Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans.
It is now established that the central nervous system plays an important role in regulating whole body metabolism and energy balance. However, the extent to which sensory systems relay environmental information to modulate metabolic events in peripheral tissues has remained poorly understood. In addition, it has been challenging to map the molecular mechanisms underlying discrete sensory modalities with respect to their role in lipid metabolism. In previous work our lab has identified instructive roles for serotonin signaling as a surrogate for food availability, as well as oxygen sensing, in the control of whole body metabolism. In this study, we now identify a role for a pair of pheromone-sensing neurons in regulating fat metabolism in C. elegans, which has emerged as a tractable and highly informative model to study the neurobiology of metabolism. A genetic screen revealed that GPA-3, a member of the Gα family of G proteins, regulates body fat content in the intestine, the major metabolic organ for C. elegans. Genetic and reconstitution studies revealed that the potent body fat phenotype of gpa-3 null mutants is controlled from a pair of neurons called ADL(L/R). We show that cAMP functions as the second messenger in the ADL neurons, and regulates body fat stores via the neurotransmitter acetylcholine, from downstream neurons. We find that the pheromone ascr#3, which is detected by the ADL neurons, regulates body fat stores in a GPA-3-dependent manner. We define here a third sensory modality, pheromone sensing, as a major regulator of body fat metabolism. The pheromone ascr#3 is an indicator of population density, thus we hypothesize that pheromone sensing provides a salient 'denominator' to evaluate the amount of food available within a population and to accordingly adjust metabolic rate and body fat levels.


The patients' perception of quality in surgery.
The benefits of measuring patient satisfaction have been increasingly acknowledged in recent years. A range of techniques has been used including analysis of complaints made by patients and/or relatives, focus group interviews following discharge, postal and telephone surveys, face-to-face interviews and critical incident analysis. Both quantitative and qualitative methodologies are often employed in patient-satisfaction research. It is suggested that a two-tier approach of methods can increase validity and reliability (i.e. utilizing qualitative approaches in order to develop a quantitative tool). Surgery will benefit through the identification of quality benchmarks based on this type of research. There must be an emphasis on incorporating the results of patient satisfaction studies into practice and the monitoring of improvements based on the identified benchmarks.


Assessment of a scoring scheme for the preoperative diagnosis of breast lumps.
The value and accuracy of a scoring system applied to clinical examination, aspiration cytology and mammography has been assessed in the diagnosis of 224 consecutive 'new' patients attending a breast clinic with a breast lump. In 72 of 99 patients with breast cancer (80%) the scores were high enough to allow definitive surgery without formal histology; all were subsequently confirmed as breast carcinomas. Cytology proved the most accurate investigation with no false positives and a correct diagnosis in 146 of 148 adequate specimens (98.6%). This system reduced the frozen section rate by 74% and allowed for a more appropriate counselling of patients prior to mastectomy.


Identification of Germline Stem Cells in Zebrafish.
Both male and female zebrafish have a population of germline stem cells that produce gametes throughout the life of the fish. These cells localize to specific regions in the gonads and can be identified because they uniquely express the nanos2 gene, which encodes a conserved regulator of translation. A method is presented here for identifying germline stem cells in the ovary and testis using a combined protocol for whole-mount fluorescent RNA in situ hybridization to detect nanos2 mRNA and immunofluorescence to detect the pan-germ cell marker Vasa.


Self-rated health and health conditions of married and unmarried men in Jamaica.
Since 1988, when Jamaica began collecting data on the living conditions of its people, men have reported seeking less health care than women. Despite this fact, the group has never been studied by researchers. The same is true about the health status of married and non-married men. The current study will 1) evaluate the changing epidemiological patterns of diseases affecting men in Jamaica; 2) determine factors that correlate with good health status of men; 3) compare and contrast the differences in health status of men, in particular marital status; and 4) determine which marital status has the greater health status. The data for this research were taken from two secondary cross-sectional surveys. A sample of 8,078 respondents 15 years and older was extracted from the 2002 survey (n=25,018 respondents) and 2,224 respondents from the 2007 sample (n=6,783 respondents). SPSS for Windows 16.0 was used to store, retrieve and analyse the data. Chi-square, analysis of variance, t-test and logistic regression were used in this paper. Married men are more likely to report an illness than never married (OR = 1.68, 95% CI = 1.45-1.95), separated, divorced or widowed men (OR = 2.62, 95% CI = 2.06-3.33). No significant statistical difference existed between the self-rated health status of married and unmarried men. This study provides a platform upon which future studies can commence as we begin to examine men's health in Jamaica.


How can model comparison help improving species distribution models?
Today, more than ever, robust projections of potential species range shifts are needed to anticipate and mitigate the impacts of climate change on biodiversity and ecosystem services. Such projections are so far provided almost exclusively by correlative species distribution models (correlative SDMs). However, concerns regarding the reliability of their predictive power are growing and several authors call for the development of process-based SDMs. Still, each of these methods presents strengths and weakness which have to be estimated if they are to be reliably used by decision makers. In this study we compare projections of three different SDMs (STASH, LPJ and PHENOFIT) that lie in the continuum between correlative models and process-based models for the current distribution of three major European tree species, Fagussylvatica L., Quercusrobur L. and Pinussylvestris L. We compare the consistency of the model simulations using an innovative comparison map profile method, integrating local and multi-scale comparisons. The three models simulate relatively accurately the current distribution of the three species. The process-based model performs almost as well as the correlative model, although parameters of the former are not fitted to the observed species distributions. According to our simulations, species range limits are triggered, at the European scale, by establishment and survival through processes primarily related to phenology and resistance to abiotic stress rather than to growth efficiency. The accuracy of projections of the hybrid and process-based model could however be improved by integrating a more realistic representation of the species resistance to water stress for instance, advocating for pursuing efforts to understand and formulate explicitly the impact of climatic conditions and variations on these processes.


[Assessment of polymerase chain reaction (PCR) to diagnose brucellosis in a Brucella infected herd].
The diagnosis of bovine brucellosis using PCR in blood and milk samples from two dairy herds were compared to in vitro isolation, complement fixation test (CF), competitive ELISA (C-ELISA) in serum, and indirect ELISA (I-ELISA) in milk. Samples were obtained from 99 cows vaccinated with Brucella abortus strain 19, from a naturally infected herd (A), whose cows were also vaccinated with B. abortus strain RB51 as adults, and 100 from brucellosis free herd (B). In herd A, PCR identified 14 B. abortus infected cows: nine infected with wild type, and five with wild type and RB51, B. abortus S 19 was not identified. B. abortus biotype 1 was isolated from one cow. All cows infected with a wild strain of B. abortus were positive in serologic tests. Brucella was not found in herd B using PCR. Serological test showed 100% sensitivity related to PCR. The specificity for CF, C-ELISA and I-ELISA was 100%, 99% and 95% respectively. PCR could be useful to identify Brucella biotypes and to complement serologic tests.


Treacher Collins syndrome: unmasking the role of Tcof1/treacle.
Treacher Collins syndrome (TCS) is a rare congenital birth disorder characterized by severe craniofacial defects. The syndrome is associated with mutations in the TCOF1 gene which encodes a putative nucleolar phosphoprotein known as treacle. An animal model of the severe form of TCS, generated through mutation of the mouse homologue Tcof1 has recently revealed significant insights into the etiology and pathogenesis of TCS (Dixon and Dixon, 2004; Dixon et al., 2006; Jones et al 2008). During early embryogenesis in a TCS individual, an excessive degree of neuroepithelial apoptosis diminishes the generation of neural crest cells. Neural crest cells are a migratory stem and progenitor cell population that generates most of the tissues of the head including much of the bone, cartilage and connective tissue. It has been hypothesized that mutations in Tcof1 disrupt ribosome biogenesis to a degree that is insufficient to meet the proliferative needs of the neuroepithelium and neural crest cells. This causes nucleolar stress activation of the p53-dependent apoptotic pathway which induces neuroepithelial cell death. Interestingly however, chemical and genetic inhibition of p53 activity can block the wave of apoptosis and prevent craniofacial anomalies in Tcof1 mutant mice [Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, Rey JP, et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med 2008;14:125-33]. These findings shed new light on potential therapeutic avenues for the prevention of not only TCS but also other congenital craniofacial disorders which share a similar etiology and pathogenesis.


Complications and Resource Utilization Associated With Mechanical Ventilation in a Medical Intensive Care Unit in 2013.
Evolving strategies for ventilator management could reduce the frequency of complications, but there is limited information about complications in contemporary intensive care units. We retrospectively collected information about patient demographics, chest x-ray abnormalities, complications, including pneumothoraces, ventilator-associated events, self-extubation, and resource utilization in 174 patients who required mechanical ventilation in 2013. The mean age was 57.8 ± 16.8 years, the number of ventilator days was 7.5 ± 7, and the overall in-hospital mortality was 32.2%. The mean fluid balance per day during the mechanical ventilation period was 1539 ± 1721 mL. Three (1.7%) patients developed pneumothoraces, and 5 patients required chest tubes. Twenty-five (14.4%) patients had ventilator-associated events. Ten patients had episodes of self-extubation, and 11 had episodes of failed extubation. Chest X-rays showed new or increasing infiltrates in 113 (64.9%) patients and new or increasing pleural effusions in 29 (16.7%) patients. These patients had 1.2 ± 0.4 X-rays per day on the ventilator, and they had 10.0 ± 9.4 arterial blood gases and 0.7 ± 0.7 central lines. The frequency of ventilator-associated complications was low in this study. However, these patients frequently developed increasing infiltrates, and these outcomes need attention during patient management and are a potential focus for future studies.


Structural requirements for rapid inactivation and voltage dependence in splice variants of lobster Shaker potassium channels.
We studied the properties of currents generated in Xenopus oocytes by nine splice variants of the spiny lobster Shaker gene. These isoforms differ in their amino termini and in the P-loop region of the pore. Both the voltage dependence and kinetic properties of the currents varied significantly, depending on which amino terminus was present. A cluster of net positive charges at the N-terminus was not necessary for rapid inactivation: negatively charged N-termini also inactivated rapidly. There was no obvious correlation between N-terminus length and inactivation rate. These N-terminal effects were additive with a separate set of voltage and kinetic properties controlled by the two alternative P-loop exons.


Extended Ponseti method for failed tenotomy in idiopathic clubfeet: a pilot study.
We evaluated the outcome of a new protocol of an extended Ponseti method in the management of idiopathic club foot with residual equinus following failed Achilles tenotomy. We also compared the failed with a successful tenotomy group to analyze the parameters for failure. The Ponseti technique-treated idiopathic club foot patients with failed percutaneous Achilles tenotomy (failure to achieve <15° dorsiflexion) were treated by continued stretching casts, with a weekly change for a further 3 weeks. Final dorsiflexion more than 15° if achieved with the above protocol was recorded as a success. Twenty-six (16%) patients with failed Achilles tenotomy and residual equinus out of a total of 161 patients with primary idiopathic club foot were tested with the protocol. Ten (38.5%) failed patients had bilateral foot involvement and 16 (61.5%) had unilateral foot involvement. A total of seven (26.9%) patients achieved the end point dorsiflexion of more than 15° in one further cast, 10 (38.5%) in two casts, and four (15.4%) in three casts, respectively. Overall success of the extended Ponseti protocol was achieved in 21/26 (80.8%) patients. The patient's age, precasting initial Pirani score, number of Ponseti casts, pretenotomy Pirani score, and pretenotomy ankle joint dorsiflexion were statistically different in the failed compared with the successful tenotomy group. The tested extended Ponseti protocol showed a success rate of 80.8% in salvaging failed tenotomy cases. The failed tenotomy group was relatively older at presentation, had high precasting and pretenotomy Pirani scores, received extra number of Ponseti casts, and less pretenotomy ankle joint dorsiflexion compared with successful feet.


Autoradiographic localization of beta-adrenergic receptors in human large coronary arteries.
The distribution of beta-adrenergic receptors in sections of the human right and left coronary arteries and of the anterior intraventricular branch was studied by the use of combined in vitro radioreceptor binding and autoradiographic techniques. [125I]Cyanopindolol was used as a ligand for beta-adrenergic receptors. Binding of the radioligand to sections of the three coronary arteries under study was saturable, stereoselective, reversible, and displaceable by antagonists and agonists with the rank order of potency expected for beta-adrenergic receptors. Analysis of binding isotherms indicated maximum binding capacities of 41.5 fmol/mg protein for the right coronary artery, 35.4 fmol/mg protein for the left coronary artery, and 25.7 fmol/mg protein for the anterior interventricular branch. Dissociation constants were approximately 35 pM in the arteries examined. The relative amounts of beta 1- and beta 2-receptor subtypes were as follows: 72% beta 1-receptors and 28% beta 2-receptors in the right coronary artery; 65% beta 1-receptors and 35% beta 2-receptors in the left coronary artery; 40% beta 1-receptors and 60% beta 2-receptors in the anterior interventricular branch. The results of autoradiographic analysis revealed a predominance of beta 1-receptors in the medial layer. beta 2-Receptors were localized primarily in the adventitia, in the adventitia-media border, and in the intimal layer. These results should lead to a better understanding of the mechanisms involved in the control of coronary circulation in humans.


Assessing the environmental effects of ICT and renewable energy: roles of financial development, innovation, and trade.
In today's world of rapidly expanding economies, the fundamental aim of most nations is to raise the quality of living for their citizens. The investigation aims to analyze how environmental rules affect the emergence of environmentally conscious economies. This research focused on China's 26 provinces to investigate the elements influencing green economic development. These components included information and communication technology (ICT), industrial structure (IND), human capital (EDU), and foreign direct investment. Spatial modeling and SBM methods were utilized to show that there is still a connection between the variables after all these years using yearly time series data that began in 2000. Overall, the results suggest that environmental regulation helps green economic development (GDE), whereas industrial structure significantly hinders. Similar to the previous point, information and communication technology has a favorable influence on building a sustainable economy. The problem of ensuring long-term economic growth via information and communication technology is complicated and has scholars engaged in exciting discussion. The expansion of the green economy is also affected by factors such as human capital and foreign direct investment. This study's findings illuminate the economic effects of environmental regulations and support the contention that such laws are necessary for accomplishing the win-win goals of green economic development and environmental protection. This means that the research provides a fresh perspective to consider the monetary effects of environmental restrictions.


Selective Electrocatalytic Oxidation of Nitrogen to Nitric Acid Using Manganese Phthalocyanine.
Ammonia is produced through the energy-intensive Haber-Bosch process, which undergoes catalytic oxidation for the production of commercial nitric acid by the senescent Ostwald process. The two energy-intensive industrial processes demand for process sustainability. Hence, single-step electrocatalysis offers a promising approach toward a more environmentally friendly solution. Herein, we report a 10-electron pathway associated one-step electrochemical dinitrogen oxidation reaction (N2OR) to nitric acid by manganese phthalocyanine (MnPc) hollow nano-structures under ambient conditions. The catalyst delivers a nitric acid yield of 513.2 μmol h-1 gcat-1 with 33.9% Faradaic efficiency @ 2.1 V versus reversible hydrogen electrode. The excellent N2OR performances are achieved due to the specific-selectivity, presence of greater number of exposed active sites, recyclability, and long period stability. The extended X-ray absorption fine structure confirms that Mn atoms are coordinated to the pyrrolic and pyridinic nitrogen via Mn-N4 coordination. Density functional theory-based theoretical calculations confirm that the Mn-N4 site of MnPc is the main active center for N2OR, which suppresses the oxygen evolution reaction. This work provides a new arena about the successful example of one step nitric acid production utilizing a Mn-N4 active site-based metal phthalocyanine electrocatalyst by dinitrogen oxidation for the development of a carbon-neutral sustainable society.


Promoting Cell Fusion by Polyvalent DNA Ligands.
Artificially induced in vitro cell fusion is one essential technique that has been extensively used for biological studies. Nevertheless, there is a lack of robust and efficient method to produce fused cells efficiently. Herein, we proposed to use cell-membrane-anchored polyvalent DNA ligands (PDL) to bring cells into close proximity by forming clusters to enhance PEG-induced cell fusion. PDL of complementary sequences are separately anchored onto different population of cells through cholesterol-induced hydrophobic insertion into lipid membrane. Cells are clustered via mixing cells of complementary PDL prior to cell fusion. PDL exhibited strong stability on cell membrane, induced efficient cell clustering, and eventually achieved cell fusion efficiently in combination with PEG induction. We demonstrated homogeneous and heterogeneous cell fusion of high yield on various cell types. This report presented a programmable yet robust technique for achieving efficient cell fusion that hold great application potentials.


Quaternary-Ammonium-Modulated Surface-Enhanced Raman Spectroscopy Effect: Discovery, Mechanism, and Application for Highly Sensitive In Vitro Sensing of Acetylcholine.
Quaternary ammonium (QA) plays multiple roles in biological functions, whose dysregulation may result in multiple diseases. However, how to efficiently detect QA-based materials such as acetylcholine (ACh) still remains a great challenge, especially in complex biological environments. Here, a new effect [called quaternary-ammonium-modulated surface-enhanced Raman spectroscopy (QAM-SERS) effect] is discovered, showing that the existence of QA will modulate the intensity of SERS signals in a concentration-dependent manner. When the QAM-SERS effect is used, a new method is easily developed for in vitro detection of ACh with an extremely high sensitivity and an ultrawide dynamic range. Particularly, the linear dynamic range can be freely tuned to adapt for various physiological samples. As a proof-of-concept experiment, the time-dependent secretion of ACh from PC12 cells was successfully monitored using the QAM-SERS method, which were under either the stimulation of potassium ions or the incubation of drugs. The discovery of the QAM-SERS effect provides an easy and universal strategy for detecting ACh as well as other QA-contained molecules, which can also inspire new insights into the roles that QA could play in biology and chemistry.


Hepatocellular carcinoma in a Hokkaido brown bear (Ursus arctos yesoensis).
Hepatocellular carcinoma with metastases to lymph nodes and adrenal glands was found in a 26-year-old male Hokkaido brown bear (Ursus arctos yesoensis). Left hepatic lobe was largely replaced by well-differentiated neoplastic cells, whereas poorly differentiated tumor cells had proliferated in part of the left hepatic lobe, in scattered nodules in the remaining liver tissue, and at the metastatic sites. Immunoreactivity for hepatocyte antigen (hepatocyte paraffin 1 antibody) and alpha-fetoprotein was observed in both well- and poorly differentiated neoplastic cells in the liver and metastatic foci. To our knowledge, this case is the first report of hepatocellular carcinoma in brown bears.


Incidence, Clinical Characteristics and Outcomes of Early Hyperbilirubinemia in Critically Ill Patients: Insights From the MARS Study.
To investigate the incidence, clinical characteristics and outcomes of early hyperbilirubinemia in critically ill patients. This is a post hoc analysis of a prospective multicenter cohort study. Patients with measured bilirubin levels within the first 2 days after ICU admission were eligible. Patients with liver cirrhosis were excluded. The primary endpoint was the incidence of early hyperbilirubinemia, defined as bilirubin ≥33 μmol/L within 2 days after ICU admission. Secondary endpoints included clinical characteristics of patients with versus patients without early hyperbilirubinemia, and outcomes up to day 30. Of 4,836 patients, 559 (11.6%) patients had early hyperbilirubinemia. Compared to patients without early hyperbilirubinemia, patients with early hyperbilirubinemia presented with higher severity of illness scores, and higher incidences of sepsis and organ failure. After adjustment for confounding variables, early hyperbilirubinemia remained associated with mortality at day 30 (odds ratio, 1.31 [95%-confidence interval 1.06-1.60]; P = 0.018). Patients with early hyperbilirubinemia and thrombocytopenia (interaction P-value = 0.005) had a higher likelihood of death within 30 days (odds ratio, 2.61 [95%-confidence interval 2.08-3.27]; P < 0.001) than patients with early hyperbilirubinemia and a normal platelet count (odds ratio, 1.09 [95%-confidence interval 0.75-1.55]; P = 0.655). Early hyperbilirubinemia occurs frequently in the critically ill, and these patients present with higher disease severity and more often with sepsis and organ failures. Early hyperbilirubinemia has an association with mortality, albeit this association was only found in patients with concomitant thrombocytopenia.


Total synthesis of biologically active 20S-hydroxyvitamin D3.
A total synthetic strategy of 20S-hydroxyvitamin D3 [20S-(OH)D3] involving modified synthesis of key intermediates 7 and 12, Grignard reaction to stereoselectively generate 20S-OH and Wittig-Horner coupling to establish D3 framework, was completed in 16 steps with an overall yield of 0.4%. The synthetic 20S-(OH)D3 activated vitamin D receptor (VDR) and initiated the expression of downstream genes. In addition, 20S-(OH)D3 showed similar inhibitory potency as calcitriol [1,25(OH)2D3] on proliferation of melanoma cells.


Syndromic versus laboratory-based diagnosis of cervical infections among female sex workers in Benin: implications of nonattendance for return visits.
The syndromic diagnostic approach is the most realistic and cost-effective strategy for controlling sexually transmitted infections (STIs) in the developing world. Its potential advantages should be evaluated. The goal of the current study was to examine whether the syndromic approach might diagnose more cases of cervicitis due to Neisseria gonorrhoeae or Chlamydia trachomatis than laboratory tests. The participants were 481 female sex workers in Benin, screened for STIs and treated on the basis of the clinical findings. They were asked to return to the clinic within 10 days for laboratory test results and appropriate treatment when necessary. The prevalence of cervical infections was 24.5%. In comparison to the gold standard, the sensitivity of the syndromic diagnosis approach for the detection of N gonorrhoeae/C trachomatis infections was 48.3%; that of the locally performed laboratory tests was 74.6%. However, the sensitivity of the laboratory tests dropped to 28.8% when it was taken into consideration that 57.6% of the infected women did not return to the clinic within 10 days. The syndromic diagnosis approach should continue to be used for female sex workers in Benin because returning for treatment is problematic. Presumptive treatment at their initial visit could be a complement to this approach, given the high prevalence of cervicitis in this population.


[Group learning in medical education].
The implementation of group learning in medical education puts special demands on the participants, but also offers pedagogical benefits, which may be conductive to the efficient learning of facts, skills and attitudes. The group makes it possible to verify or modify the learned material, which is an important part of preparing for a career as a doctor. Students develop a dependence on others when solving problems in groups, whereas as clinicians they are often alone when confronted with problems demanding quick decisions. In this article we discuss some of the pedagogical principles involved in group learning and make suggestions on how to apply them to learning based on problem solving and other forms of group learning in the medical curriculum.


Determination of Intracellular Esterase Activity Using Ratiometric Raman Sensing and Spectral Phasor Analysis.
Carboxylesterases (CEs) are a class of enzymes that catalyze the hydrolysis of esters in a variety of endogenous and exogenous molecules. CEs play an important role in drug metabolism, in the onset and progression of disease, and can be harnessed for prodrug activation strategies. As such, the regulation of CEs is an important clinical and pharmaceutical consideration. Here, we report the first ratiometric sensor for CE activity using Raman spectroscopy based on a bisarylbutadiyne scaffold. The sensor was shown to be highly sensitive and specific for CE detection and had low cellular cytotoxicity. In hepatocyte cells, the ratiometric detection of esterase activity was possible, and the result was validated by multimodal imaging with standard viability stains used for fluorescence microscopy within the same cell population. In addition, we show that the detection of localized ultraviolet damage in a mixed cell population was possible using stimulated Raman scattering microscopy coupled with spectral phasor analysis. This sensor demonstrates the practical advantages of low molecular weight sensors that are detected using ratiometric Raman imaging and will have applications in drug discovery and biomedical research.


Brain and liver oxidative stress after sertraline and haloperidol treatment in mice.
Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal side effects. Sertraline is an antidepressant drug which has been reported to cause extrapyramidal symptoms. We aimed to see whether treatment with sertraline would worsen the effect of haloperidol on oxidative stress in the brains of mice. Sertraline (10 or 20 mg/kg), haloperidol (2 mg/kg), haloperidol combined with sertraline or saline was administered daily via the subcutaneous route and mice were euthanized 10 days later when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (nitrite) levels, total antioxidant capacity (TAC), acetylcholinesterase (AChE), catalase and paraoxonase 1 (PON1) activities were determined in the brain and liver. Sertraline monotherapy did not alter GSH, MDA, TAC or nitrite in the brain. Haloperidol decreased GSH and TAC and increased MDA and nitrite. The combined treatment with sertraline and haloperidol resulted in increased MDA, but to a lesser extent than haloperidol monotherapy. A significant increase in GSH and TAC and decreased nitrite was observed after the combination treatment was compared with haloperidol monotherapy. Catalase activity decreased with sertraline or haloperidol treatment. PON1 activity decreased with sertraline and haloperidol monotherapy and showed a further decrease with the combination therapy compared with haloperidol monotherapy. AChE activity decreased after haloperidol and increased with the combination treatment compared with haloperidol monotherapy. In the liver, GSH was unaltered after sertraline, haloperidol or their combination. MDA increased with sertraline, haloperidol and their combination. TAC decreased after combination therapy. Nitric oxide increased after sertraline, haloperidol or their combination. PON1 activity decreased with sertraline, haloperidol and with sertraline-haloperidol co-treatment. Sertraline did not worsen brain oxidative stress-induced with haloperidol, however, liver peroxidation increased. Sertraline decreased catalase and PON1 activity which might expose the brain to further oxidative insults.


Vortex dynamics in a coarsening two-dimensional XY model.
The vortex velocity distribution function for a two-dimensional coarsening nonconserved O(2) time-dependent Ginzburg-Landau model is determined numerically and compared to theoretical predictions. In agreement with these predictions the distribution function scales with the average vortex speed which is inversely proportional to t(x), where t is the time after the quench and x is near 1/2. We find the entire curve, including a large speed algebraic tail, in good agreement with the theory.


Endoscopic retrograde cholangiopancreatography-related perforations: Diagnosis and management.
Endoscopic retrograde cholangiopancreatography (ERCP) has become an important therapeutic modality for biliary and pancreatic disorders. Perforation is one of the most feared complications of ERCP and endoscopic sphincterotomy. A MEDLINE search was performed from 2000-2014 using the keywords "perforation", "ERCP" and "endoscopic sphincterotomy". All articles including more than nine cases were reviewed. The incidence of ERCP-related perforations was low (0.39%, 95%CI: 0.34-0.69) with an associated mortality of 7.8% (95%CI: 3.80-13.07). Endoscopic sphincterotomy was responsible for 41% of perforations, insertion and manipulations of the endoscope for 26%, guidewires for 15%, dilation of strictures for 3%, other instruments for 4%, stent insertion or migration for 2% and in 7% of cases the etiology was unknown. The diagnosis was made during ERCP in 73% of cases. The mechanism, site and extent of injury, suggested by clinical and radiographic findings, should guide towards operative or non-operative management. In type I perforations early surgical repair is indicated, unless endoscopic closure can be achieved. Patients with type II perforations should be treated initially non-operatively. Non-operative treatment includes biliary stenting, fasting, intravenous fluid resuscitation, nasogastric drainage, broad spectrum antibiotics, percutaneous drainage of fluid collections. Non-operative treatment was successful in 79% of patients with type II injuries, with an overall mortality of 9.4%. Non-operative treatment was sufficient in all patients with type III injuries. Surgical technique depends on timing, site and size of defect and clinical condition of the patient. In conclusion, diagnosis is based on clinical suspicion and clinical and radiographic findings. Whilst surgery is usually indicated in patients with type I injuries, patients with type II or III injuries should be treated initially non-operatively. A minority of them will finally require surgical intervention.


Tuning Superhydrophobic Nanostructures To Enhance Jumping-Droplet Condensation.
It was recently discovered that condensation growing on a nanostructured superhydrophobic surface can spontaneously jump off the surface, triggered by naturally occurring coalescence events. Many reports have observed that droplets must grow to a size of order 10 μm before jumping is enabled upon coalescence; however, it remains unknown how the critical jumping size relates to the topography of the underlying nanostructure. Here, we characterize the dynamic behavior of condensation growing on six different superhydrophobic nanostructures, where the topography of the nanopillars was systematically varied. The critical jumping diameter was observed to be highly dependent upon the height, diameter, and pitch of the nanopillars: tall and slender nanopillars promoted 2 μm jumping droplets, whereas short and stout nanopillars increased the critical size to over 20 μm. The topology of each surface is successfully correlated to the critical jumping diameter by constructing an energetic model that predicts how large a nucleating embryo needs to grow before it can inflate into the air with an apparent contact angle large enough for jumping. By extending our model to consider any possible surface, it is revealed that properly designed nanostructures should enable nanometric jumping droplets, which would further enhance jumping-droplet condensers for heat transfer, antifogging, and antifrosting applications.


Treatment typically provided for comorbid anxiety disorders.
To study whether the extent and type of treatment for comorbid anxiety disorders varies for patients with depression, hypertension, diabetes, and heart disease treated by general medical clinicians. Data are from 2189 general medical patients with and without comorbid anxiety disorders in the Medical Outcomes Study. Treatment data were based on clinician reports of counseling provided during a visit and patient reports of recent medication use. Patients with comorbid anxiety disorders were more likely to receive treatments for anxiety disorders than those without anxiety disorders. Among those with anxiety disorders, the use of psychosocial counseling and psychotropic medication was greater for patients with depression than for patients without depression who had chronic medical conditions. Minor tranquilizers were used more commonly than antidepressants, regardless of the type of comorbid condition. Among patients with anxiety disorders, those visiting medical subspecialists were more likely to use minor tranquilizers than those visiting family practitioners or internists. Patients of family physicians with chronic medical conditions (but not with depression) were less likely than similar patients of internists to use minor tranquilizers whether or not anxiety disorders were present. Anxiety disorders co-occurring with another disease (medical illness or depression) increases the likelihood of counseling and the use of psychotropic medication in the general medical sector. Patients with a chronic medical illness with or without comorbid anxiety disorders visiting family physicians are less likely to use minor tranquilizers than those visiting subspecialists or internists.


Imido-hydrido complexes of Mo(IV): catalysis and mechanistic aspects of hydroboration reactions.
Imido-hydrido complexes (ArN)Mo(H)(Cl)(PMe3)3 (1) and (ArN)Mo(H)2(PMe3)3 (2) (Ar = 2,6-diisopropylphenyl) catalyse a variety of hydroboration reactions, including the rare examples of addition of HBCat to nitriles to form bis(borylated) amines RCH2N(BCat)2. Stoichiometric reactivity of complexes 1 and 2 with nitriles and HBCat suggest that catalytic reactions proceed via a series of agostic borylamido and borylamino complexes. For complex 1, catalysis starts with addition of nitriles across the Mo-H bond to give (ArN)Mo(Cl)(N[double bond, length as m-dash]CHR)(PMe3)2; whereas for complex 2 stoichiometric reactions suggest initial addition of HBCat to form the agostic complex Mo(H)2(PMe3)3(η(3)-NAr-HBcat) (16).


Clinical patterns and genomic profiling of recurrent 'ultra-low risk' endometrial cancer.
Despite good prognosis for patients with low-risk endometrial cancer, a small subset of women with low-grade/low-stage endometrial cancer experience disease recurrence and death. The aim of this study was to characterize clinical features and mutational profiles of recurrent, low-grade, non-myoinvasive, 'ultra-low risk' endometrioid endometrial adenocarcinomas. We retrospectively identified patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA endometrioid endometrial cancers who underwent primary surgery at our institution, between January 2009 and February 2017, with follow-up of ≥12 months. 'Ultra-low risk' was defined as FIGO tumor grade 1, non-myoinvasive, and lacking lymphovascular space invasion. Tumor-normal profiling using massively parallel sequencing targeting 468 genes was performed. Microsatellite instability was assessed using MSIsensor. DNA mismatch repair (MMR) protein proficiency was determined by immunohistochemistry. A total of 486 patients with ultra-low risk endometrioid endometrial cancers were identified: 14 (2.9%) of 486 patients developed a recurrence. Median follow-up for non-recurrent endometrioid endometrial cancers: 34 (range 12-116) months; for recurrent endometrioid endometrial cancers: 50.5 (range 20-116) months. Patients with recurrent disease were older, had lower body mass index, and were most commonly non-White (p=0.025, p<0.001, and p<0.001, respectively). Other clinical characteristics did not differ. MMR immunohistochemistry was obtained for 211 (43%) tumors: 158 (75%) MMR-proficient and 53 (25%) MMR-deficient. Primary tumors of 9 recurrent and 27 non-recurrent endometrioid endometrial cancers underwent mutational profiling. Most were microsatellite stable (6/9, 67% recurrent; 25/27, 93% non-recurrent). Recurrent PTEN and PIK3CA mutations were present in both groups. Exon 3 CTNNB1 hotspot mutations were found in 4/9 (44%) recurrent and 8/27 (30%) non-recurrent (p=0.44). Patients diagnosed with ultra-low risk endometrioid endometrial cancers have an overall excellent prognosis. However, in our study, 2.9% of patients with no identifiable clinical or pathologic risk factors developed recurrence. Further work is warranted to elucidate the mechanism for recurrence in this population.


Gynecomastia and sexual impotence associated with methotrexate treatment.
Methotrexate (MTX) is the disease modifying antirheumatic drug most frequently used for rheumatoid and psoriatic arthritis (PsA). Several reports associate sexual dysfunction to MTX use. We describe 2 cases of sexual impotence and gynecomastia in patients with PsA treated with MTX. Although the mechanism underlying MTX induced sexual dysfunction is unknown, the potential consequences should be taken in account in view of the steady increase in the number of patients.


[Experimental research on prevention and treatment of fatty liver rats with Abrus cantoniensis].
To investigate the effects of Abrus cantoniensis (AC) on blood lipid metabolism, pathomorphological change of the liver and fenestrae of liver sinus endothelial cell (LSEC) in fatty liver disease rats. SD rats were divided into 7 groups: blank control group,fatty liver model group, simvastatin group (7.2 mg/kg), Gynostemma pentaphyllum group (16.2 mg/kg), high dose (40 g/kg), middle dose (20 g/kg) and low dose (10 g/kg) of AC groups. All rats except blank control group were fed with high fat diet for the first 3 weeks, then treated with different conditions as previously mentioned for the next 3 weeks while keep on feeding with high fat diet. At the 43rd day,the abdominal aortic blood was collected for measuring the serum concentration of AST, ALT, TC, TG, HDL-C, LDL-C, and liver tissues were taken to make pathological sections for observation by optical microscope or were prepared for scanning electronic microscope. The levels of AST, ALT, TC, TG, LDL-C were obviously decreased while HDL-C were increased in fatty liver rats by AC high dose. Meanwhile the cell morphology of liver tissues and the fenestraes of LSEC were improved as well. AC can ameliorate the levels of blood lipid in fatty liver rats and improve the pathological change of liver tissues. To some extent AC has the function of prevention and treatment of fatty liver.


Dehydrogenative Aromatization and Sulfonylation of Pyrrolidines: Orthogonal Reactivity in Photoredox Catalysis.
Oxidative dehydrogenative aromatization and selective sulfonylation reactions of N-heterocycles under visible-light photoredox catalysis were established. The mild reaction conditions make this approach an appealing and versatile strategy to functionalize/oxidize pyrrolidines whereby arylsulfonyl chlorides were identified to be both catalyst regeneration and sulfonylation reagents.


Electroantennogram and behavioral responses of the imported fire ant, Solenopsis invicta Buren, to an alarm pheromone component and its analogues.
A characteristic behavior in ants is to move rapidly to emission sources of alarm pheromones. The addition of ant alarm pheromones to bait is expected to enhance its attractiveness. To search for candidate compounds for bait enhancement in fire ant control, 13 related alkylpyrazine analogues in addition to synthetic alarm pheromone component were evaluated for electroantennogram (EAG) and behavioral activities in Solenopsis invicta. Most compounds elicited dose-dependent EAG and behavioral responses. There exists a correlation between the EAG and behavioral responses. Among the 14 tested alkylpyrazines, three compounds, 2-ethyl-3,6(5)-dimethyl pyrazine (1), 2,3,5-trimethylpyrazine (7), and 2,3-diethyl-5-methylpyrazine (12), elicited significant alarm responses at a dose range of 0.1-1000 ng. Further bait discovery bioassay with the three most active alkylpyrazines demonstrated that food bait accompanied by sample-treated filter paper disk attracted significantly more fire ant workers in the first 15 min period. EAG and behavioral bioassays with pure pheromone isomers accumulated by semi-preparative high-performance liquid chromatography demonstrated that 2-ethyl-3,6-dimethylpyrazine was significantly more active than 2-ethyl-3,5-dimethylpyrazine.


Ab initio energies of nonconducting crystals by systematic fragmentation.
A systematic method for approximating the ab initio electronic energy of molecules from the energies of molecular fragments has been adapted to estimate the total electronic energy of crystal lattices. The fragmentation method can be employed with any ab initio electronic structure method and allows optimization of the crystal structure based on ab initio gradients. The method is demonstrated on SiO(2) polymorphs using the Hartree-Fock approximation, second order Moller-Plesset perturbation theory, and the quadratic configuration interaction method with single and double excitations and triple excitations added perturbatively .


Response of marine copepods to a changing tropical environment: winners, losers and implications.
Background. Climate change concurrent with anthropogenic disturbances can initiate serial changes that reverberate up the food chain with repercussions for fisheries. To date, there is no information available concerning the combined effects of global warming and human impacts on tropical marine food webs. While temperate copepods respond differently to warming and environmental stressors, the extent to which tropical copepods can adapt to rising temperature of already warm waters remains unknown. We hypothesize that sea warming and other anthropogenic disturbances over the long term will have the greatest impact on the copepod community in nearshore waters where their effects are accentuated, and therefore vulnerable and resilient species could be identified. Methods. Zooplankton samples were collected during two time periods (1985-86 and 2014-15) interposed by marked anthropogenic disturbances, and at the same five stations located progressively from inshore to offshore in Klang Strait, Malaysia, following the asymmetrical before-after-control-impact (BACI) design. Copepods were identified to species, and results were interpreted by univariate (ANOVA) and multivariate (PERMANOVA, PCO) analyses of the computed species abundance and diversity measures. Results. Copepod total abundance was not significantly different among stations but higher after disturbance than before disturbance. However, changes in the abundance of particular species and the community structure between time periods were dramatic. Coastal large-bodied calanoid species (e.g., Acartia spinicauda, Calanopia thompsoni, Pseudodiaptomus bowmani and Tortanus forcipatus) were the most vulnerable group to disturbance. This however favored the opportunistic species (e.g., Oithona simplex, O. attenuata, Hemicyclops sp., Pseudomacrochiron sp. and Microsetella norvegica). Small-bodied copepods (e.g., Paracalanus sp., Parvocalanus crassirostris and Euterpina acutifrons) were unaffected. Centropages tenuiremis was likely an introduced species. There was no significant loss in species richness of copepods despite the dramatic changes in community structure. Discussion. Sea warming and other human-induced effects such as eutrophication, acidification and coastal habitat degradation are likely the main factors that have altered copepod community structure. The large-bodied estuarine and coastal calanoid copepods are surmised to be vulnerable to eutrophication and hypoxia, while both resilient and opportunistic species are largely unaffected by, or adaptable to, degraded coastal environments and observed sea surface temperature (SST) rise. It is forecasted that SST rise with unmitigated anthropogenic impacts will further reduce large-bodied copepod species the favoured food for fish larvae with dire consequences for coastal fish production.


Rehabilitation interventions during acute care of stroke patients.
The immediate care of a stroke patient admitted to hospital is best provided in a dedicated stroke unit, within which all of the key components of care can be coordinated. Neurologic diagnosis and intervention and general medical care are essential elements of acute stroke management. However, optimal outcome requires a comprehensive and multidisciplinary approach, which includes rehabilitation interventions. During the initial phases of care, rehabilitation interventions are mostly passive and emphasize prevention of secondary co-impairments such as contractures, pressure ulcers, and deconditioning. Rehabilitation interventions should be incorporated into care protocols for all patients and should begin immediately. As the patient becomes stable, more intensive therapy can be initiated in preparation for transition into the postacute phase of active rehabilitation.


Molecular distribution of elastase between its two main inhibitors: direct quantitation of elastase-alpha 2-macroglobulin complex with a novel ELISA technique.
A novel enzyme-linked immunosorbent assay for the quantitation of elastase linked to alpha 2-macroglobulin (alpha 2M) (elastase-alpha 2M complex, EMC) in body fluids is presented. The assay has a lower detection limit of 1.5 ng bound elastase per ml. The critical factor allowing immunological detection of alpha 2M-bound elastase is the addition of phenyl methyl sulphonyl fluoride (PMSF) to the assay buffer. The assay has been used to quantitate EMC in plasma and serum of healthy volunteers, and assess the distribution of elastase between its two main inhibitors, alpha 2M and alpha 1-proteinase inhibitor (API). EMC levels in serum samples from volunteers were significantly higher than in plasma (26.9 vs 21.9 ng/ml, p = 0.05, Student's t-test for paired samples). The API-bound elastase levels were 70.2 and 170.1 ng/ml in plasma and serum respectively (statistically significantly higher in serum, p less than 0.0001). The ratio of macroglobulin to alpha 1-proteinase-bound elastase levels was 0.333 in plasma and 0.168 in serum (p less than 0.0001). As alpha 2M bound elastase retains some proteolytic activity, direct measurement of circulating levels in inflammatory conditions should be of interest.


[Expectant management of premature rupture of fetal membranes before completion of the 35th week of pregnancy--retrospective analysis of 44 cases].
44 cases of preterm premature rupture of fetal membranes (PPROM) before 35 completed weeks of gestation were analyzed retrospectively. Expectative management was based on infection diagnosis, vaginal disinfection and in case of signs of infection on systemic antibiotic therapy. Glucocorticoids for induction of lung maturity were generally administered. Perinatal mortality was 11.4%, after exclusion of one congenital anomaly 9.3% respectively. Lung immaturity was the main cause of neonatal death. Only 5 neonates developed clinical infection, with 4 of these showing prepartal maternal signs of infection. Maternal signs of infection are not a specific signal for later neonatal infection. Cerebral bleeding complications and pathological neurologic status occurred in 10/39 and 8/39 cases respectively. Cesarean section rate amounted to 15/44 (34%).


[Transrectal ultrasonography of the prostate (author's transl)].
A French instrumentation for transrectal ultrasonography of the prostate by means of a rectal probe containing a rotative transducer is presented. Typical ultrasonographic images are shown. Accurate information on the size of the gland is obtained by this method and adenomas can easily be distinguished from adenocarcinomas. The method might eventually be of considerable value for the screening of asymptomatic subjects and early detection of prostatic cancer.


Olfaction in Olfactory Groove Meningiomas.
Clinical examination, including pre- and postoperative assessment of olfaction, is essential in evaluating surgical outcomes in patients with olfactory groove meningiomas (OGMs). A review of a recent series revealed a lack of assessment of olfaction in most of the studies. Tests determining olfactory detection should be used to reveal olfactory dysfunction. Specialized examination techniques (e.g., electro-olfactography, olfactory evoked potentials, and functional magnetic resonance imaging) are currently used in research. Prospective analysis of 13 patients who underwent surgical resection of OGMs from December 2013 to December 2017 was performed. Data on clinical presentation, pre- and postoperative neurologic examinations, complications, recurrences, adjuvant treatment, and follow-up outpatient examinations were recorded. Olfactory function was assessed using the Sniffin' Sticks odor identification test preoperatively, postoperatively, and 1 year after surgery. All the meningiomas were resected via unilateral craniotomy, and gross total resection was achieved in all cases. Surgery-related permanent morbidity was 7.7% and overall mortality 0%. For the eight patients with preoperative normosmia, five remained normosmic (62.5%), one deteriorated to hyposmia (12.5%), and two deteriorated to anosmia (25%). For the two patients with preoperative hyposmia, one remained hyposmic and one deteriorated to anosmia. For the three anosmic patients, two remained anosmic, and one improved to hyposmia.The intact olfactory function preoperatively was associated with a better olfactory outcome. Overall, 62.5% of these patients remained normosmic, and none of the hyposmic or anosmic patients normalized their olfaction.Higher meningioma volume is associated with worse olfactory function before surgery (normosmia in 16.7% versus 100.0% in less voluminous) and following the surgery (normosmia in 16.7% versus 57.1% less voluminous).The unilateral surgical approach enabled the anatomical preservation of the contralateral olfactory nerve in 76.9% of our patients. Functional normosmia was achieved in 50% and hyposmia in 30% of these cases. Assessment of olfactory function is both vital in preoperative decision making (surgical approach, radicality of resection) and when evaluating surgical outcome. Preoperative normosmia seems to be the most important prognostic factor for functional olfactory outcome. In normosmic patients the olfaction was preserved in 62.5% of cases. Moreover, higher meningioma volume is associated with worse olfactory function before and following the surgery. The greatest advantage of the unilateral surgical approach is anatomical preservation of the contralateral olfactory nerve with a satisfactory functional outcome. These results support a proactive approach, with early surgical resection using a unilateral approach even in cases with less voluminous OGMs that enables the preservation of olfactory function in a significant proportion of patients.


Improved Electrochemical Alkaline Seawater Oxidation over Cobalt Carbonate Hydroxide Nanowire Array by Iron Doping.
Constructing efficient and low-cost oxygen evolution reaction (OER) catalysts operating in seawater is essential for green hydrogen production but remains a great challenge. In this study, we report an iron doped cobalt carbonate hydroxide nanowire array on nickel foam (Fe-CoCH/NF) as a high-efficiency OER electrocatalyst. In alkaline seawater, such Fe-CoCH/NF demands an overpotential of 387 mV to drive 500 mA cm-2, superior to that of CoCH/NF (597 mV). Moreover, it achieves excellent electrochemical and structural stability in alkaline seawater.


Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease?
Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, and despite recent advances in hypertension control, anemia management, and dialysis adequacy, mortality remains high. Improved understanding of nontraditional risk factors, including those present at early phases in CKD, may lead to novel therapeutic strategies. CKD has been demonstrated to be an independent risk factor for cardiovascular disease in the general population, but data are lacking as to the associated potential abnormalities that occur in association with reduced glomerular filtration rate (GFR), which may contribute to this increased risk. Data are accumulating regarding the role of abnormalities of calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) in cardiovascular disease. Vitamin D deficiency is present even in the early stages of CKD. Vitamin D plays a central role in calcium-phosphorus homeostasis, regulation of PTH, and formation and maintenance of bone. However, until recently, vitamin D has not been considered to have a biologic role in CKD beyond mineral regulation, or has been considered as a negative factor contributing to soft tissue and cardiovascular calcification. In light of recent observational studies showing an association of vitamin D therapy and survival benefit in hemodialysis patients, the effects of vitamin D on cardiovascular system have become a heavily debated issue. A Medline search was performed to identify relevant literature describing the role of vitamin D in the pathogenesis of cardiovascular disease. Both the experimental and clinical literatures in English were reviewed. The accumulating published data demonstrate both associative relationships and mechanisms for biologic plausibility. The following three potential mechanisms may be important for the protective effects of vitamin D against cardiovascular disease mortality: vitamin D can inhibit various aspects of inflammation, which have been established as a key pathogenic mechanism in atherosclerosis; vitamin D exerts an antiproliferative effect on myocardial cell hypertrophy and proliferation, which underlies the pathogenesis of congestive heart failure; and vitamin D acts as a negative endocrine regulator for the renin-angiotensin system, which itself plays an important independent role in hypertension and cardiovascular health. Vitamin D deficiency might be an underestimated nonclassical risk factor for cardiovascular disease in CKD. Based on a review of the evidence, from both basic science and clinical studies, this article supports the possible protective role of vitamin D beyond its effect on mineral metabolism, and suggests the need for ongoing evaluation of the role of vitamin D in cardiovascular health in the CKD population.


Heterogeneous Strain Distribution Based Programmable Gated Microchannel for Ultrasensitive and Stable Strain Sensing.
Developing highly sensitive strain sensors requires conduction pathways capable of rapidly switching between disconnection and reconnection in response to strain. Ion channels in living organisms exactly control the channel switch through protein-composed gates, achieving changeable ion currents. Herein, inspired by the gating characteristics of the ion channels, a programmable fluidic strain sensor enhanced by gating ion pathways through heterogeneous strain distribution of discrete micropillars is proposed. During stretching, the contraction and closure of the widthwise gaps between discrete micropillars greatly weaken or even nearly cut off the conduction pathway, resulting in orders of magnitude increase in resistance and thus ultrahigh sensitivity. By adjusting the combination form and structural parameters of the discrete micropillars in the fluidic channel, the sensitivity and strain range can be customized. Thus, a gauge factor of up to 45 300 and a stretch range of 590% are obtained. Benefiting from the fluidic gating mechanism, no mechanical mismatch can be observed at the interface, breaking through the sensing stability issue of flexible sensors. The proposed sensor can be used to detect the full range of human motion, and integrated into a data glove to achieve human-machine interaction.


RNF115 Inhibits the Post-ER Trafficking of TLRs and TLRs-Mediated Immune Responses by Catalyzing K11-Linked Ubiquitination of RAB1A and RAB13.
The subcellular localization and intracellular trafficking of Toll-like receptors (TLRs) critically regulate TLRs-mediated antimicrobial immunity and autoimmunity. Here, it is demonstrated that the E3 ubiquitin ligase RNF115 inhibits the post-endoplasmic reticulum (ER) trafficking of TLRs and TLRs-mediated immune responses by catalyzing ubiquitination of the small GTPases RAB1A and RAB13. It is shown that the 14-3-3 chaperones bind to AKT1-phosphorylated RNF115 and facilitate RNF115 localizing on the ER and the Golgi apparatus. RNF115 interacts with RAB1A and RAB13 and catalyzes K11-linked ubiquitination on the Lys49 and Lys61 residues of RAB1A and on the Lys46 and Lys58 residues of RAB13, respectively. Such a modification impairs the recruitment of guanosine diphosphate (GDP) dissociation inhibitor 1 (GDI1) to RAB1A and RAB13, a prerequisite for the reactivation of RAB proteins. Consistently, knockdown of RAB1A and RAB13 in Rnf115+/+ and Rnf115-/- cells markedly inhibits the post-ER and the post-Golgi trafficking of TLRs, respectively. In addition, reconstitution of RAB1AK49/61R or RAB13K46/58R into Rnf115+/+ cells but not Rnf115-/- cells promotes the trafficking of TLRs from the ER to the Golgi apparatus and from the Golgi apparatus to the cell surface, respectively. These findings uncover a common and step-wise regulatory mechanism for the post-ER trafficking of TLRs.


EAU guidelines on prostate cancer.
To present a summary of the 2007 version of the European Association of Urology (EAU) guidelines on prostate cancer (PCa). A literature review of the new data emerging from 2004 to 2007 was performed by the working panel. The guidelines have been updated, and the level of evidence/grade of recommendation was added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. A full version is available at the EAU Office or at www.uroweb.org. Systemic prostate biopsy under ultrasound guidance is the preferred diagnostic method. Active treatment is mostly recommended for patients with localized disease and a long life expectancy, with radical prostatectomy being shown to be superior to watchful waiting in a prospective randomized trial. Nerve-sparing radical prostatectomy represents the approach of choice in organ-confined disease; neoadjuvant androgen deprivation demonstrates no improvement of outcome variables. Radiation therapy should be performed with at least 72 and 78 Gy in low-risk and intermediate- to high-risk PCa, respectively. Monotherapeutic androgen deprivation is the standard of care in metastatic PCa; intermittent androgen deprivation might be an alternative treatment option for selected patients. Follow-up is largely based on prostate-specific antigen and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy with docetaxel has emerged as the reference treatment for metastatic hormone-refractory PCa. The knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.


Wearable devices for seizure detection: Practical experiences and recommendations from the Wearables for Epilepsy And Research (WEAR) International Study Group.
The Wearables for Epilepsy And Research (WEAR) International Study Group identified a set of methodology standards to guide research on wearable devices for seizure detection. We formed an international consortium of experts from clinical research, engineering, computer science, and data analytics at the beginning of 2020. The study protocols and practical experience acquired during the development of wearable research studies were discussed and analyzed during bi-weekly virtual meetings to highlight commonalities, strengths, and weaknesses, and to formulate recommendations. Seven major essential components of the experimental design were identified, and recommendations were formulated about: (1) description of study aims, (2) policies and agreements, (3) study population, (4) data collection and technical infrastructure, (5) devices, (6) reporting results, and (7) data sharing. Introducing a framework of methodology standards promotes optimal, accurate, and consistent data collection. It also guarantees that studies are generalizable and comparable, and that results can be replicated, validated, and shared.


The postoperative analgesia of retrolaminar block in patients undergoing surgery with general anesthesia: a systematic review.
Postoperative pain has always been a difficult problem in anesthesia management. The neurological block technique has been used for postoperative analgesia management, but compared with the traditional block method, the effect of postoperative analgesia after layer block is still controversial, and a clear literature review is needed. This systematic review's goal was to investigate RLB's impact on postoperative analgesia. The literature search was performed using the PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Patients aged 18 years who underwent retrolaminar block were considered eligible. The article must report the results of the original study related to postoperative analgesia. The characteristics of the study sample and evaluating the RLB for postoperative analgesia were extracted from each included article and concluded. Eleven randomized controlled trials (726 patients) were included. After summarizing the analysis of the results of RLB on changing postoperative analgesia indexes in different surgeries, we concluded that PVB is better used for postoperative analgesia compared with RLB. The analgesic effect of RLB provides advantages compared with EPSB, SCPB, etc. Based on the results of this review, RLB can be applied to thoracic surgery, abdominal surgery and parotid surgery, but its analgesic effect is not significant enough, and further research is needed in the future to provide stronger evidence for postoperative analgesia in surgical patients.


Ticks of Alabama: the fauna and spatial distribution of medically important species across the state.
The last statewide survey of hard ticks in Alabama was in 1972. To address this deficit, we examined the distribution of the medically important species across the state, Ixodes scapularis (Say), Dermacentor variabilis (Say), Amblyomma americanum (L.), and A. maculatum (Koch), between April, 2018 and February, 2021. Collections primarily involved dragging (April to July) and examination of harvested deer (November to February). A total of 2,927 ticks was collected from 110 sites; three species, I. scapularis, A. americanum, and D. variabilis, represented 91.70% of all ticks collected. Amblyomma americanum and D. variabilis were the most common species encountered in drags; I. scapularis dominated deer collections. Dermacentor variabilis was never found on deer, whereas D. albipictus was only found on deer. Stepwise regression (AIC) of drag data was linked to several site variables. Results suggest a linear response along a south (low abundance) to north (high abundance) gradient, in addition to increased abundance at sites with lower temperatures and greater precipitation and canopy cover.


[Changes in knowledge of HIV/AIDS and attitudes for PWA in Tokyo: 1992-1995].
In order to assess changes in knowledge of HIV/AIDS and attitude for People With HIV/AIDS (PWA), interview surveys (Dec. 1992, Jan. 1994, Jan. 1995) were carried out annually on random samples of the general public in Tokyo, age between 15-69 years. In total, 4,270 individuals were sampled, with an average response rate of 63.2%. Answers were scored and classified in 12 sex and age sub-groups. Additionally, correlations between scores of questions and social indices were analyzed. The results of the study are as follows: 1) The 15-19, 20-29 and 30-39 age groups showed higher scores on knowledge about HIV transmission modes. During the entire study period, the score increased in 7 groups, but decreased in 5 groups. 2) The 30-39 and 40-49 age groups showed higher scores on knowledge about HIV antibody test. During the period, the score increased in 11 groups, and among them 6 groups showed statistically significant (p < 0.05) increases. However, the score decreased in 9 groups at the third survey. 3) The 15-19, 20-29 and 30-39 age groups showed higher scores on acceptable attitudes for PWA. During the period, the score increased in all groups, and among them 3 groups showed statistically significant (p < 0.05) increases. 4) Rank correlations between two scores-knowledge quantity about the transmission modes and acceptable attitudes for PWA-were positive (0.2 < R) and statistically significant (p < 0.05) in 11 groups at the first survey, 9 groups at the second, and 6 groups at the third. 5) During the entire study period, 6 groups showed positive correlations (0.7 < R) between two changes: (1) score of knowledge about the transmission modes and (2) score of acceptable attitudes. 6) During the entire study period, 10 groups showed positive correlations (0.7 < R) between two changes: (1) score of acceptable attitudes and (2) number of newspaper articles regarding acceptance or discrimination of the PWA. 7) Knowledge about HIV/AIDS in the general public in Tokyo showed increase in younger generation, but there is concern of decrease in the older generation. These result indicate that acceptable attitude forward PWA are affected by related knowledge about the transmission modes and mass-media information, and must be considered in HIV/AIDS programs.


Effects of neonatal sympathetic denervation on amylase secretion in the adult rat parotid gland: difference in beta 1- and beta 2-adrenoceptor response.
Changes in amylase secretion and cyclic AMP accumulation in response to various secretagogues were studied in parotid glands of adult rats subjected to neonatal sympathetic denervation by unilateral excision of the superior cervical ganglion. Denervation decreased the gland content of amylase and both basal and the stimulated levels of cyclic AMP were elevated. The secretory cells of neonatally denervated glands exhibited enhanced maximal enzyme discharge in response to beta-adrenoceptor agonists. However, the selective beta 1-agonist, prenalterol was not effective in this respect whereas an enhanced maximal secretory response to the beta 2-selective agonist, terbutaline, was particularly prominent. DBcAMP was also more efficient in inducing amylase release from the denervated gland. The result of the present study demonstrate that the usual dominance of the beta 1-adrenoceptor subtype in eliciting amylase release is lost, implying that the differentiation of the beta-adrenoceptor into its subtypes is altered by neonatal sympathetic denervation.


Varying effects of different β-glucans on the maturation of porcine monocyte-derived dendritic cells.
β-Glucans are well known for their immunomodulatory capacities in humans and mice. For this reason, together with the European ban on growth-promoting antibiotics, β-glucans are intensively used in pig feed. However, as shown in the present study, there is much variation in the stimulatory capacities of β-glucans from different sources. Since dendritic cells (DCs) are the first cells that are encountered after an antigen is taken up by the intestinal epithelial cell barrier, we decided to investigate the effect of two concentrations (5 and 10 μg/ml) of five commercial β-glucan preparations, differing in structure and source, on porcine monocyte-derived dendritic cells (MoDCs). Although all β-glucans gave rise to a significant reduction of the phagocytic activity of DCs, only Macrogard induced a significant phenotypic maturation. In addition to Macrogard, zymosan, another β-glucan derived from Saccharomyces cerevisiae, and curdlan also significantly improved the T-cell-stimulatory capacity of MoDCs. Most interesting, however, is the cytokine secretion profile of curdlan-stimulated MoDCs, since only curdlan induced significant higher expression levels of interleukin-1β (IL-1β), IL-6, IL-10, and IL-12/IL-23p40. Since the cytokine profile of DCs influences the outcome of the ensuing immune response and thus may prove valuable in intestinal immunity, a careful choice is necessary when β-glucans are used as dietary supplement.


PERSPECTIVE: CHASE-AWAY SEXUAL SELECTION: ANTAGONISTIC SEDUCTION VERSUS RESISTANCE.
A model of sexual selection that leads to the evolution of exaggerated male display characters that is based on antagonistic coevolution between the sexes is described. The model is motivated by three lines of research: intersexual conflict with respect to mating, sensory exploitation, and the evolution of female resistance, as opposed to preference, for male display traits. The model generates unique predictions that permit its operation to be distinguished from other established models of sexual selection. One striking prediction is that females will frequently win the coevolutionary arms race with males, leaving them encumbered with costly ornaments that have little value except that their absence understimulates females. Examples from the literature suggest that the model may have broad application in nature. The chase-away model is a special case of the more general phenomenon of Interlocus Contest Evolution (ICE).


Infections after shoulder arthroplasty are correlated with higher anesthetic risk score: a case-control study in Brazil.
Shoulder arthroplasty (SA) has been performed by many years for the treatment of several conditions, including osteoarthritis and proximal humeral fractures following trauma. Surgical site infection (SSI) following Shoulder arthroplasty remains a challenge, contributing to increased morbidity and costs. Identification of risk factors may help implementing adequate strategies to prevent infection. We aimed to identify pre- and intra-operative risk factors associated with deep infections after Shoulder arthroplasty. An unmatched case-control study was conducted to describe the prevalence, clinical and microbiological findings, and to evaluate patient and surgical risk factors for prosthetic shoulder infection (PSI), among 158 patients who underwent SA due to any reason, at a tertiary public university institution. Risk factors for PSI was assessed by uni- and multivariate analyses using multiple logistic regression. 168 SA from 158 patients were analyzed, with an overall infection rate of 9.5% (16/168 cases). Subjects undergoing SA with American Society of Anesthesiologists (ASA) grade III or higher (odds ratio [OR]=5.30, 95% confidence interval [CI]=1.58-17.79, p<0.013) and presenting local hematoma after surgery (odds ratio [OR]=7.10, 95% confidence interval [CI]=1.09-46.09, p=0.04) had higher risk for PSI on univariate analysis. However, only ASA score grade III or higher remained significant on multivariate analysis (OR=4.74, 95% CI=1.33-16.92, p=0.016). Gram-positive cocci and Gram-negative bacilli were equally isolated in 50% of cases; however, the most commonly detected bacterium was Pseudomonas aeruginosa (18.7%). This study provides evidence suggesting that patient-related known factors such as higher ASA score predisposes to shoulder arthroplasty-associated infection. Furthermore, unusual pathogens associated with PSI were identified.


PKC activity and PKC-alpha mRNA content are reduced in serum-derived human neuroblastoma cells without concomitant induction of differentiation.
Protein kinase C (PKC) is a serine/threonine kinase which is thought to play an important role in cellular proliferation and differentiation. PKC activity is stimulated physiologically by diacylglycerol and experimentally by phorbol esters. Long-term exposure of human neuroblastoma cells to phorbol esters results in down-regulation of PKC activity and induction of neuronal differentiation. In this study, we explored the hypothesis that reduced PKC expression is necessary for differentiation of the human neuroblastoma cell line SK-N-SH. PKC activity and PKC-alpha mRNA levels were assayed in cultured SK-N-SH cells over a period of several days in the presence or absence of serum. These determinants of PKC expression were compared with several known markers of neuroblastoma differentiation, including neurite outgrowth and steady-state levels of c-myc and GAP43 mRNA. We observed steady losses of PKC activity and PKC-alpha mRNA content after transfer of cells to serum-free or chemically defined media. However, morphological and biochemical differentiation of SK-N-SH cells occurred only in chemically defined medium, perhaps due to the presence of insulin. We conclude that while loss of PKC may be associated with neuroblastoma differentiation, diminished PKC alone is not sufficient to induce or support the differentiation process.


Overproduction of collagen and diminished SOCS1 expression are causally linked in fibroblasts from idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal pulmonary disorder, and its pathology is characterized by parenchymal fibrosis. To investigate the characteristics of fibroblasts in IPF, we obtained eight fibroblast cell lines from lungs with IPF and eight lines from normal lungs. We found that the fibroblasts from IPF spontaneously produced higher amounts of type I collagen and had lower expression levels of SOCS1 than fibroblasts from normal lung. By using mouse fibroblasts, we demonstrated the causal relationship between them: the deficiency of SOCS1 in fibroblasts resulted in increased collagen production, whereas overexpression of SOCS1 suppressed collagen production. IFN-gamma suppressed spontaneous collagen production even in SOCS1-deficient fibroblasts, indicating that IFN-gamma inhibition is SOCS1-independent. In contrast, IFN-gamma suppressed the increase of collagen production induced by IL-4 in wild type fibroblasts but not SOCS1-deficient fibroblasts, suggesting IFN-gamma acted exclusively via SOCS1 in this case. Following IFN-gamma stimulation, the amount of SOCS1 mRNA expressed by IPF fibroblasts was comparable to that of normal fibroblasts. Thus, the extent of SOCS1 increase after stimulation by IFN-gamma was significantly higher in IPF fibroblasts. The extent to which IFN-gamma inhibited collagen production was also larger in IPF fibroblasts than in normal fibroblasts. These results suggest that the exaggerated production of collagen observed in fibroblasts from IPF is causally related to the diminished expression of SOCS1, and IPF fibroblasts are more susceptible to IFN-gamma because of decreased expression of SOCS1.


Superelastic Behavior of Ti-Nb Alloys Obtained by the Laser Engineered Net Shaping (LENS) Technique.
The effect of Nb content on microstructure, mechanical properties and superelasticity was investigated for a series of Ti-xNb alloys, fabricated by the laser engineered net shaping method, using elemental Ti and Nb powders. The microstructure of as-deposited materials consisted of columnar β-phase grains, elongated in the built direction. However, due to the presence of undissolved Nb particles during the deposition process, an additional heat treatment was necessary. The observed changes in mechanical properties were explained in relation to the phase constituents and deformation mechanisms. Due to the elevated oxygen content in the investigated materials (2 at.%), the specific deformation mechanisms were observed at lower Nb content in comparison to the conventionally fabricated materials. This made it possible to conclude that oxygen increases the stability of the β phase in β-Ti alloys. For the first time, superelasticity was observed in Ti-Nb-based alloys fabricated by the additive manufacturing method. The highest recoverable strain of 3% was observed in Ti-19Nb alloy as a result of high elasticity and reverse martensitic transformation stress-induced during the loading.


Solid state p-type dye-sensitized solar cells: concept, experiment and mechanism.
Solid state p-type dye-sensitized solar cells (p-ssDSCs) have been proposed and fabricated for the first time, using the organic dye P1 as the sensitizer on mesoporous NiO and phenyl-C61-butyric acid methyl ester (PCBM) as the electron conductor. The p-ssDSC has shown an impressive open circuit photovoltage of 620 mV. Femtosecond and nanosecond transient absorption spectroscopy has given evidence for sub-ps hole injection from the excited P1 to NiO, followed by electron transfer from P1˙(-) to PCBM.


Caffeinated coffee consumption, cardiovascular disease, and heart valve disease in the elderly (from the Framingham Study).
The relation between caffeinated coffee consumption and heart disease morbidity and mortality is of great interest given the extensive use of this beverage. A recent prospective epidemiologic study found a strong protective association in elderly subjects without moderate to severe hypertension in the NHANES. To test this association in the Framingham Heart Study population, in which cardiovascular risk factors and health behaviors were carefully documented, Cox regression analyses were conducted for 1,354 subjects aged 65.4 to 96.6 years at study entry. There were 210 deaths from cardiovascular disease and 118 from coronary heart disease (CHD) during 10.1 years of follow-up. A significant negative association between caffeinated coffee consumption and CHD mortality was observed for subjects with systolic blood pressure (BP) <160 mm Hg and diastolic BP <100 mm Hg. The decrease in risk of CHD mortality for any caffeinated coffee versus none was 43% (95% confidence interval 9 to 64). This decreased risk appeared to be caused primarily by an inverse prospective relation between caffeinated coffee consumption and the development or progression of heart valve disease. The decrease in risk of heart valve disease for subjects with systolic BP <160 mm Hg and diastolic BP <100 mm Hg for any caffeinated coffee versus none was 43% (95% confidence interval 4 to 66). In conclusion, caffeinated coffee consumption was associated with lower risk of CHD mortality and heart valve disease development or progression in older Framingham subjects without moderate or severe hypertension.


Low buoyant density proteoglycans from saline and dissociative extracts of embryonic chicken retinas.
Retinas were labeled in culture with [3H]glucosamine or [3H]leucine and [35S]sulfate and extracted sequentially with physiologically balanced saline and 4 M guanidine HCl. They were dialyzed into associative conditions (0.5 M NaCl) and chromatographed on agarose columns. Under these conditions, some of the proteoglycans were associated in massive complexes that showed low buoyant densities when centrifuged in CsCl density gradients under dissociative conditions (4 M guanidine HCl). Much of the label in these complexes was in molecules other than proteoglycans. Most of the proteoglycans, however, were included on the agarose columns, where they appeared to be constitutionally of low buoyant density. They resisted attempts to separate potential low buoyant density contaminants from the major proteoglycans by direct CsCl density gradient centrifugation or by the fractionation of saline or 8 M urea extracts on diethylaminoethyl-Sephacel. The diethylaminoethyl-Sephacel fractions were either subjected to CsCl density gradient centrifugation or were chromatographed on Sephacryl S-300, in both cases before and after alkaline cleavage, to confirm the presence of typical O-linked glycosaminoglycans. The medium and balanced salt extracts were enriched in chondroitin sulfate and other sulfated macromolecules, possibly highly sulfated oligosaccharides, that resisted digestion by chondroitinase ABC but were electrophoretically less mobile than heparan sulfate. Guanidine HCl or urea extracts of the residues were mixtures of high and low density proteoglycans that were enriched in heparan sulfate.


Prolonged expression of lipopolysaccharide (LPS)-induced inflammatory genes in whole blood requires continual exposure to LPS.
Blood-borne lipopolysaccharide (LPS) is thought to be a major inducer of sepsis; however, it remains controversial whether an ongoing exposure to LPS is required to maintain the underlying systemic inflammatory response. To address this question, we have studied the expression of tumor necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL-1 beta), and the procoagulant protein tissue factor induced by LPS ex vivo in whole human blood. The addition of a 1-ng/ml bolus of LPS to blood rapidly induced mRNA expression of all three genes. The mRNA levels peaked after 1 to 2 h, depending on the gene, and then declined to baseline after approximately 5 h. The decline in mRNA expression was not caused by a loss of responsiveness of the blood cells to LPS but rather correlated with the neutralization of LPS inflammatory activity by plasma components. Furthermore, administering a 1-ng/ml dose of LPS in six hourly aliquots of 167 pg/ml greatly prolonged the expression of mRNAs and induced a much greater release of TNF-alpha and IL-1 beta protein than did a single bolus. Dosing by repeated additions was more effective than a single bolus in inducing secretion of TNF-alpha and IL-1 beta at LPS levels of < or = 10 ng/ml, which corresponded to the LPS neutralization capacity of plasma. Finally, both mRNA expression and protein secretion induced by repeated administration of LPS were rapidly reversed by the addition of the LPS-neutralizing protein, bactericidal/permeability-increasing protein, even after several hours of stimulation. These results indicate that continuous or repeated exposure to LPS is required to maintain the expression of inflammatory genes and that the activated state is rapidly reversed with LPS neutralization.


The association of household food security, household characteristics and school environment with obesity status among off-reserve First Nations and Métis children and youth in Canada: results from the 2012 Aboriginal Peoples Survey.
Indigenous children are twice as likely to be classified as obese and three times as likely to experience household food insecurity when compared with non- Indigenous Canadian children. The purpose of this study was to explore the relationship between food insecurity and weight status among Métis and off-reserve First Nations children and youth across Canada. We obtained data on children and youth aged 6 to 17 years (n = 6900) from the 2012 Aboriginal Peoples Survey. We tested bivariate relationships using Pearson chi-square tests and used nested binary logistic regressions to examine the food insecurity-weight status relationship, after controlling for geography, household and school characteristics and cultural factors. Approximately 22% of Métis and First Nations children and youth were overweight, and 15% were classified as obese. Over 80% of the sample was reported as food secure, 9% experienced low food security and 7% were severely food insecure. Off-reserve Indigenous children and youth from households with very low food security were at higher risk of overweight or obese status; however, this excess risk was not independent of household socioeconomic status, and was reduced by controlling for household income, adjusted for household size. Negative school environment was also a significant predictor of obesity risk, independent of demographic, household and geographic factors. Both food insecurity and obesity were prevalent among the Indigenous groups studied, and our results suggest that a large proportion of children and youth who are food insecure are also overweight or obese. This study reinforces the importance of including social determinants of health, such as income, school environment and geography, in programs or policies targeting child obesity.


Permissive underfeeding: its appropriateness in patients with obesity, patients on parenteral nutrition, and non-obese patients receiving enteral nutrition.
The concept of permissive underfeeding is based on the rationale that higher nutrient intake is detrimental from a metabolic and functional perspective. Animal studies have demonstrated improved morbidity and mortality with energy restriction. Studies with obese patients have demonstrated that a hypocaloric feeding regimen can promote nitrogen equilibrium and minimize negative nitrogen balance without causing weight loss. In critically ill patients, permissive underfeeding with parenteral nutrition has not been well studied, although some benefit is apparent. In enterally fed patients, more research exists but the data are not generated from prospective controlled trials. Studies of enterally supported patients demonstrate an association between higher caloric intake and decreased morbidity and mortality. Despite limited research, provision of reduced energy intake in critically ill patients and obese patients may result in improved metabolic control, reduce the detrimental effects of overfeeding, and promote improved patient outcomes.


Recognising and responding to communication and swallowing difficulties in Parkinson's disease.
Communication difficulties, including hypokinetic dysarthria and swallowing difficulties (dysphagia), affect a large percentage of people diagnosed with Parkinson's disease. Onset of these symptoms has been identified in up to 78% of people with early-stage Parkinson's disease. Communication difficulties are frequently disregarded until they have a significant impact on quality of life, while the person may often be unaware of indicators of dysphagia and the associated risk of aspiration pneumonia. The aim of this article is to increase awareness of the importance of identifying and addressing the communication and swallowing difficulties experienced by people living with Parkinson's disease. Early identification, regular review and monitoring enable the clinician to support the implementation of evidence-based, effective interventions. Collaboration with the multidisciplinary team, including speech pathology, is needed to enable the person to live well with Parkinson's disease and to prevent aspiration pneumonia, a leading cause of death in Parkinson's disease. A vignette prepared in collaboration with a person living with Parkinson's disease and his wife provides an 'insider perspective' of the pervasive impact of difficulties with communication and swallowing.


Structural and functional analogue of the active site of polysulfide reductase from Wolinella succinogenes.
Synthesis of [PPh4]2[Mo(SPh)2(S2C2(CN)2)2] (2) from [PPh4]2[MoO(S2C2(CN)2)2] (1) has been achieved to mimic the postulated [Mo(S)6] core of polysulfide reductase with two thiolates and two bis(ene-dithiolate) ligands. Compound 2 reacts with polysulfide to yield H2S, modeling the function of polysulfide reductase. The facile conversion of 2 back to 1 in moist solvent suggests that the interconversion of the [MoIV = O] and [MoIV - X] (X = O-Ser, S-Cys, Se-Cys) moieties might occur in the DMSO reductase class of enzymes under appropriate hydrophobic/hydrophilic conditions.


A dilemma of fibrous dysplasia versus chronic osteomyelitis of the clavicle.
An 11-year-old child presented to the emergency department in 2005 with episodes of pain in his right clavicle. No history of trauma was noted and he was systemically well with no clinical signs of acute inflammation. He was extensively investigated and a diagnosis of fibrous dysplasia of the right clavicle was reached on histology. He developed periodic relapses of pain in the clavicle. He has been followed up since 2005, his most recent follow-up being in November 2011. The clinical dilemma of fibrous dysplasia versus chronic osteomyelitis is illustrated by highlighting this case.


Pharmacokinetics and bioequivalence study of two brands of loxoprofen tablets in healthy volunteers.
The aims of this study were to assess the pharmacokinetics and bioequivalence of two brands of loxoprofen (CAS 80832-23-6) 60 mg tablets in healthy male volunteers. The several pharmacokinetic parameters were evaluated after an oral administration after an overnight fast according to a single dose, two-sequence, and cross-over randomized design with a 1-week washout interval. Serial blood samples were collected throughout 10 h after administration of the reference and test drug. Plasma was analyzed by validated HPLC with UV detection. Several pharmacokinetic parameters, including AUC(infnity), AUC(t), C(max), T(max), T1/2, and Ke were determined from blood concentrations of both formulations. AUC(t), AUC(infinity) and C(max) were evaluated for bioequivalence after log-transformation of data using ANOVA with 90% confidence interval level. The parametric 90% confidence intervals of AUC(t), AUC(infinity), and C(max) were 90.13-106.34%, 91.43-106.94%, and 91.17-108.53%, respectively. All of the tested parameters were within the acceptable range of 80-125%. Based on these statistical considerations, it was concluded that the test drug was bioequivalent to the reference drug.


In vivo imaging of epileptic foci in rats using a miniature probe integrating diffuse optical tomography and electroencephalographic source localization.
The goal of this work is to establish a new dual-modal brain-mapping technique based on diffuse optical tomography (DOT) and electroencephalographic source localization (ESL) that can chronically/intracranially record optical/electroencephalography (EEG) data to precisely map seizures and localize the seizure-onset zone and associated epileptic brain network. The dual-modal imaging system was employed to image seizures in an experimental acute bicuculline methiodide rat model of focal epilepsy. Depth information derived from DOT was used as constraint in ESL to enhance the image reconstruction. Groups of animals were compared based on localization of seizure foci, either at different positions or at different depths. This novel imaging technique successfully localized the seizure-onset zone in rat induced by bicuculline methiodide injected at a depth of 1, 2, and 3 mm, respectively. The results demonstrated that the incorporation of the depth information from DOT into the ESL image reconstruction resulted in more accurate and reliable ESL images. Although the ESL images showed a horizontal shift of the source localization, the DOT identified the seizure focus accurately. In one case, when the bicuculline methiodide (BMI) was injected at a site outside the field of view (FOV) of the DOT/ESL interface, ESL gave false-positive detection of the focus, while DOT showed negative detection. This study represents the first to identify seizure-onset zone using implantable DOT. In addition, the combination of DOT/ESL has never been documented in neuroscience and epilepsy imaging. This technology will enable us to precisely measure the neural activity and hemodynamic response at exactly the same tissue site and at both cortical and subcortical levels.


Consequences of the electronic tuning of latent ruthenium-based olefin metathesis catalysts on their reactivity.
Two ruthenium olefin metathesis initiators featuring electronically modified quinoline-based chelating carbene ligands are introduced. Their reactivity in RCM and ROMP reactions was tested and the results were compared to those obtained with the parent unsubstituted compound. The studied complexes are very stable at high temperatures up to 140 °C. The placement of an electron-withdrawing functionality translates into an enhanced activity in RCM. While electronically modified precatalysts, which exist predominantly in the trans-dichloro configuration, gave mostly the RCM and a minor amount of the cycloisomerization product, the unmodified congener, which preferentially exists as its cis-dichloro isomer, shows a switched reactivity. The position of the equilibrium between the cis- and the trans-dichloro species was found to be the crucial factor governing the reactivity of the complexes.


Advanced Practice Nurse-Led Statewide Collaborative to Reduce Falls in Hospitals.
Thirty-eight hospitals participated in falls prevention team training, followed by coaching and mentoring over 3 months to develop unit-based initiatives to reduce falls. Initiatives centered on fall risk assessment, rounding, or postfall assessment. Paired t test of the pre-/postintervention fall rates of 23 of the hospitals revealed reduced fall rates (P < .01). The estimated mean decrease was 1.7 falls per 1000 patient days (95% confidence limits of 0.7-2.7).


[Use of intra-stromal corneal ring segments (INTACS) in refractive surgery].
Implantation of intrastromal corneal rings segments is a new refractive procedure. INTACS consists of 2 separate segments placed in the midperipheral cornea, in specially preparing lamellar channels. Polymethylo methacrylate rings, which flatter the anterior curvature of the cornea. The peripheral localization of these rings leaves the central cornea untouched. The 2 main advantages of the INTACS are, that it preserves the corneal center and is removable. Segments serve for the reduction of myopia from -1.00 D to -5.00 D. The refractive correction is modulated by INTACS thickness, which ranged from 0.25 to 0.45 mm.


Propagation of Astrovirus VA1, a Neurotropic Human Astrovirus, in Cell Culture.
Astrovirus VA1/HMO-C (VA1; mamastrovirus 9) is a recently discovered astrovirus genotype that is divergent from the classic human astroviruses (mamastrovirus 1). The gastrointestinal tract is presumed to be the primary site of infection and pathogenicity for astroviruses. However, VA1 has been independently detected in brain tissue of five cases of human encephalitis. Studies of the pathogenicity of VA1 are currently impossible because there are no reported cell culture systems or in vivo models that support VA1 infection. Here, we describe successful propagation of VA1 in multiple human cell lines. The initial inoculum, a filtered clinical stool sample from the index gastroenteritis case cluster that led to the discovery of VA1, was first passaged in Vero cells. Serial blind passage in Caco-2 cells yielded increasing copies of VA1 RNA, and multistep growth curves demonstrated a >100-fold increase in VA1 RNA 72 h after inoculation. The full-length genomic and subgenomic RNA strands were detected by Northern blotting, and crystalline lattices of viral particles of ∼26-nm diameter were observed by electron microscopy in infected Caco-2 cells. Unlike other human astrovirus cell culture systems, which require addition of exogenous trypsin for continued propagation, VA1 could be propagated equally well with or without the addition of trypsin. Furthermore, VA1 was sensitive to the type I interferon (IFN-I) response, as VA1 RNA levels were reduced by pretreatment of Caco-2 cells with IFN-β1a. The ability to propagate VA1 in cell culture will facilitate studies of the neurotropism and neuropathogenesis of VA1.IMPORTANCE Astroviruses are an emerging cause of central nervous system infections in mammals, and astrovirus VA1/HMO-C is the most prevalent astrovirus in cases of human encephalitis. This virus has not been previously propagated, preventing elucidation of the biology of this virus. We describe the first cell culture system for VA1, a key step necessary for the study of its ability to cause disease.