Protocol for pilot cluster RCT of project respect: a school-based intervention to prevent dating and relationship violence and address health inequalities among young people.
Dating and relationship violence (DRV)-intimate partner violence during adolescence-encompasses physical, sexual and emotional abuse. DRV is associated with a range of adverse health outcomes including injuries, sexually transmitted infections, adolescent pregnancy and mental health issues. Experiencing DRV also predicts both victimisation and perpetration of partner violence in adulthood.Prevention targeting early adolescence is important because this is when dating behaviours begin, behavioural norms become established and DRV starts to manifest. Despite high rates of DRV victimisation in England, from 22 to 48% among girls and 12 to 27% among boys ages 14-17 who report intimate relationships, no RCTs of DRV prevention programmes have taken place in the UK. Informed by two school-based interventions that have shown promising results in RCTs in the USA-Safe Dates and Shifting Boundaries-Project Respect aims to optimise and pilot a DRV prevention programme for secondary schools in England. Design: optimisation and pilot cluster RCT. Trial will include a process evaluation and assess the feasibility of conducting a phase III RCT with embedded economic evaluation. Cognitive interviewing will inform survey development.Participants: optimisation involves four schools and pilot RCT involves six (four intervention, two control). All are secondary schools in England. Baseline surveys conducted with students in years 8 and 9 (ages 12-14). Follow-up surveys conducted with the same cohort, 16 months post-baseline. Optimisation sessions to inform intervention and research methods will involve consultations with stakeholders, including young people.Intervention: school staff training, including guidance on reviewing school policies and addressing 'hotspots' for DRV and gender-based harassment; information for parents; informing students of a help-seeking app; and a classroom curriculum for students in years 9 and 10, including a student-led campaign.Primary outcome: the primary outcome of the pilot RCT will be whether progression to a phase III RCT is justified. Testing within the pilot will also determine which of two existing scales is optimal for assessing DRV victimisation and perpetration in a phase III RCT. This will be the first RCT of an intervention to prevent DRV in the UK. If findings indicate feasibility and acceptability, we will undertake planning for a phase III RCT of effectiveness. ISRCTN, ISRCTN 65324176. Registered 8 June 2017.


Evaluation of vertebroplasty with a validated outcome measure: the Roland-Morris Disability Questionnaire.
Vertebroplasty is rapidly disseminating as a treatment for vertebral compression fractures, but its efficacy has not been assessed with a well-validated, back pain-specific instrument. We report the use of the Roland-Morris Disability Questionnaire (RDQ) in patients undergoing vertebroplasty for painful osteoporotic compression fractures. Retrospective review of patients treated with vertebroplasty who completed the RDQ and 2 verbal pain scales (0-10) for pain at rest and pain with activity at baseline, 1 week, 1 month, 6 months, and 1 year post-vertebroplasty. Changes in outcome measures were analyzed by using a paired t test and correlations were assessed with Spearman rho. Multiple linear regression was used to analyze the relationship between baseline scores and independent variables. One hundred thirteen patients were treated at 164 vertebral levels. At baseline, RDQ scores were associated with rest and activity pain (P < .001 and P = .002, respectively) but were not associated with other independent variables. All 3 outcome scores decreased by 1 week and remained improved through maximal follow-up (P < .001). RDQ scores improved by a mean of 7.0 points at 1 week and remained improved at 1 year (P = .02). RDQ scores correlated with both rest and activity pain, but the absolute correlation was slightly better (+0.15 on average) with activity pain. Patients who underwent vertebroplasty experienced relief of back pain and symptoms, as shown by improvement in verbal pain and RDQ scores. The RDQ correlates well with measures of pain, shows clinically significant improvement and is responsive to changes across time. More important, the RDQ provides an easily administered, well-validated, back pain-specific outcome measure that could be adopted to assess vertebroplasty outcomes.


Pediatric experience with recombinant hepatitis B vaccines and relevant safety and immunogenicity studies.
Yeast-derived recombinant hepatitis B vaccines have replaced plasma-derived vaccines in the United States and have now been given to millions of infants and children throughout the world. Routine immunization of infants in the United States with hepatitis B vaccine has been endorsed as the optimal means to prevent infection. The recombinant vaccines have an excellent safety record; most children have no adverse reactions whereas a few experience only minor local and systemic reactions that resolve within a short time. Both of the vaccines licensed in the United States are highly immunogenic in infants and children who complete a three dose vaccination sequence. Approximately 95 to 100% achieve protective levels of antibody to hepatitis B surface antigen (> or = 10 mIU/ml) after three doses. Immunization may begin at birth or at 1 to 2 months of age, and hepatitis B vaccine may be given simultaneously with other routine childhood vaccines. Antibody levels to hepatitis B surface antigen gradually wane over time, and the duration of maintaining protective levels correlates strongly with the peak level achieved. The protective efficacy against perinatal transmission from mothers who are positive for hepatitis B surface antigen and e antigen is 90 to 100% when the first dose of vaccine is administered at birth with hepatitis B immunoglobulin. In highly endemic populations immunization in infancy also protects against horizontal transmission from chronically infected family members. Studies currently in progress will determine the duration of protection, the potential need for booster doses and the feasibility of combining antigens in multivalent vaccines.


Laparoscopic Training in Urology Residency Programs: A Systematic Review.
Laparoscopy is a widespread surgical approach for many urological conditions. Achieving prof-ciency in laparoscopic surgery requires considerable effort due to the steep learning curve. Several residency programs include standardized laparoscopic training periods in their curricula. Our aim was to systematically analyze the evidence on the current status of training in laparoscopy in different residency programs in urology. We performed a systematic review of PubMed/Medline and the Cochrane library, in February 2018, according to the Preferred Reporting Items for the Systematic Review and Meta-Analyses Statement. Identified reports were reviewed according to the previously defined inclusion criteria. Eight publications, comprising a total of 985 urology residents, were selected for inclusion in this analysis. There was a wide variation between training programs in terms of exposure to laparoscopy. Most residents considered that training in lap-aroscopy was inadequate during residency and had a low degree of confidence in independently performing laparo-scopic procedures by the end of the residency. Only North American residents reported high degrees of confidence in the possibility of performing laparoscopic procedures in the uture, whereas the remaining residents, namely from European countries, reported considerably lower degrees of confidence. There were considerable differences between national urology residency programs in terms of exposure to laparoscopy. Most residents would prefer higher exposure to laparoscopy throughout their residencies.


Assessment of the efficacy of early phase parameters by (123)I-MIBG dynamic imaging for distinguishing Lewy body-related diseases from Parkinson's syndrome.
The aim of this study was to assess the efficacy of early phase washout rate (early WR) and area under the time-activity curve (AUTAC) by (123)I-metaiodobenzylguanidine (MIBG) dynamic chest imaging for distinguishing Lewy body-related diseases (LBRD) from Parkinson's syndrome (PS) and reducing examination time. Sixty-two patients with suspected LBRD who underwent (123)I-MIBG dynamic imaging in early phase were retrospectively selected. The early WR and AUTAC were calculated from (123)I-MIBG dynamic data of the heart. We evaluated the relationships between proposed and conventional parameters by using Spearman's rank correlation coefficient. Differences in parameters between LBRD and PS groups were tested for statistical significance using the Mann-Whitney U test. The diagnostic performance of all parameters for distinguishing LBRD from PS was assessed in terms of receiver operating characteristic (ROC) analysis. Additionally, combination diagnostic performance and concordance rate between early phase parameters and late H/M ratio by kappa statistics were also assessed. The early WR and AUTAC showed a positive and negative correlation with conventional parameters. Both the early WR and AUTAC of LBRD group were significantly distinguishable from those of the PS group (p < 0.001). Area under the ROC curve of the early WR (0.98) was greater than that of AUTAC (0.91). The diagnostic performance of combination of the early phase parameters was 93 % sensitivity and 100 % specificity. Moreover, the early phase parameters showed excellent agreement with late H/M ratio (k = 0.93). The early WR and AUTAC showed high performance for distinguishing LBRD from PS, and the combination diagnosis with early H/M ratio and early WR contribute to improve the diagnostic performance. Thus, these parameters would be useful for reducing the examination time of myocardial (123)I-MIBG scintigraphy to diagnose LBRD.


Lp(a): Addressing a Target for Cardiovascular Disease Prevention.
To review the current recommendations for lipoprotein(a) (Lp(a)) screening, the evidence behind the thresholds for increased cardiovascular disease (CVD) risk, and the available data supporting Lp(a) lowering. Lp(a) is almost entirely genetically determined and has an independent causal association with CVD. Measurement of Lp(a) is challenging given the structural heterogeneity of apolipoprotein a (apo(a)), for which isoform-insensitive immunoassays should be used. Current guidelines do not recommend treatment to lower Lp(a) but rather focus on intensified preventive measures including low-density lipoprotein cholesterol (LDL-C) lowering in patients with high Lp(a). Evidence suggests that levels higher than 50 mg/dL (125 nmol/L) identify significantly increased CVD risk. Mendelian randomization studies suggest that in order to have a clinically significant reduction in coronary heart disease, Lp(a) levels should be reduced by at least 60-70 mg/dL to attain a significant benefit. Ongoing studies of targeted therapy with antisense oligonucleotides (ASO) have shown promising reductions in Lp(a) up to 80%, but a cardiovascular outcomes trial is needed. There is unquestionably an increased risk for CVD in patients with elevated Lp(a); however, measurement assay issues and the lack of Lp(a)-targeted therapies with proven outcome reduction limit the clinical utility of this important risk factor. Available evidence suggesting specific thresholds for clinically significant CVD risk are based on European or Caucasian populations, not accounting for important racial differences. Novel Lp(a)-targeted emerging therapies may need to account for an expected reduction of at least 60-70 mg/dL to achieve a clinically significant benefit.


Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies.
Long-term data are essential to assess the safety of biologic agents for the treatment of psoriasis. To evaluate the incidence of adverse events of interest (AEIs), including all-cause mortality, major adverse cardiovascular events (MACE), malignancy (excluding nonmelanoma skin cancer), and serious infections (SI), in patients treated for psoriasis in clinical practice settings. PSOLAR is a large, ongoing, observational study of patients receiving, or eligible to receive, biologic or systemic therapy for psoriasis. Cumulative incidence rates of AEIs per 100 patient-years (PY) are reported across treatment cohorts: (1) infliximab, (2) ustekinumab, (3) other biologics (eg, adalimumab and etanercept), and (4) non-biologic agents. Significant predictors of each AEI were identified using Cox proportional hazards regression methodology. PSOLAR is now fully enrolled at 12095 patients followed for 31818PY. The cumulative rate was 0.46/100PY for death, 0.36/100PY for MACE, 0.68/100PY for malignancy, and 1.50/100PY for SI. Increasing age was a significant predictor of all AEIs. A history of cardiovascular disease, malignancy, and significant infection was associated with a higher risk of developing MACE, malignancy, and SI, respectively. Exposure to infliximab (Hazard Ratio [HR]=3.101, P<0.001) and exposure to other biologics (HR=1.736, P<0.001) were significant predictors of SI. Use of immunomodulators (HR=1.954, P=0.005) was a significant predictor of MACE. Compared with non-biologic therapy, the use of biologic agents was not a significant predictor of death, MACE, or malignancy. Based on PSOLAR data through 2013, no new safety concerns were observed with infliximab for all-cause mortality, MACE, or malignancy; the data suggest that infliximab was associated with serious infections.


A Web Service Protocol Realizing Interoperable Internet of Things Tasking Capability.
The Internet of Things (IoT) is an infrastructure that interconnects uniquely-identifiable devices using the Internet. By interconnecting everyday appliances, various monitoring, and physical mashup applications can be constructed to improve human's daily life. In general, IoT devices provide two main capabilities: sensing and tasking capabilities. While the sensing capability is similar to the World-Wide Sensor Web, this research focuses on the tasking capability. However, currently, IoT devices created by different manufacturers follow different proprietary protocols and are locked in many closed ecosystems. This heterogeneity issue impedes the interconnection between IoT devices and damages the potential of the IoT. To address this issue, this research aims at proposing an interoperable solution called tasking capability description that allows users to control different IoT devices using a uniform web service interface. This paper demonstrates the contribution of the proposed solution by interconnecting different IoT devices for different applications. In addition, the proposed solution is integrated with the OGC SensorThings API standard, which is a Web service standard defined for the IoT sensing capability. Consequently, the Extended SensorThings API can realize both IoT sensing and tasking capabilities in an integrated and interoperable manner.


Non-muscle myosin IIB (Myh10) is required for epicardial function and coronary vessel formation during mammalian development.
The coronary vasculature is an essential vessel network providing the blood supply to the heart. Disruptions in coronary blood flow contribute to cardiac disease, a major cause of premature death worldwide. The generation of treatments for cardiovascular disease will be aided by a deeper understanding of the developmental processes that underpin coronary vessel formation. From an ENU mutagenesis screen, we have isolated a mouse mutant displaying embryonic hydrocephalus and cardiac defects (EHC). Positional cloning and candidate gene analysis revealed that the EHC phenotype results from a point mutation in a splice donor site of the Myh10 gene, which encodes NMHC IIB. Complementation testing confirmed that the Myh10 mutation causes the EHC phenotype. Characterisation of the EHC cardiac defects revealed abnormalities in myocardial development, consistent with observations from previously generated NMHC IIB null mouse lines. Analysis of the EHC mutant hearts also identified defects in the formation of the coronary vasculature. We attribute the coronary vessel abnormalities to defective epicardial cell function, as the EHC epicardium displays an abnormal cell morphology, reduced capacity to undergo epithelial-mesenchymal transition (EMT), and impaired migration of epicardial-derived cells (EPDCs) into the myocardium. Our studies on the EHC mutant demonstrate a requirement for NMHC IIB in epicardial function and coronary vessel formation, highlighting the importance of this protein in cardiac development and ultimately, embryonic survival.


Genome-wide analysis in endangered populations: a case study in Barbaresca sheep.
Analysis of genomic data is becoming increasingly common in the livestock industry and the findings have been an invaluable resource for effective management of breeding programs in small and endangered populations. In this paper, with the goal of highlighting the potential of genomic analysis for small and endangered populations, genome-wide levels of linkage disequilibrium, measured as the squared correlation coefficient of allele frequencies at a pair of loci, effective population size, runs of homozygosity (ROH) and genetic diversity parameters, were estimated in Barbaresca sheep using Illumina OvineSNP50K array data. Moreover, the breed's genetic structure and its relationship with other breeds were investigated. Levels of pairwise linkage disequilibrium decreased with increasing distance between single nucleotide polymorphisms. An average correlation coefficient <0.25 was found for markers located up to 50 kb apart. Therefore, these results support the need to use denser single nucleotide polymorphism panels for high power association mapping and genomic selection efficiency in future breeding programs. The estimate of past effective population size ranged from 747 animals 250 generations ago to 28 animals five generations ago, whereas the contemporary effective population size was 25 animals. A total of 637 ROH were identified, most of which were short (67%) and ranged from 1 to 10 Mb. The genetic analyses revealed that the Barbaresca breed tended to display lower variability than other Sicilian breeds. Recent inbreeding was evident, according to the ROH analysis. All the investigated parameters showed a comparatively narrow genetic base and indicated an endangered status for Barbaresca. Multidimensional scaling, model-based clustering, measurement of population differentiation, neighbor networks and haplotype sharing distinguished Barbaresca from other breeds, showed a low level of admixture with the other breeds considered in this study, and indicated clear genetic differences compared with other breeds. Attention should be given to the conservation of Barbaresca due to its critical conservation status. In this context, genomic information may have a crucial role in management of small and endangered populations.


Receipt of previous diagnoses and endoscopy and outcome from esophageal adenocarcinoma: a population-based study with temporal trends.
Endoscopic screening of the at-risk population with chronic gastroesophageal reflux disease (GERD) for the presence of intestinal metaplasia or Barrett's esophagus has been suggested as a method to reduce mortality from esophageal adenocarcinoma. There are only limited data regarding the use, effectiveness, and temporal trends of this strategy. All patients aged 68 years and older with a new diagnosis of adenocarcinoma of the esophagus from 1994 to 2002 were identified from a linked tumor registry health claims database. Using claims from 1991 to 2002, the use of endoscopy as well as a diagnosis of GERD or Barrett's esophagus during the time interval from 3 years through 6 months prior to diagnosis were measured. The association of these measures with early-stage cancer (in situ, local) and long-term survival was determined, as well as changes over time. We identified 2,754 patients, including 30.8% at early stage. Previous endoscopy had been performed in 11.5% of patients, and GERD and Barrett's esophagus diagnoses were recorded in 22.4 and 8.1% of patients, respectively. Barrett's esophagus diagnosis was strongly associated with both early-stage cancer (odds ratio 3.68, confidence interval (CI) 1.30-10.40) and survival (hazard ratio 0.45, CI 0.25-0.80). A GERD diagnosis was associated only with early stage, and endoscopy was associated only with survival. There was no association of year of diagnosis with stage or survival. Although only a minority of at-risk patients were identified, the findings are consistent with the beneficial effects of recognition. Despite the development of practice guidelines, we were unable to demonstrate any temporal increases in diagnostic frequency or endoscopic utilization, which highlights the challenges that clinicians face.


Crew resource management in the ICU: the need for culture change.
Intensive care frequently results in unintentional harm to patients and statistics don't seem to improve. The ICU environment is especially unforgiving for mistakes due to the multidisciplinary, time-critical nature of care and vulnerability of the patients. Human factors account for the majority of adverse events and a sound safety climate is therefore essential. This article reviews the existing literature on aviation-derived training called Crew Resource Management (CRM) and discusses its application in critical care medicine. CRM focuses on teamwork, threat and error management and blame free discussion of human mistakes. Though evidence is still scarce, the authors consider CRM to be a promising tool for culture change in the ICU setting, if supported by leadership and well-designed follow-up.


Genetic Analysis of Invasive Conehead Termites (Blattodea: Termitidae) Reveals a Single Origin for Two Populations in Florida.
In 2001, Nasutitermes corniger (Motschulsky), common name conehead termite, were discovered near a marina in Dania Beach, FL, where the invasive species was probably transported from its native range in Central and South America or the Caribbean. In January 2016, an infestation was found in Pompano Beach, Florida, approximately 21 km north of the Dania Beach population. This study compares variants in seven microsatellite loci across specimens from 11 nests in Dania Beach and 8 nests in Pompano Beach. Results are consistent with all N. corniger in both locations being descendants of a single introduced colony, spreading within Broward County, FL through human transport of infested materials. No more than four alleles were found at any of the seven microsatellite loci analyzed, inferring that a single Queen and King, or multiple sibling reproductives descended from a monogamous pair, headed the colony that arrived in Florida. The potential economic and environmental impacts of this invasive termite are enormous due to its broad diet, including agricultural crops and orchards, native and ornamental plants, natural landscapes, and structures. Conspicuous tunnels and aboveground nests are the key aspects of N. corniger biology that render colonies vulnerable to discovery and control. The now proven ability of N. corniger to establish breeding populations in the United States, to cause extensive property and landscape destruction, and to spread by human transport underscores the need for continued aggressive efforts toward eradication of known infestations as well as quick operational actions the next time invasive N. corniger are discovered.


Age-associated increase in PGE2 synthesis and COX activity in murine macrophages is reversed by vitamin E.
We previously showed that increased macrophage and PGE2 production with age is due to enhanced cyclooxygenase (COX) activity and COX-2 expression. This study determined the effect of vitamin E supplementation on macrophage PGE2 synthesis in young and old mice and its underlying mechanism. Mice were fed 30 or 500 parts per million vitamin E for 30 days. Lipopolysaccharide (LPS)-stimulated macrophages from old mice produced significantly more PGE2 than those from young mice. Vitamin E supplementation reversed the increased PGE2 production in old mice but had no effect on macrophage PGE2 production in young mice. In both LPS-stimulated and unstimulated macrophages, COX activity was significantly higher in old than in young mice at all intervals. Vitamin E supplementation completely reversed the increased COX activity in old mice to levels comparable to those of young mice but had no effect on macrophage COX activity of young mice or on COX-1 and COX-2 protein or COX-2 mRNA expression in young or old mice. Thus vitamin E reverses the age-associated increase in macrophage PGE2 production and COX activity. Vitamin E exerts its effect posttranslationally, by inhibiting COX activity.


Cell death induced autophagy contributes to terminal differentiation of skin and skin appendages.
In the adult mammalian skin, cells are constantly renewing, differentiating and moving upward, to finally die in a yet not fully understood manner. Here, we provide evidence that macroautophagy/autophagy has a dual role in the skin. In addition to its known catabolic protective role as an evolutionary conserved upstream regulator of lysosomal degradation, we show that autophagy induced cell death (CDA) occurs in epithelial lineage-derived organs, such as the inter-follicular epidermis, the sebaceous- and the Harderian gland. By utilizing GFP-LC3 transgenic and ATG7-deficient mice, we show that CDA is initiated during terminal differentiation at a stage when the cells have become highly resistant to apoptosis. In these transitional cells, the Golgi compartment expands, which accounts for the formation of primary lysosomes, and the nucleus starts to condense. During CDA a burst of autophagosome formation is observed, first the endoplasmic reticulum (ER) is phagocytosed followed by autophagy of the nucleus. By this selective form of cell death, most of the cytoplasmic organelles are degraded, but structural proteins remain intact. In the absence of autophagy, consequently, parts of the ER, ribosomes, and chromatin remain. A burst of autophagy was stochastically observed in single cells of the epidermis and collectively in larger areas of ductal cells, arguing for a coordinated induction. We conclude that autophagy is an integral part of cell death in keratinocyte lineage cells and participates in their terminal cell fate.Abbreviations: Atg7: autophagy related 7; BECN1: beclin 1; CDA: cell death-induced autophagy; Cre: Cre-recombinase; DAPI: 4',6-diamidino-2-phenylindole; ER: endoplasmatic reticulum; GFP: green fluorescent protein; HaGl: haderian gland; IVL: involucrin; KRT14: keratin 14; LD: lipid droplet; LSM: laser scanning microscope; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PN: perinuclear space; RB: residual body; rER: rough endoplasmatic reticulum; SB: sebum; SG-SC: stratum granulosum - stratum corneum; SGl: sebaceous gland; SQSTM1: sequestosome 1; TEM: transmission electron microscopy; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labelling.


Comparison between HIV- and CMV-specific T cell responses in long-term HIV infected donors.
The mechanisms underlying non-progression in HIV-1 infection are not well understood; however, this state has been associated previously with strong HIV-1-specific CD8+ T cell responses and the preservation of proliferative CD4+ T cell responses to HIV-1 antigens. Using a combination of interferon-gamma (IFN-gamma) ELISpot assays and tetramer staining, the HIV-1-specific CD8+ T cell populations were quantified and characterized in untreated long-term HIV-1-infected non-progressors and individuals with slowly progressive disease, both in relation to CD4+ T cell responses, and in comparison with responses to cytomegalovirus (CMV) antigens. High levels of CD8+ T cell responses specific for HIV-1 or CMV were observed, but neither their frequency nor their phenotype seemed to differ between the two patient groups. Moreover, while CMV-specific CD4+ T cell responses were preserved in these donors, IFN-gamma release by HIV-1-specific CD4+ T cells was generally low. These data raise questions with regard to the role played by CD8+ T cells in the establishment and maintenance of long-term non-progression.


OTX2 represses myogenic and neuronal differentiation in medulloblastoma cells.
The brain development transcription factor OTX2 is overexpressed and/or genomically amplified in most medulloblastomas, but the mechanistic basis for its contributions in this setting are not understood. In this study, we identified OTX2 as a transcriptional repressor and a gatekeeper of myogenic and neuronal differentiation in medulloblastoma cells. OTX2 binds to the MyoD1 core enhancer through its homeobox domain, and the remarkable repressor activity exhibited by the homeobox domain renders OTX2 transcriptionally repressive. RNA interference-mediated attenuation of OTX2 expression triggered myogenic and neuronal differentiation in vitro and prolonged the survival in an orthotopic medulloblastoma mouse model. Conversely, inducing myogenic conversion of medulloblastoma cells led to the loss of OTX2 expression. In medullomyoblastoma, a medulloblastoma subtype containing muscle elements, myogenic cells share cytogenetic signatures with the primitive tumor cells and OTX2 expression was lost in the differentiated myogenic cells. Thus, OTX2 functions via its homeobox domain as a suppressor of differentiation, and the loss of OTX2 expression is linked to the myogenesis in medullomyoblastoma. Together, our findings illustrate the origin of muscle cells in medullomyoblastomas and the oncogenic mechanism of OTX2 as a repressor of diverse differentiating potential.


[Utilization of the MVA-immunization schedule from the view point of the public health service].
The world-wide smallpox eradication program sponsored by the WHO has been successful. Furthermore the legislation regarding smallpox vaccination in the Federal Republic of Germany has been given a new form. The place of the previous mass-vaccination has been taken by vaccination of individuals. Under this aspect safe procedures for vaccination are required. Any vaccination used by Public Health Service has to fulfill the following criteria: High protection against the disease without adverse side-effects or risks; it should be simple to administer and applicable under ordinary circumstances. For primary vaccination against smallpox the MVA-vaccination meets these demands entirely. It is reported about own experiences with 700 vaccinations using the attenuated virus "MVA"; complete documentation is given. Not a single complication nor any adverse side-effects have been seen. The Public Health Service has gained great experience in the field of vaccination. It is responsible for the protection of the individual as well as the public, as it is undesirable that there develops and unvaccinated group within the population. The individual claim a complete protection through vaccination which should be absolutely free of any risk.


The use of quick-brain magnetic resonance imaging in the evaluation of shunt-treated hydrocephalus.
Children with shunt-treated hydrocephalus are exposed to serious amounts of radiation when undergoing computerized tomography (CT) scanning. The authors report their clinical experience with single-shot fast-spin echo (SSFSE) (quick-brain) magnetic resonance (MR) imaging as the modality of choice for the workup and follow up of patients in whom a shunt has been placed to treat hydrocephalus. A retrospective chart review was performed to obtain data on all cases in which a quick-brain MR image was acquired for either symptomatic workup or asymptomatic follow-up examination of shunt-treated hydrocephalus. Data regarding demographics, origin of hydrocephalus, MR imaging indications and findings, use of sedation, imaging-related complications, use of adjunctive CT scanning, details of shunt revision, and cause of shunt malfunction were collected. The authors found that SSFSE MR imaging is a sufficient, radiation-free diagnostic alternative to CT scanning that minimizes movement artifact and duration of scanning and eliminates the need for sedation. In light of these findings, the authors propose that quick-brain MR imaging replace CT scanning as the diagnostic modality of choice in examining and following shunt-treated patients because it offers significant advantages.


Pharmacology of P2X channels.
Significant progress in understanding the pharmacological characteristics and physiological importance of homomeric and heteromeric P2X channels has been achieved in recent years. P2X channels, gated by ATP and most likely trimerically assembled from seven known P2X subunits, are present in a broad distribution of tissues and are thought to play an important role in a variety of physiological functions, including peripheral and central neuronal transmission, smooth muscle contraction, and inflammation. The known homomeric and heteromeric P2X channels can be distinguished from each other on the basis of pharmacological differences when expressed recombinantly in cell lines, but whether this pharmacological classification holds true in native cells and in vivo is less well-established. Nevertheless, several potent and selective P2X antagonists have been discovered in recent years and shown to be efficacious in various animal models including those for visceral organ function, chronic inflammatory and neuropathic pain, and inflammation. The recent advancement of drug candidates targeting P2X channels into human trials, confirms the medicinal exploitability of this novel target family and provides hope that safe and effective medicines for the treatment of disorders involving P2X channels may be identified in the near future.


Estimating Kidney Failure Risk Using Electronic Medical Records.
The four-variable kidney failure risk equation (KFRE) is a well-validated tool for patients with GFR <60 ml/min per 1.73 m2 and incorporates age, sex, GFR, and urine albumin-creatinine ratio (ACR) to forecast individual risk of kidney failure. Implementing the KFRE in electronic medical records is challenging, however, due to low ACR testing in clinical practice. The aim of this study was to determine, when ACR is missing, whether to impute ACR from protein-to-creatinine ratio (PCR) or dipstick protein for use in the four-variable KFRE, or to use the three-variable KFRE, which does not require ACR. Using electronic health records from OptumLabs Data Warehouse, patients with eGFR <60 ml/min per 1.73 m2 were categorized on the basis of the availability of ACR testing within the previous 3 years. For patients missing ACR, we extracted urine PCR and dipstick protein results, comparing the discrimination of the three-variable KFRE (age, sex, GFR) with the four-variable KFRE estimated using imputed ACR from PCR and dipstick protein levels. There were 976,299 patients in 39 health care organizations; 59% were women, the mean age was 72 years, and mean eGFR was 47 ml/min per 1.73 m2. The proportion with ACR testing was 19% within the previous 3 years. An additional 2% had an available PCR and 36% had a dipstick protein; the remaining 43% had no form of albuminuria testing. The four-variable KFRE had significantly better discrimination than the three-variable KFRE among patients with ACR testing, PCR testing, and urine dipstick protein levels, even with imputed ACR for the latter two groups. Calibration of the four-variable KFRE was acceptable in each group, but the three-variable equation showed systematic bias in the groups that lacked ACR or PCR testing. Implementation of the KFRE in electronic medical records should incorporate ACR, even if only imputed from PCR or urine dipstick protein levels.


Impact of intravenous lipid emulsion infusion on the stratum corneum barrier function in patients receiving parenteral nutrition.
The importance of the lipid matrix of stratum corneum (SC) in epidermal barrier function is well documented. Intravenous lipid emulsions (ILE) provide essential fatty acids (EFAs), main components of the SC lipid matrix. The objective of this study was to investigate the influence of ILE upon SC barrier function. The skin barrier was assessed by measuring transepidermal water loss (TEWL). Patients receiving lipid-containing parenteral nutrition (LCPN) were compared to patients receiving lipid-free PN (LFPN). In addition, a before/after LCPN introduction study was set up to limit the influence of inter-individual variability. Twenty-six patients receiving LCPN and seven patients receiving LFPN were included. Median age was not significantly different between the two groups. The TEWL of the LCPN group (9.05 g/m2/h) was significantly lower than the TEWL of the LFPN group (12.1 g/m2/h; Wilcoxon test: p = 0.016). The relative variation of TEWL before and after ILE treatment of 5 studied patients was 21.29 ± 10.28 %. ILE improve epidermal barrier function when compared to lipid-free parenteral treatments. Results of the before/after study confirm this conclusion and the usefulness of ILE intake for preventing excessive TEWL. SC barrier function improvement could be a choice criterion between the different ILE generations, in particular in burn patients and premature neonates.


Transcondylar Fossa Approach to Unruptured Vertebral Artery and Vertebral Artery-Posterior Inferior Cerebellar Artery Aneurysms: Surgical Outcome.
Surgical treatment of vertebral artery (VA) and VA-proximal posterior inferior cerebellar artery (PICA) aneurysms poses a special challenge to the operating surgeon because of the complex anatomy of the neck and the location of the aneurysm. We report our surgical results of unruptured VA and VA-PICA aneurysms operated on through the transcondylar fossa approach. We retrospectively analyzed the data of 20 patients with unruptured VA and VA-PICA aneurysms who were treated by the transcondylar fossa approach in a single institution from November 2014 to March 2018. Data including clinical profile, radiology, complications, and outcome were analyzed. Five patients had VA aneurysms and 15 had VA-PICA aneurysms. All were unruptured aneurysms, and 4 patients were symptomatic. All underwent surgical treatment through the transcondylar fossa approach. Proximal VA occlusion alone for 4 patients along with revascularization for 3 patients was performed. Twelve patients underwent clipping and 1 underwent wrapping of the aneurysm. The transcondylar fossa approach was adequate to expose the aneurysms successfully. There were no intraoperative complications encountered. Only 3 patients had transient postoperative complications. Follow-up imaging showed complete occlusion of all clipped aneurysms and complete thrombosis of the sac in all patients with proximal VA occlusion with or without revascularization. Although the incidence of rupture of asymptomatic unruptured VA and VA-PICA aneurysms is low, they should be considered for surgical treatment because they carry higher early mortality and morbidity after rupture. The transcondylar fossa approach provides adequate exposure of the aneurysm without permanent lower cranial nerve morbidity.


Are lipid phase transitions responsible for chilling damage in human platelets?
In previous studies we have proposed that the well-known chilling-induced activation of human blood platelets can be ascribed at least in part to a thermotropic phase transition in membrane lipids. The evidence that this is the case is reviewed and amplified in this review, followed by an examination of the available physical data concerning phase transitions in lipid mixtures that mimic the mixture found in platelet membranes. Assuming complete mixing at all temperatures and equal contributions of the members of the mixture to the phase transition, the lipid mixture found in platelets should give values for Tm ranging from about 1 degrees C to about 16 degrees C, depending on the isomers present in the mixture. (The former value is not in agreement with the observed Tm, but the latter is in excellent agreement.) However, examination of the phase diagram for a binary pair of lipids found in platelet membranes shows that ideal mixing almost certainly does not occur; instead of a linear phase diagram, a convex one was obtained. This shape for the phase diagram, which would displace Tm to an unexpectedly elevated temperature, is in agreement with previously published phase diagrams for mixtures of this type. The prediction, based on thermodynamic properties of lipids found in the platelets, is that Tm will be displaced upward in more complex mixtures of the composition found in platelets, a prediction that requires experimental testing.


Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study.
Vitamin D insufficiency may increase the risk for cardio metabolic disturbances in patients with primary hyperparathyroidism (PHPT). To analyze the vitamin D status and indices of the metabolic syndrome in PHPT patients and the effect of vitamin D supplementation after parathyroid adenomectomy (PTX). Double-blinded, randomized clinical trial (ClinicalTrials.gov identifier: NCT00982722) performed at Karolinska University Hospital, Sweden, April 2008 to November 2011. One hundred and fifty consecutive patients with PHPT (119 women) were randomized after PTX, 75 to oral treatment with calcium carbonate 1000 mg daily and 75 to calcium carbonate 1000 mg and cholecalciferol 1600 IU daily over 12 months. Changes in metabolic profile and ambulatory blood pressure (BP) were analyzed. Main outcome measures were changes in metabolic factors, BP, and body composition. The 25-hydroxyvitamin D (25-OH-D)-level was <50 nmol/l in 76% of the patients before PTX. After PTX, glucose, insulin, and IGF1 decreased, while the 25-OH-D and the IGF-binding protein 1 increased and remained unchanged at follow-up after study medication. One year of vitamin D supplementation resulted in lower parathyroid hormone (PTH) (40 (34-52) vs 49 (38-66) ng/l) and higher 25-OH-D (76 (65-93) vs 49 (40-62) nmol/l; P<0.05). Other laboratory parameters were stable compared with after PTX. Systolic BP decreased and total bone mineral content increased in both groups. Except for the lowering of the PTH level, no additive effect of vitamin D supplementation was seen. However, PTX proved effective in reducing insulin resistance.


Regulation of systemic energy homeostasis by serotonin in adipose tissues.
Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.


Upfront Brain Treatments Followed by Lung Surgery Improves Survival for Stage IV Non-small Cell Lung Cancer Patients With Brain Metastases: A Large Cohort Analysis.
Background: Current treatment guidelines for stage IV non-small cell lung cancer (NSCLC) with brain metastases recommend brain treatments, including surgical resection and radiotherapy (RT), in addition to resection of the primary lung tumor. Here, we investigate the less-studied impact of treatment sequence on the overall survival. Methods: The National Cancer Database was queried for NSCLC patients with brain metastases who underwent surgical resection of the primary lung tumor (n = 776). Kaplan-Meier survival curves with log-rank test and propensity score stratified Cox regression with Wald test were used to evaluate the associations between various treatment plans and overall survival (OS). Results: Compared to patients who did not receive any brain treatment (median OS = 6.05 months), significantly better survival was observed for those who received brain surgery plus RT (median OS = 26.25 months, p < 0.0001) and for those who received brain RT alone (median OS = 14.49 months, p < 0.001). Patients who received one upfront brain treatment (surgery or RT) before lung surgery were associated with better survival than those who received lung surgery first (p < 0.05). The best survival outcome (median OS 27.1 months) was associated with the sequence of brain surgery plus postoperative brain RT followed by lung surgery. Conclusions: This study shows the value of performing upfront brain treatments followed by primary lung tumor resection for NSCLC patients with brain metastases, especially the procedure of brain surgery plus postoperative brain RT followed by lung surgery.


Dietary Intake of Magnesium or Calcium and Chemotherapy-Induced Peripheral Neuropathy in Colorectal Cancer Patients.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe side-effect in colorectal cancer (CRC) patients. This study assessed the association between habitual dietary intake of magnesium or calcium and prevalence and severity of chronic CIPN in CRC patients receiving adjuvant chemotherapy. For this prospective cohort study, 196 CRC patients were considered. Magnesium and calcium intake was determined using a food frequency questionnaire at diagnosis, during and after chemotherapy. Chronic CIPN was assessed 12 months after diagnosis using the quality of life questionnaire CIPN20. Prevalence ratios were calculated to assess the association between magnesium or calcium intake and the prevalence of CIPN. Multivariable linear regression analysis was used to assess the association between magnesium or calcium intake and severity of CIPN. CIPN was reported by 160 (82%) patients. Magnesium intake during chemotherapy was statistically significantly associated with lower prevalence of CIPN (prevalence ratio (PR) 0.53, 95% confidence interval (CI) 0.32, 0.92). Furthermore, higher dietary intake of magnesium during (β -1.08, 95% CI -1.95, -0.22) and after chemotherapy (β -0.93, 95% CI -1.81, -0.06) was associated with less severe CIPN. No associations were found for calcium intake and the prevalence and severity of CIPN. To conclude, we observed an association between higher dietary magnesium intake and lower prevalence and severity of CIPN in CRC patients.


Non-flooded riparian Amazon trees are a regionally significant methane source.
Inundation-adapted trees were recently established as the dominant egress pathway for soil-produced methane (CH4) in forested wetlands. This raises the possibility that CH4 produced deep within the soil column can vent to the atmosphere via tree roots even when the water table (WT) is below the surface. If correct, this would challenge modelling efforts where inundation often defines the spatial extent of ecosystem CH4 production and emission. Here, we examine CH4 exchange on tree, soil and aquatic surfaces in forest experiencing a dynamic WT at three floodplain locations spanning the Amazon basin at four hydrologically distinct times from April 2017 to January 2018. Tree stem emissions were orders of magnitude larger than from soil or aquatic surface emissions and exhibited a strong relationship to WT depth below the surface (less than 0). We estimate that Amazon riparian floodplain margins with a WT < 0 contribute 2.2-3.6 Tg CH4 yr-1 to the atmosphere in addition to inundated tree emissions of approximately 12.7-21.1 Tg CH4 yr-1. Applying our approach to all tropical wetland broad-leaf trees yields an estimated non-flooded floodplain tree flux of 6.4 Tg CH4 yr-1 which, at 17% of the flooded tropical tree flux of approximately 37.1 Tg CH4 yr-1, demonstrates the importance of these ecosystems in extending the effective CH4 emitting area beyond flooded lands. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'.


14-3-3ε and ζ regulate neurogenesis and differentiation of neuronal progenitor cells in the developing brain.
During brain development, neural progenitor cells proliferate and differentiate into neural precursors. These neural precursors migrate along the radial glial processes and localize at their final destination in the cortex. Numerous reports have revealed that 14-3-3 proteins are involved in many neuronal activities, although their functions in neurogenesis remain unclear. Here, using 14-3-3ε/ζ double knock-out mice, we found that 14-3-3 proteins are important for proliferation and differentiation of neural progenitor cells in the cortex, resulting in neuronal migration defects and seizures. 14-3-3 deficiency resulted in the increase of δ-catenin and the decrease of β-catenin and αN-catenin. 14-3-3 proteins regulated neuronal differentiation into neurons via direct interactions with phosphorylated δ-catenin to promote F-actin formation through a catenin/Rho GTPase/Limk1/cofilin signaling pathway. Conversely, neuronal migration defects seen in the double knock-out mice were restored by phosphomimic Ndel1 mutants, but not δ-catenin. Our findings provide new evidence that 14-3-3 proteins play important roles in neurogenesis and neuronal migration via the regulation of distinct signaling cascades.


Molecular mechanisms of polyploidy and hybrid vigor.
Hybrids such as maize (Zea mays) or domestic dog (Canis lupus familiaris) grow bigger and stronger than their parents. This is also true for allopolyploids such as wheat (Triticum spp.) or frog (i.e. Xenopus and Silurana) that contain two or more sets of chromosomes from different species. The phenomenon, known as hybrid vigor or heterosis, was systematically characterized by Charles Darwin (1876). The rediscovery of heterosis in maize a century ago has revolutionized plant and animal breeding and production. Although genetic models for heterosis have been rigorously tested, the molecular bases remain elusive. Recent studies have determined the roles of nonadditive gene expression, small RNAs, and epigenetic regulation, including circadian-mediated metabolic pathways, in hybrid vigor, which could lead to better use and exploitation of the increased biomass and yield in hybrids and allopolyploids for food, feed, and biofuels.


Experiences of bereaved family caregivers with shared decision making in palliative cancer treatment: a qualitative interview study.
Patients with incurable cancer face complex medical decisions. Their family caregivers play a prominent role in shared decision making processes, but we lack insights into their experiences. In this study, we explored how bereaved family caregivers experienced the shared decision making process. We performed a qualitative interview study with in-depth interviews analysed with inductive content analysis. We used a purposive sample of bereaved family caregivers (n = 16) of patients with cancer treated in a tertiary university hospital in the Netherlands. Four themes were identified: 1. scenarios of decision making, 2. future death of the patient 3. factors influencing choices when making a treatment decision, and 4. preconditions for the decision making process. Most family caregivers deferred decisions to the patient or physician. Talking about the patient's future death was not preferred by all family caregivers. All family caregivers reported life prolongation as a significant motivator for treatment, while the quality of life was rarely mentioned. A respectful relationship, close involvement, and open communication with healthcare professionals in the palliative setting were valued by many interviewees. Family caregivers' experiences and needs seemed to be overlooked during medical encounters. Family caregivers of deceased patients with cancer mentioned life prolongation, and not quality of life, as the most important treatment aim. They highly valued interactions with the medical oncologist and being involved in the conversations. We advise medical oncologists to take more effort to involve the family caregiver, and more explicitly address quality of life in the consultations.


Effects of an opal termination codon preceding the nsP4 gene sequence in the O'Nyong-Nyong virus genome on Anopheles gambiae infectivity.
The genomic RNA of an alphavirus encodes four different nonstructural proteins, nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation terminates at an opal termination codon between nsP3 and nsP4. The polyprotein P1234 is produced when translational readthrough occurs or when the opal termination codon has been replaced by a sense codon in the alphavirus genome. Evolutionary pressures appear to have maintained genomic sequences encoding both a stop codon (opal) and an open reading frame (arginine) as a general feature of the O'nyong-nyong virus (ONNV) genome, indicating that both are required at some point. Alternate replication of ONNVs in both vertebrate and invertebrate hosts may determine predominance of a particular codon at this locus in the viral quasispecies. However, no systematic study has previously tested this hypothesis in whole animals. We report here the results of the first study to investigate in a natural mosquito host the functional significance of the opal stop codon in an alphavirus genome. We used a full-length cDNA clone of ONNV to construct a series of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal, ochre, or amber stop codon. The presence of an opal stop codon upstream of nsP4 nearly doubled (75.5%) the infectivity of ONNV over that of virus possessing a codon for the amino acid arginine at the corresponding position (39.8%). Although the frequency with which the opal virus disseminated from the mosquito midgut did not differ significantly from that of the arginine virus on days 8 and 10, dissemination did began earlier in mosquitoes infected with the opal virus. Although a clear fitness advantage is provided to ONNV by the presence of an opal codon between nsP3 and nsP4 in Anopheles gambiae, sequence analysis of ONNV RNA extracted from mosquito bodies and heads indicated codon usage at this position corresponded with that of the virus administered in the blood meal. These results suggest that while selection of ONNV variants is occurring, de novo mutation at the position between nsP3 and nsP4 does not readily occur in the mosquito. Taken together, these results suggest that the primary fitness advantage provided to ONNV by the presence of an opal codon between nsP3 and nsP4 is related to mosquito infectivity.


Glycerol hydrogenolysis promoted by supported palladium catalysts.
Catalytic hydrogenolysis, with high conversion and selectivity, promoted by supported palladium substrates in isopropanol and dioxane at a low H(2) pressure (0.5 MPa), is reported for the first time. The catalysts, characterized by using BET isotherms, transmission electron microscopy (TEM), temperature-programmed reduction (TPR), powder X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), were obtained by coprecipitation and impregnation techniques. The coprecipitation method allows catalysts with a metal-metal or a metal-support interaction to be obtained, which enhances the catalytic performance for both the conversion of glycerol and the selectivity to 1,2-propanediol. Analogous reactions carried out with catalysts prepared by using impregnation are less efficient. A study of the solvent and temperature effect is also presented. The obtained results allow the hydrogenolysis mechanism to be inferred; this involves both the direct replacement of the carbon-bonded OH group by an incoming hydrogen or the formation of hydroxyacetone as an intermediate, which subsequently undergoes a hydrogenation process to give 1,2-propanediol. Finally, catalytic tests on a large-scale reaction at a higher H(2) pressure and recycling of the samples were carried out with the better performing catalysts (Pd/CoO and Pd/Fe(2)O(3) prepared by using coprecipitation) to verify possible industrial achievements.


Coastal retreat and improved water quality mitigate losses of seagrass from sea level rise.
The distribution and abundance of seagrass ecosystems could change significantly over the coming century due to sea level rise (SLR). Coastal managers require mechanistic understanding of the processes affecting seagrass response to SLR to maximize their conservation and associated provision of ecosystem services. In Moreton Bay, Queensland, Australia, vast seagrass meadows supporting populations of sea turtles and dugongs are juxtaposed with the multiple stressors associated with a large and rapidly expanding human population. Here, the interactive effects of predicted SLR, changes in water clarity, and land use on future distributions of seagrass in Moreton Bay were quantified. A habitat distribution model of present day seagrass in relation to benthic irradiance and wave height was developed which correctly classified habitats in 83% of cases. Spatial predictions of seagrass and presence derived from the model and bathymetric data were used to initiate a SLR inundation model. Bathymetry was iteratively modified based on SLR and sedimentary accretion in seagrass to simulate potential seagrass habitat at 10 year time steps until 2100. The area of seagrass habitat was predicted to decline by 17% by 2100 under a scenario of SLR of 1.1 m. A scenario including the removal of impervious surfaces, such as roads and houses, from newly inundated regions, demonstrated that managed retreat of the shoreline could potentially reduce the overall decline in seagrass habitat to just 5%. The predicted reduction in area of seagrass habitat could be offset by an improvement in water clarity of 30%. Greater improvements in water clarity would be necessary for larger magnitudes of SLR. Management to improve water quality will provide present and future benefits to seagrasses under climate change and should be a priority for managers seeking to compensate for the effects of global change on these valuable habitats.


Recruitment near conspecific adults and the maintenance of tree and shrub diversity in a neotropical forest.
According to the Janzen-Connell hypothesis for the maintenance of species diversity, recruitment is inhibited in the immediate vicinity of adults by herbivores and pathogens. This reduces the per capita ability of abundant species to reproduce, relative to less common species, and gives rare or competitively inferior species a greater chance to persist. We tested this hypothesis in a 50-ha mapped plot of tropical moist forest on Barro Colorado Island, Panama, by investigating the spatial patterns of sapling recruitment in 80 species of trees and shrubs. Two censuses of adults and saplings were carried out, in 1982 and in 1985. Recruits were defined as saplings of 1-8 cm dbh (diameter breast height) appearing in the 1985 census that were not present in 1982. The distance from each recruit to its nearest conspecific adult neighbor was measured. At various distances from adults, the number of conspecific recruits and the number of recruits of all species were tallied. The ratio of recruits of species i to all recruits was taken as an estimate of the probability that species i would occupy that site as an adult. A few species showed a significant reduction in recruitment probability close to adults, but more species showed a significant increase, and many other species showed no significant spatial pattern. Among canopy trees, about a third of the species showed some sign of local reduction in recruitment, but the distance over which the effect extended was usually less than 5 m; however, the most abundant canopy tree, Trichilia tuberculata, showed a sharp reduction in recruitment probability up to 10 m from adults. In treelets and shrubs, most species showed strong peaks in recruitment probability close to adults. Thus, most recruitment patterns did not fit the prediction of Janzen and Connell; however, two to three of the most common species may have reached densities at which a depression in local recruitment is regulating abundance.


Influence of cell culture conditions and passage number on the response of membrane voltage to ATP and angiotensin II in rat mesangial cells.
The influence of passage number and different culture conditions on the effect of ATP and angiotensin II (A II) on membrane voltage (Vm) of rat mesangial cells (MC) was examined with the patch clamp technique in slow and fast whole cell recordings. MC were characterized immunologically and grown in standard medium in primary culture (PC) and long-term culture up to passage 21 in the presence of 90 g/l fetal calf serum (LTC/+FCS) or without or with 5 g/l FCS for 1-3 days (LTC/-FCS). In all three series the studies were performed in a FCS-free Ringer-like solution. Vm of MC did not differ in the series (PC: -49 +/- 1 mV, n = 151; LTC/+FCS: -52 +/- 1 mV, n = 49; LTC/-FCS: -51 +/- 1 mV, n = 44). In primary culture and long-term cultured MC up to passage 8, FCS (ED50 approximately 5 g/l), ATP (ED50 approximately 2 x 10(-6) mol/l) and A II (ED50 approximately 5 x 10(-10) mol/l) induced a depolarization of Vm. Reduction of extracellular Cl- concentration (from 145 to 32 mmol/l) had no effect on Vm but led to an increased depolarization of Vm by FCS, ATP and A II. In long-term cultured MC above passage 8 grown with 90 g/l FCS both ATP and A II induced a concentration-dependent hyperpolarization of Vm, which was attenuated in increased extracellular K+ concentration (from 3.6 to 33.6 mmol/l). In long-term cultured MC beyond passage 8, grown without or with a reduced FCS concentration of 5 g/l, ATP and A II led to a transient depolarization of Vm, which was increased in the presence of 32 mmol/l extracellular Cl-. The depolarization was followed by a hyperpolarization, which was attenuated in the presence of increased extracellular K+. The data indicate that vasoactive agents depolarize Vm of MC in primary culture by activating a Cl- conductance, whereas they hyperpolarize Vm by activation of a K+ conductance in long-term cultured MC grown with FCS. The latter effect was partially reversed when FCS was omitted.


Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro.
Endotoxemia is responsible for severe illness in horses. Individuals can become clinically unresponsive to the endotoxin molecule after an initial exposure; a phenomenon referred to as 'endotoxin tolerance' (ET). ET has been observed clinically in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMC) in vitro, and to describe selected cytokine responses which are associated with ET. ET was induced by culturing cells with three concentrations of endotoxin, and evaluated after a second dose of endotoxin given to challenge the cells. The relative mRNA expression of IL-10 and IL-12 was measured by use of quantitative PCR. ET was induced in all cells exposed to the 2-step endotoxin challenge. The relative mRNA expression of IL-10 in tolerized cells was not different from positive control cells. In contrast, the relative mRNA expression of IL-12 in tolerized cells was decreased by 15-fold after the second endotoxin challenge. This experiment demonstrated a reliable method for the ex vivo induction of ET in equine PBMC. A marked suppression of IL-12 production is associated with ET.


Comparison of Sinonasal Histopathological Changes in Biological Treatment of Eosinophilic Chronic Rhinosinusitis.
Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τb = -8.47, p < 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = -2.37, p = 0.02). Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.


Benzodiazepine administration during adult cardiac surgery: a survey of current practice among Canadian anesthesiologists working in academic centres.
Benzodiazepines are commonly administered during cardiac surgery because of their limited effect on hemodynamics and presumed role in preventing intraoperative awareness. Recent concerns about an increased risk of delirium with benzodiazepines have resulted in decreased usage in the intensive care unit and in geriatric perioperative practice. Little is known, however, about current benzodiazepine usage in the setting of adult cardiac surgery. We contacted all academic anesthesia departments in Canada to identify practicing attending cardiac anesthesiologists; this group constituted our sampling frame. Information regarding participant demographics, benzodiazepine usage, type, dose, and other administration details were obtained by electronic survey. Responses were analyzed descriptively. The survey was completed by 243/346 (70%) of cardiac anesthesiologists. Eleven percent of respondents do not administer benzodiazepines. Midazolam was the most commonly used benzodiazepine, with a mean (standard deviation) dose of 4.9 (3.8) mg given to an average patient. When respondents were asked the proportion of patients that they gave benzodiazepines, the response was bimodal. The most common considerations that influenced benzodiazepine use were patient age (73%), patient anxiety (63%), history of alcohol/drug/benzodiazepine use (60%), and the presence of risk factors for intraoperative awareness (44%). Benzodiazepine use is common among academic cardiac anesthesiologists in Canada. Nonetheless, heterogeneity exists between individual practices, suggesting clinical equipoise between restrictive and liberal administration of benzodiazepines for cardiac anesthesia. L'administration de benzodiazépines pendant la chirurgie cardiaque chez l'adulte: évaluation de la pratique actuelle des anesthésiologistes canadiens exerçant en milieu universitaire.


[Difficulties arising in rendering emergency psychiatric care to persons who committed suicide].
The author singles out the problems arising when rendering emergency psychiatric care to subjects liable to autoaggressive behavior. He analyzes and classifies the clinical experience gained by physicians of a special psychiatric emergency care center of Moscow and comes to a conclusion that a physician of an ambulance team should take into consideration the clinical, social, personality, and legal factors. Possible approaches to solution of the mentioned problems are outlined: creation of a net of "critical" departments, of a centralized data bank for information about registered patients, close relationships with legal organs and social services; he emphasizes that patients examined by physicians of psychoneurological centers should by no means be left alone till transportation teams arrive.


Placental adaptations in a nonhuman primate model of gestational protein restriction.
We previously demonstrated decreased placental perfusion, reduced amniotic fluid protein content, and increased pregnancy loss in a nonhuman primate model of gestational protein restriction. Here, our objective was to link these detrimental findings with a functional placental assessment. As blood flow is critical to maternal-fetal exchange, we hypothesized that a protein-restricted diet would impair placental taurine uptake. Pregnant rhesus macaques were maintained on either control chow (CON, n = 5), a 33% protein-restricted diet (PR33, n = 5), or a 50% PR diet (PR50, n = 5) prior to and throughout pregnancy. Animals were delivered on gestational day 135 (G135; term is G168). Taurine activity was determined in fresh placental villous explants. Taurine transporter (TauT) protein expression, placental growth factor (PLGF), and insulin-like growth factor (IGF)-1 and IGF-2 protein concentrations were measured, and histological assessment was performed. Fetal body weights and placental weights were comparable between all three groups at G135. Placental taurine uptake was decreased in PR33- and PR50-fed animals compared to CON, yet TauT expression was unchanged across groups. PLGF was significantly increased in PR50 vs. CON, with no change in IGF-1 or IGF-2 expression in placental homogenate from PR-fed animals. Accelerated villous maturation was observed in all PR50 cases, three of five PR33, and was absent in CON. We demonstrate conserved fetal growth, despite a decrease in placental taurine uptake. Increased expression of PLGF and expansion of the syncytiotrophoblast surface area in the severely protein-restricted animals suggest a compensatory mechanism by the placenta to maintain fetal growth.


The example of gastrointestinal damage induced by ionising radiation: are there accessible markers?
Ionising radiation exposure occurs during radiotherapy, diagnostic tests or by accident. In all cases the gastrointestinal tract, which is highly sensitive to radiation, may be at risk. Each region may respond differently to radiation exposure which to some extent is reflected by clinical symptoms. The evaluation of injury, whether acute or chronic, depends on the utilization of a variety of techniques. It appears that no definitive tests exist and that a multiparametric analysis should be undertaken. This review addresses the question of accessible markers associated with radiation-induced intestinal pathologies. Several approaches are discussed which include clinical observations, measurement of faecal parameters, changes in inflammatory mediators and possible applications of imaging techniques.


Evidence for motor learning in Parkinson's disease: acquisition, automaticity and retention of cued gait performance after training with external rhythmical cues.
People with Parkinson's disease (PD) have difficulty learning new motor skills. Evidence suggests external stimuli (cues) may enhance learning; however, this may be specific to cued rather than non-cued performance. We aimed to test effects of cued training on motor learning in PD. We defined motor learning as acquisition (single task), automaticity (dual task) and retention of single- and dual-task performance (follow-up). 153 subjects with PD received 3 weeks cued gait training as part of a randomised trial (the RESCUE trial). We measured changes in cued gait performance with three external rhythmical cues (ERC) (auditory, visual and somatosensory) during single and dual tasks after training and 6 weeks follow-up. Gait was tested without cues to compare specificity of learning (transfer). Subjects were 'on' medication and were cued at preferred step frequency during assessment. Accelerometers recorded gait and walking speed, step length and step frequency were determined from raw data. Data were analysed with SAS using linear regression models. Walking speed and step length significantly increased with all cues after training during both single- and dual-task gait and these effects were retained. Training effects were not specific to cued gait and were observed in dual-task step length, and walking speed however was more limited in single-task non-cued gait. These results support the use of ERC to enhance motor learning in PD as defined by increased acquisition, automaticity and retention. They also highlight the potential for sustained improvement in walking and complex task performance.


Prevention of hemorrhagic complications after dental extractions into open heart surgery patients under anticoagulant therapy: the use of leukocyte- and platelet-rich fibrin.
Leukocyte- and platelet-rich fibrin (L-PRF) is a biomaterial commonly used in periodontology and implant dentistry to improve healing and tissue regeneration, particularly as filling material in alveolar sockets to regenerate bone for optimal dental implant placement. The objective of this work was to evaluate the use of L-PRF as a safe filling and hemostatic material after dental extractions (or avulsions) for the prevention of hemorrhagic complications in heart surgery patients without modification of the anticoagulant oral therapy. Fifty heart surgery patients under oral anticoagulant therapy who needed dental extractions were selected for the study. Patients were treated with L-PRF clots placed into 168 postextraction sockets without modification of anticoagulant therapy (mean international normalized ratio = 3.16 ± 0.39). Only 2 patients reported hemorrhagic complications (4%), all of which resolved a few hours after the surgery by compression and hemostatic topical agents. Ten patients (20%) showed mild bleeding, which spontaneously resolved or was resolved by minimal compression less than 2 hours after surgery. No case of delayed bleeding was reported. The remaining 38 patients (76%) showed an adequate hemostasis after the dental extractions. In all cases, no alveolitis or painful events were reported, soft tissue healing was quick, and wound closure was always complete at the time of suture removal one week after surgery. The proposed protocol is a reliable therapeutic option to avoid significant bleeding after dental extractions without the suspension of the continuous oral anticoagulant therapy in heart surgery patients. Other applications of the hemostatic and healing properties of L-PRF should be investigated in oral implantology.


Hereditary gastrointestinal polyposis syndromes.
Hereditary gastrointestinal polyposis syndromes can be divided into adenomatous and hamartomatous types. Familial adenomatous polyposis coli (FAPC) is the prototype adenomatous polyposis syndrome and is defined by the autosomal dominant transmission of multiple (more than 100) colorectal adenomas. Virtually all affected patients develop colorectal carcinoma if untreated. Adenomas may develop also in the stomach and small bowel in FAPC patients, but the incidence of carcinoma in these sites is low. A variety of extracolonic manifestations has been reported in FAPC, with the name Gardner's syndrome applied to kindreds with osteomas of the skull and mandible, multiple epidermal cysts, and other skin and soft-tissue lesions. In Turcot's syndrome, brain tumors are present. The distinction between Gardner's and Turcot's syndromes and classical FAPC has become blurred because of marked overlap between them; some authorities consider them to be varying manifestations of a single genetic defect. The hamartomatous polyposes include Peutz-Jeghers syndrome, familial juvenile polyposis, Cowden's disease, intestinal ganglioneuromatosis, and the Ruvalcaba-Myrhe-Smith syndrome. The incidence of gastrointestinal cancer in patients with Peutz-Jeghers syndrome and familial juvenile polyposis exceeds that in the normal population, but is relatively low. In Cowden's disease, the gastrointestinal tract may be the site of multiple hamartomas, but there is no associated increase in the incidence of gastrointestinal cancers; instead, there is an increased incidence of carcinoma of the breast and thyroid. Intestinal ganglioneuromatosis occurs in von Recklinghausen's disease, in association with multiple endocrine neoplasia, type 2b, or as an isolated abnormality. Patients with ganglioneuromatosis do not appear to have an increased risk of developing gastrointestinal cancer. Ruvalcaba-Myrhe-Smith syndrome comprises macrocephaly, mental deficiency, an unusual craniofacial appearance, hamartomatous intestinal polyposis, and pigmented macules on the penis. No increased risk of developing cancer has been identified in the few reported cases.


Influence of the molecular weight and size dispersion of the electroluminescent polymer on the performance of air-stable hybrid light-emitting diodes.
The influence of the chain length and the molecular weight distribution of the electroluminescent polymer on the carrier transport properties and morphology of air stable hybrid light-emitting diodes is reported. It is found that variations between diverse as-received commercial batches play a major role in the performance of the devices, whose maximum luminance can differ up to 2 orders of magnitude. Through complementary optoelectronic, structural, and morphological characterization techniques, we provide insights into the relationship between charge dynamics and the structure of polymeric electroluminescent materials. The carrier dynamics are found to be dominated by both the polymeric chain length and the hole transport, which in turn is dependent on the concentration of trap states. Furthermore, the chain length is seen to affect the morphology of the active layer.


Handling Regional Variation in Health State Preferences within a Country.
Health state preferences vary among countries, and country-specific value sets are important in health care reimbursement decisions. When decisions are made at the regional level, regional variation in health state preferences may be important. We propose that shrinkage analysis and Bland-Altman plots can be a helpful way to investigate regional variation. The presence of regional variation can be investigated by introducing interactions between regions and the regression coefficients in the scoring algorithm. When variation is present, regional scoring algorithms can be derived through shrinkage analysis. The impact of using regional algorithms in place of the national algorithm can be investigated using simulation and illustrated using Bland-Altman plots. We applied this methodological approach to the Canadian EQ-5D-5L valuation study, which used time-tradeoff (TTO) tasks to elicit health state preferences from 1073 participants from 4 regions (Alberta, British Columbia, Ontario, and Quebec). There were statistically significant interactions between the fixed effects of the scoring algorithm and region. On computing regional scoring algorithms and applying them to the EQ-5D-5L health states reported by our population, the mean utility using the Canada-wide scoring algorithm was 0.87 (standard error, 0.0013), compared to 0.85 (0.0013) on using the algorithm for Alberta, 0.80 (0.0013) on using the algorithm for British Columbia, 0.91 (0.0013) for Ontario, and 0.89 (0.0014) for Quebec. When health care falls under regional jurisdiction, shrinkage estimators can be used to generate regional scoring algorithms for the EQ-5D-5L and Bland-Altman plots used to assess the importance of regional variation in health state preferences. Our results suggest that mean health state preferences vary among Canada's regions and make a sizable impact on estimates of population mean utility.


The 5'-terminal structure of poly(A)-containing RNA of soybean seeds.
Poly(A)-containing RNA from soybean seeds was isolated by affinity chromatography on poly(U)-Sepharose. Translation of poly(A)-containing RNA was inhibited by the addition of m7GMP. Treatment of the poly(A)-containing RNA with periodate followed by aniline (a chemical removal of 5'-terminal m7G) resulted in a marked reduction of mRNA activity. mRNA activity of the treated RNA was partially restored when S-adenosyl methionine (SAM) was included the wheat germ cell-free system. End groups of the poly(A)-containing RNA were labeled by oxidation with periodate and reduction with [3H]borohydride. Analysis of nuclease digests of 3H-labeled poly(A)-containing RNA showed the existence of materials with a charge between --2 and--3 and/or between --3 and--4 which contain pyrophosphate linkages. These results imply the presence of 5'-terminal capped structures, m7G(5')PPp(5')N and m7G(5')PPP(5')Nm, in soybean poly(A)-containing RNA.


In Vivo Effectiveness of Several Antimicrobial Locks To Eradicate Intravascular Catheter Coagulase-Negative Staphylococci Biofilms.
Tunneled central venous catheter (TCVC) related infection remains a challenge in the care of hemodialysis patients. We aimed to determine the best antimicrobial lock therapy (ALT) to eradicate coagulase-negative staphylococci (CoNS) biofilms. We studied the colonization status of the catheter every 30 days by quantitative blood cultures (QBC) drawn through all catheter lumens. Those patients with a significant culture (i.e.,100 to 1,000 CFU/mL) of a CoNS were classified as patients with a high risk of developing catheter-related bloodstream infections (CRBSI). They were assigned to receive daptomycin, vancomycin, teicoplanin lock solution, or the standard of care (SoC) (i.e., heparin lock). The primary endpoint was to compare eradication ability (i.e., negative QBC for 30 days after ending ALT) rates between different locks and the SoC. A second objective was to analyze the correlation between ALT exposure and isolation of CoNS with antimicrobial resistance. Daptomycin lock was associated with a significant higher eradication success than with the SoC: 85% versus 30% (relative risk [RR] = 14, 95% confidence interval [CI] = 2.4 - 82.7); followed by teicoplanin locks with a 83.3% success (RR = 11.7; 95% CI = 2 - 70.2). We observed CoNs isolates with a higher teicoplanin MIC in patients with repeated teicoplanin locks exposure (coefficient = 0.3; 95% CI = 0.11 - 0.47). However, teicoplanin MICs decreased in patients treated with vancomycin locks (coefficient = -0.56; 95% CI = -0.85 - -0.02). Methicillin-resistance decreased with accumulative ALT (RR = 0.82; 95% CI = 0.69 - 0.98). In this study, daptomycin locks achieve the highest eradication rate of CoNS from hemodialysis catheters in vivo.


The road to pluripotence: the research response to the embryonic stem cell debate.
The controversies surrounding embryonic stem cell research have prompted scientists to invent beyond restrictive national policy and moral concerns. The impetus behind these reports comes from different sources, including individually held moral beliefs, societal pressures and resource constraints, both biological and financial. Along with other contributions to public policy such as advocacy or public testimony, experimentation and scientific curiosity are perhaps more natural responses scientists use to surmount impediments to research. In a research context, we review the history of the first stem cell discoveries, and describe scientific efforts leading up to recent reports of pluripotent lines made without the use of human embryos and eggs. We argue that despite the promise of these new lines, we must not lose sight of fundamental questions remaining at the frontiers of embryology and early human development. The answers to these questions will impact studies of genetics, cell biology and diseases such as cancer, autoimmunity and disorders of development. Human embryonic stem cell research is barely a decade old. The recent pace of discovery--in spite of federal restrictions--is testament to the potential of these cells to uncover some of biology's most intractable mysteries.


Change of Nutritional Status Assessed Using Subjective Global Assessment Is Associated With All-Cause Mortality in Incident Dialysis Patients.
Subjective global assessment (SGA) is associated with mortality in end-stage renal disease (ESRD) patients. However, little is known whether improvement or deterioration of nutritional status after dialysis initiation influences the clinical outcome. We aimed to elucidate the association between changes in nutritional status determined by SGA during the first year of dialysis and all-cause mortality in incident ESRD patients. This was a multicenter, prospective cohort study. Incident dialysis patients with available SGA data at both baseline and 12 months after dialysis commencement (n = 914) were analyzed. Nutritional status was defined as well nourished (WN, SGA A) or malnourished (MN, SGA B or C). The patients were divided into 4 groups according to the change in nutritional status between baseline and 12 months after dialysis commencement: group 1, WN to WN; group 2, MN to WN; group 3, WN to MN; and group 4, MN to MN. Cox proportional hazard analysis was performed to clarify the association between changes in nutritional status and mortality. Being in the MN group at 12 months after dialysis initiation, but not at baseline, was a significant risk factor for mortality. There was a significant difference in the 3-year survival rates among the groups (group 1, 92.2%; group 2, 86.0%; group 3, 78.2%; and group 4, 63.5%; log-rank test, P < 0.001). Multivariate Cox regression analysis revealed that the mortality risk was significantly higher in group 3 than in group 1 (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.27-6.03, P = 0.01) whereas the mortality risk was significantly lower in group 2 compared with group 4 (HR 0.35, 95% CI 0.17-0.71, P < 0.01) even after adjustment for confounding factors. Moreover, mortality risk of group 3 was significantly higher than in group 2 (HR 2.89, 95% CI 1.22-6.81, P = 0.02); there was no significant difference between groups 1 and 2. The changes in nutritional status assessed by SGA during the first year of dialysis were associated with all-cause mortality in incident ESRD patients.


Probiotic potential of lactic acid bacteria isolated from fermented dairy milks on antiproliferation of colon cancer cells.
Fifty-four strains of lactic acid bacteria obtained from fermented dairy milks were investigated for possible use as probiotics and for colon cancer biological products. Five of these strains inhibited growth of eight food-borne pathogens including Helicobacter pylori, Escherichia coli, and Salmonella typhimurium. Three of these strains survived at pH 2.5 and in 0.3% bile salts. Additionally they produced no haemolysis, were resistant to kanamycin and adhered to Caco-2 cells. 16S rRNA gene sequences of probiotic strains indicated that RM11 and RM28 were Enterococcus faecium and Lactobacillus fermentum, respectively. Both the cultured medium and live whole cells from probiotic strains were tested for antiproliferation of colon cancer cells through MTT and Trypan Blue exclusion assays. The probiotic strains of E. faecium RM11 and L. fermentum RM28 also triggered antiproliferation of colon cancer cells at the rates of 21-29%, and 22-29%, respectively. This suggested that both strains could be used as potential probiotics in functional food or for colon cancer biological products.


Labour exploitation and health: a case series of men and women seeking post-trafficking services.
Research on the health of trafficked men and on the health problems associated with trafficking for labor exploitation are extremely limited. This study analysed data from a case series of anonymised case records of a consecutive sample of 35 men and women who had been trafficked for labor exploitation in the UK and who were receiving support from a non-governmental service between June 2009 and July 2010. Over three-quarters of our sample was male (77 %) and two-thirds aged between 18 and 35 years (mean 32.9 years, SD 10.2). Forty percent reported experiencing physical violence while they were trafficked. Eighty-one percent (25/31) reported one or more physical health symptoms. Fifty-seven percent (17/30) reported one or more post-traumatic stress symptoms. A substantial proportion of men and women who are trafficked for labor exploitation may experience violence and abuse, and have physical and mental health symptoms. People who have been trafficked for forced labor need access to medical assessment and treatment.


Formalin-induced nociceptive responses in diabetic mice.
In non-diabetic mice, s.c. injection of formalin to the hindpaw had a biphasic effect: an immediate nociceptive response (first-phase) followed by a tonic response (second-phase). However, only the immediate nociceptive response was observed in diabetic mice. The duration of the first-phase response was significantly longer in diabetic mice than in non-diabetic mice. In diabetic mice, when spantide, an antagonist of substance P, reduced the duration of the nociceptive response in the first-phase to the levels that were observed in non-diabetic mice, the second-phase response appeared. The second phase also became apparent in diabetic mice after pretreatment with naltrindole (3 mg/kg), an antagonist of delta-opioid receptors. These results suggest that a negative control system, which is mediated by delta-opioid receptors and links substance P with somatostatin-mediated nociceptive transmission, may inhibit the formalin-induced second-phase of the nociceptive response in diabetic mice.


Relationship between gender role attitude and fertility rate in women referring to health centers in Mashhad in 2013.
Fertility rate apparently is a non-interventional behavior, but in practice, it is influenced by social values and norms in which culture and traditional beliefs play a significant role. In this regard, some studies have shown that gender roles can be associated with reproductive behaviors. With regard to the importance of annual reduction of population growth rate and its outcomes, the present study was performed to determine the relationship between gender role attitude and fertility rate in women referring to Mashhad health centers in 2013. The present study is an analytical cross-sectional and multistage sampling study performed on 712 women. Data were collected by a questionnaire consisting of two sections: Personal information and gender role attitude questionnaire that contained two dimensions, i.e. gender stereotypes and gender egalitarianism. Its validity was determined by content validity and its reliability by internal consistency (r = 0.77). Data were analyzed by SPSS software version 16. Initial analysis of the data indicated that there was a significant relationship between acceptance of gender stereotypes (P = 0.008) and gender egalitarianism (P < 0.001), and fertility. There was also a direct association between acceptance of gender stereotypes and fertility rate (r = 0.13) and an indirect association between egalitarianism and fertility rate (r = -0.15). The results of the present study indicate that there is an association between gender role attitude and fertility. Paying attention to women's attitude is very important for successful planning in the improvement of fertility rate and population policy.


Clostridium difficile-associated colitis.
To review the basic microbiology, pathogenesis of disease, and diagnosis of the nosocomial pathogen Clostridium difficile and to examine therapies recommended by the Canadian Task Force on Preventive Health Care. QUALITY OF EVIDENCE MEDLINE: was searched using MeSH headings. Controlled trials for therapy were sought, but case-control studies and observational reviews were included. Clostridium difficile causes approximately 20% of cases of diarrhea associated with antibiotics, including clindamycin and the second- and third-generation cephalosporins. Diarrhea is usually mild, but can be severe; extreme cases develop toxic megacolon. Diagnosis is dependent on demonstrating presence of clostridial toxin in stool specimens or of pseudomembranes through sigmoidoscopy. First-line therapy for C. difficile diarrhea is restricted to metronidazole. Second-line therapy for treatment failure is vancomycin. For relapse, a second course of metronidazole is recommended; tapering courses of vancomycin and probiotics are used for multiple recurrences. Clostridium difficile is an important nosocomial pathogen requiring prudent use of antibiotics and strict infection-control policies to prevent large health care costs.


Overview article: Impact of primary and secondary care collaboration on hospitalization for chronic heart failure: Two comparative studies.
In the past decade, a legal framework was created in Germany that promotes intense collaboration at the interface between primary and secondary care. This overview article distinguishes between the effects of two complementary programs aimed at improving ambulatory care in Baden-Wuerttemberg: (1) general practitioner-centered care (GPCC), which strengthens the role of general practitioners, and (2) collaborative cardiology care (CCC), which coordinates primary and cardiology care. The overview article presents two already published studies that assess the impact of the programs on hospitalizations in patients with chronic heart failure (CHF) based on claims data from 2016. The hospitalization rate of patients enrolled in GPCC (N=75,096) and CCC (N=13,404) were compared with corresponding control groups (N=65,618 and N=8,776 respectively). The hospitalization rate in GPCC was lower than in the control group (risk ratio 0.97; 95% CI: 0.95-0.99, P=0.0024). GPCC patients with CHF that received specialist cardiology care as part of CCC had significantly lower hospitalization rates than those receiving standard cardiology care (risk ratio 0.92; 0.88-0.97, P=0.0014). This overwiew study shows that reforming medical care and compensation at the interface between general practice and specialist care can lead to fewer hospital admissions in patients with CHF. Overall, this article underlines the importance of collaboration between primary care physicians and specialists for patients with CHF that are receiving ambulatory care.


Safeguarding the Caribbean's future: making the case to research the direct and indirect impacts of climate change on youth mental health and wellbeing.
This article makes a call for attention to paid on the development of a research agenda for studying the impact of climatic events on youth mental health in the Caribbean. It details the climate injustices that the region faces and the potential mental health problem which can arise from climatic events. It makes a call for interdisciplinary research and a multi stakeholder approach to dealing with this potential issue.


Salivary pepsin as an independent predictor of treatment response for laryngopharyngeal reflux: prospective cohort study with multivariate analysis.
To analyze the predictive value of salivary pepsin for treatment outcomes in laryngopharyngeal reflux (LPR) using multivariate analysis that includes various associated factors. This prospective cohort study was conducted between August 2020 and August 2022. Patients with LPR who had symptoms lasting more than 1 month and a reflux symptom index (RSI) of 14 or higher were enrolled. The participants received a 2-month regimen of proton pump inhibitors (PPIs) treatment and lifestyle modification. Salivary pepsin was checked using fasting saliva before treatment. Salivary pepsin was detected more frequently in the good treatment response group (61.1%), compared to 14.3% in the poor response group. Similarly, patients with higher compliance to lifestyle modifications (> 90%) had a higher chance of a good response (91.7%) compared to those with lower compliance, who had a 53.8% chance of a good response. Other clinical factors have no significant association with treatment response. In multivariate analysis, both pretreatment salivary pepsin and higher compliance with lifestyle modification were found to be independent factors for treatment response (OR 14.457, CI 1.075 ~ 194.37 for both). This study found that positive salivary pepsin and strict lifestyle modification are independent predictors of treatment outcomes in LPR.


A scalable empathic-mindset intervention reduces group disparities in school suspensions.
Suspensions remove students from the learning environment at high rates throughout the United States. Policy and theory highlight social groups that face disproportionately high suspension rates-racial-minoritized students, students with a prior suspension, and students with disabilities. We used an active placebo-controlled, longitudinal field experiment (Nteachers = 66, Nstudents = 5822) to test a scalable "empathic-mindset" intervention, a 45- to 70-min online exercise to refocus middle school teachers on understanding and valuing the perspectives of students and on sustaining positive relationships even when students misbehave. In preregistered analyses, this exercise reduced suspension rates especially for Black and Hispanic students, cutting the racial disparity over the school year from 10.6 to 5.9 percentage points, a 45% reduction. Significant reductions were also observed for other groups of concern. Moreover, reductions persisted through the next year when students interacted with different teachers, suggesting that empathic treatment with even one teacher in a critical period can improve students' trajectories through school.