title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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The influence of race and ethnicity on complications and mortality after orthopedic surgery: a systematic review of the literature. | The decision to perform orthopedic surgery requires substantial discretion and judgment. Similar conditions have been associated with health care disparities in other fields, but the extent of racial and ethnic disparities in orthopedics is unknown. To evaluate the quality of extant orthopedic literature on health care disparities. This study is a systematic review. Eligible studies reported complications and/or mortality stratified by minority group after orthopedic surgery in an American population. Queries of PubMed, Embase, Scopus, and Web of Science were performed. Included papers were abstracted regarding complication and/or mortality rates for whites and minority populations, statistical findings, and whether a health care disparity was reported. Statistical associations between study characteristics and the identification of disparities were evaluated using the χ test. The literature search returned 2604 studies, of which 33 met inclusion criteria. All but 3 works dealt with spine surgery or joint replacement. Twenty-one publications (64%) documented health care disparities. Forty-four percent of efforts investigating outcomes for Hispanics and 36% of works documenting results for non-whites recorded a disparity. Investigations reporting on African Americans were significantly more likely to identify health care inequalities (77%) as compared with non-white (P=0.02) cohorts. Patients from racial and ethnic minority populations seem to be at increased risk of complications and/or mortality following spine surgical or joint replacement procedures. There is insufficient evidence to support generalization to the entire orthopedic field. Studies specific to African American patients identify health care disparities at a significantly higher rate than those utilizing non-white cohorts. | 25,100,230 | [
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Uncovering continuous and transient monitoring profiles in event-based prospective memory. | The present study implemented response time distribution modeling to better characterize context-specific attention dynamics underlying task interference due to possessing a prospective memory intention. During a three-phase paradigm in which prospective memory cues appeared only in the final phase, prospective memory performance was better when participants were informed at encoding of the context in which cues were to appear than when participants were not informed. Additionally, task interference increased during the third phase when the cue context was previously specified. Ex-Gaussian parameter estimates revealed that task interference during the third phase was due to a greater relative frequency of longer latencies, rather than an overall increase in latencies across all trials, suggesting that participants relied primarily on transient, rather than continuous, monitoring processes to support cue detection. Functionally, variability in transient and continuous monitoring profiles was predictive of prospective memory cue detection. More generally, the results from the present study suggest that ex-Gaussian parameter estimation procedures may provide a fruitful avenue for better understanding how attention is differentially allocated to ongoing tasks, what processes might underlie monitoring behavior, and how this behavior is related to eventual intention fulfillment. | 25,100,232 | [
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A switch from canonical to noncanonical Wnt signaling mediates early differentiation of human neural stem cells. | Wnt/β-catenin signaling is essential for neurogenesis but less is known about β-catenin-independent Wnt signals. We show here that Wnt/activator protein-1 (AP-1) signaling drives differentiation of human embryonic stem cell and induced pluripotent stem cell-derived neural progenitor cells. Neuronal differentiation was accompanied by a reduction in β-catenin/Tcf-dependent transcription and target gene expression, increased levels and/or phosphorylation of activating transcription factor 2 (ATF2), cyclic AMP response element-binding protein, and c-Jun, and increased AP-1-dependent transcription. Inhibition of Wnt secretion using the porcupine inhibitors IWP-2 and Wnt-C59 blocked neuronal differentiation, while activation or inhibition of Wnt/β-catenin signaling had no effect. Neuronal differentiation increased expression of several Wnt genes, including WNT3A, silencing of which reduced differentiation. Addition of recombinant Wnt-3a to cells treated with IWP-2 or Wnt-C59 increased AP-1 levels and restored neuronal differentiation. The effects of Wnt-3a could not be blocked by addition of Dkk-1 or IWR-1, suggesting the involvement of noncanonical signaling. Consistent with this, restoration of neuronal differentiation by Wnt-3a was reduced by inhibition of Jun N-terminal kinase (JNK) and by gene silencing of ATF2. Together, these observations suggest that β-catenin-independent Wnt signals promote neural stem/progenitor cell differentiation in a signaling pathway involving Wnt-3a, JNK, and ATF2. | 25,100,239 | [
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Validation of the Pangao PG-800B11 blood pressure monitor according to the European Society of Hypertension and the British Hypertension Society protocols. | The study aimed to determine the accuracy of the fully automated oscillometric upper-arm blood pressure (BP) monitor Pangao PG-800B11 according to the European Society of Hypertension-International Protocol (ESH-IP) revision 2010 and the British Hypertension Society (BHS) protocol 1993. Data from 33 participants were initially examined according to the ESH-IP revision 2010. Furthermore, 52 participants were then enrolled to fulfill the BHS protocol requirements. In all participants, sequential left arm measurements were performed by two trained observers using a mercury sphygmomanometer and one supervisor using the device. The protocols' requirements were followed precisely. The device passed all parts of the ESH protocol for systolic blood pressure (SBP) and diastolic blood pressure (DBP) and was graded A according to the criteria of the BHS protocol for both SBP and DBP. The A/A grade was achieved in low (<130/80 mmHg), medium (130-160/80-100 mmHg), and high (>160/100 mmHg) BP categories. The mean BP difference between PG-800B11 and observers in the 85 participants was -0.6±5.0 mmHg for SBP and -0.6±4.5 mmHg for DBP; thus, the device also fulfilled the requirements of the Association for the Advancement of Medical Instrumentation (AAMI). The Pangao PG-800B11 passed all requirements of the ESH-IP revision 2010 and achieved A/A grade of the BHS protocol across a wide range of BPs. | 25,100,264 | [
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Nitric oxide and carbon monoxide antagonize TGF-β through ligand-independent internalization of TβR1/ALK5. | Transforming growth factor (TGF)-β plays a central role in vascular homeostasis and in the pathology of vascular disease. There is a growing appreciation for the role of nitric oxide (NO) and carbon monoxide (CO) as highly diffusible, bioactive signaling molecules in the vasculature. We hypothesized that both NO and CO increase endocytosis of TGF-β receptor type 1 (TβR1) in vascular smooth muscle cells (VSMCs) through activation of dynamin-2, shielding cells from the effects of circulating TGF-β. In this study, primary cultures of VSMCs from Sprague-Dawley rats were treated with NO-releasing molecule 3 (a NO chemical donor), CO-releasing molecule 2 (a CO chemical donor), or control. NO and CO stimulated dynamin-2 activation in VSMCs. NO and CO promoted time- and dose-dependent endocytosis of TβR1. By decreasing TβR1 surface expression through this dynamin-2-dependent process, NO and CO diminished the effects of TGF-β on VSMCs. These findings help explain an important mechanism by which NO and CO signal in the vasculature by decreasing surface expression of TβR1 and the cellular response to TGF-β. | 25,100,282 | [
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Angiotensin II type 2 receptor regulates ROMK-like K⁺ channel activity in the renal cortical collecting duct during high dietary K⁺ adaptation. | The kidney adjusts K⁺ excretion to match intake in part by regulation of the activity of apical K⁺ secretory channels, including renal outer medullary K⁺ (ROMK)-like K⁺ channels, in the cortical collecting duct (CCD). ANG II inhibits ROMK channels via the ANG II type 1 receptor (AT1R) during dietary K⁺ restriction. Because AT1Rs and ANG II type 2 receptors (AT2Rs) generally function in an antagonistic manner, we sought to characterize the regulation of ROMK channels by the AT2R. Patch-clamp experiments revealed that ANG II increased ROMK channel activity in CCDs isolated from high-K⁺ (HK)-fed but not normal K⁺ (NK)-fed rats. This response was blocked by PD-123319, an AT2R antagonist, but not by losartan, an AT1R antagonist, and was mimicked by the AT2R agonist CGP-42112. Nitric oxide (NO) synthase is present in CCD cells that express ROMK channels. Blockade of NO synthase with N-nitro-l-arginine methyl ester and free NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt completely abolished ANG II-stimulated ROMK channel activity. NO enhances the synthesis of cGMP, which inhibits phosphodiesterases (PDEs) that normally degrade cAMP; cAMP increases ROMK channel activity. Pretreatment of CCDs with IBMX, a broad-spectrum PDE inhibitor, or cilostamide, a PDE3 inhibitor, abolished the stimulatory effect of ANG II on ROMK channels. Furthermore, PKA inhibitor peptide, but not an activator of the exchange protein directly activated by cAMP (Epac), also prevented the stimulatory effect of ANG II. We conclude that ANG II acts at the AT2R to stimulate ROMK channel activity in CCDs from HK-fed rats, a response opposite to that mediated by the AT1R in dietary K⁺-restricted animals, via a NO/cGMP pathway linked to a cAMP-PKA pathway. | 25,100,281 | [
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Determinants of cervical screening services uptake among 18-49 year old women seeking services at the Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu, Kenya. | Kenyan women aged ≥ 15 years are at risk of developing cervical cancer. Currently, cervical cytology reduces cervical cancer incidence, since it allows for early diagnosis and treatment. Uptake of cervical screening services is a priority research area in Kenya. Central to the success of any screening programme is its ability to identify, reach out and screen the defined target population. Cervical screening coverage in Kenya is currently at 3.2%. In Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) in Nyanza, the number screened for cervical cancer is low (averagely 3/day). Thus the current study sought to identify factors influencing uptake of cervical screening services at the facility. In a cross-sectional study, knowledge, perceptions and cues for action associated with self-reported cervical screening uptake were explored. The targeted population (n = 424), purposively selected were women of child-bearing age (18-49 years) visiting JOOTRH. Data on socio-demographic status (age, level of education, marital status, job status, income level), knowledge of cervical cancer, perceptions on severity and susceptibility to the disease were collected using self-administered structured questionnaires. Statistical significance of differences in proportions were determined by chi-square analyses while logistic regression analyses were used to identify determinants of self-reported uptake of the service. Self-reported screening uptake was 17.5%. There was a strong positive association between age (P < 0.0001), level of education (P < 0.0001) and income levels (P = 0.005) with the uptake of the service. Knowledge level on the signs and symptoms of cervical cancer was an important determinant for being screened for cervical cancer (P < 0.0001). Furthermore, those who said they didn't know about the disease (OR, 26.84, 95% CI, 6.07-118.61, P < 0.0001) or were not aware about susceptibility to it (OR, 2.37, 95% CI, 1.10-5.08, P = 0.02) had a higher likelihood of not being screened. On cues for action, those who attended the child welfare clinic were more likely to be screened (OR, 2.31, 95% CI, 1.17-3.93, P = 0.03). Knowledge, perception of higher susceptibility and attending child welfare clinic are key determinants of self-reported uptake of cervical screening. Increasing knowledge, enhancing health education and providing free services may increase uptake among women population in such settings. | 25,100,298 | [
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Low-temperature scanning tunneling microscopy study of double-decker DyPc2 on Pb Surface. | Low-temperature scanning tunneling microscopy (STM), scanning tunneling spectroscopy and dI/dV mapping techniques have been applied to study double-decker DyPc₂ molecules on Pb(111) films grown on silicon wafers. The DyPc₂ molecules firstly self-assemble into a monolayer where two neighbouring molecules form an azimuthal angle of 6°. Scattered DyPc₂ molecules in the second layer can be stabilized on top of the first self-assembled monolayer, adopting a co-axial alignment with the underlying molecules. With the reference to the new layer assembled by Pc molecules generated by the cracking of DyPc₂ molecules on the substrate at or above room temperature, the molecular configuration can be directly deduced from STM imaging. The two Pc ligands in the same double-decker molecule rotate 45° with respect to each other. The dI/dV mapping of the individual DyPc₂ molecules in the second layer shows that they can appear as either four-lobed or eight-lobed features in the STM images depending on the bias voltage employed. | 25,100,303 | [
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Signatures of active and passive optimized Lévy searching in jellyfish. | Some of the strongest empirical support for Lévy search theory has come from telemetry data for the dive patterns of marine predators (sharks, bony fishes, sea turtles and penguins). The dive patterns of the unusually large jellyfish Rhizostoma octopus do, however, sit outside of current Lévy search theory which predicts that a single search strategy is optimal. When searching the water column, the movement patterns of these jellyfish change over time. Movement bouts can be approximated by a variety of Lévy and Brownian (exponential) walks. The adaptive value of this variation is not known. On some occasions movement pattern data are consistent with the jellyfish prospecting away from a preferred depth, not finding an improvement in conditions elsewhere and so returning to their original depth. This 'bounce' behaviour also sits outside of current Lévy walk search theory. Here, it is shown that the jellyfish movement patterns are consistent with their using optimized 'fast simulated annealing'--a novel kind of Lévy walk search pattern--to locate the maximum prey concentration in the water column and/or to locate the strongest of many olfactory trails emanating from more distant prey. Fast simulated annealing is a powerful stochastic search algorithm for locating a global maximum that is hidden among many poorer local maxima in a large search space. This new finding shows that the notion of active optimized Lévy walk searching is not limited to the search for randomly and sparsely distributed resources, as previously thought, but can be extended to embrace other scenarios, including that of the jellyfish R. octopus. In the presence of convective currents, it could become energetically favourable to search the water column by riding the convective currents. Here, it is shown that these passive movements can be represented accurately by Lévy walks of the type occasionally seen in R. octopus. This result vividly illustrates that Lévy walks are not necessarily the result of selection pressures for advantageous searching behaviour but can instead arise freely and naturally from simple processes. It also shows that the family of Lévy walkers is vastly larger than previously thought and includes spores, pollens, seeds and minute wingless arthropods that on warm days disperse passively within the atmospheric boundary layer. | 25,100,323 | [
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Microgel microenvironment primes adipose-derived stem cells towards an NP cells-like phenotype. | Cell therapy of the degenerated intervertebral disc is limited by the lack of appropriate cell sources, thus new strategies for the differentiation of stem cells towards a nucleus pulposus (NP)-like phenotype need investigation. In the current study, it is hypothesized that spherical niche-like structures composed of type II collagen and hyaluronan (HA) mimic the NP microenvironment and promote the differentiation of adipose-derived stem cells (ADSCs) towards an NP-like phenotype. ADSCs are embedded in microgels of different concentrations of collagen II/HA. Cells' response to the different environments is studied by characterizing differences in cells' viability, morphology, and gene expression. After 21 days of culture, ADSCs maintain ± 80% viability in all the conditions tested. Moreover, microgels with higher concentration of collagen are stable and maintain cells in a rounder shape. In presence of differentiation media, cells are able to differentiate in all the conditions tested, but in a more pronounced manner in the microgel with a higher concentration of collagen. By tuning microgels' properties, it is possible to influence ADSCs' phenotype and ability to differentiate. Indeed, when cultured in high concentrations of collagen, ADSCs expresses high levels of collagen II, aggrecan, SOX9, and low levels of collagen I. | 25,100,329 | [
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Does secretin stimulation add to magnetic resonance cholangiopancreatography in characterising pancreatic cystic lesions as side-branch intraductal papillary mucinous neoplasm? | To assess the value of secretin during magnetic resonance cholangiopancreatography (MRCP) in demonstrating communication between cystic lesions and the pancreatic duct to help determine the diagnosis of side-branch intraductal papillary mucinous neoplasm (SB-IPMN). This is an IRB-approved, HIPAA-compliant retrospective study of 29 SB-IPMN patients and 13 non-IPMN subjects (control) who underwent secretin-enhanced MRCP (s-MRCP). Two readers blinded to the final diagnosis reviewed three randomised image sets: (1) pre-secretin HASTE, (2) dynamic s-MRCP and (3) post-secretin HASTE. Logistic regression, generalised linear models and ROC analyses were used to compare pre- and post-secretin results. There was no significant difference in median scores for the pre-secretin [reader 1: 1; reader 2: 2 (range -2 to 2)] and post-secretin HASTE [reader 1: 1; reader 2: 1 (range -2 to 2)] in the SB-IPMN group (P = 0.14), while the scores were lower for s-MRCP [reader 1: 0.5 (range -2 to 2); reader 2: 0 (range -1 to 2); P = 0.016]. There was no significant difference in mean maximum diameter of SB-IPMN on pre- and post-secretin HASTE, and s-MRCP (P > 0.05). Secretin stimulation did not add to MRCP in characterising pancreatic cystic lesions as SB-IPMN. Magnetic resonance cholangiopancreatography (MRCP) is used to evaluate pancreatic cystic lesions. Intraductal papillary mucinous neoplasm (IPMN) is a type of pancreatic cystic neoplasm. Secretin administration does not facilitate the diagnosis of IPMN on MRCP. | 25,100,335 | [
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Return to activity after concussion affects dual-task gait balance control recovery. | Recent work has identified deficits in dual-task gait balance control for up to 2 months after adolescent concussion; however, how resumption of preinjury physical activities affects recovery is unknown. The objective of this study is to examine how return to activity (RTA) affects recovery from concussion on measures of symptom severity, cognition, and balance control during single-task and dual-task walking. Nineteen adolescents with concussion who returned to preinjury activity within 2 months after injury and 19 uninjured, matched controls completed symptom inventories, computerized cognitive testing, and single-task and dual-task gait analyses. Concussion participants were assessed at five time points: within 72 h, 1 wk, 2 wk, 1 month, and 2 months postinjury. Control participants were assessed at the same time points as their matched concussion counterparts. RTA day was documented as the postinjury day in which physical activity participation was allowed. The effect of returning to physical activity was assessed by examining the percent change on each dependent variable across time before and directly after the RTA. Data were analyzed by two-way mixed effects ANOVAs. After the RTA day, concussion participants significantly increased their total center-of-mass medial/lateral displacement (P = 0.009, ηp = .175) and peak velocity (P = 0.048, ηp = 0.104) during dual-task walking when compared with pre-RTA data, whereas no changes for the concussion group or between groups were detected on measures of single-task walking, forward movement, or cognition. Adolescents with concussion displayed increased center-of-mass medial/lateral displacement and velocity during dual-task walking after RTA, suggesting a regression of recovery in gait balance control. This study reinforces the need for a multifaceted approach to concussion management and continued monitoring beyond the point of clinical recovery. | 25,100,340 | [
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[Multiple gastrointestinal stromal tumors during nilotinib treatment for chronic myelogenous leukemia in a patient with neurofibromatosis type 1]. | A 60-year-old woman with neurofibromatosis type 1 presented to our hospital with melena. She reported a 1-year history of treatment with nilotinib hydrochloride hydrate for chronic myelogenous leukemia. Contrast-enhanced abdominal computed tomography revealed multiple intestinal tumors that were subsequently diagnosed as gastrointestinal stromal tumors (GIST) using single-balloon enteroscopy. Although the tumors showed no significant change over 1 year, partial jejunal resection was performed to confirm the diagnosis. Immunohistochemically, the tumors were GIST. | 25,100,347 | [
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[Long-term survival following resection of a leiomyosarcoma originating from the inferior vena cava]. | We describe the case of a 46-year-old woman in which a large intra-abdominal tumor was detected using computed tomography. It was a low-density, homogeneous, 7 cm tumor, adjacent to the inferior vena cava (IVC). The tumor, along with a portion of the anterior wall of the IVC, was surgically resected. The tumor originated from the IVC wall, and histopathological examination revealed a diagnosis of leiomyosarcoma. The patient is alive without recurrence 10 years after surgery. Although this disease is rare and typically has a poor prognosis, complete resection with long-term survival is achievable. | 25,100,353 | [
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[Three cases of childhood-onset autoimmune pancreatitis]. | Here we present 3 cases of childhood-onset autoimmune pancreatitis: 2 cases in boys aged 4 and 16 years, diagnosed with ulcerative colitis; 1 case in a previously healthy 10-year-old boy. All 3 boys presented with abdominal pain associated with elevated pancreatic enzyme levels. Immunoglobulin G4 levels were elevated only in the 16-year-old boy. However, pancreatic enlargement together with narrowing of the main pancreatic duct was evident on computed tomography in all 3 cases. Autoimmune pancreatitis is an uncommon disease in childhood, and only 3 cases affecting patients under 17 years of age have previously been reported in Japan. Autoimmune pancreatitis may be latent in children with pancreatitis who have chronic or intermittent abdominal symptoms. In addition, it is necessary to recognize autoimmune pancreatitis as a complication of pediatric inflammatory bowel disease. The clinical features of pediatric autoimmune pancreatitis remain unclear, and an accumulation of cases is necessary. | 25,100,354 | [
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Metformin may be associated with false-negative cancer detection in the gastrointestinal tract on PET/CT. | Concurrent therapy with the antihyperglycemic drug metformin can hinder the detection of malignancy in the abdominal and pelvic portions of 18F-fluordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging performed for the diagnosis or staging of malignancy, as well as for treatment response and radiation therapy planning. This is due to the metformin-induced increase in intestinal FDG radiotracer uptake. We aim to bring this potentially important interaction to the attention of clinicians who care for cancer patients with diabetes. We searched MEDLINE (from 1970 to January 2014) and Google Scholar for relevant English-language articles using the following search terms: "metformin and FDG/PET, metformin and bowel uptake, metformin, and cancer, metformin and the intestine, metformin pharmacokinetics, hyperglycemia and FDG/PET." We reviewed the reference lists of pertinent articles with respect to metformin gut physiology, impact on FDG uptake and the effect on diagnostic accuracy of abdominalpelvic PET/CT scans with concurrent metformin therapy. We reviewed the action of metformin in the intestine, with particular emphasis on the role of metformin in PET/CT imaging and include a discussion of clinical studies on the topic to help refine knowledge and inform practice. Finally, we discuss aspects pertinent to the management of type 2 diabetes (T2D) patients on metformin undergoing PET/CT. Metformin leads to intense, diffusely increased FDG uptake in the colon, and to a lesser degree, the small intestine, which limits the diagnostic capabilities of FDG PET/CT scanning and may mask gastrointestinal malignancies. We suggest that metformin be discontinued 48 hours before FDG PET/CT scanning is performed in oncology patients. More rigorous data are needed to support the widespread generalizability of this recommendation. | 25,100,379 | [
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Decreased Inpatient Mortality in Obese Patients with Abdominal Nets. | Neuroendocrine tumors (NETs) of the abdomen are rare tumors with an incidence of 3.56 per 100,000 in the general population. Obesity is a growing public health problem with varying effects on severity of other disease. We investigated the association between obesity and inpatient morbidity/mortality in patients with abdominal neuroendocrine tumors utilizing the Nationwide Inpatient Sample (NIS). We analyzed data from the NIS database to investigate the association between obesity and abdominal NETs using patient information from 22,096 patient-discharges from January 1, 2009 to December 31, 2010. We demonstrate that obesity is strongly associated with decreased rates of inpatient mortality in patients with NET (OR = 0.6, multivariate P = 0.02) and that malnutrition is associated with nearly 5-fold higher odds of inpatient mortality (multivariate P < 0.0005). We did not find a statistical interaction between obesity and malnutrition; however, patients who were both malnourished and obese had a lower association with mortality risk than purely malnourished patients. Our data suggests that nutritional status may be an important factor in inpatient mortality in patients with NETs with obesity being protective. | 25,100,391 | [
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A restorative approach for class II resin composite restorations: a two-year follow-up. | This clinical report describes a restorative technique used to replace two Class II resin composite restorations on the upper premolars. A sectional matrix band was used in conjunction with an elastic ring (Composi-Tight) to obtain tight proximal contact. A nanofilled resin composite (Filtek Supreme Ultra) was incrementally applied using oblique layers to reduce the C-factor, each layer being no more than 2 mm thick, and then light cured for 20 seconds with a light-emitting diode lamp (EliparFreeLight 2 LED Curing Light) with a power density of 660 mW/cm(2). A centripetal technique was used to restore the lost tooth structure from the periphery toward the center of the cavity in order to achieve a better contour and anatomy with less excess, thereby minimizing the use of rotary instruments during the finishing procedures. Finally, the resin composite restorations were finished and polished, and a surface sealer (Perma Seal) was applied to fill small gaps and defects that may have been present on the surfaces and margins of the restorations after the finishing and polishing procedures. | 25,100,407 | [
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Smoking cessation among African American and white smokers in the Veterans Affairs health care system. | We examined whether a proactive care smoking cessation intervention designed to overcome barriers to treatment would be especially effective at increasing cessation among African Americans receiving care in the Veterans Health Administration. We analyzed data from a randomized controlled trial, the Veterans Victory over Tobacco study, involving a population-based electronic registry of current smokers (702 African Americans, 1569 whites) and assessed 6-month prolonged smoking abstinence at 1 year via a follow-up survey of all current smokers. We also examined candidate risk adjustors for the race effect on smoking abstinence. The interaction between patient race and intervention condition (proactive care vs. usual care) was not significant. Overall, African Americans had higher quit rates than Whites (13% vs. 9%; P < .006) regardless of condition. African Americans quit at higher rates than Whites. These findings may be a result of the large number of veterans receiving smoking cessation services and the lack of racial differences in receipt of these services as well as racial differences in smoking history, self-efficacy, and motivation to quit that favor African Americans. | 25,100,424 | [
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Apoptosis inducing effects of Kuding tea polyphenols in human buccal squamous cell carcinoma cell line BcaCD885. | Tea polyphenols are functional substances present in tea. Kuding tea as a traditional drink also contains these compounds. After 25, 50 and 100 μg/mL of Kuding tea polyphenol treatment for 48 h, cell proliferation of human buccal squamous cell carcinoma cell line BcaCD885 was inhibited, and the 100 μg/mL of Kuding tea polyphenol showed the highest inhibitory rate at 72.3%. Compared to the lower concentration, the 100 μg/mL of Kuding tea polyphenols significantly (p < 0.05) induced apoptosis as determined by flow cytometry analysis, the content of sub-G1 cancer cells was 32.7%. By RT-PCR and western blot assays, Kuding tea polyphenol significantly induced apoptosis in BcaCD885 cancer cells (p < 0.05) by upregulating caspase-3, caspase-8, caspase-9, Fas/FasL, Bax, p53, p21, E2F1, p73 and downregulating Bcl-2, Bcl-xL, HIAP-1, and HIAP-2 mRNA and protein expressions. Kuding tea polyphenols thus present apoptosis inducing effects in vitro. | 25,100,434 | [
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Genetic polymorphisms in Pakistani women with polycystic ovary syndrome. | Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility. Although the genetic basis of PCOS is not well understood, it is a common metabolic and endocrine disorder. This study investigates the possible genomic variants associated with PCOS in Pakistani women from the Punjab region. DNA samples from 96 patients with genetically unrelated PCOS and 96 controls were analyzed by direct sequencing to determine the polymorphisms of different loci on follicle-stimulating hormone receptor (fshr), follicle-stimulating hormone β (fshrβ), luteinizing hormone chorionic gonadotropin (lhcgr), luteinizing hormone β (lhβ), estrogen receptor α (esr1), and estrogen receptor β (esr2) genes. Significant associations were observed within the genotype frequencies, allele frequencies, and multi-single-nucleotide polymorphism (SNP) haplotype analysis of most polymorphisms studied. This study identified new SNPs at positions 605+52 Del/T in lhcgr genes occurring in this particular subpopulation. The strong r (2) value suggests that polymorphisms in the fshr and esr1 genes were in linkage disequilibrium. Our study provides evidence of statistically significant associations between susceptibility to PCOS in Pakistani women and the gene polymorphisms mentioned earlier. This suggests that the susceptible loci for PCOS lie within or very close to the chromosomal regions spanning these genes. | 25,100,445 | [
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Learning to BREATHE: an intervention to foster mindfulness in adolescence. | During adolescence, young people are traversing exciting and also challenging stages in their development. Mindfulness, if taught in a developmentally appropriate way, has the potential to be an asset in adolescents' lives. Developmentally appropriate approaches of mindfulness intervention during adolescence need to consider adolescents' social contexts (for example, school setting, peer group, family), their cognitive and emotional stages in development, and age-specific strength and vulnerabilities. This chapter puts mindfulness education into a developmental perspective, and presents the Learning to BREATHE program as a school-based universal intervention for adolescents. The authors describe developmental dimensions and themes of the program, and discuss common challenges of program implementation in schools. A case example of bringing the Learning to BREATHE program into the school context is provided. | 25,100,493 | [
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Hematopoietic stem cell aging and chronic lymphocytic leukemia pathogenesis. | Human malignancies develop through the multistep acquisition of critical somatic mutations during the clinical course. Regarding hematological malignancies, recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are considered to directly originate from differentiated mature lymphocytes; however, we previously reported that the propensity to generate clonal B cells had already been acquired at the HSC stage in CLL patients. Similarly, HSC involvement has been reported in the pathogenesis of mature T cell lymphomas. These studies indicate that, in mature lymphoid, if not all, malignancies, HSCs should be considered as the critical cellular target in the oncogenic process. The prevalence of these hematological malignancies dramatically increases with age, and the effect of aging HSCs should thus be taken into account when investigating the stepwise malignant transformation process of these age-associated malignancies. | 25,100,497 | [
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Where are lengths of stay longer and total charges higher for pediatric burn patients? | Treatment of pediatric burn patients is costly and may require long length of stay in the hospital (LOS). Establishing where these LOS and charges are highest is warranted. The current study investigated whether pediatric burn patients had higher total charges and longer LOS when seen at teaching hospitals, when compared with nonteaching hospitals. The study reviewed inpatient admissions for pediatric burn patients in 2003, 2006, and 2009 by using the Kids' Inpatient Database, which is part of the Healthcare Cost and Utilization Project. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 940-947 were used to define burn injury, LOS, total charges, and type of hospital. The authors tested for differences between the LOS and total charges between children seen at three types of hospitals (pediatric, nonpediatric/teaching, nonpediatric/nonteaching) while adjusting for traditional risk factors (eg age, total burn surface area) by using generalized linear mixed-effects modeling. A total of N=28,777 children had burn injuries (n=16,115, 56.0% seen at pediatric hospitals; n=9353, 32.5% seen at nonpediatric/teaching hospitals; and n=3309, 11.5% seen at nonpediatric/nonteaching hospitals). Pediatric burn patients seen at pediatric hospitals, unadjusted, have significantly longer LOS (5.54 days vs 4.25 days and 4.00 days, P<.001) and more total charges in 2009 dollars ($31,319 vs $24,413 and $21,499, P<.001). In addition, patients seen at pediatric hospitals had significantly more total burn surface area (P<.001), more comorbidities (P=.021), and were younger (P<.001). After adjusting for total burn surface area, number of comorbidities, and age, no differences existed between teaching and nonteaching hospitals for LOS (P=.481) or total charges (P=.758). Although pediatric burn patients may have increased LOS and total charges when seen at teaching hospitals, when taking an unadjusted perspective, this may be an artifact that teaching hospitals see pediatric burn patients who are younger, have more comorbidities, and have more total burn surface area. As such, after adjustment, type of hospital may have no influence on LOS and total charges. | 25,100,537 | [
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Results of a prospective randomized controlled trial of early ambulation for patients with lower extremity autografts. | It is common practice to keep those patients with lower extremity autografts immobile until post-operative day (POD) 5. There is however inherent risks associated with even short periods of immobility. As of now there are no randomized controlled trials looking at early ambulation of patients with lower extremity autografts in the burn community.The objective of this study was to show that patients who begin ambulation within 24 hours of lower extremity autografting will have no increased risk of graft failure than those patients who remain immobile until POD 5. Thirty-one subjects who received autografts to the lower extremity were randomized after surgery into either the early ambulation group (EAG;17 subjects) or the standard treatment group (STG;14 subjects). Those subjects randomized to the EAG began ambulating with physical therapy on POD 1. Subjects in the STG maintained bed rest until POD 5. There was no difference in the number of patients with graft loss in either the EAG or STG on POD 5, and during any of the follow-up visits. No subjects required regrafting. There was a significant difference in the mean minutes of ambulation, with the EAG ambulating longer than the STG (EAG 23.4 minutes [SD 12.03], STG 14.1 [SD 9.00], P=.0235) on POD 5. Burn patients with lower extremity autografts can safely ambulate on POD 1 without fear of graft failure compared with those patients that remain on bed rest for 5 days. | 25,100,538 | [
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Insights into DNA hydroxymethylation in the honeybee from in-depth analyses of TET dioxygenase. | In mammals, a family of TET enzymes producing oxidized forms of 5-methylcytosine (5mC) plays an important role in modulating DNA demethylation dynamics. In contrast, nothing is known about the function of a single TET orthologue present in invertebrates. Here, we show that the honeybee TET (AmTET) catalytic domain has dioxygenase activity and converts 5mC to 5-hydroxymethylcytosine (5hmC) in a HEK293T cell assay. In vivo, the levels of 5hmC are condition-dependent and relatively low, but in testes and ovaries 5hmC is present at approximately 7-10% of the total level of 5mC, which is comparable to that reported for certain mammalian cells types. AmTET is alternatively spliced and highly expressed throughout development and in adult tissues with the highest expression found in adult brains. Our findings reveal an additional level of flexible genomic modifications in the honeybee that may be important for the selection of multiple pathways controlling contrasting phenotypic outcomes in this species. In a broader context, our study extends the current, mammalian-centred attention to TET-driven DNA hydroxymethylation to an easily manageable organism with attractive and unique biology. | 25,100,549 | [
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Hierarchical activated mesoporous phenolic-resin-based carbons for supercapacitors. | A series of hierarchical activated mesoporous carbons (AMCs) were prepared by the activation of highly ordered, body-centered cubic mesoporous phenolic-resin-based carbon with KOH. The effect of the KOH/carbon-weight ratio on the textural properties and capacitive performance of the AMCs was investigated in detail. An AMC prepared with a KOH/carbon-weight ratio of 6:1 possessed the largest specific surface area (1118 m(2) g(-1)), with retention of the ordered mesoporous structure, and exhibited the highest specific capacitance of 260 F g(-1) at a current density of 0.1 A g(-1) in 1 M H2 SO4 aqueous electrolyte. This material also showed excellent rate capability (163 F g(-1) retained at 20 A g(-1)) and good long-term electrochemical stability. This superior capacitive performance could be attributed to a large specific surface area and an optimized micro-mesopore structure, which not only increased the effective specific surface area for charge storage but also provided a favorable pathway for efficient ion transport. | 25,100,552 | [
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SNAI2 controls the undifferentiated state of human epidermal progenitor cells. | The transcription factor, SNAI2, is an inducer of the epithelial to mesenchymal transition (EMT) which mediates cell migration during development and tumor invasion. SNAI2 can also promote the generation of mammary epithelial stem cells from differentiated luminal cells when overexpressed. How SNAI2 regulates these critical and diverse functions is unclear. Here, we show that the levels of SNAI2 expression are important for epidermal cell fate decisions. The expression of SNAI2 was found to be enriched in the basal layer of the interfollicular epidermis where progenitor cells reside and extinguished upon differentiation. Loss of SNAI2 resulted in premature differentiation whereas gain of SNAI2 expression inhibited differentiation. SNAI2 controls the differentiation status of epidermal progenitor cells by binding to and repressing the expression of differentiation genes with increased binding leading to further transcriptional silencing. Thus, the levels of SNAI2 binding to genomic targets determine the differentiation status of epithelial cells with increased levels triggering EMT and dedifferentiation, moderate (physiological) levels promoting epidermal progenitor function, and low levels leading to epidermal differentiation. | 25,100,569 | [
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Dosage-dependent effect of dopamine D2 receptor activation on motor cortex plasticity in humans. | The neuromodulator dopamine plays an important role in synaptic plasticity. The effects depend on receptor subtypes, affinity, concentration level, and the kind of neuroplasticity induced. In animal experiments, dopamine D2-like receptor stimulation revealed partially antagonistic effects on plasticity, which might be explained by dosage dependency. In humans, D2 receptor block abolishes plasticity, and the D2/D3, but predominantly D3, receptor agonist ropinirol has a dosage-dependent nonlinear affect on plasticity. Here we aimed to determine the specific affect of D2 receptor activation on neuroplasticity in humans, because physiological effects of D2 and D3 receptors might differ. Therefore, we combined application of the selective D2 receptor agonist bromocriptine (2.5, 10, and 20 mg or placebo medication) with anodal and cathodal transcranial direct current stimulation (tDCS), which induces nonfocal plasticity, and with paired associative stimulation (PAS) generating a more focal kind of plasticity in the motor cortex of healthy humans. Plasticity was monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. For facilitatory tDCS, bromocriptine prevented plasticity induction independent from drug dosage. However, its application resulted in an inverted U-shaped dose-response curve on inhibitory tDCS, excitability-diminishing PAS, and to a minor degree on excitability-enhancing PAS. These data support the assumption that modulation of D2-like receptor activity exerts a nonlinear dose-dependent effect on neuroplasticity in the human motor cortex that differs from predominantly D3 receptor activation and that the kind of plasticity-induction procedure is relevant for its specific impact. | 25,100,602 | [
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Frontoparietal representations of task context support the flexible control of goal-directed cognition. | Cognitive control allows stimulus-response processing to be aligned with internal goals and is thus central to intelligent, purposeful behavior. Control is thought to depend in part on the active representation of task information in prefrontal cortex (PFC), which provides a source of contextual bias on perception, decision making, and action. In the present study, we investigated the organization, influences, and consequences of context representation as human subjects performed a cued sorting task that required them to flexibly judge the relationship between pairs of multivalent stimuli. Using a connectivity-based parcellation of PFC and multivariate decoding analyses, we determined that context is specifically and transiently represented in a region spanning the inferior frontal sulcus during context-dependent decision making. We also found strong evidence that decision context is represented within the intraparietal sulcus, an area previously shown to be functionally networked with the inferior frontal sulcus at rest and during task performance. Rule-guided allocation of attention to different stimulus dimensions produced discriminable patterns of activation in visual cortex, providing a signature of top-down bias over perception. Furthermore, demands on cognitive control arising from the task structure modulated context representation, which was found to be strongest after a shift in task rules. When context representation in frontoparietal areas increased in strength, as measured by the discriminability of high-dimensional activation patterns, the bias on attended stimulus features was enhanced. These results provide novel evidence that illuminates the mechanisms by which humans flexibly guide behavior in complex environments. | 25,100,605 | [
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Examining multiracial youth in context: ethnic identity development and mental health outcomes. | Although multiracial individuals are the fastest growing population in the United States, research on the identity development of multiracial adolescents remains scant. This study explores the relationship between ethnic identity, its components (affirmation, exploration), and mental health outcomes (anxiety, depressive symptoms) within the contexts of schools for multiracial adolescents. The participants were multiracial and monoracial minority and majority high school students (n = 4,766; 54.6% female). Among the participants, 88.1% were Caucasian, 7.4% were African American, and 4.5% were multiracial. The research questions examined the relationship between ethnic identity exploration and affirmation on mental health outcomes and explored the role school context plays in this relationship. The findings suggested that multiracial youth experience more exploration and less affirmation than African Americans, but more than Caucasians. In addition, multiracial youth were found to have higher levels of mental health issues than their monoracial minority and majority peers. Specifically, multiracial youth had higher levels of depressive symptoms than their African American and Caucasian counterparts. Multiracial and Caucasian youth had similar levels of anxiety but these levels were significantly higher than African Americans. School diversity did not influence mental health outcomes for multiracial youth. These findings provide insight into the experiences of multiracial youth and underscore the importance of further investigating factors that contribute to their mental health outcomes. | 25,100,614 | [
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Breastfeeding duration and asthma in Puerto Rican children. | Little is known about breastfeeding and asthma in Puerto Ricans, the ethnic group most affected by this disease in the US. We examined the relation between the currently recommended duration of breastfeeding and asthma in school-aged Puerto Rican children. Case-control study of 1,127 Puerto Rican children aged 6-14 years living in Hartford, Connecticut (n = 449) and San Juan, Puerto Rico (n = 678). Parental recall of breastfeeding was categorized based on duration and according to current guidelines (i.e., none, 0-6 months, and >6 months). Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. We used logistic regression for the multivariate analysis, which was conducted separately for each study site and for the combined cohort. All multivariate models were adjusted for age, gender, household income, atopy, maternal asthma, body mass index, early-life exposure to environmental tobacco smoke, and (for the combined cohort) study site. After adjustment for covariates, children who were breastfed for up to 6 months had 30% lower odds of asthma (95% CI = 0.5-1.0, P = 0.04) than those who were not breastfed. In this analysis, breastfeeding for longer than 6 months was not significantly associated with asthma (OR = 1.5, 95% CI = 1.0-2.4, P = 0.06). Our results suggest that breastfeeding for up to 6 months (as assessed by parental recall) is associated with decreased odds of asthma in Puerto Rican children, and that there is no additional beneficial effect of breastfeeding for over 6 months. These results support current recommendations on the duration of breastfeeding in an ethnic group at risk for asthma. | 25,100,626 | [
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Preparation of budesonide nanosuspensions for pulmonary delivery: Characterization, in vitro release and in vivo lung distribution studies. | The main objective of the present article was to prepare stable and well-dispersible budesonide (BUD) nanosuspensions by microfluidizer method. The morphology, particle size, and zeta potential of formulation were investigated and in vitro release and in vivo lung distribution were evaluated. Characterizations showed that BUD nanosuspensions were spherical in shape with a smooth surface. The measured average particle size was 122.5 ± 6.3 nm, and ζ potential was - 13.6 ± 0.4 mV. In vitro release behavior of three batches BUD nanosuspensions had a good reproduction. The deposition distribution of BUD different formulations was measured using a modified multi-stage liquid collision method. The data showed that BUD nanosuspensions have the most outstanding deposition distribution with fine particle ratio 82.2%. Compared with normal particle and micronized particles, nanosuspensions were easier to be distributed in lung. After inhalation of 1 h, the drug concentration can reach 872.9 ng/g, which was extremely significantly different from normal particles (p < 0.01) and significantly different from micronized particles (p < 0.05). | 25,100,657 | [
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"Let's get Wasted!" and Other Apps: Characteristics, Acceptability, and Use of Alcohol-Related Smartphone Applications. | Smartphone applications ("apps") offer a number of possibilities for health promotion activities. However, young people may also be exposed to apps with incorrect or poor quality information, since, like the Internet, apps are mostly unregulated. Little is known about the quality of alcohol-related apps or what influence they may have on young people's behavior. To critically review popular alcohol-related smartphone apps and to explore young people's opinions of these apps, their acceptability, and use for alcohol-related health promotion. First, a content analysis of 500 smartphone apps available via Apple iTunes and Android Google Play stores was conducted. Second, all available blood alcohol concentration (BAC) apps were tested against four individual case profiles of known BAC from a previous study. Third, two focus group discussions explored how young people use alcohol-related apps, particularly BAC apps. 384 apps were included; 50% (192) were entertainment apps, 39% (148) were BAC apps, and 11% (44) were health promotion and/or stop drinking-related apps. When testing the BAC apps, there was wide variation in results, with apps tending to overestimate BAC scores compared with recorded scores. Participants were skeptical of the accuracy of BAC apps, and there was an overall concern that these apps would be used as a form of entertainment, further encouraging young people to drink, rather than reduce their drinking and risk taking. The majority of popular alcohol-related apps encouraged alcohol consumption. Apps estimating blood alcohol concentration were widely available but were highly unreliable. Health departments and prominent health organizations need to endorse alcohol smartphone apps that are accurate and evidence-based to give specific apps credibility in the ever-expanding market of unregulated apps. | 25,100,681 | [
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Social life histories: jackdaw dominance increases with age, terminally declines and shortens lifespan. | Behaviour may contribute to changes in fitness prospects with age, for example through effects of age-dependent social dominance on resource access. Older individuals often have higher dominance rank, which may reflect a longer lifespan of dominants and/or an increase in social dominance with age. In the latter case, increasing dominance could mitigate physiological senescence. We studied the social careers of free-living jackdaws over a 12 year period, and found that: (i) larger males attained higher ranks, (ii) social rank increased with age within individuals, and (iii) high-ranked individuals had shorter lifespan suggesting that maintaining or achieving high rank and associated benefits comes at a cost. Lastly, (iv) social rank declined substantially in the last year an individual was observed in the colony, and through its effect on resource access this may accelerate senescence. We suggest that behaviour affecting the ability to secure resources is integral to the senescence process via resource effects on somatic state, where behaviour may include not only social dominance, but also learning, memory, perception and (sexual) signalling. Studying behavioural effects on senescence via somatic state may be most effective in the wild, where there is competition for resources, which is usually avoided in laboratory conditions. | 25,100,696 | [
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The geomagnetic environment in which sea turtle eggs incubate affects subsequent magnetic navigation behaviour of hatchlings. | Loggerhead sea turtle hatchlings (Caretta caretta) use regional magnetic fields as open-ocean navigational markers during trans-oceanic migrations. Little is known, however, about the ontogeny of this behaviour. As a first step towards investigating whether the magnetic environment in which hatchlings develop affects subsequent magnetic orientation behaviour, eggs deposited by nesting female loggerheads were permitted to develop in situ either in the natural ambient magnetic field or in a magnetic field distorted by magnets placed around the nest. In orientation experiments, hatchlings that developed in the normal ambient field oriented approximately south when exposed to a field that exists near the northern coast of Portugal, a direction consistent with their migratory route in the northeastern Atlantic. By contrast, hatchlings that developed in a distorted magnetic field had orientation indistinguishable from random when tested in the same north Portugal field. No differences existed between the two groups in orientation assays involving responses to orbital movements of waves or sea-finding, neither of which involves magnetic field perception. These findings, to our knowledge, demonstrate for the first time that the magnetic environment present during early development can influence the magnetic orientation behaviour of a neonatal migratory animal. | 25,100,699 | [
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Acrosome reaction and Ca²⁺ imaging in single human spermatozoa: new regulatory roles of [Ca²⁺]i. | The spermatozoa acrosome reaction (AR) is essential for mammalian fertilization. Few methods allow visualization of AR in real time together with Ca²⁺ imaging. Here, we show that FM4-64, a fluorescent dye used to follow exocytosis, reliably reports AR progression induced by ionomycin and progesterone in human spermatozoa. FM4-64 clearly delimits the spermatozoa contour and reports morphological cell changes before, during, and after AR. This strategy unveiled the formation of moving tubular appendages, emerging from acrosome-reacted spermatozoa, which was confirmed by scanning electron microscopy. Alternate wavelength illumination allowed concomitant imaging of FM4-64 and Fluo-4, a Ca²⁺ indicator. These AR and intracellular Ca²⁺ ([Ca²⁺]i) recordings revealed that the presence of [Ca²⁺]i oscillations, both spontaneous and progesterone induced, prevents AR in human spermatozoa. Notably, the progesterone-induced AR is preceded by a second [Ca²⁺]i peak and ~40% of reacting spermatozoa also manifest a slow [Ca²⁺]i rise ~2 min before AR. Our findings uncover new AR features related to [Ca²⁺]i. | 25,100,708 | [
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Vildagliptin stimulates endothelial cell network formation and ischemia-induced revascularization via an endothelial nitric-oxide synthase-dependent mechanism. | Dipeptidyl peptidase-4 inhibitors are known to lower glucose levels and are also beneficial in the management of cardiovascular disease. Here, we investigated whether a dipeptidyl peptidase-4 inhibitor, vildagliptin, modulates endothelial cell network formation and revascularization processes in vitro and in vivo. Treatment with vildagliptin enhanced blood flow recovery and capillary density in the ischemic limbs of wild-type mice, with accompanying increases in phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). In contrast to wild-type mice, treatment with vildagliptin did not improve blood flow in ischemic muscles of eNOS-deficient mice. Treatment with vildagliptin increased the levels of glucagon-like peptide-1 (GLP-1) and adiponectin, which have protective effects on the vasculature. Both vildagliptin and GLP-1 increased the differentiation of cultured human umbilical vein endothelial cells (HUVECs) into vascular-like structures, although vildagliptin was less effective than GLP-1. GLP-1 and vildagliptin also stimulated the phosphorylation of Akt and eNOS in HUVECs. Pretreatment with a PI3 kinase or NOS inhibitor blocked the stimulatory effects of both vildagliptin and GLP-1 on HUVEC differentiation. Furthermore, treatment with vildagliptin only partially increased the limb flow of ischemic muscle in adiponectin-deficient mice in vivo. GLP-1, but not vildagliptin, significantly increased adiponectin expression in differentiated 3T3-L1 adipocytes in vitro. These data indicate that vildagliptin promotes endothelial cell function via eNOS signaling, an effect that may be mediated by both GLP-1-dependent and GLP-1-independent mechanisms. The beneficial activity of GLP-1 for revascularization may also be partially mediated by its ability to increase adiponectin production. | 25,100,725 | [
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Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis. | In multiple sclerosis (MS), lymphocyte--in particular B cell--transit between the central nervous system (CNS) and periphery may contribute to the maintenance of active disease. Clonally related B cells exist in the cerebrospinal fluid (CSF) and peripheral blood (PB) of MS patients; however, it remains unclear which subpopulations of the highly diverse peripheral B cell compartment share antigen specificity with intrathecal B cell repertoires and whether their antigen stimulation occurs on both sides of the blood-brain barrier. To address these questions, we combined flow cytometric sorting of PB B cell subsets with deep immune repertoire sequencing of CSF and PB B cells. Immunoglobulin (IgM and IgG) heavy chain variable (VH) region repertoires of five PB B cell subsets from MS patients were compared with their CSF Ig-VH transcriptomes. In six of eight patients, we identified peripheral CD27(+)IgD(-) memory B cells, CD27(hi)CD38(hi) plasma cells/plasmablasts, or CD27(-)IgD(-) B cells that had an immune connection to the CNS compartment. Pinpointing Ig class-switched B cells as key component of the immune axis thought to contribute to ongoing MS disease activity strengthens the rationale of current B cell-targeting therapeutic strategies and may lead to more targeted approaches. | 25,100,740 | [
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Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice. | Insulin-like growth factor 2 (IGF2) was recently found to play a critical role in memory consolidation in rats and mice, and hippocampal or systemic administration of recombinant IGF2 enhances memory. Here, using a gene therapy-based approach with adeno-associated virus (AAV), we show that IGF2 overexpression in the hippocampus of aged wild-type mice enhances memory and promotes dendritic spine formation. Furthermore, we report that IGF2 expression decreases in the hippocampus of patients with Alzheimer's disease, and this leads us to hypothesize that increased IGF2 levels may be beneficial for treating the disease. Thus, we used the AAV system to deliver IGF2 or IGF1 into the hippocampus of the APP mouse model Tg2576 and demonstrate that IGF2 and insulin-like growth factor 1 (IGF1) rescue behavioural deficits, promote dendritic spine formation and restore normal hippocampal excitatory synaptic transmission. The brains of Tg2576 mice that overexpress IGF2 but not IGF1 also show a significant reduction in amyloid levels. This reduction probably occurs through an interaction with the IGF2 receptor (IGF2R). Hence, IGF2 and, to a lesser extent, IGF1 may be effective treatments for Alzheimer's disease. | 25,100,745 | [
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Osteochondral lesions of the talus: a current concepts review and evidence-based treatment paradigm. | Osteochondral lesions of the talar dome are increasingly diagnosed and are a difficult pathology to treat. Conservative treatment yields best results in pediatric patients, often leaving surgical options for adult populations. There is a paucity of long-term data and comparisons of treatment options. Arthroscopic bone marrow stimulation is a common first-line treatment for smaller lesions. Despite promising short to medium term clinical results, bone marrow stimulation results in fibrocartilagenous tissue that incurs differing mechanical and biological properties compared with normal cartilage. Autologous osteochondral transplantation has demonstrated promising clinical results in the short to medium term for larger, cystic lesions and can restore the contact pressure of the joint. However, concerns remain over postoperative cyst formation and donor site morbidity. Recent developments have emphasized the usefulness of biological adjuncts such as platelet-rich plasma and concentrated bone marrow aspirate, as well as particulate juvenile cartilage, in augmenting reparative and replacement strategies in osteochondral lesion treatment. The purpose of this article is to review diagnosis and treatment of talar osteochondral lesions so that current practice guidelines can be more efficiently used given the available treatment strategies. A treatment paradigm based on current evidence is described. Therapeutic, Level V, Expert Opinion. | 25,100,765 | [
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Outcome of All-Inside Second-Generation Meniscal Repair: Minimum Five-Year Follow-up. | Meniscal repair and preservation are the goal, when possible, of the treatment of meniscal injury. Current research on second-generation all-inside repair systems has been limited to a maximum of three years of follow-up. The purpose of this study was to evaluate the mid-term clinical success (at more than five years) of meniscal repair performed with a second-generation all-inside repair device, both as an isolated procedure and with a concomitant anterior cruciate ligament (ACL) reconstruction. This is a retrospective review of patients who underwent meniscal repair with use of the all-inside FAST-FIX Meniscal Repair System (Smith & Nephew Arthroscopy, Andover, Massachusetts) from December 1999 to January 2007. Eighty-three meniscal repairs (in eighty-one patients) were identified, and follow-up data were obtained for seventy-five (90%). Twenty-six (35%) of the meniscal repairs were performed as isolated procedures. Clinical failure was defined as repeat surgical intervention involving resection or revision repair. Clinical outcomes were also assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, and the Marx activity score. The minimum duration of follow-up was five years (average, seven years). Twelve patients (16%) had failure of the meniscal repair, at an average of forty-seven months (range, fifteen to ninety-five months). The data did not offer enough statistical evidence, at alpha = 0.05, to establish a difference in average patient age, patient sex, or number of sutures utilized between successful repairs and failures. There was no difference in the failure rate between isolated repairs (12%; 95% confidence interval [CI]: -0.76% to 23.76%) and those performed with concurrent ACL reconstruction (18%; 95% CI: 7.47% to 29.13%), and the average time to failure was similar between these two groups (48.1 months versus 46.6 months, p = 0.939). Postoperative KOOS and IKDC outcome scores were also similar between the groups. This report of mid-term follow-up results of primary second-generation all-inside meniscal repair demonstrates its effectiveness both as an isolated procedure and when it is performed with concurrent ACL reconstruction. After a minimum of five years of follow-up, 84% of the patients continued to demonstrate successful repair. Treatment success was further supported by favorable results on patient-based outcome measures. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. | 25,100,778 | [
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Deep Surgical Site Infection Following 2344 Growing-Rod Procedures for Early-Onset Scoliosis: Risk Factors and Clinical Consequences. | Deep surgical site infection may change the course of growing-rod treatment of early-onset scoliosis. Our goal was to assess the effect of this complication on subsequent treatment. A multicenter international database was retrospectively reviewed; 379 patients treated with growing-rod surgery and followed for a minimum of two years were identified. Deep surgical site infection was defined as any infection requiring surgical intervention. Forty-two patients (11.1%; twenty-five males and seventeen females) developed at least one deep surgical site infection. The mean age at the initial growing-rod surgery was 6.3 years (range, 0.6 to 13.2 years) and the mean duration of follow-up was 5.3 years (range, 2.2 to 14.3 years). The mean interval between the initial surgery and the first deep surgical site infection was 2.8 years (range, 0.02 to 7.9 years). Ten (2.6%) of the 379 patients developed deep surgical site infection before the first lengthening. Twenty-nine patients (7.7%) developed the infection during the course of the lengthening procedures, and three patients (0.8%) developed it after final fusion surgery. Thirty (13.6%) of 221 patients with stainless-steel implants had at least one deep surgical site infection compared with twelve (8%) of 150 patients with titanium implants (p < 0.05). (The remaining patients were treated with chromium-cobalt implants.) Twenty-two (52.4%) of the forty-two patients with deep surgical site infection underwent implant removal, which was complete in thirteen and partial in nine. Growing-rod treatment was terminated in two patients with partial removal and six patients with complete removal. An increased risk of deep surgical site infection was associated with stainless-steel implants (odds ratio [OR] = 5.7), non-ambulatory status (OR = 2.9), and the number of revisions before the development of deep surgical site infection (OR = 3.3). Neuromuscular etiology and non-ambulatory status increased the possibility of implant removal to treat infection (p < 0.05). The prevalence of deep surgical site infection associated with growing-rod surgery is higher than that associated with standard pediatric spinal fusion (historical data). Non-ambulatory status, more revisions, and stainless-steel implants increased the risk of deep surgical site infection. After eight surgical procedures, the risk of deep surgical site infection increased to approximately 50%. When patients have implant removal, efforts should be made to retain one longitudinal implant to continue treatment. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. | 25,100,781 | [
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Prevalence and correlates of smoking and cessation-related behavior among survivors of ten cancers: findings from a nationwide survey nine years after diagnosis. | Smoking is detrimental to recovery and survival from cancer, but many cancer survivors continue to smoke. Information is lacking on smoking patterns of survivors many years after diagnosis and correlates of smoking status and patterns, likelihood of quitting, and intentions to quit. Cross-sectional analyses were conducted among survivors of 10 cancers recruited by stratified random sampling from cancer registries in a nationwide, longitudinal, quality-of-life study (n = 2,938). Approximately 9 years after diagnosis, 9.3% of all survivors were current (past 30-day) smokers. Smoking prevalence was highest among survivors of bladder (17.2%), lung (14.9%), and ovarian (11.6%) cancers. Most current smokers (83%) smoked daily, averaging 14.7 cigarettes per day (cpd). Forty percent of daily smokers smoked more than 15 cpd. Nondaily smokers smoked a mean of 10.9 days in the last 30 days and averaged 5.7 cpd on smoking days. Current smoking was associated with younger age, lower education and income, and greater alcohol consumption. Quitting after diagnosis was associated with having a smoking-related cancer. Roughly, a third of current smokers intended to quit, 40% within the next month. The odds of intending to quit were lower if survivors were married, older, or smoked more. This population-based study indicated that smoking can persist long after initial diagnosis and at high levels and identified characteristics associated with quitting and intentions to quit. Findings can be used to identify survivors most at risk for continued smoking and to inform tailoring of cessation treatments for survivors. | 25,100,826 | [
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Human rhinovirus 16 causes Golgi apparatus fragmentation without blocking protein secretion. | The replication of picornaviruses has been described to cause fragmentation of the Golgi apparatus that blocks the secretory pathway. The inhibition of major histocompatibility complex class I upregulation and cytokine, chemokine and interferon secretion may have important implications for host defense. Previous studies have shown that disruption of the secretory pathway can be replicated by expression of individual nonstructural proteins; however the situation with different serotypes of human rhinovirus (HRV) is unclear. The expression of 3A protein from HRV14 or HRV2 did not cause Golgi apparatus disruption or a block in secretion, whereas other studies showed that infection of cells with HRV1A did cause Golgi apparatus disruption which was replicated by the expression of 3A. HRV16 is the serotype most widely used in clinical HRV challenge studies; consequently, to address the issue of Golgi apparatus disruption for HRV16, we have systematically and quantitatively examined the effect of HRV16 on both Golgi apparatus fragmentation and protein secretion in HeLa cells. First, we expressed each individual nonstructural protein and examined their cellular localization and their disruption of endoplasmic reticulum and Golgi apparatus architecture. We quantified their effects on the secretory pathway by measuring secretion of the reporter protein Gaussia luciferase. Finally, we examined the same outcomes following infection of cells with live virus. We demonstrate that expression of HRV16 3A and 3AB and, to a lesser extent, 2B caused dispersal of the Golgi structure, and these three nonstructural proteins also inhibited protein secretion. The infection of cells with HRV16 also caused significant Golgi apparatus dispersal; however, this did not result in the inhibition of protein secretion. Importance: The ability of replicating picornaviruses to influence the function of the secretory pathway has important implications for host defense. However, there appear to be differences between different members of the family and inconsistent results when comparing infection with live virus to expression of individual nonstructural proteins. We demonstrate that individual nonstructural HRV16 proteins, when expressed in HeLa cells, can both fragment the Golgi apparatus and block secretion, whereas viral infection fragments the Golgi apparatus without blocking secretion. This has major implications for how we interpret mechanistic evidence derived from the expression of single viral proteins. | 25,100,828 | [
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The Epstein-Barr virus (EBV) glycoprotein B cytoplasmic C-terminal tail domain regulates the energy requirement for EBV-induced membrane fusion. | The entry of enveloped viruses into host cells is preceded by membrane fusion, which in Epstein-Barr virus (EBV) is thought to be mediated by the refolding of glycoprotein B (gB) from a prefusion to a postfusion state. In our current studies, we characterized a gB C-terminal tail domain (CTD) mutant truncated at amino acid 843 (gB843). This truncation mutant is hyperfusogenic as monitored by syncytium formation and in a quantitative fusion assay and is dependent on gH/gL for fusion activity. gB843 can rescue the fusion function of other glycoprotein mutants that have null or decreased fusion activity in epithelial and B cells. In addition, gB843 requires less gp42 and gH/gL for fusion, and can function in fusion at a lower temperature than wild-type gB, indicating a lower energy requirement for fusion activation. Since a key step in fusion is the conversion of gB from a prefusion to an active postfusion state by gH/gL, gB843 may access this activated gB state more readily. Our studies indicate that the gB CTD may participate in the fusion function by maintaining gB in an inactive prefusion form prior to activation by receptor binding. Importance: Diseases resulting from Epstein-Barr virus (EBV) infection in humans range from the fairly benign disease infectious mononucleosis to life-threatening cancer. As an enveloped virus, EBV must fuse with a host cell membrane for entry and infection by using glycoproteins gH/gL, gB, and gp42. Among these glycoproteins, gB is thought to be the protein that executes fusion. To further characterize the function of the EBV gB cytoplasmic C-terminal tail domain (CTD) in fusion, we used a previously constructed CTD truncation mutant and studied its fusion activity in the context of other EBV glycoprotein mutants. From these studies, we find that the gB CTD regulates fusion by altering the energy requirements for the triggering of fusion mediated by gH/gL or gp42. Overall, our studies may lead to a better understanding of EBV fusion and entry, which may result in novel therapies that target the EBV entry step. | 25,100,836 | [
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Coinfection with Streptococcus pneumoniae modulates the B cell response to influenza virus. | Pathogen-specific antibodies (Abs) protect against respiratory infection with influenza A virus (IAV) and Streptococcus pneumoniae and are the basis of effective vaccines. Sequential or overlapping coinfections with both pathogens are common, yet the impact of coinfection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in mice coinfected with IAV and S. pneumoniae and that this response differs, depending on the order of pathogen exposure. In mice exposed to S. pneumoniae prior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4(+) T follicular helper (TFH) cell numbers. In contrast, secondary S. pneumoniae infection exaggerates early antiviral antibody-secreting cell formation, and at later times, levels of GCs, TFH cells, and antiviral serum IgG are elevated. Mice exposed to S. pneumoniae prior to IAV do not maintain the initially robust GC response in secondary lymphoid organs and exhibit reduced antiviral serum IgG with diminished virus neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective antiviral Abs and may partially explain the differential susceptibility to and disease outcomes from IAV infection in humans. Importance: Respiratory tract coinfections, specifically those involving influenza A viruses and Streptococcus pneumoniae, remain a top global health burden. We sought to determine how S. pneumoniae coinfection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection. | 25,100,838 | [
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Effect of formaldehyde inactivation on poliovirus. | Inactivated polio vaccines, which have been used in many countries for more than 50 years, are produced by treating live poliovirus (PV) with formaldehyde. However, the molecular mechanisms underlying virus inactivation are not well understood. Infection by PV is initiated by virus binding to specific cell receptors, which results in viral particles undergoing sequential conformational changes that generate altered structural forms (135S and 80S particles) and leads to virus cell entry. We have analyzed the ability of inactivated PV to bind to the human poliovirus receptor (hPVR) using various techniques such as ultracentrifugation, fluorescence-activated cell sorting flow cytometry and real-time reverse transcription-PCR (RT-PCR). The results showed that although retaining the ability to bind to hPVR, inactivated PV bound less efficiently in comparison to live PV. We also found that inactivated PV showed resistance to structural conversion in vitro, as judged by measuring changes in antigenicity, the ability to bind to hPVR, and viral RNA release at high temperature. Furthermore, viral RNA from inactivated PV was shown to be modified, since cDNA yields obtained by RT-PCR amplification were severely reduced and no infectious virus was recovered after RNA transfection into susceptible cells. Importance: This study represents a novel insight into the molecular mechanisms responsible for poliovirus inactivation. We show that inactivation with formaldehyde has an effect on early steps of viral replication as it reduces the ability of PV to bind to hPVR, decreases the sensitivity of PV to convert to 135S particles, and abolishes the infectivity of its viral RNA. These changes are likely responsible for the loss of infectivity shown by PV following inactivation. Techniques used in this study represent new approaches for the characterization of inactivated PV products and could be useful in developing improved methods for the production and quality control testing of inactivated polio vaccines. Measuring the antigenicity, capsid stability, and RNA integrity of inactivated PV samples could help establishing the optimal balance between the loss of infectivity and the preservation of virus antigenicity during inactivation. | 25,100,844 | [
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Development of Behavioral Control and Associated vmPFC-DLPFC Connectivity Explains Children's Increased Resistance to Temptation in Intertemporal Choice. | Human civilization is based on the successful pursuit of long-term goals, requiring the ability to forego immediate pleasure for the sake of larger future rewards. This ability improves with age, but the precise cognitive and neural mechanisms underlying its development remain elusive. The developmental changes could result either from younger children valuing immediate rewards more strongly or because older children become better at controlling their impulses. By implementing 2 tasks, a choice-independent valuation task and an intertemporal choice task, both behaviorally and using fMRI in twenty 6- to 13-year old children, we show developmental improvements in behavioral control to uniquely account for age-related changes in temporal discounting. We show further that overcoming temptation during childhood occurs as a function of an age-related increase in functional coupling between value signals in the ventromedial prefrontal cortex and brain regions dedicated to behavioral control, such as left dorsolateral prefrontal cortex during choice. These findings can help to devise measures that reduce the substantial costs of impatience to society. | 25,100,855 | [
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Improved calibration of the human mitochondrial clock using ancient genomes. | Reliable estimates of the rate at which DNA accumulates mutations (the substitution rate) are crucial for our understanding of the evolution and past demography of virtually any species. In humans, there are considerable uncertainties around these rates, with substantial variation among recent published estimates. Substitution rates have traditionally been estimated by associating dated events to the root (e.g., the divergence between humans and chimpanzees) or to internal nodes in a phylogenetic tree (e.g., first entry into the Americas). The recent availability of ancient mitochondrial DNA sequences allows for a more direct calibration by assigning the age of the sequenced samples to the tips within the human phylogenetic tree. But studies also vary greatly in the methodology employed and in the sequence panels analyzed, making it difficult to tease apart the causes for the differences between previous estimates. To clarify this issue, we compiled a comprehensive data set of 350 ancient and modern human complete mitochondrial DNA genomes, among which 146 were generated for the purpose of this study and estimated substitution rates using calibrations based both on dated nodes and tips. Our results demonstrate that, for the same data set, estimates based on individual dated tips are far more consistent with each other than those based on nodes and should thus be considered as more reliable. | 25,100,861 | [
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Introduction of Inhaled Nitrous Oxide and Oxygen for Pain Management during Labour - Evaluation of Patients' and Midwives' Satisfaction. | <bAim:</b Effective pain management during labour is important because pain affects the birth experience. Epidural analgesia is effective but often it may not be possible; however, inhaled analgesia offers another option. Use of inhaled nitrous oxide and oxygen for pain management in labour is well established in obstetrics but is still not used much in Germany. This study aimed to investigate the acceptance of the inhaled analgesia of inhaled nitrous oxide and oxygen by midwives and pregnant women during labour. <bMaterial and Methods:</b In this observational study carried out between April and September 2013, a total of 66 pregnant women received inhaled nitrous oxide and oxygen during labour on request and after prior assessment of suitability. After the birth, all of the women and the responsible midwives were interviewed about their experience and satisfaction with the inhaled analgesia. <bResults:</b A statistically significant reduction of pain was achieved with nitrous oxide and oxygen. The inhaled analgesia was mostly used by women who refused epidural analgesia. The likelihood of using inhaled nitrous oxide and oxygen again was reported as higher for patients who tolerated it well (p = 0.0129) and used it in the second stage of labour (p = 0.0003) and when bearing down (p = 0.0008). <bConclusion:</b Inhaled nitrous oxide and oxygen is an effective method for pain management during labour and is accepted well by women in labour and by midwives. | 25,100,880 | [
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Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) in the pre-Columbian culture of Colombia. | Mucopolysaccharidosis type VI or Maroteaux Lamy syndrome is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B, the clinical features include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism, with intelligence usually normal. We present evidence of the possible existence of Maroteaux Lamy syndrome in pre-Columbian pottery 2000 years ago, in the Colombo-Ecuadorian Pacific coast of the Tumaco-Tolita culture. | 25,100,895 | [
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Quality of life in non-infectious uveitis patients on immunosuppressive therapy. | To assess visual function and vision related quality of life in patients with non-infectious posterior or panuveitis treated with immunosuppressives. Forty-three patients with non-inflammatory posterior or panuveitis were enrolled in this prospective study. All subjects underwent a detailed interview, complete ophthalmic examination, quality of life assessment using National Eye Institute Visual Function Questionnaire (VFQ-25), visual function evaluation (visual acuity and visual field) at baseline and at a sixth month follow up visit. The mean NEI-VFQ 25 composite score of the subjects with posterior or panuveitis was 58.0 (± 24.1). There was a statistically significant improvement (P = 0.004) in the composite score following treatment from 58.0 (± 24.1) to 74.3 (± 22.0) with effect size of 1.03. The psychological well-being and general health subscales showed significant improvement in the mean score following immunosuppressive therapy. While considering the visual function tests, there was a three-line improvement in the visual acuity score and changeover in the visual field severity from moderate to early defect with corresponding improvement in the visual field pattern. Though most of the patients complained of side effects such as tiredness, gastrointestinal upset and weight gain, there was improvement in the general health subscale. The significant improvement in the general health subscale despite side-effects shows that the benefit of immunosuppressive outweighs the risks of the therapy and this may also reflect the relatively low impact of these side-effects on the quality of life. This study shows that the use of immunosuppressives improves the quality of life of the individual. | 25,100,906 | [
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Bilateral choroidal osteoma with choroidal neovascular membrane treated with bevacizumab in a child. | Choroidal osteoma is a rare benign tumor. We report a male child diagnosed with bilateral choroidal osteoma, high myopia and secondary choroidal neovascularization (CNV) membrane in one eye. Co-existence of posterior staphyloma made the clinical diagnosis of choroidal osteoma difficult due to the osteoma filling the depression of the posterior staphyloma. Typical findings on fundus fluorescein angiography, optical coherence tomography, B-scan and indocyanine green angiography confirmed the diagnosis. A review of literature was performed. CNV secondary to choroidal osteoma was treated with intravitreal bevacizumab and it responded well. Regular follow-up is essential for recurrence of CNV and decalcification of the osteoma. | 25,100,914 | [
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Computationally Efficient Multiconfigurational Reactive Molecular Dynamics. | It is a computationally demanding task to explicitly simulate the electronic degrees of freedom in a system to observe the chemical transformations of interest, while at the same time sampling the time and length scales required to converge statistical properties and thus reduce artifacts due to initial conditions, finite-size effects, and limited sampling. One solution that significantly reduces the computational expense consists of molecular models in which effective interactions between particles govern the dynamics of the system. If the interaction potentials in these models are developed to reproduce calculated properties from electronic structure calculations and/or ab initio molecular dynamics simulations, then one can calculate accurate properties at a fraction of the computational cost. Multiconfigurational algorithms model the system as a linear combination of several chemical bonding topologies to simulate chemical reactions, also sometimes referred to as "multistate". These algorithms typically utilize energy and force calculations already found in popular molecular dynamics software packages, thus facilitating their implementation without significant changes to the structure of the code. However, the evaluation of energies and forces for several bonding topologies per simulation step can lead to poor computational efficiency if redundancy is not efficiently removed, particularly with respect to the calculation of long-ranged Coulombic interactions. This paper presents accurate approximations (effective long-range interaction and resulting hybrid methods) and multiple-program parallelization strategies for the efficient calculation of electrostatic interactions in reactive molecular simulations. | 25,100,924 | [
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Impurities of crude glycerol and their effect on metabolite production. | Glycerol is a valuable raw material for the production of industrially useful metabolites. Among many promising applications for the use of glycerol is its bioconversion to high value-added compounds, such as 1,3-propanediol (1,3-PD), succinate, ethanol, propionate, and hydrogen, through microbial fermentation. Another method of waste material utilization is the application of crude glycerol in blends with other wastes (e.g., tomato waste hydrolysate). However, crude glycerol, a by-product of biodiesel production, has many impurities which can limit the yield of metabolites. In this mini-review we summarize the effects of crude glycerol impurities on various microbial fermentations and give an overview of the metabolites that can be synthesized by a number of prokaryotic and eukaryotic microorganisms when cultivated on glycerol. | 25,100,926 | [
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Dopamine-induced tyrosine phosphorylation of NR2B (Tyr1472) is essential for ERK1/2 activation and processing of novel taste information. | Understanding the heterosynaptic interaction between glutamatergic and neuromodulatory synapses is highly important for revealing brain function in health and disease. For instance, the interaction between dopamine and glutamate neurotransmission is vital for memory and synaptic plasticity consolidation, and it is known to converge on extracellular signal-regulated kinase (ERK)-MAPK signaling in neurons. Previous studies suggest that dopamine induces N-methyl-D-aspartate (NMDA) receptor phosphorylation at the NR2B Y1472 subunit, influencing receptor internalization at the synaptic plasma membrane. However, it is unclear whether this phosphorylation is upstream to and/or necessary for ERK1/2 activation, which is known to be crucial for synaptic plasticity and memory consolidation. Here, we tested the hypothesis that tyrosine phosphorylation of NR2B at Y1472 is correlated with ERK1/2 activation by dopamine and necessary for it as well. We find that dopamine receptor D1, but not D2, activates ERK1/2 and leads to NR2BY1472 phosphorylation in the mature hippocampus and cortex. Moreover, our results indicate that NR2B Y1472 phosphorylation is necessary for ERK1/2 activation. Importantly, application of dopamine or the D1 receptor agonist SKF38393 to hippocampal slices from NR2B F1472 mutant mice did not result in ERK1/2 activation, suggesting this site is not only correlated with ERK1/2 activation by dopamine stimulation, but also necessary for it. In addition, NR2B F1472 mice show impairment in learning of attenuation of taste neophobia but not associative taste learning. Our study shows that the dopaminergic and glutamatergic transmission converge on the NMDA receptor itself, at the Y1472 site of the NR2B subunit, and that this convergence is essential for ERK1/2 activation in the mature brain and for processing new sensory information in the cortex. | 25,100,942 | [
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How cognitive enhancement can change our duties. | This theoretical paper draws the scientific community's attention to how pharmacological cognitive enhancement may impact on society and law. Namely, if safe, reliable, and effective techniques to enhance mental performance are eventually developed, then this may under some circumstances impose new duties onto people in high-responsibility professions-e.g., surgeons or pilots-to use such substances to minimize risks of adverse outcomes or to increase the likelihood of good outcomes. By discussing this topic, we also hope to encourage scientists to bring their expertise to bear on this current public debate. | 25,100,952 | [
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Comparison of the effects of transdermal and oral rivastigmine on cognitive function and EEG markers in patients with Alzheimer's disease. | Alzheimer's disease (AD) is the most common cause of dementia in older patients. Rivastigmine (RV, Exelon, Novartis), a reversible cholinesterase inhibitor, improves clinical manifestations of AD and may enhance ACh-modulated electroencephalogram (EEG) alpha frequency. This pilot study aimed to determine the effects of two formulations of RV [transdermal patch (RV-TDP) and oral capsules (TV-CP)] on alpha frequency, in particular the posterior dominant rhythm, and cognitive function [assessed by the Mini-Mental State Examination (MMSE)] in patients with AD. Subjects with AD were assigned to receive either RV-TDP 10 cm(2) or RV-CP 12 mg/day. All patients underwent EEG recordings at the beginning and end of the 18-month study period using P3, P4, O1, and O2 electrodes, each at high (10.5-13.0 Hz) and low (8.0-10.5 Hz) frequency. MMSE scores were determined at the start of the study (T0) and at three successive 6-month intervals (T1, T2, and T3). RV-TDP administration (n = 10) maintained cognitive function as evidenced by stable MMSE scores from baseline to 18 months (21.07 ± 2.4-21.2 ± 3.1) compared with a decrease in MMSE score with RV-CP (n = 10) over 18 months [18.3 ± 3.6-13.6 ± 5.06 (adjusted for covariates p = 0.006)]. MMSE scores were significantly different between treatment groups from 6 months (p = 0.04). RV-TDP also increased the spectral power of alpha waves in the posterior region measured with electrode P3 in a significantly great percentage of patients than TV-CP from baseline to 18 months; 80% vs 30%, respectively [p = 0.025 (χ (2) test)]. RV-TDP was associated with a greater proportion of patients with increased posterior region alpha wave spectral power and significantly higher cognitive function at 18 months, compared with RV-CP treatment. Our findings suggest that RV-TDP provides an effective long-term management option in patients with AD compared with oral RV-CP. This study is a pilot, open-label study with a clear explorative purpose and with a small number of patients. Further randomized, double-blind, placebo-controlled trial studies with a bigger sample size as well as healthy controls are needed to support these initial results. | 25,100,996 | [
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The types of hepatic myofibroblasts contributing to liver fibrosis of different etiologies. | Liver fibrosis results from dysregulation of normal wound healing, inflammation, activation of myofibroblasts, and deposition of extracellular matrix (ECM). Chronic liver injury causes death of hepatocytes and formation of apoptotic bodies, which in turn, release factors that recruit inflammatory cells (neutrophils, monocytes, macrophages, and lymphocytes) to the injured liver. Hepatic macrophages (Kupffer cells) produce TGFβ1 and other inflammatory cytokines that activate Collagen Type I producing myofibroblasts, which are not present in the normal liver. Secretion of TGFβ1 and activation of myofibroblasts play a critical role in the pathogenesis of liver fibrosis of different etiologies. Although the composition of fibrogenic myofibroblasts varies dependent on etiology of liver injury, liver resident hepatic stellate cells and portal fibroblasts are the major source of myofibroblasts in fibrotic liver in both experimental models of liver fibrosis and in patients with liver disease. Several studies have demonstrated that hepatic fibrosis can reverse upon cessation of liver injury. Regression of liver fibrosis is accompanied by the disappearance of fibrogenic myofibroblasts followed by resorption of the fibrous scar. Myofibroblasts either apoptose or inactivate into a quiescent-like state (e.g., stop collagen production and partially restore expression of lipogenic genes). Resolution of liver fibrosis is associated with recruitment of macrophages that secrete matrix-degrading enzymes (matrix metalloproteinase, collagenases) and are responsible for fibrosis resolution. However, prolonged/repeated liver injury may cause irreversible crosslinking of ECM and formation of uncleavable collagen fibers. Advanced fibrosis progresses to cirrhosis and hepatocellular carcinoma. The current review will summarize the role and contribution of different cell types to populations of fibrogenic myofibroblasts in fibrotic liver. | 25,100,997 | [
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Special delivery: distributing iron in the cytosol of mammalian cells. | Eukaryotic cells contain hundreds of proteins that require iron cofactors for activity. These iron enzymes are located in essentially every subcellular compartment; thus, iron cofactors must travel to every compartment in the cell. Iron cofactors exist in three basic forms: Heme, iron-sulfur clusters, and simple iron ions (also called non-heme iron). Iron ions taken up by the cell initially enter a kinetically labile, exchangeable pool that is referred to as the labile iron pool. The majority of the iron in this pool is delivered to mitochondria, where it is incorporated into heme and iron-sulfur clusters, as well as non-heme iron enzymes. These cofactors must then be distributed to nascent proteins in the mitochondria, cytosol, and membrane-bound organelles. Emerging evidence suggests that specific systems exist for the distribution of iron cofactors within the cell. These systems include membrane transporters, protein chaperones, specialized carriers, and small molecules. This review focuses on the distribution of iron ions in the cytosol and will highlight differences between the iron distribution systems of simple eukaryotes and mammalian cells. | 25,101,000 | [
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How incorporation of scents could enhance immersive virtual experiences. | Under normal everyday conditions, senses all work together to create experiences that fill a typical person's life. Unfortunately for behavioral and cognitive researchers who investigate such experiences, standard laboratory tests are usually conducted in a nondescript room in front of a computer screen. They are very far from replicating the complexity of real world experiences. Recently, immersive virtual reality (IVR) environments became promising methods to immerse people into an almost real environment that involves more senses. IVR environments provide many similarities to the complexity of the real world and at the same time allow experimenters to constrain experimental parameters to obtain empirical data. This can eventually lead to better treatment options and/or new mechanistic hypotheses. The idea that increasing sensory modalities improve the realism of IVR environments has been empirically supported, but the senses used did not usually include olfaction. In this technology report, we will present an odor delivery system applied to a state-of-the-art IVR technology. The platform provides a three-dimensional, immersive, and fully interactive visualization environment called "Brain and Behavioral Laboratory-Immersive System" (BBL-IS). The solution we propose can reliably deliver various complex scents during different virtual scenarios, at a precise time and space and without contamination of the environment. The main features of this platform are: (i) the limited cross-contamination between odorant streams with a fast odor delivery (< 500 ms), (ii) the ease of use and control, and (iii) the possibility to synchronize the delivery of the odorant with pictures, videos or sounds. How this unique technology could be used to investigate typical research questions in olfaction (e.g., emotional elicitation, memory encoding or attentional capture by scents) will also be addressed. | 25,101,017 | [
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Phonological working memory and reading in students with dyslexia. | To investigate parameters related to fluency, reading comprehension and phonological processing (operational and short-term memory) and identify potential correlation between the variables in Dyslexia and in the absence of reading difficulties. One hundred and fifteen students from the third to eighth grade of elementary school were grouped into a Control Group (CG) and Group with Dyslexia (GDys). Reading of words, pseudowords and text (decoding); listening and reading comprehension; phonological short-term and working memory (repetition of pseudowords and Digit Span) were evaluated. The comparison of the groups showed significant differences in decoding, phonological short-term memory (repetition of pseudowords) and answers to text-connecting questions (TC) on reading comprehension, with the worst performances identified for GDys. In this group there were negative correlations between pseudowords repetition and TC answers and total score, both on listening comprehension. No correlations were found between operational and short-term memory (Digit Span) and parameters of fluency and reading comprehension in dyslexia. For the sample without complaint, there were positive correlations between some parameters of reading fluency and repetition of pseudowords and also between answering literal questions in listening comprehension and repetition of digits on the direct and reverse order. There was no correlation with the parameters of reading comprehension. GDys and CG showed similar performance in listening comprehension and in understanding of explicit information and gap-filling inference on reading comprehension. Students of GDys showed worst performance in reading decoding, phonological short-term memory (pseudowords) and on inferences that depends on textual cohesion understanding in reading. There were negative correlations between pseudowords repetition and TC answers and total score, both in listening comprehension. | 25,101,021 | [
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Time course of auditory streaming: do CI users differ from normal-hearing listeners? | In a complex acoustical environment, the auditory system decides which stimulus components originate from the same source by forming auditory streams, where temporally non-overlapping stimulus portions are considered to originate from one source if their stimulus characteristics are similar. The mechanisms underlying streaming are commonly studied by alternating sequences of A and B signals which are often tones with different frequencies. For similar frequencies, they are grouped into one stream. Otherwise, they are considered to belong to different streams. The present study investigates streaming in cochlear implant (CI) users, where hearing is restored by electrical stimulation of the auditory nerve. CI users listened to 30-s long sequences of alternating A and B harmonic complexes at four different fundamental frequency separations, ranging from 2 to 14 semitones. They had to indicate as promptly as possible after sequence onset, if they perceived one stream or two streams and, in addition, any changes of the percept throughout the rest of the sequence. The conventional view is that the initial percept is always that of a single stream which may after some time change to a percept of two streams. This general build-up hypothesis has recently been challenged on the basis of a new analysis of data of normal-hearing listeners. Using the same experimental paradigm and analysis, the present study found that the results of CI users agree with those of the normal-hearing listeners: (i) the probability of the first decision to be a one-stream percept decreased and that of a two-stream percept increased as Δf increased, and (ii) a build-up was only found for 6 semitones. Only the time elapsed before the listeners made their first decision of the percept was prolonged as compared to normal-hearing listeners. The similarity in the data of the CI user and the normal-hearing listeners indicates that the quality of stream formation is similar in these groups of listeners. | 25,101,035 | [
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Compulsivity in anorexia nervosa: a transdiagnostic concept. | The compulsive nature of weight loss behaviors central to anorexia nervosa (AN), such as relentless self-starvation and over-exercise, has led to the suggestion of parallels between AN and other compulsive disorders such as obsessive-compulsive disorder (OCD) and addictions. There is a huge unmet need for effective treatments in AN, which has high rates of morbidity and the highest mortality rate of any psychiatric disorder, yet a grave paucity of effective treatments. Viewing compulsivity as a transdiagnostic concept, seen in various manifestations across disorders, may help delineate the mechanisms responsible for the persistence of AN, and aid treatment development. We explore models of compulsivity that suggest dysfunction in cortico-striatal circuitry underpins compulsive behavior, and consider evidence of aberrancies in this circuitry across disorders. Excessive habit formation is considered as a mechanism by which initially rewarding weight loss behavior in AN may become compulsive over time, and the complex balance between positive and negative reinforcement in this process is considered. The physiological effects of starvation in promoting compulsivity, positive reinforcement, and habit formation are also discussed. Further research in AN may benefit from a focus on processes potentially underlying the development of compulsivity, such as aberrant reward processing and habit formation. We discuss the implications of a transdiagnostic perspective on compulsivity, and how it may contribute to the development of novel treatments for AN. | 25,101,036 | [
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Temptation in the background: non-consummatory exposure to food temptation enhances self-regulation in boys but not in girls. | The abundance of calorie-dense low-nutrient food in everyday life raises the question as to how children deal with such opportunities. We investigate whether pre-exposure to the object of temptation in a situation that discourages consumption boosts children's ability to resist similar temptation subsequently. We show that 7-12-year-old boys, but not girls, demonstrate increased resistance to a temptation after pre-exposure to a similar temptation. Future research might explore the role of exposure to temptation in girls. | 25,101,042 | [
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Interaction and self-correction. | In this paper, I address the question of how to account for the normative dimension involved in conceptual competence in a naturalistic framework. First, I present what I call the naturalist challenge (NC), referring to both the phylogenetic and ontogenetic dimensions of conceptual possession and acquisition. I then criticize two models that have been dominant in thinking about conceptual competence, the interpretationist and the causalist models. Both fail to meet NC, by failing to account for the abilities involved in conceptual self-correction. I then offer an alternative account of self-correction that I develop with the help of the interactionist theory of mutual understanding arising from recent developments in phenomenology and developmental psychology. | 25,101,044 | [
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Killing two birds with one stone: trans-kingdom suppression of PAMP/MAMP-induced immunity by T3E from enteropathogenic bacteria. | Within the past decade, remarkable similarities between the molecular organization of animal and plant systems for non-self discrimination were revealed. Obvious parallels exist between the molecular structures of the receptors mediating the recognition of pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs) with plant pattern recognition receptors strikingly resembling mammalian Toll-like receptors. Mitogen-activated protein kinase cascades, leading to the transcriptional activation of immunity-associated genes, illustrate the conservation of whole molecular building blocks of PAMP/MAMP-induced signaling. Enteropathogenic Salmonella and Escherichia coli use a type three secretion system (T3SS) to inject effector proteins into the mammalian host cell to subvert defense mechanisms and promote gut infection. Lately, disease occurrence was increasingly associated with bacteria-contaminated fruits and vegetables and common themes have emerged with regard to whether and how effectors target innate immune responses in a trans-kingdom manner. We propose that numerous Salmonella or E. coli effectors may be active in planta and tend to target central components (hubs) of immune signaling pathways. | 25,101,059 | [
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Production possibility frontiers in phototroph:heterotroph symbioses: trade-offs in allocating fixed carbon pools and the challenges these alternatives present for understanding the acquisition of intracellular habitats. | Intracellular habitats have been invaded by a remarkable diversity of organisms, and strategies employed to successfully reside in another species' cellular space are varied. Common selective pressures may be experienced in symbioses involving phototrophic symbionts and heterotrophic hosts. Here I refine and elaborate the Arrested Phagosome Hypothesis that proposes a mechanism that phototrophs use to gain access to their host's intracellular habitat. I employ the economic concept of production possibility frontiers (PPF) as a useful heuristic to clearly define the trade-offs that an intracellular phototroph is likely to face as it allocates photosynthetically-derived pools of energy. Fixed carbon can fuel basic metabolism/respiration, it can support mitotic division, or it can be translocated to the host. Excess photosynthate can be stored for future use. Thus, gross photosynthetic productivity can be divided among these four general categories, and natural selection will favor phenotypes that best match the demands presented to the symbiont by the host cellular habitat. The PPF highlights trade-offs that exist between investment in growth (i.e., mitosis) or residency (i.e., translocating material to the host). Insights gained from this perspective might help explain phenomena such as coral bleaching because deficits in photosynthetic production are likely to diminish a symbiont's ability to "afford" the costs of intracellular residency. I highlight deficits in our current understanding of host:symbiont interactions at the molecular, genetic, and cellular level, and I also discuss how semantic differences among scientists working with different symbiont systems may diminish the rate of increase in our understanding of phototrophic-based associations. I argue that adopting interdisciplinary (in this case, inter-symbiont-system) perspectives will lead to advances in our general understanding of the phototrophic symbiont's intracellular niche. | 25,101,064 | [
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Demonstrating microbial co-occurrence pattern analyses within and between ecosystems. | Co-occurrence patterns are used in ecology to explore interactions between organisms and environmental effects on coexistence within biological communities. Analysis of co-occurrence patterns among microbial communities has ranged from simple pairwise comparisons between all community members to direct hypothesis testing between focal species. However, co-occurrence patterns are rarely studied across multiple ecosystems or multiple scales of biological organization within the same study. Here we outline an approach to produce co-occurrence analyses that are focused at three different scales: co-occurrence patterns between ecosystems at the community scale, modules of co-occurring microorganisms within communities, and co-occurring pairs within modules that are nested within microbial communities. To demonstrate our co-occurrence analysis approach, we gathered publicly available 16S rRNA amplicon datasets to compare and contrast microbial co-occurrence at different taxonomic levels across different ecosystems. We found differences in community composition and co-occurrence that reflect environmental filtering at the community scale and consistent pairwise occurrences that may be used to infer ecological traits about poorly understood microbial taxa. However, we also found that conclusions derived from applying network statistics to microbial relationships can vary depending on the taxonomic level chosen and criteria used to build co-occurrence networks. We present our statistical analysis and code for public use in analysis of co-occurrence patterns across microbial communities. | 25,101,065 | [
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Rescue of mutant fitness defects using in vitro reconstituted designer transposons in Mycoplasma mycoides. | With only hundreds of genes contained within their genomes, mycoplasmas have become model organisms for precise understanding of cellular processes, as well as platform organisms for predictable engineering of microbial functions for mission-critical applications. Despite the availability of "whole genome writing" in Mycoplasma mycoides, some traditional methods for genetic engineering are underdeveloped in mycoplasmas. Here we demonstrate two facile transposon-mediated approaches for introducing genes into the synthetic cell based on M. mycoides. The marker-less approach involves preparing a fragment containing only a small genomic region of interest with flanking transposase-binding sites, followed by in vitro transposase loading and introduction into the cells. The marker-driven approach involves cloning an open reading frame (ORF) of interest into a vector containing a marker for mycoplasma transformation, as well as sites for transposase loading and random genomic integration. An innovative feature of this construct is to use a single promoter to express the transformation marker and the introduced ORF. The marker-driven approach can be conveniently applied to any exogenous or synthetic gene without any information on the effect of the gene on the strain, whereas the marker-less approach requires that the fragment has a recognizable effect. Using the marker-less method, we found that a region containing the nusG gene rescues a slow growth phenotype of a strain containing a larger deletion encompassing this gene. Using the marker-driven approach, we better defined this finding, thereby establishing that nusG is required for a normal growth rate in synthetic M. mycoides. These methods are suitable for complementation tests to identify genes responsible for assorted functions lacking in deletion mutants. These approaches are also expected to facilitate rapid testing of various natural and engineered genes or gene clusters from numerous sources in M. mycoides. | 25,101,070 | [
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A comprehensive analysis of the Omp85/TpsB protein superfamily structural diversity, taxonomic occurrence, and evolution. | Members of the Omp85/TpsB protein superfamily are ubiquitously distributed in Gram-negative bacteria, and function in protein translocation (e.g., FhaC) or the assembly of outer membrane proteins (e.g., BamA). Several recent findings are suggestive of a further level of variation in the superfamily, including the identification of the novel membrane protein assembly factor TamA and protein translocase PlpD. To investigate the diversity and the causal evolutionary events, we undertook a comprehensive comparative sequence analysis of the Omp85/TpsB proteins. A total of 10 protein subfamilies were apparent, distinguished in their domain structure and sequence signatures. In addition to the proteins FhaC, BamA, and TamA, for which structural and functional information is available, are families of proteins with so far undescribed domain architectures linked to the Omp85 β-barrel domain. This study brings a classification structure to a dynamic protein superfamily of high interest given its essential function for Gram-negative bacteria as well as its diverse domain architecture, and we discuss several scenarios of putative functions of these so far undescribed proteins. | 25,101,071 | [
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Biodiversity of Aspergillus section Flavi in Europe in relation to the management of aflatoxin risk. | Aflatoxins and the producing fungi Aspergillus section Flavi are widely known as the most serious and dangerous mycotoxin issue in agricultural products. In Europe, before the outbreak of aflatoxins on maize (2003-2004) due to new climatic conditions, their contamination was confined to imported foods. Little information is available on molecular biodiversity and population structure of Aspergillus section Flavi in Europe. Preliminary reports evidenced the massive presence of Aspergillus flavus L -morphotype as the predominant species in maize field, no evidence of the highly toxigenic S-morphotype and of other aflatoxigenic species are reported. The risk of a shift in traditional occurrence areas for aflatoxins is expected in the world and in particular in South East of Europe due to the increasing average temperatures. Biological control of aflatoxin risk in the field by atoxigenic strains of A. flavus starts to be widely used in Africa and USA. Studies are necessary on the variation of aflatoxin production in populations of A. flavus to characterize stable atoxigenic A. flavus strains. The aim of present article is to give an overview on biodiversity and genetic variation of Aspergillus section Flavi in Europe in relation to the management of aflatoxins risk in the field. | 25,101,075 | [
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The role of pattern-recognition receptors in graft-versus-host disease and graft-versus-leukemia after allogeneic stem cell transplantation. | Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with curative potential for certain aggressive hematopoietic malignancies. Its success is limited by acute graft-versus-host disease (GVHD), a life-threatening complication that occurs when allo-reactive donor T cells attack recipient organs. There is growing evidence that microbes and innate pattern-recognition receptors (PRRs) such as toll-like receptors (TLR) and nod-like receptors (NLR) are critically involved in the pathogenesis of acute GVHD. Currently, a widely accepted model postulates that intensive chemotherapy and/or total-body irradiation during pre-transplant conditioning results in tissue damage and a loss of epithelial barrier function. Subsequent translocation of bacterial components as well as release of endogenous danger molecules stimulate PRRs of host antigen-presenting cells to trigger the production of pro-inflammatory cytokines (cytokine storm) that modulate T cell allo-reactivity against host tissues, but eventually also the beneficial graft-versus-leukemia (GVL) effect. Given the limitations of existing immunosuppressive therapies, a better understanding of the molecular mechanisms that govern GVHD versus GVL is urgently needed. This may ultimately allow to design modulators, which protect from GvHD but preserve donor T-cell attack on hematologic malignancies. Here, we will briefly summarize current knowledge about the role of innate immunity in the pathogenesis of GVHD and GVL following allo-HSCT. | 25,101,080 | [
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The role of mycorrhizal associations in plant potassium nutrition. | Potassium (K(+)) is one of the most abundant elements of soil composition but it's very low availability limits plant growth and productivity of ecosystems. Because this cation participates in many biological processes, its constitutive uptake from soil solution is crucial for the plant cell machinery. Thus, the understanding of strategies responsible of K(+) nutrition is a major issue in plant science. Mycorrhizal associations occurring between roots and hyphae of underground fungi improve hydro-mineral nutrition of the majority of terrestrial plants. The contribution of this mutualistic symbiosis to the enhancement of plant K(+) nutrition is not well understood and poorly studied so far. This mini-review examines the current knowledge about the impact of both arbuscular mycorrhizal and ectomycorrhizal symbioses on the transfer of K(+) from the soil to the plants. A model summarizing plant and fungal transport systems identified and hypothetically involved in K(+) transport is proposed. In addition, some data related to benefits for plants provided by the improvement of K(+) nutrition thanks to mycorrhizal symbioses are presented. | 25,101,097 | [
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Turnover of protein phosphorylation evolving under stabilizing selection. | Most proteins are regulated by posttranslational modifications and changes in these modifications contribute to evolutionary changes as well as to human diseases. Phosphorylation of serines, threonines, and tyrosines are the most common modifications identified to date in eukaryotic proteomes. While the mode of action and the function of most phosphorylation sites remain unknown, functional studies have shown that phosphorylation affects protein stability, localization and ability to interact. Two broad modes of action have been described for protein phosphorylation. The first mode corresponds to the canonical and qualitative view whereby single phosphorylation sites act as molecular switches that either turn on or off specific protein functions through direct or allosteric effects. The second mode is more akin to a rheostat than a switch. In this case, a group of phosphorylation sites in a given protein region contributes collectively to the modification of the protein, irrespective of the precise position of individual sites, through an aggregate property. Here we discuss these two types of regulation and examine how they affect the rate and patterns of protein phosphorylation evolution. We describe how the evolution of clusters of phosphorylation sites can be studied under the framework of complex traits evolution and stabilizing selection. | 25,101,120 | [
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Optimisation and in vivo evaluation of pectin based drug delivery system containing curcumin for colon. | The higher incidences of side effects of existing drugs have shifted researchers and clinicians to explore the dietary phytoconstituents for its therapeutic potentials. The present study is based on compression coated curcumin tablet for the colon. Curcumin has anti-inflammatory and antioxidant properties. Curcumin presents a bioavailability problem due to poor solubility. An inclusion complex was formed with hydroxypropyl-β-cyclodextrin to enhance the solubility. In this study, the core tablet of curcumin inclusion complex was compressed between the layers of polymer blend of pectin and Eudragit S100. The 3(2) full factorial design was utilised for optimization of the formulation. The polymer ratio (X1) and coat thickness (X2) presented significant effects on the selected responses, i.e., percent drug release after 4 hours (Y240) and difference in percent drug release between 4th and 6th hour (Y diff) in presence of pectinase enzyme. The results revealed that higher coat weight (600 mg) and higher level of pectin ratio (70% w/w) protected the curcumin tablet till ascending colon. The in vivo studies by roentgenography method using human volunteers supported these observations. Hence, it can be concluded that the combination of pectin and Eudrgit S100 makes the system biodegradable and pH dependent for targeting the drug to the colon. | 25,101,127 | [
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Privacy-preserving restricted boltzmann machine. | With the arrival of the big data era, it is predicted that distributed data mining will lead to an information technology revolution. To motivate different institutes to collaborate with each other, the crucial issue is to eliminate their concerns regarding data privacy. In this paper, we propose a privacy-preserving method for training a restricted boltzmann machine (RBM). The RBM can be got without revealing their private data to each other when using our privacy-preserving method. We provide a correctness and efficiency analysis of our algorithms. The comparative experiment shows that the accuracy is very close to the original RBM model. | 25,101,139 | [
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Pilot Testing and Preliminary Psychometric Validation of the Polish Translation of the EORTC INFO25 Questionnaire: Validation of the Polish version of INFO25-pilot study. | The quality of information that oncological patients receive from health care professionals is an underestimated issue in Poland and Eastern European countries. There is lack of sufficient data on this subject. The European Organization for Research and Treatment of Cancer (EORTC) supplies a new tool for measuring the quality of information provided to cancer patients. The purpose of the study is the translation into Polish, pilot testing and preliminary validation of the EORTC information module (INFO25). Following the EORTC translation procedures, forward and back translations of the questionnaire were performed (English → Polish, Polish → English). The intermediate version of the INFO25 was pilot-tested together with the general questionnaire of quality of life (EORTC QLQ-C30). Reliability, validity and known-group comparison tests were performed. A total of 21 patients with different cancer diagnoses were recruited into the study (7 women and 14 men; mean age of 60,2 years, age range 25-73 years). Apart from filling out the INFO25, patients were interviewed about the difficulties with answering every questionnaire item. Patients' comments were analyzed and minor language changes were made to the initial translation. The internal consistency of the INFO25 showed a reliability of 0,78. The final version of the Polish translation of the INFO25 module was obtained and approved by the EORTC Quality of Life Department. It can now be used in clinical setting and for scientific purposes. | 25,101,146 | [
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Validation of high throughput sequencing and microbial forensics applications. | High throughput sequencing (HTS) generates large amounts of high quality sequence data for microbial genomics. The value of HTS for microbial forensics is the speed at which evidence can be collected and the power to characterize microbial-related evidence to solve biocrimes and bioterrorist events. As HTS technologies continue to improve, they provide increasingly powerful sets of tools to support the entire field of microbial forensics. Accurate, credible results allow analysis and interpretation, significantly influencing the course and/or focus of an investigation, and can impact the response of the government to an attack having individual, political, economic or military consequences. Interpretation of the results of microbial forensic analyses relies on understanding the performance and limitations of HTS methods, including analytical processes, assays and data interpretation. The utility of HTS must be defined carefully within established operating conditions and tolerances. Validation is essential in the development and implementation of microbial forensics methods used for formulating investigative leads attribution. HTS strategies vary, requiring guiding principles for HTS system validation. Three initial aspects of HTS, irrespective of chemistry, instrumentation or software are: 1) sample preparation, 2) sequencing, and 3) data analysis. Criteria that should be considered for HTS validation for microbial forensics are presented here. Validation should be defined in terms of specific application and the criteria described here comprise a foundation for investigators to establish, validate and implement HTS as a tool in microbial forensics, enhancing public safety and national security. | 25,101,166 | [
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Orbital Volumetry in Graves' Orbitopathy: Muscle and Fat Involvement in relation to Dysthyroid Optic Neuropathy. | Purpose. We wanted to investigate the relative significance of fat and muscle enlargement in the development of dysthyroid optic neuropathy (DON) in Graves' orbitopathy (GO). Methods. Preoperative coronal CT scans of 13 patients with and without DON who subsequently underwent orbital decompression were retrospectively analyzed. Thirteen patients imaged for unilateral orbital fractures served as controls. Results. The retrobulbar muscle volume was 2.1 ± 0.5 cm(3) (mean ± SD) in controls, 4.3 ± 1.5 cm(3) in GO without DON, and 4.7 ± 1.7 cm(3) in GO with DON. The retrobulbar fat volume was 5.4 ± 1.6 cm(3) in controls, 8.7 ± 8.0 cm(3) in GO without DON, and 9.4 ± 3.1 cm(3) in GO with DON. The muscle and fat volumes were higher in patients with GO than in controls (P < 0.001), but the volumes in orbits with and without DON were not significantly different. The volume of the optic nerve were similar in the 3 groups. The number of apical, coronal 2 mm thick slices with no fat was 2.9 ± 0.9 in normal orbits, it was 4.1 ± 1.0 in GO orbits without DON and 5.3 ± 0.8 in GO orbits with DON (P = 0.007). Conclusion. Apical muscle enlargement may be more important than orbital fat enlargement in the development of DON. However, the fact that apical crowding and muscle enlargement also occur in orbits without DON suggests that other factors also play a role in the development of DON. | 25,101,183 | [
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Temporal Characteristics of High-Frequency Lower-Limb Oscillation during Freezing of Gait in Parkinson's Disease. | A cardinal feature of freezing of gait (FOG) is high frequency (3-8 Hz) oscillation of the legs, and this study aimed to quantify the temporal pattern of lower-body motion prior to and during FOG. Acceleration data was obtained from sensors attached to the back, thighs, shanks, and feet in 14 Parkinson's disease patients performing timed-up-and-go tasks, and clinical assessment of FOG was performed by two experienced raters from video. A total of 23 isolated FOG events, defined as occurring at least 5 s after gait initiation and with no preceding FOG, were identified from the clinical ratings. The corresponding accelerometer records were analyzed within a 4 s window centered at the clinical onset of freezing. FOG-related high-frequency oscillation (an increase in power in the 3-8 Hz band >3 SD from baseline) followed a distal to proximal onset pattern, appearing at the feet, shanks, thighs, and then back over a period of 250 ms. Peak power tended to decrease as the focus of oscillation moved from feet to back. There was a consistent delay (mean 872 ms) between the onset of high frequency oscillation at the feet and clinical onset of FOG. We infer that FOG is characterized by high frequency oscillation at the feet, which progresses proximally and is mechanically damped at the torso. | 25,101,189 | [
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Role of Th17 Cells in the Pathogenesis of Human IBD. | The gastrointestinal tract plays a central role in immune system, being able to mount efficient immune responses against pathogens, keeping the homeostasis of the human gut. However, conditions like Crohn's disease (CD) or ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD), are related to an excessive and uncontrolled immune response against normal microbiota, through the activation of CD4(+) T helper (Th) cells. Classically, IBD was thought to be primarily mediated by Th1 cells in CD or Th2 cells in UC, but it is now known that Th17 cells and their related cytokines are crucial mediators in both conditions. Th17 cells massively infiltrate the inflamed intestine of IBD patients, where they produce interleukin- (IL-) 17A and other cytokines, triggering and amplifying the inflammatory process. However, these cells show functional plasticity, and they can be converted into either IFN- γ producing Th1 cells or regulatory T cells. This review will summarize the current knowledge regarding the regulation and functional role of Th17 cells in the gut. Deeper insights into their plasticity in inflammatory conditions will contribute to advancing our understanding of the mechanisms that regulate mucosal homeostasis and inflammation in the gut, promoting the design of novel therapeutic approaches for IBD. | 25,101,191 | [
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Therapy of hypoparathyroidism by replacement with parathyroid hormone. | Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (QoL) seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT) possesses, nevertheless, a number of challenges. If PTH is injected only once a day, fluctuations in calcium levels may occur resulting in hypercalcemia in the hours following an injection. Twice-a-day injections seem to cause less fluctuation in plasma calcium but do stimulate bone turnover to above normal. Most recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range). Further studies are needed to assess the long-term effects. If beneficial, it seems likely that standard treatment of HypoPT in the future will change into replacement therapy with the missing hormone. | 25,101,193 | [
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Dendritic cells matured in the presence of TLR ligands overcome the immunosuppressive functions of regulatory T cells. | Toll like receptor (TLR)-stimulated dendritic cells (DCs) are able to overcome the inhibitory activity of regulatory T cells (Tregs) and induce the proliferation of effector T cells. TLR-activated DCs secrete a soluble factor and act directly on Tregs to convert them into interferon γ-secreting T<subH</sub1-like cells that express the transcription factor T-bet. | 25,101,219 | [
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Location, location, location: CD103 demarcates intraepithelial, prognostically favorable CD8<sup>+</sup> tumor-infiltrating lymphocytes in ovarian cancer. | Although high levels of tumor-infiltrating lymphocytes (TILs) generally correlate with good prognosis in high-grade serous ovarian cancer (HGSC) patients, little is known about the phenotype or specificity of these cells. We have recently demonstrated that TIL expressing the intra-epithelial lymphocyte marker CD103 (official name, integrin α<subE</sub, ITGAE) abundantly infiltrate HGSCs, strongly correlating with increased disease-specific survival. | 25,101,220 | [
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Eleutherodactylus frogs show frequency but no temporal partitioning: implications for the acoustic niche hypothesis. | Individuals in acoustic communities compete for the use of the sound resource for communication, a problem that can be studied as niche competition. The acoustic niche hypothesis presents a way to study the partitioning of the resource, but the studies have to take into account the three dimensions of this niche: time, acoustic frequency, and space. I used an Automated Digital Recording System to determine the partitioning of time and acoustic frequency of eight frogs of the genus Eleutherodactylus from Puerto Rico. The calling activity was measured using a calling index. The community exhibited no temporal partitioning since most species called at the same time, between sunset and midnight. The species partitioned the acoustic frequency of their signals, which, in addition to the microhabitat partitioning, can provide some insight into how these species deal with the problem. This data also suggest that monitoring projects with this group should take place only before midnight to avoid false negatives. | 25,101,228 | [
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Toll-like receptor 2 regulates the barrier function of human bronchial epithelial monolayers through atypical protein kinase C zeta, and an increase in expression of claudin-1. | We investigated the role of Toll-like receptor (TLR) 2 in maintaining the integrity of the airway epithelial barrier using the human bronchial epithelial cell line Calu-3. Activation of TLR2 by its ligands, Pam3CysSK4 and Peptidoglycan showed a concentration dependent increase in epithelial barrier function, as measured by transepithelial electrical resistance (TEER). This was confirmed by a decrease in paracellular flux of fluorescein sodium. This TLR2 induced increase in TEER was significantly reduced by pretreatment with polyclonal anti-human TLR2-neutralizing antibody. TLR2 stimulation in Calu-3 cell monolayers resulted in an increased expression of the tight junction proteins claudin-1 and ZO-1, and a decreased expression of occludin, at both the mRNA and protein levels. A pseudosubstrate inhibitor to PKCζ significantly prevented the TLR2 mediated increase in barrier function. It also prevented the increase in claudin-1 in a concentration dependent manner up to 1 µM. TLR2 stimulation led to an increase in phosphorylation of atypical PKC ζ, which was prevented by the pseudosubstrate inhibitor in a concentration dependent manner. Taken together, our observations support a model whereby increased tight junction barrier function induced by activation of TLR2 occurs through increased expression of claudin-1, and through modulation of PKC ζ activity. | 25,101,232 | [
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Animal models in osteosarcoma. | Osteosarcoma (OS) is the most common non-hematologic primary tumor of bone in children and adults. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for non-metastatic disease approaching 70%. However, most OS tumors are high grade and tend to rapidly develop pulmonary metastases. Despite clinical advances, patients with metastatic disease or relapse have a poor prognosis. Toward a better understanding of the molecular pathogenesis of human OS, several genetically modified OS mouse models have been developed and will be reviewed here. However, better animal models that more accurately recapitulate the natural progression of the disease are needed for the development of improved prognostic and diagnostic markers as well as targeted therapies for both primary and metastatic OS. | 25,101,245 | [
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Effect of an oxygenating agent on oral bacteria in vitro and on dental plaque composition in healthy young adults. | Oral bacteria live in symbiosis with the host. Therefore, when mouthwashes are indicated, selective inhibition of taxa contributing to disease is preferred instead of broad-spectrum antimicrobials. The potential selectivity of an oxygenating mouthwash, Ardox-X® (AX), has not been assessed. The aim of this study was to determine the antimicrobial potential of AX and the effects of a twice-daily oral rinse on dental plaque composition. In vitro, 16 oral bacterial strains were tested using agar diffusion susceptibility, minimum inhibitory and minimum bactericidal concentration tests. A pilot clinical study was performed with 25 healthy volunteers. Clinical assessments and microbiological sampling of supragingival plaque were performed at 1 month before the experiment (Pre-exp), at the start of the experiment (Baseline) and after the one-week experimental period (Post-exp). During the experiment individuals used AX mouthwash twice daily in absence of other oral hygiene measures. The microbiological composition of plaque was assessed by 16S rRNA gene amplicon sequencing. AX showed high inter-species variation in microbial growth inhibition. The tested Prevotella strains and Fusobacterium nucleatum showed the highest sensitivity, while streptococci and Lactobacillus acidophilus were most resistant to AX. Plaque scores at Pre-exp and Baseline visits did not differ significantly (p = 0.193), nor did the microbial composition of plaque. During a period of 7-days non-brushing but twice daily rinsing plaque scores increased from 2.21 (0.31) at Baseline to 2.43 (0.39) Post-exp. A significant microbial shift in composition was observed: genus Streptococcus and Veillonella increased while Corynebacterium, Haemophilus, Leptotrichia, Cardiobacterium and Capnocytophaga decreased (p ≤ 0.001). AX has the potential for selective inhibition of oral bacteria. The shift in oral microbiome after 1 week of rinsing deserves further research. | 25,101,249 | [
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Oxidation stability of biodiesel fuels and blends using the Rancimat and PetroOXY methods. Effect of 4-allyl-2,6-dimethoxyphenol and catechol as biodiesel additives on oxidation stability. | IN THE PRESENT WORK, SEVERAL FATTY ACID METHYL ESTERS (FAME) HAVE BEEN SYNTHESIZED FROM VARIOUS FATTY ACID FEEDSTOCKS: used frying olive oil, pork fat, soybean, rapeseed, sunflower, and coconut. The oxidation stabilities of the biodiesel samples and of several blends have been measured simultaneously by both the Rancimat method, accepted by EN14112 standard, and the PetroOXY method, prEN16091 standard, with the aim of finding a correlation between both methodologies. Other biodiesel properties such as composition, cold filter plugging point (CFPP), flash point (FP), and kinematic viscosity have also been analyzed using standard methods in order to further characterize the biodiesel produced. In addition, the effect on the biodiesel properties of using 4-allyl-2,6-dimethoxyphenol and catechol as additives in biodiesel blends with rapeseed and with soybean has also been analyzed. The use of both antioxidants results in a considerable improvement in the oxidation stability of both types of biodiesel, especially using catechol. Adding catechol loads as low as 0.05% (m/m) in blends with soybean biodiesel and as low as 0.10% (m/m) in blends with rapeseed biodiesel is sufficient for the oxidation stabilities to comply with the restrictions established by the European EN14214 standard. An empirical linear equation is proposed to correlate the oxidation stability by the two methods, PetroOXY and Rancimat. It has been found that the presence of either catechol or 4-allyl-2,6-dimethoxyphenol as additives affects the correlation observed. | 25,101,258 | [
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Minimally invasive multiport surgery of the lateral skull base. | Minimally invasive procedures minimize iatrogenic tissue damage and lead to a lower complication rate and high patient satisfaction. To date only experimental minimally invasive single-port approaches to the lateral skull base have been attempted. The aim of this study was to verify the feasibility of a minimally invasive multiport approach for advanced manipulation capability and visual control and develop a software tool for preoperative planning. Anatomical 3D models were extracted from twenty regular temporal bone CT scans. Collision-free trajectories, targeting the internal auditory canal, round window, and petrous apex, were simulated with a specially designed planning software tool. A set of three collision-free trajectories was selected by skull base surgeons concerning the maximization of the distance to critical structures and the angles between the trajectories. A set of three collision-free trajectories could be successfully simulated to the three targets in each temporal bone model without violating critical anatomical structures. A minimally invasive multiport approach to the lateral skull base is feasible. The developed software is the first step for preoperative planning. Further studies will focus on cadaveric and clinical translation. | 25,101,276 | [
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Effect of health education on willingness to undergo HIV screening among antenatal attendees in a teaching hospital in north central Nigeria. | Testing for HIV during pregnancy provides a useful opportunity to institute treatment for HIV as required as well as protect the unborn baby. The aim of this study was to evaluate the effect of health education on the willingness of antenatal attendees to be screened for HIV. This was a quasiexperimental study involving the sequential enrolment of 122 pregnant women attending antenatal care who were at a gestational age of between 13 and 28 weeks for the study group and subsequent enrolment of the same one month after for the control. Two-stage analysis was done with the use of descriptive statistics and bivariate analysis. Level of significance was set at 5%. Mean age of the study respondents was 27.6 ± 4.6 years while that of the control was 27.5 ± 4.8 years. Majority of the respondents were married in both study, 88 (72.7%), and control groups 84 (72.4%), 76.1% of the study group and 79.3% of the control group had at least secondary education, and 39.7% of the study group and 37.9% of the control group were primigravidae. Before intervention, 88.4% of the study group and 88.8% of the control group were willing to undergo voluntary HIV screening. There was an increase in this number after intervention (P < 0.05). Age, education, occupation, marital status, and parity were not significantly associated with a willingness to be screened for HIV before and after intervention among the study or control groups. Health education as a strategy to enhance voluntary counseling and testing uptake in antenatal settings is advocated. | 25,101,281 | [
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Prevention of peritendinous adhesions using an electrospun DegraPol polymer tube: a histological, ultrasonographic, and biomechanical study in rabbits. | One of the great challenges in surgical tendon rupture repair is to minimize peritendinous adhesions. In order to reduce adhesion formation, a physical barrier was applied to a sutured rabbit Achilles tendon, with two different immobilization protocols used postoperatively. Thirty New Zealand white rabbits received a laceration on the Achilles tendon, sutured with a 4-strand Becker suture, and half of the rabbits got a DegraPol tube at the repair site. While fifteen rabbits had their treated hind leg in a 180° stretched position during 6 weeks (adhesion provoking immobilization), the other fifteen rabbits were recasted with a 150° position after 3 weeks (adhesion inhibiting immobilization). Adhesion extent was analysed macroscopically, via ultrasound and histology. Inflammation was determined histologically. Biomechanical properties were analysed. Application of a DegraPol tube reduced adhesion formation by approximately 20%--independently of the immobilization protocol. Biomechanical properties of extracted specimen were not affected by the tube application. There was no serious inflammatory reaction towards the implant material. Implantation of a DegraPol tube tightly set around a sutured tendon acts as a beneficial physical barrier and prevents adhesion formation significantly--without affecting the tendon healing process. | 25,101,292 | [
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... |
Elosulfase alfa. | Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome, is an inherited, lysosomal storage disorder caused by genetic mutations in N-acetylgalactosamine-6-sulfatase (GALNS) enzyme gene. GALNS is essential for breakdown of glycosaminoglycans. The disease is characterized by the early onset of severe skeletal dysplasia resulting in significant disability by the second decade of life. Until recently there have been no available treatments other than surgery and palliative care. BioMarin Pharmaceutical developed elosulfase alfa, a recombinant human GALNS coproduced with sulfatase-modifying factor 1, as an enzyme replacement therapy for patients with MPS IVA. In clinical studies, enzyme replacement therapy with elosulfase alfa significantly improved physical endurance, respiratory function, growth and quality of life in patients with MPS IVA. Treatment increased clearance of glycosaminoglycans and induced gene expression consistent with improved chondrocyte function. Elosulfase alfa is approved for the treatment of MPS IVA in the U.S. and Europe. | 25,101,330 | [
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A report from the 167th American Psychiatric Association Annual Meeting (May 3-7 - New York, U.S.A.). | Sharing space with a fashion fair, the American Psychiatric Association's Annual Meeting took place at the Javits Center on the West side of Manhattan where psychiatrists and psychiatry-focused neuroscientists met to discuss the latest advances in antipsychotic, antidepressant and related therapies. Mixing psychiatry with fashion was a psychedelic experience, but the meeting was too busy to give more than a passing glimpse to screens showing the newest trends in fashion. Revival of old styles? That in a sense also happened in psychiatry, with experts defending the current place of lithium in therapeutics. Newest, youngest look? That was also true for psychiatry, with new investigational therapeutics challenging the place of older treatment approaches because of improved efficacy, better safety and tolerability, or easier administration. What about these patchwork trends? This again was met in psychiatry, with combination therapies aimed at a more comprehensive control of underlying processes in diseases such as schizophrenia. And these nice complements, or a few highlights? Psychiatric therapies also include augmentation strategies, which were discussed during this year's meeting along with examples of the previously mentioned approaches that are included in the following report. | 25,101,333 | [
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Etanercept-induced cystic acne. | Tumor necrosis factor α antagonists are potent biologics used to treat a variety of autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn disease, psoriasis, and psoriatic arthritis. These medications are known to have many side effects (eg, infusion reactions, cytopenia, risk for infection, heart failure); however, only a few cases of acne vulgaris have been associated with the use of these biologics, particularly infliximab and adalimumab. We report a rare case of etanercept-induced cystic acne. | 25,101,341 | [
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Simultaneous multiplexed quantification of nicotine and its metabolites using surface enhanced Raman scattering. | The detection and quantification of xenobiotics and their metabolites in man is important for drug dosing, therapy and for substance abuse monitoring where longer-lived metabolic products from illicit materials can be assayed after the drug of abuse has been cleared from the system. Raman spectroscopy offers unique specificity for molecular characterization and this usually weak signal can be significantly enhanced using surface enhanced Raman scattering (SERS). We report here the novel development of SERS with chemometrics for the simultaneous analysis of the drug nicotine and its major xenometabolites cotinine and trans-3'-hydroxycotinine. Initial experiments optimized the SERS conditions and we found that when these three determinands were analysed individually that the maximum SERS signals were found at three different pH. These were pH 3 for nicotine and pH 10 and 11 for cotinine and trans-3'-hydroxycotinine, respectively. Tertiary mixtures containing nicotine, cotinine and trans-3'-hydroxycotinine were generated in the concentration range 10(-7)-10(-5) M and SERS spectra were collected at all three pH values. Chemometric analysis using kernel-partial least squares (K-PLS) and artificial neural networks (ANNs) were conducted and these models were validated using bootstrap resampling. All three analytes were accurately quantified with typical root mean squared error of prediction on the test set data being 5-9%; nicotine was most accurately predicted followed by cotinine and then trans-3'-hydroxycotinine. We believe that SERS is a powerful approach for the simultaneous analysis of multiple determinands without recourse to lengthy chromatography, as demonstrated here for the xenobiotic nicotine and its two major xenometabolites. | 25,101,355 | [
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Effect of the biopolymer mixing ratio on the formation of electrostatically coupled whey protein-κ- and ι-carrageenan networks in the presence and absence of oil droplets. | The rheological properties of 1.0% (w/w) whey protein isolate (WPI)-κ-/ι-carrageenan (CG) mixtures were investigated during a slow acidification process by glucono-δ-lactone from pH 7.00 to ∼4.20 as a function of biopolymer mixing ratio and in the presence and absence of oil droplets. In all cases, electrostatic coupled biopolymer and emulsion gel networks were formed at pH values corresponding to where attractive interactions between WPI and CG began. Formed WPI-CG complexes were found to be surface active, capable of lowering interfacial tension and forming viscoelastic interfacial films within emulsion-based systems. Both biopolymer and emulsion-based gels increased in strength and elasticity as the CG content increased, regardless of the type of CG present. However, WPI-ι-CG coupled networks were stronger than WPI-κ-CG networks, presumably due to the higher number of sulfate groups attracting the WPI molecules. | 25,101,482 | [
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Interceptive management for multiple eruption disturbances: a follow-up evaluation. | The aim of this report was to show the management of a case with an impacted central maxillary incisor caused by odontoma in a young patient with two mesiodentes in the region of the nasal floor. A 9-year-old girl was seen in the Department of Orthodontics of the University of Rome 'Tor Vergata'. Radiographic images showed intraosseous impaction of the maxillary right central incisor due to an odontoma. The treatment plan consisted of three stages: removal of the odontoma; rapid maxillary expansion (RME) in order to improve the intraosseous tooth position; surgical exposure and orthodontic traction of the impacted central incisor to its right position. At the end of the treatment the patient showed stable occlusal, functional, and periodontal results. In our therapeutic strategy the application of RME may improve the intraosseous position of incisor, minimizing space loss and surgical intervention to recover the impacted tooth. A three-year follow-up of the stability and periodontal health showed that the tooth placed in the occlusion maintained both esthetics and function. | 25,101,500 | [
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0.25... |
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