Recent studies have shown that stearoyl-CoA desaturase (SCD), an enzyme for long-chain mono-unsaturated fatty acid (LCMUFA) synthesis, is a key factor that defines HCV replication efficiency. Systemic exposure to SCD-1 inhibor induces some side effects in the eyes and skin. Thus, systemic SCD-1 inhibitors are considered inappropriate for HCV therapy. To avoid the side effects of systemic SCD-1 inhibitors, the liver - specific SCD-1 inhibitor, MK8245, was synthesized; it showed antidiabetic effects in diabetic model mice with no side effects. In the phase 1 clinical study on measurement of MK8245 tolerability, no significant side effects were reported (ClinicalTrials.gov Identifier: NCT00790556). Therefore, we thought liver - specific SCD-1 inhibitors would be suitable agents for HCV - infected patients. MK8245 was evaluated using recombinant HCV culture systems. Considering current HCV treatments, to avoid the emergence of direct anti-viral agents - resistant viruses, combination therapy with direct anti-viral agents and host - targeted agents would be optimal. With this viewpoint, we confirmed MK8245 's additive or synergistic anti-HCV effects on current direct anti-viral agents and interferon-alpha therapy. The results suggest that MK8245 is an option for anti-HCV multi-drug therapy with a low risk of emergence of drug-resistant HCV without significant side effects.
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Relation of Left Ventricular Mass and Infarct Size in Anterior Wall ST-Segment Elevation Acute Myocardial Infarction (from the EMBRACE STEMI Clinical Trial) Biomarker measures of infarct size and myocardial salvage index (MSI) are important surrogate measures of clinical outcomes after a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post hoc analysis of Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE) ST-Segment Elevation Myocardial Infarction (STEMI) trial evaluates the association between left ventricular (LV) mass and infarct size as assessed by areas under the curve for creatine kinase-MB (CK-MB) and troponin I release over the first 72 hours (CK-MB area under the curve [AUC] and troponin I [TnI] AUC) and the MSI. Patients with first anterior STEMI, occluded left anterior descending artery, and available LV mass measurement in EMBRACE STEMI trial were included (n = 100) (ClinicalTrials.govNCT01572909). MSI, end-diastolic LV mass on day 4 cardiac magnetic resonance, and CK-MB and troponin I concentrations were evaluated by a core laboratory. After saturated multivariate analysis, dominance analysis was performed to estimate the contribution of each independent variable to the predicted variance of each outcome. In multivariate models that included age, gender, body surface area, lesion location, smoking, and ischemia time, LV mass remained independently associated with biomarker measures of infarct size (CK-MB AUC p = 0.02, TnI AUC p = 0.03) and MSI (p = 0.003). Dominance analysis demonstrated that LV mass accounted for 58%, 47%, and 60% of the predicted variances for CK-MB AUC, TnI AUC, and MSI, respectively. In conclusion, LV mass accounts for approximately half of the predicted variance in biomarker measures of infarct size. It should be considered as an adjustment variable in studies evaluating infarct size.
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Parkinson subtype -specific Granger-causal coupling and coherence frequency in the subthalamic area Previous work on Parkinson's disease (PD) has indicated a predominantly afferent coupling between affected arm muscle activity and electrophysiological activity within the subthalamic nucleus (STN). So far, no information is available indicating which frequency components drive the afferent information flow in PD patients. Non-directional coupling e.g. by measuring coherence is primarily established in the beta band as well as at tremor frequency. Based on previous evidence it is likely that different subtypes of the disease are associated with different connectivity patterns. Therefore, we determined coherence and causality between local field potentials (LFPs) in the STN and surface electromyograms (EMGs) from the contralateral arm in 18 akinetic-rigid (AR) PD patients and 8 tremor-dominant (TD) PD patients. During the intraoperative recording, patients were asked to lift their forearm contralateral to the recording side. Significantly more afferent connections were detected for the TD patients for tremor -periods and non- tremor -periods combined as well as for only tremor periods. Within the STN 74% and 63% of the afferent connections are associated with coherence from 4-8Hz and 8-12Hz, respectively. However, when considering only tremor -periods significantly more afferent than efferent connections were associated with coherence from 12 to 20Hz across all recording heights. No difference between efferent and afferent connections is seen in the frequency range from 4 to 12Hz for all recording heights. For the AR patients, no significant difference in afferent and efferent connections within the STN was found for the different frequency bands. Still, for the AR patients dorsal of the STN significantly more afferent than efferent connections were associated with coherence in the frequency range from 12 to 16Hz. These results provide further evidence for the differential pathological oscillations and pathways present in AR and TD Parkinson patients.
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Incidence and growth of Salmonella enterica on the peel and pulp of avocado (Persea americana) and custard apple (Annona squamosa) The aim of this study was to assess the incidence and to estimate the growth kinetic parameters (maximum growth rate, μ; lag time, λ; and maximum population, κ) of Salmonella on the peel and pulp of avocado (Perseaamericana var. americana) and custard apple (Annona squamosa L.) as affected by temperature (10-30°C). The incidence of Salmonella was assessed on the peel and pulp of the fruits (n=200 of each fruit), separately, totalizing 800 analyses. Only three samples of custard apple pulp were positive for Salmonella enterica and the three isolates recovered belonged to serotype S. Typhimurium. Salmonella was not recovered from avocado and custard apple peel s and from avocado pulp. Generally, the substrate (pulp or peel) of growth did not affect μ values of S. enterica (p>0.05). Very similar μ values were found for S. enterica inoculated in custard apple and avocado. S. enterica presented the highest λ in the peel of the fruits. The growth of S. enterica resulted in larger λ in custard apple in comparison to avocado. For example, the λ of S. enterica in the pulp of custard apple and avocado were 47.0±0.78h and 10.0±3.78h, respectively. The lowest values of κ were obtained at the lower storage temperature conditions (10°C). For instance, κ values of 3.7±0.06log CFU/g and 2.9±0.03log CFU/g were obtained from the growth of S. enterica in avocado and custard apple pulps at 10°C (p<0.05), respectively. On the other hand, at 30°C, κ values were 6.5±0.25log CFU/g and 6.5±0.05log CFU/g, respectively. Significantly higher κ were obtained from the growth of S. enterica in the pulp than in the peel of the fruits (p<0.05). For instance, the growth of S. enterica in the pulp of avocado led to a κ value of 6.5±0.25log CFU/g, while in the peel led to a κ value of 4.6±0.23log CFU/g (p<0.05). In general, growth kinetic parameters indicated that avocado comprises a better substrate than custard apple for the growth of S. enterica. The square root model fitted to the data obtained in this study and to the growth data available in the literature for other tropical low acid fruits indicated high variability in μ and λ of Salmonella. The results obtained in this study show that whole low acid tropical fruits can harbor Salmonella, and that this foodborne pathogen can not only survive but also grow both on the peel and pulp of low acid tropical fruits, such as avocado and custard apple.
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Photocatalytic and antibacterial response of biosynthesized gold nanoparticles Increase in the bacterial resistance to available antibiotics and water contamination by different toxic organic dyes are both severe problems throughout the world. To overcome these concerns, new methodologies including synthesis of nontoxic, human friendly and efficient nanoparticles is required. These nanoparticles not even inhibit the growth of microorganisms but are also effective in the degradation of toxic organics in waste water thus providing a clean and human friendly environment. The use of plants extracts to synthesize and stabilize noble metal nanoparticles have been considered as safe, cost-effective, eco-benign and green approach nowadays. In the present study, Longan fruit juice proficiently reduced ionic gold (Au(+3)) to gold nanoparticles (AuNPs) as well as mediated the stabilization of AuNPs. The antibacterial activity of AuNPs was carried out against both gram positive and gram negative bacteria using agar well diffusion method, followed by the determination of Minimum inhibitory concentration (MIC) values. AuNPs were found to have significant antibacterial activity against Escherichia coli with MIC values of 75μg/ml while outstanding MIC values of 50μg/ml against Staphylococcus areous and Basilus subtilus. AuNPs revealed significant photocatalytic degradation (76%) of methylene blue in time period of 55 min, indicating the effective photocatalytic property of biosynthesized AuNPs (K=0.29/min, r(2)=0.95). The considerable antibacterial and photocatalytic activities of the photosynthesized AuNPs can be attributed towards their small size, spherical morphology and uniform dispersion. Our finding suggests the possible therapeutic potential of biogenic AuNPs in the development of new antibacterial agents as well as in the development of effective photocatalysts.
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Ictal unilateral blinking is an unreliable lateralizing sign in tuberous sclerosis complex Ictal unilateral blinking is an uncommon but reportedly reliable lateralizing sign, indicating an ipsilateral seizure focus. We aimed to determine its lateralizing utility in patients with tuberous sclerosis complex (TSC). We reviewed the video-EEGs of 92 children with TSC and drug-resistant epilepsy. Eleven (12%) had seizures with unilateral blinking, of which 10 underwent epilepsy surgery. Lateralization of seizures was inferred from other semiology, ictal scalp EEG and outcome following tuberectomy. Seizures manifesting with unilateral blinking were focal motor in four patients, focal motor evolving into epileptic spasms in six, and epileptic spasms with focal features in one. Associated unilateral facial contraction was seen in five patients and arm jerking in four. Lateralized scalp ictal rhythms were seen in seven patients. Following tuberectomies, seven patients are seizure free and two had >90% reduction. Overall lateralization of seizures with unilateral blinking was contralateral in six patients and ipsilateral in four. When unilateral blinking was early in seizures, overall lateralization was more often contralateral (6/7 patients, PPV 85%). Ictal unilateral blinking is not infrequent but unreliable in lateralizing seizures in TSC. Unrecognized seizure propagation to contralateral symptomatogenic regions and potentially different mechanisms may account for the variable lateralization.
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A remarkable new species of Eutrichopoda Townsend, 1908 (Diptera: Tachinidae: Phasiinae) A new Tachinidae species, Eutrichopoda flavipenna sp. nov. (Diptera: Tachinidae: Phasiinae), from Brazil and Paraguay is described and illustrated by photographs and line drawings. The remarkable yellow, feather-like setae on the hind tibia distinguishes the new species from all other species in the tribe Trichopodini.
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Lateral hypothalamus orexinergic system modulates the stress effect on pentylenetetrazol induced seizures through corticotropin releasing hormone receptor type 1 Stress is a trigger factor for seizure initiation which activates hypothalamic pituitary adrenal (HPA) axis as well other brain areas. In this respect, corticotropin releasing hormone (CRH) and lateral hypothalamus (LH) orexinergic system are involved in seizure occurrence. In this study, we investigated the role of LH area and orexin expression in (mediation of) stress effect on pentylenetetrazol (PTZ) - induced seizures with hippocampal involvement. Two mild foot shock stresses were applied to intact and adrenalectomized animals; with or without CRHr1 blocking (NBI 27914) in the LH area. Then, changes in orexin production were evaluated by RT-PCR. Intravenous PTZ infusion (25 mg/ml) - induced convulsions were scored upon modified Racine scale. Finally, hippocampal glutamate and GABA were evaluated to study excitability changes. We demonstrated that the duration and severity of convulsions in stress - induced as well as adrenalectomized group were increased. Plasma corticosterone (CRT) level and orexin mRNA expression were built up in the stress and/or seizure groups. Furthermore, glutamate and GABA content was increased and decreased respectively due to stress and seizures. In contrast, rats receiving CRHr1 inhibitor showed reduced severity and duration of seizures, increased GABA, decreased glutamate and corticosterone and also orexin mRNA compared to the inhibitor free rats. Stress and adrenalectomy induced augmenting effect on seizure severity and duration and the subsequent reduction due to CRHr1 blocking with parallel orexin mRNA changes, indicated the likely involvement of CRH1r induced orexin expression of the LH in gating stress effect on convulsions.
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A parametric ribcage geometry model accounting for variations among the adult population The objective of this study is to develop a parametric ribcage model that can account for morphological variations among the adult population. Ribcage geometries, including 12 pair of ribs, sternum, and thoracic spine, were collected from CT scans of 101 adult subjects through image segmentation, landmark identification (1016 for each subject), symmetry adjustment, and template mesh mapping (26,180 elements for each subject). Generalized procrustes analysis (GPA), principal component analysis (PCA), and regression analysis were used to develop a parametric ribcage model, which can predict nodal locations of the template mesh according to age, sex, height, and body mass index (BMI). Two regression models, a quadratic model for estimating the ribcage size and a linear model for estimating the ribcage shape, were developed. The results showed that the ribcage size was dominated by the height (p=0.000) and age - sex - interaction (p=0.007) and the ribcage shape was significantly affected by the age (p=0.0005), sex (p=0.0002), height (p=0.0064) and BMI (p=0.0000). Along with proper assignment of cortical bone thickness, material properties and failure properties, this parametric ribcage model can directly serve as the mesh of finite element ribcage models for quantifying effects of human characteristics on thoracic injury risks.
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Hyaluronan Depolymerization by Megakaryocyte Hyaluronidase-2 Is Required for Thrombopoiesis Hyaluronan is the predominant glycosaminoglycan component of the extracellular matrix with an emerging role in hematopoiesis. Modulation of hyaluronan polymer size is responsible for its control over cellular functions, and the balance of hyaluronan synthesis and degradation determines its molecular size. Although two active somatic hyaluronidases are expressed in mammals, only deficiency in hyaluronidase-2 (Hyal-2) results in thrombocytopenia of unknown mechanism. Our results reveal that Hyal-2 knockout mice accumulate hyaluronan within their bone marrow and within megakaryocytes, the cells responsible for platelet generation. Proplatelet formation by Hyal-2 knockout megakaryocytes was disrupted because of abnormal formation of the demarcation membrane system, which was dilated and poorly developed. Importantly, peptide-mediated delivery of exogenous hyaluronidase rescued deficient proplatelet formation in murine and human megakaryocytes lacking Hyal-2. Together, our data uncover a previously unsuspected mechanism of how hyaluronan and Hyal-2 control platelet generation.
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Vitamin D serum level is associated with Child-Pugh score and metabolic enzyme imbalances, but not viral load in chronic hepatitis B patients Vitamin D deficiency is common in patients with chronic liver diseases. However, vitamin D status in persons with chronic hepatitis B virus (HBV) infection is not consistently reported. Specifically, the impact of liver dysfunction on vitamin D status has not been well addressed.We recruited a group of patients (n = 345) with chronic hepatitis B (n = 115), hepatitis B related cirrhosis (n = 115), and age - and gender -matched healthy controls (n = 115). Serum 25-hydroxyvitamin D3 [25(OH)D3], its related metabolic enzymes, intact parathyroid hormone were measured. Calcium, magnesium, and phosphorus were obtained from medical record. Serum 25(OH)D3 levels in chronic hepatitis B patients (7.83 ± 3.47 ng/mL) were significantly lower than that in healthy controls (9.76 ± 4.36 ng/mL, P < 0.001), but significantly higher than that in hepatitis B-related cirrhotic patients (5.21 ± 3.67 ng/mL, P < 0.001). Furthermore, 25(OH)D3 decreased stepwise with higher Child-Pugh classification. However, there were no significant differences in 25(OH)D3 levels between (1) hepatitis B e antigen (HBeAg +) and HBeAg(-) persons, or (2) among persons with different HBV viral load, or (3) between treatment naïve and patients on antiviral therapy. Multiple logistic regression analyses confirmed that higher Child-Pugh score was independently associated with 25(OH)D3 deficiency (<10 ng/mL) with an odds ratio of 1.20 (confidence interval 1.03-1.39, P = 0.016). Levels of cytochrome P450 (CYP) 27A1 were significantly decreased, whereas levels of CYP24A1 were significantly elevated in cirrhotic patients .These results suggest that decreasing vitamin D levels are likely to be a result, rather than a cause, of liver dysfunction and irrespective of HBV viral load. Reduction in 25(OH)D3 levels is possibly due to downregulation of the synthetic hydroxylase CYP27A1 and concurrent upregulation of degrading CYP24A1 in patients with liver cirrhosis.
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359 Delayed Treatment of Ruptured Arteriovenous Malformations: Is It Ok to Wait? Emergent surgery on a ruptured brain arteriovenous malformation (AVM) is indicated for a large hematoma in an acutely deteriorating patient. The majority of ruptured AVMs, however, present in clinically stable patients with neurological deficits. Controversy exists with respect to the timing of treatment for ruptured AVMs in these stable patients. This study aims to determine the safety of delaying AVM treatment in clinically stable patients by investigating the rate of rehemorrhage in a cohort of patients with ruptured brain AVMs. Patients presenting to our institution from January 2000 to December 2015 with ruptured brain AVMs treated at least 4 weeks posthemorrhage were included in the analysis. Exclusion criteria were ruptured AVMs that required emergent surgery involving AVM resection, previous treatment at another institution, or subacute AVM treatment. The primary outcome measure was time from initial hemorrhage to rehemorrhage. Patient follow-up data were included up until the point of AVM treatment. Of the 103 ruptured AVMs (49 M:54 F) meeting inclusion criteria, the median time from rupture to treatment or rehemorrhage was 112 days (interquartile range [IQR]: 110). Six (5.8%) patients rehemorrhaged in a median of 248 days (IQR: 1331). Two of these patients rehemorrhaged on the same day of their index hemorrhage. The total at-risk period was 19 445 patient - days, yielding a rehemorrhage risk of 11.3% per patient - year, or 0.93% per patient - month. Our data support stabilizing a patient after the initial AVM rupture. It is safe to closely monitor the patient, initiate the rehabilitation process, and then, in a semielective manner, bring the patient back for treatment. Delaying intervention for 4 weeks after initial hemorrhage subjects the patient to a low (<1%) risk of rehemorrhage.
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Prescribing Patterns in Outpatient Clinics of Township Hospitals in China: A Comparative Study before and after the 2009 Health System Reform Objective: China introduced a series of health reforms in 2009, including a national essential medicines policy and a medical insurance system for primary care institutions. This study aimed to determine the changing prescribing patterns associated with those reforms in township hospitals. Methods: A multi-stage stratified random cluster sampling method was adopted to identify 29 township hospitals from six counties in three provinces. A total of 2899 prescriptions were collected from the participating township hospitals using a systematic random sampling strategy. Seven prescribing indicators were calculated and compared between 2008 and 2013, assessing use of medicines (antibiotics and adrenal corticosteroids) and polypharmacy, administration route of medicines (injections), and affordability of medicines. Results: Significant changes in prescribing patterns were found. The average number of medicines and costs per- prescription dropped by about 50%. The percentage of prescriptions requiring antibiotics declined from 54% to 38%. The percentage of prescriptions requiring adrenal corticosteroid declined from 14% to 4%. The percentage of prescriptions requiring injections declined from 54% to 25%. Despite similar changing patterns, significant regional differences were observed. Conclusions: Significant changes in prescribing patterns are evident in township hospitals in China. Overprescription of antibiotics, injections and adrenal corticosteroids has been reduced. However, salient regional disparities still exist. Further studies are needed to determine potential shifts in the risk of the inappropriate use of medicines from primary care settings to metropolitan hospitals.
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Neural activity promotes long-distance, target - specific regeneration of adult retinal axons Axons in the mammalian CNS fail to regenerate after injury. Here we show that if the activity of mouse retinal ganglion cells (RGCs) is increased by visual stimulation or using chemogenetics, their axons regenerate. We also show that if enhancement of neural activity is combined with elevation of the cell-growth -promoting pathway involving mammalian target of rapamycin (mTOR), RGC axons regenerate long distances and re-innervate the brain. Analysis of genetically labeled RGCs revealed that this regrowth can be target specific: RGC axons navigated back to their correct visual targets and avoided targets incorrect for their function. Moreover, these regenerated connections were successful in partially rescuing a subset of visual behaviors. Our findings indicate that combining neural activity with activation of mTOR can serve as powerful tool for enhancing axon regeneration, and they highlight the remarkable capacity of CNS neurons to re-establish accurate circuit connections in adulthood.
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Expression of WNT10A Gene in Oral Squamous Cell Carcinoma Oral squamous cell carcinoma (OSCC) constitutes the most frequent malignant tumour of the oral cavity. Considering the significant roles the Wnt family plays in physiological and pathological events, this study aims to investigate WNT10A gene expression in OSCC. The cohort was composed of 59 specimens: 49 with OSCC and 10 controls. Total RNA from the samples was extracted, cDNA was synthesized and Real-time PCR analyses were performed, with β-ACTIN as internal control. The number of OSCC samples for the 4 TNM stages was: 5 (10.2%) stage I, 10 (20.4%) stage II, 9 (18.3%) stage III, and 25 (51.1%) stage IV. For Real-Time PCR analysis, significant difference was found between control samples and OSCC stage IV (p < 0.01). Higher levels of WNT10A expression was observed in OSCC stage IV suggesting a potential role in tumour progression.
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Predicting Risk of Suicide Attempt Using History of Physical Illnesses From Electronic Medical Records Although physical illnesses, routinely documented in electronic medical records (EMR), have been found to be a contributing factor to suicides, no automated systems use this information to predict suicide risk. The aim of this study is to quantify the impact of physical illnesses on suicide risk, and develop a predictive model that captures this relationship using EMR data. We used history of physical illnesses (except chapter V: Mental and behavioral disorders) from EMR data over different time-periods to build a lookup table that contains the probability of suicide risk for each chapter of the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes. The lookup table was then used to predict the probability of suicide risk for any new assessment. Based on the different lengths of history of physical illnesses, we developed six different models to predict suicide risk. We tested the performance of developed models to predict 90-day risk using historical data over differing time-periods ranging from 3 to 48 months. A total of 16,858 assessments from 7399 mental health patients with at least one risk assessment was used for the validation of the developed model. The performance was measured using area under the receiver operating characteristic curve (AUC). The best predictive results were derived (AUC =0.71) using combined data across all time-periods, which significantly outperformed the clinical baseline derived from routine risk assessment (AUC =0.56). The proposed approach thus shows potential to be incorporated in the broader risk assessment processes used by clinicians. This study provides a novel approach to exploit the history of physical illnesses extracted from EMR (ICD-10 codes without chapter V-mental and behavioral disorders) to predict suicide risk, and this model outperforms existing clinical assessments of suicide risk.
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A Retrospective Review of Forensic Odontology Reports Written by the Joint POW/MIA Accounting Command Central Identification Laboratory for Remains Identified from the Korean War As of August 2014, the Joint POW/MIA Accounting Command has identified the remains of 1980 previously unknown U.S. service members; 280 were from the Korean War. To determine the accuracy and completeness of the available antemortem (AM) dental records, a review of the AM / postmortem (AM / PM) dental record comparisons from 233 Forensic Odontology Reports written in support of remains identified from the Korean War was performed. Seventy-two AM / PM comparisons resulted in exact dental chartings while 161 contained discrepancies which were explainable. Explainable discrepancies include undocumented treatment (103), incorrectly charted third molars as missing (82), differing opinions of specific molars present / missing (20), and erroneous treatment documentation and/or misidentification of teeth present / missing (22, other than molars). Reassessment has revealed varying levels of completeness for our available AM dental records, the need to thoroughly review our computerized comparisons, adjust our comparisons to include molar pattern variations / third molars, and updating our database comparison program.
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Predicting Sources of Dissolved Organic Nitrogen to an Estuary from an Agro - Urban Coastal Watershed Dissolved organic nitrogen (DON) is the nitrogen (N) -containing component of dissolved organic matter (DOM) and in aquatic ecosystems is part of the biologically-reactive nitrogen pool that can degrade water quality in N - sensitive waters. Unlike inorganic N (nitrate and ammonium) DON is comprised of many different molecules of variable reactivity. Few methods exist to track the sources of DON in watersheds. In this study, DOM excitation-emission matrix (EEM) fluorescence of eight discrete DON sources was measured and modeled with parallel factor analysis (PARAFAC) and the resulting model (" FluorMod ") was fit to 516 EEMs measured in surface waters from the main stem of the Neuse River and its tributaries, located in eastern North Carolina. PARAFAC components were positively correlated to DON concentration and principle components analysis (PCA) was used to confirm separation of the eight sources. Model validation was achieved by measurement of source samples not included in the model development with an error of <10%. Application of FluorMod to surface waters of streams within the Neuse River Basin showed while >70% of DON was attributed to natural sources, non-point sources, such as soil and poultry litter leachates and street runoff, accounted for the remaining 30%. This result was consistent with changes in land use from urbanized Raleigh metropolitan area to the largely agricultural Southeastern coastal plain. Overall, the predicted fraction of non-point DON sources was consistent with previous reports of increased organic N inputs in this river basin, which are suspected of impacting the water quality of its estuary.
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Effect of nivolumab on health-related quality of life in patients with treatment-naïve advanced melanoma: results from the phase III CheckMate 066 study Nivolumab has shown significant survival benefit and a favorable safety profile compared with dacarbazine chemotherapy among treatment-naïve patients with metastatic melanoma in the CheckMate 066 phase III study. Results from the health-related quality of life (HRQoL) analyses from CheckMate 066 are presented. HRQoL was evaluated at baseline and every 6 weeks while on treatment using the European Organisation for Research and Treatment of Care (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire (EQ-5D). Via a multi-step statistical plan, data were analyzed descriptively, cross-sectionally, and longitudinally, adjusting for baseline covariates, in patients having baseline plus ≥1 post-baseline assessment. Baseline-adjusted completion rates for all HRQoL questionnaires across treatment arms were 65% and 70% for dacarbazine and nivolumab, respectively, and remained similar throughout treatment. The mean baseline HRQoL scores were similar for patients treated with nivolumab and dacarbazine. Baseline HRQoL levels with nivolumab were maintained over time. This exploratory analysis showed a between-arm difference in favor of nivolumab on the EQ-5D utility index and clinically meaningful EQ-5D improvements from baseline at several time points for patients receiving nivolumab. Patients treated with nivolumab did not show increased symptom burden as assessed by the EORTC QLQ-C30. No HRQoL change was noted with dacarbazine patients up to week 43, although the high attrition rate after week 13 did not allow any meaningful analyses. Patients receiving nivolumab deteriorated significantly later than those receiving dacarbazine on several EORTC QLQ-C30 scales and the EQ-5D utility index. In addition to prolonged survival, these exploratory HRQoL results show that nivolumab maintains baseline HRQoL levels to provide long-term quality of survival benefit, compared with dacarbazine in patients with advanced melanoma.
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Risk stratification of prostate cancer utilizing apparent diffusion coefficient value and lesion volume on multiparametric MRI To evaluate the performance of apparent diffusion coefficient (ADC) and lesion volume in potentially risk - stratifying patients with prostate cancer (PCa). Men with elevated prostate-specific antigen or abnormal digital rectal exam underwent a 3T multiparametric magnetic resonance imaging (mpMRI) with endorectal coil. ADC maps were calculated using b values of 0, 500, 1000, and 1500; additional images were obtained with b value of 2000. We prospectively enrolled 312 men with lesions suspicious for cancer (suspicion score 2-5) on mpMRI. MRI/ultrasound fusion-guided prostate biopsies were performed. Mean ADC of suspicious lesions were correlated against lesion volume, Gleason and D'Amico risk. The cancer detection rate of fusion biopsy per lesion was 45.6% (206/452). Cancerous lesions were larger (median volume: 0.40 vs. 0.30 cm(3); P = 0.016). The median ADC (×10(-6) mm(2) /sec) for lesions negative and positive for PCa were 984.5 and 666.5, respectively (P < 0.0001). The AUC of ADC in predicting PCa was 0.79. Larger lesions were associated with higher risk PCa (Gleason and D'Amico) and lower ADC (all P < 0.0001). The mean ADC of suspicious lesions on mpMRI was inversely correlated, while lesion volume had a direct correlation with PCa detection. Future follow-up studies are needed to assess longitudinal cancer risks of suspicious mpMRI lesions. 2 J. Magn. Reson. Imaging 2017;45:610-616.
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Vestibular ablation and a semicircular canal prosthesis affect postural stability during head turns In our study, we examined postural stability during head turns for two rhesus monkeys: one animal study contrasted normal and mild bilateral vestibular ablation and a second animal study contrasted severe bilateral vestibular ablation with and without prosthetic stimulation. The monkeys freely stood, unrestrained on a balance platform and made voluntary head turns between visual targets. To quantify each animals ' posture, motions of the head and trunk, as well as torque about the body's center of mass, were measured. In the mildly ablated animal, we observed less foretrunk sway in comparison with the normal state. When the canal prosthesis provided electric stimulation to the severely ablated animal, it showed a decrease in trunk sway during head turns. Because the rhesus monkey with severe bilateral vestibular loss exhibited a decrease in trunk sway when receiving vestibular prosthetic stimulation, we propose that the prosthetic electrical stimulation partially restored head velocity information. Our results provide an indication that a semicircular canal prosthesis may be an effective way to improve postural stability in patients with severe peripheral vestibular dysfunction.
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Expression of metalloproteinases (MMP-2 and MMP-9) in basal-cell carcinoma The aim of this study was to compare the expressions of mRNA for metalloproteinases (MMP-2 and MMP-9) and type IV collagen in two different histological types of basal-cell carcinoma (BCCs; nodular and infiltrative) and in normal tissues from the tumor interface. The study included biopsy specimens of the skin involved with BCC and normal skin adjacent the lesion. The expressions of mRNA for MMP-2, MMP-9 and type IV collagen were determined by means of RT-PCR (Reverse transcription polymerase chain reaction). The level of type IV collagen mRNA in nodular and infiltrative BCCs turned out to be significantly lower, and the expressions of MMP-2 and MMP-9 mRNA significantly higher than in normal tissues adjacent to these tumors. The expression of mRNA for MMP-9 but not for MMP-2 was significantly higher in infiltrative BCCs than in the nodular BCCs. In turn, normal tissues adjacent to nodular BCCs showed significantly higher levels of mRNA for MMP-2 and significantly lower levels of type IV collagen mRNA than the normal tissues from the interface of infiltrative BCCs. The findings suggest that MMP-2 and MMP-9 could be used as prognostic factors of BCCs.
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Effects of Covering Surgical Wounds with Polyglycolic Acid Sheets for Posttonsillectomy Pain Postoperative pain is a remaining issue in tonsillectomy. Polyglycolic acid (PGA) is a biocompatible material used for absorbent suture reinforcement, and its sheet has been applied for covering defects after resection of oral carcinoma. The aim of this study is to examine whether the attachment of a PGA sheet to surgical wounds would reduce posttonsillectomy pain. In this prospective single-blind study, 17 consecutive adult patients were recruited who needed to undergo tonsillectomy, mainly due to habitual tonsillitis. Following bilateral tonsillectomies, a PGA sheet was attached with fibrin glue to only 1 side, without notification to patients of which side. Postoperative pain of each side was separately evaluated with a visual analog scale at 4 time points: before each meal and before sleep. Postoperative pain of both the PGA sheet -attached and nonattached sides was most severe before breakfast among 4 time points. Postoperative pain measured before breakfast was significantly more severe in the PGA sheet -attached side than the nonattached side. As such, this study provided solid data on the negative effects of PGA sheeting on posttonsillectomy pain.
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Slow-Growing Large Irritation Fibroma of the Anterior Hard Palate: A Case Report Using Immunohistochemical Analysis Irritation fibromas are recognized as fibrous lesions, usually reactive hyperplasias; however, the mechanism of enlargement is unclear. This paper reports on an abnormally large irritation fibroma of extremely gradual growth. The immunohistochemical features (CD34, α-SMA, vimentin, Ki-67, and TGF-α) of this irritation fibroma are presented to distinguish reactive hyperplasia from other true fibrous neoplasm diseases. In the only previous study, it was reported that the expression of TGF-α might be associated with the development of oral fibromas. Therefore, we investigated the relationship between this exceptionally-large fibrous lesion of extremely slow growth and the immunohistochemical reactivity of TGF-α, finding that, in contrast to the previous study, TGF-α was not expressed. This is the first study to evaluate the enlargement mechanism of such a large irritation fibroma using the approach of immunohistochemical analysis, and it indicates that such analysis can help elucidate the diverse causes and enlargement mechanisms of irritation fibromas.
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Mass-spectrometry analysis of histone post-translational modifications in pathology tissue using the PAT-H-MS approach Aberrant histone post-translational modifications (hPTMs) have been implicated with various pathologies, including cancer, and may represent useful epigenetic biomarkers. The data described here provide a mass spectrometry -based quantitative analysis of hPTMs from formalin-fixed paraffin-embedded (FFPE) tissues, from which histones were extracted through the recently developed PAT-H-MS method. First, we analyzed FFPE samples from mouse spleen and liver or human breast cancer up to six years old, together with their corresponding fresh frozen tissue. We then combined the PAT-H-MS approach with a histone -focused version of the super-SILAC strategy -using a mix of histones from four breast cancer cell lines as a spike-in standard - to accurately quantify hPTMs from breast cancer specimens belonging to different subtypes. The data, which are associated with a recent publication (Pathology tissue - quantitative mass spectrometry analysis to profile histone post-translational modification patterns in patient samples (Noberini, 2015) [1]), are deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD002669.
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Pregnancy suppresses the daily rhythmicity of core body temperature and adipose metabolic gene expression in the mouse Maternal adaptations in lipid metabolism are crucial for pregnancy success due to the role of white adipose tissue as an energy store and the dynamic nature of energy needs across gestation. Because lipid metabolism is regulated by the rhythmic expression of clock genes, it was hypothesised that maternal metabolic adaptations involve changes in both adipose clock gene expression and the rhythmic expression of downstream metabolic genes. Maternal core body temperature (Tc) was investigated as a possible mechanism driving pregnancy -induced changes in clock gene expression. Gonadal adipose tissue and plasma were collected from C57Bl/6J mice before and on days 6, 10, 14 and 18 of pregnancy (term = d19) at 4 hourly intervals across a 24-h period. Adipose expression of clock genes and downstream metabolic genes were determined by RT-qPCR and Tc was measured by intraperitoneal temperature loggers. Adipose clock gene expression showed robust rhythmicity throughout pregnancy, but absolute levels varied substantially across gestation. Rhythmic expression of the metabolic genes Lipe, Pnpla2 and Lpl was clearly evident before pregnancy; however, this rhythmicity was lost with the onset of pregnancy. Tc rhythm was significantly altered by pregnancy with a 65% decrease in amplitude by term and a 0.61°C decrease in mesor between days 6 and 18. These changes in Tc, however, did not appear to be linked to adipose clock gene expression across pregnancy. Overall, our data show marked adaptations in the adipose clock in pregnancy, with an apparent decoupling of adipose clock and lipolytic / lipogenic gene rhythms from early in gestation.
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Bilateral en-masse distalization of maxillary posterior teeth with skeletal anchorage: a case report The aim of this study was to introduce a new method for bilateral distal movement of the entire maxillary posterior segment. A 17- year - old girl with Class I skeletal malocclusion (end-to-end molar relationships, deviated midline and space deficiency for left maxillary canine) was referred for orthodontic treatment. She did not accept maxillary first premolars extraction. A modified Hyrax appliance (Dentaurum Ispringen, Germany) was used for bilateral distalization of maxillary posterior teeth simultaneously. Expansion vector was set anteroposteriorly. Posterior legs of Hyrax were welded to first maxillary molar bands. All posterior teeth on each side consolidated with a segment of 0.017 × 0.025-in stainless steel wire from the buccal side. Anterior legs of Hyrax were bent into eyelet form and attached to the anterior palate with two mini-screws (2 × 10 mm) (Jeil Medical Corporation Seoul, South Korea). Hyrax opening rate was 0.8 mm per month. Lateral cephalometric radiographs were used to evaluate the extent of distal movement. 3.5-mm distalization of posterior maxillary teeth was achieved in five months. A nearly bodily distal movement without anchorage loss was obtained. The mini-screw -supported modified Hyrax appliance was found to be helpful for achieving en-masse distal movement of maxillary posterior teeth.
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Histone deacetylase inhibitors regulate P-gp expression in colorectal cancer via transcriptional activation and mRNA stabilization Histone deacetylase inhibitors (HDACIs) are emerging as a novel class of anti-tumor drugs. But the effect of HDACIs in tumors treatment has been disappointing, which mainly due to the acquisition of resistance to HDACIs. However, the underlying mechanisms have not been clearly understood. In this study, it was found that HDACIs SAHA and TSA increased P-gp expression in CRC cells, which has been well known to contribute to drug resistant. The mechanisms underlying these effects were investigated. We showed that HDACIs enhanced transcriptional activity of P-gp protein encoding gene ABCB1. HDACIs treatment also increased the protein and mRNA expression of STAT3, but not PXR, CAR, Foxo3a or β-catenin, which are known to be involved in ABCB transcription regulation. Interestingly, knockdown of STAT3 significantly attenuated HDACIs - induced P-gp up-regulation in colorectal cancer cells, suggesting that STAT3 plays a crucial role in HDACIs - up-regulated P-gp. Furthermore, this study revealed for the first time that HDACIs enhanced the stability of ABCB1 at post-transcriptional level. Taken together, these results proved that HDACIs induced P-gp expression by two distinct ways, transcriptional activation and mRNA stabilization. Our results suggested that more attention should be paid to the cancer treatment using HDACIs since they will induce multidrug resistance in cancer cells.
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Mother - Infant Emotion Regulation at Three Months: The Role of Maternal Anxiety, Depression and Parenting Stress While the association between anxiety and postpartum depression is well known, few studies have investigated the relationship between these two states and parenting stress. Furthermore, a number of studies have found that postpartum depression affects mother - infant emotion regulation, but there has been only one study on anxiety and emotion regulation and no studies at all on parenting stress and emotion regulation. Therefore, the primary aim of our study is to identify, in a community sample of 71 mothers, the relationship between maternal depression, anxiety, and parenting stress. The second aim is to examine the relationship between anxiety, postpartum depression, and parenting stress and mother - infant emotion regulation assessed at 3 months. Mother - infant interaction was coded with a modified version of the Infant Caregiver and Engagement Phases (ICEP) using a microanalytic approach. The Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI), and Parenting Stress Index-Short Form (PSI-SF) were administered to the mothers to assess depression, anxiety, and parenting stress, respectively. Analysis revealed correlations between anxiety and depression, showing that parenting stress is associated with both states. In a laboratory observation, depression was correlated with both negative maternal states and negative dyadic matches as well as infant positive / mother negative mismatches; anxiety was correlated with both negative maternal states and infant negative states as well as mismatches involving one of the partners having a negative state. Multiple regression analysis showed that anxiety is a greater predictor than depression of less adequate styles of mother - infant emotion regulation. Parenting stress was not shown to predict such regulation.
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Medical Devices; Gastroenterology-Urology Devices; Classification of the Metallic Biliary Stent System for Benign Strictures. Final order The Food and Drug Administration (FDA) is classifying the metallic biliary stent system for benign strictures into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the metallic biliary stent system for benign strictures ' classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.
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Environmental Exposure to Cadmium: Health Risk Assessment and its Associations with Hypertension and Impaired Kidney Function Cadmium (Cd) is a toxic metal. This study was aimed to estimate the potential health risks in a Cd - polluted district in China, and examine the relationship between urinary cadmium (UCd) and hypertension and impaired kidney function at low exposure levels (UCd: GM 1.3 μg/g creatinine). Blood pressure measurement, questionnaires, and collection of urinary samples were conducted from 217 residents. Environmental samples, food, and cigarette samples were collected and detected to estimate the risks posed by Cd and the contribution of inhalation, ingestion, and dermal contact pathways to these risks. A logistic regression model was used in examining associations between exposure and hypertension and impaired kidney function. Results show that this population is at high risk. For non-smokers, incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) are 1.74E-04 and 2.96, and for smokers, they are 1.07E-03 and 52.5, respectively. Among all exposure pathways, smoking and foods cause the major increases in ILCR and HQ. UCd is significantly associated with hypertension (odds ratio (OR) = 1.468; 95% confidence interval (CI): 1.104, 1.953; P = 0.008) and impaired kidney function (OR = 1.902, 95% CI: 1.054, 3.432; P = 0.033). The results demonstrate that Cd can potentially lead to adverse health effects.
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Altererythrobacter confluentis sp. nov., isolated from water of an estuary environment A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated KEM-4T, was isolated from water of an estuary environment on the Yellow Sea, South Korea, and subjected to a polyphasic taxonomic study. Strain KEM-4T grew optimally at pH 7.0-8.0, at 30 °C and in the presence of 1.0-2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences showed that strain KEM-4T fell within the clade comprising the type strains of Altererythrobacter species, clustering with the type strains of Altererythrobacter aestiaquae, Altererythrobacter gangjinensis and Altererythrobacter luteolus showing 95.0-96.5 % sequence similarity. Sequences similarities to the type strains of the other Altererythrobacter species were 93.1-95.1 %. Strain KEM-4T contained Q-10 as the predominant ubiquinone and C18:1 ω7c, summed feature 3 (C16:1 ω6c and/or C16:1 ω7c) and C17:1 ω6c as the major fatty acids. The major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid. The DNA G+C content of strain KEM-4T was 59.5 mol%. Differential phenotypic properties, together with the phylogenetic distinctiveness, revealed that strain KEM-4T is separated from recognized Altererythrobacter species. On the basis of the data presented, strain KEM-4T is considered to represent a novel species of the genus Altererythrobacter, for which the name Altererythrobacter confluentis sp. nov. is proposed. The type strain of is KEM-4T (= KCTC 52259T = NBRC 112305T).
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Nonstenotic carotid plaque on CT angiography in patients with cryptogenic stroke To determine whether large (≥3 mm thick) but nonstenotic (<50%) carotid artery atherosclerotic plaque predominantly occurs ipsilateral rather than contralateral to cryptogenic stroke. This was a cross-sectional observational study. Using a stroke registry, we identified consecutive patients with anterior circulation embolic stroke of undetermined source (ESUS). Using CT angiography, we measured carotid plaque size (thickness, mm) and carotid artery stenosis (North American Symptomatic Carotid Endarterectomy Trial method) for each patient. We dichotomized plaque size at several predefined thresholds and calculated the frequency of plaque size above each threshold ipsilateral vs contralateral to stroke. We included 85 patients with ESUS. Plaque with thickness ≥5 mm was present ipsilateral to stroke in 11% of patients, and contralateral in 1% (9/85 vs 1/85; p = 0.008). Plaque with thickness ≥4 mm was present ipsilateral to stroke in 19% of patients, and contralateral in 5% (16/85 vs 4/85; p = 0.002). Plaque with thickness ≥3 mm was present ipsilateral to stroke in 35% of patients, and contralateral in 15% (30/85 vs 13/85; p = 0.001). There was no difference in percentage stenosis ipsilateral vs contralateral to stroke (p = 0.98), and weak correlation between plaque size and stenosis (R(2) = 0.26, p < 0.001). Large but nonstenotic carotid artery plaque is considerably more common ipsilateral than contralateral to cryptogenic stroke, suggesting that nonstenotic plaque is an underrecognized cause of stroke. We measured plaque size using CT angiography, a method that could be easily implemented in clinical practice.
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Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis Patients with painful knee osteoarthritis (OA) demonstrate hyperalgesia and altered pain-modulatory responses. While some prior work has demonstrated cross-sectional associations between laboratory and clinical pain measures, it is unknown whether individual variability in quantitative sensory testing (QST) responses at baseline can prospectively predict analgesic treatment responses. Patients with knee OA (n = 35) were compared on QST responses to a demographically -matched pain-free control group (n = 39), after which patients completed a month-long treatment study of diclofenac sodium topical gel (1 %), applied up to 4 times daily. OA patients demonstrated reduced pain thresholds at multiple anatomic sites, as well as reduced conditioned pain modulation (CPM) and enhanced temporal summation of pain. The most pain-sensitive patients tended to report the most intense and neuropathic OA pain. Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of neuropathic symptoms. Baseline CPM scores, an index of endogenous pain-inhibitory capacity, were prospectively associated with treatment -related changes in clinical pain. Specifically, participants with higher CPM at baseline (i.e., better functioning endogenous pain - inhibitory systems) showed more reduction in pain at the end of treatment (p < .05). These results support prior findings of amplified pain sensitivity and reduced pain-inhibition in OA patients. Moreover, the moderate to strong associations between laboratory-based measures of pain sensitivity and indices of clinical pain highlight the clinical relevance of QST in this sample. Finally, the prospective association between CPM and diclofenac response suggests that QST-based phenotyping may have utility in explaining inter-patient variability in long-term analgesic treatment outcomes. ClinicalTrials .Gov Identifier: NCT01383954. Registered June 22, 2011.
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In Vitro Assays for the Discovery of PCSK9 Autoprocessing Inhibitors PCSK9 plays a significant role in regulating low-density lipoprotein (LDL) cholesterol levels and has become an important drug target for treating hypercholesterolemia. Although a member of the serine protease family, PCSK9 only catalyzes a single reaction, the autocleavage of its prodomain. The maturation of the proprotein is an essential prerequisite for the secretion of PCSK9 to the extracellular space where it binds the LDL receptor and targets it for degradation. We have found that a construct of proPCSK9 where the C-terminal domain has been truncated has sufficient stability to be expressed and purified from Escherichia coli for the in vitro study of autoprocessing. Using automated Western analysis, we demonstrate that autoprocessing exhibits the anticipated first-order kinetics. A high-throughput time-resolved fluorescence resonance energy transfer assay for autocleavage has been developed using a PCSK9 monoclonal antibody that is sensitive to the conformational changes that occur upon maturation of the proprotein. Kinetic theory has been developed that describes the behavior of both reversible and irreversible inhibitors of autocleavage. The analysis of an irreversible lactone inhibitor validates the expected relationship between potency and the reaction end point. An orthogonal liquid chromatography-mass spectrometry assay has also been implemented for the confirmation of hits from the antibody-based assays.
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Abstract and Effector-Selective Decision Signals Exhibit Qualitatively Distinct Dynamics before Delayed Perceptual Reports Electrophysiological research has isolated neural signatures of decision formation in a variety of brain regions. Studies in rodents and monkeys have focused primarily on effector-selective signals that translate the emerging decision into a specific motor plan, but, more recently, research on the human brain has identified an abstract signature of evidence accumulation that does not appear to play any direct role in action preparation. The functional dissociations between these distinct signal types have only begun to be characterized, and their dynamics during decisions with deferred actions with or without foreknowledge of stimulus-effector mapping, a commonly studied task scenario in single-unit and functional imaging investigations, have not been established. Here we traced the dynamics of distinct abstract and effector-selective decision signals in the form of the broad-band centro-parietal positivity (CPP) and limb-selective β-band (8-16 and 18-30 Hz) EEG activity, respectively, during delayed - reported motion direction decisions with and without foreknowledge of direction - response mapping. With foreknowledge, the CPP and β-band signals exhibited a similar gradual build-up following evidence onset, but whereas choice - predictive β-band activity persisted up until the delayed response, the CPP dropped toward baseline after peaking. Without foreknowledge, the CPP exhibited identical dynamics, whereas choice - selective β-band activity was eliminated. These findings highlight qualitative functional distinctions between effector-selective and abstract decision signals and are of relevance to the assumptions founding functional neuroimaging investigations of decision-making. Neural signatures of evidence accumulation have been isolated in numerous brain regions. Although animal neurophysiology has largely concentrated on effector-selective decision signals that translate the emerging decision into a specific motor plan, recent research on the human brain has isolated abstract neural signatures of decision formation that are independent of specific sensory and motor requirements. Here, we examine the functional distinctions between the two distinct classes of decision variable signal during decisions with deferred actions with and without foreknowledge of stimulus-effector mapping. We find salient distinctions in the dynamics of abstract versus effector-selective decision signals in the human brain, in terms of sustainment through response delays and contingency on foreknowledge of stimulus-response mapping.
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Prevalence of gastrointestinal parasites in dogs of Palampur, Himachal Pradesh A total of 246 faecal / scat samples of the dogs were screened by direct and floatation concentration technique to study the gastrointestinal (GI) tract parasitism in dogs of Palampur, Himachal Pradesh, India. Detailed coprological examination targeting different seasons, age groups and living styles of the dogs revealed an overall 28.04 % of GI parasitism with highest prevalence in summer season (37.87 %). Stray dogs harbored 47.29 % GI parasites in comparison to 19.19 % of pet dogs. Highest prevalence of GI parasitism was observed in the pups, below 3 months of age (39.13 %), followed by the dogs with the age ranging from 3 months to 1 year (26.38 %) and lowest in dogs of the age ranging from 1 to 3 years (6.77 %). Amongst all the parasites, Toxocara canis (44.93 %) infection was highest, followed by Dipylidium caninum (17.39 %) and hookworms (15.94 %).
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Developing Community - Level Policy and Practice to Reduce Traffic - Related Air Pollution Exposure The literature consistently shows associations of adverse cardiovascular and pulmonary outcomes with residential proximity to highways and major roadways. Air monitoring shows that traffic - related pollutants (TRAP) are elevated within 200-400 m of these roads. Community - level tactics for reducing exposure include the following: 1) HEPA filtration; 2) Appropriate air-intake locations; 3) Sound proofing, insulation and other features; 4) Land-use buffers; 5) Vegetation or wall barriers; 6) Street-side trees, hedges and vegetation; 7) Decking over highways; 8) Urban design including placement of buildings; 9) Garden and park locations; and 10) Active travel locations, including bicycling and walking paths. A multidisciplinary design charrette was held to test the feasibility of incorporating these tactics into near - highway housing and school developments that were in the planning stages. The resulting designs successfully utilized many of the protective tactics and also led to engagement with the designers and developers of the sites. There is a need to increase awareness of TRAP in terms of building design and urban planning.
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Learning Is Better with the Hands Free: The Role of Posture in the Memory of Manipulable Objects Grounded cognition proposes that memory shares processing resources with sensorimotor systems. The aim of the present study was to show that motor simulation participates in the conceptual representation of manipulable objects in long-term memory. In two experiments, lists of manipulable and nonmanipulable objects were presented. Participants were instructed to memorize the items while adopting different postures. In the control condition, they had to keep their hands at rest in front of them. In the interference condition, participants had to keep their hands crossed behind their back to make their hands less free for action. After each list, participants had to perform first a distractive task, and then an oral free recall. The results showed that the interfering posture produced a specific decrease in the recall of manipulable objects, but not of nonmanipulable ones. This decrease was similar when the items were presented as pictures (Experiment 1) or as words (Experiment 2), thus excluding a purely visual effect. These results provide strong evidence that the motor simulation plays a role in the memory trace of the object.
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Developing and Field Testing a Community Based Youth Initiative to Increase Tuberculosis Awareness in Remote Arctic Inuit Communities Inuit in Canada have the highest reported tuberculosis (TB) incidence rate in Canada, even higher than other Canadian Indigenous groups. The aim of this study was to increase TB awareness among Inuit youth and their communities by equipping those who can best reach this population with a community based, youth focused, education initiative built on interventions adapted from a previous TB awareness study. The Taima TB Youth Education Initiative was a field test case study of a knowledge translation (KT) strategy aimed at community members who provide health education in these communities. In the first stage of this study, interventions from a larger TB awareness campaign were adapted to focus on youth living in remote Inuit communities. During the second stage of the study, investigators field tested the initiative in two isolated Inuit communities. It was then applied by local implementation teams in two other communities. Evaluation criteria included feasibility, acceptability, knowledge uptake and health behavior change. Implementation of the adapted KT interventions resulted in participation of a total of 41 youth (19 females, 22 males) with an average age of 16 years (range 12-21 years) in four different communities in Nunavut. Community celebration events were attended by 271 community members where TB messaging were presented and discussed. All of the health care workers and community members surveyed reported that the adapted interventions were acceptable and a useful way of learning to some extent. Knowledge uptake measures indicated an average TB knowledge score of 64 out of 100. Local partners in all four communities indicated that they would use the Taima TB Youth Education Initiative again to raise awareness about TB among youth in their communities. The TB awareness interventions adapted for the Taima TB Youth Education Initiative were acceptable to the Inuit communities involved in the study. They resulted in uptake of knowledge among participants. Implementation by local implementation teams was feasible as evidenced by the participation and attendance of youth and community members in all communities. The ability to implement the interventions by local implementation teams indicates there is potential to scale up in other remote communities in the arctic setting.
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An efficient approach to identify different chemical markers between fibrous root and rhizome of Anemarrhena asphodeloides by ultra high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry with multivariate statistical analysis An ultra high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry approach coupled with multivariate statistical analysis was established and applied to rapidly distinguish the chemical differences between fibrous root and rhizome of Anemarrhena asphodeloides. The datasets of tR-m/z pairs, ion intensity and sample code were processed by principal component analysis and orthogonal partial least squares discriminant analysis. Chemical markers could be identified based on their exact mass data, fragmentation characteristics, and retention times. And the new compounds among chemical markers could be isolated rapidly guided by the ultra high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and their definitive structures would be further elucidated by NMR spectra. Using this approach, twenty-four markers were identified on line including nine new saponins and five new steroidal saponins of them were obtained in pure form. The study validated this proposed approach as a suitable method for identification of the chemical differences between various medicinal parts in order to expand medicinal parts and increase the utilization rate of resources.
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Baby FaceTime: can toddlers learn from online video chat? There is abundant evidence for the ' video deficit ': children under 2 years old learn better in person than from video. We evaluated whether these findings applied to video chat by testing whether children aged 12-25 months could form relationships with and learn from on-screen partners. We manipulated social contingency: children experienced either real-time FaceTime conversations or pre-recorded Videos as the partner taught novel words, actions and patterns. Children were attentive and responsive in both conditions, but only children in the FaceTime group responded to the partner in a temporally synced manner. After one week, children in the FaceTime condition (but not the Video condition) preferred and recognized their Partner, learned more novel patterns, and the oldest children learned more novel words. Results extend previous studies to demonstrate that children under 2 years show social and cognitive learning from video chat because it retains social contingency. A video abstract of this article can be viewed at: https://youtu.be/rTXaAYd5adA.
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Dental Students ' Educational Environment and Perceived Stress: The University of Malaya Experience An equitable and positive learning environment fosters deep self-directed learning in students and, consequently, good practice in their profession. Although demotivating weaknesses may lead to repeated day-to-day stress with a cascade of deleterious consequences at both personal and professional levels, a possible relationship between these parameters has not been reported. This study was undertaken to determine the relationship between students ' perceptions of their educational environment and their stress levels. Sixty-one first year students at the Dental Faculty, University of Malaya, Malaysia participated. The Dundee Ready Education Environment Measure (DREEM) was used to determine educational environment while self-rated perceived stress level was measured by the Depression Anxiety Stress Scale (DASS). Most students (62.39%) showed positive perceptions for the total and five domains of DREEM. The highest percentage was observed for " Students perception of learning " (64.04%) while the lowest was for " Students ' social self- perception " (60.32%). At the same time, 61% of students showed high perceived stress levels. However, this was not associated with their DREEM scores. Although a positive perception of their educational environment was found, minor corrective measures need to be implemented. Furthermore, longitudinal studies on an annual basis would provide useful input for strategic planning purposes.
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Bacterial Suppression of RNA Polymerase II - Dependent Host Gene Expression Asymptomatic bacteriuria (ABU) is a bacterial carrier state in the urinary tract that resembles commensalism at other mucosal sites. ABU strains often lack the virulence factors that characterize uropathogenic Escherichia coli (E. coli) strains and therefore elicit weak innate immune responses in the urinary tract. In addition, ABU strains are active modifiers of the host environment, which they influence by suppressing RNA polymerase II (Pol II)- dependent host gene expression. In patients inoculated with the ABU strain E. coli 83972, gene expression was markedly reduced after 24 h (>60% of all regulated genes). Specific repressors and activators of Pol II - dependent transcription were modified, and Pol II Serine 2 phosphorylation was significantly inhibited, indicating reduced activity of the polymerase. This active inhibition included disease -associated innate immune response pathways, defined by TLR4, IRF-3 and IRF-7, suggesting that ABU strains persist in human hosts by active suppression of the antibacterial defense. In a search for the mechanism of inhibition, we compared the whole genome sequences of E. coli 83972 and the uropathogenic strain E. coli CFT073. In addition to the known loss of virulence genes, we observed that the ABU strain has acquired several phages and identified the lytic Prophage 3 as a candidate Pol II inhibitor. Intact phage particles were released by ABU during in vitro growth in human urine. To address if Prophage 3 affects Pol II activity, we constructed a Prophage 3 negative deletion mutant in E. coli 83972 and compared the effect on Pol II phosphorylation between the mutant and the E. coli 83972 wild type (WT) strains. No difference was detected, suggesting that the Pol II inhibitor is not encoded by the phage. The review summarizes the evidence that the ABU strain E. coli 83972 modifies host gene expression by inhibition of Pol II phosphorylation, and discusses the ability of ABU strains to actively create an environment that enhances their persistence.
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Evaluation of the effects of an offer of a monetary incentive on the rate of questionnaire return during follow-up of a clinical trial: a randomised study within a trial A systematic review on the use of incentives to promote questionnaire return in clinical trials suggest they are effective, but not all studies have sufficient funds to use them. Promising an incentive once data are returned can reduce the cost-burden of this approach, with possible further cost-savings if the offer were restricted to reminder letters only. This study aimed to evaluate the effect of promising a monetary incentive at first mailout versus a promise on reminder letters only. This was a randomised Study Within A Trial (SWAT) nested within BUMPES, a multicentre randomised controlled trial of maternal position in the late stage of labour in women with an epidural. The follow-up questionnaire asked for information on the women's health, wellbeing and health service use one year following the birth of their baby. Women who consented to be contacted were randomised to a promise of a monetary incentive at first mailout or a promise on reminder letters only. Women were given an option of completing the questionnaire on paper or on online. The incentive was posted out on receipt of a completed questionnaire. The primary outcome was the overall return rate, and secondary outcomes were the return rate without any chasing from the study office, and the total cost of the vouchers. A total of 1,029 women were randomised, 508 to the first mailout group and 518 to the reminder group. There was no evidence to suggest a difference between groups in the overall return rate (adjusted RR 1.03 (95 % CI 0.96 to 1.11), however the proportion returned without chasing was higher in the first mailout group (adjusted RR 1.22, 95 % CI 1.07 to 1.39). The total cost of the vouchers per participant was higher in the first mailout group (mean difference £4.56, 95 % CI £4.02 to £5.11). Offering a monetary incentive when a reminder is required could be cost-effective depending on the sample size of the study and the resources available to administer the reminder letters. The BUMPES Trial is registered with Current Controlled Trials: ISRCTN35706297, 26(th) August 2009.
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HIF-1α expression and high microvessel density are characteristic features in serrated colorectal cancer Serrated colorectal adenocarcinoma (SAC) is a morphologically distinct subtype of colorectal cancer (CRC), in which increased HIF-1α mRNA expression and HIF-1α protein stabilization are typical features. Here we aimed to further elucidate HIF-1α protein expression in serrated and non-serrated colorectal carcinomas (CRCs) and their precursor lesions and its association with vascular endothelial growth factor (VEGF) and microvascular density (MVD). HIF-1α and VEGF expressions were determined immunohistochemically in 134 serrated polyps (SPs), 104 non-serrated adenomas (NSAs), 81 SACs, and 74 matched conventional adenocarcinomas (CCs) and were correlated with morphology, clinicopathological features, and MVD. In premalignant lesions, both HIF-1α and VEGF were expressed in the vast majority of SPs and NSAs. In CRCs, HIF-1α protein was also present in 77.8 % of SACs, while only 20.3 % of CCs were HIF-1α proficient. MVD was significantly higher in SACs, but the serrated morphology was the only significant predictor of MVD in CRC in multivariate analyses. HIF-1α protein is often stabilized in well-vascularized SACs, suggesting hypoxia - independent stabilization of HIF-1α. Moreover, HIF-1α stabilization did not associate with oncogenic activation of BRAF or KRAS or Von Hippel-Lindau (VHL) mutation. Prevalent HIF-1α expression in SAC and its precursors support the importance of HIF-1α -mediated pathways for the serrated route of colorectal carcinogenesis.
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Structure-Activity Studies of β-Hairpin Peptide Inhibitors of the Plasmodium falciparum AMA1 - RON2 Interaction The interaction between apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2) plays a key role in the invasion of red blood cells by Plasmodium parasites. Disruption of this critical protein-protein interaction represents a promising avenue for antimalarial drug discovery. In this work, we exploited a 13-residue β-hairpin based on the C-terminal loop of RON2 to probe a conserved binding site on Plasmodium falciparum AMA1. A series of mutations was synthetically engineered into β-hairpin peptides to establish structure-activity relationships. The best mutations improved the binding affinity of the β-hairpin peptide by ~7-fold for 3D7 AMA1 and ~14-fold for FVO AMA1. We determined the crystal structures of several β-hairpin peptides in complex with AMA1 in order to define the structural features and specific interactions that contribute to improved binding affinity. The same mutations in the longer RON2sp2 peptide (residues 2027-2055 of RON2) increased the binding affinity by >30-fold for 3D7 and FVO AMA1, producing KD values of 2.1nM and 0.4nM, respectively. To our knowledge, this is the most potent strain -transcending peptide reported to date and represents a valuable tool to characterize the AMA1 - RON2 interaction.
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[ "Haemophilus", "influenzae", "type", "b", "meningitis", "in", "a", "vaccinated", "and", "immunocompetent", "child", "Invasive", "Haemophilus", "influenzae", "type", "b", "(", "Hib", ")", "disease", "decreased", "dramatically", "after", "the", "introduction", "of", "conjugate", "vaccine", "in", "routine", "immunization", "schedules", ".", "We", "report", "a", "case", "of", "a", "fifteen", "-", "months", "-", "old", "girl", ",", "previously", "healthy", "and", "vaccinated", ",", "admitted", "in", "the", "emergency", "room", "with", "fever", "and", "vomiting", ".", "She", "was", "irritable", "and", "the", "Brudzinski", "'", "s", "sign", "was", "positive", ".", "The", "cerebrospinal", "fluid", "(", "CSF", ")", "analysis", "showed", "pleocytosis", "and", "high", "protein", "level", ".", "Empiric", "intravenous", "antibiotics", "(", "ceftriaxone", "and", "vancomycin", ")", "were", "administered", "for", "suspected", "bacterial", "meningitis", "during", "10", "days", ".", "Serotyping", "of", "the", "Haemophilus", "influenzae", "strain", "found", "in", "CSF", "revealed", "a", "serotype", "b", ".", "After", "one", "year", "of", "follow", "-", "up", "no", "Hib", "meningitis", "sequelae", "were", "noted", ".", "Despite", "vaccination", "compliance", "and", "absence", "of", "risk", "factors", ",", "invasive", "Hib", "disease", "can", "occur", "due", "to", "vaccine", "failure", ".", "Efforts", "to", "keep", "the", "low", "incidence", "of", "invasive", "Hib", "disease", "should", "be", "directed", "to", "the", "maintenance", "of", "high", "vaccination", "coverage", "rates", ",", "combined", "with", "the", "notification", "and", "surveillance", "strategies", "already", "implemented", "in", "each", "country" ]
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Haemophilus influenzae type b meningitis in a vaccinated and immunocompetent child Invasive Haemophilus influenzae type b (Hib) disease decreased dramatically after the introduction of conjugate vaccine in routine immunization schedules. We report a case of a fifteen-months-old girl, previously healthy and vaccinated, admitted in the emergency room with fever and vomiting. She was irritable and the Brudzinski's sign was positive. The cerebrospinal fluid (CSF) analysis showed pleocytosis and high protein level. Empiric intravenous antibiotics (ceftriaxone and vancomycin) were administered for suspected bacterial meningitis during 10 days. Serotyping of the Haemophilus influenzae strain found in CSF revealed a serotype b. After one year of follow-up no Hib meningitis sequelae were noted. Despite vaccination compliance and absence of risk factors, invasive Hib disease can occur due to vaccine failure. Efforts to keep the low incidence of invasive Hib disease should be directed to the maintenance of high vaccination coverage rates, combined with the notification and surveillance strategies already implemented in each country.
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BRG1 in the Nucleus Accumbens Regulates Cocaine-Seeking Behavior Drug addiction is defined as a chronic disease characterized by compulsive drug seeking and episodes of relapse despite prolonged periods of drug abstinence. Neurobiological adaptations, including transcriptional and epigenetic alterations in the nucleus accumbens, are thought to contribute to this life-long disease state. We previously demonstrated that the transcription factor SMAD3 is increased after 7 days of withdrawal from cocaine self-administration. However, it is still unknown which additional factors participate in the process of chromatin remodeling and facilitate the binding of SMAD3 to promoter regions of target genes. Here, we examined the possible interaction of BRG1 -also known as SMARCA4, an adenosine triphosphatase -containing chromatin remodeler -and SMAD3 in response to cocaine exposure. The expression of BRG1, as well as its binding to SMAD3 and target gene promoter regions, was evaluated in the nucleus accumbens and dorsal striatum of rats using western blotting, co-immunoprecipitation, and chromatin immunoprecipitation following abstinence from cocaine self-administration. Rats were assessed for cocaine-seeking behaviors after either intra-accumbal injections of the BRG1 inhibitor PFI3 or viral-mediated overexpression of BRG1. After withdrawal from cocaine self-administration, BRG1 expression and complex formation with SMAD3 are increased in the nucleus accumbens, resulting in increased binding of BRG1 to the promoter regions of Ctnnb1, Mef2d, and Dbn1. Intra-accumbal infusion of PFI3 attenuated, whereas viral overexpression of Brg1 enhanced, cocaine-reinstatement behavior. BRG1 is a key mediator of the SMAD3 -dependent regulation of cellular and behavioral plasticity that mediates cocaine seeking after a period of withdrawal.
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The blood lipid regulation of Monascus -produced monascin and ankaflavin via the suppression of low-density lipoprotein cholesterol assembly and stimulation of apolipoprotein A1 expression in the liver Monascin (MS) and ankaflavin (AK) produced by Monascus purpureus NTU 568 were proven to show excellent hypolipidemic effects in our previous studies; however, the mechanism is still unclear. This study used MS, AK, and monacolin K as test substances and performed tests on rats fed high-fat and high-cholesterol diet for 8 weeks. The lipid levels and the related protein levels of the rats were assessed to understand the effects of MS, AK, and monacolin K on lipid metabolism. MS and AK lowered low-density lipoprotein cholesterol (LDL-C) and preserved high-density lipoprotein cholesterol contents. MS and AK inhibited acetyl-coenzyme A acetyltransferase, microsomal triglyceride transfer protein, and apolipoprotein (apo) B-100 expression, thereby preventing LDL assembly. In addition, enhanced LDL - receptor expression increased the transport of LDL-C to the liver for metabolism. MS and AK also significantly increase apo A1 expression, which facilitates high-density lipoprotein cholesterol formation. Monascus - fermented MS and AK can perform blood lipid regulation via the suppression of LDL-C assembly and stimulation of apo A1 expression in liver.
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Acoustic Analysis Before and After Voice Therapy for Laryngeal Pathology Background Voice problems caused by pathologies in vocal folds are well known. Some types of laryngeal pathologies have certain acoustic characteristics. Objective evaluation helps characterize the voice and voice problems providing supporting evidences, severity of disorders. It helps assess the response to the treatment and measures the outcomes. Objective The objective of the study is to determine the effectiveness of the voice therapy and quantify the results objectively by voice parameters. Method Study includes 61 patients who presented with different types of laryngeal pathologies. Acoustic analyses and voice assessment was done with Dr. Speech ver 4 (Tiger DRS Inc.). Acoustic parameters including fundamental frequency, jitters, shimmers, Harmonic to noise ratio (HNR), Normalized noise energy (NNE) were analyzed before and after voice therapy. Result Bilateral vocal nodules were the most common pathologies comprising 44.26%. All acoustic parameters showed a significant difference after the therapy (p<0.05) except for NNE. Dysphonia due to vocal fold polyp showed no improvement even after voice therapy (p>0.05). Conclusion Acoustic analysis provides an objective, recordable data regarding the voice parameters and its pathologies. Though, few pathology require alternative therapy rather than voice therapy, overall it has a good effect on glottic closure. As the voice therapy can improve the different indices of voice, it can be viewed as imperative part of treatment and to monitor progression.
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MALDI-TOF mass spectrometry for the identification of lactic acid bacteria isolated from a French cheese: The Maroilles In this study we identified the culturable population of mesophilic lactic acid bacteria (LAB) from a French cheese Maroilles made either with raw or pasteurized milk using MALDI-TOF mass spectrometry (MS). Samples from rind and heart of Maroilles cheese were used, the LAB were selected on MRS agar at 30°C and 197 Gram-positive and catalase-negative strains were subjected to identification by MALDI-TOF MS profiling. All strains were unambiguously identified: 105 strains from Maroilles made with raw milk (38 on the rind and 67 in the heart) and 92 strains from Maroilles made with pasteurized milk (39 on the rind and 53 in the heart). MALDI-TOF MS identification allowed identification of three genera belonging to LAB including Lactobacillus, Enterococcus and Leuconostoc. Lactobacillus was the most represented genus with seven species: Lactobacillus plantarum (L. plantarum), L. paracasei, L. curvatus, L. rhamnosus, L. fructivorans, L. parabuchneri, L. brevis found in Maroilles made with both kind of milk. The correlation between the 16S rDNA -based identification performed on selected strains and those obtained by MALDI-TOF-MS demonstrates that this fast, economically affordable, robust and reliable method for bacteria characterisation stands as an attractive alternative to the commonly-used methods and its application in food industry is discussed.
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Is there a role for surgical resection in patients with pancreatic cancer with liver metastases responding to chemotherapy? New chemotherapeutic regimens have improved survival for stage IV pancreatic ductal adenocarcinoma and occasionally major response of liver metastases can be observed. Aim of this work is to analyze the outcomes of patients undergoing primary chemotherapy for liver metastases from pancreatic cancer and to evaluate the results of surgical resection. Retrospective analysis. patients with extra-hepatic metastases, patients with Eastern Cooperative Oncology Group performance status ≥3, patients undergoing supportive care alone. 127 patients were identified. Liver metastases were unilobar in 28.5% of patients. Chemotherapy regimens included gemcitabine alone or in association with other agents (44%), oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX 8%), and cisplatin, gemcitabine plus capecitabine and epirubicin (PEXG) or capecitabine and docetaxel (PDXG) or epirubicin and fluorouracil (PEFG) (48%). 56 patients (44%) had a complete (7%) or partial response (37%). surgical resection was carried out in 11 patients (8.5%). Median overall survival was 11 months for the entire cohort and 15 months for those with partial / complete response. In this sub-group median survival was significantly longer (46 versus 11 months) for patients undergoing resection (P < 0.0001). Independent predictors of overall survival were chemotherapy with multiple agents (HR: 0.512), surgical resection (HR: 0.360), >5 liver metastases at diagnosis (HR: 3.515), and CA 19.9 reduction < 50% of baseline value (HR: 2.708). Surgical resection of primary pancreatic tumor with or without residual liver disease can be considered in selected cases after primary chemotherapy and it is associated with improved survival.
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Applying a participatory approach to the promotion of a culture of respect during childbirth Disrespect and abuse (D&A) during facility-based childbirth is a topic of growing concern and attention globally. Several recent studies have sought to quantify the prevalence of D&A, however little evidence exists about effective interventions to mitigate disrespect and abuse, and promote respectful maternity care. In an accompanying article, we describe the process of selecting, implementing, and evaluating a package of interventions designed to prevent and reduce disrespect and abuse in a large urban hospital in Tanzania. Though that study was not powered to detect a definitive impact on reducing D&A, the results showed important changes in intermediate outcomes associated with this goal. In this commentary, we describe the factors that enabled this effect, especially the participatory approach we adopted to engage key stakeholders throughout the planning and implementation of the program. Based on our experience and findings, we conclude that a visible, sustained, and participatory intervention process; committed facility leadership; management support; and staff engagement throughout the project contributed to a marked change in the culture of the hospital to one that values and promotes respectful maternity care. For these changes to translate into dignified care during childbirth for all women in a sustainable fashion, institutional commitment to providing the necessary resources and staff will be needed.
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Prevalence and Self-recognition of Chronic Constipation: Results of an Internet Survey Although chronic constipation is a common symptom, to date no international consensus has been reached regarding its definition. The aims of this study were (1) to investigate defecation habits and (2) to examine the prevalence of constipation using the Japanese Society of Internal Medicine (JSIM) and the Rome III criteria using an online survey. An online questionnaire composed of items on the frequency, interval, form of defecation, the management, and self-recognition of constipation (reference standard of constipation) was created. A total of 5155 valid responses were received. In addition, constipation symptoms were evaluated through a survey using the JSIM and the Rome III criteria. In the internet survey, 28.4% of the respondents considered themselves to be constipated. Stratified by sex, significantly more females (37.5%) than males (19.1%) considered themselves to be constipated (P < 0.001). The prevalence of constipation among the respondents was 28.0% using the Rome III, but only 10.1% using the JSIM. The diagnostic accuracy was 73.2% for the Rome III and 78.1% for the JSIM, while the diagnostic specificity was 81.1% for the Rome III and 97.5% for the JSIM. However, the diagnostic sensitivities for both measures were low, at 52.2% and 29.2% for the Rome III and the JSIM, respectively. The online survey developed for this study was able to provide clarification regarding defecation patterns. The results also suggest a discrepancy between the self-recognized prevalence of constipation in Japan and prevalence of constipation based on the JSIM criteria.
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Development of Community Based Learning and Education system within Undergraduate Medical Curriculum of Patan Academy of Health Sciences In response to continuing health disparities between rural and urban population, Patan Academy of Health Sciences (PAHS) was established in 2008. It aimed to produce physicians who would be able and willing to serve in the rural areas. In order to empower them with understanding and tools to address health issues of rural population, an innovative curriculum was developed. This paper aims to describe the community based learning and education (CBLE) system within the overall framework of PAHS undergraduate medical curriculum. A Medical School Steering Committee (MSSC) comprising of a group of committed medical educators led the curriculum development process. The committee reviewed different medical curricula, relevant literatures, and held a series of consultative meetings with the stakeholders and experts within and outside Nepal. This process resulted in defining the desirable attributes, terminal competencies of the graduates, and then the actual development of the entire curriculum including CBLE. Given the critical importance of population health, 25% of the curricular weightage was allocated to the Community Health Sciences (CHS). CBLE system was developed as the primary means of delivering CHS curriculum. The details of CBLE system was finalized for implementation with the first cohort of medical students commencing their studies from June 2010. The CBLE, a key educational strategy of PAHS curriculum, is envisaged to improve retention and performance of PAHS graduates and, thereby, health status of rural population. However, whether or not that goal will be achieved needs to be verified after the graduates join the health system.
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Antihypertensive medicines utilization: A decade-long nationwide study of octogenarians, nonagenarians and centenarians Gaining an insight into the utilization of antihypertensive medicines against a background of evolving hypertension treatment guidelines that might not be relevant to the oldest old is important. The aim of the present study was to characterize the overall trends in the utilization of antihypertensive medicines in the oldest old by therapeutic class and chemical type, stratified by age and sex over a decade. Antihypertensive medicines utilization was examined using the therapeutic and chemical groups based on the World Health Organization Collaborating Center for Drug Statistics Mythology's Anatomical Therapeutic Chemical classification system for all individuals aged ≥80 years. Regression and repeated cross-sectional analyses was carried out, and defined daily dose was used to describe the utilization per thousand older people per day. Utilization of antihypertensive medicines increased over the decade from 187.28 in 2005 to 205.01 defined daily dose per thousand older people per day in 2014, and shifted from mainly diuretics to angiotensin-converting enzyme inhibitors. Interestingly, with the exception of diuretics, utilization of all medicines decreased gradually with increasing age. Single products use increased by 1.48-fold in 2014 compared with 2005, and for fixed-dose combinations the increase was 1.41-fold for the same period. The increased utilization of angiotensin-converting enzyme inhibitors is consistent with recommendations from cardiovascular guidelines formulated from large randomized control trials that often exclude the oldest old. Interestingly, the utilization of beta-blockers decreased and diuretics increased in centenarians. The utilization of calcium channel blockers and angiotensin-converting enzyme inhibitors across the study period increased in all age categories. Geriatr Gerontol Int 2016; ••: ••-••.
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Autoimmune Myelofibrosis in Systemic Lupus Erythematosus Report of Two Cases and Review of the Literature Autoimmune myelofibrosis (AIMF) is a rare entity of steroid - responsive bone marrow fibrosis that accompanies a variety of autoimmune diseases, particularly systemic lupus erythematosus (SLE). Rarely it may occur in patients with autoimmune markers but no definable autoimmune disease (Primary-AIMF). We report the cases of two young women with SLE - associated AIMF (SLE - AIMF). The first patient was a young woman who had pancytopenia, massive splenomegaly and reticulin fibrosis in the marrow biopsy. The pancytopenia and splenomegaly resolved completely within weeks of treatment with corticosteroids. Repeat marrow biopsy showed marked regression of marrow fibrosis. The second patient was a young woman with fever, anasarca, bicytopenia and reticulin fibrosis in the marrow biopsy. Steroid therapy resulted in rapid clinical improvement and resolution of pancytopenia. A review of the literature revealed a total of 30 patients with SLE - AIMF reported to- date. Patients with SLE - AIMF are young women with SLE and blood cytopenia who are found to have increased bone marrow reticulin on marrow biopsy. Steroid therapy results in rapid hematological recovery and regression of marrow fibrosis. Whether AIMF is one of several hematological complications of SLE, or represents a unique and distinct subset of patients with SLE in not clear. Prospective studies with longer follow-up are needed to better define the prevalence and clinical spectrum of SLE - AIMF.
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Experimental study of GeneXpert(®) system in the diagnosis of extra-pulmonary tuberculosis To explore the application value of GeneXpert MTB/RIF for detection of extra-pulmonary tuberculosis and resistance to rifampin. A total of 150 samples were collected, including 33 needle aspirates from lymphoid tuberculosis, 23 needle aspirates from spinal tuberculosis, 49 from tuberculous pleural effusions, 24 from cerebrospinal fluid of tuberculous cephalomeningitis, and 21 urinary sediment samples from renal tuberculosis. Smear microscopy, mycobacterium tuberculosis culture and the MTB/RIF method were used to examine these samples and their positive rates were compared. Rifampin susceptibility tests was performed for culture-positive strains using proportion method, which was compared with the result from GeneXpert MTB/RIF method. Of the 150 cases of extra-pulmonary tuberculosis, 17 samples were smear-positive, with a sensitivity of 11.3% (17/150); 30 were culture-positive with a sensitivity of 20.0% (30/150); and 96 were positive by MTB/RIF method with a sensitivity of 64.0% (96/150). There was a significant difference between MTB/RIF method and the culture method (χ(2)=59.61, P<0.01). The differences were also significant when the MTB/RIF method was compared with the smear method (χ(2)=88.60, P<0.01) or compared with culture plus smear methods (χ(2)=4.26, P<0.05). Separately, the differences were statistically significant between GeneXpert MTB/RIF method and other 2 methods for diagnosis of lymphoid tuberculosis (n=33, χ(2)=20.56, P<0.01 vs. culture method; χ(2)=27.13, P<0.01 vs. smear results) while no difference was found between culture and smear method (χ(2)=0.67, P>0.05), spinal tuberculosis (n=23, χ(2)=12.74, P<0.01 vs. culture method; χ(2)=14.81, P< 0.01 vs. smear method), tuberculous pleurisy (n=49, χ(2)=32.34, P<0.01 vs. culture method; χ(2)=49.69, P<0.01 vs. smear method) and renal tuberculosis (n=21, χ(2)=4.20, P<0.05 vs. culture method; χ(2) =8.40, P<0.01 vs. smear results). The sensitivity for tuberculous meningitis had no difference among these 3 methods (n=24, P>0.05). Rifampicin-resistance of the strains from the 30 culture-positive cases of extra-pulmonary tuberculosis (20.0%, 6/30) exhibited agreement with GeneXpert MTB/RIF test. The simplicity and high sensitivity of GeneXpert MTB/RIF technology make it a good diagnostic test for rapid detection of extra-pulmonary tuberculosis and resistance to rifampin.
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Influence of climatic factors on the flight activity of the stingless bee Partamona orizabaensis and its competition behavior at food sources Stingless bee s have evolved several ways to share contested resources to ensure the coexistence between different species. Partamona orizabaensis quickly exploits food sources by fast and direct recruitment that does not rely on scent marks deposited on substrates. In this study we show that the flight activity of P. orizabaensis is influenced by weather conditions, with higher activity during periods of colder temperatures, higher relative humidity and even during rainfall. We showed that the outcome of aggression experiments between the non-aggressive species P. orizabaensis and its aggressive competitor Trigona fuscipennis is influenced by the number of bees that arrive early after food source discovery. Therefore, the increased activity during less favorable weather conditions and the fast recruitment of nestmates following the discovery of a food source, as observed for P. orizabaensis, may be adaptations that evolved to coexist even with more aggressive and dominant species of stingless bees, with which P. orizabaensis has to compete for resources.
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Withdrawal of Anticancer Therapy in Advanced Disease Because of Side Effects Withdrawal of chemotherapy because of side effects may be due to" problems with toxicity "or" patient refusal "." Problems with toxicity "is intended to secure patient safety and decisions about it are primarily made by the oncologist. On the other hand," patient refusal "is influenced by the degree of distress the patient is experiencing and the patient's preference. Providing sufficient medical information is essential in decision making, because it is a decision made by the patient. In addition, the perception of side effects has changed owing to progress in supportive therapy in recent years. In particular, cancer patients are concerned about changes in appearance. In our study(4/2015 to 3/2016), chemotherapy was withdrawn because of side effects during treatment for solid carcinomas in 8%(4/51)of the patients. Two of these patients experienced liver function disorders, and 2 developed interstitial pneumonitis. Patient refusal was observed in 2%(1/51)of the patients.
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Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK -Rearranged Lung Cancer Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression. Second-generation inhibitors are generally effective even in the absence of crizotinib - resistant ALK mutations, likely reflecting incomplete inhibition of ALK by crizotinib in many cases. Herein, we analyzed 103 repeat biopsies from ALK -positive patients progressing on various ALK inhibitors. We find that each ALK inhibitor is associated with a distinct spectrum of ALK resistance mutations and that the frequency of one mutation, ALK(G1202R), increases significantly after treatment with second-generation agents. To investigate strategies to overcome resistance to second-generation ALK inhibitors, we examine the activity of the third-generation ALK inhibitor lorlatinib in a series of ceritinib - resistant, patient -derived cell lines, and observe that the presence of ALK resistance mutations is highly predictive for sensitivity to lorlatinib, whereas those cell lines without ALK mutations are resistant. Secondary ALK mutations are a common resistance mechanism to second-generation ALK inhibitors and predict for sensitivity to the third-generation ALK inhibitor lorlatinib. These findings highlight the importance of repeat biopsies and genotyping following disease progression on targeted therapies, particularly second-generation ALK inhibitors. Cancer Discov; 6(10); 1118-33. ©2016 AACRSee related commentary by Qiao and Lovly, p. 1084This article is highlighted in the In This Issue feature, p. 1069.
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Targeted DNA Sequencing Reveals Patterns of Local Progression in the Pancreatic Remnant Following Resection of Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas The aim of this study was to characterize patterns of local progression following resection for pancreatic intraductal papillary mucinous neoplasms (IPMN) using targeted next-generation sequencing (NGS). Progression of neoplastic disease in the remnant pancreas following resection of IPMN may include development of a new IPMN or ductal adenocarcinoma (PDAC). However, it is not clear whether this progression represents recurrence of the same neoplasm or an independent second neoplasm. Targeted-NGS on genes commonly mutated in IPMN and PDAC was performed on tumors from (1) 13 patients who developed disease progression in the remnant pancreas following resection of IPMN; and (2) 10 patients who underwent a resection for PDAC and had a concomitant IPMN. Mutations in the tumors were compared in order to determine the relationship between neoplasms. In parallel, clinical and pathological characteristics of 260 patients who underwent resection of noninvasive IPMN were reviewed to identify risk factors associated with local progression. We identified 3 mechanisms underlying local progression in the remnant pancreas: (1) residual microscopic disease at the resection margin, (2) intraparenchymal spread of neoplastic cells, leading to an anatomically separate but genetically related recurrence, and (3) multifocal disease with genetically distinct lesions. Analysis of the 260 patients with noninvasive IPMNs showed that family history of pancreatic cancer (P = 0.027) and high-grade dysplasia (HGD) (P = 0.003) were independent risk factors for the development of an IPMN with HGD or an invasive carcinoma in the remnant pancreas. Using NGS, we identify distinct mechanisms for development of metachronous or synchronous neoplasms in patients with IPMN. Patients with a primary IPMN with HGD or with positive family history are at an increased risk to develop subsequent high-risk neoplasms in the remnant pancreas.
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Serum ferritin levels as a useful diagnostic marker for the distinction of systemic juvenile idiopathic arthritis and Kawasaki disease The clinical features and laboratory parameters of patients with Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (s-JIA) tend to overlap. Furthermore, there have been no definitive biomarkers for these disease s, making clinical diagnosis difficult. The purpose of this study was to investigate the diagnostic value of serum ferritin levels for differentiating KD from s-JIA and predicting the disease severity of KD. We analyzed 228 patients with KD and 81 patients with s-JIA. Serum ferritin levels were compared between patients with s-JIA and KD. Furthermore, serum ferritin levels in patients with KD were compared with respect to clinical features such as responsiveness to intravenous immunoglobulin (IVIG) therapy. Serum ferritin levels in KD patients with no response to IVIG therapy were significantly higher than those in KD patients with a good response to IVIG therapy. Serum ferritin levels in patients with KD needing plasma exchange (PE) were significantly higher than those in patients not needing PE. However, serum ferritin levels overlapped between severe KD patients with nonresponsiveness to IVIG therapy or needing PE and other patients with mild KD. Furthermore, patients with s-JIA showed a distinct elevation of serum ferritin levels compared with KD patients. The cutoff value of serum ferritin levels for differentiating KD from s-JIA was 369.6 ng/ml. Serum ferritin levels were significantly elevated in s-JIA patients compared with KD patients. Measurement of serum ferritin levels can be useful for differentiating s-JIA from KD.
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Phenozan, a Synthetic Phenolic Antioxidant, Inhibits the Development of Spontaneous Tumors in Rats and Mice Synthetic phenolic antioxidant β-(4-hydroxy-3,5-di-tert-butylphenyl) propionic acid, named phenozan, is a potential antiepileptic drug. In pre-clinical trials this substance did not manifest any toxicity, and also inhibited the development of some spontaneous tumors in animals. The purpose of this study was to evaluate inhibiting effect of phenozan on spontaneous carcinogenesis in rats and mice. In experiments with rats LIO and mice SHR of local breeding, with high spontaneous tumor incidence, phenozan was dissolved in sunflower oil and administered by gavage in therapeutic dose 5 mg/kg 3 times per week for 18 months. There were no any signs of toxicity and differences in weight of animals during the phenozan treatment compared with the control (sunflower oil). Phenozan significantly reduced the overall incidence and multiplicity of all tumors but only multiplicity of malignant tumors, compared with the control. Moreover a significant decrease of overall incidence and multiplicity was observed in pituitary and breast tumors in females and only overall multiplicity of tumors of pituitary and lymphoid tissue in males. In mice phenozan reduced overall incidence and multiplicity of lung tumors (in females) and also overall multiplicity of all tumors (in females) and only malignant tumors (in males). These findings allow us to classify phenozan as anticarcinogenic agent. Anticarcinogenic activity of phenozan is important because clinical study of this drug as the possible antiepileptic drug goes along and it is known that such drugs are designed for long-term use.
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Towards next-generation sequencing analytics for foodborne RNA viruses: Examining the effect of RNA input quantity and viral RNA purity Detection and identification of viruses in food samples are technically challenging due largely to the low viral copy number in contaminated food items, and the lack of effective culture enrichment methods that are amenable to regulatory applications for many of the common foodborne viruses. Using an Illumina MiSeq platform and two hepatitis A virus (HAV) cell-culture adapted strains as a representative enteric virus species, this study examined the limits of single-stranded RNA (ssRNA) viral detection following next-generation sequencing without pre-amplification of the viral genome. Complete viral genome sequences were obtained from HAV samples of varying purities and with an input as low as 2ng total RNA containing 1.4×10(5) copies of viral RNA. In addition, single nucleotide variations were reproducibly detected over the range of concentrations examined, and their identity confirmed by alternate sequencing technology. In summary, next-generation sequencing technology has the potential for sensitive detection / identification of a viral genome at a low copy number. This study provides a benchmark for metagenomic sequencing application as is required for virus detection in complex food matrices using a culture -independent diagnostic approach.
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Long-Term Safety Follow-Up of Subjects Previously Treated with Non-Replicating Retroviral Vector -Based Gene Therapies Our objective was to evaluate the life-long safety profile of gene therapy using retroviral (non-replicating) vectors (nRCR), or cell products in 127 subjects with hemophilia, human immunodeficiency virus (HIV), or cancer, previously treated with such gene therapy. We assessed the occurrence of serious adverse events (SAEs), deaths and presence of replication competent retrovirus (RCR). A total of 23 subjects remained until the data cut-off date of 31 July 2013 and provided safety information of up to 18 years. Of the 104 subjects who discontinued, the primary reason was loss to follow-up (47.2 %; n = 60). The follow-up period for the 60 subjects lost to follow-up was 7-10 years. A total of 41 subjects experienced at least one SAE, and 15 subjects died. We reviewed SAEs and cause of death (none related to the active therapy), but no evidence was found for safety signals related to new malignancy or neurologic, rheumatological, autoimmune, or hematologic disorder. RCR results were negative, indicating no evidence for in vivo vector persistence. Despite the loss of follow-up, which is the limiting factor in this long-term safety trial, the findings from this long-term follow-up study are encouraging.
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Growth arrest of lung carcinoma cells (A549) by polyacrylate - anchored peroxovanadate by activating Rac1 - NADPH oxidase signalling axis Hydrogen peroxide is often required in sublethal, millimolar concentrations to show its oxidant effects on cells in culture as it is easily destroyed by cellular catalase. Previously, we had shown that diperoxovanadate, a physiologically stable peroxovanadium compound, can substitute H2O2 effectively in peroxidation reactions. We report here that peroxovanadate when anchored to polyacrylic acid (PAPV) becomes a highly potent inhibitor of growth of lung carcinoma cells (A549). The early events associated with PAPV treatment included cytoskeletal modifications, increase in GTPase activity of Rac1, accumulation of the reactive oxygen species, and also increase in phosphorylation of H2AX (γH2AX), a marker of DNA damage. These effects persisted even at 24 h after removal of the compound and culminated in increased levels of p53 and p21 together with growth arrest. The PAPV -mediated growth arrest was significantly abrogated in cells pre-treated with the N-acetylcysteine, Rac1 knocked down by siRNA and DPI an inhibitor of NADPH oxidase. In conclusion, our results show that polyacrylate derivative of peroxovanadate efficiently arrests growth of A549 cancerous cells by activating the axis of Rac1 - NADPH oxidase leading to oxidative stress and DNA damage.
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Fractal analysis of the ischemic transition region in chronic ischemic heart disease using magnetic resonance imaging To introduce a novel hypothesis and method to characterise pathomechanisms underlying myocardial ischemia in chronic ischemic heart disease by local fractal analysis (FA) of the ischemic myocardial transition region in perfusion imaging. Vascular mechanisms to compensate ischemia are regulated at various vascular scales with their superimposed perfusion pattern being hypothetically self-similar. Dedicated FA software (" FraktalWandler ") has been developed. Fractal dimensions during first-pass (FDfirst-pass) and recirculation (FDrecirculation) are hypothesised to indicate the predominating pathomechanism and ischemic severity, respectively. Twenty-six patients with evidence of myocardial ischemia in 108 ischemic myocardial segments on magnetic resonance imaging (MRI) were analysed. The 40th and 60th percentiles of FDfirst-pass were used for pathomechanical classification, assigning lesions with FDfirst-pass ≤ 2.335 to predominating coronary microvascular dysfunction (CMD) and ≥2.387 to predominating coronary artery disease (CAD). Optimal classification point in ROC analysis was FDfirst-pass = 2.358. FDrecirculation correlated moderately with per cent diameter stenosis in invasive coronary angiography in lesions classified CAD (r = 0.472, p = 0.001) but not CMD (r = 0.082, p = 0.600). The ischemic transition region may provide information on pathomechanical composition and severity of myocardial ischemia. FA of this region is feasible and may improve diagnosis compared to traditional noninvasive myocardial perfusion analysis. • A novel hypothesis and method is introduced to pathophysiologically characterise myocardial ischemia. • The ischemic transition region appears a meaningful diagnostic target in perfusion imaging. • Fractal analysis may characterise pathomechanical composition and severity of myocardial ischemia.
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Detailed Morphology of All Life Stages of the Agave Red Worm, Comadia redtenbacheri (Hammerschmidt) (Lepidoptera: Cossidae) The agave red worm, Comadia redtenbacheri (Hammerschmidt), is an important source of food and income in Mexico. Despite its importance, several aspects of its biology, morphology, and behavior remain poorly studied. In this work, we describe and illustrate the morphology of all the life stages that may aid in understanding certain aspects of its biology. To obtain all life stages, last instar larvae were collected from agave plants and allowed to pupate; after the adults emerged, they were allowed to mate and oviposit. The frenulum is longer in males; epiphysis I is longer in females than in males; the abdomen bears two types of tubercles of unknown function. Eggs present a reticulate chorion; primary rosette cells are highly variable in shape; the micropylar formula is (10-14): (12-13). First instar larvae are white, becoming red as they develop; L3 in the prothorax is subprimary; the SV setal group in A1 is comprised of only SV1 on first instar larvae; last instars have several secondary setae. Pupae are adecticous and obtect; there are rows of spines on the dorsum of the abdomen. The biological significance of some of the findings is discussed.
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Scald burn, a preventable injury: Analysis of 4306 patients from a major tertiary care center Scalds have distinct epidemiological and predisposing risk factors amongst all types of burns. Though scald affects all age groups, the brunt falls on the minor age groups. It may result in major physical disabilities and significant loss of school years. Apart from the economic burden on family, major scald burn may compromise overall development of the affected children. Most of the scald injuries occur in domestic settings and are preventable. Despite improvement in living conditions, the incidence of scald burn has failed to decline. Our aim was to study the detailed epidemiology and severity of scald burn amongst all age groups. A retrospective study was carried out from the records of all burn patients who attended a tertiary burn care center from January 2013 and December 2014. Data of the patients with scald injury was segregated and analyzed using Microsoft excel spreadsheet. 10,175 burn patients attended the burn casualty during the study period, of which 42.3% had sustained scald. 56.85% of patients were under 15 years of age with preschool children (36.4%) being the prime victims of scald. The % TBSA involved is also relatively larger in children. Scald follows definite seasonal variation peaking in winters. 36.8% patients arrived to the hospital without any first aid. 74.2% of patients reported to casualty with in 24hours after sustaining scald injury. The median time interval between injury and reporting to casualty was 3hours 30 minutes. This study concludes that the scald is injury of all age groups, though majority of them are children. The first aid is not given to large number of patients and late reporting is quite common. These are the factors which may affect the course of scald burn. Spreading public awareness regarding safe household practises and educating them for proper first aid management after scald may have significant impact on the burden of care and outcome.
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Epigenotype, genotype, and phenotype analysis of patients in Taiwan with Beckwith-Wiedemann syndrome Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder predisposing to tumorigenesis that results from abnormal expression or function of imprinted genes of chromosome 11p15.5. Forty-seven patients in Taiwan with clinical suspicion of BWS were referred for diagnostic testing based on methylation profiling of H19 -associated imprinting center (IC) 1 and KCNQ1OT1 -associated IC2 using high-resolution melting analysis, multiplex ligation-dependent probe amplification, or high-resolution quantitative methylation profiling. Twenty-eight patients received a clinical diagnosis of BWS (the presence of 3 major features or 2 major features and at least 1 minor feature), 18 had suspected BWS (the presence of at least 1 major feature), and 1 had isolated Wilms' tumor. Nineteen patients were identified with IC2 hypomethylation (including 1 with isolated Wilms' tumor), 1 with IC1 hypermethylation, 2 with paternal uniparental disomy, and 1 with CDKN1C mutation. Several clinical features were found to be statistically different (P<0.05) between the 2 groups- clinical diagnosis of BWS (n=28) or suspected BWS (n=18)-including macroglossia, pre- or postnatal gigantism, abdominal wall defect, ear creases, facial nevus flammeus, BWS score, and the molecular diagnosis rate. Molecular lesion was detected in 81% of patients with the presence of three major features, compared with 33% and 28% of those with two or one major feature, respectively. The mean BWS score was 5.6 for 19 subjects with "IC2 hypomethylation ", compared with 3.8 for 2 subjects with pUPD. The BWS score of one subject with CDKN1C mutation and one with IC1 hypermethylation was 6 and 7, respectively. The BWS score was positively correlated with the molecular diagnosis rate (P<0.01). The BWS database of epigenotype, genotype, and phenotype is expected to promote better genetic counseling and medical care of these patients.
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Assessing Commercially Available Personal Health Records for Home Health: Recommendations for Design Home health nurses and clients experience unmet information needs when transitioning from hospital to home health. Personal health records (PHRs) support consumer -centered information management activities. Previous work has assessed PHRs associated with healthcare providers, but these systems leave home health nurses unable to access necessary information. To evaluate the ability of publically available PHRs to accept, manage, and share information from a home health case study. Two researchers accessed the publically available PHRs on myPHR.com, and attempted to enter, manage, and share the case study data. We qualitatively described the PHR features, and identified gaps between the case study information and PHR functionality. Eighteen PHRs were identified in our initial search. Seven systems met our inclusion criteria, and are included in this review. The PHRs were able to accept basic medical information. Gaps occurred when entering, managing, and/or sharing data from the acute care and home health episodes. The PHRs that were reviewed were unable to effectively manage the case study information. Therefore, increasing consumer health literacy through these systems may be difficult. The PHRs that we reviewed were also unable to electronically share their data. The gap between the existing functionality and the information needs from the case study may make these PHRs difficult to use for home health environments. Additional work is needed to increase the functionality of the PHR systems to better fit the data needs of home health clients.
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A Web-based Alternative Non-animal Method Database for Safety Cosmetic Evaluations Animal testing was used traditionally in the cosmetics industry to confirm product safety, but has begun to be banned; alternative methods to replace animal experiments are either in development, or are being validated, worldwide. Research data related to test substances are critical for developing novel alternative tests. Moreover, safety information on cosmetic materials has neither been collected in a database nor shared among researchers. Therefore, it is imperative to build and share a database of safety information on toxicological mechanisms and pathways collected through in vivo, in vitro, and in silico methods. We developed the CAMSEC database (named after the research team; the Consortium of Alternative Methods for Safety Evaluation of Cosmetics) to fulfill this purpose. On the same website, our aim is to provide updates on current alternative research methods in Korea. The database will not be used directly to conduct safety evaluations, but researchers or regulatory individuals can use it to facilitate their work in formulating safety evaluations for cosmetic materials. We hope this database will help establish new alternative research methods to conduct efficient safety evaluations of cosmetic materials.
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Update on the Role of Cardiac Magnetic Resonance in Acquired Nonischemic Cardiomyopathies Cardiomyopathies refer to a variety of myocardial disorders without underlying coronary artery disease, valvular heart disease, hypertension, or congenital heart disease. Several imaging modalities are available, but cardiac magnetic resonance (CMR) has now established itself as a crucial imaging technique in the evaluation of several cardiomyopathies. It not only provides comprehensive information on structure and function, but also can perform tissue characterization, which helps in establishing the etiology of cardiomyopathy. CMR is also useful in establishing the diagnosis, providing guidance for endomyocardial biopsy, accurate quantification of function, volumes, and fibrosis, prognostic determination, risk stratification, and monitoring response to therapy. In this article, we review the current role of CMR in the evaluation of several acquired nonischemic cardiomyopathies, particularly focusing on recent advances in knowledge. We also discuss in detail a select group of common acquired nonischemic cardiomyopathies.
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Modern Image-Guided Intensity-Modulated Radiotherapy for Oropharynx Cancer and Severe Late Toxic Effects: Implications for Clinical Trial Design Late toxic effects are common after definitive radiotherapy and chemoradiotherapy for oropharynx cancer and are considered a significant contributor to decreased quality of life for survivors. The incidence of severe late toxic effects may be reduced by modern narrow-margin image-guided intensity-modulated radiotherapy (IG-IMRT), current supportive care improvements, and the changing epidemiology of oropharynx cancer. Assess the incidence of severe late toxic effects after modern definitive non-operative treatment for oropharynx cancer. For this single-institution retrospective review, 156 patients with stage I-IVB squamous cell carcinoma of the oropharynx treated between April 2009 and February 2015 at a tertiary-referral academic multidisciplinary head and neck practice were recruited. Definitive narrow-margin IG-IMRT to a dose of 66 Gy (to convert milligray to rad, multiply by 0.1) or higher with or without concurrent cisplatin. The primary outcome was the prospectively collected 2- year cumulative incidence of severe late toxic effects (Common Terminology Criteria for Adverse Events grade 3 or higher) occurring 3 months or more after radiotherapy. Toxic effect end points investigated included esophageal stricture requiring dilation, aspiration pneumonia hospitalization, vocal dysfunction, delayed feeding tube insertions, and osteoradionecrosis. Feeding tube dependence at 1 year was also considered a severe late toxic effect. Secondary outcomes collected include physician -reported grade 2 or higher neck fibrosis and xerostomia. The competing risks of recurrence and death were accounted for using the Gray method. One-hundred fifty-six patients (median [range] age, 58 [37-96] years) were identified; 130 patients (83%) were HPV positive. Concurrent cisplatin was delivered in 131 patients (84%) and 5 patients (3%) underwent an adjuvant neck dissection. The median (range) follow-up for survivors was 22 (4-73) months from diagnosis. The projected 2- year locoregional control was 93% (95% CI, 88.4%-97.6%) and overall survival was 88% (95% CI, 82.2%-94.0%). Thirty-eight patients (23%) required a feeding tube during treatment. The cumulative incidence of severe late toxic effects adjusted for competing risks at 2- year posttreatment was 2.3% (95% CI, 0%-5.6%). One patient required free-flap reconstruction for grade 3 osteoradionecrosis at 47 months. At 1 year, 2 patients (1%) experienced grade 2 neck fibrosis and 38 patients (23%) experienced grade 2 xerostomia. These results suggest that severe late toxic effects after modern definitive IG-IMRT, with or without cisplatin, for oropharynx cancer is likely uncommon. The importance of late toxic effect reduction in current and future investigational strategies, including clinical trials, should be considered.
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Axially Chiral Dimeric Naphthalene and Naphthoquinone Metabolites, from Root Cultures of the West African Liana Triphyophyllum peltatum Root cultures of the West African liana Triphyophyllum peltatum were initiated from stem explants of in vitro cultivated shoots. From these organ cultures, three new binaphthalenes, one binaphthoquinone, and two (bi)naphthalene glucosides were isolated, with substitution patterns related to those of the naphthylisoquinoline alkaloids, which are the "normal" main metabolites of T. peltatum. The structures of the diglucoside dioncoquinoside A (1) and of the axially chiral biaryls triphyoquinols A1 (3), A2 (4), and B (5), triphyoquinoside A (6), and triphyoquinone A (7) were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and by application of electronic circular dichroism (ECD) spectroscopy in combination with the exciton chirality method and quantum-chemical ECD calculations. The root cultures likewise produced the known alkaloids dioncophylline A (8), 5'-O-demethyldioncophylline A (9), dioncopeltine A (10), habropetaline A (11), and 5'-O-methyldioncophylline D (12a/b), the naphthalene glucoside plumbaside A (2), and the naphthoquinones plumbagin (13), droserone (14), and 8-hydroxydroserone (15).
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Tubular, lactating, and ductal adenomas are devoid of MED12 Exon2 mutations, and ductal adenomas show recurrent mutations in GNAS and the PI3K-AKT pathway Adenomas of the breast are rare benign tumors although single cases with malignant behavior have been reported. However, the genetic basis of these tumors is unknown. Employing targeted next generation sequencing of 50 cancer-related genes as well as Sanger sequencing, we profiled a cohort of 18 mammary adenomas comprising 9 ductal, 6 tubular, and 3 lactating adenoma. Missense mutations were detected in 8 of the 18 cases (44%). Specifically, five (56%) ductal adenomas and three (50%) tubular adenomas harbored mutated genes. No mutations were detected in lactating adenomas. Three of the nine ductal adenomas showed mutant AKT1 (p.E17K) with two of them harboring an additional GNAS mutation (p.R201C). One case had mutant PIK3CA (p.H1047R) and another case a mutation in GNAS (p.R201C). The three cases of mutated tubular adenomas showed mutations in either MET or FGFR3. Of note, we did not detect copy number changes and none of the cases including tubular adenomas had mutations in exon 2 of MED12. Our results suggest that ductal adenomas are related to papillomas of the breast and screening for mutations in exon 2 of MED12 might help to facilitate differential diagnosis between tubular adenoma and fibroadenoma in difficult cases. Lastly, our data exemplarily demonstrate that mutations in cancer-related genes per se do not indicate malignancy but occur in benign tumors. © 2016 Wiley Periodicals, Inc.
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EctD -mediated biotransformation of the chemical chaperone ectoine into hydroxyectoine and its mechanosensitive channel -independent excretion Ectoine and its derivative 5-hydroxyectoine are cytoprotectants widely synthesized by microorganisms as a defense against the detrimental effects of high osmolarity on cellular physiology and growth. Both ectoines possess the ability to preserve the functionality of proteins, macromolecular complexes, and even entire cells, attributes that led to their description as chemical chaperones. As a consequence, there is growing interest in using ectoines for biotechnological purposes, in skin care, and in medical applications. 5-Hydroxyectoine is synthesized from ectoine through a region- and stereo-specific hydroxylation reaction mediated by the EctD enzyme, a member of the non-heme-containing iron(II) and 2-oxoglutarate -dependent dioxygenases. This chemical modification endows the newly formed 5-hydroxyectoine with either superior or different stress- protecting and stabilizing properties. Microorganisms producing 5-hydroxyectoine typically contain a mixture of both ectoines. We aimed to establish a recombinant microbial cell factory where 5-hydroxyectoine is (i) produced in highly purified form, and (ii) secreted into the growth medium. We used an Escherichia coli strain (FF4169) defective in the synthesis of the osmostress protectant trehalose as the chassis for our recombinant cell factory. We expressed in this strain a plasmid -encoded ectD gene from Pseudomonas stutzeri A1501 under the control of the anhydrotetracycline -inducible tet promoter. We chose the ectoine hydroxylase from P. stutzeri A1501 for our cell factory after a careful comparison of the in vivo performance of seven different EctD proteins. In the final set-up of the cell factory, ectoine was provided to salt-stressed cultures of strain FF4169 (pMP41; ectD (+)). Ectoine was imported into the cells via the osmotically inducible ProP and ProU transport systems, intracellularly converted to 5-hydroxyectoine, which was then almost quantitatively secreted into the growth medium. Experiments with an E. coli mutant lacking all currently known mechanosensitive channels (MscL, MscS, MscK, MscM) revealed that the release of 5-hydroxyectoine under osmotic steady-state conditions occurred independently of these microbial safety valves. In shake-flask experiments, 2.13 g l(-1) ectoine (15 mM) was completely converted into 5-hydroxyectoine within 24 h. We describe here a recombinant E. coli cell factory for the production and secretion of the chemical chaperone 5-hydroxyectoine free from contaminating ectoine.
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Remote monitoring of patients with cardiac implantable electronic devices: a Southeast Asian, single-centre pilot study Remote monitoring of cardiac implantable electronic devices (CIED) has been shown to improve patient safety and reduce in-office visits. We report our experience with remote monitoring via the Medtronic CareLink(®) network. Patients were followed up for six months with scheduled monthly remote monitoring transmissions in addition to routine in-office checks. The efficacy of remote monitoring was evaluated by recording compliance to transmissions, number of device alerts requiring intervention and time from transmission to review. Questionnaires were administered to evaluate the experiences of patients, physicians and medical technicians. A total of 57 patients were enrolled; 16 (28.1%) had permanent pacemakers, 34 (59.6%) had implantable cardioverter defibrillators and 7 (12.3%) had cardiac resynchronisation therapy defibrillators. Overall, of 334 remote transmissions scheduled, 73.7% were on time, 14.5% were overdue and 11.8% were missed. 84.6% of wireless transmissions were on time, compared to 53.8% of non-wireless transmissions. Among all transmissions, 4.4% contained alerts for which physicians were informed and only 1.8% required intervention. 98.6% of remote transmissions were reviewed by the second working day. 73.2% of patients preferred remote monitoring. Physicians agreed that remote transmissions provided information equivalent to in-office checks 97.1% of the time. 77.8% of medical technicians felt that remote monitoring would help the hospital improve patient management. No adverse events were reported. Remote monitoring of CIED is safe and feasible. It has possible benefits to patient safety through earlier detection of arrhythmias or device malfunction, permitting earlier intervention. Wireless remote monitoring, in particular, may improve compliance to device monitoring. Patients may prefer remote monitoring due to possible improvements in quality of life.
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c-Src Suppresses Dendritic Cell Antitumor Activity via T Cell Ig and Mucin Protein-3 Receptor The enhanced expression of T cell Ig and mucin protein-3 (TIM-3) on tumor - associated dendritic cells (DCs) attenuates antitumor effects of DNA vaccines. To identify a potential target (or targets) for reducing TIM-3 expression on tumor - associated DCs, we explored the molecular mechanisms regulating TIM-3 expression. In this study, we have identified a novel signaling pathway (c-Src → Bruton's tyrosine kinase → transcription factors Ets1, Ets2, USF1, and USF2) necessary for TIM-3 upregulation on DCs. Both IL-10 and TGF-β, which are produced in the tumor microenvironment, upregulated TIM-3 expression on DCs via this pathway. Suppressed expression of c-Src or downstream Bruton's tyrosine kinase, Ets1, Ets2, USF1, or USF2 blocked IL-10- and TGF-β - induced TIM-3 upregulation on DCs. Notably, in vivo knockdown of c-Src in mice reduced TIM-3 expression on tumor - associated DCs. Furthermore, adoptive transfer of c-Src - silenced DCs in mouse tumors enhanced the in vivo antitumor effects of immunostimulatory CpG DNA; however, TIM-3 overexpression in c-Src - silenced DCs blocked this effect. Collectively, our data reveal the molecular mechanism regulating TIM-3 expression in DCs and identify c-Src as a target for improving the efficacy of nucleic acid -mediated anticancer therapy.
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Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight / obese men Gut microbial -derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men. In this randomized, double-blind crossover trial, six overweight / obese men [body mass index (BMI) 25-35 kg/m(2)] underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions. A feeding catheter was endoscopically positioned at the beginning of each period and remained in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were repeatedly collected for 2 h during fasting and postprandial conditions. Distal colonic 180 mmol/l acetate infusions increased fasting fat oxidation (1.78±0.28 compared with -0.78±0.89 g fat 2 h(-1), P=0.015), fasting peptide YY (PYY, P=0.01) and postprandial glucose and insulin concentrations (P<0.05), and tended to increase fasting plasma acetate (P=0.069) compared with placebo. Distal 100 mmol/l acetate administration tended to decrease fasting tumour necrosis factor-α (TNF-α; P=0.067) compared with placebo. In contrast, proximal colonic acetate infusions showed no effects on substrate metabolism, circulating hormones or inflammatory markers. In conclusion distal colonic acetate infusions affected whole-body substrate metabolism, with a pronounced increase in fasting fat oxidation and plasma PYY. Modulating colonic acetate may be a nutritional target to treat or prevent metabolic disorders.
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Multiplexing Fluorescence Anisotropy Using Frequency Encoding In this report, a method to multiplex fluorescence anisotropy measurements is described using frequency encoding. As a demonstration of the method, simultaneous competitive immunoassays for insulin and glucagon were performed by measuring the ratio of bound and free Cy5-insulin and FITC-glucagon in the presence of their respective antibodies. A vertically polarized 635 nm laser was pulsed at 73 Hz and used to excite Cy5-insulin, while a vertically polarized 488 nm laser pulsed at 137 Hz excited FITC-glucagon. The total emission was split into parallel and perpendicular polarizations and collected onto separate photomultiplier tubes. The signals from each channel were demodulated using a fast Fourier transform, resolving the contributions from each fluorophore. Anisotropy calculations were carried out using the magnitude of the peaks in the frequency domain. The method produced the expected shape of the calibration curves with limits of detection of 0.6 and 5 nM for insulin and glucagon, respectively. This methodology could readily be expanded to other biological systems and further multiplexed to monitor increased numbers of analytes.
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Foreign-body ingestion in Egyptian children: a 10- year experience of endoscopic intervention in a tertiary hospital There was a lack of data about foreign body (FB) ingestion among Middle-East children. We conducted a retrospective analysis of FB ingestion among Egyptian children and determined the predictors that affect the occurrence of complications. This retrospective study was carried out on 1546 patients ' ≤ 13 years old, presented with FB ingestion and were in need of endoscopic removal of FB. There were 711 males (46%) and 835 females (54%) (mean age 4.56 ±2.26 years). Symptoms were present in 1414 patients (91.5%) while complications were present in 137 patients (8.9%). There was a significant difference between complicated and non-complicated cases as regard higher age group, duration of impaction, site of impaction and type of FB (p= 0.001, 0.001, 0.001 and <0.001, respectively). The highest rate of complications was observed in FB impacted in duodenum and those without symptoms while symptomatic cases and impaction in upper esophagus were associated with higher success rate of removal.
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Learning in Complex Environments: The Effects of Background Speech on Early Word Learning Although most studies of language learning take place in quiet laboratory settings, everyday language learning occurs under noisy conditions. The current research investigated the effects of background speech on word learning. Both younger (22- to 24-month-olds; n = 40) and older (28- to 30-month-olds; n = 40) toddlers successfully learned novel label - object pairings when target speech was 10 dB louder than background speech but not when the signal-to-noise ratio (SNR) was 5 dB. Toddlers (28- to 30-month-olds; n = 26) successfully learned novel words with a 5-dB SNR when they initially heard the labels embedded in fluent speech without background noise, before they were mapped to objects. The results point to both challenges and protective factors that may impact language learning in complex auditory environments.
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Content of cardiolipin of the membrane and sensitivity to cationic surfactants in Pseudomonas putida To establish the role of cardiolipin (CL) of the membrane in response to the presence of tetradecyltrimethylammonium in Pseudomonas putida A (ATCC 12633). Two ORFs of Ps. putida A (ATCC 12633), which in Ps. putida KT2440 encode the putative CL synthase genes cls and cls2, were cloned, sequenced and mutated. Only the double mutant lacking cls and cls2 showed a reduction of the CL content, 83% lower than the amount produced by the wild-type. Accompanying this change was a 40% decrease in the content of unsaturated fatty acid. Consequently, the membrane of the mutant was more rigid than the one of the parental strain, as observed using fluorescence polarization techniques. The mutant strain showed reduced viability in the presence of tetradecyltrimethylammonium. The incorporation of exogenous CL into its membrane relieved sensitivity to the cationic detergent. Pseudomonas Putida cells with low levels of CL die in the presence of tetradecyltrimethylammonium, because they cannot counter the fluidizing effect of the cationic surfactant. The modification in the membrane phospholipids composition allows knowing the adaptation strategy of Ps. putida when these bacteria are exposed to cationic surfactant.
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NADPH oxidase-produced superoxide mediated a 50-Hz magnetic field -induced epidermal growth factor receptor clustering A 50-Hz magnetic field (MF) was found to induce epidermal growth factor receptor (EGFR) clustering in our previous study. The aim of this work was to investigate the molecular mechanisms that mediated MF -induced EGFR clustering. Human amniotic epithelial (FL) cells were exposed to a 50-Hz MF. Total reactive oxygen species (ROS), cytoplasmic and mitochondrial superoxide production were detected by DCFH-DA, DHE and MitoSOX, respectively. EGFR clustering was analyzed using confocal microscopy after indirect immunofluorescence staining. Results showed that exposing FL cells to MF at intensity higher than 0.2 mT for 15 min enhanced total ROS production. Additionally, enhanced total ROS and cytoplasmic superoxide production were observed after exposing cells to MF at 0.4 mT for 5, 15, or 30 min, while mitochondrial superoxide production for 15 or 30 min. Pretreatment with Nox inhibitor, DPI, effectively inhibited MF -induced cytoplasmic superoxide production and subsequent EGFR clustering while mitochondrial superoxide production was not affected. Nox-produced superoxide mediated a 50- Hz magnetic field -induced EGFR clustering.
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Biosynthetic Gene Cluster for Surugamide A Encompasses an Unrelated Decapeptide, Surugamide F Genome mining is a powerful method for finding novel secondary metabolites. In our study on the biosynthetic gene cluster for the cyclic octapeptides surugamides A-E (inhibitors of cathepsin B), we found a putative gene cluster consisting of four successive non-ribosomal peptide synthetase (NRPS) genes, surA, surB, surC, and surD. Prediction of amino acid sequence based on the NRPSs and gene inactivation revealed that surugamides A-E are produced by two NRPS genes, surA and surD, which were separated by two NRPS genes, surB and surC. The latter genes are responsible for the biosynthesis of an unrelated peptide, surugamide F. The pattern of intercalation observed in the sur genes is unprecedented. The structure of surugamide F, a linear decapeptide containing one 3-amino-2-methylpropionic acid (AMPA) residue, was determined by spectroscopic methods and was confirmed by solid-phase peptide synthesis.
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Pain and alcohol consumption among older adults: findings from the World Health Organization Study on global AGEing and adult health, Wave 1 To investigate cross-sectional associations between self-reported recent pain and alcohol use / abstinence, and previous - day pain and previous - week alcohol consumption in adults aged 50 + in six low - and middle-income countries (LMICs). The WHO Study on global AGEing and adult health (SAGE) Wave 1 (2007-2010) in China, Ghana, India, Mexico, Russia and South Africa is the data source. Prevalence of alcohol use / abstinence is reported by previous - day and previous - month pain. Multinomial logistic regressions (crude and adjusted for sex and country) tested associations between recent pain and alcohol use in the pooled multicountry sample. Across the six SAGE countries, about one-third of respondents reported alcohol use, being highest in Russia (74%) and lowest in India (16%). Holding the effects of sex and country constant, compared with abstainers, people with previous - day pain were more likely to be previous - day or other users. With regard to the quantity and frequency of alcohol use, people with previous - day pain were more likely to be non-heavy drinkers. Overall, we found that, in this population of older adults in six LMICs, recent pain was associated with moderate use of alcohol, although there were differences between countries. The findings provide a platform for country - specific research to better understand bi-directional associations between pain and alcohol in older adults.
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Pregnancy at high altitude in the Andes leads to increased total vessel density in healthy newborns The developing human fetus is able to cope with the physiological reduction in oxygen supply occurring in utero. However, it is not known if microvascularization of the fetus is augmented when pregnancy occurs at high altitude. Fifty-three healthy term newborns in Puno, Peru (3,840 m) were compared with sea - level controls. Pre- and postductal arterial oxygen saturation (SpO2) was determined. Cerebral and calf muscle regional tissue oxygenation was measured using near infrared spectroscopy (NIRS). Skin microcirculation was noninvasively measured using incident dark field imaging. Pre- and postductal SpO2 in Peruvian babies was 88.1 and 88.4%, respectively, which was 10.4 and 9.7% lower than in newborns at sea level (P < 0.001). Cerebral and regional oxygen saturation was significantly lower in the Peruvian newborns (cerebral: 71.0 vs. 74.9%; regional: 68.5 vs. 76.0%, P < 0.001). Transcutaneously measured total vessel density in the Peruvian newborns was 14% higher than that in the newborns born at sea level (29.7 vs. 26.0 mm/mm(2); P ≤ 0.001). This study demonstrates that microvascular vessel density in neonates born to mothers living at high altitude is higher than that in neonates born at sea level.
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Morphological and enzymatic response of the thermotolerant fungus Fomes sp. EUM1 in solid state fermentation under thermal stress Thermotolerance of the fungus Fomes sp. EUM1 was evaluated in solid state fermentation (SSF). This thermotolerant strain improved both hyphal invasiveness (38%) and length (17%) in adverse thermal conditions exceeding 30°C and to a maximum of 40°C. In contrast, hyphal branching decreased by 46% at 45°C. The production of cellulases over corn stover increased 1.6-fold in 30°C culture conditions, xylanases increased 2.8-fold at 40°C, while laccase production improved 2.7-fold at 35°C. Maximum production of lignocellulolytic enzymes was obtained at elevated temperatures in shorter fermentation times (8 to 6 days), although the proteases appeared as a thermal stress response associated with a drop in lignocellulolytic activities. Novel and multiple isoenzymes of xylanase (four bands) and cellulase (six bands) were secreted in the range of 20-150 kDa during growth in adverse temperature conditions. However, only a single laccase isoenzyme (46 kDa) was detected. This is the first report describing the advantages of a thermotolerant white-rot fungus in SSF. These results have important implications for large-scale SSF, where effects of metabolic heat are detrimental to growth and enzyme production, which are severely affected by the formation of high temperature gradients.
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Brood size constrains the development of endothermy in blue tits Altricial birds are unable to maintain body temperature when exposed to low ambient temperatures during the first days after hatching. Thermoregulatory capacity begins to form as postnatal development progresses, and eventually nestlings become homeothermic. Several factors may influence this development at both the level of the individual and the level of the whole brood, but to our knowledge no studies have focused on the effect of brood size per se on the development of endothermy in individual nestlings. We performed cooling experiments on blue tit (Cyanistes caeruleus) nestlings in the field, to study how different experimental brood sizes affected the development of endothermy in individual nestlings and the thermal environment experienced by the whole brood in the nest. Nestlings from all experimental brood sizes showed a decrease in cooling rate as they grew older, but birds from reduced broods showed an earlier onset of endothermy compared with nestlings from enlarged and control broods. This difference manifested during early development and gradually disappeared as nestlings grew older. The thermal environment in the nests differed between treatments during nestling development, such that nest temperature in reduced broods was lower than that in enlarged broods during all days and during nights at the end of the experimental period. We suggest that the development of endothermy in blue tit nestlings is not ontogenetically fixed, but instead may vary according to differences in developmental, nutritional and thermal conditions as determined by brood size.
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Elevated Plasma Level of Interferon-λ1 in Chronic Spontaneous Urticaria: Upregulated Expression in CD8(+) and Epithelial Cells and Induction of Inflammatory Cell Accumulation Interferon- (IFN-) λ1 is regarded as a potent bio-active molecule in innate immunity. However, little is known about its role in chronic spontaneous urticaria (CSU). We therefore investigated expression of IFN-λ1 in CSU, its cellular location, and its influence on inflammatory cell accumulation by using flow cytometry analysis, skin tissue dispersion, immunohistochemical stain, and a mouse peritoneal inflammation model. The results showed that level of IFN-λ1 was 2.0-fold higher in plasma of the patients with CSU than the level in healthy control (HC) subjects. Among leukocytes examined, only CD8(+) T cells expressed more IFN-λ1 in CSU blood. Double labeling immunohistochemical staining revealed that IFN-λ1 (+) inflammatory cells such as mast cells, eosinophils, B cells, neutrophils, and macrophages were mainly located in dermis, whereas epidermis tissue highly expressed IFN-λ1. IFN-λ1 induced a dose-dependent increase in number of eosinophils, lymphocytes, mast cells, macrophages, and neutrophils in the peritoneum of mice at 6 h following injection, which was inhibited by pretreatment of the animals with anti-intercellular adhesion molecule- (ICAM-) 1 and/or anti-L-selectin antibodies. In conclusion, IFN-λ1 is likely to play a role in the pathogenesis of CSU. Blocking IFN-λ1 production may help to reduce the accumulation of inflammatory cells in the involved CSU skin.
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Translating Neurocognitive Models of Auditory-Verbal Hallucinations into Therapy: Using Real-time fMRI - Neurofeedback to Treat Voices Auditory-verbal hallucinations (AVHs) are frequent and disabling symptoms, which can be refractory to conventional psychopharmacological treatment in more than 25% of the cases. Recent advances in brain imaging allow for a better understanding of the neural underpinnings of AVHs. These findings strengthened transdiagnostic neurocognitive models that characterize these frequent and disabling experiences. At the same time, technical improvements in real-time functional magnetic resonance imaging (fMRI) enabled the development of innovative and non-invasive methods with the potential to relieve psychiatric symptoms, such as fMRI -based neurofeedback (fMRI - NF). During fMRI - NF, brain activity is measured and fed back in real time to the participant in order to help subjects to progressively achieve voluntary control over their own neural activity. Precisely defining the target brain area / network(s) appears critical in fMRI - NF protocols. After reviewing the available neurocognitive models for AVHs, we elaborate on how recent findings in the field may help to develop strong a priori strategies for fMRI - NF target localization. The first approach relies on imaging -based " trait markers " (i.e., persistent traits or vulnerability markers that can also be detected in the presymptomatic and remitted phases of AVHs). The goal of such strategies is to target areas that show aberrant activations during AVHs or are known to be involved in compensatory activation (or resilience processes). Brain regions, from which the NF signal is derived, can be based on structural MRI and neurocognitive knowledge, or functional MRI information collected during specific cognitive tasks. Because hallucinations are acute and intrusive symptoms, a second strategy focuses more on " state markers ." In this case, the signal of interest relies on fMRI capture of the neural networks exhibiting increased activity during AVHs occurrences, by means of multivariate pattern recognition methods. The fine-grained activity patterns concomitant to hallucinations can then be fed back to the patients for therapeutic purpose. Considering the potential cost necessary to implement fMRI - NF, proof-of-concept studies are urgently required to define the optimal strategy for application in patients with AVHs. This technique has the potential to establish a new brain imaging -guided psychotherapy for patients that do not respond to conventional treatments and take functional neuroimaging to therapeutic applications.
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The Crystal Structure of the C-Terminal Domain of the Salmonella enterica PduO Protein: An Old Fold with a New Heme-Binding Mode The two-domain protein PduO, involved in 1,2-propanediol utilization in the pathogenic Gram-negative bacterium Salmonella enterica is an ATP: Cob(I)alamin adenosyltransferase, but this is a function of the N-terminal domain alone. The role of its C-terminal domain (PduOC) is, however, unknown. In this study, comparative growth assays with a set of Salmonella mutant strains showed that this domain is necessary for effective in vivo catabolism of 1,2-propanediol. It was also shown that isolated, recombinantly-expressed PduOC binds heme in vivo. The structure of PduOC co-crystallized with heme was solved (1.9 Å resolution) showing an octameric assembly with four heme moieities. The four heme groups are highly solvent-exposed and the heme iron is hexa-coordinated with bis-His ligation by histidines from different monomers. Static light scattering confirmed the octameric assembly in solution, but a mutation of the heme - coordinating histidine caused dissociation into dimers. Isothermal titration calorimetry using the PduOC apoprotein showed strong heme binding (K d = 1.6 × 10(-7) M). Biochemical experiments showed that the absence of the C-terminal domain in PduO did not affect adenosyltransferase activity in vitro. The evidence suggests that PduOC: heme plays an important role in the set of cobalamin transformations required for effective catabolism of 1,2-propanediol. Salmonella PduO is one of the rare proteins which binds the redox-active metabolites heme and cobalamin, and the heme-binding mode of the C-terminal domain differs from that in other members of this protein family.
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The Therapeutic Effect of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis Aim. To assess the efficacy of berberine in the treatment of nonalcoholic fatty liver disease through meta-analysis. Method. We searched Embase, Pubmed, Cochrane Library, and so forth, until March 2016 for randomized controlled trials using berberine to treat NAFLD. Result. Six randomized controlled trials involving 501 patients were included in this study. The results showed that the efficacy of reducing TC, LDL, ALT, 2hPG, and HbA1c in NAFLD patients of the berberine group were significantly higher than that of control group. The subgroup analyses on TG, AST, and FBG indicated that treatment combined with berberine decreased TG level in NAFLD patients significantly. Compared with other drugs, berberine alone decreased TG level in NAFLD patients significantly. We also conducted a descriptive analysis on insulin resistance and radiography results that berberine can improve NAFLD patients ' insulin resistance and fatty liver. Conclusion. According to analysis result, berberine has positive efficacy on blood lipids, blood glucose, liver function, insulin resistance, and fatty liver condition of NAFLD patients. However, due to the limitation of number and quality of trials included, more clinical randomized controlled trials with high quality are needed for further verification of the efficacy of berberine on NAFLD patients.
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Perfusion Angiography in Acute Ischemic Stroke Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and T max, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely.
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A new marker for breast cancer diagnosis, human epididymis protein 4: A preliminary study Breast cancer is the most frequently diagnosed cancer type in women. Tumor markers have been widely used for assessing the treatment response and early diagnosis of recurrence. Human epididymis protein 4 (HE4) is expressed in ductal carcinoma of the breast tissue; however, its serum levels and their diagnostic and prognostic potential in breast cancer have not been investigated, which was therefore the aim of the present study. The serum levels of HE4 were determined in 36 breast cancer patients, 11 ovarian cancer patients and 16 healthy volunteers. The association between clinicopathological characteristics of breast cancer and serum HE4 levels was investigated. A significant difference in the median serum levels of HE4 was identified between breast cancer patients, ovarian cancer patients and healthy volunteers (P=0.013). The cutoff value for the prediction of breast cancer was determined at >13.24 pmol/l for HE4, with a sensitivity of 61.11%, specificity of 68.75%, positive predictive value of 81.48%, negative predictive value of 44.0% and accuracy of 63.46%. Furthermore, a positive correlation between the serum levels of HE4 and cancer antigen 15-3 was determined (r=0.399, P=0.026). To the best of our knowledge, the present study was the first to determine the diagnostic value of serum HE4 for breast cancer. A significant elevation of serum HE4 levels in patients with breast cancer compared with that in healthy controls was identified. HE4 may serve as a novel biomarker for the diagnosis of breast cancer.