Suicide and suicide attempts in adults: exploring suicide risk 24 months after a psychiatric emergency room visit.
Suicide risk (including attempted and completed suicide) should be measured over short periods of time after contacting health services. The objective of this study was to identify the patterns of attempted and completed suicides within 24-months of a psychiatric emergency department visit, as well as to investigate predictive risk factors, including sociodemographic and clinical variables, previous suicidal behavior, and service utilization. A convenience sample (n=147), recruited at a general hospital's psychiatric emergency room, included patients with suicidal ideation, suicidal plans or previous suicide attempts. These patients were followed for 24 months, focusing on two main outcomes: attempted and completed suicides. After six months there were no completed suicides and 36 suicide attempts, while after 24 months there were seven completed suicides and 69 suicide attempts. A final logistic regression model for suicide attempts at 24 months identified somatic pathology and the number of previous psychiatric hospitalizations as predictive factors, with a good area under the receiver operating characteristic curve. The findings showed distinct patterns of attempted and completed suicides over time, indicating the importance of a systematic multidisciplinary suicide risk evaluation in psychiatric emergency rooms.


[Professional health of military servicewomen].
For the last few years there were enlarged possibilities of completing of troops by military servicewomen. Coincidently with this, there were increased requirements for military servicewomen. On the base of postulate of three levels of professional health, determining effectiveness of professional activity (social-psychological, psychological and physiological) there was realized a research of morbidity and functional state of organism of military servicewomen, of relations of these indexes with effectiveness of discharging of professional responsibilities. Was marked, that military servicewomen in other equal conditions of health care achieve the required indexes by high personal adaptation potential, neuro-psychoic tolerance, adherence to collective forms of military work, adequate orientation in concrete situation, rapid elaboration of strategy of behavior and socialization. The got data permitted to make a system-structure analyze of professional health of military servicewomen and on it's base to determine directions of improvement of their medical maintenance.


Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer.
There are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor. Our purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease. A large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel. After adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease. These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.


Regulation of dharma/bozozok by the Wnt pathway.
The zebrafish homeobox gene dharma/bozozok (boz) is required for the formation and/or function of the Nieuwkoop center and the subsequent induction of the Spemann organizer. dharma is expressed soon after the midblastula transition in the dorsal blastomeres and the dorsal yolk syncytial layer (YSL). We found that the expression of dharma was upregulated or ectopically induced by misexpression of a Wnt protein and cytoplasmic components of the Wnt signaling pathway and downregulated by the expression of dominant-negative Tcf3. A 1.4-kbp fragment of the dharma promoter region contains consensus sequences for Tcf/Lef binding sites. This promoter region recapitulated the Wnt-dependent and dorsal dharma expression pattern when it was fused to luciferase or GFP. Deletion and point mutant analyses revealed that the Tcf/Lef binding sites were required to drive this expression pattern. These data established that dharma/boz functions between the dorsal determinants-mediated Wnt signals and the formation of the Nieuwkoop center.


Phylogenomic analyses reveal novel relationships among snake families.
Snakes are a diverse and important group of vertebrates. However, relationships among the major groups of snakes have remained highly uncertain, with recent studies hypothesizing very different (and typically weakly supported) relationships. Here, we address family-level snake relationships with new phylogenomic data from 3776 nuclear loci from ultraconserved elements (1.40million aligned base pairs, 52% missing data overall) sampled from 29 snake species that together represent almost all families, a dataset ∼100 times larger than used in previous studies. We found relatively strong support from species-tree analyses (NJst) for most relationships, including three largely novel clades: (1) a clade uniting the boas, pythons and their relatives, (2) a clade placing cylindrophiids and uropeltids with this clade, and (3) a clade uniting bolyeriids (Round Island boas) with pythonids and their relatives (xenopeltids and loxocemids). Relationships among families of advanced snakes (caenophidians) were also strongly supported. The results show the potential for phylogenomic analyses to resolve difficult groups, but also show a surprising sensitivity of the analyses to the inclusion or exclusion of outgroups.


Measuring brain atrophy with a generalized formulation of the boundary shift integral.
Brain atrophy measured using structural magnetic resonance imaging (MRI) has been widely used as an imaging biomarker for disease diagnosis and tracking of pathologic progression in neurodegenerative diseases. In this work, we present a generalized and extended formulation of the boundary shift integral (gBSI) using probabilistic segmentations to estimate anatomic changes between 2 time points. This method adaptively estimates a non-binary exclusive OR region of interest from probabilistic brain segmentations of the baseline and repeat scans to better localize and capture the brain atrophy. We evaluate the proposed method by comparing the sample size requirements for a hypothetical clinical trial of Alzheimer's disease to that needed for the current implementation of BSI as well as a fuzzy implementation of BSI. The gBSI method results in a modest but reduced sample size, providing increased sensitivity to disease changes through the use of the probabilistic exclusive OR region.


Inter-laboratory study of an LC-MS/MS method for simultaneous determination of deoxynivalenol and its acetylated derivatives, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol in wheat.
To validate an LC-MS/MS method for simultaneous determination of deoxynivalenol (DON) and its acetylated derivatives, 3-acetyl-deoxynivalenol (3ADON) and 15-acetyl-deoxynivalenol (15ADON), in wheat using a multifunctional column, an inter-laboratory study was performed in 9 laboratories using one blank wheat sample, three spiked wheat samples (10, 50, 150 µg/kg) and one naturally contaminated wheat sample. The recoveries ranged from 98.8 to 102.6% for DON, 89.3 to 98.7% for 3ADON, and from 84.9 to 90.0% for 15ADON. The relative standard deviations for repeatability (RSDR) and reproducibility (RSDR) of DON were in the ranges of 7.2-11.3% and 9.5-22.6%, respectively. For 3ADON, the RSDR ranged from 5.3 to 9.5% and the RSDR ranged from 16.1 to 18.0%, while for 15ADON, the RSDR ranged from 6.2 to 11.2% and the RSDR ranged from 17.0 to 27.2%. The HorRat values for the three analytes ranged from 0.4 to 1.2. These results validate this method for the simultaneous determination of DON and its acetylated derivatives, 3ADON and 15ADON.


Togolese lay people's and health professionals' views about the acceptability of physician-assisted suicide.
To study the views on the acceptability of physician-assisted-suicide (PAS) of lay people and health professionals in an African country, Togo. In February-June 2012, 312 lay people and 198 health professionals (75 physicians, 60 nurses and 63 health counsellors) in Togo judged the acceptability of PAS in 36 concrete scenarios composed of all combinations of four factors: (a) the patient's age, (b) the level of incurability of the illness, (c) the type of suffering and (d) the patient's request for PAS. In all scenarios, the patients were women receiving the best possible care. The ratings were subjected to cluster analysis and analyses of variance. Most lay people (59%) were not systematically opposed to PAS, whereas most health professionals (80%) were systematically opposed to it. The most important factors in increasing acceptability among people not systematically opposed were advanced age of the patient and incurability of the illness. Additional acceptability was provided by the patient's request to have her life ended, although much less so than in studies in Western countries, and by suffering characterised by complete dependence rather than by extreme physical pain. These empirical findings--the first ones gathered in the African continent--suggest that most Togolese lay people are not categorically for or against PAS, but judge its degree of acceptability as a function of concrete circumstances.


Anticancer activity of essential oils: a review.
Natural essential oil constituents play an important role in cancer prevention and treatment. Essential oil constituents from aromatic herbs and dietary plants include monoterpenes, sesquiterpenes, oxygenated monoterpenes, oxygenated sesquiterpenes and phenolics among others. Various mechanisms such antioxidant, antimutagenic and antiproliferative, enhancement of immune function and surveillance, enzyme induction and enhancing detoxification, modulation of multidrug resistance and synergistic mechanism of volatile constituents are responsible for their chemopreventive properties. This review covers the most recent literature to summarize structural categories and molecular anticancer mechanisms of constituents from aromatic herbs and dietary plants.


Bridging Integrator-1 protein loss in Alzheimer's disease promotes synaptic tau accumulation and disrupts tau release.
Polymorphisms associated with BIN1 confer the second greatest risk for developing late onset Alzheimer's disease. The biological consequences of this genetic variation are not fully understood, however BIN1 is a binding partner for tau. Tau is normally a highly soluble cytoplasmic protein, but in Alzheimer's disease tau is abnormally phosphorylated and accumulates at synapses to exert synaptotoxicity. The purpose of this study was to determine if alterations to BIN1 and tau in Alzheimer's disease promote the damaging redistribution of tau to synapses, as a mechanism by which BIN1 polymorphisms may increase risk of developing Alzheimer's disease. We show that BIN1 is lost from the cytoplasmic fraction of Alzheimer's disease cortex, and this is accompanied by the progressive mislocalization of phosphorylated tau to synapses. We confirmed proline 216 in tau as critical for tau interaction with the BIN1-SH3 domain and show that phosphorylation of tau disrupts this binding, suggesting that tau phosphorylation in Alzheimer's disease disrupts tau-BIN1 associations. Moreover, we show that BIN1 knockdown in rat primary neurons to mimic BIN1 loss in Alzheimer's disease brain, causes the damaging accumulation of phosphorylated tau at synapses and alterations in dendritic spine morphology. We also observed reduced release of tau from neurons upon BIN1 silencing, suggesting that BIN1 loss disrupts the function of extracellular tau. Together, these data indicate that polymorphisms associated with BIN1 that reduce BIN1 protein levels in the brain likely act synergistically with increased tau phosphorylation to increase risk of Alzheimer's disease by disrupting cytoplasmic tau-BIN1 interactions, promoting the damaging mis-sorting of phosphorylated tau to synapses to alter synapse structure, and by reducing the release of physiological forms of tau to disrupt tau function.


Cyber-Analytics: Identifying Discriminants of Data Breaches.
In this study, the relationship between data breach characteristics and the number of individuals affected by these violations was considered. Data were acquired from the Department of Health and Human Services breach reporting database and analyzed using SPSS. Regression analyses revealed that the hacking/IT incident breach type and network server breach location were the most significant predictors of the number of individuals affected; however, they were not predictive when combined. Moreover, network server location and unauthorized access/disclosure breach type were predictive when combined. Additional analyses of variance revealed that covered entity type and business associate presence were significant predictors, while the geographic region of a breach occurrence was insignificant. The results of this study revealed several associations between healthcare breach characteristics and the number of individuals affected, suggesting that more individuals are affected in hacking/IT incidents and network server breaches independently and that network server breach location and unauthorized access/disclosure breach type were predictive in combination.


Exotic Attractors of the Nonequilibrium Rabi-Hubbard Model.
We explore the phase diagram of the dissipative Rabi-Hubbard model, as could be realized by a Raman-pumping scheme applied to a coupled cavity array. There exist various exotic attractors, including ferroelectric, antiferroelectric, and incommensurate fixed points, as well as regions of persistent oscillations. Many of these features can be understood analytically by truncating to the two lowest lying states of the Rabi model on each site. We also show that these features survive beyond mean field, using matrix product operator simulations.


Adipose tissue recruitment of leukocytes.
In December of 2003, two seminal articles describing the presence of macrophages in obese adipose tissue were published. These adipose tissue macrophages (ATMs) are inflammatory and promote local and systemic insulin resistance. Due to the continuing rise in obesity around the world, understanding how these ATMs contribute to metabolic disorders is of much interest. Chemokines have been extensively studied for their role in ATM recruitment. Deficiency or antagonism of chemokine receptors that interact with multiple chemokine ligands reduces ATM accumulation. ATMs are now defined as either classically (M1) or alternatively (M2) activated. Peroxisome proliferator-activated receptor activation and adiponectin promote an M2-polarized state resulting in improved insulin sensitivity. Finally, recent studies have provided evidence that T lymphocytes, natural killer T cells, mast cells, and B cells also enter adipose tissue and may interact with macrophages and adipocytes. Literature published during the past year has shown that macrophage recruitment to adipose tissue is only one of the important mediators of obesity-related insulin resistance. The phenotype of ATMs and recruitment of other immune cells to the adipose tissue play key roles in the overall contribution of adipose tissue to systemic metabolic outcomes of obesity.


Taxonomic revision of the endemic Cameroonian freshwater crab genus Louisea Cumberlidge, 1994 (Crustacea, Decapoda, Brachyura, Potamonautidae), with descriptions of two new species from Nkongsamba and Yabassi.
The taxonomy of the freshwater crab genus Louisea Cumberlidge, 1994, is reviewed based on type material and newly obtained specimens from three different localities in southwestern Cameroon. The genus is endemic to Cameroon and previously included two species: L. edeaensis (Bott, 1969) (type species) from Lake Ossa wetland complex (altitudes below 400 m asl) and L. balssi (Bott, 1959) from Kumba and Mt. Manengouba (altitudes above 1300 m asl). Here two new species of Louisea are described based on morphological and/or genetic data: L. nkongsamba sp. nov. from the Nlonako Ecological Reserve (1000-1400 m asl) in the sub-montane zone and L. yabassi sp. nov. from Yabassi in the lowlands. A redescription and amended diagnostic features of L. edeaensis and L. balssi are provided, and the genus diagnosis is updated to accommodate all four species. An identification key is also provided for the species of Louisea. A tree of phylogenetic relationships based on three mtDNA loci (COI, 12S rRNA, and 16S rRNA) supports the taxonomic revision, and indicates speciation of Louisea species along an altitudinal gradient, but further phylogenetic analyses are needed to understand whether this can lend support to the hypothesis that there is a montane centre of speciation along the Cameroon Volcanic Line. The phylogenetic tree also shows that Buea Cumberlidge, Mvogo Ndongo, Clark & Daniels, 2019 and Potamonemus Cumberlidge & Clark, 1992 are sister genera that may be derived from the Louisea lineage.


[Invasive disease caused by Streptococcus pneumoniae: a 7-year study].
The purpose of this study was to study the epidemiology of invasive childhood pneumococcal infection in our hospital. The records of all children attending our hospital from whom Streptococcus pneumoniae was isolated from the blood or CSF were reviewed. Serotyping and MIC were performed at C.N.M.V.S. (Majadahonda). Seventy-one pneumococci were isolated in 70 patients. The annual incidence increased from 0.14% to 0.40%. The clinical entities were: bacteremia without focus (45%), pneumonia (29.6%), meningitis (12.7%), cellulitis (5.6%), mastoiditis (5.6%) and endocarditis (1.4%). The age of 72% of the patients was less than 3 years. In 26.8% of the cases, the patient had an underlying disease and/or was previously hospitalized. The antibiotic susceptibility pattern was: penicillin (MIC < or = 0.06 microgram/ml) 45.7%, cefotaxime (MIC < or = 0.5 microgram/ml) 82.8% and erythromycin (MIC < or = 0.5 microgram/ml) 70%. Penicillin resistance of the isolated pneumococci was more often present in the group with risk factors than in those without such risk factors (p < 0.05). There were 13 different serotypes, the most prevalent were 6 (23%), 19 (17%), 14 (14%) and 23 (12%) and the most frequently penicillin-resistant (Resistant N(o)/Total N(o) were: 6 (15/15), 9 (4/4), 14 (8/9) and 23 (6/8). Streptococcus pneumoniae is a common cause of invasive infections in children in our hospital. There was a high prevalence of serotype 6 (penicillin-resistant) as compared to in adults where serotype 3 (penicillin-susceptible) is the most prevalent. A higher rate of antibiotic resistant strains associated with risk factors (underlying disease or nosocomial acquisition), probably related to prior antibiotic use, was observed.


Anisotropic electrokinetic transport in channels modified with patterned polymer brushes.
Molecular dynamics simulations have been used to predict the transport dynamics of fluids through nanochannels with polymer patterning surfaces. The effects of different parameters, such as separation between polymer stripes, solvent quality, and direction and strength of the electric field, were explored in terms of electroosmotic flow transport characteristics, conformational dynamics of the polymer brush and ion distribution. Anisotropic electrokinetic transport becomes significant due to the surface patterning of polymers when the direction of the electric field is changed. At the separation between adjacent polymer stripes comparable to the chain length, local strong flow close to the bare surfaces weakens dramatically under the electric field along the stripe direction. However, when the electric field is switched to the direction perpendicular to the stripes, the flow is enhanced considerably. The coupling of the polymer solvent quality further richens and complicates the transport behaviors. We explain the physical mechanism of the electroosmotic flow in complex polymer patterning channels by analyzing the interrelationship among various properties.


[A case of chromophobe cell renal carcinoma].
We report a case of chromophobe cell renal carcinoma. A 59-year-old female was admitted to our hospital with asymptomatic gross hematuria. Abdominal computerized tomography showed an approximately 4 cm. minimally enhancing mass in the left kidney. Angiography revealed a hypovascular tumor in the left kidney. Under the diagnosis of renal cell carcinoma, left radical nephrectomy was performed. The cut surface of the tumor was beige in color with few foci of hemorrhage and necrosis. Microscopically, the tumor was composed of the cells with voluminous reticulated cytoplasm stained lightly with routine hematoxylin and eosin. Hale's colloidal iron staining demonstrated a positive cytoplasmic reaction. Pathological diagnosis was chromophobe cell renal carcinoma. Chromophobe cell renal carcinoma is a recently established subtype of renal cell carcinoma, which has rarely been reported in Japan.


[Efforts to gain further insight into unexplained deaths among children].
Child abuse can be overlooked as a cause of death, particularly in cases in which there is initially no known cause of death and the death remains unexplained. To rectify this serious situation, both the government and member of parliament Arib have developed proposals to amend the procedures found in the Burial and Cremation Act regarding the deaths of minors. The government hopes to promote closer post-mortem examination for those paediatric cases, including sudden infant death syndrome, in which the cause of death remains unexplained by requiring further investigation into the cause of death (the so-called NODO procedure). Arib proposed a bill in May 2006 that would require all deceased minors to be examined by a forensic expert. Arguments against the latter proposal include the unnecessary burden it would place on surviving relatives of children who die of clearly natural causes. At this time, the NODO procedure proposed by the government appears to be the more rational choice. At the same time, training for medical professionals, particularly general practitioners and paediatricians, should give ample attention to identifying injuries caused by child abuse and how best to deal with the parents.


Adjuvant therapy with pegylated interferon-alfa2b vs observation in stage II B/C patients with ulcerated primary: Results of the European Organisation for Research and Treatment of Cancer 18081 randomised trial.
Subgroup analyses of two large EORTC adjuvant interferon-alpha2b (IFNα-2b) vs observation randomised trials demonstrated that a treatment benefit was observed only in patients with an ulcerated melanoma without palpable nodes (hazard ratio [HR] for recurrence-free survival [RFS] was 0.69). This was confirmed by a meta-analysis of 15 adjuvant IFN trials (HR: 0.79). In the EORTC 18081 trial, sentinel node-negative stage II patients with an ulcerated primary melanoma were 1:1 randomised between pegylated (PEG)-IFNα-2b at 3 μg/kg/week subcutaneously and observation, for 2 years, or until disease recurrence or unacceptable toxicity in spite of dose adjustments to maintain an Eastern Cooperative Oncology Group performance status of 0 or 1. Main end-point was RFS. Secondary end-points included distant metastasis-free survival (DMFS), overall survival, and safety (EudraCT Number: 2009-010273-20). Between February 2013 and January 2017, only 112 patients were randomised, 56 in each arm. The trial was stopped early for lack of recruitment. At a 3.4-year median follow-up, the estimated HR for the PEG-IFNα-2b group compared with the observation group regarding RFS was 0.66 (95% confidence interval [CI]: 0.32-1.37), and the 3-year RFS rate was 80.0% (95% CI: 65.7-88.8%) and 72.9% (95% CI: 58.3-83.0%), respectively. DMFS was prolonged: HR: 0.39 (95% CI: 0.15-0.97), and the 3-year DMFS rate was 90.6% (95% CI: 78.9-96.0%) vs 76.4% (95% CI: 62.1-85.9%). One patient in the PEG-IFNα-2b group died compared with 4 in the observation group. Fifty-four patients started PEG-IFNα-2b treatment, 16 (29%) completed 2 years of treatment, 2 (4%) stopped due to recurrence, 23 (43%) due to toxicity and 14 (25%) due to other reasons. The EORTC 18081 PEG-IFNα-2b randomised trial, observed a similar HR (0.69) for RFS as the previous EORTC trials (0.69). In countries without access to new drugs, adjuvant (PEG)-IFNα-2b treatment is an option for patients with ulcerated melanomas without palpable nodes.


Pharmacological Treatment of Cognitive Symptoms in Major Depressive Disorder.
Cognitive dysfunction is a core transdiagnostic domain of Major Depressive Disorder (MDD) and is a principal determinant of functional recovery. However, it has been insufficiently targeted within the current therapeutic framework for MDD. To highlight these unmet cognitive needs in MDD. An article search was conducted using PubMed from inception to November 2016: Major Depressive Disorder (and/or variant) was cross-referenced with the following terms: antidepressants, augmentation, cognition, cognitive deficits, cognitive dysfunction, functional outcomes, mechanism of action, and treatment. Articles informed by observational studies, clinical trials, and review articles relevant to the discussion of cognition and cognitive impairment in MDD were included for review. Additional terms and citations previously not identified in the initial search were obtained from a manual review of article reference lists. Cognitive deficits in MDD are replicable, non-specific, and clinically significant. Abnormalities in the domains of learning/memory, executive function, attention, concentration, and processing speed are consistently reported. Only two antidepressants (i.e., duloxetine and vortioxetine) have established procognitive effects utilizing rigorous methodology in MDD. Most antidepressants improve cognitive function(s), but the extent to which they directly exert pro-cognitive effects is not yet understood. Cognitive dysfunction in MDD is a principal determinant of patient-reported outcomes (e.g., psychosocial function). Healthcare providers are encouraged to screen for cognitive dysfunction in MDD and familiarize themselves with the efficacy profiles of antidepressants on disparate cognitive domains.


Optical online monitoring of uric acid removal during dialysis.
This study estimates the total removal of uric acid (TR(UA)) by online UV absorbance measurements in the spent dialysate in two different dialysis centers in Estonia and Sweden. Sixteen dialysis patients were included. All dialysate was collected that gave the reference for TR(UA). Two regression models were investigated: one for each patient (UV1) and one for the entire material (UV2). TR(UA) from the three methods was in the same order but showed a statistically significant difference when the UV2 model was built on data from both centers together. TR(UA), (n = 56) was (mean +/- SD, micromol): 5,854 +/- 1,377 for reference, 6,117 +/- 1,795 for UV1 and 5,762 +/- 1,591 for UV2. Six patients were monitored 1 year after the first study session, using the same models as the previous year, still having a nonsignificant difference. The results show the possibility of estimating TR(UA) by using UV absorbance. The method appeared to be reliable also in long-term patient monitoring.


Sex bias in neuroscience and biomedical research.
Female mammals have long been neglected in biomedical research. The NIH mandated enrollment of women in human clinical trials in 1993, but no similar initiatives exist to foster research on female animals. We reviewed sex bias in research on mammals in 10 biological fields for 2009 and their historical precedents. Male bias was evident in 8 disciplines and most prominent in neuroscience, with single-sex studies of male animals outnumbering those of females 5.5 to 1. In the past half-century, male bias in non-human studies has increased while declining in human studies. Studies of both sexes frequently fail to analyze results by sex. Underrepresentation of females in animal models of disease is also commonplace, and our understanding of female biology is compromised by these deficiencies. The majority of articles in several journals are conducted on rats and mice to the exclusion of other useful animal models. The belief that non-human female mammals are intrinsically more variable than males and too troublesome for routine inclusion in research protocols is without foundation. We recommend that when only one sex is studied, this should be indicated in article titles, and that funding agencies favor proposals that investigate both sexes and analyze data by sex.


[Strictureplasty in the surgical treatment of complicated Crohn's disease].
Crohns disease is a panintestinal chronic inflammatory condition. Its remitting-relapsing behaviour may require in the single patient repeated surgeries, with the aim of resolving the complications of the disease. The awereness that surgery cannot resolve the disease has led, in the last years, to the development of new "conservative surgical techniques", which preserve as much of the intestinal tissue as possible. These techniques are minimal resection and strictureplasty (SP). Aim of the study was to perform a prospective analysis of the long-term outcome of SP in a consecutive series of patients undergoing surgery for complicated Crohns Disease at the Division of general surgery, L. Sacco University Hospital, Milano, Italia. During the period of October 1992 to June 2002, 286 patients underwent surgical procedures for jejunoileal Crohns disease. 116 of them underwent SP resulting in a total of 217 procedures, of which: 111 Heineke-Mikulicz SP (51.2%), 36 ileoileal side-to-side SP (16.6%), 40 ileoceacal SP (18.4%) and the remaining 30 ileocolic SP (13.8%), as previously described by A.M. Taschieri. Fiftyone of the patients (23.5%) had concomitantly a minimal bowel resection. Postoperative mortality was nil, while in 3 cases (2.59%) repeated surgery was necessary due to postsurgical complications. Time-to-event estimates were performed using the Kaplan-Meier function. mortality, morbidity, and long-term results in this population of patients who underwent SP are encouraging and in line with reports in the international literature. It is suggested that SP together with minimal bowel resections, may be considered as first line surgical therapy in patients with Crohns Disease.


The risk of drug overdose death among adults with select types of disabilities in the United States - A longitudinal study using nationally representative data.
Disability is associated with increased risk of drug overdose mortality, but previous studies use coarse and inconsistent methods to identify adults with disabilities. This investigation makes use of the US Department of Health and Human Services disability questions to estimate the risk of drug overdose death among US adults using seven established disability categories. The longitudinal Mortality Disparities in American Communities study was used to determine disability status among a nationally representative sample of adults age ≥ 18 in 2008 (n = 3,324,000). Through linkage to the National Death Index, drug overdose deaths were identified through 2019. Adults in mutually-exclusive disability categories (hearing, vision, cognitive, mobility, complex activity, ≥2 limitations) were compared to adults with no reported disabilities using adjusted hazard ratios (aHRs) and controlling for demographic and socioeconomic covariates. The risk of drug overdose death varied considerably by disability type, as adults in some disability categories displayed only marginally significant risk, while adults in other disability categories displayed substantially elevated risk. Compared to non-disabled adults, the risk of drug overdose death was highest among adults with ≥2 limitations (aHR = 3.0, 95% CI = 2.8-3.3), cognitive limitation (aHR = 2.6, 95% CI = 2.3-2.9), mobility limitation (aHR = 2.6, 95% CI = 2.3-2.9), complex activity limitation (aHR = 2.3, 95% CI = 1.8-2.9), hearing limitation (aHR = 1.6, 95% CI = 1.3-1.9), and vision limitation (aHR = 1.3, 95% CI = 1.0-1.7). The examination of specific disability categories revealed unique associations that were not apparent in previous research. These findings can be used to focus overdose prevention efforts on the populations at greatest risk for drug-related mortality.


Early childhood trauma and disorders of extreme stress as predictors of treatment outcome with chronic posttraumatic stress disorder.
History of early childhood trauma was prevalent and highly correlated with Disorders of Extreme Stress Not Otherwise Specified (DESNOS) in a sample of veterans in inpatient treatment for chronic posttraumatic stress disorder (PTSD). DESNOS predicted reliable change on a variety of measures of psychiatric symptomatology (including PTSD) and psychosocial functioning independently of the effects of PTSD diagnosis and early childhood trauma history. DESNOS also predicted treatment outcome on PTSD and quality of life measures after controlling for the effects of ethnicity, war zone trauma exposure severity, initial level of symptomatic severity or quality of life, Axis I (PTSD and major depression) and Axis II (personality disorder) diagnostic status, and early childhood trauma history. Early childhood trauma was not predictive of outcome. DESNOS appears to play an important role in assessment and treatment planning for psychotherapeutic rehabilitation of chronic PTSD.


Interferon Receptor Trafficking and Signaling: Journey to the Cross Roads.
Like most plasma membrane proteins, type I interferon (IFN) receptor (IFNAR) traffics from the outer surface to the inner compartments of the cell. Long considered as a passive means to simply control subunits availability at the plasma membrane, an array of new evidence establishes IFNAR endocytosis as an active contributor to the regulation of signal transduction triggered by IFN binding to IFNAR. During its complex journey initiated at the plasma membrane, the internalized IFNAR complex, i.e. IFNAR1 and IFNAR2 subunits, will experience post-translational modifications and recruit specific effectors. These finely tuned interactions will determine not only IFNAR subunits destiny (lysosomal degradation vs. plasma membrane recycling) but also the control of IFN-induced signal transduction. Finally, the IFNAR system perfectly illustrates the paradigm of the crosstalk between membrane trafficking and intracellular signaling. Investigating the complexity of IFN receptor intracellular routes is therefore necessary to reveal new insight into the role of IFNAR membrane dynamics in type I IFNs signaling selectivity and biological activity.


Optical coherence tomography angiography in intermediate uveitis-related cystoid macular edema.
Cystoid macular edema (CME) is the leading cause of permanent visual impairment in patients with uveitis, particularly in patients with intermediate uveitis (IU). This study was aimed at comparing the changes in the macular microvasculature in patients with IU with uveitic non-responsive CME and without macular edema. In this case-control study, 55 eyes of patients with IU were assessed for macular microvascular structures, including vascular density, foveal avascular zone (FAZ) measurement, and vascular morphological changes, using spectral-domain optical coherence tomography angiography (OCT-A) with the AngioVue OCT-A system. We divided patients into the following two groups: the case group, including 30 eyes with IU-related non-responsive CME, and the control group, including 25 eyes with IU without macular edema. Participants in the case and control groups had comparable age (P = 0.753) and sex (P = 0.124) distributions. Superficial capillary plexus vessel density in the case group was significantly decreased in the whole image (P = 0.027) and the parafoveal area (P = 0.001) compared to the control group. However, there were no statistically significant differences between the two groups in terms of foveal superficial vessel density, deep capillary plexus vessel density, FAZ area, FAZ perimeter, FAZ acircularity index, or foveal vessel density in a 300-µm-wide annulus around the FAZ (all P > 0.05). Vascular morphological changes, such as the capillary tuft, telangiectatic vessels, or micro-aneurism, were not different in the overview images of the OCT-A printout between the two groups. The mean superficial capillary plexus vessel density was lower in eyes with IU-related nonresponsive CME than in those without macular edema. We observed more cystoid spaces in SCP than in DCP. Microcystic changes in the inner retina and ischemia may be the underlying cause in eyes with nonresponsive CME. Future prospective longitudinal studies with healthy, matched controls are warranted to confirm our findings.


Initiatorless Photopolymerization of Liquid Crystal Monomers.
Liquid crystal monomers are widely employed in industry to prepare optical compensating films as well as extend or enhance the properties of certain display modes. Because of the thermotropic nature of liquid crystalline materials, polymerization of liquid crystalline monomers (sometimes referred to as reactive mesogens) is often initiated by radical photoinitiation (photopolymerization) of (meth)acrylate functional groups. Here, we report on the initiatorless photopolymerization of commercially available liquid crystalline monomers upon exposure to 365 nm UV light. Initiatorless polymerization is employed to prepare thin films as well as polymer stabilizing networks in mixtures with low-molar-mass liquid crystals. EPR and FTIR confirm radical generation upon exposure to 365 nm light and conversion of the acrylate functional groups. A potential mechanism is proposed, informed by control experiments that indicate that the monomers undergo a type II Norrish mechanism. The initiatorless polymerization of the liquid crystalline monomers yield liquid crystalline polymer networks with mechanical properties that can be equal to those prepared with conventional radical photoinitiators. We demonstrate that initiatorless polymerization of display modes significantly increases the voltage holding ratio, which could result in a reduction in drive voltages in flat-panel televisions and hand-held devices, extending battery life and reducing power consumption.


A co-infection with two gastrointestinal nematodes alters host immune responses and only partially parasite dynamics.
Given their global distribution and abilities to persist in the host, helminths can play a crucial role in affecting risk of infections by increasing individual variation in infection. Helminth co-infections are of particular interest because by altering host immune responses, they can modify host susceptibility and thus intensity and transmission of other parasites/pathogens. The dynamics of co-infection were examined using two helminths of the European rabbit. Individuals were simultaneously challenged with a primary dose of both parasites, and changes in intensity were examined in relation to local and systemic immune responses. Both helminths persisted in co-infected rabbits; however, contrasting dynamics and immune responses were observed. Graphidium strigosum intensity was high throughout the co-infection, while Trichostrongylus retortaeformis intensity decreased but was not completely cleared. A Th2 response was observed against G. strigosum, while a mixed Th1/Th2 profile was found to T. retortaeformis. A comparison with our previous work on single infections showed that G. strigosum intensity was higher in co-infected than single infected hosts, while T. retortaeformis showed no significant changes. Differences were also observed in the cytokine profiles, blood cell concentrations and antibody trends. Overall, host variability during helminth co-infections can be generated by significant differences in immune responses and/or parasite dynamics.


Accumulation of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone in alkaloid genotypes of burley tobacco during postharvest processing: comparisons with N'-nitrosonornicotine and probable nitrosamine precursors.
Recent work showed that 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was present in some cured tobacco and was more carcinogenic than N'-nitrosonornicotine (NNN). In the present investigation, the concentration relationships of NNK, NNN, and their probable precursors, i.e., nitrite, nitrate, and alkaloids, were determined: (a) after the growth of Ky 14 burley tobacco under different shade conditions followed by air curing; and (b) during preparation of air-cured and homogenized-leaf-cured (HLC) burley tobaccos from conventionally grown tobaccos of different alkaloid genotypes. A capillary gas chromatography-nitrogen-phosphorus detector procedure was developed and utilized for quantitative determinations of NNK and NNN. NNK contents ranged from 0.2 to 0.5 micrograms/g in air-cured Ky 14 tobacco lamina from leaves grown under 0 to 65% shade (100, 65, and 35% of natural daylight). The highest NNK concentrations were from 45% shade-grown lamina from lower leaf positions on stalks. Concentrations of NNK did not correlate significantly with those of either nitrate or total alkaloids calculated over all shade treatments and stalk positions. During HLC tobacco processing, the following significant correlations of NNK with precursor content changes were found for each of four burley alkaloid genotypes calculated over the four successive stages of processing: NNN (r = 1.0); and nitrate (r = -0.9). NNK also correlated negatively with nicotine concentration changes (r = -0.9) in the low-alkaloid and high-alkaloid isolines during processing. After a 20-h incubation period under aerobic conditions followed by a 1-h standing period without aeration, substantial increases of NNK were observed in each burley line. The increased NNK contents ranged from 9-fold for the low-alkaloid isoline to 99-fold for the nornicotine-converter line. Increases in NNK content (27 to 69%) also occurred during the air drying stage; further increases occurred during a 15-month storage period at ambient conditions. After the HLC process and prolonged storage, maximal NNK contents were observed in each tobacco genotype in the following order of increasing NNK content: Ky 14 cultivar, 79 micrograms/g; low-alkaloid line, 80 micrograms/g; nornicotine converter line, 102 micrograms/g; and high-alkaloid line, 177 micrograms/g. At the beginning of a controlled environmental storage period used for high-alkaloid and low-alkaloid isoline air-cured and HLC tobaccos, NNK contents correlated with nitrite (r = 1.0) and nitrate (r = -0.9) calculated over the two curing regimens.(ABSTRACT TRUNCATED AT 400 WORDS)


[Non-invasive techniques in diagnosis of steatosis and fibrosis in nonalcoholic fatty liver disease].
Diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD) is one of the most actual problems of modern hepatology. Ultrasound elastometry is alternative method to determine the density of the liver tissue. The efficiency of the method was confirmed by a large amount of data in patients with viral hepatitis. However, the diagnostic value of elastometry was not studied enough in patients with NAFLD. THE AIM OF THE RESEARCH: to study the possibility of non-invasive diagnostic methods of examination in a complex assessment of the liver in patients with NAFLD. We studied 24 patients with signs of NAFLD and a long persistent elevation of liver enzymes. All patients underwent a needle biopsy of the liver. We conducted a comparative analysis of the results of the morphological study of the liver tissue with ultrasound elastometry, computed tomography of the liver, biochemical blood tests. Among biochemical liver enzymes ALT was a marker of NAFLD which characterized the transformation of steatosis to steatohepatitis. The combined ALT and GGT increase reflected the high activity of inflammation in the liver tissue. Elastometry results were comparable to the histological features in all liver fibrosis stages, but the maximum diagnostic accuracy was observed at the late stages. The area under the ROC-curves showed the highest precision in the F2-F3 stages, the lowest value - in the F1 stage. Imprecision of the method in the early stages of fibrosis may be due to the hepatic steatosis in NAFLD and high biochemical activity with cholestasis signs. Patients with early-stage liver fibrosis diagnosed with elastometry need additional examination using other methods of noninvasive diagnostic tools.


Modeling and Implementation of Multi-Position Non-Continuous Rotation Gyroscope North Finder.
Even when the Global Positioning System (GPS) signal is blocked, a rate gyroscope (gyro) north finder is capable of providing the required azimuth reference information to a certain extent. In order to measure the azimuth between the observer and the north direction very accurately, we propose a multi-position non-continuous rotation gyro north finding scheme. Our new generalized mathematical model analyzes the elements that affect the azimuth measurement precision and can thus provide high precision azimuth reference information. Based on the gyro's principle of detecting a projection of the earth rotation rate on its sensitive axis and the proposed north finding scheme, we are able to deduct an accurate mathematical model of the gyro outputs against azimuth with the gyro and shaft misalignments. Combining the gyro outputs model and the theory of propagation of uncertainty, some approaches to optimize north finding are provided, including reducing the gyro bias error, constraining the gyro random error, increasing the number of rotation points, improving rotation angle measurement precision, decreasing the gyro and the shaft misalignment angles. According them, a north finder setup is built and the azimuth uncertainty of 18" is obtained. This paper provides systematic theory for analyzing the details of the gyro north finder scheme from simulation to implementation. The proposed theory can guide both applied researchers in academia and advanced practitioners in industry for designing high precision robust north finder based on different types of rate gyroscopes.


Hydrogen sulfide-producing variants of Escherichia coli.
Seventeen strains of H(2)S-producing variants of Escherichia coli were isolated from specimens submitted for microbiological study (ten from stool, five from urine, and two from postmortem material). Production of H(2)S was unstable in several strains; however, other than their production of H(2)S, all strains closely resembled typical E. coli in their biochemical reactions. In vitro susceptibilities of the H(2)S-producing variants to antimicrobics closely resembled those of typical E. coli in this laboratory.


Unveiling the non-covalent interactions of molecular homodimers by dispersion-corrected DFT calculations and collision-induced broadening of ro-vibrational transitions: application to (CH2F2)2 and (SO2)2.
Thermodynamic and spectroscopic properties of molecular complexes featuring non-covalent interactions, such as van der Waals forces and hydrogen bonds, are of fundamental interest in many fields, ranging from chemistry and biology to nanotechnology. In the present work the homodimers of difluoromethane (CH2F2) and sulfur dioxide (SO2) are investigated theoretically using dispersion-corrected density functional theory (DFT-D3) and experimentally by tunable diode laser (TDL) infrared (IR) spectroscopy. The dissociation energies of (CH2F2)2 and (SO2)2 are determined experimentally from the broadening of the ro-vibrational transitions of the corresponding monomers collisionally perturbed by a range of damping gases. The resulting dissociation energies are 2.79 ± 0.32 and 2.62 ± 0.16 kcal mol(-1) for the CH2F2 and SO2 dimers, respectively. Six to nine different stationary points on the PES of the two complexes are investigated theoretically at the DFT-D3 level, retrieving the corresponding dissociation energies, structures and rotational constants. Computations are carried out by employing six different density functionals (BLYP, TPSS, B3LYP, PBE0, TPSSh, and PW6B95) in conjunction with def2-TZVP and in a few cases def2-QZVP basis sets. DFT-D3 dissociation energies are benchmarked against reference values from CCSD(T)/CBS computations, and furthermore compared to experimental ones. A very good agreement between theory and experiment is attained, showing that DFT-D3 provides a significant improvement over standard DFT. This work shows that dissociation energies of homodimers can be consistently derived from collisional broadening cross sections and that interaction energies at various DFT-D3 levels (nearly) reach the accuracy of highly correlated wavefunction methods.


Myeloid body associations in the frog pigment epithelium.
Myeloid bodies are found in the retinal pigment epithelium of certain vertebrate species. They are organized structural forms of the smooth endoplasmic reticulum which are usually seen as stacks of flattened, smooth saccules having a circular or lens-shaped configuration. Our findings in the frog Rana pipiens suggest that changes occur in the structure of the myeloid bodies which are related to the phase of the diurnal lighting cycle. At certain times, the myeloid bodies are found closely associated with other cytoplasmic organelles, notably the nucleus and oil droplet. In addition these associations can be induced by incubation of the isolated eyecup in the presence of guanosine 3',5'-monophosphate.


Defining a common set of indicators to monitor road accidents in the European Union.
currently road accidents are mostly monitored through mortality and injury rates. This paper reports the methodology and the results of a project set forth by the European Union (EU) and coordinated by the WHO aimed at identifying and evaluating a core set of indicators to monitor the causal chain of road accident health effects. The project is part of the ECOEHIS (Development of Environment and Health Indicators for European Union Countries). a group of experts (WG), identified 14 indicators after a review of the information collected at the EU level, each of them representing a specific aspect of the DPSEEA (Driving, Pressure, State, Exposure, Effect, Action) model applied and adapted to the road accidents. Each indicator was scored according to a list of 16 criteria chosen by the WG. Those found to have a high score were analysed to determine if they were compatible with EU legislation and then tested in the feasibility study. 11 of the 14 indicators found to be relevant and compatible with the criteria of selection were proposed for the feasibility study. Mortality, injury, road accident rate, age of vehicle fleet, and distance travelled are the indicators recommended for immediate implementation. after overcoming the limitations that emerged (absence of a common definition of death by road accident and injury severity, underestimation of injuries, differences in information quality) this core set of indicators will allow Member States to carry out effective internal/external comparisons over time.


Predicting features of breast cancer with gene expression patterns.
Data from gene expression arrays hold an enormous amount of biological information. We sought to determine if global gene expression in primary breast cancers contained information about biologic, histologic, and anatomic features of the disease in individual patients. Microarray data from the tumors of 129 patients were analyzed for the ability to predict biomarkers [estrogen receptor (ER) and HER2], histologic features [grade and lymphatic-vascular invasion (LVI)], and stage parameters (tumor size and lymph node metastasis). Multiple statistical predictors were used and the prediction accuracy was determined by cross-validation error rate; multidimensional scaling (MDS) allowed visualization of the predicted states under study. Models built from gene expression data accurately predict ER and HER2 status, and divide tumor grade into high-grade and low-grade clusters; intermediate-grade tumors are not a unique group. In contrast, gene expression data is inaccurate at predicting tumor size, lymph node status or LVI. The best model for prediction of nodal status included tumor size, LVI status and pathologically defined tumor subtype (based on combinations of ER, HER2, and grade); the addition of microarray-based prediction to this model failed to improve the prediction accuracy. Global gene expression supports a binary division of ER, HER2, and grade, clearly separating tumors into two categories; intermediate values for these bio-indicators do not define intermediate tumor subsets. Results are consistent with a model of regional metastasis that depends on inherent biologic differences in metastatic propensity between breast cancer subtypes, upon which time and chance then operate.


Association Between Multiple Lines of Active Therapy and Prognosis in Esophageal Squamous Cell Carcinoma.
Esophageal squamous cell carcinoma (ESCC) is a critical threat to health and life. More than half of ESCC patients have recurrent or metastatic disease. Most late-stage patients undergo first-line treatment but experience further progression. Many of these patients have good performance status and are able to receive second-line therapy and even further treatments rather than best supportive care. Our analysis aimed to explore whether multiple lines of active treatment are beneficial in ESCC patients. We conducted a retrospective cohort study. Univariate and multivariate survival analyses were used to identify whether the number of active treatment lines was related to prognosis. All analyses and the corresponding survival curves were based on the Cox proportional hazard regression model and the Kaplan-Meier method. Comparisons between groups were conducted using the t-test, chi-square test, and Fisher's exact test, as applicable. Of a total of 138 patients with recurrent or metastatic disease, 66 (61.1%) received one line of active treatment, and 42 (38.9%) patients received two and more lines. Multiple lines of active therapy were statistically significantly associated with better prognosis (crude hazard ratio (HR) (95% confidence interval (CI))=0.21 (0.06-0.73)), even after adjusting for relevant confounders (adjusted HR (95% CI)=0.19 (0.04-0.86)). More grade 3-4 hepatotoxicity patients were observed in the multiple-line treatment group (p=0.033). A small number of patients were cured by palliative management; these patients were more likely to have received both systematic and local treatment than other patients with repeated progression (9/15 versus 40/117, p=0.051). Multiple lines of active treatment are related to prolonged survival in recurrent and metastatic ESCC patients, and adverse effects are acceptable. Comprehensive therapy modalities are recommended.


Refractive Outcomes of Retropupillary Fixated Iris-Claw Lens for Exchange of the Dislocated Intraocular Lens Using Modified Scleral Incisions.
To evaluate refractive outcomes after retropupillary iris-claw intraocular lens (IOL) implantation and to compare postoperative astigmatism from (1) a conventional 5.5-mm sclerocorneal incision, (2) an L-shaped scleral tunnel incision, and (3) a frown scleral tunnel incision. This was a retrospective study of eyes undergoing dislocated IOL exchange for a retropupillary iris-claw IOL. Uncorrected and corrected distance visual acuity (UDVA and CDVA) and postoperative complications were evaluated until postoperative months 24. The refractive outcomes and the surgically induced astigmatism (SIA) vector were compared between groups. The medical records of 107 eyes from 107 patients with mean age of 65.31 ± 12.15 years were reviewed. Eyes with a frown incision showed the best UDVA, followed by those with L-shaped and conventional incisions (P = 0.003). Eyes with an L-shaped incision or frown incision had a lower SIA than that of the conventional incision group at postoperative 6 months (mean ± standard deviation [SD] SIA, 0.86 ± 0.85 D, 0.63 ± 0.37 D, and 1.70 ± 1.27 D for frown incision, L-shaped incision, and conventional incisions, respectively; P = 0.004). The frown incision and L-shaped incision induced a significantly smaller SIA than the conventional incisions, which was associated with better UDVA postoperatively.


Identification of a metabolic signature for multidimensional impairment and mortality risk in hospitalized older patients.
A combination of several metabolic and hormonal adaptations has been proposed to control aging. Little is known regarding the effects of multiple deregulations of these metabolic and hormonal systems in modulating frailty and mortality in hospitalized elderly patients. We measured 17 biological serum parameters from different metabolic/hormonal pathways in 594 hospitalized elderly patients followed up to 1 year who were stratified into three groups according to their multidimensional impairment, evaluated by a Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI). The mortality incidence rates were 7% at 1 month and 21% at 1 year. Our data show that frailty and mortality rate were positively associated with chronic inflammation and with a down-regulation of multiple endocrine factors. Of the 17 biomarkers examined, blood levels of IGF-1, triiodothyronine, C-reactive protein, erythrocyte sedimentation rate, white blood cell and lymphocyte counts, iron, albumin, total cholesterol, and LDL-c were significantly associated with both MPI severity grade and mortality. In multivariate Cox proportional hazard model, the following biomarkers most strongly predicted the risk of mortality (adjusted hazard ratio (HR) per 1 quintile increment in predictor distribution): IGF-1 HR = 0.71 (95% CI: 0.63-0.80), CRP HR = 1.48 (95% CI: 1.32-1.65), hemoglobin HR = 0.82 (95% CI: 0.73-0.92), and glucose HR = 1.17 (95% CI: 1.04-1.30). Multidimensional impairment assessed by MPI is associated with a distinctive metabolic 'signature'. The concomitant elevation of markers of inflammation, associated with a simultaneous reduction in multiple metabolic and hormonal factors, predicts mortality in hospitalized elderly patients.


Response to adrenocorticotropic hormone or corticotrophin-releasing hormone and vasopressin in lactating cows fed an immunomodulatory supplement under thermoneutral or acute heat stress conditions.
Adrenal responsiveness was tested in nonpregnant, lactating Holstein dairy cows fed diets supplemented with OmniGen-AF (OG; Phibro Animal Health Corp., Teaneck, NJ), an immune modulator, and in nonsupplemented control (CON) cows following bolus infusions of a combination of corticotropin-releasing hormone (CRH; 0.3 µg/kg of BW) and arginine vasopressin (VP; 1.0 µg/kg of BW) or ACTH (0.1 IU/kg of BW) in 2 environments: thermoneutral [TN; temperature-humidity index (THI) <60] for 24 h/d and heat stress (HS; THI >68 for 17 h/d). Cows (506) were initially fed OG (n = 254) or CON (n = 252) diets for 44 d before selection of a subgroup of cows (n = 12; 6 OG, 6 CON) for the study. The 2 subgroups were balanced for parity, milk yield, and days in milk. All cows were transported to and housed in 2 environmentally controlled rooms at the University of Arizona Agricultural Research Complex (Tucson). Cows were given 3 d to acclimate to the rooms and then underwent 12 d of TN conditions and then 8 d of HS conditions for a total of 24 d on experiment. Cows were infused with CRH-VP on d 9 of TN and on d 1 of HS and with ACTH on d 10 of TN and on d 2 of HS. Hormone infusions took place at 1000 h (0 h) on each infusion day. Blood samples, taken in 30-min intervals, were first collected at 0800 h (-2 h) and were drawn until 1800 h (8 h). Before infusion, serum progesterone was elevated in OG cows compared with CON cows. Infusion of releasing factors (CRH-VP or ACTH) caused increases in serum cortisol and progesterone, but cortisol release was greater in CON cows than in OG cows during HS, whereas progesterone did not differ between the 2 treatments. Serum ACTH increased following infusion of releasing factors, but this increase was greater following CRH-VP infusion than ACTH infusion. Serum bovine corticosteroid-binding globulin also increased following infusion of releasing factors in both treatment groups, but this increase was greater during HS in cows fed OG. The free cortisol index (FCI) increased following CRH-VP and ACTH and was higher in HS than in TN for both OG and CON cows. However, the FCI response was blunted in OG cows compared with CON cows during HS. Heat stress enhanced the adrenal response to releasing factors. Additionally, the adrenal cortisol and FCI response to releasing factors was reduced during acute heat stress in cows fed OG. Collectively, these data suggest that OG supplementation reduced the adrenal responsiveness to factors regulating cortisol secretion during acute HS.


Obstructive Jaundice due to Pancreatic Involvement as an Initial Presentation of Adult Acute Lymphoblastic Leukemia.
Acute lymphoblastic leukemia (ALL) is a heterogeneous group of lymphoid disorders characterized by monoclonal proliferation and expansion of immature lymphoid cells in the bone marrow, blood, and other organs. It commonly presents with nonspecific symptoms such as lethargy, easy bruising, and weight loss. In this article, we present the case of a 48-year-old male who presented to the hospital with painless jaundice resulting from pancreatic infiltration, initially thought to be due to pancreatic or hepatobiliary malignancy. He was later diagnosed with ALL by lymph node biopsy and peripheral blood flow cytometry immunophenotyping and was transferred to a cancer treatment centre for unilateral bone marrow biopsy and further management. Our case highlights the rare occurrence of pancreatic infiltration in ALL.


[Changing pattern and frequency of lung cancer in Mexico].
To assess the frequency, histological type and the epidemiological pattern of lung cancer (LC), during a 40 year period, at the National Institute of Respiratory Diseases (INER). This cross-sectional study was conducted in 1999. Data were abstracted from the INER's service reports for 1983-1996 and the surgical pathology archives for 1957-1996. Data from 1961 patients were analyzed, to obtain frequency measures on: the characteristics of INER LC patient admissions, age, sex, histological studies, specimens and diagnoses. Between 1983-1996, LC ranked eighth to second place in INER inpatient admissions. Results were grouped by decades. In the first two decades (1957-1976), 9% of patients were female; 32% in the third (1977-1986), and 38% in the last decade (1987-1996). Epidermoid cell carcinoma was more frequent in the two first decades (61%) and adenocarcinoma in the last two, (41% and 62%, respectively.) LC is currently more frequent in women, and adenocarcinoma is the most frequent neoplasia.


[Reparative regeneration of bone tissue in white rats administered metabolically active organic acids in the diet].
The effect of the addition into the diet of succinic and hydroxysuccinic acids on the reparative process was studied in white rats with experimental healing of the diaphysial fracture of the thigh. The feeding of rats of succinic acid (1 g per animal during experiment) for 10 days led to a significantly higher chemical maturity of the callus (low content of organic components and high content of mineral substances). An opposite effect was revealed in analogous experiments with hydroxysuccinic acid. The data obtained may serve the theoretical basis for the design of optimal diets for patients with injuries to the bones.


Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury.
γδ T cells located near the epithelial barrier are integral components of local inflammatory and innate immune responses. We have previously reported the presence of choroidal γδ T cells in a model of chronic degeneration of the retinal pigment epithelium (RPE). The goals of the current study were to further define the functions of choroidal γδ T cells and to explore the underlying mechanisms of their action. Our data demonstrate that choroidal γδ T cells are activated by RPE injury in response to NaIO3 treatment, and that they express genes that encode immunosuppressive cytokines, such as IL-4 and IL-10. γδ-T-cell-deficient mice developed profound RPE and retinal damage at doses that caused minimal effects in wild-type mice, and adoptive transfer of γδ T cells prevented sensitization. Intravitreal injection of IL-4 and IL-10 ameliorated RPE toxicity that was induced by NaIO3Ex vivo coculture of γδ T cells with RPE explants activated the production of anti-inflammatory cytokines via an aryl hydrocarbon receptor (AhR)-dependent mechanism. AhR deficiency abolished the protective effects of γδ T cells after adoptive transfer. Collectively, these findings define important roles for choroid γδ T cells in maintaining tissue homeostasis in the outer retina.-Zhao, Z., Liang, Y., Liu, Y., Xu, P., Flamme-Wiese, M. J., Sun, D., Sun, J., Mullins, R. F., Chen, Y., Cai, J. Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury.


[PARENTERAL-ENTERAL AND SEEPING CORRECTION IN MULTIDISCIPLINARY HOSPITAL].
Nutrition science continues to flourish, building on recent advances in genetics, bioengineering, and technological Sciences. The article presents the main directions of modern nutrition and the prospects for its development in the multidisciplinary hospital.


A model of the mammalian circadian oscillator including the REV-ERBalpha module.
Many cellular and physiological processes have been shown to display a rhythm of about 24 hours. This so-called circadian rhythm is based on a system of interlocked negative and positive molecular feedback loops. Here we extend a previous model of the circadian oscillator by including REV-ERBalpha as an additional component. This new model will allow us to investigate the function of an additional negative feedback loop via REV-ERBalpha. We obtain circadian oscillations with the correct period and phase relations between clock components. Parameter variations that correspond to clock-gene mutations reproduce experimental results: With parameter variations mimicking the Bmal1(-/-) and the Per2(Brdm1) mutation the oscillations cease to exist. In contrast, the system shows sustained oscillations if we use a parameter set that reflects the Rev-erbalpha mutation. The model also accounts for the differential effect of the Cry1(-/-) and Cry2(-/-) mutations on the circadian period. The simulations of the extended model indicate that the original model is robust with respect to the incorporation of the additional component. Depending on the kinetics of the Per2/Cry transcriptional activation by BMAL1, an increasing BMAL1 expression leads to either an increase or decrease of the clock period. This indicates that overexpression experiments could help to characterize the impact of BMAL1 on Per2/Cry transcription.


The Age of Independence, Revisited: Parents and Interracial Union Formation Across the Life Course1.
Romantic relationships that cross racial lines have grown since anti-miscegenation laws were deemed unconstitutional. In The Age of Independence, Rosenfeld argued that parental influence over children's mate selection processes had waned. Rosenfeld, however, was not able to test this supposition directly because of his reliance on cross-sectional census data. Using Waves I and III of Add Health for a cohort of individuals from 1994 to 2002, we examine whether parents matter in shaping their offspring's romantic attachments, by exploring whether adolescent reports of maternal closeness and parental control are associated with youth's likelihood of being in an interracial relationship in emerging adulthood. We find that parental factors do influence emerging adults' romantic relationships; these associations vary by race, ethnicity, and gender. Among white men, maternal closeness in adolescence reduces the likelihood of being in an interracial relationship in emerging adulthood. Parental control elevates the odds of being in an interracial relationship among black and Hispanic women. We also find that parental decisions on where families live shape offspring's choices, as relative exogamous group size in adolescence is associated with interracial union formation in later life. Our findings suggest that parental influence remains salient in the partner choices made by emerging adults.


The complete coding sequence of the human A-raf-1 oncogene and transforming activity of a human A-raf carrying retrovirus.
The complete 606 amino acid sequence of the human A-raf oncogene has been deduced from the 2453 nucleotide sequence of a human T cell cDNA. A cysteine-rich region located near the amino terminus, which is highly conserved in A-raf and c-raf, shows significant homology with protein kinase C. A 5' deleted fragment of the cDNA has been incorporated into a murine retrovirus which endows the virus with the ability to transform cells in vivo and in vitro. Functionally, human A-raf is similar to v-raf and v-mos in that transformation is independent of ras gene function.


Behavioral and cognitive predictors of educational outcomes in pediatric traumatic brain injury.
Research reveals mixed results regarding the utility of standardized cognitive and academic tests to predict educational outcomes in youth following a traumatic brain injury (TBI). Yet, deficits in everyday school-based outcomes are prevalent after pediatric TBI. The current study used path modeling to test the hypothesis that parent ratings of adolescents' daily behaviors associated with executive functioning (EF) would predict long-term functional educational outcomes following pediatric TBI, even when injury severity and patient demographics were included in the model. Furthermore, we contrasted the predictive strength of the EF behavioral ratings with that of a common measure of verbal memory. A total of 132 adolescents who were hospitalized for moderate to severe TBI were recruited to participate in a randomized clinical intervention trial. EF ratings and verbal memory were measured within 6 months of the injury; functional educational outcomes were measured 12 months later. EF ratings and verbal memory added to injury severity in predicting educational competence post injury but did not predict post-injury initiation of special education. The results demonstrated that measurement of EF behaviors is an important research and clinical tool for prediction of functional outcomes in pediatric TBI.


The Effects of Creatine Monohydrate on Permeability of Coronary Artery Endothelium and Level of Blood Lipoprotein in Diabetic Rats.
Creatine monohydrate has beneficial effects on serum glucose. This study aimed to investigate the effects of creatine on serum biochemical markers and permeability of coronary arteries among diabetic rats. 32 Wistar rats, which weighed 150-200 grams were randomly divided into 4 groups including: group I, control; group II, creatine monohydrate; group III, diabetic rats; and group IV, diabetic rats + creatine. Creatine monohydrate was applied by 400 mg/kg/daily for 5 months. Animals' weights and blood samples were taken before and after the study. Endothelial permeability rate was measured by Evans Blue method. Data were analysed by SPSS 16. At the end of fifth month, rats' weights in diabetic group under treatment with creatine, compared to those without, increased significantly (p<0.0001). Also, the serum levels of triglyceride (TG), cholesterol, glucose and low density lipoprotein (LDL)- cholesterol decreased significantly among those under treatment with creatine (p<0.05), but high density lipoprotein (HDL)- cholesterol increased significantly (p<0.002). Permeability rate of coronary arteries was reduced significantly in the diabetic group treated by creatine compared to untreated groups, closed to the intact group (p<0.001). Results of this study showed that creatine monohydrate caused an improvement of serum biochemical markers associated with diabetes and reduced the permeability rate of coronary arteries among diabetic rats.


Nanomechanical mass sensing and stiffness spectrometry based on two-dimensional vibrations of resonant nanowires.
One-dimensional nanomechanical resonators based on nanowires and nanotubes have emerged as promising candidates for mass sensors. When the resonator is clamped at one end and the atoms or molecules being measured land on the other end (which is free to vibrate), the resonance frequency of the device decreases by an amount that is proportional to the mass of the atoms or molecules. However, atoms and molecules can land at any position along the resonator, and many biomolecules have sizes that are comparable to the size of the resonator, so the relationship between the added mass and the frequency shift breaks down. Moreover, whereas resonators fabricated by top-down methods tend to vibrate in just one dimension because they are usually shaped like diving boards, perfectly axisymmetric one-dimensional nanoresonators can support flexural vibrations with the same amplitude and frequency in two dimensions. Here, we propose a new approach to mass sensing and stiffness spectroscopy based on the fact that the nanoresonator will enter a superposition state of two orthogonal vibrations with different frequencies when this symmetry is broken. Measuring these frequencies allows the mass, stiffness and azimuthal arrival direction of the adsorbate to be determined.


Inhibition of neutrophil NADPH oxidase assembly by a myristoylated pseudosubstrate of protein kinase C.
To further define the role played by protein kinase C (PKC) in the activation of the neutrophil NADPH oxidase, we have utilized a pseudosubstrate of PKC which was myristoylated at the N terminus. In electropermeabilized neutrophils, the myristoylated pseudosubstrate Phe-Ala-Arg-Lys-Gly-Ala-Leu-Arg-Gln (myr-psi PKC) inhibited PMA-induced protein phosphorylations and activation of the NADPH oxidase, induced either by PMA or by the receptor agonist formyl-methionyl-leucyl-phenylalanine. Both the pseudosubstrate lacking the N-terminal myristate (psi PKC) and a myristoylated control peptide (Phe-Ala-Glu-Asp-Gly-Ala-Leu-Glu-Gln, myr-CP) were without effect on these responses. The myristoylated pseudosubstrate was also tested in a cell-free system, in which NADPH oxidase activation can be achieved by addition of SDS and guanosine 5'-3-O-(thio)triphosphate in a staurosporine-insensitive manner. Myr-psi PKC, but not psi PKC or myr-CP, proved to be a potent inhibitor of NADPH oxidase activity in the cell-free system, indicating that the inhibition observed in permeabilized neutrophils may have been caused by an effect other than PKC inhibition. In the presence of myr-psi PKC, translocation in the cell-free system of the cytosolic oxidase components p47-phox and p67-phox to the plasma membrane was inhibited. From these results we conclude that myristoylation profoundly increases the ability of pseudosubstrates of PKC to inhibit not only PKC-mediated phosphorylations, but also NADPH oxidase activation. The latter effect, however, is most probably not related to PKC inhibition but may indicate a critical role of the membrane surface charge in the translocation of the cytosolic oxidase components p47-phox and p67-phox.


Joint project of the International Network of Agencies for Health Technology Assessment--Part 2: Managing the diffusion of positron emission tomography with health technology assessment.
Since 1997, members of the International Network of Agencies for Health Technology Assessment (INAHTA) have collaborated on a Joint Project to track the diffusion, evaluation, and clinical policy of positron emission tomography (PET). Part 2 of this updated Joint Project report summarizes HTA-based strategies for directing the clinical use of PET and a discussion on the value of HTA in managing the diffusion of high cost diagnostic technologies, which were presented at an INAHTA-sponsored workshop at the Health Technology Assessment International Annual Meeting in 2004 on strategies for managing high cost diagnostic technologies. A summary of the workshop proceedings is presented. Sharing assessment work, universal agreement in assessment conclusions, stakeholder input, and modeling techniques help manage the uncertainty in the evidence base while targeting clinical use of PET toward the most promising indications. Emphasis on HTA findings, linkage between financing of clinical PET and outcome evaluation, and targeted dissemination of scientific findings empower providers to reduce unnecessary utilization and contain costs within a quality improvement framework. Above all, a trustworthy source of HTA information and a process that is conducive to using scientific evidence as the basis for decision making are essential for managing the diffusion of complex and costly diagnostic technologies in patient care.


Bright Transparent Scintillators with High Fraction BaCl2 : Eu2+ Nanocrystals Precipitation: An Ionic-Covalent Hybrid Network Strategy toward Superior X-Ray Imaging Glass-Ceramics.
Metal halide crystals are bright but hygroscopic scintillator materials that are widely used in X-ray imaging and detectors. Precipitating them in situ in glass to form glass ceramics (GCs) scintillator offers an efficient avenue for large-scale preparation, high spatial resolution, and excellent stability. However, precipitating a high fraction of metal halide nanocrystals in glass to maintain high light yield remains a challenge. Herein, an ionic-covalent hybrid network strategy for constructing GCs scintillator with high crystallinity (up to ≈37%) of BaCl2 : Eu2+ nanocrystals is presented. Experimental data and simulations of glass structure reveal that the Ba2+ -Cl- clustering promotes the high crystallization of BaCl2 nanocrystals. The ultralow phonon energy (≈200 cm-1 ) of BaCl2 nanocrystals and good Eu reduction effect enable high photoluminescence inter quantum efficiency (≈80.41%) in GC. GCs with varied crystallinity of BaCl2 : Eu2+ nanocrystals demonstrate efficient radioluminescence and tunable scintillator performance. They either outperform Bi4 Ge3 O14 single crystal by over 132% steady-state light yield or provide impressive X-ray imaging resolutions of 20 lp mm-1 . These findings provide a new design strategy for developing bright transparent GCs scintillators with a high fraction of metal halide nanocrystals for X-ray high-resolution imaging applications.


Understanding differences in health behaviors by education.
Using a variety of data sets from two countries, we examine possible explanations for the relationship between education and health behaviors, known as the education gradient. We show that income, health insurance, and family background can account for about 30 percent of the gradient. Knowledge and measures of cognitive ability explain an additional 30 percent. Social networks account for another 10 percent. Our proxies for discounting, risk aversion, or the value of future do not account for any of the education gradient, and neither do personality factors such as a sense of control of oneself or over one's life.


Canadian Rheumatology Association Meeting Virtual Congress February 24 - 26, 2021.
The 75th Annual Meeting of The Canadian Rheumatology Association was held virtually on February 24-26, 2021. The program consisted of presentations covering original research, symposia, awards, and lectures. Highlights of the meeting include the following 2021 Award Winners: Distinguished Rheumatologist, Rachel Shupak; Distinguished Investigator, Sasha Bernatsky; Distinguished Teacher-Educator, Elaine Yacyshyn; Emerging Investigator, Zahi Touma; Ian Watson Award for the Best Abstract on SLE Research by a Trainee, Raffaella Carlomagno; Phil Rosen Award for the Best Abstract on Clinical or Epidemiology Research by a Trainee, Kimberley Yuen; Best Abstract by a Rheumatology Resident, Ariane Barbacki; Best Abstract on Basic Science Research by a Trainee, Andrew Kwan; Best Abstract by a Post-Graduate Research Trainee, Luiza Grazziotin; Best Abstract on Quality Care Initiatives in Rheumatology, Nadia Luca; Best Abstract by a Medical Student, Daniel Levin; Best Abstract by an Undergraduate Student, Anson Lee; Best Abstract by a Rheumatology Post-Graduate Research Trainee, Jennifer Lee; Best Abstract on Research by Young Faculty, Lihi Eder; Best Abstract on Spondyloarthritis Research, Sandeep Dhillon; Practice Reflection Award, Gold, Stephanie Gottheil; CRA Master Awards, Ciarán M. Duffy, Mary-Ann Fitzcharles, James M. Henderson. Lectures and other events included: Keynote Lecture by Danielle Martin: Delivering on What Matters: Lessons from Canada's Response to the COVID-19 Pandemic; State of the Art Lecture by Michael Libman: Vaccination and Travel: Should I or Shouldn't I?; Dunlop-Dottridge Lecture by Dan Kastner: Rheumatic Disease and the Human Condition; and the Great Debate: Be it Resolved that Telemedicine Allows Rheumatologists to Provide Excellent Care to Patients with Autoimmune Rheumatic Diseases. Arguing for: Alexandra Saltman and Tommy Gerschman, and against: Brent Ohata and Jocelyne Murdoch. Topics including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, psoriatic arthritis, spondyloarthritis, vasculitis, osteoarthritis, fibromyalgia, and their respective diagnoses, treatments, and outcomes are reflected in the abstracts, which we are pleased to publish in this issue of The Journal.


Constitutive expression of tetracycline resistance mediated by a Tn10-like element in Haemophilus parainfluenzae results from a mutation in the repressor gene.
The Tn10-like constitutively expressed tetracycline resistance determinant from a Haemophilus parainfluenzae strain was cloned in Escherichia coli. Toxicity resulting from expression on multicopy plasmids necessitated its being cloned on a low-copy plasmid vector or in cells containing the Tn10-encoded repressor. Constitutive expression of tetracycline resistance was found to result from the synthesis of a truncated inactive repressor molecule. Instead of the 23-kilodalton repressor found in other Tn10-containing strains, this determinant encoded a 14.5-kilodalton molecule. The DNA sequence of the 700-base-pair region spanning the repressor gene and promoter-operator regions of the Haemophilus determinant was identical to that of the same region of Tn10, except for the absence of a single T X A base pair in the repressor gene. This deletion leads to premature termination of the protein. Antisera to the repressor suggested that the repressor was also absent in a second independently isolated H. parainfluenzae strain bearing a Tn10-like constitutive tetracycline resistance determinant.


Requirements for kissing-loop-mediated dimerization of human immunodeficiency virus RNA.
Sequences from the 5' end of type 1 human immunodeficiency virus RNA dimerize spontaneously in vitro in a reaction thought to mimic the initial step of genomic dimerization in vivo. Dimer initiation has been proposed to occur through a "kissing-loop" interaction involving a specific RNA stem-loop element designated SL1: the RNA strands first interact by base pairing through a six-base GC-rich palindrome in the loop of SL1, whose stems then isomerize to form a longer interstrand duplex. We now report a mutational analysis aimed at defining the features of SL1 RNA sequence and secondary structure required for in vitro dimer formation. Our results confirm that mutations which destroy complementarity in the SL1 loop abolish homodimer formation, but that certain complementary loop mutants can heterodimerize. However, complementarity was not sufficient to ensure dimerization, even between GC-rich loops, implying that specific loop sequences may be needed to maintain a conformation that is competent for initial dimer contact; the central GC pair of the loop palindrome appeared critical in this regard, as did two or three A residues which normally flank the palindrome. Neither the four-base bulge normally found in the SL1 stem nor the specific sequence of the stem itself was essential for the interaction; however, the stem structure was required, because interstrand complementarity alone did not support dimer formation. Electron microscopic analysis indicated that the RNA dimers formed in vitro morphologically resembled those isolated previously from retroviral particles. These results fully support the kissing-loop model and may provide a framework for systematically manipulating genomic dimerization in type 1 human immunodeficiency virus virions.


Infectious clone construction of dengue virus type 2, strain Jamaican 1409, and characterization of a conditional E6 mutation.
A full-length infectious cDNA clone (ic) was constructed from the genome of the dengue virus type 2 (DENV-2) Jamaica83 1409 strain, pBAC1409ic, by using a bacterial artifical chromosome plasmid system. Infectious virus was generated and characterized for growth in cell culture and for infection in Aedes aegypti mosquitoes. During construction, an isoleucine to methionine (Ile-->Met) change was found at position 6 in the envelope glycoprotein sequence between low- and high-passage DENV-2 1409 strains. In vitro-transcribed genomic RNA of 1409ic with E6-Ile produced infectious virions following electroporation in mosquito cells, but not mammalian cells, while 1409ic RNA with an E6-Met mutation produced virus in both cell types. Moreover, DENV-2 1409 with the E6-Ile residue produced syncytia in C6/36 cell culture, whereas viruses with E6-Met did not. However, in vitro cell culture-derived growth-curve data and in vivo mosquito-infection rates revealed that none of the analysed DENV-2 strains differed from each other.


The influence of N-acetyl-L-cysteine on oxidative stress and nitric oxide synthesis in stimulated macrophages treated with a mustard gas analogue.
Sulphur mustard gas, 2, 2'-dichlorodiethyl sulphide (HD), is a chemical warfare agent. Both mustard gas and its monofunctional analogue, 2-chloroethyl ethyl sulphide (CEES), are alkylating agents that react with and diminish cellular thiols and are highly toxic. Previously, we reported that lipopolysaccharide (LPS) significantly enhances the cytotoxicity of CEES in murine RAW 264.7 macrophages and that CEES transiently inhibits nitric oxide (NO) production via suppression of inducible NO synthase (iNOS) protein expression. NO generation is an important factor in wound healing. In this paper, we explored the hypotheses that LPS increases CEES toxicity by increasing oxidative stress and that treatment with N-acetyl-L-cysteine (NAC) would block LPS induced oxidative stress and protect against loss of NO production. NAC stimulates glutathione (GSH) synthesis and also acts directly as a free radical scavenger. The potential therapeutic use of the antibiotic, polymyxin B, was also evaluated since it binds to LPS and could thereby block the enhancement of CEES toxicity by LPS and also inhibit the secondary infections characteristic of HD/CEES wounds. We found that 10 mM NAC, when administered simultaneously or prior to treatment with 500 muM CEES, increased the viability of LPS stimulated macrophages. Surprisingly, NAC failed to protect LPS stimulated macrophages from CEES induced loss of NO production. Macrophages treated with both LPS and CEES show increased oxidative stress parameters (cellular thiol depletion and increased protein carbonyl levels). NAC effectively protected RAW 264.7 cells simultaneously treated with CEES and LPS from GSH loss and oxidative stress. Polymyxin B was found to partially block nitric oxide production and diminish CEES toxicity in LPS-treated macrophages. The present study shows that oxidative stress is an important mechanism contributing to CEES toxicity in LPS stimulated macrophages and supports the notion that antioxidants could play a therapeutic role in preventing mustard gas toxicity. Although NAC reduced oxidative stress in LPS stimulated macrophages treated with CEES, it did not reverse CEES-induced loss of NO production. NAC and polymyxin B were found to help prevent CEES toxicity in LPS-treated macrophages.


Antimicrobial activities of BMY-28142, cefbuperazone, and cefpiramide compared with those of other cephalosporins.
The antimicrobial activities of BMY-28142, cefbuperazone (BMY-25182; formerly T-1982), and cefpiramide (WY-44635; formerly SM-1652) were compared with those of cefmenoxime, cefoperazone, cefotaxime, ceftizoxime, and moxalactam. BMY-28142 was the most active cephalosporin against the majority of aerobic and facultatively anaerobic microorganisms studied. Its spectrum of activity was very similar to that of cefotaxime. However, BMY-28142, cefbuperazone, cefmenoxime, cefotaxime, ceftizoxime, and moxalactam were equivalent in activity and rate of killing against members of the family Enterobacteriaceae. Cefpiramide was considerably less active than the other cephalosporins against the Enterobacteriaceae.


A 25 year experience of perineal hernia repair.
Though perineal hernias remain rare, the incidence is reportedly rising. Secondary to the historical rarity, optimal method of repair and outcomes after repair remain poorly understood. Therefore, we reviewed the past 25 years of our institutional experience with perineal hernia repair. A retrospective review of an institution-maintained database was conducted from January 1, 1994 to January 31, 2018 for patients undergoing perineal hernia repair. Data were collected on patient characteristics, operative technique, and post-operative outcomes. Twenty-one patients (n = 12 male) underwent perineal hernia repair in the study period with two-thirds of the operations occurring in the most recent 7 years (since January 1, 2011). The median time to repair was 13 months (range 2-127) after index operation. The approach was transabdominal in nine, perineal in nine, and combined in three. Mesh, a tissue flap, or a combination of these was used in 19 of the cases and 6 additional abdominal wall hernias were repaired concurrently. Post-operative complications consisted of superficial surgical-site infection (n = 2), infected seroma (n = 1), and a missed enterotomy (n = 1). Follow-up ranged from 0 to 112 months (median 2 months) and only one recurrence was noted. Presentation for repair of perineal hernia has increased at our instituion over the past 2 decades. Outcomes did not differ between the three repair approaches and the choice of mesh or tissue-based repair. Surgeons should base these decisions on hernia complexity and local tissue conditions.


Clinicopathologic Correlation of a Subretinal Proliferative Vitreoretinopathy Band in a Patient with Chronic Recurrent Retinal Detachment.
Proliferative vitreoretinopathy is a well-known cause of failure of retinal detachment surgery. The purpose of this case report is to illustrate the clinical occurrence and histopathology of a horizontal subretinal band ("clothesline" configuration) creating recurrent and persistent retinal detachment. A 67-year-old Hispanic female with diabetes type 2 and a history of retinal detachment surgery in the left eye (OS) presented with decreased vision OS. Best corrected visual acuity at this recent presentation was 20/80 OS. Clinical examination disclosed a recurrent inferior retinal detachment and a subretinal "clothesline" fibrotic band. Surgical removal of the subretinal band was performed. Histopathological evaluation of longitudinal and transverse sections of the band revealed a cable-like configuration composed predominantly of glial differentiation, RPE differentiation, and collagen, based on morphology and immunohistochemical staining. There was focal smooth muscle and neuroendocrine cell differentiation, as detected with smooth muscle actin (SMA) and S100 staining, respectively. Cross-sections demonstrated pigmented fibrocellular tissue with foci of cells staining positive for S100 and keratin peripherally around the tissue, suggestive of RPE differentiation. Scattered foci of SMA-positive cells suggested mild myoblastic differentiation. This case report presents further information on the structure and orientation of the cellular components of subretinal band proliferative vitreoretinopathy. Cells suggestive of Müller cell differentiation compose the central aspect of the band, alongside collagen fibers. RPE differentiation is variably present peripherally in the band, likely reflective of proliferating RPE encircling the subretinal fibrous tissue. A mild amount of myofibroblastic differentiation was present within the band of tissue, correlating with the clinical findings of subretinal tissue contraction and localized retinal detachment.


Ligand activation of peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) inhibits chemically induced skin tumorigenesis.
Peroxisome proliferator-activated receptor (PPAR)beta/delta-null mice exhibit enhanced tumorigenesis in a two-stage chemical carcinogenesis model as compared with wild-type mice. Previous work showed that ligand activation of PPARbeta/delta induces terminal differentiation and inhibits proliferation of primary keratinocytes, and this effect does not occur in the absence of PPARbeta/delta expression. In the present studies, the effect of ligand activation of PPARbeta/delta on skin tumorigenesis was examined using both in vivo and ex vivo skin carcinogenesis models. Inhibition of chemically induced skin tumorigenesis was observed in wild-type mice administered GW0742, and this effect was likely the result of ligand-induced terminal differentiation and inhibition of replicative DNA synthesis. These effects were not found in similarly treated PPARbeta/delta-null mice. Ligand activation of PPARbeta/delta also inhibited cell proliferation and induced terminal differentiation in initiated/neoplastic keratinocyte cell lines representing different stages of skin carcinogenesis. These studies suggest that topical administration of PPARbeta/delta ligands may be useful as both a chemopreventive and/or a chemotherapeutic approach to inhibit skin cancer.


Works-in-progress: guiding junior scientists through career development applications.
Career development awards are important to the professional careers of many junior scientists. Designed to launch researchers as independent scientists earlier in their careers, such grants release them from full schedules of teaching and clinical service, protecting their time for research and publishing. Yet few know how best to embark on this crucial endeavor. We pilot tested a faculty-facilitated, biweekly working group for postdoctoral fellows and junior faculty preparing career development applications. Based on their needs and interests, sessions included didactic activities, structured panel discussions, identification of resources, and individual guidance. For those unable to attend regularly, e-mail kept them informed of information shared and lessons learned, as summarized by participants on a rotating basis. Although success in terms of funded applications is yet unknown, preliminary evaluation suggests high satisfaction among the participants. Ultimately, if successful, a low-cost, easy-to-administer working group approach such as this can add great value to any training program.