title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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A wire transposition technique for recanalization of chronic complex central venous occlusions. | A minimal-invasive interventional technique for recanalization of complex chronic central venous total occlusions is described to overcome difficulties in case of failure of common approaches. We present a patient with a central venous occlusion that caused severe venous congestion of her upper extremity and significant impairment of her forearm hemodialysis shunt. Since the usual transbrachial and transfemoral attempts for recanalization of occluded right subclavian, brachiocephalic, superior vena cava, and proximal internal jugular veins (IJV) failed, the approach was changed to a transjugular access. Only the IJV and subclavian vein occlusions were passed from transjugular. The key procedure was the switch of a jugular-brachial wire to a femoral-brachial setting. The wire transposition was achieved by snaring the looped stiff end of the jugular-brachial wire outside the jugular sheath from the opposite femoral access. Different approaches should be considered for the recanalization of challenging central venous occlusions. After failed attempts via common access sites, a guidewire transposition maneuver using a combined approach may be particularly helpful for safe and effective endovascular treatment of complex situations. | 25,178,813 | [
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Stimulation of oxidative phosphorylation by calcium in cardiac mitochondria is not influenced by cAMP and PKA activity. | Cardiac oxidative ATP generation is finely tuned to match several-fold increases in energy demand. Calcium has been proposed to play a role in the activation of ATP production via PKA phosphorylation in response to intramitochondrial cAMP generation. We evaluated the effect of cAMP, its membrane permeable analogs (dibutyryl-cAMP, 8-bromo-cAMP), and the PKA inhibitor H89 on respiration of isolated pig heart mitochondria. cAMP analogs did not stimulate State 3 respiration of Ca2 +-depleted mitochondria (82.2 ± 3.6% of control), in contrast to the 2-fold activation induced by 0.95 μM free Ca2 +, which was unaffected by H89. Using fluorescence and integrating sphere spectroscopy, we determined that Ca2 + increased the reduction of NADH (8%), and of cytochromes bH (3%), c1 (3%), c (4%), and a (2%), together with a doubling of conductances for Complex I + III and Complex IV. None of these changes were induced by cAMP analogs nor abolished by H89. In Ca2 +-undepleted mitochondria, we observed only slight changes in State 3 respiration rates upon addition of 50 μM cAMP (85 ± 9.9%), dibutyryl-cAMP (80.1 ± 5.2%), 8-bromo-cAMP (88.6 ± 3.3%), or 1 μM H89 (89.7 ± 19.9%) with respect to controls. Similar results were obtained when measuring respiration in heart homogenates. Addition of exogenous PKA with dibutyryl-cAMP or the constitutively active catalytic subunit of PKA to isolated mitochondria decreased State 3 respiration by only 5–15%. These functional studies suggest that alterations in mitochondrial cAMP and PKA activity do not contribute significantly to the acute Ca2 + stimulation of oxidative phosphorylation | 25,178,840 | [
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Disability in post-earthquake Haiti: prevalence and inequality in access to services. | To assess the prevalence of disability and service needs in post-earthquake Haiti, and to compare the inclusion and living conditions of people with disabilities to those without disabilities. A population-based prevalence survey of disability was undertaken in 2012 in Port-au-Prince region, which was at the centre of the earthquake in 2010. Sixty clusters of 50 people aged 5 + years were selected with probability proportionate to size sampling and screened for disability (Washington Group short set questionnaire). A case-control study was undertaken, nested within the survey, matching cases to controls by age, gender and cluster. There was additional case finding to identify further children with disabilities. Information was collected on: socioeconomic status, education, livelihood, health, activities, participation and barriers. The prevalence of disability was 4.1% (3.4-4.7%) across 3132 eligible individuals. The earthquake was the second leading cause of disability. Disability was more common with increasing age, but unrelated to poverty. Large gaps existed in access of services for people with disabilities. Adults with disabilities were less likely to be literate or work and more likely to visit health services than adults without disabilities. Children with disabilities were less likely to be currently enrolled at school compared to controls. Children and adults with disabilities reported more activity limitations and participation restriction. Further focus is needed to improve inclusion of people with disabilities in post-earthquake Haiti to ensure that their rights are fulfilled. Almost one in six households in this region of Haiti included a person with a disability, and the earthquake was the second leading cause of disability. Fewer than half of people who reported needing medical rehabilitation had received this service. The leading reported barriers to the uptake of health services included financial constraints (50%) and difficulties with transport (40%). People with disabilities did not participate equally in education or employment and had poorer access to health care. | 25,178,862 | [
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Why wait? The effect of wait-times on subsequent help-seeking among families looking for children's mental health services. | Placement on a wait-list may increase families' help-seeking efforts, leading them to contact more than one children's mental health (MH) agency/professional. Two issues were examined in the current study: 1) Does time on a wait-list for families impact the time to contact a new agency for children's MH services? 2) What are the effects of predisposing (e.g., child age), need (e.g., child psychopathology), and enabling/system-level factors (e.g., parent treatment history) on the length of time parents wait before they contact a new agency for help with their child's MH problems? A total of 273 families seeking help for their child (64% boys, M = 10.7 years old, SD = 3.3) were asked about their contact with MH agencies/professionals during the previous year. Survival analyses, modeling time from initial wait-list placement to when a new agency was contacted, were conducted separately for families who did (n = 114), and those who did not (n = 159), receive help prior to contacting a new agency. Almost half of wait-listed families contacted a new agency by the end of the study period. Longer wait-time was associated with a greater likelihood of seeking help at a second agency with 25% of families contacting a new agency within the first month of being wait-listed. Parents with previous treatment experience and families living in areas with more agencies contacted a new agency sooner. Subsequent help-seeking behaviour suggests parents' intolerance for lengthy treatment delays may result in disorganized pathways to care. These findings suggest a highly fragmented service delivery system. | 25,178,864 | [
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Carnosic acid induces autophagic cell death through inhibition of the Akt/mTOR pathway in human hepatoma cells. | The therapeutic goal of cancer treatment is now geared towards triggering tumour-selective cell death with autophagic cell death being required for the chemotherapy of apoptosis-resistant cancer. In this study, Carnosic acid (CA), a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), significantly induced autophagic cell death in HepG2 cells. Ca treatment caused the formation of autophagic vacuoles produced an increasing ratio of LC3-II to LC3-I in a time- and dose-dependent manner but had no effect on the levels of autophagy-related protein ATG6 and ATG13 expression. Autophagy inhibitors, 3-methyladenine (3-MA), chloroquine and bafilomycin A1, or ATG genes silencing in HepG2 cells significantly inhibited CA-induced autophagic cell death. The CA treatment decreased the levels of phosphorylated Akt and mTOR without any effects on PI3K or PTEN. Most importantly, overexpression of Akt and knockdown of PTEN attenuated autophagy induction in CA-treated cells. Taken together, our results indicated that CA induced autophagic cell death through inhibition of the Akt/mTOR pathway in human hepatoma cells. These findings suggest that CA has a great potential for the treatment of hepatoma via autophagic induction. | 25,178,877 | [
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Chronic cough: a herald symptom of thoracic aortic aneurysm in a patient with a bicuspid aortic valve. | Chronic cough has a wide differential, of which thoracic aortic aneurysm is a rare but potentially devastating cause. We present a patient with previous aortic valve replacement for a bicuspid valve who had been suffering from a chronic cough for 8 months and who developed subsequent voice hoarseness. This had been initially managed in the community with trials of steroid inhalers, steroid nasal sprays and proton pump inhibitors to no avail. He was referred to cardiology and chest clinics. An urgent CT aortogram was requested given his widened mediastinum on chest radiograph, cardiac history of bicuspid valve and symptoms. This revealed a large aneurysm of the thoracic aorta with chronic dissection that required urgent operative intervention. His cough resolved 6 weeks postoperatively. The purpose of this report is to highlight thoracic aortic aneurysms as a potential rare differential for chronic cough and as a complication of patients with bicuspid aortic valves. | 25,178,892 | [
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A mixed methods study of food safety knowledge, practices and beliefs in Hispanic families with young children. | Children are at a higher risk for foodborne illness. The objective of this study was to explore food safety knowledge, beliefs and practices among Hispanic families with young children (≤10 years of age) living within a Midwestern state. A convergent mixed methods design collected qualitative and quantitative data in parallel. Food safety knowledge surveys were administered (n = 90) prior to exploration of beliefs and practices among six focus groups (n = 52) conducted by bilingual interpreters in community sites in five cities/towns. Descriptive statistics determined knowledge scores and thematic coding unveiled beliefs and practices. Data sets were merged to assess concordance. Participants were female (96%), 35.7 (±7.6) years of age, from Mexico (69%), with the majority having a low education level. Food safety knowledge was low (56% ± 11). Focus group themes were: Ethnic dishes popular, Relating food to illness, Fresh food in home country, Food safety practices, and Face to face learning. Mixed method analysis revealed high self confidence in preparing food safely with low safe food handling knowledge and the presence of some cultural beliefs. On-site Spanish classes and materials were preferred venues for food safety education. Bilingual food safety messaging targeting common ethnic foods and cultural beliefs and practices is indicated to lower the risk of foodborne illness in Hispanic families with young children. | 25,178,898 | [
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Do portrayals of women in action convey another ideal that women with little self-determination feel obligated to live up to? Viewing effects on body image evaluations and eating behaviors. | Theoretical and empirical research suggests that valuing the body in terms of its functionality and physical competence (rather than its appearance) may improve women's relationships with their body and food. We tested this proposition by investigating women's responses to contrasting portrayals of the female body as a function of viewers' general motivation (SD: self-determined vs NSD: non self-determined). A sample of undergraduate women (N = 91) was randomly assigned to view a "body-as-process" video, a "body-as-object" video, and a neutral video. Afterwards, participants completed measures of appearance and competence self-appraisals and were then offered three varieties of chocolate bars to sample and evaluate. Their actual intake (g) along with motives to exert self-control (identified vs introjected) were assessed. Negative viewing effects were obtained for both the "body-as-process" and the "body-as-object" videos and these effects were exacerbated by participants' motivation. Women with a NSD motivation evaluated their appearance and competence more negatively post-exposure. They also endorsed more guilt-related reasons (introjected motives) to exert control over their consumption of chocolate which predicted diminished intake. These findings suggest that portrayals of female athleticism and physical competence may represent another ideal that women with a NSD motivation feel obligated to live up to. | 25,178,899 | [
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Delivery-related knowledge of mothers of NICU infants compared with well-baby-nursery infants. | The objective of this study was to compare the knowledge of mothers of newborns in a neonatal intensive care unit (NICU) and well-baby nursery (WBN) regarding their understanding of term gestation, delivery mode safety, and elective late preterm delivery. Mothers of newborns admitted to either an NICU (n=88) or a WBN (n=145) were surveyed (March 2008-September 2010). Of all mothers, regardless of infant location, 7% were unable to define term gestation, 33% were unaware that scheduling delivery at 35-36 weeks is not advisable, and 30% lacked the knowledge that cesareans are not safer than vaginal deliveries. Multivariate regression models show that socioeconomic and demographic factors underlie many knowledge gaps, and surprisingly, models confirmed that the site (NICU versus WBN) of the infant was not a significant factor related to maternal knowledge. This study revealed gaps in mothers' understanding of the medical implications of premature delivery even though most mothers knew the correct length of term gestation. Unexpectedly, NICU mothers who had a child with significant illness and who encountered multiple health care providers did not have improved understanding of perinatal risks. We conclude that all women need to be educated on the significance of the mode and the timing of delivery. | 25,178,903 | [
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Prokaryotic membrane vesicles: new insights on biogenesis and biological roles. | Biogenesis and trafficking of membrane vesicles are essential and well-studied processes in eukaryotes. In contrast, vesiculation in bacteria is not well understood. Outer membrane vesicles (OMVs) are produced in Gram-negative bacteria by blebbing of the outer membrane. In addition to the roles in pathogenesis, cell-to-cell communication and stress response, recent work has suggested that OMVs play important roles in immunomodulation and the establishment and balance of the gut microbiota. In this review we discuss the known and novel roles of OMVs and the different biogenesis models proposed, and address the evidence for cargo selection into OMVs. We also discuss the growing evidence for the existence of membrane vesicles in Gram-positive bacteria and Archaea. Due to their biological importance and promising applications in vaccinology, the biogenesis of OMVs is an important topic in microbiology. | 25,178,905 | [
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An inverse association between West Nile virus serostatus and avian malaria infection status. | Various ecological and physiological mechanisms might influence the probability that two or more pathogens may simultaneously or sequentially infect a host individual. Concurrent infections can have important consequences for host condition and fitness, including elevated mortality risks. In addition, interactions between coinfecting pathogens may have important implications for transmission dynamics. Here, we explore patterns of association between two common avian pathogens (West Nile virus and avian malaria parasites) among a suburban bird community in Chicago, IL, USA that share mosquito vectors. We surveyed 1714 individual birds across 13 species for both pathogens through established molecular protocols. Field investigations of haemosporidian and West Nile virus (WNV) infections among sampled birds yielded an inverse association between WNV serostatus and Plasmodium infection status. This relationship occurred in adult birds but not in juveniles. There was no evidence for a relationship between Haemoproteus infection and WNV serostatus. We detected similar prevalence of Plasmodium among birds captured with active WNV infections and spatiotemporally paired WNV-naïve individuals of the same species, demonstrating that the two pathogens can co-infect hosts. Mechanisms explaining the negative association between WNV serostatus and Plasmodium infection status remain unclear and must be resolved through experimental infection procedures. However, our results highlight potential interactions between two common avian pathogens that may influence their transmission among hosts. This is especially relevant considering that West Nile virus is a common zoonotic pathogen with public health implications. Moreover, both pathogens are instructive models in infectious disease ecology, and infection with either has fitness consequences for their avian hosts. | 25,178,911 | [
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Being a neighbor to Syria: a retrospective analysis of patients brought to our clinic for cranial gunshot wounds in the Syrian civil war. | Toward the end of 2010, the Arab spring, the waves of revolutionary demonstrations and protests influenced also Syria, where violent clashes turned into a civil war. Hundreds of thousands of people became refugees. The use of excessive force unfortunately culminated in numerous deaths and injuries in many cities. Being the closest city to Aleppo, Damascus and Homs, the biggest cities of Syria, Antioch/Hatay has been the city where initial emergency treatments were performed. For this reason, we examined and retrospectively analyzed the medical records of the patients treated in the clinics of our hospital due to cranial gunshot wounds during the war. The medical records of 186 patients who were injured in the Syrian War and brought to, followed up and treated in the Neurosurgery Clinic of Mustafa Kemal University, Faculty of Medicine in Hatay, a Turkish city on the Syrian border, between April 2011 and June 2013. A total of 186 patients were evaluated in a period of more than 2 years. Of all 91.4% of the patients were adults (male/female: 152/18) and 8.6% of them were pediatric patients (male/female: 14/2). The average age of the patients was 31 years, with an age range of between 2 months and 67 years. According to Glasgow coma score (GCS) of the patients at the time of admission, GCS was 3 in 32 patients (17.2%), between 4 and 7 in 70 patients (37.6%), and between 8 and 15 in 84 patients (45.1%). We observed that the patients with GCS of 4-7 had a significantly lower mortality among the 56 patients treated surgically compared with the 14 patients treated medically. Cranial gunshot wounds are responsible for high mortality and morbidity. A multiplicity of factors plays a role on morbidity and mortality. These are the duration of transport, the injury pattern, the velocities of the weapons used, and the Glasgow Coma Scales of the patients at the time of admission. The authors recommend that the patients with cranial gunshot wounds who has GCS of 4-7 should be aggressively treated including surgery as well. We do not recommend surgical treatment for patients with GCS of 3. All our experiences show that treatment of gunshot wounds will continue to be a matter of debate, about which there is more to learn. The data presented in this study will once again demonstrate the seriousness of the event, and will, perhaps, contribute to the peace negotiations to end the war. | 25,178,917 | [
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Bioinspired orientation-dependent friction. | Spatular terminals on the toe pads of a gecko play an important role in directional adhesion and friction required for reversible attachment. Inspired by the toe pad design of a gecko, we study friction of polydimethylsiloxane (PDMS) micropillars terminated with asymmetric (spatular-shaped) overhangs. Friction forces in the direction of and against the spatular end were evaluated and compared to friction forces on symmetric T-shaped pillars and pillars without overhangs. The shape of friction curves and the values of friction forces on spatula-terminated pillars were orientation-dependent. Kinetic friction forces were enhanced when shearing against the spatular end, while static friction was stronger in the direction toward the spatular end. The overall friction force was higher in the direction against the spatula end. The maximum value was limited by the mechanical stability of the overhangs during shear. The aspect ratio of the pillar had a strong influence on the magnitude of the friction force, and its contribution surpassed and masked that of the spatular tip for aspect ratios of >2. | 25,178,923 | [
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Unilateral NMR investigation of multifunctional treatments on stones based on colloidal inorganic and organic nanoparticles. | Consolidation and protection are among the most important treatments usually carried out in conservation of stone artifacts and monuments. In this paper, portable unilateral NMR and conventional techniques were used for investigating new multifunctional treatments based on tetraethoxysilane, silica, and polytetrafluoroethylene nanoparticles. The study was carried out on a very complex and heterogeneous porous stone such as tuff. NMR study allowed to obtain detailed information on the penetration depth of treatments, the hydrophobic effect, and changes in the open porosity caused by treatments. Physical and chemical inhomogeneities between the impregnated layers of tuff and the layers underneath were also detected. The average pores radius and pores interconnection obtained from NMR diffusion measurements were used for the first time to compare effects of different consolidating and/or protective treatments on stone. Because unilateral NMR technique is neither destructive nor invasive, investigation of treatments can be also carried out and optimized directly on buildings and monuments of interest for Cultural Heritage. | 25,178,927 | [
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Who am I? The relationship between self-concept uncertainty and materialism. | It is well accepted that materialism may result in a number of negative consequences, hence the importance of improving its understanding. In this paper, we propose that materialism negatively relates to self-concept uncertainty. Uncertainty about oneself is aversive and those feeling uncertain may use the possession of material objects as a way to reduce the uncertainty. Inasmuch as material objects can serve as concrete signs of self-worth, self-concept uncertainty can therefore relate to more materialism. Over two studies, one in Australia and the other in the US, with a total of 390 participants, our research demonstrates that lower clarity about one's self-concept associates with higher levels of materialism. While this result holds for both genders, this relationship is considerably stronger for women compared to men. We also find that lower self-concept clarity relates to higher compulsive buying. We further demonstrate that materialism relates to higher positive moods during shopping, and also relates to higher negative moods after shopping, more notably negative moods towards what was purchased. This effect is significant even when controlling for general affective states. | 25,178,953 | [
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Hydroxy-tryptophan containing derivatives of tritrpticin: modification of antimicrobial activity and membrane interactions. | Tritrpticin is an antimicrobial peptide with a strong microbicidal activity against Gram-positive and Gram-negative bacteria as well as fungi. The 13-residue peptide is essentially symmetrical and possesses a unique cluster of three Trp residues near the center of its amino acid sequence. The mechanism of action of tritrpticin is believed to involve permeabilization of the cytoplasmic membrane of susceptible bacteria. However it has been suggested that intracellular targets may also play a role in its antimicrobial activity. In this work the mechanism of action of several tritrpticin derivatives was studied through substitution of the three Trp residues with 5-hydroxy-tryptophan (5OHW), a naturally occurring non-ribosomal amino acid. Although it is more polar, 5OHW preserves many of the biophysical and biochemical properties of Trp, allowing the use of fluorescence spectroscopy and NMR techniques to study the interaction of the modified peptides with membrane mimetics. Single or triple 5OHW substitution did not have a large effect on the MIC of the parent peptide against Escherichia coli and Bacillus subtilis. However, the mechanism of action was altered by simultaneously replacing all three Trp with 5OHW. Our results suggest that the inner membrane of Gram-negative bacteria did not constitute the main target of this particular tritrpticin derivative. Since the addition of a hydroxyl group to the indole motif of the Trp residue was able to modify the mechanism of action of the peptides, our data confirm the importance of the Trp cluster in tritrpticin. This work also shows that 5OHW constitutes a new probe to modulate the antimicrobial activity and mechanism of action of other Trp-rich antimicrobial peptides. | 25,178,967 | [
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Clinical handovers between prehospital and hospital staff: literature review. | Clinical handover plays a vital role in patient care and has been investigated in hospital settings, but less attention has been paid to the interface between prehospital and hospital settings. This paper reviews the published research on these handovers. A computerised literature search was conducted for papers published between 2000 and 2013 using combinations of terms: 'handover', 'handoff', 'prehospital', 'ambulance', 'paramedic' and 'emergency' and citation searching. Papers were assessed and included if determined to be at least moderate quality with a primary focus on prehospital to hospital handover. 401 studies were identified, of which 21 met our inclusion criteria. These revealed concerns about communication and information transfer, and themes concerning context, environment and interprofessional relationships. It is clear that handover exchanges are complicated by chaotic and noisy environments, lack of time and resources. Poor communication is linked to behaviours such as not listening, mistrust and misunderstandings between staff. While standardisation is offered as a solution, notably in terms of the use of mnemonics (alphabetical memory aids), evidence for benefit appears inconclusive. This review raises concerns about handovers at the interface between prehospital and hospital settings. The quality of existing research in this area is relatively poor and further high-quality research is required to understand this important part of emergency care. We need to understand the complexity of handover better to grasp the challenges of context and interprofessional relationships before we reach for tools and techniques to standardise part of the handover process. | 25,178,977 | [
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No longer an untreatable disease: how targeted and immunotherapies have changed the management of melanoma patients. | The discovery that BRAF is a driver oncogene in cancer, and complementary improvements in our understanding of the immune system have resulted in new targeted and immune-therapies for metastatic melanoma. Targeted therapies achieve impressive clinical results in carefully selected patients but the development of resistance seems inevitable in most cases. Conversely, immune-checkpoints inhibitors can achieve long-term remission and cures, but in a smaller proportion of patients, and biomarkers to predict which patients will respond are not available. Nevertheless, melanoma has led the evolution of cancer treatment from relatively nonspecific cytotoxic agents to highly selective therapies and here we review the lessons from this paradigm shift in treatment and the opportunities for further improvements in outcomes for melanoma patients. | 25,178,978 | [
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Differences determined by optical coherence tomography volumetric analysis in non-culprit lesion morphology and inflammation in ST-segment elevation myocardial infarction and stable angina pectoris patients. | While the current methodology for determining fibrous cap (FC) thickness of lipid plaques is based on manual measurements of arbitrary points, which could lead to high variability and decreased accuracy, it ignores the three-dimensional (3-D) morphology of coronary artery disease. To compare, utilizing optical coherence tomography (OCT) assessments, volumetric quantification of FC, and macrophage detection using both visual assessment and automated image processing algorithms in non-culprit lesions of STEMI and stable angina pectoris (SAP) patients. Lipid plaques were selected from 67 consecutive patients (1 artery/patient). FC was manually delineated by a computer-aided method and automatically classified into three thickness categories: FC < 65 μm (i.e., thin-cap fibroatheroma [TCFA]), 65-150 μm, and >150 μm. Minimum thickness, absolute categorical surface area, and fractional luminal area of FC were analyzed. Automated detection and quantification of macrophage was performed within the segmented FC. A total of 5,503 cross-sections were analyzed. STEMI patients when compared with SAP patients had more absolute categorical surface area for TCFA (0.43 ± 0.45 mm(2) vs. 0.15 ± 0.25 mm(2) ; P = 0.011), thinner minimum FC thickness (31.63 ± 17.09 µm vs. 47.27 ± 26.56 µm, P = 0.012), greater fractional luminal area for TCFA (1.65 ± 1.56% vs. 0.74 ± 1.2%, P = 0.046), and greater macrophage index (0.0217 ± 0.0081% vs. 0.0153 ± 0.0045%, respectively, P < 0.01). The novel OCT-based 3-D quantification of the FC and macrophage demonstrated thinner FC thickness and larger areas of TCFA coupled with more inflammation in non-culprit sites of STEMI compared with SAP. | 25,178,981 | [
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Sustained, new, never, and discontinued tobacco cessation services adopters. | This study examined longitudinal adoption patterns of tobacco cessation (TC) counseling and TC pharmacotherapy in substance use disorder treatment programs and baseline predictors (program characteristics and program culture) of these patterns 12-months later. Telephone survey data were collected in 2010 from 685 randomly sampled program administrators working in geographically representative treatment programs across the U.S. Regarding TC counseling, about 41% of programs never adopt, 33% sustain, and 27% change adoption patterns. Concerning TC pharmacotherapy, about 62% of programs never adopt, 19% sustain, and 18% change adoption patterns. The three most consistent predictors of counseling adoption patterns are TC reimbursement, TC financial resource availability, and smoking culture. For TC pharmacotherapy adoption patterns, the most consistent predictors include profit status, TC reimbursement, level of care, TC financial resource availability, and smoking culture. Findings provide insights into program characteristics and program culture as both potential barriers and facilitators of longitudinal TCS adoption. | 25,178,991 | [
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Induction of apoptosis in cervical cancer cells by the duplex drug 5-FdU-ECyd, coupling 2'-deoxy-5-fluorouridine and 3'-C-ethinylcytidine. | Therapeutic options are limited for patients with advanced cervical cancer, and more effective drugs with favorable side-effect profiles are needed. We developed a nucleoside analogue duplex drug (5-FdU-ECyd), in which the DNA synthesis inhibitor 5-fluorodeoxyuridine is coupled to the RNA synthesis inhibitor 3'-C-ethinylcytidine. We therefore aimed to test its efficacy in cervical carcinoma cells in vitro and to establish its mechanism of action. The cytotoxic effects of 5-FdU-ECyd on cervical cancer cells were assessed using the MTT assay, clonality assays, FACScan analysis, and its effect on cancer cell spheroids. Mechanisms of cell death were analyzed by Western blotting for apoptosis and autophagy pathways and mitochondrial membrane potential. HeLa, CaSki, SiHa, and Me180 cervical cancer cells were highly sensitive to 5-FdU-ECyd in both 2- and 3-dimensional cancer models. The cell death induced by 5-FdU-ECyd was associated with characteristic morphological and biochemical signs of apoptosis, including nuclear chromatin condensation and fragmentation, PARP cleavage, and a breakdown in mitochondrial membrane potential. 5-FdU-ECyd treatment led to an early S-phase arrest and drastically reduced expression of the anti-apoptosis protein Mcl-1 and increased signaling via the JNK and p38 MAPK pathways. 5-FdU-ECyd is highly cytotoxic in cervical cancer cells and exploits apoptosis pathways that might be specific to cancer, but not normal cells. 5-FdU-ECyd might represent a new chemotherapeutic option for patients with advanced or treatment refractory cervical cancer. | 25,178,996 | [
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Unsuspected allergic contact dermatitis to alcohol swabs following neurosurgery. | We report a case of a 12-year-old girl with severe allergic contact dermatitis following neurosurgery secondary to topical use of isopropyl alcohol swabs. Alcohol swabs should not be overlooked as potential allergens. In our case, it was initially assumed that the cause of her reaction was either tapes or topical local anaesthetic. | 25,179,004 | [
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On the coordination chemistry of phosphinecarboxamide: assessing ligand basicity. | We describe the coordination chemistry of the primary phosphine PH2C(O)NH2 (phosphinecarboxamide) towards group 6 transition-metals. Experimental and theoretical studies reveal that this novel species has comparable electronic properties to PH3. | 25,179,007 | [
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Use of a nutrition support protocol to increase enteral nutrition delivery in critically ill patients. | Early enteral nutrition is recommended for patients in intensive care units, but nutrition provision is often hindered by a variety of unit-specific problems. To evaluate the impact of a nutrition support protocol on nutrition prescription and delivery in the intensive care unit. Nutrition-related data from 73 patients receiving mechanical ventilation who were treated in an adult medical intensive care unit before introduction of an enteral nutrition support protocol were retrospectively compared with data for 87 patients admitted after implementation of the protocol. After implementation of the protocol, enteral nutrition was started significantly earlier (P = .007) and enteral feeding goals were reached significantly faster (6 vs 10 days, P < .001) than before. Prescription of enteral nutrition on the first day of invasive mechanical ventilation increased from 38% before to 54% after (P = .03) implementation of the protocol. Prescribed and delivered nutrition doses on the first 2 days of mechanical ventilation also increased significantly (P < .001) after the protocol was implemented. Nasojejunal feeding tubes were used in 52% of patients before and 56% of patients after protocol implementation P = .63). Jejunal tubes were placed earlier after the protocol was implemented than before (median 5 vs 6.5 days), and when a jejunal tube was in place, feeding goals were reached faster (median 2 vs 3 days, P = .002). Implementing an enteral nutrition support protocol shortened the time to reach feeding goals. Jejunal feeding tubes were necessary in more than half of the patients, and with a jejunal feeding tube in place, feeding goals were reached rapidly. | 25,179,035 | [
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In vitro testing the potential of a novel chimeric IgG variant for inhibiting collagen fibrils formation in recurrent hereditary gingival fibromatosis: chimeric antibody in a gingival model. | Gingival fibromatosis is a progressive enlargement of the gingiva. It may hinder oral cavity hygiene and result in underlying bone loss. The long-term benefits of surgery cannot be predicted. On the other hand, alternative, efficient and non-invasive methods are not available at present. The aim of this study was to test the inhibitory effects of a chimeric IgG variant on collagen fibril formation in the cell culture of gingival fibroblasts taken from a patient with hereditary gingival fibromatosis with a high propensity for recurrence. Gingival biopsies were collected from the mandibular gingiva and used for histological evaluation as well as to establish a fibroblast culture. A histological evaluation was made in haematoxylin-eosin and Heidenhain's trichrome stained tissue sections. The inhibitory effect of a chimeric antibody on collagen fibril formation was determined in fibroblast cultures by using a collagen-specific Western blot and immunofluorescent staining. A histological evaluation revealed epithelial acanthosis with singular elongated rete pegs extending into the underlying connective tissue stroma that consisted of locally abundant, irregular collagen bundles. Based on observations with an in vitro model we conclude that a chimeric anti-collagen antibody efficiently inhibits collagen fibril accumulation in cell culture derived from diffuse, hereditary gingival fibromatosis that is characterized by a high propensity for recurrence (high proliferation index). Employing cell cultures from standardized group of patients with recurrent hereditary gingival fibromatosis as well as standarizing relevant 3D (tissue-like) models will be crucial for further tests of the antibody. | 25,179,091 | [
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Fabrication of an anti-viral air filter with SiO₂-Ag nanoparticles and performance evaluation in a continuous airflow condition. | In this study, SiO2 nanoparticles surface coated with Ag nanoparticles (SA particles) were fabricated to coat a medium air filter. The pressure drop, filtration efficiency, and anti-viral ability of the filter were evaluated against aerosolized bacteriophage MS2 in a continuous air flow condition. A mathematical approach was developed to measure the anti-viral ability of the filter with various virus deposition times. Moreover, two quality factors based on the anti-viral ability of the filter, and a traditional quality factor based on filtration efficiency, were calculated. The filtration efficiency and pressure drop increased with decreasing media velocity and with increasing SA particle coating level. The anti-viral efficiency also increased with increasing SA particle coating level, and decreased by with increasing virus deposition time. Consequently, SA particle coating on a filter does not have significant effects on filtration quality, and there is an optimal coating level to produce the highest anti-viral quality. | 25,179,108 | [
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Replication of Brucella abortus and Brucella melitensis in fibroblasts does not require Atg5-dependent macroautophagy. | Several intracellular bacterial pathogens have evolved subtle strategies to subvert vesicular trafficking pathways of their host cells to avoid killing and to replicate inside the cells. Brucellae are Gram-negative facultative intracellular bacteria that are responsible for brucellosis, a worldwide extended chronic zoonosis. Following invasion, Brucella abortus is found in a vacuole that interacts first with various endosomal compartments and then with endoplasmic reticulum sub-compartments. Brucella establishes its replication niche in ER-derived vesicles. In the past, it has been proposed that B. abortus passed through the macroautophagy pathway before reaching its niche of replication. However, recent experiments provided evidence that the classical macroautophagy pathway was not involved in the intracellular trafficking and the replication of B. abortus in bone marrow-derived macrophages and in HeLa cells. In contrast, another study showed that macroautophagy favoured the survival and the replication of Brucella melitensis in infected RAW264.7 macrophages. This raises the possibility that B. abortus and B. melitensis followed different intracellular pathways before replicating. In the present work, we have addressed this issue by comparing the replication rate of B. abortus and B. melitensis in embryonic fibroblasts derived from wild-type and Atg5-/- mice, Atg5 being a core component of the canonical macroautophagic pathway. Our results indicate that both B. abortus S2308 and B. melitensis 16M strains are able to invade and replicate in Atg5-deficient fibroblasts, suggesting that the canonical Atg5-dependent macroautophagic pathway is dispensable for Brucella replication. The number of viable bacteria was even slightly higher in Atg5-/- fibroblasts than in wild-type fibroblasts. This increase could be due to a more efficient uptake or to a better survival rate of bacteria before the beginning of the replication in Atg5-deficient cells as compared to wild-type cells. Moreover, our data show that the infection with B. abortus or with B. melitensis does not stimulate neither the conversion of LC3-I to LC3-II nor the membrane recruitment of LC3 onto the BCV. Our study suggests that like Brucella abortus, Brucella melitensis does not subvert the canonical macroautophagy to reach its replicative niche or to stimulate its replication. | 25,179,110 | [
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High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media. | The purpose of this study was to use high resolution three-dimensional (3D) magnetic resonance imaging (MRI) to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12-20 weeks (n=12), were used in this study. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple. Approximately 20-25μL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p<0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p<0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers. | 25,179,139 | [
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Life Origination Hydrate Theory (LOH-Theory) and the explanation of the biological diversification. | The Life Origination Hydrate Theory (LOH-Theory) considers the life origination process as a sequence of thermodynamically caused regular and inevitable chemical transformations regulated by universal physical and chemical laws. The LOH-Theory bears on a number of experimental, thermodynamic, observation, and simulation researches. N-bases, riboses, nucleosides, and nucleotides and DNAs and RNAs are formed repeatedly within structural cavities of localizations of underground and underseabed honeycomb CH4-hydrate deposits from CH4 and nitrate and phosphate ions that diffused into the hydrate structures; proto-cells and their agglomerates originated from these DNAs and from the same minerals in the semi-liquid soup after liquation of the hydrate structures. Each localization gave rise to a multitude of different DNAs and living organisms. The species diversity is caused by the spatial and temporal repeatability of the processes of living matter origination under similar but not identical conditions, multiplicity of the DNA forms in each living matter origination event, variations in the parameters of the native medium, intraspecific variations, and interspecific variations. The contribution of the last to the species diversity is, likely, significant for prokaryotes and those eukaryotes that are only at low steps of their biological organization; however, in the light of the LOH-Theory, of available long-term paleontological investigations, and of studies of reproduction of proliferous organisms, we conclude that, in toto, the contribution of interspecific variations to the species diversity was earlier overestimated by some researchers. The reason of this overestimation is that origination of scores of «spores» of different organisms in any one event and multiple reproductions of such events in time and Earth's space were not taken into consideration. | 25,179,143 | [
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Metformin exaggerates phenylephrine-induced AMPK phosphorylation independent of CaMKKβ and attenuates contractile response in endothelium-denuded rat aorta. | Metformin, a widely prescribed antidiabetic drug, has been shown to reduce the risk of cardiovascular disease, including hypertension. Its beneficial effect toward improved vasodilation results from its ability to activate AMPK and enhance nitric oxide formation in the endothelium. To date, metformin regulation of AMPK has not been fully studied in intact arterial smooth muscle, especially during contraction evoked by G protein-coupled receptor (GPCR) agonists. In the present study, ex vivo incubation of endothelium-denuded rat aortic rings with 3mM metformin for 2h resulted in significant accumulation of metformin (∼ 600 pmoles/mg tissue), as revealed by LC-MS/MS MRM analysis. However, metformin did not show significant increase in AMPK phosphorylation under these conditions. Exposure of aortic rings to a GPCR agonist (e.g., phenylephrine) resulted in enhanced AMPK phosphorylation by ∼ 2.5-fold. Importantly, in metformin-treated aortic rings, phenylephrine challenge showed an exaggerated increase in AMPK phosphorylation by ∼ 9.7-fold, which was associated with an increase in AMP/ATP ratio. Pretreatment with compound C (AMPK inhibitor) prevented AMPK phosphorylation induced by phenylephrine alone and also that induced by phenylephrine after metformin treatment. However, pretreatment with STO-609 (CaMKKβ inhibitor) diminished AMPK phosphorylation induced by phenylephrine alone but not that induced by phenylephrine after metformin treatment. Furthermore, attenuation of phenylephrine-induced contraction (observed after metformin treatment) was prevented by AMPK inhibition but not by CaMKKβ inhibition. Together, these findings suggest that, upon endothelial damage in the vessel wall, metformin uptake by the underlying vascular smooth muscle would accentuate AMPK phosphorylation by GPCR agonists independent of CaMKKβ to promote vasorelaxation. | 25,179,145 | [
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Wireless mobile technology to improve workflow and feasibility of MR-guided percutaneous interventions. | A wireless interactive display and control device combined with a platform-independent web-based user interface (UI) was developed to improve the workflow for interventional magnetic resonance imaging (iMRI). The iMRI-UI enables image acquisition of up to three independent slices using various pulse sequences with different contrast weighting. Pulse sequence, scan geometry and related parameters can be changed on the fly via the iMRI-UI using a tablet computer for improved lesion detection and interventional device targeting. The iMRI-UI was validated for core biopsies with a liver phantom ([Formula: see text] [Formula: see text] 40) and Thiel soft-embalmed human cadavers ([Formula: see text] [Formula: see text] 24) in a clinical 1.5T MRI scanner. The iMRI-UI components and setup were tested and found conditionally MRI-safe to use according to current ASTM standards. Despite minor temporary touch screen interference at a close distance to the bore ([Formula: see text]20 cm), no other issues regarding quality or imaging artefacts were observed. The 3D root-mean-square distance error was [Formula: see text] (phantom)/[Formula: see text] mm (cadaver), and overall procedure times ranged between 12 and 22 (phantom)/20 and 55 min (cadaver). The wireless iMRI-UI control setup enabled fast and accurate interventional biopsy needle placements along complex trajectories and improved the workflow for percutaneous interventions under MRI guidance in a preclinical trial. | 25,179,151 | [
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Induction of complementary function reductase enzymes in colon cancer cells by dithiole-3-thione versus sodium selenite. | Cellular induction of reductase enzymes can alter the susceptibility of cells toward drugs and chemicals. In this study, we compared the capacity of a single dose of sodium selenite and 3H-1,2-dithiole-3-thione (D3T) to influence the drug-relevant reducing capacity of HT29 cells over time, and defined the protein-specific contribution to this activity on the basis of selected reaction monitoring mass spectrometry. Thioredoxin reductase 1 (TrxR1) protein levels and activity were inducible up to 2.2-fold by selenium. In contrast, selenium had only a minor influence on prostaglandin reductase 1 (PTGR1) and quinone oxidoreductase 1 (NQO1) activity and protein levels. D3T, a strong Nrf2 inducer, induced all the reductases and additionally increased the cytotoxicity of hydroxymethylacylfulvene, a bioreductive DNA-alkylating drug. The data and experimental approaches allow one to define induction potency for reductase enzymes PTGR1, TrxR1, and NQO1 in HT29 cells and link these to changes in drug cytotoxicity. | 25,179,160 | [
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The Nigeria Independent Accountability Mechanism for maternal, newborn, and child health. | Since the 2010 launch of the UN Secretary-General's Global Strategy for Women's and Children's Health, worldwide political energy coalesced around improving the health of women and children. Nigeria acted on a key recommendation emerging from the Global Strategy and became one of the first countries to establish an independent group known as the Nigeria Independent Accountability Mechanism (NIAM). NIAM aims to track efforts on progress related to Nigeria's roadmap for the health of women and children. It includes eminent people from outside government to ensure independence, and is recognized within government to analyze and report on progress. The concept of NIAM received approval at various national and international forums, as well as from the Nigeria Federal Ministry of Health. This experience provides an example of connecting expertise and groups with the government to influence and accelerate progress in maternal, newborn, and child health. Engagement between government and civil society should become the norm rather than the exception to achieve national goals. | 25,179,169 | [
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Linking polymorphic p53 response elements with gene expression in airway epithelial cells of smokers and cancer risk. | Chronic cigarette smoking exposes airway epithelial cells to thousands of carcinogens, oxidants and DNA-damaging agents, creating a field of molecular injury in the airway and altering gene expression. Studies of cytologically normal bronchial epithelial cells from smokers have identified transcription-based biomarkers that may prove useful in early diagnosis of lung cancer, including a number of p53-regulated genes. The ability of p53 to regulate transcription is critical for tumor suppression, and this suggests that single-nucleotide polymorphisms (SNPs) in functional p53 binding sites (p53 response elements, or p53REs) that affect gene expression could influence susceptibility to cancer. To connect p53RE SNP genotype with gene expression and cancer risk, we identified a set of 204 SNPs in putative p53REs, and performed cis expression quantitative trait loci (eQTL) analysis, assessing associations between SNP genotypes and mRNA levels of adjacent genes in bronchial epithelial cells obtained from 44 cigarette smokers. To further test and validate these genotype-expression associations, we searched published eQTL studies from independent populations and determined that 53% (39/74) of the bronchial epithelial eQTLs were observed in at least one of other studies. SNPs in p53REs were also evaluated for effects on p53-DNA binding using a quantitative in vitro protein-DNA binding assay. Last, based on linkage disequilibrium, we found 6 p53RE SNPs associated with gene expression were identified as cancer risk SNPs by either genome-wide association studies or candidate gene studies. We provide an approach for identifying and evaluating potentially functional SNPs that may modulate the airway gene expression response to smoking and may influence susceptibility to cancers. | 25,179,167 | [
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MicroRNA-34 family expression in bovine gametes and preimplantation embryos. | Oocyte fertilization and successful embryo implantation are key events marking the onset of pregnancy. In sexually reproducing organisms, embryogenesis begins with the fusion of two haploid gametes, each of which has undergone progressive stages of maturation. In the final stages of oocyte maturation, minimal transcriptional activity is present and regulation of gene expression occurs primarily at the post-transcriptional level. MicroRNAs (miRNA) are potent effectors of post-transcriptional gene silencing and recent evidence demonstrates that the miR-34 family of miRNA are involved in both spermatogenesis and early events of embryogenesis. The profile of miR-34 miRNAs has not been characterized in gametes or embryos of Bos taurus. We therefore used quantitative reverse transcription PCR (qRT-PCR) to examine this family of miRNAs: miR-34a, -34b and -34c as well as their precursors in bovine gametes and in vitro produced embryos. Oocytes were aspirated from antral follicles of bovine ovaries, and sperm cells were isolated from semen samples of 10 bulls with unknown fertility status. Immature and in vitro matured oocytes, as well as cleaved embryos, were collected in pools. Gametes, embryos and ovarian and testis tissues were purified for RNA. All members of the miR-34 family are present in bovine spermatozoa, while only miR-34a and -34c are present in oocytes and cleaved (2-cell) embryos. Mir-34c demonstrates variation among different bulls and is consistently expressed throughout oocyte maturation and in the embryo. The primary transcript of the miR-34b/c bicistron is abundant in the testes and present in ovarian tissue but undetectable in oocytes and in mature spermatozoa. The combination of these findings suggest that miR-34 miRNAs may be required in developing bovine gametes of both sexes, as well as in embryos, and that primary miR-34b/c processing takes place before the completion of gametogenesis. Individual variation in sperm miR-34 family abundance may offer potential as a biomarker of male bovine fertility. | 25,179,211 | [
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Designing hybrid onconase nanocarriers for mesothelioma therapy: a Taguchi orthogonal array and multivariate component driven analysis. | Onconase (ONC) is a member of a ribonuclease superfamily that has cytostatic activity against malignant mesothelioma (MM). The objective of this investigation was to develop bovine serum albumin (BSA)-chitosan based hybrid nanoformulations for the efficient delivery of ONC to MM while minimizing the exposure to normal tissues. Taguchi orthogonal array L9 type design was used to formulate ONC loaded BSA nanocarriers (ONC-ANC) with a mean particle size of 15.78 ± 0.24 nm (ζ = -21.89 ± 0.11 mV). The ONC-ANC surface was hybridized using varying chitosan concentrations ranging between 0.100 and 0.175% w/v to form various ONC loaded hybrid nanocarriers (ONC-HNC). The obtained data set was analyzed by principal component analysis (PCA) and principal component regressions (PCR) to decode the effects of investigated design variables. PCA showed positive correlations between investigated design variables like BSA, ethanol dilution, and total ethanol with particle size and entrapment efficiency (EE) of formulated nanocarriers. PCR showed that the particle size depends on BSA, ethanol dilution, and total ethanol content, while EE was only influenced by BSA content. Further analysis of chitosan and TPP effects used for coating of ONC-ANC by PCR confirmed their positive impacts on the particle size, zeta potential, and prolongation of ONC release compared to uncoated ONC-ANC. PCR analysis of preliminary stability studies showed increase in the particle size and zeta potential at lower pH. However, particle size, zeta potential, and EE of developed HNC were below 63 nm, 31 mV, and 96%, respectively, indicating their stability under subjected buffer conditions. Out of the developed formulations, HNC showed enhanced inhibition of cell viability with lower IC50 against human MM-REN cells compared to ONC and ONC-ANC. This might be attributed to the better cell uptake of HNC, which was confirmed in the cell uptake fluorescence studies. These studies indicated that a developed nanotherapeutic approach might aid in reducing the therapeutic dose of ONC, minimizing adverse effects by limiting the exposure of ONC to normal tissues, and help in the development of new therapeutic forms and routes of administration. | 25,179,221 | [
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Score_set: a CAPRI benchmark for scoring protein complexes. | Critical Assessment of PRedicted Interactions (CAPRI) has proven to be a catalyst for the development of docking algorithms. An essential step in docking is the scoring of predicted binding modes in order to identify stable complexes. In 2005, CAPRI introduced the scoring experiment, where upon completion of a prediction round, a larger set of models predicted by different groups and comprising both correct and incorrect binding modes, is made available to all participants for testing new scoring functions independently from docking calculations. Here we present an expanded benchmark data set for testing scoring functions, which comprises the consolidated ensemble of predicted complexes made available in the CAPRI scoring experiment since its inception. This consolidated scoring benchmark contains predicted complexes for 15 published CAPRI targets. These targets were subjected to 23 CAPRI assessments, due to existence of multiple binding modes for some targets. The benchmark contains more than 19,000 protein complexes. About 10% of the complexes represent docking predictions of acceptable quality or better, the remainder represent incorrect solutions (decoys). The benchmark set contains models predicted by 47 different predictor groups including web servers, which use different docking and scoring procedures, and is arguably as diverse as one may expect, representing the state of the art in protein docking. The data set is publicly available at the following URL: http://cb.iri.univ-lille1.fr/Users/lensink/Score_set. | 25,179,222 | [
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'Bubble-free' electrochemical delamination of CVD graphene films. | The production of large amounts of hydrogen bubbles, typical of electrochemical delamination methods based on the electrolysis of water, results in mechanical damage to graphene during the delamination, transfer, and drying steps. Here a novel 'bubble-free' delamination method is introduced which exploits the electrochemical dissolution of native copper oxide at a potential lower than that required for the formation of hydrogen bubbles, enabling the production of defect-free graphene stack. | 25,179,223 | [
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Curcumin derivative with the substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PS1 mice. | Recent evidence supports the amyloid cascade hypothesis that a pathological change of amyloid β (Aβ) in the brain is an initiating event in Alzheimer's disease (AD). Accordingly, modulating the abnormal Aβ aggregation is considered a potential therapeutic target in AD. Curcumin, a low-molecular-weight polyphenol derived from the well-known curry spice turmeric, has shown favorable effects on preventing or treating AD pathology. The present study investigated the effects of curcumin and 2 novel curcumin derivatives, FMeC1 and FMeC2, on AD pathology in APPswe/PS1dE9 double transgenic mice. Mice fed a chow diet that contained FMeC1 for 6 months showed a reduction in insoluble Aβ deposits and glial cell activity together with reduced cognitive deficits, compared to animals receiving a control diet or with curcumin or FMeC2 in their diet. Both curcumin and FMeC1 modulated the formation of Aβ aggregates; however, only FMeC1 significantly attenuated the cell toxicity of Aβ. These results indicate that FMeC1 may have potential for preventing AD. | 25,179,227 | [
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Role of 5-HT7 receptors in the inhibition of the vasodepressor sensory CGRPergic outflow in pithed rats. | The role of calcitonin gene-related peptide (CGRP) in the modulation of vascular tone has been widely documented. Indeed, electrical stimulation of the perivascular sensory outflow in pithed rats induces vasodepressor responses by activation of CGRP receptors. This study investigated the role of 5-HT7 receptors in the inhibition of the rat vasodepressor sensory outflow. Male Wistar pithed rats were pretreated with i.v. continuous infusions of hexamethonium and methoxamine, followed by physiological saline or AS-19 (a 5-HT7 receptor agonist). Then, electrical stimulation of the spinal cord resulted in frequency-dependent decreases in DBP. The infusions of AS-19, as compared to those of saline, inhibited the vasodepressor responses induced by electrical stimulation without affecting those to i.v. bolus injections of exogenous α-CGRP. This inhibition by AS-19 was abolished by the antagonists pimozide (5-HT7) or sulfisoxazole (ETA), but not by indomethacin (COX1/2) or losartan (AT1), at doses that did not affect per se the electrically-induced vasodepressor responses. Interestingly, glibenclamide (an ATP-dependent K(+) channel blocker) attenuated these vasodepressor responses. The present results suggest that AS-19-induced inhibition of the rat vasodepressor sensory CGRPergic outflow is mainly mediated by 5-HT7 receptors via endothelin release, with the possible involvement of ATP-dependent K(+) channels. | 25,179,247 | [
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Metabolic imaging in non-small-cell lung cancer radiotherapy. | Metabolic imaging by positrons emission tomography (PET) offers new perspectives in the field of non-small-cell lung cancer radiation therapy. First, it can be used to refine the way nodal and primary tumour target volumes are selected and delineated, in better agreement with the underlying tumour reality. In addition, the non-invasive spatiotemporal mapping of the tumour biology and the organs at risk function might be further used to steer radiation dose distribution. Delivering higher dose to low responsive tumour area, in a way that better preserves the normal tissue function, should thus reconcile the tumour radiobiological imperatives (maximising tumour local control) with dose related to the treatment safety (minimising late toxicity). By predicting response early in the course of radiation therapy, PET may also participate to better select patients who are believed to benefit most from treatment intensification. Altogether, these technological advances open avenues to in-depth modify the way the treatment plan is designed and the dose is delivered, in better accordance with the radiobiology of individual solid cancers and normal tissues. | 25,179,249 | [
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[Intensity-modulated radiotherapy in head and neck cancer: ethics and methodology]. | Numerous studies have shown that intensity-modulated radiation therapy is the standard technique for the radiation treatment of head and neck cancers. Intensity-modulated radiation therapy reduces side effects (xerostomia, dysphagia, fibrosis, etc.) and improves the results for cancer localizations with highly complex shapes such as the cavum or nasal cavity. Intensity-modulated radiation therapy is also a costly technique that necessitates a numerous staff, highly trained, with regular practice. If this technique cannot be available (understaffing, overwork, etc.) the choice between entrusting the patient to a colleague and treating the patient with a less sophisticated technique such as 3-dimensional conformal radiation therapy depends on different objective and ethical criteria. | 25,179,256 | [
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Narrowing the localization of the region breakpoint in most frequent Robertsonian translocations. | Despite that Robertsonian translocations (ROBs) are the most common chromosomal rearrangements in humans (1/1000 individuals), an exact breakpoint and the molecular mechanisms leading to their formation are still not well known. This is partly due to the fact that Human Genome Project did not provide any map or sequence for the acrocentric short arms. The main aim of our studies was to narrow the breakpoints in de novo arising and in familial cases of the most frequently occurring ROBs, using eight, previously not tested clones derived from 21p. Our results from PCR and FISH analysis showed that only the clones CR382285, CR382287, and a small fragment of CR382332 are retained in the examined ROBs. Moreover, interphase FISH on monochromosomal hybrids verified the orientation of studied clones in relation to centromeres of chromosomes 14 and 21. Given our results, we propose localization of the breakpoints in or nearby to clone CR382332. Summarizing, our results allowed to narrow the region where the breakpoints are localized and demonstrated that their position could be the same in all common ROBs. | 25,179,263 | [
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Gastrointestinal involvement in systemic sclerosis. | Systemic sclerosis is an autoimmune chronic disease characterised by microvascular, muscular and immunologic abnormalities that lead to progressive and systemic deposition of connective tissue in the skin and internal organs. The gastrointestinal tract is often overlooked by physicians but it is the most affected organ after the skin, from the mouth to the anus. Indeed, 80% of SSc patients may present with gastrointestinal involvement. Gastrointestinal manifestations range from bloating and heartburn to dysphagia and anorectal dysfunction to severe weight loss and malabsorption. However, the gastrointestinal involvement is rarely the direct cause of death, but has great impact on quality of life and leads to several comorbidities that subsequently affect patients' survival. Treatments, including nutritional support and prokinetics provide limited benefits and do not arrest the progressive course of the disease, but earlier detection of gastrointestinal involvement may reduce the risk of complications such as malnutrition. | 25,179,275 | [
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Pathophysiology of systemic sclerosis: state of the art in 2014. | Major work has been done in order to improve the understanding of systemic sclerosis (SSc) pathogenesis. A number of new experimental models have been set up, that should help to understand the disease pathogenesis and test new therapeutic targets. Reactive oxygen species represent a hallmark of the pathogenesis of SSc, both at the fibroblast and at the endothelial cell levels. Although a large number of genetic studies have been conducted, it is still difficult to identify a genetic background specific to SSc, and the major progress in this setting is probably the identification of an interferon signature. Besides endothelial cells and fibroblasts, major development has been made in the understanding of the role of B cells and autoantibodies in the pathogenesis of SSc. Plasmacytoid dendritic cells seem to play a major role in the pathogenesis of SSc through the secretion of CXCL4, although these data will need to be confirmed in the near future. | 25,179,277 | [
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Evaluation of quadrupole-time-of-flight mass spectrometry in comprehensive two-dimensional gas chromatography. | Quadrupole time-of-flight mass spectrometry (Q-TOFMS) has been evaluated with respect to its applicability in comprehensive two-dimensional gas chromatography (GC×GC). At a maximum acquisition frequency, while approximately 50 full accurate mass spectra on disk were acquired per s (50Hz) in scan mode, the sampling rate in target mode (MS/MS) was strongly dependent on the number of target ions selected. The number of selected precursor ions per time window proportionally decreased the acquisition rate for each ion; one precursor ion ≅31.35Hz; two ions ≅16.68Hz; and for 8 precursor ions, a sampling rate of just 4.18Hz was found. When Q-TOFMS was used in simultaneous mode, where in addition to the acquisition of target ion MS/MS signals, it also collects the full mass spectrum, sampling rates were even lower. It is demonstrated that Q-TOFMS generates sufficient data points over each peak in GC×GC operation in scan mode using TOFMS acquisition only, or is able to collect sufficient data points for relatively wide chromatographic peaks (≥600ms) in the target mode (MS/MS), however only if one or two precursor ions are selected per time window. Mass accuracy was found to perform within specification (<5ppm), even for the fastest acquisition operation (50Hz). Spectral deconvolution is demonstrated to work better in GC×GC than in 1D GC mode. Data visualisation in target GC×GC mode presents difficulties when there are overlapping target windows comprising different numbers of precursor ions. | 25,179,286 | [
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Clinical observations in alopecia areata: Implications and hypotheses. | Alopecia areata (AA) is a T-cell-mediated hair loss disorder but the exact cause is unknown. In this report we describe patterns of onset, regrowth and relapse in AA and propose potential underlying mechanisms. We believe that these aspects of AA require integration into modern theories of AA pathogenesis. | 25,179,296 | [
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Maximal acetylcholine dose of 200 μg into the left coronary artery as a spasm provocation test: comparison with 100 μg of acetylcholine. | As a spasm provocation test of acetylcholine (ACH), incremental dose up (20/50/100 μg) into the left coronary artery (LCA) is recommended in the guidelines established by Japanese Circulation Society. Recently, Ong et al. reported the ACOVA study which maximal ACH dose was 200 μg in the LCA. We compared the angiographic findings between ACH 100 μg and ACH 200 μg in the LCA and also examined the usefulness and safety of ACH 200 μg in Japanese patients without variant angina. As a spasm provocation test, we performed intracoronary injection of ACH 200 μg after ACH 100 μg in 88 patients (55 males, 68.4 ± 11.7 years old) including 59 ischemic heart disease (IHD) patients and 29 non-IHD patients. Positive spasm was defined as >99 % transient stenosis (focal spasm) or 90 % severe diffuse vasoconstriction (diffuse spasm). Positive spasm by ACH 200 μg was significantly higher than that by ACH 100 μg (36 pts: 40.9 % vs. 17 pts: 19.3 %, p < 0.01). Diffuse distal spasm on the left anterior descending artery was more recognized in ACH 200 μg than in ACH 100 μg (30.7 vs. 13.6 %, p < 0.01). In 29 rest angina patients, positive spasm by ACH 200 μg (19 pts) was significantly higher than that by ACH 100 μg (7 pts) (65.5 vs. 24.1 %, p < 0.01). No serious irreversible complications were found during ACH 200 μg. Administration of ACH 200 μg into the LCA was safe and useful. We may reexamine the maximal ACH dose into the LCA. | 25,179,297 | [
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Effect of a ventilator-focused intervention on the rate of Acinetobacter baumannii infection among ventilated patients. | Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia, often as a result of ventilator equipment contamination. Evidence-based guidance on optimal care of ventilator equipment to prevent infection is lacking. Here, we report on a significant and persistent reduction in A baumannii infection rates achieved by introducing a strict policy on ventilator care. We implemented an institution-wide ventilator care policy that included routine exchange of breathing circuits and external bacterial filters (every 7-14 days) and replacement followed by routine sterilization of internal bacterial filters (every 4-8 weeks). We analyzed sputum cultures and patient outcomes among ventilated patients before and after the intervention. Between January 2012 and March 2013, 321 patients ventilated for more than 3 days comprised the study cohort. Health care-associated A baumannii acquisition was significantly reduced during the postintervention period (33% vs 16%; odds ratio, 0.39; 95% confidence interval, 0.23-0.67; P = .0008). Additionally, the median time to A baumannii acquisition was significantly longer postintervention (59 vs 21 days; P < .0001). A baumannii ventilator-associated pneumonia risk was also reduced postintervention (odds ratio, 0.39; P = .005). Implementing a stricter standard of ventilator care than that currently defined in published guidelines can significantly decrease health care-associated A baumannii acquisition and related adverse outcomes among ventilated patients. | 25,179,333 | [
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Evaluation of the short-term and long-term effect of a short series of hand hygiene campaigns on improving adherence in a tertiary care hospital in India. | Hand hygiene compliance at our institution was monitored by direct observation before and after a series of 2 hand hygiene awareness campaigns across an18-month time period to analyze the effect of these campaigns. A total of 5,059 opportunities for hand hygiene were observed. Compliance increased from 28.1% (95% confidence interval [CI], 18.7%-43.2%) to 42.5% (95% CI, 30.7%-54.8%) after the 2 campaigns (P < .0001) but dropped to 36.4% (95% CI, 30.5%-44.5%) after 2 years (P < .001). Three of the 8 intensive care units that showed a significant increase after the campaigns did not maintain the increased compliance at 2 years' follow-up. We conclude that educational programs should be repeatedly conducted to maintain high adherence to hand hygiene standards in health care settings. | 25,179,336 | [
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Evaluation of 2 sets of screening criteria for ventilator-associated pneumonia in a children's hospital. | We compared current Centers for Disease Control and Prevention surveillance criteria with the newer adult screening criteria (ASC) for identifying pediatric ventilator-associated pneumonia (VAP). Possible cases of VAP identified by ASC (n = 17) and cases of VAP identified by the older current surveillance criteria (n = 15) are comparable, but only 9 were identified by both. Positive end expiratory pressure was inferior to fraction of inspired oxygen in identifying ventilator-associated conditions by ASC. | 25,179,337 | [
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Challenge of managing distal femur fractures with long-stemmed total knee implants. | Treatment of distal femur fractures by long-stemmed total knee arthroplasty (TKA) is challenging, because of poor bone stock, decreased blood supply, history of multiple knee surgeries and an absence of standard treatment. Few published studies are available concerning this. The purpose of this study was to share surgical technique and better describe our patients' comorbidities, which add to the challenge of managing individuals with these fractures. Between August 2008 and September 2013, seven patients presented to our level I trauma center with distal femoral fractures associated with long-stemmed TKA implants. Their average age was 68.71 years (range, 52-81 years).The most common mechanism of injury was fall (five patients), followed by a traumatic fracture of the femur while walking (one patient), and being lifted out of bed (the one nonambulatory patient). This retrospective study reports a treatment protocol, including surgical technique, and short-term outcome in seven patients in whom locking compression plates (LCP) were used. Six fractures were classified as Rorabeck type II, and one as type III. The average time to full-weight-bearing was 5.5 months. At this institution, good short-term results have been achieved by using an LCP with screws placed proximal to the long-stem and distal to the fracture. The six patients all achieved full-weight-bearing,taking an average of 5.5 months (range, 3-7 months). LCP is an effective form of management of distal femur fractures around long stem TKAs. An individualized operative approach possibly incorporating bone-graft substitutes, cerclage wire and a post-operative bone stimulator is recommended. | 25,179,356 | [
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Laser scanning photothermal microscopy: fast detection and imaging of gold nanoparticles. | We report on the design and construction of a laser scanning photothermal microscope and present images of gold nanoparticles of size as small as 5 nm. Laser scanning method allows fast image acquisition at 80 μs pixel dwell time so that a 500 × 500 pixel image is acquired in 20 s. Photothermal imaging at fast time scales can have potential applications in variety of fields including tracking of biomolecular transport processes. | 25,179,372 | [
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Preappointment testing for BRAF/KIT mutation in advanced melanoma: a model in molecular data delivery for individualized medicine. | The emergence of individualized medicine is driven by developments in precision diagnostics, epitomized by molecular testing. Because treatment decisions are being made based on such molecular data, data management is gaining major importance. Among data management challenges, creating workflow solutions for timely delivery of molecular data has become pivotal. This study aims to design and implement a scalable process that permits preappointment BRAF/KIT mutation analysis in melanoma patients, allowing molecular results necessary for treatment plans to be available before the patient's appointment. Process implementation aims to provide a model for efficient molecular data delivery for individualized medicine. We examined the existing process of BRAF/KIT testing in melanoma patients visiting our institution for oncology consultation. We created 5 working groups, each designing a specific segment of an alternative process that would allow preappointment BRAF/KIT testing and delivery of results. Data were captured and analyzed to evaluate the success of the alternative process. For 1 year, 35 (59%) of 55 patients had prior BRAF/KIT testing. The remaining 20 patients went through the new process of preappointment testing; results were available at the time of appointment for 12 patients (overall preappointment results availability, 85.5%). The overall process averaged 13.4 ± 4.7 days. In conclusion, we describe the successful implementation of a scalable workflow solution that permits preappointment BRAF/KIT mutation analysis and result delivery in melanoma patients. This sets the stage for further applications of this model to other conditions, answering an increasing demand for robust delivery of molecular data for individualized medicine. | 25,179,409 | [
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Self-efficacy and affect as mediators between pain dimensions and emotional symptoms and functional limitation in women with fibromyalgia. | The aim of this study was to investigate the role of self-efficacy and affect as mediators of the relationship between pain and several fibromyalgia (FM) symptoms (functional limitation, depression, and anxiety). We evaluated 144 women with FM for self-reported pain (numerical pain scale), pressure pain sensitivity (pressure pain thresholds), functional limitation (Fibromyalgia Impact Questionnaire), self-efficacy (Chronic Pain Self-Efficacy Scale), depression-anxiety (Hospital Anxiety and Depression Scale), and positive-negative affect (Positive-Negative Affect Scale). Mediating analyses were conducted with ordinary least squares multiple regression analysis. The results demonstrated that self-reported pain and pressure pain sensitivity exhibited significant relationships with functional limitation, anxiety, depression, self-efficacy, and affect. Affect mediated the relationship between pressure pain sensitivity and anxiety, whereas self-efficacy was the mediating variable between self-reported pain and functional limitation and depression. Our results support a complex nature of pain in women presenting with FM, as cognitive and emotional variables have different mediator relationships between pain dimensions and functional and emotional outcomes in women with FM. | 25,179,423 | [
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Study of structural, electronic and optical properties of tungsten doped bismuth oxychloride by DFT calculations. | First-principle calculations have been carried out to investigate structural stabilities, electronic structures and optical properties of tungsten doped bismuth oxychloride (BiOCl). The structures of substitutional and interstitial tungsten, and in the form of WO6-ligand-doped BiOCl are examined. The substitutional and interstitial tungsten doping leads to discrete midgap states within the forbidden band gap, which has an adverse effect on the photocatalytic properties. On the other hand, the WO6-ligand-doped BiOCl structure induces a continuum of hybridized states in the forbidden gap, which favors transport of electrons and holes and could result in enhancement of visible light activity. In addition, the band gap of WO6-BiOCl decreases by 0.25 eV with valence band maximum (VBM) shifting upwards compared to that of pure BiOCl. By calculating optical absorption spectra of pure BiOCl and WO6-ligand-doped BiOCl structure, it is found that the absorption peak of the WO6-ligand-doped BiOCl structure has a red shift towards visible light compared with that of pure BiOCl, which agrees well with experimental observations. These results reveal the tungsten doped BiOCl system as a promising material in photocatalytic decomposition of organics and water splitting under sunlight irradiation. | 25,179,434 | [
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Epidemiology of Clostridium difficile: a hospital-based descriptive study in Argentina and Mexico. | A prospective study was conducted in four tertiary hospitals in Argentina and Mexico in order to describe the occurrence of Clostridium difficile infection (CDI) in these settings. The objective was to evaluate the incidence of CDI in at-risk populations in Argentina (one center) and Mexico (three centers) and to further explore potential study sites for vaccine development in this region. A prospective, descriptive, CDI surveillance study was conducted among hospitalized patients aged ≥40 years who had received ≥48h of antibiotic treatment. Stool samples were collected from those with diarrhea within 30 days after starting antibiotics and analyzed for toxins A and B by ELISA, and positive samples were further tested by toxinogenic culture and restriction endonuclease analysis type assay. Overall, 466 patients were enrolled (193 in Argentina and 273 in Mexico) of whom 414 completed the follow-up. Of these, 15/414 (3.6%) experienced CDI episodes occurring on average 18.1 days after admission to hospital and 15.9 days after the end of antibiotics treatment. The incidence rate of CDI was 3.1 (95% CI 1.7-5.2) per 1000 patient-days during hospitalization, and 1.1 (95% CI 0.6-1.8) per 1000 patient-days during the 30-day follow-up period. This study highlighted the need for further evaluation of the burden of CDI in both countries, including the cases occurring after discharge from hospital. | 25,179,510 | [
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Overuse of compression ultrasound for patients with lower extremity cellulitis. | Compression ultrasound (CUS) is often ordered in hospitalized patients with cellulitis to assess for deep vein thrombosis (DVT). Despite this common practice, the rate of use and utility of CUS has not been well described. We conducted a retrospective cohort study of adult patients with lower extremity cellulitis hospitalized between October 1, 2008 and September 30, 2013 at an academic medical center. Cases meeting inclusion criteria were reviewed for the use of CUS, the indication for CUS, the occurrence of DVT, and the 3 month follow-up occurrence of DVT after discharge. A total of 239 patients were identified using ICD-9 coding data with a discharge diagnosis of cellulitis or abscess of leg. Of these, 183 met criteria for inclusion in the study, 133 of whom had CUS to assess for DVT (73%). Of the 133 who received CUS, 11 studies found DVTs (8%). Of the 11 DVTs, 8 had been previously diagnosed, and 3 were new. Of the new DVTs, only one was ipsilateral to the leg with cellulitis. Most patients admitted with lower extremity cellulitis received CUS to assess for DVT. Despite this common practice, the rate of acute ipsilateral DVT was low and matched the rate of acute contralateral DVT. Previously diagnosed DVTs were commonly re-imaged. Overall the use of CUS had minimal impact on patient management and the routine use of CUS to assess for DVT in hospitalized patients with cellulitis appears to be unnecessary. | 25,179,516 | [
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Molecular basis of the clotting defect in a bleeding patient missing the Asp-185 codon in the factor X gene. | Factor X (FX) is a vitamin K-dependent plasma zymogen, which following activation to factor Xa (FXa), converts prothrombin to thrombin in the blood clotting cascade. It was recently demonstrated that a natural variant of FX carrying the Asp-185 deletion (FX-D185del, chymotrypsinogen numbering) was associated with mild bleeding in a patient with severe FX deficiency. In this study, we expressed FX-D185del in mammalian cells and characterized its properties in appropriate kinetic assays in purified systems. We discovered that while the FX variant can be normally activated by physiological activators; both amidolytic and proteolytic activities of the mutant are dramatically impaired. Interestingly, factor Va (FVa) significantly improved the proteolytic defect when the mutant protease was assembled into the prothrombinase complex. Thus, in contrast to >50-fold catalytic defect in the absence of FVa, the variant activated prothrombin with only ~2.5-fold decreased catalytic efficiency in the presence of the cofactor. The FXa variant dramatically lost its susceptibility to inhibition by antithrombin and tissue factor pathway inhibitor, thus exhibiting ~2-3 orders of magnitude lower reactivity with the plasma inhibitors. Further studies revealed that Na(+) no longer activates the variant protease, suggesting that the functionally important allosteric linkage between the Na(+)-binding and the P1-binding sites of the protease has been eliminated. These results suggest that the lower catalytic efficiency of FXa-D185del in the bleeding patient may be partially compensated by the loss of its reactivity with plasma inhibitors, possibly explaining the basis for the paradoxical severe FX deficiency with only mild bleeding tendency for this mutation. | 25,179,519 | [
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Assessing accuracy in citizen science-based plant phenology monitoring. | In the USA, thousands of volunteers are engaged in tracking plant and animal phenology through a variety of citizen science programs for the purpose of amassing spatially and temporally comprehensive datasets useful to scientists and resource managers. The quality of these observations and their suitability for scientific analysis, however, remains largely unevaluated. We aimed to evaluate the accuracy of plant phenology observations collected by citizen scientist volunteers following protocols designed by the USA National Phenology Network (USA-NPN). Phenology observations made by volunteers receiving several hours of formal training were compared to those collected independently by a professional ecologist. Approximately 11,000 observations were recorded by 28 volunteers over the course of one field season. Volunteers consistently identified phenophases correctly (91% overall) for the 19 species observed. Volunteers demonstrated greatest overall accuracy identifying unfolded leaves, ripe fruits, and open flowers. Transitional accuracy decreased for some species/phenophase combinations (70% average), and accuracy varied significantly by phenophase and species (p < 0.0001). Volunteers who submitted fewer observations over the period of study did not exhibit a higher error rate than those who submitted more total observations. Overall, these results suggest that volunteers with limited training can provide reliable observations when following explicit, standardized protocols. Future studies should investigate different observation models (i.e., group/individual, online/in-person training) over subsequent seasons with multiple expert comparisons to further substantiate the ability of these monitoring programs to supply accurate broadscale datasets capable of answering pressing ecological questions about global change. | 25,179,528 | [
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Effects of temperature on mortality in Hong Kong: a time series analysis. | Although interest in assessing the impacts of hot temperature and mortality in Hong Kong has increased, less evidence on the effect of cold temperature on mortality is available. We examined both the effects of heat and cold temperatures on daily mortality in Hong Kong for the last decade (2002-2011). A quasi-Poisson model combined with a distributed lag non-linear model was used to assess the non-linear and delayed effects of temperatures on cause-specific and age-specific mortality. Non-linear effects of temperature on mortality were identified. The relative risk of non-accidental mortality associated with cold temperature (11.1 °C, 1st percentile of temperature) relative to 19.4 °C (25th percentile of temperature) was 1.17 (95% confidence interval (CI): 1.04, 1.29) for lags 0-13. The relative risk of non-accidental mortality associated with high temperature (31.5 °C, 99th percentile of temperature) relative to 27.8 °C (75th percentile of temperature) was 1.09 (95% CI: 1.03, 1.17) for lags 0-3. In Hong Kong, extreme cold and hot temperatures increased the risk of mortality. The effect of cold lasted longer and greater than that of heat. People older than 75 years were the most vulnerable group to cold temperature, while people aged 65-74 were the most vulnerable group to hot temperature. Our findings may have implications for developing intervention strategies for extreme cold and hot temperatures. | 25,179,530 | [
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Evaluation of an immunological score to assess the risk of severe infection in heart recipients. | We previously reported how specific humoral and cellular immunological markers that are readily available in clinical practice can be used to identify heart transplant recipients (HTR) at risk of developing severe infections. In this study, we perform an extended analysis to identify immunological profiles that could prove to be superior to individual markers in assessing the risk of infection early after heart transplantation. In a prospective follow-up study, we evaluated 100 HTR at 1 week after transplantation. Laboratory tests included determination of immunoglobulin (Ig) levels (IgG, IgA, IgM), complement factors (C3 and C4), and lymphocyte subsets (CD3+, CD4+, CD8+ T cells, B cells, and natural killer [NK] cells). The prevalence of infection during the first 3 months was registered at scheduled visits after transplantation. Severe infections were defined as all infections requiring hospitalization and intravenous antimicrobial therapy. During follow-up, 33 patients (33%) developed severe infections. The individual risk factors of severe infection, according to the Cox regression analysis, were as follows: IgG <600 mg/dL (hazard ratio [HR], 2.41; 95% confidence interval [CI], 1.21-4.78; P = 0.012), C3 <80 mg/dL (HR, 4.65; 95% CI, 2.31-9.38; P < 0.0001), C4 <18 mg/dL (HR 2.30, 95% CI, 1.15-4.59; P = 0.018), NK count <30 cells/μL (HR 4.07, 95% CI, 1.76-9.38; P = 0.001), and CD4 count <350 cells/μL (HR, 3.04; 95% CI, 1.47-6.28; P = 0.0027). An immunological score was created. HRs were used to determine the number of points assigned to each of the 5 previously mentioned individual risk factors. The score was obtained from the sum of these factors. In the multivariate Cox regression analysis, the immunological score was useful for identifying patients at risk of infection and was the only variable that maintained a significant association with the development of infection, after adjustment for the 5 individual factors. Patients with an immunological score ≥13 were at the highest risk of severe infections (HR, 9.29; 95% CI, 4.57-18.90; P < 0.0001). This score remained significantly associated with the risk of severe infection after adjustment for clinical risk factors of infection. An immunological score was useful for identifying HTR at risk of developing severe infections. If this score is validated in multicenter studies, it could be easily introduced into clinical practice. | 25,179,534 | [
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Ellagic acid enhances morphine analgesia and attenuates the development of morphine tolerance and dependence in mice. | According to our previous study, ellagic acid has both dose-related central and peripheral antinociceptive effect through the opioidergic and l-arginine-NO-cGMP-ATP sensitive K(+) channel pathways. In the present study, the systemic antinociceptive effects of ellagic acid in animal models of pain, and functional interactions between ellagic acid and morphine in terms of analgesia, tolerance and dependence were investigated. Ellagic acid (1-30mg/kg; i.p.) showed significant and dose-dependent antinociceptive effects in the acetic acid-induced writhing test. Intraperitoneal ellagic acid acutely interacted with morphine analgesia in a synergistic manner in this assay. Ellagic acid (1-10mg/kg; i.p.) also exerted analgesic activity in the hot-plate test. Pre-treatment with naloxone (1mg/kg; i.p.) significantly reversed ellagic acid, morphine as well as ellagic acid-morphine combination-induced antinociceptin in these two tests. More importantly, when co-administered with morphine, ellagic acid (1-10mg/kg) effectively blocked the development of tolerance to morphine analgesia in the hot-plate test. Likewise, ellagic acid dose-dependently prevented naloxone-precipitated withdrawal signs including jumping and weight loss. Ellagic acid treatment (1-30mg/kg; i.p.) had no significant effect on the locomotion activity of animals using open-field task. Therefore, these results showed that ellagic acid has notable systemic antinociceptive activity for both tonic and phasic pain models. Altogether, ellagic acid might be used in pain relief alone or in combination with opioid drugs because of enhancing morphine analgesia and preventing morphine-induced tolerance to analgesia and dependence. | 25,179,576 | [
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Defective channels lead to an impaired skin barrier. | Channels are integral membrane proteins that form a pore, allowing the passive movement of ions or molecules across a membrane (along a gradient), either between compartments within a cell, between intracellular and extracellular environments or between adjacent cells. The ability of cells to communicate with one another and with their environment is a crucial part of the normal physiology of a tissue that allows it to carry out its function. Cell communication is particularly important during keratinocyte differentiation and formation of the skin barrier. Keratinocytes in the skin epidermis undergo a programme of apoptosis-driven terminal differentiation, whereby proliferating keratinocytes in the basal (deepest) layer of the epidermis stop proliferating, exit the basal layer and move up through the spinous and granular layers of the epidermis to form the stratum corneum, the external barrier. Genes encoding different families of channel proteins have been found to harbour mutations linked to a variety of rare inherited monogenic skin diseases. In this Commentary, we discuss how human genetic findings in aquaporin (AQP) and transient receptor potential (TRP) channels reveal different mechanisms by which these channel proteins function to ensure the proper formation and maintenance of the skin barrier. | 25,179,597 | [
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B56-PP2A regulates motor dynamics for mitotic chromosome alignment. | Proper alignment of duplicated chromosomes at the metaphase plate involves both motor-driven chromosome movement and the functional and physical end-on connection (K-fiber formation) between the kinetochore and the plus-end of microtubules. The B56 family of protein phosphatase 2A (PP2A) regulatory subunits (B56-PP2A), through their interaction with the mitotic checkpoint protein BUBR1, are required for proper chromosome alignment, but the underlying mechanism(s) has remained elusive. Here, we show that B56-PP2A promotes chromosome alignment primarily by balancing chromosome movement towards the metaphase plate, rather than by directly establishing stable K-fibers. Notably, the poleward movement of chromosomes in cells depleted of the B56 family can be rescued by depletion of HSET (also known as kinesin-14 or KIFC1), a major minus-end-directed motor protein. Strikingly, K-fiber formation can be restored if chromosome movement to the metaphase plate is rescued in B56-depleted cells. Furthermore, the B56-BUBR1 interaction is required for promoting motor-driven chromosome movement towards the metaphase plate. Thus, we propose that B56-PP2A functions in mitotic chromosome alignment by balancing chromosome movement towards the metaphase plate, which is essential for the subsequent establishment of stable and functional kinetochore-microtubule attachments, and mitotic exit. | 25,179,604 | [
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Revision workshops in elementary mathematics enhance student performance in routine laboratory calculations. | The ability to understand and implement calculations required for molarity and dilution computations that are routinely undertaken in the laboratory are essential skills that should be possessed by all students entering an undergraduate Life Sciences degree. However, it is increasingly recognized that the majority of these students are ill equipped to reliably carry out such calculations. There are several factors that conspire against students' understanding of this topic, with the alien concept of the mole in relation to the mass of compounds and the engineering notation required when expressing the relatively small quantities typically involved being two key examples. In this report, we highlight teaching methods delivered via revision workshops to undergraduate Life Sciences students at the University of Nottingham. Workshops were designed to 1) expose student deficiencies in basic numeracy skills and remedy these deficiencies, 2) introduce molarity and dilution calculations and illustrate their workings in a step-by-step manner, and 3) allow students to appreciate the magnitude of numbers. Preworkshop to postworkshop comparisons demonstrated a considerable improvement in students' performance, which attenuated with time. The findings of our study suggest that an ability to carry out laboratory calculations cannot be assumed in students entering Life Sciences degrees in the United Kingdom but that explicit instruction in the form of workshops improves proficiency to a level of competence that allows students to prosper in the laboratory environment. | 25,179,614 | [
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The psychiatric ward as a therapeutic space: systematic review. | Hospital care is still an integral part of mental healthcare services. But the impact of ward design on treatment outcomes is unclear. To review the effects of ward design on patient outcomes and patient and staff well-being. A systematic review of literature was carried out on Medline, Embase and PsycINFO. Papers on psychogeriatric and child and adolescent wards were excluded as these necessitate specific safety features. Twenty-three papers were identified. No strong causal links between design and clinical outcomes were found. Private spaces and a homely environment may contribute to patient well-being. Different stakeholders may experience ward design in conflicting ways; design has a symbolic and social dimension for patients. Data on the impact of design on treatment outcomes are inconclusive. Rigorous randomised controlled trials, qualitative studies and novel methods are called for. Different stakeholders' responses to the ward as a symbolic environment merit further investigation. | 25,179,622 | [
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Cofilin recruits F-actin to SPCA1 and promotes Ca2+-mediated secretory cargo sorting. | The actin filament severing protein cofilin-1 (CFL-1) is required for actin and P-type ATPase secretory pathway calcium ATPase (SPCA)-dependent sorting of secretory proteins at the trans-Golgi network (TGN). How these proteins interact and activate the pump to facilitate cargo sorting, however, is not known. We used purified proteins to assess interaction of the cytoplasmic domains of SPCA1 with actin and CFL-1. A 132-amino acid portion of the SPCA1 phosphorylation domain (P-domain) interacted with actin in a CFL-1-dependent manner. This domain, coupled to nickel nitrilotriacetic acid (Ni-NTA) agarose beads, specifically recruited F-actin in the presence of CFL-1 and, when expressed in HeLa cells, inhibited Ca(2+) entry into the TGN and secretory cargo sorting. Mutagenesis of four amino acids in SPCA1 that represent the CFL-1 binding site also affected Ca(2+) import into the TGN and secretory cargo sorting. Altogether, our findings reveal the mechanism of CFL-1-dependent recruitment of actin to SPCA1 and the significance of this interaction for Ca(2+) influx and secretory cargo sorting. | 25,179,631 | [
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Predictive significance of absolute lymphocyte count and morphology in adults with a new onset peripheral blood lymphocytosis. | Lymphocytosis is commonly encountered in the haematology laboratory. Evaluation of blood films is an important screening tool for differentiating between reactive and malignant processes. The optimal lymphocyte number to trigger morphological evaluation of the smear has not been well defined in the literature. Likewise, the significance of lymphocyte morphology has not been well studied and there are no consensus guidelines or follow-up recommendations available. We attempt to evaluate the significance of lymphocyte morphology and to define the best possible cut-off value of absolute lymphocyte count for morphology review. 71 adult patients with newly detected lymphocytosis of 5.0×10(9)/L or more were categorised to either a reactive process or a lymphoproliferative disorder. We performed statistical analysis and morphology review to compare the difference in age, gender, lymphocyte count and morphological features between the two groups. Receiver operating characteristic analysis was performed to determine an optimal lymphocyte number to trigger morphology review. Lymphoproliferative disorders are associated with advanced age and higher lymphocyte count. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of lymphocyte morphology as a screening test were 0.9, 0.59, 0.60, 0.58 and 0.71, respectively. The optimal cut-off of lymphocyte number for morphology review was found to be close to 7×10(9)/L. We found a moderate interobserver agreement for the morphological assessment. 'Reactive' morphology was very predictive of a reactive process, but 'malignant' morphology was a poor predictor of a lymphoproliferative disorder. | 25,179,641 | [
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Exercise equipment preferences among adults with spinal cord injury. | Cross-sectional. To evaluate exercise equipment preferences and compare cardiometabolic demand for passive hybrid and arm-only exercise among adults with paraplegia (PP) and those with tetraplegia (TP). Four community exercise programmes. Thirty-six adults (mean age: 41.1±12.1 years) with chronic (11.4±10.7 years post injury) TP (C3-C8; n=17) or PP (T3-T12; n=19) were recruited. Participants completed 20 min of submaximal aerobic exercise at moderate to vigorous intensity on four types of aerobic exercise equipment: arm cycle ergometer (ACE), arm glider (AG), arm-leg recumbent stepper (ALRS), and arm-leg cycle ergometer (ALCE). Participants also completed 3 sets of 10 repetitions of resistance exercise using wall pulleys (WP) and weight stack (WS) equipment. A questionnaire was administered to evaluate equipment preference. Heart rate (HR) and oxygen uptake (VO2) were measured in a subset of participants (n=9) during submaximal aerobic exercise. Arm-only exercise modes were perceived as being safer than passive hybrid exercise modes. There were no differences in perceived enjoyment between equipment types and groups. There were significant group but not equipment differences in HR (TP: 101.4 bpm; PP: 124.9 bpm) and VO2 (TP: 6.5 ml•kg(-1)•min(-1); PP: 10.5 mL•kg(-1)•min(-1)) during submaximal aerobic exercise. In this cross-community assessment of exercise equipment preferences after spinal cord injury (SCI), arm-only exercise modes were perceived as safer than hybrid exercise modes and there were no differences between equipment types in physiological responses. | 25,179,653 | [
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Study design to develop and pilot-test a web intervention for partners of military service members with alcohol misuse. | Alcohol misuse among military service members from the recent conflicts in Iraq and Afghanistan is over two times higher compared to misuse in the civilian population. Unfortunately, in addition to experiencing personal consequences from alcohol misuse, partners and family members of alcohol-misusing service members also suffer in negative ways from their loved one's drinking. These family members represent important catalysts for helping their loved ones identify problem drinking and overcoming the barriers to seeking care. This paper describes the protocol to a pilot study evaluating a 4-session, web-based intervention (WBI) for concerned partners (CPs) of service members with alcohol misuse. The WBI will be adapted from the Community Reinforcement and Family Training (CRAFT) intervention. In the first phase, we will develop and beta-test the WBI with 15-20 CPs. In the second phase, we will randomize CPs to WBI (n = 50) or to delayed-WBI (n = 50) and evaluate the impact of the WBI on CPs' perceptions of service member help-seeking and drinking, as well as the CP's well-being and relationship satisfaction 3 months after the intervention. In the third phase, we will recruit 15-20 service members whose partners have completed the study. We will interview the service members to learn how the CP-focused WBI affected them and to assess whether they would be receptive to a follow-on WBI module to help them. This project has the potential to benefit a large population of military service members who may be disproportionately affected by recent conflicts and whose drinking misuse would otherwise go undetected and untreated. It also develops a new prevention model that does not rely on service members or partners attending a hospital or clinical facility to access care. NCT02073825. | 25,179,672 | [
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EEG biofeedback for autism spectrum disorder: a commentary on Kouijzer et al. (2013). | Research conducted by Kouijzer et al. (Appl Psychophysiol Biofeedback 38(1):17-28, 2013) compared the effects of skin conductance biofeedback and EEG-biofeedback on patients with autistic spectrum disorders to determine their relative efficacy. While they found a difference between treatment and control groups, there was no significant difference on many variables between the two treatment groups. From this, the increase in symptom alleviation from autistic spectrum disorder was attributed to non-specific factors surrounding the study. We now offer alternative explanations for their findings and propose different options for future studies. We hypothesize that the location and type of neurofeedback used adversely impacted the findings. We speculate that had they used a form of EEG-biofeedback that can combat deficiencies in connectivity and also trained the areas of the brain most affected by autism, there may have then been a significant difference between the effectiveness of EEG-biofeedback versus skin conductance biofeedback. | 25,179,674 | [
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Resident mesenchymal progenitors of articular cartilage. | Articular cartilage has poor capacity of self-renewal and repair. Insufficient number and activity of resident mesenchymal (connective tissue) progenitors is likely one of the underlying reasons. Chondroprogenitors reside not only in the superficial zone of articular cartilage but also in other zones of articular cartilage and in the neighboring tissues, including perichondrium (groove of Ranvier), synovium and fat pad. These cells may respond to injury and contribute to articular cartilage healing. In addition, marrow stromal cells can migrate through subchondral bone when articular cartilage is damaged. We should develop drugs and methods that correctly stimulate resident progenitors for improvement of repair and inhibition of degenerative changes in articular cartilage. | 25,179,676 | [
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Glucose increases interleukin-12 gene expression and production in stimulated peripheral blood mononuclear cells of type 2 diabetes patients. | Lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) of type 2 diabetes patients produce more interleukin (IL)-12 under glucose treatment. The aim of this study was to determine whether increased IL-12 response in hyperglycemic LPS-stimulated PBMCs is due to increased gene expression or osmolarity. LPS-stimulated PBMCs of 13 type 2 diabetes patients and 8 healthy controls were used for culture in the presence or absence of glucose or mannitol for 24 h. The IL-12 gene expressions of PBMCs and IL-12 protein levels in supernatants were evaluated. After 24 h, the stimulated PBMCs of diabetes patients expressed more IL-12 mRNA and produced more IL-12 protein following glucose treatment than those without glucose treatment and with mannitol treatment. Stimulated PBMCs of controls did not express more IL-12 mRNA and produce more IL-12 protein following glucose treatment than those without glucose treatment and with mannitol treatment. Glucose increases the IL-12 production in stimulated PBMCs of diabetes patients through increased IL-12 gene expression. | 25,179,705 | [
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Laboratory evaluation of phenotypic detection methods of methicillin-resistant Staphylococcus aureus. | Although conventional antibiotic susceptibility tests are most commonly performed for methicillin-resistant Staphylococcus aureus (MRSA), the results of these phenotypic tests are dependent on the standardization of the culture conditions. The aim of the study was to evaluate the conventional phenotypic screening tests in comparison to the mecA gene polymerase chain reaction (PCR). One hundred and two clinical isolates of MRSA identified by the oxacillin disk diffusion were subjected to PCR for the mecA gene and by the cefoxitin disk diffusion test and culture on oxacillin screen agar, mannitol salt agar, and methicillin-resistant Staphylococcus aureus Agar (MeReSA) selective medium, for MRSA. Although all 102 isolates were resistant in oxacillin and cefoxitin disk diffusion, 92 (90.1%) isolates were positive for the mecA gene. The sensitivities of the mannitol salt agar, MeReSA agar, and oxacillin screen agar were 89.13, 97.82, and 98.91%, respectively. The oxacillin screen agar may be recommended for confirming methicillin resistance in the disk diffusion test in resource-poor settings, where molecular methods are not available. | 25,179,712 | [
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Impact of the gut microbiota, prebiotics, and probiotics on human health and disease. | Recent studies have revealed that the gut microbiota regulates many physiological functions, ranging from energy regulation and cognitive processes to toxin neutralization and immunity against pathogens. Accordingly, alterations in the composition of the gut microbiota have been shown to contribute to the development of various chronic diseases. The main objectives of this review are to present recent breakthroughs in the study of the gut microbiota and show that intestinal bacteria play a critical role in the development of different disease conditions, including obesity, fatty liver disease, and lung infection. We also highlight the potential application of prebiotics and probiotics in maintaining optimal health and treating chronic inflammatory and immunity-related diseases. | 25,179,725 | [
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Activation of the vascular niche supports leukemic progression and resistance to chemotherapy. | Understanding the intricate cellular components of the bone marrow microenvironment can lead to the discovery of novel extrinsic factors that are responsible for the initiation and progression of leukemic disease. We have shown that endothelial cells (ECs) provide a fertile niche that allows for the propagation of primitive and aggressive leukemic clones. Activation of the ECs by vascular endothelial growth factor (VEGF)-A provides cues that enable leukemic cells to proliferate at higher rates and also increases the adhesion of leukemia to ECs. Vascular endothelial growth factor A-activated ECs decrease the efficacy of chemotherapeutic agents to target leukemic cells. Inhibiting VEGF-dependent activation of ECs by blocking their signaling through VEGF receptor 2 increases the susceptibility of leukemic cells to chemotherapy. Therefore, the development of drugs that target the activation state of the vascular niche could prove to be an effective adjuvant therapy in combination with chemotherapeutic agents. | 25,179,751 | [
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Molecular surveillance of pvdhfr, pvdhps, and pvmdr-1 mutations in Plasmodium vivax isolates from Yunnan and Anhui provinces of China. | Plasmodium vivax is the predominant species of human malaria parasites present in China. Although sulphadoxine-pyrimethamine (SP) and chloroquine (CQ) have been widely used for malaria treatment in China, the resistance profiles of these drugs are not available. Analysis of dihydrofolate reductase (dhfr), dihydropteroate synthase (dhps), and multidrug resistance (mdr-1) gene mutations in P. vivax isolates is a valuable molecular approach for mapping resistance to SP and CQ. This study investigates the prevalence of pvdhfr, pvdhps, and pvmdr-1 of P. vivax clinical isolates from China and provides baseline molecular epidemiologic data on SP- and CQ-associated resistance in P. vivax. Plasmodium vivax clinical isolates were collected from two malaria-endemic regions of China, subtropical (Xishuangbanna, Yunnan province) and temperate (Bozhou, Anhui province), from 2009 to 2012. All isolates were analysed for single nucleotide polymorphism haplotypes in pvdhfr, pvdhps, and pvmdr-1 using direct DNA sequencing. In pvdhfr, 15% of Xishuangbanna isolates carried wild-type (WT) allele, whereas the majority of isolates carried mutant genes with substitutions at five codons. Eight mutant haplotypes of pvdhfr were detected, while limited polymorphism of pvdhfr was found in Bozhou isolates. A size polymorphism was present in pvdhfr, with the three-repeat type being the most predominate in both Xishuangbanna (79%) and Bozhou (97%) isolates. In pvdhps, mutations at four codons were detected in Xishuangbanna isolates leading to six haplotypes, including WT allele, single-mutation, double-mutation, and triple-mutation alleles. All Bozhou isolates carried WT pvhdps. In pvmdr-1, isolates from Xishuangbanna carried mutations at codons Y976F and F1076L, whereas all isolates from Bozhou had only a single mutation at codon F1076L. Plasmodium vivax isolates from subtropical and temperate zones of China are shown to have dramatically different frequencies and patterns of mutations in pvdhfr, pvdhps, and pvmdr-1. Whereas P. vivax populations in subtropical China are highly resistant to SP and CQ, those in the temperate zone may still be susceptible to SP and CQ. This information is useful for establishing treatment policy and provides a baseline for molecular surveillance of drug-resistant P. vivax in these areas. | 25,179,752 | [
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Long-term clinical effects of ventricular pacing reduction with a changeover mode to minimize ventricular pacing in a general pacemaker population. | Right ventricular pacing (VP) has been hypothesized to increase the risk in heart failure (HF) and atrial fibrillation (AF). The ANSWER study evaluated, whether an AAI-DDD changeover mode to minimize VP (SafeR) improves outcome compared with DDD in a general dual-chamber pacemaker population. ANSWER was a randomized controlled multicentre trial assessing SafeR vs. standard DDD in sinus node disease (SND) or AV block (AVB) patients. After a 1-month run-in period, they were randomized (1 : 1) and followed for 3 years. Pre-specified co-primary end-points were VP and the composite of hospitalization for HF, AF, or cardioversion. Pre-specified secondary end-points were cardiac death or HF hospitalizations and cardiovascular hospitalizations. ANSWER enrolled 650 patients (52.0% SND, 48% AVB) at 43 European centres and randomized in SafeR (n = 314) or DDD (n = 318). The SafeR mode showed a significant decrease in VP compared with DDD (11.5 vs. 93.6%, P < 0.0001 at 3 years). Deaths and syncope did not differ between randomization arms. No significant difference between groups [HR = 0.78; 95% CI (0.48-1.25); P = 0.30] was found in the time to event of the co-primary composite of hospitalization for HF, AF, or cardioversion, nor in the individual components. SafeR showed a 51% risk reduction (RR) in experiencing cardiac death or HF hospitalization [HR = 0.49; 95% CI (0.27-0.90); P = 0.02] and 30% RR in experiencing cardiovascular hospitalizations [HR = 0.70; 95% CI (0.49-1.00); P = 0.05]. SafeR safely and significantly reduced VP in a general pacemaker population though had no effect on hospitalization for HF, AF, or cardioversion, when compared with DDD. | 25,179,761 | [
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Successful thrombectomy for coronary embolism likely due to floating aortic plaque in ascending aorta. | A 70-year-old man with chest pain underwent coronary intervention for acute myocardial infarction. We immediately performed coronary thrombectomy with aspiration catheter and collected solid material as a result. After aspiration, we achieved thrombolysis in myocardial infarction trial (TIMI)-flow grade 3 without stenosis. Transesophageal echocardiography showed no intracardiac thrombus but pronounced mobile aortic plaque in ascending aorta. Transthoracic echocardiography showed moderate aortic regurgitation. A histological examination of retrieved material revealed severe calcified atherosclerotic plaque without thrombotic components. Thereby, coronary embolism in this case may have been caused by embolism of flaked aortic plaque, which was possibly carried by aortic regurgitation flow. | 25,179,773 | [
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Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome? | The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen-antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary. | 25,179,813 | [
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A novel minisequencing single-nucleotide polymorphism marker of the lysozyme gene detects high hatchability of Tsaiya ducks (Anas platyrhynchos). | Lysozyme, one of the major albumen antimicrobials, can break down the polysaccharide walls of a broad spectrum of bacteria. This study presents a novel lysozyme marker of high hatchability in the form of minisequencing single-nucleotide polymorphisms (SNPs). Recently, lysozyme was identified by complementary DNA microarray analysis as one of several differentially expressed genes noted to influence hatchability and recognized as a marker candidate for animal marker-assisted selection. Higher levels (P < 0.05) of lysozyme mRNA (via real-time polymerase chain reaction analysis) and protein (in Western blotting results) were found to be associated with a high-hatchability phenotype. In the preliminary sequence analysis of this study, TsLy1-1 and TsLy1-2 primer pairs, designed according to the lysozyme sequence, were used to amplify small-scale genomic DNA samples from animals in two extreme groups of hatchability. Sequence analysis of the amplified 763-bp DNA products clearly showed that AA and GG genotypes of SNP g.390A > G were from the ducks of the low- and high-hatchability groups, respectively. The SNP g.390A > G also created a new specificity protein 1 transcription factor binding site in the lysozyme gene. Primer pairs of TsLy2-1 and TsLy2-2 then probed the amplified 763-bp DNA products to produce a shorter fragment for easier minisequencing analysis to divide 114 ducks into GG, GA, and AA genotypes. The GG ducks had the highest hatchability, representing that a new lysozyme SNP marker of good hatchability performance can be used for the purpose of marker-assisted selection in Tsaiya ducks. | 25,179,861 | [
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Characterization of Acetobacter pomorum KJY8 isolated from Korean traditional vinegar. | Acetobacter sp. strains were isolated from traditional vinegar collected in Daegu city and Gyeongbuk province. The strain KJY8 showing a high acetic acid productivity was isolated and characterized by phenotypic, chemotaxonomic, and phylogenetic inference based on 16S rRNA sequence analysis. The chemotaxonomic and phylogenetic analyses revealed the isolate to be a strain of Acetobacter pomorum. The isolate showed a G+C content of 60.8 mol%. It contained LL-diaminopimelic acid (LL-A2pm) as the cell wall amino acid and ubiquinone Q9 (H6) as the major quinone. The predominant cellular fatty acids were C18:1w9c, w12t, and w7c. Strain KJY8 grew rapidly on glucose-yeast extract (GYC) agar and formed pale white colonies with smooth to rough surfaces. The optimum cultivation conditions for acetic acid production by the KJY8 strain were 20°C and pH 3.0, with an initial ethanol concentration of 9% (w/v) to produce an acetic acid concentration of 8% (w/v). | 25,179,899 | [
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Metabolism of rutin and poncirin by human intestinal microbiota and cloning of their metabolizing α-L-rhamnosidase from Bifidobacterium dentium. | To understand the metabolism of flavonoid rhamnoglycosides by human intestinal microbiota, we measured the metabolic activity of rutin and poncirin (distributed in many functional foods and herbal medicine) by 100 human stool specimens. The average α-Lrhamnosidase activities on the p-nitrophenyl-α-L-rhamnopyranoside, rutin, and poncirin subtrates were 0.10 ± 0.07, 0.25 ± 0.08, and 0.15 ± 0.09 pmol/min/mg, respectively. To investigate the enzymatic properties, α-L-rhamnosidase-producing bacteria were isolated from the specimens, and the α-L-rhamnosidase gene was cloned from a selected organism, Bifidobacterium dentium, and expressed in E. coli. The cloned α-L-rhamnosidase gene contained a 2,673 bp sequcence encoding 890 amino acid residues. The cloned gene was expressed using the pET 26b(+) vector in E. coli BL21, and the expressed enzyme was purified using Ni(2+)-NTA and Q-HP column chromatography. The specific activity of the purified α-L-rhamnosidase was 23.3 μmol/min/mg. Of the tested natural product constituents, the cloned α-L-rhamnosidase hydrolyzed rutin most potently, followed by poncirin, naringin, and ginsenoside Re. However, it was unable to hydrolyze quercitrin. This is the first report describing the cloning, expression, and characterization of α-L-rhamnosidase, a flavonoid rhamnoglycosidemetabolizing enzyme, from bifidobacteria. Based on these findings, the α-L-rhamnosidase of intestinal bacteria such as B. dentium seem to be more effective in hydrolyzing (1-->6) bonds than (1-->2) bonds of rhamnoglycosides, and may play an important role in the metabolism and pharmacological effect of rhamnoglycosides. | 25,179,902 | [
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Synergistic interaction of Smac mimetic and IFNα to trigger apoptosis in acute myeloid leukemia cells. | Therapeutic targeting of inhibitor of apoptosis (IAP) proteins by small-molecule inhibitors such as Smac mimetic is considered as a promising anticancer strategy to elicit apoptosis. Recent advances have renewed the interest in exploiting the antileukemic activity of interferon (IFN)α for the treatment of acute myeloid leukemia (AML). Here, we identify a novel synergistic interaction of the Smac mimetic BV6 and IFNα to trigger cell death in AML cells. Calculation of combination index (CI) confirms the synergism of BV6 and IFNα. In contrast to AML cells, no synergistic toxicity of BV6 and IFNα at equimolar concentrations is found against normal peripheral blood lymphocytes. BV6 and IFNα act in concert to stimulate expression of tumor necrosis factor (TNF)α and its secretion into the supernatant, thereby initiating an autocrine/paracrine TNFα/TNF receptor 1 (TNFR1) loop that drives cell death by BV6 and IFNα. Consistently, pharmacological inhibition of TNFα by the TNFα-blocking antibody Enbrel or genetic silencing of TNFR1 significantly reduces BV6/IFNα-induced cell death. In addition, BV6/IFNα-induced cell death depends on interferon regulatory factor (IRF)1, since RNA interference-imposed knockdown of IRF1 significantly rescues cell death. In conclusion, the identification of a novel synergistic antileukemic combination of Smac mimetic and IFNα has important implications for the development of innovative treatment strategies in AML. | 25,179,908 | [
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Pharmacokinetics, pharmacodynamics, and tolerability of single ascending doses of RCT-18 in Chinese patients with rheumatoid arthritis. | RCT-18 is a novel recombinant fusion protein that targets and neutralizes B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL). This first in-human study investigated the safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of RCT-18 in patients with rheumatoid arthritis (RA). This was a single-center, randomized, single-blind, placebo-controlled study in 28 RA patients. Eligible patients were randomized 3:1 to receive single subcutaneous doses of RCT-18 (1.2, 6, 18, 60, 180, 360, 540 mg) or placebo. A 71-day observation period was scheduled for each patient, during which serial blood sampling for pharmacokinetic, pharmacodynamic, and immunogenicity assessments was performed. Safety was assessed throughout the study. RCT-18 was well tolerated, although mild infections and skin irritation occurred more frequently in patients receiving this drug. After single-dose RCT-18, the maximal serum concentration (C max) of total and free RCT-18 was reached within 1-2 days, followed by a multi-exponential decline. Mean elimination half-life for total RCT-18 and free RCT-18 was 5.7-12.8 days and 3.2-11.3 days at 6-60 mg, and 15.1-17.5 days and 18.8-36.8 days with 180-540 mg RCT-18. The formation and elimination of BLyS-RCT-18 complex were much slower, with a time to C max of 5-29 days and the elimination half-life mounting from 13.3 to 32.8 days with dose escalation. No positive reaction was detected in the immunogenicity assessments. Substantial IgM reduction was only evidenced with 540 mg RCT-18, while the response profiles of IgM/IgG were distinguishable from placebo after 180, 360, or 540 mg RCT-18. RCT-18 was safe and well tolerated up to 540-mg single doses. The serum exposure of total and free RCT-18 is linearly correlated to the weight-normalized doses of RCT-18 in dose groups receiving 180-540 mg RCT-18. The elimination half-life of BLyS-RCT-18 increased with RCT-18 doses, suggesting a shift from target-mediated disposition in 1.2-18 mg RCT-18 groups to non-specific clearance in 60-540 mg RCT-18 groups. Assuming the concentration of BLyS-RCT-18 complex and the IgM/IgG ratio are surrogate biomarkers for clinical effects of RCT-18, the dose-response relationship suggests 180-540 mg are pharmacodynamically effective doses in RCT-18 for RA patients, but the effect profile of 540 mg RCT-18 on IgM is similar to that of atacicept at pharmacodynamically effective but clinically ineffective doses. | 25,179,916 | [
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Dental students' glucometer experience and attitudes toward diabetes counseling, monitoring, and screening: a comparative study. | The objectives of this study were to compare glucometer experience and attitudes toward counseling, monitoring, and screening for diabetes between two classes of graduating students at one dental school to determine if there were differences by experience and year of graduation. Dental students graduating in 2010 and 2013 completed a survey about their experience with use of a glucometer as well as their attitudes toward and perceived barriers to performing glucose monitoring, screening, and counseling. Response rates for the two classes were 100 percent and 95.7 percent, respectively. Students in the two classes were in general agreement that activities related to glucose monitoring and counseling of patients with diabetes are within the scope and responsibility of the dental profession. Examination of their attitudes toward diabetes monitoring and counseling activities by level of glucometer experience indicated that students with more experience using a glucometer were more likely to consider these activities to be within the scope of dental practice and less likely to perceive barriers to such activities compared to those with little or no experience. In addition, regardless of experience, there was significantly higher endorsement for monitoring of patients who had already been diagnosed than for screening of patients who had not been diagnosed. This study suggests that any strategy to encourage dental students' and dentists' involvement in nontraditional health promotion activities should include ample direct clinical experience with these activities. | 25,179,922 | [
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Is off-pump coronary artery bypass surgery superior to on-pump coronary artery bypass surgery on postoperative paradoxical ventricular septal motion? | The aims of this study were to investigate the appearance of paradoxical ventricular septal motion (PSM) after coronary artery bypass graft (CABG) surgery and to identify factors that might be related to this abnormality. This prospective study included 119 consecutive patients (38 women, 81 men) who underwent CABG. Patients who underwent on-pump surgery (22 women, 45 men) and patients who underwent off-pump surgery (16 women, 36 men) were studied separately. All subjects underwent preoperative angiographic septal perfusion evaluation, pre- and postoperative echocardiography, and standard electrocardiographic and laboratory investigations, including troponin I and CK-MB levels. Multivariate logistic regression analysis was also performed for a variety of related parameters. Significant differences in EuroSCORE, length of intensive care unit stay, length of hospital stay, PSM (assessed using echocardiography), septal perfusion (observed using preoperative angiography), postoperative pleural effusion, and intensive care unit recidivism were observed between the two groups (P < .05). Moreover, postoperative PSM was correlated with septal perfusion (r = -0.687**, P < .001), type of operation (r = -0.194*, P = .035), diabetes mellitus (r = 0.273**, P = .003), carotid stenosis (r = 0.235*, P = .011), the number of distal anastomoses (r = 0.245**, P = .008), pleural effusion (r = 0.193*, P = .037), and intensive care unit recidivism (r = 0.249**, P = .007). However, multivariate analysis demonstrated that only preoperative septal perfusion (odds ratio: 0.037; 95% confidence interval: 0.011-0.128; P < .05) constitutes an independent risk factor for PSM (P < .05). This study demonstrated that preoperative septal perfusion deficiency represents an independent risk factor for postoperative PSM in patients undergoing CABG. Further investigations addressing the timing of the appearance of PSM and the correlation of this finding with perfusion imaging studies may provide new details concerning the mechanisms that underlie this abnormality. | 25,179,970 | [
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Successful rescue from cardiac arrest in a patient with postinfarction left ventricular blow-out rupture: "extra-pericardial aortic cannulation" for establishment total cardiopulmonary bypass. | We report a quick and simple technique to establish cardiopulmonary bypass (CPB) in a left ventricular (LV) blow-out rupture. A 74-year-old woman with a diagnosis of acute myocardial infarction suddenly collapsed and lost consciousness. A venous-arterial extracorporeal membrane oxygenation (ECMO) device was inserted by femoral cannulation. Emergent median sternotomy was performed. The pericardium was not opened first, and the thymus was divided to expose the ascending aorta just above the pericardial reflection. After placing two purse-string sutures on the distal ascending aorta, a 7-mm aortic cannula (Terumo, Tokyo, Japan) was inserted. The pericardium was then incised. A large volume of blood was expelled from the pericardial space, and CPB was initiated with suction drainage. A two-stage venous drainage cannula was then inserted from the right atrial appendage without hemodynamic collapse. After cardiac arrest, closure of ruptured LV wall and concomitant coronary artery bypass grafting were performed. The patient was weaned from CPB with an intra-aortic balloon pump (IABP) and the previously inserted venous-arterial ECMO. Extra-pericardial aortic cannulation is an effective and reproducible method to prepare for CPB in emergent cases of LV rupture. | 25,179,976 | [
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Motoneuron development influences dorsal root ganglia survival and Schwann cell development in a vertebrate model of spinal muscular atrophy. | Low levels of the survival motor neuron protein (SMN) cause the disease spinal muscular atrophy. A primary characteristic of this disease is motoneuron dysfunction and paralysis. Understanding why motoneurons are affected by low levels of SMN will lend insight into this disease and to motoneuron biology in general. Motoneurons in zebrafish smn mutants develop abnormally; however, it is unclear where Smn is needed for motoneuron development since it is a ubiquitously expressed protein. We have addressed this issue by expressing human SMN in motoneurons in zebrafish maternal-zygotic (mz) smn mutants. First, we demonstrate that SMN is present in axons, but only during the period of robust motor axon outgrowth. We also conclusively demonstrate that SMN acts cell autonomously in motoneurons for proper motoneuron development. This includes the formation of both axonal and dendritic branches. Analysis of the peripheral nervous system revealed that Schwann cells and dorsal root ganglia (DRG) neurons developed abnormally in mz-smn mutants. Schwann cells did not wrap axons tightly and had expanded nodes of Ranvier. The majority of DRG neurons had abnormally short peripheral axons and later many of them failed to divide and died. Expressing SMN just in motoneurons rescued both of these cell types showing that their failure to develop was secondary to the developmental defects in motoneurons. Driving SMN just in motoneurons did not increase survival of the animal, suggesting that SMN is needed for motoneuron development and motor circuitry, but that SMN in other cells types factors into survival. | 25,180,019 | [
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A DAQ-device-based continuous wave near-infrared spectroscopy system for measuring human functional brain activity. | In the last two decades, functional near-infrared spectroscopy (fNIRS) is getting more and more popular as a neuroimaging technique. The fNIRS instrument can be used to measure local hemodynamic response, which indirectly reflects the functional neural activities in human brain. In this study, an easily implemented way to establish DAQ-device-based fNIRS system was proposed. Basic instrumentation components (light sources driving, signal conditioning, sensors, and optical fiber) of the fNIRS system were described. The digital in-phase and quadrature demodulation method was applied in LabVIEW software to distinguish light sources from different emitters. The effectiveness of the custom-made system was verified by simultaneous measurement with a commercial instrument ETG-4000 during Valsalva maneuver experiment. The light intensity data acquired from two systems were highly correlated for lower wavelength (Pearson's correlation coefficient r = 0.92, P < 0.01) and higher wavelength (r = 0.84, P < 0.01). Further, another mental arithmetic experiment was implemented to detect neural activation in the prefrontal cortex. For 9 participants, significant cerebral activation was detected in 6 subjects (P < 0.05) for oxyhemoglobin and in 8 subjects (P < 0.01) for deoxyhemoglobin. | 25,180,044 | [
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Detecting ALK, ROS1 and RET Fusion Genes in Cell Block Samples. | Whether Cell block (CB) samples are applicable to detect anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and ret proto-oncogene (RET) fusion genes in lung adenocarcinoma is still unknown. In this study, 108 cytological samples that contained lung adenocarcinoma cells were collected, and made into CB. The CB samples all contained at least 30% lung adenocarcinoma cells. In these patients, 48 harbored EGFR mutation. Among the 50 EGFR wild type patients who detected fusion genes, 14 carried EML4-ALK fusion (28%), 2 had TPM3-ROS1 fusion (4%), and 3 harbored KIF5B-RET fusion (6%). No double fusions were found in one sample. Patients with fusion genes were younger than those without fusion genes (p = 0.032), but no significant difference was found in sex and smoking status (p > 0.05). In the thirty-five patients who received first-line chemotherapy, patients with fusion gene positive had disease control rate (DCR) (72.7% VS 50%, p > 0.05) and objective response rate (ORR) (9.1% VS 4.2%, p > 0.05) compared with those having fusion gene negative. The median progression free survival (mPFS) were 4.0 and 2.7 months in patients harbored fusion mutations and wild type, respectively (p > 0.05). We conclude that CB samples could be used to detect ALK, ROS1 and RET fusions in NSCLC. The frequency distribution of three fusion genes is higher in lung adenocarcinoma with wild-type EGFR, compared with unselected NSCLC patient population. Patients with fusion genes positive are younger than those with fusion gene negative, but they had no significantly different PFS in first-line chemotherapy. | 25,180,059 | [
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Examining Cultural Correlates of Active Coping Among African American Female Trauma Survivors. | African American women are at a greater risk for exposure to multiple traumatic events and are less likely to seek mental health services than White women. Many women report avoidant and passive coping strategies placing them at an increased risk for lower psychological adjustment. Thus, the purpose of the current study is to examine the role of culturally relevant factors such as spirituality, self-esteem, and social support as significant correlates of John Henryism Active Coping among African American female trauma survivors. The study utilized secondary data from the B-WISE project (Black Women in a Study of Epidemics) with a sample of 161 community-based African American women with a self-reported history of trauma. Results indicate that participants with higher self-esteem and existential well-being were more likely to cope actively with daily life stressors. However, socio-demographics were not significant correlates of John Henryism Active Coping at the multivariate level. Implications for clinical practice are discussed along with the Strong Black Woman (SBW) ideology, which may explain over-reporting of positive attributes such as self-esteem and existential well-being. Limitations of the study and directions of future research are also discussed. | 25,180,071 | [
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Functional characterization of AT-1001, an α3β4 nicotinic acetylcholine receptor ligand, at human α3β4 and α4β2 nAChR. | Genome-wide association studies linking the α3, β4, and α5 nicotinic acetylcholine receptor (nAChR) subunits to nicotine dependence suggest that α3β4* nAChR may be targets for smoking cessation pharmacotherapies. We previously reported that AT-1001, a selective α3β4* nAChR ligand binds with high affinity to rat α3β4 and human α3β4α5 nAChR, antagonizes epibatidine-induced activation of rat α3β4 nAChR in HEK cells and potently inhibits nicotine self-administration in rats. Two-electrode voltage clamp was used for functional characterization of AT-1001 at recombinant human α3β4 and α4β2 nAChR expressed in Xenopus oocytes. Concentration-response curves show that AT-1001 is a partial agonist at human α3β4 nAChR, evoking up to 35% of the maximal acetylcholine (ACh) response (50% effective concentration [EC50] = 0.37 μM). AT-1001 showed very little agonist activity at the α4β2 nAChR, evoking only 6% of the ACh response (EC50 = 1.5 μM). Pre- and co-application of various concentrations of AT-1001 with 50 μM ACh revealed a complex pattern of activation-inhibition by AT-1001 at α3β4 nAChR, which was best fitted by a 2-site equation. At α4β2 nAChR, co-exposure of AT-1001 with ACh only showed inhibition of ACh current with a shallower curve. AT-1001 is a partial agonist at the human α3β4 nAChR and causes desensitization at concentrations at which it evokes an inward current, resulting in an overall functional antagonism of α3β4 nAChR. AT-1001 does not significantly activate or desensitize α4β2 nAChR at the same concentrations as at the α3β4 nAChR, but does inhibit ACh responses at α4β2 nAChR at higher concentrations. A combination of these mechanisms may underlie the inhibition of nicotine self-administration by AT-1001, suggesting that AT-1001 and compounds from this class may have clinical potential for smoking cessation pharmacotherapy. | 25,180,076 | [
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Serum Micronutrient Status of Haart-Naïve, HIV Infected Children in South Western Nigeria: A Case Controlled Study. | Background. Though micronutrients are vital in the pathogenesis of human immunodeficiency virus infection, most studies have been conducted in adults. Knowledge of the status of key micronutrients in HIV infected African children will indicate if supplementation may be beneficial to these children living in this resource-poor region. Objectives. We sought to determine the micronutrient status and associated factors of HAART-naïve HIV infected children and compare them with those of the HIV negative controls. Methods. We enrolled 70 apparently stable HAART naïve HIV infected children. Seventy age and sex matched HIV negative children were equally enrolled as the controls. Their social class, anthropometry, clinical stage, CD4 counts, serum zinc, selenium, and vitamin C were determined. Results. The prevalence of zinc, selenium, and vitamin C deficiency in HIV infected subjects was 77.1%, 71.4%, and 70.0%, respectively, as compared to 44.3%, 18.6%, and 15.7% in HIV negative controls. Among the HIV infected subjects, 58.6% were deficient in the three micronutrients. Micronutrient status was related to the weight, clinical, and immunological stages but not BMI or social class. Conclusion. Deficiency of these key micronutrients is widely prevalent in HAART naïve HIV infected children irrespective of social class. This suggests that supplementation trial studies may be indicated in this population. | 25,180,086 | [
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Cross-synaptic synchrony and transmission of signal and noise across the mouse retina. | Cross-synaptic synchrony--correlations in transmitter release across output synapses of a single neuron--is a key determinant of how signal and noise traverse neural circuits. The anatomical connectivity between rod bipolar and A17 amacrine cells in the mammalian retina, specifically that neighboring A17s often receive input from many of the same rod bipolar cells, provides a rare technical opportunity to measure cross-synaptic synchrony under physiological conditions. This approach reveals that synchronization of rod bipolar cell synapses is near perfect in the dark and decreases with increasing light level. Strong synaptic synchronization in the dark minimizes intrinsic synaptic noise and allows rod bipolar cells to faithfully transmit upstream signal and noise to downstream neurons. Desynchronization in steady light lowers the sensitivity of the rod bipolar output to upstream voltage fluctuations. This work reveals how cross-synaptic synchrony shapes retinal responses to physiological light inputs and, more generally, signaling in complex neural networks. | 25,180,102 | [
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Coexisting papillary and clear renal cell carcinoma in the same kidney. | Renal cell carcinoma (RCC) is the most common solid lesion of the kidney. Bilateral synchronous benign and malignant renal tumors have been defined in some reports. However, unilateral concordance of malignant renal tumors is very rare and there are only a few cases that had synchronous different subtypes of malignant renal tumors arising within the same kidney. Herein, we describe a 67-year-old male patient who had clear cell RCC and papillary RCC in his right kidney that were successfully treated with radical nephrectomy. We also reviewed the pertinent literature. | 25,180,117 | [
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Neurotensin decreases the proinflammatory status of human skin fibroblasts and increases epidermal growth factor expression. | Fibroblasts colonization into injured areas during wound healing (WH) is responsible for skin remodelling and is also involved in the modulation of inflammation, as fibroblasts are immunologically active. Herein, we aimed to determine neurotensin effect on the immunomodulatory profile of fibroblasts, both in homeostatic and inflammatory conditions. Neurotensin mediated responses occurred through NTR1 or NTR3 receptors, while under inflammatory conditions NTR1 expression increase seemed to modulate neurotensin responses. Among different immunomodulatory genes, CCL11, IL-8, and IL-6 were the most expressed genes, while CCL4 and EGF were the less expressed genes. After neurotensin exposure, IL-8 mRNA expression was increased while CCL11 was decreased, suggesting a proinflammatory upregulation and chemoattractant ability downregulation of fibroblasts. Under inflammatory conditions, gene expression was significantly increased. After neurotensin exposure, CCL4 and IL-6 mRNA expression were decreased while CCL11 was increased, suggesting again a decrease in the chemoattractant capacity of fibroblasts and in their proinflammatory status. Furthermore, the expression of EGF, a crucial growth factor for skin cells proliferation and WH, was increased in all conditions. Overall, neurotensin, released by nerve fibers or skin cells, may be involved in the decrease of the chemotaxis and the proinflammatory status in the proliferation and remodelling phases of WH. | 25,180,119 | [
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Cardiovascular risk factors and comorbidities in patients with hyperuricemia and/or gout: a systematic review of the literature. | To review the available literature on the likelihood of having cardiovascular (CV) risk factors and on developing CV comorbidities in patients with gout and/or asymptomatic hyperuricemia as an evidence base for generating multinational clinical practice recommendations in the 3e (Evidence, Expertise, Exchange) Initiative in Rheumatology. A systematic literature search was carried out using MEDLINE, EMBASE, and The Cochrane Library, and abstracts presented at the 2010/2011 meetings of the American College of Rheumatology (ACR) and the European League Against Rheumatism, searching for CV risk factors and new CV comorbidities in patients with asymptomatic hyperuricemia and/or a diagnosis of gout. Trials that fulfilled predefined inclusion criteria were systematically reviewed. A total of 66 out of 8918 identified publications were included in this review. After assessment of the risk of bias, 32 articles with a high risk of bias were excluded. Data could not be pooled because of clinical and statistical heterogeneity. In general, both for asymptomatic hyperuricemia and for gout the hazard ratios for CV comorbidities were only modestly increased (1.5 to 2.0) as were the hazard ratios for CV risk factors, ranging from 1.4 to 2.0 for hypertension and from 1.0 to 2.4 for diabetes. Unlike the common opinion that patients with gout or hyperuricemia are at higher risk of developing CV disease, the actual risk to develop CV disease is either rather weak (for hyperuricemia) or poorly investigated (for gout). | 25,180,123 | [
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Knowledge management and safety compliance in a high-risk distributed organizational system. | In a safety perspective, efficient knowledge management is important for learning purposes and thus to prevent errors from occurring repeatedly. The relationship between knowledge exchange among employees and safety behavior may be of particular importance in distributed organizational systems where similar high-risk activities take place at several locations. This study develops and tests hypotheses concerning the relationship between knowledge exchange systems usage, knowledge exchange in the organizational system, and safety compliance. The operational context of the study is petroleum drilling and well operations involving distributed high-risk activities. The hypotheses are tested by use of survey data collected from a large petroleum operator company and eight of its main contractors. The results show that safety compliance is influenced by use of knowledge exchange systems and degree of knowledge exchange in the organizational system, both within and between units. System usage is the most important predictor, and safety compliance seems to be more strongly related to knowledge exchange within units than knowledge exchange between units. Overall, the study shows that knowledge management is central for safety behavior. | 25,180,134 | [
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... |
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