Evaluating Mediterranean diet adherence in university student populations: Does this dietary pattern affect students' academic performance and mental health?
Adherence to a healthy diet such as Mediterranean Diet (MD) may exert beneficial effects in university students, promoting their academic performance and quality of life, as well as their mental and physical health status. In this aspect, the present study aimed to critically analyze the current epidemiological evidence concerning MD adherence of university students' populations. PubMed database was comprehensively searched, using relative keywords. Students' dietary habits are moving away from MD guidelines towards unhealthy eating patterns, especially for those living away from home and even for students with a Mediterranean country origin. Most of the available studies have documented that poorer students' health status was associated with lower MD adherence. Higher MD adherence was correlated with lower depression risk, while higher perceived stress score with lower fruit and vegetables intake. The access of students to information and knowledge provided by courses and lectures did not effectively enhance their compliance to MD. Alarmingly enough, the majority of students, even from medical and nutritional university departments, showed inadequate knowledge on healthy eating habits. Due to the influence of diet on the quality of life and the mental and physical health of students, it is crucial to redirect research focus on this important aspect.


WNT10A gene is the second molecular candidate in a cohort of young Italian subjects with ectodermal derivative impairment (EDI).
Ectodermal dysplasias are a group of genetic disorders defined by ectodermal derivative impairment (EDI). To test the impact of the Wnt/beta-catenin pathway in the genetic screening of EDI, we performed a molecular gene study of WNT10A in 60 subjects from a population of 133 young Italian patients referred for the impairment of at least one major ectodermal-derived structure and who had a previous negative molecular screen for ectodysplasin signaling pathway genes ED1, EDAR, and EDARADD. Fourteen WNT10A mutations were identified in 33 subjects (24.8%), 11 of which were novel variants. The phenotype was evaluated through a detailed clinical examination of the major and minor ectodermal-derived structures. This study is the first to show that, after ED1, WNT10A is the second molecular candidate for EDI in a large Italian Caucasian population. The study confirmed that Phe228Ile is the most frequent WNT10A variant in Caucasian populations, and that WNT10A mutations are associated with large variability in EDI.


The role of lead as an environmental pollutant in the period of growing ecological consciousness.
On the basis of the monitoring measurement results of Kraków's environment a long-time evaluation has been presented, with regard to lead presence. The pollution with lead in a last few years was displayed in atmospheric air, soil and drinking water samples, as well as in some vegetables and food products. It was concluded that a characteristic trend regarding lead pollution of the environment could be observed; a decrease of lead level in air and in vegetables was presented, in soil and milk as well as in dairy products--remained low. Only in lettuce and parsley leaves the exceeding of the permissible lead content was confirmed. At present, in spite of the decrease of the heavy metals level in the environment, lead is still present and the health hazard to men exists, but to a lesser degree.


Regulation of aminopeptidase A expression in cervical carcinoma: role of tumor-stromal interaction and vascular endothelial growth factor.
We previously demonstrated that aminopeptidase A (APA), a membrane-bound metallopeptidase degrading bioactive peptides such as angiotensin II (Ang II), is expressed in neoplastic lesions of the uterine cervix, and that its expression is upregulated as the lesion progresses from cervical intraepithelial neoplasms (CIN) toward invasive squamous cell carcinomas (SCC). The present study investigated the regulatory mechanisms involved in APA expression and its potential role in cervical carcinoma. Immunohistochemical staining in high-grade CIN and SCC tissues showed that APA was strongly expressed at the edge of lesions adjacent to cervical stromal cells. Fluorescence-activated cell sorting analysis demonstrated that cell surface APA expression was extremely low in three human SCC cell lines, SiHa, TCS and CaSki, under basal conditions. However, both contact and noncontact cocultures with human cervical fibroblasts resulted in the induction of APA expression in these SCC cells. APA expression was also induced in vivo when TCS cells were subcutaneously inoculated into nude mice. Furthermore, APA expression and enzymatic activity were enhanced by addition of the conditioned medium (CM) from fibroblast culture, but not by heat-treated CM. Among the various cytokines tested, vascular endothelial growth factor (VEGF) significantly increased APA activity, and induction of APA by the fibroblast CM was partly inhibited by anti-VEGF neutralizing antibody. Finally, APA cDNA-transfected APA-overexpressing TCS cells significantly reduced the Ang II-induced cell invasion ability as compared with parental or control vector-transfected TCS cells, although there was no significant difference in cellular proliferation among them. These results suggested the importance of tumor-stromal interaction for the regulation of APA expression in the microenvironment of cervical carcinoma and the potential role for this peptidase in regulating tumor invasion through inactivation of Ang II activity.


Analysis of HFMD Transmissibility Among the Whole Population and Age Groups in a Large City of China.
Hand-Foot-and-Mouth-Disease (HFMD) has been widely spread in Asia, and has result in a high disease burden for children in many countries. However, the dissemination characteristics intergroup and between different age groups are still not clear. In this study, we aim to analyze the differences in the transmissibility of HFMD, in the whole population and among age groups in Shenzhen city, by utilizing mathematical models. A database that reports HFMD cases in Shenzhen city from January 2010 to December 2017 was collected. In the first stage, a Susceptive-Infected-Recovered (SIR) model was built to fit data of Shenzhen city and its districts, and Reff was used to assess transmissibility in each district. In the second stage, a cross-age groups SIR model was constructed to calculate the difference in transmissibility of reported cases among three age groups of EV71 virus: 0-3 years, 3-5 years, and over 5 years which was denoted as age group 1, 2, and 3, respectively. From 2010 to 2017, 345,807 cases of HFMD were reported in Shenzhen city, with peak incidence in spring and autumn in Shenzhen city and most of its districts each year. Analysis of the EV71 incidence data by age group revealed that age Group 1 have the highest incidence (3.13 ×10-7-2.31 ×10-4) while age group 3 had the lowest incidence (0-3.54 ×10-5). The differences in weekly incidence of EV71 between age groups were statistically significant (t12 = 7.563, P < 0.0001; t23 = 12.420, P < 0.0001; t13 = 16.996, P < 0.0001). The R2 of the SIR model Shenzhen city population-wide HFMD fit for each region was >0.5, and P < 0.001. Reff values were >1 for the vast majority of time and regions, indicating that the HFMD virus has the ability to spread in Shenzhen city over the long-term. Differences in Reff values between regions were judged by using analysis of variance (ANOVA) (F = 0.541, P = 0.744). SiIiRi-SjIjRj models between age groups had R2 over 0.7 for all age groups and P <0.001. The Reff values between groups show that the 0-2 years old group had the strongest transmissibility (median: 2.881, range: 0.017-9.897), followed by the over 5 years old group (median: 1.758, range: 1.005-5.279), while the 3-5 years old group (median: 1.300, range: 0.005-1.005) had the weakest transmissibility of the three groups. Intra-group transmissibility was strongest in the 0-2 years age group (median: 1.787, range: 0-9.146), followed by Group 1 to Group 2 (median: 0.287, range: 0-1.988) and finally Group 1 to Group 3 (median: 0.287, range: 0-1.988). The incidence rate of HFMD is high in Shenzhen city. In the data on the incidence of EV71 in each age group, the highest incidence was in the 0-2 years age group, and the lowest incidence was in the over 5 years age group. The differences in weekly incidence rate of EV71 among age groups were statistically significant. Children with the age of 0-2 years had the highest transmissibility.


What learners and teachers value most in ambulatory educational encounters: a prospective, qualitative study.
To determine what learners and teachers value most in ambulatory learning encounters and whether the choices of the two groups are in concordance. In 1996, the authors surveyed learners and teachers at a walk-in clinic immediately after each of 103 consecutive learning encounters. The participants answered two open-ended questions: (1) What was the one most valuable aspect of this learning encounter? and (2) List one thing that would make it better. Using qualitative analysis methods, two raters categorized the responses; their agreement was substantial (kappa = .75). Half the responses fit five categories: diagnosis (15%), general management (14%), physical examination skills (9%), patient selection (6%), and time issues (6%). The participants most valued general exposure to diagnosis (29%) and general management issues (29%). Regarding their suggestions for improving the encounters, 33% cited structural issues (often "more time"), while 43% had no suggestions ("nothing" or "fine as is"). Substantial concordance existed between the rankings by category of the teachers' and learners' comments, but (1) learners were more likely to rate the educational value of the encounter excellent or very good (64% vs 47%, p < .01); (2) teachers were more likely than medical students (but not interns) to place the most educational value on the physical examination (30% vs 4%, p = .001); and (3) agreement on what was most valuable in any individual encounter was poor (kappa = .03). In evaluating ambulatory educational encounters, learners and teachers placed highest value on general exposure to diagnosis and disease management; while the most commonly recommended changes related to structural issues, particularly inadequate time. While learners and teachers agreed in general on the relative ranking of teaching activities, they often found different things to be educationally salient in a particular encounter.


Effects of exogenous vitamin E supplementation on the levels of oxidants and antioxidants in chronic obstructive pulmonary disease.
Oxidative stress has been recognized as a central feature of smoke induced chronic obstructive pulmonary disease (COPD). Imbalance between oxidant and antioxidant enzymes is also an established fact in these patients. But studies in regard to stable COPD patients and effect of vitamin E supplementation are lacking. Thirty patients with COPD were included in the study. Their baseline clinical examination, spirometry, plasma malondialdehyde (MDA), alpha-tocopherol and red blood cell superoxide dismutase (SOD) levels were mea sured. Twenty healthy non-smokers who were matched for age and sex served as controls. All the above parameters were repeated after 12 weeks of supplementation with 400 IU of vitamin E daily. The mean malondialdehyde levels in the patients at baseline were higher than controls (5.91 +/- 1.23 nmol/ml vs 4.55 +/- 1.51 nmol/ml, P = 0 001), so also was plasma alpha-tocopherol levels (P < 0 001), while SOD levels were lower in the patients compared to controls (1692 +/- 259 units g/Hb vs 2451 +/- 131 units g/Hb, P < 0 001). Exogenous vitamin E (400 IU per day) supplementation did not bring about any significant change in plasma alpha-tocopherol and SOD levels. The Pearson s co-efficient of correlation between the levels of MDA, vitamin E, SOD; and spirometric measurements were not significant either on day 1 or after 12 weeks of vitamin E supplementation. The present study shows that initially the plasma lipid peroxide (MDA) levels are high and antioxidants (alpha-tocopherol and SOD) are low in patients with COPD. Exogenous supplementation with vitamin E does not have any significant effect on the spirometric measurements though it brings down the levels of MDA showing attenuation of further damage. However, inclusion of larger number of patients and supple mentation with vitamin E for longer periods may throw more light on free radical injury and protective effects of antioxidants.


Drug delivery and transport to solid tumors.
The purpose of this review is to provide an overview of the principles of and barriers to drug transport and delivery to solid tumors. This review consists of four parts. Part I provides an overview of the differences in the vasculature in normal and tumor tissues, and the relationship between tumor vasculature and drug transport. Part II describes the determinants of transport of drugs and particles across tumor vasculature into surrounding tumor tissues. Part III discusses the determinants and barriers of drug transport, accumulation, and retention in tumors. Part IV summarizes the experimental approaches used to enhance drug delivery and transport in solid tumors. Drug delivery to solid tumors consists of multiple processes, including transport via blood vessels, transvascular transport, and transport through interstitial spaces. These processes are dynamic and change with time and tumor properties and are affected by multiple physicochemical factors of a drug, multiple tumor biologic factors, and as a consequence of drug treatments. The biologic factors, in turn, have opposing effects on one or more processes in the delivery of drugs to solid tumors. The effectiveness of cancer therapy depends in part on adequate delivery of the therapeutic agents to tumor cells. A better understanding of the processes and contribution of these factors governing drug delivery may lead to new cancer therapeutic strategies.


Attachment anxiety is related to Epstein-Barr virus latency.
Attachment theory provides a framework for understanding individual differences in chronic interpersonal stress. Attachment anxiety, a type of relationship insecurity characterized by worry about rejection and abandonment, is a chronic interpersonal stressor. Stress impacts cellular immunity, including herpesvirus reactivation. We investigated whether attachment anxiety was related to the expression of a latent herpesvirus, Epstein-Barr virus (EBV), when individuals were being tested for breast or colon cancer and approximately 1 year later. Participants (N=183) completed a standard attachment questionnaire and provided blood to assess EBV viral capsid antigen (VCA) IgG antibody titers. Individuals with more attachment anxiety had higher EBV VCA IgG antibody titers than those with less attachment anxiety. The strength of the association between attachment anxiety and antibody titers was the same at both assessments. This study is the first to show an association between latent herpesvirus reactivation and attachment anxiety. Because elevated herpesvirus antibody titers reflect poorer cellular immune system control over the latent virus, these data suggest that high attachment anxiety is associated with cellular immune dysregulation.


Restoration of partially edentulous patients using dental implants with a microtextured surface: a prospective comparison of delayed and immediate full occlusal loading.
The aim of this study was to determine the clinical effectiveness of placing dental implants with microtextured surfaces into full occlusal loading at the time of placement in partially edentulous patients. Two demographically similar groups of 14 patients each were treated with a total of 92 Spline Twist Implants (Centerpulse Dental, Carlsbad, CA). Test implants were placed into immediate full occlusal loading, and control implants were restored using a conventional delayed loading procedure. Otherwise, both groups of patients received similar therapy from the same treatment team. Radiographs, periodontal indices, and Periotest values were recorded every 6 months during routine clinical follow-up appointments. The mean loading time for all prostheses was 24 months at the time of this report. No implants failed in the test group, and 1 implant failed before loading in the control group. Cumulative implant success was 98.9% for all implants placed (test group = 100%; control group = 92.9%). Periodontal measurements indicated no significant clinical differences between implants placed into immediate full occlusal loading and those loaded via a conventional delayed protocol. Immediate full occlusal loading of partial prostheses supported by microtextured implants in partially edentulous patients demonstrated excellent clinical results, with no adverse periodontal effects after 24 months of function. Additional follow-up will provide invaluable information on the long-term effects of this technique. Immediate full occlusal loading of partial prostheses supported by microtextured implants can be successfully achieved for 24 months in highly motivated patients with excellent oral hygiene.


Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver.
Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. In mouse liver, at human-equivalence (therapeutic) doses, dose-dependent loss of intercellular hepatic TJ-associated ZO-1 protein expression was evident with progressive clinical signs of liver injury. Temporal, dose-dependent and specific disruption of the TJ-associated ZO-1 and cytoskeletal-F-actin proteins, correlated with modulation of hepatic ultrastructure. Real-time impedance biosensing verified in vitro early, dose-dependent quantitative decreases in TJ and cell-substrate adhesions. Whereas treatment with NAPQI, the reactive metabolite of acetaminophen, or the PKCα-activator and TJ-disruptor phorbol-12-myristate-13-acetate, similarly reduced TJ integrity, which may implicate oxidative stress and the PKC pathway in TJ destabilization. These findings are relevant to the clinical presentation of acetaminophen-hepatotoxicity and may inform future mechanistic studies to identify specific molecular targets and pathways that may be altered in acetaminophen-induced hepatic depolarization.


The Methyltransferase Smyd1 Mediates LPS-Triggered Up-Regulation of IL-6 in Endothelial Cells.
The lysine methyltransferase Smyd1 with its characteristic catalytic SET-domain is highly enriched in the embryonic heart and skeletal muscles, participating in cardiomyogenesis, sarcomere assembly and chromatin remodeling. Recently, significant Smyd1 levels were discovered in endothelial cells (ECs) that responded to inflammatory cytokines. Based on these biochemical properties, we hypothesized that Smyd1 is involved in inflammation-triggered signaling in ECs and therefore, investigated its role within the LPS-induced signaling cascade. Human endothelial cells (HUVECs and EA.hy926 cells) responded to LPS stimulation with higher intrinsic Smyd1 expression. By transfection with expression vectors containing gene inserts encoding either intact Smyd1, a catalytically inactive Smyd1-mutant or Smyd1-specific siRNAs, we show that Smyd1 contributes to LPS-triggered expression and secretion of IL-6 in EA.hy926 cells. Further molecular analysis revealed this process to be based on two signaling pathways: Smyd1 increased the activity of NF-κB and promoted the trimethylation of lysine-4 of histone-3 (H3K4me3) within the IL-6 promoter, as shown by ChIP-RT-qPCR combined with IL-6-promoter-driven luciferase reporter gene assays. In summary, our experimental analysis revealed that LPS-binding to ECs leads to the up-regulation of Smyd1 expression to transduce the signal for IL-6 up-regulation via activation of the established NF-κB pathway as well as via epigenetic trimethylation of H3K4.


Hyaluronic acid modulates proliferation of mouse dermal fibroblasts in culture.
When the concentration of hyaluronic acid was monitored in primary cultures of mouse skin dermal fibroblasts, there was an increase in hyaluronic acid proportional to the increase in cell number during the logarithmic growth phase. The concentration reached the maximum value 2 days before the cells became confluent, and then decreased gradually. Hyaluronic acid added at 1 mg ml-1 during the logarithmic phase either promoted or inhibited cell growth, depending on the density of cells at the time when hyaluronic acid was added. Hyaluronic acid (1 mg ml-1) added to subconfluent or postconfluent cultures induced a transient DNA synthesis with a consequent increase (greater than 20%) in cell number. The effects appeared to be specific, since neither hyaluronic acid oligosaccharides nor some other types of glycosaminoglycan (chondroitin, chondroitin sulphates, heparan sulphates and heparin) had any similar effects. Dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP), at 1 mM, added to subconfluent or postconfluent cultures had promoting effects successively on hyaluronic acid synthesis and on cell growth. An increase in hyaluronic acid synthesis also occurred when dbcAMP was added to day 1 cultures in the logarithmic growth phase, but the effect on cell growth was reversed; there was an inhibition rather than a promotion. The pattern of cell density-dependent variation of the dbcAMP effect is quite similar to that observed with exogenously added hyaluronic acid. Therefore, we propose that hyaluronic acid added exogenously or supplied endogenously by increased synthesis may act as a modulator of mouse dermal fibroblast proliferation.


Emergency orthopaedic surgery in the pandemic era: A case series at Cipto Mangunkusumo national tertiary hospital in Jakarta, Indonesia.
Every emergency surgery performed is aimed at saving lives; however, during COVID-19 pandemic, surgeries are often postponed. Many existing recommendations take into account postponing surgery during a pandemic. How these surgeries can lead to increasing infection rates has not been widely published. This study aims to investigate the relationship of emergency orthopaedic surgery and the incidence rate of COVID-19. This was a case series of 14 patients. The study was performed at the emergency department unit at a national tertiary hospital in Jakarta, Indonesia. A total of 14 patients underwent orthopaedic surgery in the emergency room of our institution. The mean age of the subjects was 40.07 ± 20.5 years. Twelve (85.7%) were male patients and 2 (14.3%) were female patients. The average duration of surgery was 125 minutes. The most used type of anaesthesia was general anaesthesia for 6 operations (50%). Patients were hospitalized for an average length of 4 days. Three patients had infiltrates found on plain x-ray examination, which required further examination to determine whether the cause was COVID-19 infection or not. There was no ground glass appearance (GGO) in the three patients in further follow-up examination. We found that emergency orthopaedic surgery was not associated with increasing number of COVID-19 cases. Factors including duration of surgery, length of stay, types of anaesthesia and comorbidities were also not associated with COVID-19 cases in this study.


Aquatic ecosystems: effects of solar ultraviolet radiation and interactions with other climatic change factors.
Aquatic ecosystems are a key component of the Earth's biosphere. A large number of studies document substantial impact of solar UV radiation on individual species, yet considerable uncertainty remains with respect to assessing impacts on ecosystems. Several studies indicate that the impact of increased UV radiation appears relatively low when considering overall ecosystem response, while, in contrast, effects on individual species show considerable responses. Ecosystem response to climate variability incorporates both synergistic and antagonistic processes with respect to UV-related effects, significantly complicating understanding and prediction at the ecosystem level. The impact of climate variability on UV-related effects often becomes manifest via indirect effects such as reduction in sea ice, changes in water column bio-optical characteristics, changes in cloud cover and shifts in oceanographic biogeochemical provinces.


Gene deletions correlate with the development of alloantibodies in von Willebrand disease.
Among all patients with von Willebrand disease (vWD), alloantibodies to von Willebrand factor (vWF) have been described only in severe vWD (type III). The relationship between the development of alloantibodies and the nature of the genetic lesion in vWD is not known. In hemophilia B, large deletions within the factor IX gene appear to correlate with the occurrence of alloantibodies, whereas in hemophilia A no such correlation is apparent. We have studied 19 patients with severe recessive vWD (type III) and 19 with autosomal dominant vWD (type I) by Southern blotting with probes encompassing the full 9 kilobases (kb) of the vWF cDNA. Two apparently unrelated patients were shown to have large deletions within the vWF gene. Both patients had severe vWD (type III) and were the only patients among those studied that had inhibitory alloantibodies to vWF. The extent of deletion was similar in both patients, corresponding to at least the 3'-7.4 kb of the vWF cDNA. The deletion in each patient was estimated to exceed 110 kb. In addition, the localization of the vWF gene to chromosome 12 was confirmed, and a homologous sequence on chromosome 22 was identified.


Wearable Proximity Sensors for Monitoring a Mass Casualty Incident Exercise: Feasibility Study.
Over the past several decades, naturally occurring and man-made mass casualty incidents (MCIs) have increased in frequency and number worldwide. To test the impact of such events on medical resources, simulations can provide a safe, controlled setting while replicating the chaotic environment typical of an actual disaster. A standardized method to collect and analyze data from mass casualty exercises is needed to assess preparedness and performance of the health care staff involved. In this study, we aimed to assess the feasibility of using wearable proximity sensors to measure proximity events during an MCI simulation. In the first instance, our objective was to demonstrate how proximity sensors can collect spatial and temporal information about the interactions between medical staff and patients during an MCI exercise in a quasi-autonomous way. In addition, we assessed how the deployment of this technology could help improve future simulations by analyzing the flow of patients in the hospital. Data were obtained and collected through the deployment of wearable proximity sensors during an MCI functional exercise. The scenario included 2 areas: the accident site and the Advanced Medical Post, and the exercise lasted 3 hours. A total of 238 participants were involved in the exercise and classified in categories according to their role: 14 medical doctors, 16 nurses, 134 victims, 47 Emergency Medical Services staff members, and 27 health care assistants and other hospital support staff. Each victim was assigned a score related to the severity of his/her injury. Each participant wore a proximity sensor, and in addition, 30 fixed devices were placed in the field hospital. The contact networks show a heterogeneous distribution of the cumulative time spent in proximity by the participants. We obtained contact matrices based on the cumulative time spent in proximity between the victims and rescuers. Our results showed that the time spent in proximity by the health care teams with the victims is related to the severity of the patient's injury. The analysis of patients' flow showed that the presence of patients in the rooms of the hospital is consistent with the triage code and diagnosis, and no obvious bottlenecks were found. Our study shows the feasibility of the use of wearable sensors for tracking close contacts among individuals during an MCI simulation. It represents, to our knowledge, the first example of unsupervised data collection-ie, without the need for the involvement of observers, which could compromise the realism of the exercise-of face-to-face contacts during an MCI exercise. Moreover, by permitting detailed data collection about the simulation, such as data related to the flow of patients in the hospital, such deployment provides highly relevant input for the improvement of MCI resource allocation and management.


Clinical and field studies of human lactation: methodological considerations.
A variety of studies has been completed to assess selected methods that are presently being used or might potentially be used to evaluate lactation performance. During 64 test-weighings of infants before and after the consumption of a known amount of milk, the mean +/- SD "recovery" of milk ingestion was 94.9 +/- 13.2%. The weight of milk extracted by a mechanical pump was approximately 7% greater than the amount measured during test-weighings of infant of the same women within periods of 1 wk. To evaluate the possibility of performing abbreviated studies in field settings, the proportion of 24-h milk consumption received during 12 daytime hours was measured by test-weighings. Daytime consumption ranged from 46 to 58% of 24-h consumption (mean +/- SD = 52 +/- 3%). Attempts to predict the amount of milk consumption during 341 daytime studies from the age of infants and their frequency and duration of feedings met with limited success. Although each independent variable was significantly correlated with the amount consumed (multiple r = 0.69, p less than 0.001), the SE of the estimate (Sy.x) was relatively large. The effects of time of day and side of extraction on the volume and composition of extracted milk were determined during 24-h studies of seven women. There were significant changes in the concentration of fat (p less than 0.001) and nitrogen (p = 0.003) during the day and significant differences in the concentrations of fat (p = 0.04) and lactose (p = 0.04) and in the volume (p less than 0.001) of milk produced by each breast. The importance of these findings for the planning and interpretation of studies of human lactation is discussed.


Neural mechanisms of the mood effects on third-party responses to injustice after unfair experiences.
Behavioral decision theory argues that humans can adjust their third-party responses (e.g., punishment and compensation) to injustice by integrating unfair experiences. Typically, the mood plays an important role in such a decision-making process. However, the underlying neurocognitive bases remain largely unclear. We first employ a modified third-party justice game in which an allocator split an amount of money between oneself and a receiver. The participants can reapportion the money as observers by choosing from the following three costly options: compensate the receiver, accept the current allocation, or punish the allocator. Then, a second-party pseudo interaction is conducted where participants receive more (i.e., advantageous unfair experience) or less (i.e., disadvantageous unfair experience) than others. Finally, participants perform the third-party justice game again after unfair experiences. Here, we use functional near-infrared spectroscopy (fNIRS) to measure participants' brain activities during third-party responses to injustice. We find participants compensate more to the receiver after advantageous unfair experience, which involved enhanced positive emotion, weakened sense of unfairness, and is linked with increased activity in the right dorsolateral prefrontal cortex (rDLPFC). In contrast, participants punish more on the allocator after disadvantageous unfair experience, which might primarily stem from their negative emotional responses, strong sense of unfairness, and is associated with significantly decreased activity in the rDLPFC. Our results suggest that third-party compensation and punishment involved differential psychological and neural bases. Our findings highlight the crucial roles of second-party unfair experiences and the corresponding mood responses in third-party responses to unfairness, and unravel the intermediate neural architecture.


Clinical and epidemiological features of 15 incidents of severe infectious bovine rhinotracheitis.
Fifteen incidents of infectious bovine rhinotracheitis (IBR) were studied in herds distributed widely throughout northern Britain. Fattening beef animals (10 outbreaks), dairy cattle (four outbreaks) and suckler beef cows (one outbreak) were affected and all bar one incident occurred in housed cattle during the winter. The first signs of illness noticed were a reduced appetite, dullness, coughing and oculonasal discharge. In 13 of the incidents they were observed in cattle purchased from a market within the previous four weeks. In every outbreak, affected animals developed a serous nasal discharge which became purulent in severe cases. In the early stages the nasal mucosa was congested but later yellow-brown diphtheritic plaques developed. In such animals halitosis was always detected. Soft coughing was frequently heard but pneumonia was rarely confirmed ante mortem. Conjunctivitis and ocular discharge were a major finding in 13 incidents and, in severely affected cases, conjunctival oedema was seen. The drooling of saliva was noticed in 14 incidents but congestion of the oral mucous membranes was the only abnormality found on examination of the oral cavity. Diarrhoea was a consistent feature in one outbreak. As a result of contracting this disease beef cattle failed to put on weight for a period of one to eight weeks and the milk yield of lactating dairy cattle decreased markedly. The morbidity rate was high, being more than 90 per cent in 10 incidents. The mortality rate varied considerably but 7 to 8 per cent of the animals died, or were culled, in three outbreaks. The clinical signs were most severe on intensive units with a high turnover of cattle.


Analysis of aqueous glue coating proteins on the silk fibers of the cob weaver, Latrodectus hesperus.
Elucidation of the molecular composition and physical properties of spider glue is necessary to understand its function in the mechanics of the web and prey capture. Previous reports have indicated that components of the adhesive coating contain inorganic molecules, phosphorylated glycoproteins, lipids, and organic low-molecular mass (LMM) compounds. Using a proteomic strategy, we have investigated the viscid, aqueous components that coat different silk fiber types from the black widow spider, Latrodectus hesperus. After in-solution tryptic digestion of the aqueous protein material extracted from egg case sacs, gumfooted lines, and the web scaffolding connection joints, followed by peptide analysis using MALDI tandem TOF mass spectrometry, we demonstrate that these fibers are coated with common peptides. Utilizing a reverse genetics approach, we have isolated the cDNAs encoding two distinct fiber coating products, which we have named spider coating peptide 1 and 2 (SCP-1 and SCP-2). Secreted forms of SCP-1 and SCP-2 contain 36 and 19 amino acids, respectively, and their primary sequences display no significant similarities to ensemble repeat units from traditional fibroins. Quantitative real-time reverse transcription PCR analyses show that these mRNAs are chiefly produced by the aggregate gland. Biochemical studies also demonstrate that the SCP-1 peptide has intrinsic metal binding properties, suggesting a role of peptide-metal ion interactions with the fiber constituents to enhance thread performance. Collectively, these investigations are the first to reveal a novel role for the aggregate gland in the production of peptides that coat spider silk threads.


The Daunting Career of the Physician-Investigator.
For many years, physician-investigators have had a particularly difficult time with their academic careers, so that they have been labeled an endangered species. In this Invited Commentary, the author defines three career paths for physician-investigators-clinical researcher, clinician-scientist, and physician-scientist. Each of these pathways has common and distinct challenges that should be studied and potential improvements that should be evaluated through pilot research projects.The first challenge that all physician-investigators face is securing funding. Physicians are funded by their clinical activities, which often lures physician-investigators to increase their clinical work, particularly when research funding from the National Institutes of Health is difficult to secure and seemingly arbitrarily granted. The second challenge is an appointments, promotion, and tenure system that is not responsive to the needs of faculty working across clinical care and research, particularly when it comes to evaluating team science. Physician-investigators not working full-time in either discipline then may have trouble being promoted. The third challenge is the increasing burdens of clinical activities, particularly with the advent of electronic medical records.In this issue, two articles address overcoming the challenges faced by physician-investigators, one from the National Institutes of Health to grow the workforce and the other to offer organizational and individual solutions to support these investigators in faculty roles. These solutions are encouraging, but data about the extent of the challenges and the potential effects of the solutions are needed to make the physician-investigator career path less daunting.


Identification of spread after deliberated intraneural injection in five mammalian species: not all animal models and needle types are valid for studying the effect of intraneural injections in humans.
This research endeavors to investigate the phenomenon of intraneural spread across distinct locations: subcircumneurium, extrafascicular intraneural, intrafascicular intraneural, and intraperineurium after deliberate intraneural injections across five mammalian species. The study also aims to propose determinants influencing this spread. Furthermore, the investigation strives to ascertain the optimal animal species and needle configuration for extrapolating intraneural injection outcomes to human contexts. This study examined 60 sciatic nerves from 30 fresh and untreated cadavers of rats, rabbits, dogs, pigs, and sheep. The specimens were organized into five groups, each comprising an equal number of nerves. Histological assessments were performed on 30 nerves, involving fascicle metrics. The remaining 30 nerves underwent intentional intraneural injections, facilitated by 19G and 23G needles under ultrasound and direct visualization guidance.Heparinized erythrocytes combined with a methylene blue solution were used as a marker to analyze the extent and patterns of intraneural spread. Needle orifice measurements were obtained, and these data were overlaid onto images of both nerves and needles. This enabled a comparative evaluation of sizes and an assessment of marker diffusion. The findings indicated that sciatic nerves in rats, rabbits, and dogs were oligofascicular, characterized by larger fascicles, whereas pigs and sheep exhibited polyfascicular nerves comprised of numerous smaller fascicles. Fascicular diameters were variable across species, with dogs presenting the largest measurements. While intraneural spread was observed and documented, intrafascicular marker spreading was rare, occurring only in one rabbit specimen. Needle orifice attributes were scrutinized and visually depicted. Despite the formidable challenges associated with the practical realization of intrafascicular injection, the utilization of animal models possessing monofascicular or oligofascicular nerves, such as rats, rabbits, and dogs, in conjunction with needles featuring aperture dimensions surpassing those of the fascicles, likely contributes to the compromised reliability of investigations into intraneural injection outcomes.


Molecular mechanisms of axonal damage in inflammatory central nervous system diseases.
Axonal dysfunction and damage is an early pathological sign of autoimmune central nervous system disease, viral and bacterial infections, and brain trauma. Axonal injury has attracted considerable interest during the past few years because the degree of axonal damage appears to determine long-term clinical outcome. Advanced magnetic resonance spectroscopic imaging techniques have suggested that axonal loss and dysfunction is responsible for the persistent neurological deficits that occur in patients with multiple sclerosis. Histopathological methods have shown that axonal damage is defined primarily by dysfunction of axonal transport, and finally by complete transection and degeneration of axons. Recent studies have demonstrated that the extent of axonal damage in the primary demyelinating lesion of multiple sclerosis patients is associated with the number of activated microglia/macrophages and cytotoxic CD8+ T lymphocytes. In addition, diffuse axonal dysfunction independent of demyelination develops in normal appearing white matter, possibly due to indirect effects of inflammation. The fact that axonal damage in response to overt inflammatory reactions may occur gradually, leaving a window for therapeutical intervention, has important clinical implications. Determination of the exact molecular mechanism might help in finding new therapies for inflammatory axonal damage.


Mother-to-child transmission of HIV-1: advances and controversies of the twentieth centuries.
Mother-to-child transmission (MTCT) is the overwhelming source of HIV-1 infection in young children. According to the World Health Organization (WHO), during the year 2003, despite effective antiretroviral (ARV) therapy, there were approximately 700,000 new infections in children worldwide, the majority of whom were from resource-limited countries. Alternative protocols to the long-course and complex regimens of ARV drugs, which in high-income countries have almost eradicated HIV MTCT, have been shown to reduce early transmission rates by 38-50%. However, the accumulation of drug resistance and the long-term toxicities of ARVs mean that alternative approaches need to be developed. Furthermore, transmission via breastfeeding, which accounts for one third of all transmission events, can reduce the benefits of short-course therapies given to women for the prevention of MTCT. The complex mechanisms and determinants of HIV-1 MTCT and its prevention in the different routes of transmission are still not completely understood. Despite the large contribution that many international agencies have made during the past 10-15 years in support of observational and intervention trials, as well as basic scientific research, HIV-1 MTCT intervention trials and basic research often are not integrated, leading to the generation of a fragmented picture. Maternal RNA levels, CD4+ T-cell counts, mode of delivery and gestational age were shown to be independent factors associated with transmission. However, these markers are only partial surrogates and cannot be used as absolute predictors of MTCT of HIV-1. Studies on the role of viral characteristics, immune response and host genomic polymorphisms did not always achieve conclusive results. Although CCR5-using viruses are preferentially carried by HIV-1 infected women as well as transmitted to their infants, the 32-basepair deletion of the CCR5 gene was not shown to influence perinatal MTCT. X4 viruses are apparently hampered in MTCT, although transmission of syncytium-inducing (SI) viruses, which use CXCR4, can occur when the mother carries such virus. Recently, there has been evidence of multiple virus variant transmission during peripartum MTCT. If viral escape from cytotoxic T-lymphocyte (CTL) recognition was repeatedly detected in transmitting mothers, no conclusive results were obtained on the role of the humoral immune response. The hypothesis on the mechanisms of selection during MTCT are still an open question, and include possibly that the transmitted variant is derived from a variant in the mother that escaped immune response, or that transmission is a stochastic event with the random transmission of a limited number of viral variants, or otherwise that selection occurs in the infant through a replication advantage of some transmitted viral variants. Although global access to ARV therapy certainly remains the primary goal to achieve the immediate reduction of MTCT of HIV-1, it is also evident that new and additional innovative strategies are needed.


Retinal vessel circulation patterns visualized from a sequence of computer-aligned angiograms.
To present a computer method that can be used to combine the images from a sequence of fluorescein angiograms of the retinal microcirculation so that a composite image can be generated and a color image illustrating circulation at all points in the vascular network can be computed. This should enable more accurate comparison of retinal vascular occlusions that occur during cardiopulmonary bypass surgery. Photographic negatives of the macular region from two angiographic sequences, one taken before surgery and the other taken just before the end of bypass, were digitized, background shade corrected, and registered. Composite images were generated as minimum projection images and the filling images generated from parameters of a smooth curve fit to the filling data at every point. The composite images showed a filling pattern that more accurately reflected the maximum fluorescence at every point than any single image. The images generated from the filling data provide a new way to visualize and quantify changes in the retinal circulation. The technique demonstrates that problems arising from selection of a single frame from a filling sequence can be overcome by combining images. The technique used to generate the color-coded filling image should prove useful for any image sequence in which differential filling is of interest.


Physical interpretation of polarization-encoded images by color preview.
In the framework of Stokes parameters imaging, polarizationencoded images have four channels which makes physical interpretation of such multidimensional structures hard to grasp at once. Furthermore, the information content is intricately combined in the parameters channels which involve the need for a proper tool that allows the analysis and understanding this kind of images. In this paper we address the problem of analyzing polarization-encoded images and explore the potential of this information for classification issues and propose ad hoc color displays as an aid to the interpretation of physical properties content. The color representation schemes introduced hereafter employ a technique that uses novel Poincaré Sphere to color spaces mapping coupled with a segmentation map as an a <ital>priori</ital> information in order to allow, at best, a distribution of the information in the appropriate color space. The segmentation process relies on the fuzzy C-means clustering algorithms family where the used distances were redefined in relation with our images specificities. Local histogram equalization is applied to each class in order to bring out the intra-class's information smooth variations. The proposed methods are applied and validated with Stokes images of biological tissues.


Increasing Diagnostic Uncertainties in Children With In Utero HIV Infection.
We present a case of an in utero HIV-infected child, who on day 1 of life had a positive whole blood total nucleic acid test but viral load <20 RNA copies/mL. Dried blood spot total nucleic acid testing was negative on day 1, 10 and at 3 months, while on ART prophylaxis then positive at 5 months after prophylaxis ended. Retrospective peripheral blood mononuclear cells HIV DNA testing from day 1 of life was positive, confirming in utero infection.


Collaborative and specialized functions of Robo1 and Robo2 in spinal commissural axon guidance.
Commissural neurons project axons across the floor plate at the spinal cord ventral midline. After crossing, commissural axons turn rostrally, sort into distinct positions within the ventrolateral funiculus, and never reenter the floor plate. Robo1 and Robo2 are receptors for the midline repellents Slit1-Slit3, and upregulation of Robos in post-crossing axons allows expulsion from the floor plate and prevents recrossing. Before crossing, Robo-mediated repulsion is attenuated by the divergent family member Robo3/Rig-1. To define the relative contributions of Robo family members to commissural axon guidance in mice, we studied commissural axon trajectories in combination mutants between Robo1, Robo2, and Robo3. Our results suggest the existence of another receptor contributing to Slit repulsion because the failure of midline crossing in Robo3 mutants is rescued largely but not entirely by loss of both Robo1 and Robo2 and because axon guidance defects in mice lacking both Robo1 and Robo2 are less severe than in mice lacking all Slits. Analysis of post-crossing axon trajectories indicates that Robo1 and Robo2 collaborate to prevent axons from reentering the gray matter and projecting dorsally alongside contralateral pre-crossing axons. We also discovered a previously unappreciated division of labor between Robo1 and Robo2 in post-crossing axons. Robo2 is required for axons to project away from the floor plate into the lateral funiculus. In contrast, Robo1 prevents axonal stalling after crossing. Our results reveal specialized and complementary actions of Robo1 and Robo2 in commissural axon guidance and suggest the existence of an as yet unidentified Slit receptor.


Personality differences between patients with lichen simplex chronicus and normal population: A study of pruritus.
Itching is common to many skin disorders. The relationship between skin disease and psychological variables has been widely documented in the literature. The association between the exacerbation of skin lesions and increased levels of psychopathological conditions in response to stressful events has also been described. Lichen Simplex Chronicus (LSC) is a skin disorder characterized by itching, which seems to have a marked psychological component. However, examples of empirical evidence linking this skin disorder to personality variables, as measured by standardized personality questionnaires, are relatively few so far. The objective of this research was to investigate the involvement of certain personality variables in the development of LSC. The personality profiles of 60 patients with LSC were compared to a normative sample of the normal Spanish population, who were free of any kind of skin disease. The personality variables for the LSC group were obtained by administering the Millon Index of Personality Styles (MIPS). Participants with LSC presented personality characteristics that differed from the control group. The most significant variables were as follows: greater tendency to pain-avoidance, greater dependency on other peoples' desires, and more conforming and dutiful compared to the control group. Results are discussed in the light of other dermatological pathologies that might share some characteristics with LSC subjects. Lichen simplex chronicus patients may present differential personality characteristics that could be related to triggering and exacerbating skin lesions. Therefore, it is relevant to evaluate the personality profiles of these people to increase treatment efficiency.


Level of secreted HMGB1 correlates with severity of inflammation in chronic rhinosinusitis.
High mobility group box 1 (HMGB1) protein is a chromatin protein that functions as a proinflammatory cytokine when secreted in response to inflammatory stimuli. The purpose of this study was to determine the relationship between the HMGB1 level in nasal secretions and the severity of inflammation in chronic rhinosinusitis. This was a cross-sectional study. Nasal secretions were obtained by irrigation of the affected sinonasal cavities with normal saline. Total 63 nasal lavage fluid samples were collected from 38 patients with chronic rhinosinusitis who underwent endoscopic sinus surgery. Levels of HMGB1 and tumor necrosis factor alpha, interleukin (IL)-1β, and IL-8 were determined by enzyme-linked immunoassay. Severity of inflammation was assessed by the Lund-Mackay scoring system, which is based on preoperative computed tomography scans. Concurrent medical disorders, presence of nasal polyps, septal deviation, and allergic rhinitis were also investigated. The level of HMGB1 in nasal lavage fluid was positively correlated with the Lund-Mackay score. The score was the only factor associated with HMGB1 by univariate and multivariate analysis. Other cytokines, with the exception of IL-8, were not correlated with the Lund-Mackay score. Our results showed that HMGB1 is secreted into the extracellular area space in the upper airway, and HMGB1 levels in nasal lavage fluid correlate with severity of inflammation, as assessed by the Lund-Mackay staging system for chronic rhinosinusitis. These results provide evidence for HMGB1 as an inflammatory mediator associated with the severity of chronic rhinosinusitis.


Quadratus Lumborum Block Reduces Postoperative Opioid Consumption and Decreases Persistent Postoperative Pain Severity in Patients Undergoing Both Open and Laparoscopic Nephrectomies-A Randomized Controlled Trial.
New regional techniques can improve pain management after nephrectomy. This study was a randomized controlled trial conducted at two teaching hospitals. Patients undergoing elective open and laparoscopic nephrectomy were eligible to participate in the trial. A total of 100 patients were divided into a quadratus lumborum block (QLB) group (50 patients) and a control (CON) group (50 patients). At the end of surgery, but while still under general anesthesia, unilateral QLB with ropivacaine was performed on the side of nephrectomy for patients in the QLB group. The main measured outcome of this study was oxycodone consumption via a patient-controlled anesthesia (PCA) pump during the first 24 h following surgery; other measured outcomes included postoperative pain intensity assessment, patient satisfaction with pain management, and persistent pain evaluation. Patients undergoing QLB needed less oxycodone than those in the CON group (34.5 mg (interquartile range 23 to 40 mg) vs. 47.5 mg (35-50 mg); p < 0.001). No difference between the groups was seen in postoperative pain intensity measured on the visual analog scale, except for the evaluation at hour 2, which was in favor of the QLB group (p = 0.03). Patients who received QLB were more satisfied with postoperative pain management than the CON group. Persistent postoperative pain was assessed with the Neuropathic Pain Symptom Inventory (NPSI) at months 1, 3, and 6, and was found to be significantly lower in the QLB group at each evaluation (p < 0.001). We also analyzed the impact of the surgery type on persistent pain severity, which was significantly lower after laparoscopic procedures than open procedures at months 1, 3, and 6. QLB reduces oxycodone consumption in patients undergoing open and laparoscopic nephrectomy and decreases persistent pain severity months after hospital discharge.


Wideband spherically focused PVDF acoustic sources for calibration of ultrasound hydrophone probes.
Several broadband sources have been developed for the purpose of calibrating hydrophones. The specific configuration described is intended for the calibration of hydrophones In a frequency range of 1 to 40 MHz. All devices used 25 /spl mu/m film of PVDF bonded to a matched backing. Two had radii of curvatures (ROC) of 25.4 and 127 mm with f numbers of 3.8 and 19, respectively. Their active element diameter was 0.28 in (6.60 mm). The active diameter of the third source used was 25 mm, and it had an ROC of 254 mm and an f number of 10. The use of a focused element minimized frequency-dependent diffraction effects, resulting in a smooth variation of acoustic pressure at the focus from 1 to 40 MHz. Also, using a focused PVDF source permitted calibrations above 20 MHz without resorting to harmonic generation via nonlinear propagation.


Application of tetranucleotide frequencies for the assignment of genomic fragments.
A basic problem of the metagenomic approach in microbial ecology is the assignment of genomic fragments to a certain species or taxonomic group, when suitable marker genes are absent. Currently, the (G + C)-content together with phylogenetic information and codon adaptation for functional genes is mostly used to assess the relationship of different fragments. These methods, however, can produce ambiguous results. In order to evaluate sequence-based methods for fragment identification, we extensively compared (G + C)-contents and tetranucleotide usage patterns of 9054 fosmid-sized genomic fragments generated in silico from 118 completely sequenced bacterial genomes (40 982 931 fragment pairs were compared in total). The results of this systematic study show that the discriminatory power of correlations of tetranucleotide-derived z-scores is by far superior to that of differences in (G + C)-content and provides reasonable assignment probabilities when applied to metagenome libraries of small diversity. Using six fully sequenced fosmid inserts from a metagenomic analysis of microbial consortia mediating the anaerobic oxidation of methane (AOM), we demonstrate that discrimination based on tetranucleotide-derived z-score correlations was consistent with corresponding data from 16S ribosomal RNA sequence analysis and allowed us to discriminate between fosmid inserts that were indistinguishable with respect to their (G + C)-contents.


A novel and efficient approach to high-throughput production of HLA-E/peptide monomer for T-cell epitope screening.
Over the past two decades, there has been a great interest in the study of HLA-E-restricted αβ T cells during bacterial and viral infections, including recently SARS-CoV-2 infection. Phenotyping of these specific HLA-E-restricted T cells requires new tools such as tetramers for rapid cell staining or sorting, as well as for the identification of new peptides capable to bind to the HLA-E pocket. To this aim, we have developed an optimal photosensitive peptide to generate stable HLA-E/pUV complexes allowing high-throughput production of new HLA-E/peptide complexes by peptide exchange. We characterized the UV exchange by ELISA and improved the peptide exchange readout using size exclusion chromatography. This novel approach for complex quantification is indeed very important to perform tetramerization of MHC/peptide complexes with the high quality required for detection of specific T cells. Our approach allows the rapid screening of peptides capable of binding to the non-classical human HLA-E allele, paving the way for the development of new therapeutic approaches based on the detection of HLA-E-restricted T cells.


Prairie rattlesnake envenomation in 27 New World camelids.
Morbidity and case fatality from rattlesnake envenomation is regionally specific because of variability in relative toxicity of the species of snake encountered. A previous report of rattlesnake envenomation in New World camelids (NWC) from the western coastal United States documented high case fatality rates and guarded prognosis for survival. To describe clinical findings, treatments, and outcome of NWC with prairie rattlesnake (Crotalus viridis viridis) envenomation in the Rocky Mountain region of the United States. Twenty-seven NWC admitted to the Colorado State University Veterinary Teaching Hospital for evaluation of acute rattlesnake envenomation between 1992 and 2012. Medical records of NWC evaluated for rattlesnake envenomation as coded by the attending clinician and identified by a database search were reviewed retrospectively. Month of admission, signalment, area of bite, clinical and clinicopathologic data, treatments, and outcome were recorded. Twenty-five llamas and 2 alpacas were admitted for envenomation. Llamas were overrepresented compared to hospital caseload. The face was the most common site of envenomation, observed in 96% of recorded cases. Presenting clinical signs included fever, tachypnea, tachycardia, and respiratory distress. Nine animals required a tracheotomy. Median hospitalization time was 3 days and overall survival rate was 69%. Case fatality rate for prairie rattlesnake envenomation in NWC was lower than that reported in the Western coastal region of the United States and similar to that reported for prairie rattlesnake envenomation in horses.


Trauma Exposure and Domestic Violence Offending Severity in a Probation Sample From Post-conflict Northern Ireland.
Domestic violence is more common in post-conflict settings such as Northern Ireland. However, the extent to which trauma and related mental health problems are associated with domestic violence perpetration in the region has not yet been quantitatively assessed. The present study examines relationships between multiple traumas, mental health problems, and five indicators of domestic violence perpetration severity (causing injury, use of a weapon, breach of nonmolestation order, sexual violence, and previous police involvement). The unique risk associated with distinct types of trauma (i.e., childhood maltreatment or conflict related) was also investigated. Perpetrators' case file data (n = 405) were analyzed using hierarchical logistic regression. The rates of recorded trauma exposure and mental health difficulties were 72.3% and 63.5%, respectively. The first logistic regression analyses showed that exposure to multiple traumas was associated with increased likelihood of perpetrating injurious and sexual violence, when controlling for the covariates (odds ratios [ORs] = 1.24-1.28). The second logistic regression analyses showed that childhood maltreatment was the only trauma type to confer unique risk, a relationship that was significant only for the outcome of perpetrating injurious violence (OR = 3.06). Substance misuse was also significantly associated with perpetration of injurious violence, use of weapons, and having past police involvement (ORs = 2.49-3.50). The accumulation of traumatic experiences and substance abuse appear to act as risk factors for some indicators of offending severity. Childhood maltreatment appears to confer particularly strong risk. The findings may support a focus on trauma and substance abuse as intervention targets in post-conflict settings.


Adverse competition-related cognitions questionnaire (ACCQ): Development and preliminary validation of a measure identifying different factors of athletes' cognitions related to competitions.
This research project presents the development and preliminary validation of a German version of the Adverse Competition-related Cognitions Questionnaire (ACCQ) and comprises four studies. In Study 1, 101 athletes and 124 coaches from different team and individual sports generated a large pool of cognitions, which was reduced to an initial item pool of 54 cognitions through a multi-step procedure with different experts. In Study 2, the underlying factor structure of the questionnaire was examined by an exploratory factor analysis (N2 = 348), which revealed six factors (athletic comparison, coach devaluation, devaluation of one's own performance, appreciation by coach and family, inner resistance against competitions, and general exhaustion) with 26 items retained. Subsequently, in Study 3, the results were re-examined with a confirmatory factor analysis (CFA, N3 = 419; CFI = 0.91, RMSEA = 0.06, SRMR = 0.06). In addition, preliminary support for the construct validity (i.e., convergent, divergent, and concurrent validity) of the ACCQ was obtained by examining associations among the ACCQ subscales and theoretical correlates such as social comparison, cognitive interference, irrational performance beliefs, and fear of negative evaluation. In Study 4, a second CFA (N4 = 153; CFI = 0.89, RMSEA = 0.06, SRMR = 0.07) was conducted to test the identified 6-factor solution in a sample of high-performance competitive athletes. With its broad range of factors, the ACCQ provides a useful and valid measure for assessing different adverse competition-related cognitions, offering a wide range of potential applications in research and sport psychology practice.


Substance use and community violence: a test of the relation at the daily level.
Prior research has consistently demonstrated an association between substance use and involvement in violence among individuals with mental illness. Yet little is known about the temporal quality of this relationship, largely because longitudinal data required to address this issue are not readily available. This study examined the relationship between substance use (alcohol, marijuana, and other drug use) and violence at the daily level within a sample of mentally ill individuals at high risk for frequent involvement in violence (N = 132). Results support the serial nature of substance use and violence, with an increased likelihood of violence on days following the use of alcohol or multiple drugs, but not the inverse relationship. Implications for the utility of substance use as a risk marker for the assessment of future violence are discussed.


Concentration and pH dependency of alpha-methyldopa absorption in rat intestine.
The intestinal absorption of alpha-methyldopa from perfused segments of rat intestine was determined. Jejunal and ileal segments were studied at pH 4.5, 6.0 and 7.4 at an alpha-methyldopa concentration of 0.01 mM, and at pH 6.0 at concentrations of 0.01, 0.10 and 10 mM. Intestinal absorption was found to depend on both concentration and pH but not on segment. A weak positive correlation (r = 0.5) was observed between net water absorption and alpha-methyldopa absorption, similar to that observed for amino acids. The low intestinal wall permeability of alpha-methyldopa under normal intestinal pH conditions (pH 7.4) is consistent with the incomplete oral bioavailability of this drug.


Endothelin-1-induced placental and fetal growth restriction in the rat.
The objective of this study was to evaluate the effect of increased circulating endothelin on fetal and placental growth in the rat. Indwelling arterial and venous catheters were placed on day 14 of a 22-day gestation in timed-pregnant Sprague-Dawley rats. Saline, 0.2 nmol/kg/h endothelin, or 0.5 nmol/kg/h endothelin was continuously infused from day 15 through 21 in randomly assigned animals (n = 12 in each group). Maternal arterial blood pressure and serum endothelin levels were evaluated on days 15, 18, and 21 of gestation. On day 21, pregnancy outcome data including fetal and placental weights, litter size, and the occurrence of stillbirths were ascertained, and fetal blood was obtained for serum endothelin levels. All data were compared among the three groups, and statistical significance was determined by analysis of variance. Endothelin infusion resulted in a dose-dependent decrease in fetal and placental weights when compared to saline-treated pregnancies. A significant increase in maternal arterial blood pressure was noted only in the 0.5 nmol/kg/h endothelin group. Fetal and placental growth restriction occurred in the absence of maternal hypertension in the 0.2 nmol/kg/h group. These results demonstrate that endothelin infusion causes restriction of fetal and placental growth, even in the absence of maternal hypertension.


[Acute pancreatitis and malabsorption with tetany secondary to Crohn's disease with duodenal involvement].
Involvement of the duodenum in Crohn's disease is uncommon, and the pathomechanism of the associated acute pancreatitis remains controversial. We describe a case of Crohn's disease with duodenal involvement associated with hyperamylasemia and malabsorption showing a favorable response to steroid treatment.


Acute mountain sickness impact among travelers to Cusco, Peru.
Increasing numbers of travelers are visiting high altitude locations in the Andes. The epidemiology of acute mountain sickness (AMS) among tourists to high altitude in South America is not well understood. A cross-sectional study to evaluate the epidemiology, pre-travel preparation, and impact of AMS among travelers to Cusco, Peru (3,400 m) was performed at Cusco's International Airport during June 2010. Foreign travelers, 18 years or older, staying 15 days or less, departing Cusco were invited to participate. Demographic, itinerary, and behavioral data were collected. The Lake Louise Clinical score (LLCS) was used to assess AMS symptoms. In total, 991 travelers participated, median age 32 years (interquartile range 25-49), 55.5% female, 86.7% tourists, mostly from the United States (48.2%) and England (8.1%). Most (76.7%) flew from sea level to Cusco and 30.5% visited high altitude in the previous 2 months. Only 29.1% received AMS advice from a physician, 19% recalled advice on acetazolamide. Coca leaf products (62.8%) were used more often than acetazolamide (16.6%) for prevention. AMS was reported by 48.5% and 17.1% had severe AMS. One in five travelers with AMS altered their travel plans. Travelers older than 60 years, with recent high altitude exposure, who visited lower cities in their itinerary, or used acetazolamide were less likely to have AMS. Using coca leaf products was associated with increased AMS frequency. AMS was common and adversely impacted plans of one in five travelers. Acetazolamide was associated with decreased AMS but was prescribed infrequently. Other preventive measures were not associated with a decrease in AMS in this population. Pre-travel preparation was suboptimal.


Direct methods for the determination of lead in whole blood by anodic stripping voltammetry.
Two methods for the direct determination of lead in whole blood by anodic stripping voltammetry (ASV) are described. The procedure in both methods involved the mixing of micro blood samples with a metal releasing reagent, Metexchange, and electrochemical analysis using carbon electrodes. A multiple Anodic Stripping Analyzer equipped with composite graphite mercury electrodes and a Charge Transfer Analyzer equipped with a mercury film electrode were employed. The standard addition method was used to minimize the matrix effects of whole blood. The ASV results correlated well with those obtained by flameless atomic absorption analysis. The methods are simple, reliable, and suitable for applications in the clinical field. The procedure using the Charge Transfer Analyzer is recommended because of its sensitivity and rapidity.


Decreased GDNF mRNA expression in dorsal spinal cord of unilateral arthritic rat.
It is now well established that nerve growth factor (NGF) plays a key role in inflammation-induced hyperalgesia. It was also reported that brain derived neurotrophic factor (BDNF), another member of neurotrophins, contributed to the pain pathway as a neurotransmitter in the CNS. The present work demonstrated a down-regulation of glial cell line-derived neurotrophic factor (GDNF) mRNA expression in dorsal spinal cord in complete Freund's adjuvant-induced unilateral arthritic rats serving as a chronic pain model. The fast occurring and long lasting down-regulations suggest that GDNF might contribute to pain pathway in a way different from neurotrophins and might play a role in the maintenance of chronic pain status.


"Ciliophagy": The consumption of cilia components by autophagy.
Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) associated with respiratory epithelial cell cilia shortening and impaired mucociliary clearance (MCC). The underlying cellular and molecular mechanisms for CS-associated cilia shortening have remained incompletely understood. We have previously demonstrated increased autophagy in the lungs of COPD patients; however, whether or not this process is selective for specific autophagic targets in the lung was not elucidated. Based on observations that increased morphological and biochemical indicators of autophagy correlate with cilia shortening in our models, we posited that autophagy might regulate cilia length in response to CS in the lung. We demonstrate that CS-induced cilia shortening occurs through an autophagy-dependent mechanism mediated by the deacetylase HDAC6 (histone deacetylase 6). Autophagy-impaired (Becn1(+/-), map1lc3b(-/-), or Hdac6(-/Y)) mice resist CS-induced cilia shortening. Furthermore, cilia components are identified as autophagic substrates during CS exposure. Assessment of airway cilia function using a 3D MCC assay demonstrates that Becn1(+/-), map1lc3b(-/-), and Hdac6(-/Y) mice or mice injected with the HDAC6 inhibitor tubastatin A are protected from CS-associated mucociliary dysfunction. We concluded that an autophagy-dependent pathway regulates cilia length during CS exposure, which identifies new pathways and targets in COPD.


Paternally transmitted FMR1 alleles are less stable than maternally transmitted alleles in the common and intermediate size range.
Fragile X syndrome, a form of X-linked mental retardation, results from the hyperexpansion of a CGG trinucleotide repeat located in the 5' untranslated region of the fragile X mental retardation (FMR1) gene. Relatively little is known about the initial mutation that causes a stable allele to become unstable and, eventually, to expand to the full mutation. In the present study, we have examined 1,452 parent-child transmissions of alleles of common (< or =39 repeats) or intermediate (40-59 repeats) sizes to study the initial mutation events. Of these, 201 have been sequenced and haplotyped. Using logistic regression analysis, we found that parental origin of transmission, repeat size (for unsequenced alleles), and number of the 3' CGGs (for sequenced alleles) were significant risk factors for repeat instability. Interestingly, transmission of the repeat through males was less stable than that through females, at the common- and intermediate-size level. This pattern differs from that seen for premutation-size alleles: paternally transmitted alleles are far more stable than maternally transmitted alleles. This difference that depends on repeat size suggests either a different mutational mechanism of instability or an increase in selection against sperm as their repeat size increases.


[Evolution of prostate cancer brachytherapy].
Curietherapy, more commonly named brachytherapy, is one of the oldest irradiation techniques used for prostate cancer. Prostate brachytherapy evolved according to the scientific and technological progress. After a historical reminder of the evolution of prostate brachytherapy, different technical aspects are discussed: low-dose rate brachytherapy using permanent or temporary implants, high-dose rate brachytherapy as well as new imaging modalities. Prostate brachytherapy indications are listed regarding to the evidence-based medicine data for low, intermediate and high risks prostate cancers. Potential indications and new research programs (focal therapy, high-dose rate, single-dose brachytherapy) are also presented.


The Peer Context of Dieting: The Relationship between Young Adults' Dieting Frequency and Their Friends' Weight-Related Characteristics.
Previous research found that weight-related behaviors and body weight tends to be similar between individuals and peers. Rather little is known how different domains of weight-related behaviors co-evolve in peer networks. Hence, this study explores how young adults' self-reported dieting relates to perceived body weight and weight control behaviors of their peers. A Swedish two-wave panel survey with ego-centric network data was analyzed with negative binomial regression models. Nineteen-year-old men and women in the first wave, and 23-year-olds in the follow-up sample were examined. Men at age 19 showed an increased dieting propensity when being exposed to underweight peers. Compared to men, women's dieting at age 19 was more strongly related to their own body image concerns, and peers' weight-related behaviors like physical exercising and unhealthy eating. The associations between dieting and peers' weight-related characteristics for men and women deteriorated from age 19 to age 23. The findings suggest that women's dieting-in comparison to dieting in men-is more strongly related to the peer context. The decrease in associations between men's and women's dieting and peers' weight-related characteristics from age 19 to age 23 may reflect a weakened importance of the peer context in early adulthood.


Aflatoxin B1: metabolism, toxicology, and its involvement in oxidative stress and cancer development.
Aflatoxins are a class of carcinogenic mycotoxins produced by Aspergillus fungi, which are widely distributed in nature. Aflatoxin B1 (AFB1) is the most toxic of these compounds and its metabolites have a variety of biological activities, including acute toxicity, teratogenicity, mutagenicity and carcinogenicity, which has been well-characterized to lead to the development of hepatocellular carcinoma (HCC) in humans and animals. This review focuses on the metabolism of AFB1, including epoxidation and DNA adduction, as it concerns the initiation of cancer and the underlying mechanisms. In addition to DNA adduction, inflammation and oxidative stress caused by AFB1 can also participate in the occurrence of cancer. Therefore, the main carcinogenic mechanism of AFB1 related ROS is summarized. This review also describes recent reports of AFB1 exposures in occupational settings. It is hoped that people will pay more attention to occupational health, in order to reduce the incidence of cancer caused by occupational exposure.


Initial examination of microwave pretreatment on primary, secondary and mixed sludges before and after anaerobic digestion.
The effects of microwave pretreatment on disintegration and mesophilic digestion of waste activated sludge (WAS), primary sludge (PS), combined (PS + WAS) sequencing batch reactor (SBR) sludge and anaerobically digested biocake were investigated by both household and bench scale industrial types microwaves at temperatures below and above boiling point. Pretreatment variables, temperature, intensity (cooking rate) and sludge concentration had statistically significant effects on solubilization. The microwave pretreatment also increased the bioavailability of sludge components under batch anaerobic digestion and enhanced the dewaterability of pretreated sludges after digestion. However, the level of improvements in solubilization and biodegradation from different waste sludges were different. While the largest improvement in ultimate biodegradation was observed in WAS, microwave irradiation only affected the rate of biodegradation of pretreated PS samples. Similarly, relatively lower solubilization ratios achieved for combined - SBR sludge was attributed to high sludge age of extended aeration SBR unit. It is possible that initial sludge characteristics may influence final pretreatment outcomes so that general statements of performance cannot always be made.


Extracellular sphingosine 1-phosphate stimulates formation of ethanolamine from phosphatidylethanolamine: modulation of sphingosine 1-phosphate-induced mitogenesis by ethanolamine.
In this work, we determined the effects of sphingosine 1-phosphate (S1P) on phospholipase D (PLD)-mediated hydrolysis of phosphatidylethanolamine (PtdEtn), and evaluated the effects of the water-soluble product ethanolamine on S1P-induced DNA synthesis in NIH 3T3 cells. In [14C]ethanolamine-labelled cells, S1P (0.5-5 microM) stimulated PLD-mediated hydrolysis of PtdEtn 1.5-2.1-fold. Down-regulation of protein kinase C by chronic (24 h) treatment of cells with 300 nM PMA, or pretreatments (10 min) with the cell-permeant calcium chelator 1,2-bis-(O-aminophenoxy)-ethane-N,N, N',N'-tetra-acetic acid tetra-acetoxymethyl ester led to the inhibition of S1P-induced PtdEtn hydrolysis. S1P alone was a weak inducer of DNA synthesis, but its effects were enhanced by phosphocholine (PCho), insulin, ATP or PMA. Ethanolamine (5-100 microM) did not modify the mitogenic effect of S1P alone, whereas at 50-100 microM concentrations it actually enhanced the mitogenic effect of PCho via a mitogen-activated protein (MAP) kinase-independent mechanism. In contrast, 5-20 microM concentrations of ethanolamine, which correspond to normal blood ethanolamine levels in humans, strongly inhibited DNA synthesis induced by S1P plus PCho via a MAP kinase-dependent mechanism; importantly, less or no inhibition was observed with 50-100 microM concentrations of ethanolamine. At 5-50 microM concentrations, ethanolamine also inhibited the synergistic mitogenic effects of both S1P plus insulin (22-27% inhibition) and PCho plus ATP (45-73% inhibition) but not those of S1P plus PMA or S1P plus ATP. The results indicate that S1P stimulates PLD-mediated hydrolysis of PtdEtn by a mechanism that may involve a regulatory protein kinase C isoform. Increased formation of ethanolamine by PLD-mediated PtdEtn hydrolysis or by other means may be required for maximal stimulation of DNA synthesis by S1P in the presence of insulin, and particularly PCho.


Enhancement of the spin polarization of an Fe3O4(100) surface by nitric oxide adsorption.
The geometric, electronic and magnetic properties of a nitric oxide (NO) adsorbed Fe3O4(100) surface have been investigated using density functional theory (DFT) calculations. NO molecules preferentially bond with surface Fe(B) atoms via their N atoms. The generalized gradient approximation (GGA) is not recommended to be used in such a strongly correlated system since it provides not only an overestimation of the adsorption energy and an underestimation of the Fe(B)-N bond length, but also magnetic quenching of the adsorbate and the bonded Fe(B) atoms. In contrast, a tilted geometry and magnetization of the adsorbate and the bonded Fe(B) atom are obtained after including the strong on-site Coulomb interactions through a Hubbard term (GGA+U). The spin-down 2π* states of the NO molecule are filled and broadened due to the adsorbate-substrate interaction and the molecule-molecule interaction. The surface spin polarization close to the Fermi level is expected to be greatly enhanced by the NO adsorption which has significance for interface design in spintronic devices.


Bronchopleural fistula after lung ablation: Experience in two cases and literature review.
Bronchopleural fistula (BPF) complicating lung tumor ablation is rare but severe. The purpose of this article was to study its characteristics and treatments. Two of 682 (0.3%) sessions of lung microwave ablation (MWA) were complicated with BPF and documented. Two electronic databases were searched for reported cases of BPF after lung tumor ablation. Case selection and data collection were done by 3 independent reviewers. A 56-year-old man and a 61-year-old woman developed BPF after MWA and died. Thirteen cases (mean age 63.8, 61.5% male) of BPF with adequate information were identified from 8 articles. Of the 13 cases, 5 (38.5%) had pulmonary co-morbidity, 3 (23.1%) had a history of pulmonary surgery, 7 (53.8%) had a target tumor adjacent or abutting pulmonary pleura, and 6 (46.2%) developed severe infections. After chest tube placement, pleurodesis, endoscopic therapy, surgery, and other treatments, 12 were cured and 1 died of BPF and pneumonia. BPF is a rare but severe complication of lung ablation, and the management needs a multidisciplinary and individualized treatment strategy.


High-resolution computed tomography of the lung in children with cystic fibrosis: technical factors.
A standard technique that controls for respiratory motion and lung volumes during imaging is necessary if high-resolution computed tomography is to be used as an outcome measure in children with cystic fibrosis. End-inspiratory and expiratory imaging allows for the detection and differentiation of early lung disease. In children ages 0-5 years, a noninvasive controlled ventilation technique is ideal, and can be used in combination with raised-volume infant pulmonary function tests. In older children, a spirometric-assisted or spirometric-triggered technique should be used. With optimal technique, radiation dose settings (kVp and mA) can be lowered to achieve a diagnostic screening high-resolution computed tomography of the lungs at a dose equivalent to that of the chest radiograph.


Anthropogenic Pollution Intervenes the Recovery Processes of Soil Archaeal Community Composition and Diversity From Flooding.
Archaea play vital roles in global biogeochemical cycles, particularly in nitrification and methanogenesis. The recovery of archaeal community following disturbance is essential for maintaining the stability of ecosystem function. To examine whether the archaeal community could recover from water flooding and assess the influence of anthropogenic pollution on the autogenic recovery, soil samples from two riparian zones with contrasting pollution background were investigated. Collected samples in each area were divided into three groups of reference, flooding, and recovery according to the flooded state of each site. The results showed that the archaeal abundance was resilient to the disturbances of both water flooding and anthropogenic pollution. More similar community composition and diversity appeared between the recovery and reference groups in the area with low anthropogenic pollution. It indicated that high anthropogenic pollution could result in less resilience of archaeal community. The co-occurrence network further revealed that the archaeal community in the area of low anthropogenic pollution exhibited more associations suggesting a higher ecosystem stability. The better recovery of archaeal community was associated with the high resilience ability. The Nitrososphaerales was the key taxon maintaining the better recovery of the archaeal community from the disturbances due to its high resilience index and quantitative dominance. Overall, archaeal community has the capability of autogenic recovery, the process of which might be intervened by anthropogenic pollution, and then potentially affects the ecosystem functions of the riparian system.


Tobacco and alcohol sales in community pharmacies: policy statements from U.S. professional pharmacy associations.
To characterize the extent to which state and national professional pharmacy associations have implemented formal policies addressing the sale of tobacco and alcohol products in community pharmacies. To determine existence of tobacco and alcohol policies, national professional pharmacy associations (n = 10) and state-level pharmacy associations (n = 86) affiliated with the American Pharmacists Association (APhA) and/or the American Society of Health-System Pharmacists (ASHP) were contacted via telephone and/or e-mail, and a search of the association websites was conducted. Of 95 responding associations (99%), 14% have a formal policy opposing the sale of tobacco products in pharmacies and 5% have a formal policy opposing the sale of alcohol in pharmacies. Of the associations representing major tobacco-producing states, 40% have a formal policy against tobacco sales in pharmacies, significantly more than the 8% of non-tobacco state associations with such policies. Among national professional pharmacy associations, only APhA and ASHP have formal policy statements opposing the sale of both tobacco and alcohol in pharmacies. Most state-level professional pharmacy associations affiliated with these two national organizations have no formal policy statement or position.


Comparing cancer risk estimates using occupational record linkage approaches in male Florida firefighters.
Firefighters have an increased risk of cancer, but variations in reported results could be due to differences in occupational case ascertainment. This study compares cancer risk estimates generated by identifying firefighters from their occupational title available in the Florida Cancer Data System (FCDS) versus identification by a linkage method between the FCDS and the Florida State Fire Marshal's Office. Florida firefighter employment records (1972-2012; n = 109,009) were linked with FCDS data (1981-2014; ~3.3 million records), identifying 3760 primary cancers in male firefighters. Using the FCDS occupational data field we identified 1831 male cancer cases in those classified as firefighters, first-line supervisors of firefighting and prevention workers, fire inspectors, emergency medical technicians, or paramedics. Age and calendar year-adjusted odds ratios (aOR) and 95% confidence intervals for firefighters versus non-firefighters were calculated for both groups. For skin cancers the risk estimate for FCDS-indentified firefighters was substantially lower than in the employment-record-linked firefighters (aOR = 1.06; 0.87-1.29 vs. 1.54; 1.37-1.73), but for endocrine system cancers it was greater (aOR = 2.36; 1.77-3.14 vs. 2.08; 1.71-2.53). Remaining cancer risk estimates were in the same direction for the two samples except for lymphoma (aOR = 1.10; 0.90-1.34 vs. 0.86; 0.75-0.99). Reliance on occupational title in cancer registry records to characterize firefighter cancer risk may result in estimates that are over- or underestimated depending on cancer site. The authors recommend moving toward national linkages between cancer registries and certification or other administrative records, which are a vital resource for firefighter cancer research.


Localized energy coupling during photophosphorylation by chromatophores of Rhodopseudomonas capsulata N22.
The principle of the dual inhibitor titration method for testing models of electron-transport phosphorylation is outlined, and the method is applied to the study of photophosphorylation in bacterial chromatophores. It is concluded that energy coupling is strictly localized in nature in this system, in the sense that free energy released by a particular electron-transport chain may be used only by a particular H+-ATP synthase. Dual inhibitor titrations using the uncoupler SF 6847 and the H+-ATP synthase inhibitor oligomycin indicate that uncouplers act by shuttling rapidly between the localized energy-coupling sites.


Base of support feedback in gait rehabilitation.
The purpose of this study was to investigate the effect of feedback information about base of support in gait rehabilitation. Sixteen individuals with hemiparesis resulting in narrow base of support, were randomly placed into two equal groups, experimental and control. The experimental group was provided with a portable device that provided extrinsic auditory feedback information about base of support incorporated in the functional context of conventional gait therapy, whereas the control group received a conventional gait therapy only. Changes in step width with treatment were assessed with step print technique. The experimental group of subjects improved their step width with treatment from 0.09 +/- 0.003 m to 0.16 +/- 0.006 m while individuals assigned to the control group showed smaller improvement from 0.099 +/- 0.004 m to 0.13 +/- 0.003 m. While both groups demonstrated statistically significant improvement (p < 0.05), the level of recovery of step width seen in the experimental group was greater.


TRPV1 acts as a synaptic protein and regulates vesicle recycling.
Electrophysiological studies demonstrate that transient receptor potential vanilloid subtype 1 (TRPV1) is involved in neuronal transmission. Although it is expressed in the peripheral as well as the central nervous system, the questions remain whether TRPV1 is present in synaptic structures and whether it is involved in synaptic processes. In the present study we gathered evidence that TRPV1 can be detected in spines of cortical neurons, that it colocalizes with both pre- and postsynaptic proteins, and that it regulates spine morphology. Moreover, TRPV1 is also present in biochemically prepared synaptosomes endogenously. In F11 cells, a cell line derived from dorsal-root-ganglion neurons, TRPV1 is enriched in the tips of elongated filopodia and also at sites of cell-cell contact. In addition, we also detected TRPV1 in synaptic transport vesicles, and in transport packets within filopodia and neurites. Using FM4-64 dye, we demonstrate that recycling and/or fusion of these vesicles can be rapidly modulated by TRPV1 activation, leading to rapid reorganization of filopodial structure. These data suggest that TRPV1 is involved in processes such as neuronal network formation, synapse modulation and release of synaptic transmitters.


Advances in SARS-CoV-2: a systematic review.
In December 2019, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection broke out in Wuhan, China. However, we still lack a comprehensive understanding of this emerging virus. In this manuscript, we collected relevant articles and reviewed the characteristics about SARS-CoV-2. We performed an online search on PubMed and Web of Science with the keywords COVID-19, 2019-nCoV and SARS-CoV-2, and summarized the epidemiology, virology, clinical features and treatments of SARS-CoV-2 infection. We retrieved 157 published papers about SARS-CoV-2 from January, 2020 to April, 2020. We found that SARS-CoV-2 was a kind of virus with low mortality rate and high infectivity. This virus can enter human cells through angiotensin-converting enzyme 2 (ACE2) in alveoli and activate immune response in human body. SARS-CoV-2 infection can be classified as asymptomatic, mild, common, severe, and critical. We summarized antiviral drugs against SARS-CoV-2, such as remdesivir, hydroxychloroquine and favipiravir. Because the vaccine of SARS-CoV-2 is developing, more clinical studies are needed to verify the safety and efficacy of these treatments. SARS-CoV-2 is a novel coronavirus that has caused a global pandemic. We should pay more attention to prevent SARS-CoV-2 and try to control it sooner.


Metabolic, immunological and clinical characteristics in newly diagnosed Asian diabetes patients aged 12-40 years.
To describe the clinical, biochemical and immunological characteristics of young-onset diabetes in Asia. Clinical, biochemical and immunological variables were assessed in 919 newly diagnosed (duration less than 12 months) young onset Asian diabetic patients aged between 12 and 40 years. The subjects constituted 57% Chinese, 29% Indians and 14% Malays, recruited from diabetes centres in China, Hong Kong, India, Malaysia and Singapore. The mean age (+/- sd) was 31.6 +/- 7.2 years, with the majority (66%) in the 31-40 years age group. Mean body mass index (BMI) (+/- sd) was 25.3 +/- 5.0 kg/m2 with 47% exceeding the suggested Asian cut-off point for obesity (BMI > or = 25). Ethnic difference in clinical characteristics included BMI, blood pressure, mode of treatment and degree of insulin resistance. Most patients had a clinical presentation of Type 2 diabetes. About 10% had a classical combination of ketotic presentation, presence of autoimmune-markers and documented insulin deficiency indicative of Type 1 diabetes. Forty-eight percent were receiving oral hypoglycaemic agents (OHAs) while 31% were on diet only, 18% were receiving insulin and 2% were on a combination of insulin and OHA. Young onset diabetes patients in Asia represent a heterogeneous group in terms of their clinical and biochemical characteristics and classical Type 1 diabetes is relatively uncommon. The 5-year follow up study will determine the progress of these patients and help to clarify the natural history.


Structural enzymology of Helicobacter pylori methylthioadenosine nucleosidase in the futalosine pathway.
The recently discovered futalosine pathway is a promising target for the development of new antibiotics. The enzymes involved in this pathway are crucial for the biosynthesis of the essential prokaryotic respiratory compound menaquinone, and as the pathway is limited to few bacterial species such as the gastric pathogen Helicobacter pylori it is a potential target for specific antibiotics. In this report, the crystal structure of an H. pylori methylthioadenosine nucleosidase (MTAN; an enzyme with broad specificity and activity towards 6-amino-6-deoxyfutalosine), which is involved in the second step of menaquinone biosynthesis, has been elucidated at a resolution of 1.76 Å and refined with R factors of Rwork = 17% and Rfree = 21%. Activity studies on the wild type and active-site mutants show that the hydrolysis of 6-amino-6-deoxyfutalosine follows a mechanism similar to that of Escherichia coli MTAN. Further evidence for this mode of action is supplied by the crystal structures of active-site mutants. Through the use of reaction intermediates, the structures give additional evidence for the previously proposed nucleosidase mechanism. These structures and the confirmed reaction mechanism will provide a structural basis for the design of new inhibitors targeting the futalosine pathway.