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Objectives. To specify symptoms and measure prevalence of psychological distress among incarcerated people in long-term solitary confinement. Methods. We gathered data via semistructured, in-depth interviews; Brief Psychiatric Rating Scale (BPRS) assessments; and systematic reviews of medical and disciplinary files for 106 randomly selected people in solitary confinement in the Washington State Department of Corrections in 2017. We performed 1-year follow-up interviews and BPRS assessments with 80 of these incarcerated people, and we present the results of our qualitative content analysis and descriptive statistics. Results. BPRS results showed clinically significant symptoms of depression, anxiety, or guilt among half of our research sample. Administrative data showed disproportionately high rates of serious mental illness and self-harming behavior compared with general prison populations. Interview content analysis revealed additional symptoms, including social isolation, loss of identity, and sensory hypersensitivity. Conclusions. Our coordinated study of rating scale, interview, and administrative data illustrates the public health crisis of solitary confinement. Because 95% or more of all incarcerated people, including those who experienced solitary confinement, are eventually released, understanding disproportionate psychopathology matters for developing prevention policies and addressing the unique needs of people who have experienced solitary confinement, an extreme element of mass incarceration.

Objectives. To evaluate whether the Operation Peacemaker Fellowship, an innovative firearm violence-prevention program implemented in Richmond, California, was associated with reductions in firearm and nonfirearm violence. Methods. We compiled city- and jurisdiction-level quarterly counts of violent firearm and nonfirearm incidents from statewide records of deaths from and hospital visits for homicide and assault (2005-2016) and from nationwide crime records of homicides and aggravated assaults (1996-2015). We applied a generalization of the synthetic control method to compare observed patterns in firearm and nonfirearm violence after implementation of the program (June 2010) to those predicted in the absence of the program, using a weighted combination of comparison cities or jurisdictions. Results. The program was associated with reductions in firearm violence (annually, 55% fewer deaths and hospital visits, 43% fewer crimes) but also unexpected increases in nonfirearm violence (annually, 16% more deaths and hospital visits, 3% more crimes). These associations were unlikely to be attributable to chance for all outcomes except nonfirearm homicides and assaults in crime data. Conclusions. The Operation Peacemaker Fellowship may have been effective in reducing firearm violence in Richmond but may have increased nonfirearm violence.

Objective: To assess whether participation in a culturally tailored nutrition education program increases diet quality of Hispanic mothers., Design: A randomized controlled trial., Setting: Community centers and universities., Participants: Sixty-five mothers (35 in experimental group, 30 in control group) completed pre- and postworkshop surveys. Eligibility criteria included being of Mexican or Puerto Rican descent and having a child between the ages of 6 and 18 years who could participate in the workshops with the parent., Intervention: Families in the experimental group participated in a 6-week workshop series that included weekly nutrition education classes., Main Outcome Measure: Diet quality was assessed by the Rate Your Plate questionnaire., Analysis: Repeated measures ANOVA was used to compare differences between the experimental and control groups. A Wilcoxon signed rank test was conducted to test for significant shifts in categorization pre- and postprogram., Results: There was a significant change in diet quality categorization after participating in the workshops (P < .001, effect size 0.39). No changes were found in the control group., Conclusions and Implications: Abriendo Caminos was effective at increasing the diet quality of Hispanic mothers who participated the most in the program. More research is needed in this at-risk population to determine the relationships among nutrition knowledge, diet quality, and achievement of healthy weight., (Published by Elsevier Inc.)

Microtubules are intracellular filaments that define in space and in time a large number of essential cellular functions such as cell division, morphology and motility, intracellular transport and flagella and cilia assembly. They are therefore essential for spermatozoon and oocyte maturation and function, and for embryo development. The dynamic and functional properties of the microtubules are in large part defined by various classes of interacting proteins including MAPs (microtubule associated proteins), microtubule-dependent motors, and severing and modifying enzymes. Multiple mechanisms regulate these interactions. One of them is defined by the high diversity of the microtubules themselves generated by the combination of different tubulin isotypes and by several tubulin post-translational modifications (PTMs). This generates a so-called tubulin code that finely regulates the specific set of proteins that associates with a given microtubule thereby defining the properties and functions of the network. Here we provide an in depth review of the current knowledge on the tubulin isotypes and PTMs in spermatozoa, oocytes, and preimplantation embryos in various model systems and in the human species. We focus on functional implications of the tubulin code for cytoskeletal function, particularly in the field of human reproduction and development, with special emphasis on gamete quality and infertility. Finally, we discuss some of the knowledge gaps and propose future research directions., (© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Purpose: Glaucoma is the leading cause of blindness in humans, affecting 2% of the population. This disorder can be classified into various types including primary, secondary, glaucoma with angle closure and with open angle. The prevalence of distinct types of glaucoma differs for each particular region of the world. One of the most common types of this disease is primary open-angle glaucoma (POAG), which is a complex inherited disorder characterized by progressive retinal ganglion cell death, optic nerve head excavation and visual field loss. Nowadays, POAG is considered an optic neuropathy, while intraocular pressure is proposed to play a fundamental role in its pathophysiology and especially in optic disk damage. However, the exact mechanism of optic nerve head damage remains a topic of debate. This literature review aims to bring together the information on the pathophysiology of primary open-angle glaucoma, particularly focusing on neuroinflammatory mechanisms leading to the death of the retinal ganglion cell., Methods: A literature search was done on PubMed using key words including primary open-angle glaucoma, retinal ganglion cells, Müller cells, glutamate, glial cells, ischemia, hypoxia, exitotoxicity, neuroinflammation, axotomy and neurotrophic factors. The literature was reviewed to collect the information published about the pathophysiologic mechanisms of RGC death in the POAG, from a neuroinflammatory and neurotoxicity perspective., Results: Proposed mechanisms for glaucomatous damage are a result of pressure in RGC followed by ischemia, hypoxia of the ONH, and consequently death due to glutamate-induced excitotoxicity, deprivation of energy and oxygen, increase in levels of inflammatory mediators and alteration of trophic factors flow. These events lead to blockage of anterograde and retrograde axonal transport with ensuing axotomy and eventually blindness., Conclusions: The damage to ganglion cells and eventually glaucomatous injury can occur via various mechanisms including baric trauma, ischemia and impact of metabolic toxins, which triggers an inflammatory process and secondary degeneration in the ONH.

Successful fertilization in mammals depends on the sperm's ability to initiate intracellular Ca 2+ oscillations in the egg, a phenomenon that is elicited by Sperm-oocyte activating factors (SOAFs), whose quantitative and/or qualitative defect might result in fertilization failure. One such proposed factor is Post-acrosomal WW domain-binding protein (PAWP/WBP2NL), although its ability to activate human oocytes has been questioned and its implication in human fertilization failure remains unknown. Here, we sought to determine if PAWP/WBP2NL expression and distribution in sperm cells associate with low/complete fertilization failure in males participating in intracytoplasmic sperm injection (ICSI) cycles. This prospective study was conducted on eight couples referred for elective ICSI with either the woman's own (n = 4) or a donor eggs (n = 4). Eight sperm donor samples used in ICSI, which resulted in normal fertilization rates, were used as the control group. For each male patient and donor sperm, PAWP/WBP2NL sequence, protein expression, and cellular distribution were analyzed by PCR amplification-sequencing, Western blot, and immunofluorescence, respectively. PAWP/WBP2NL was present in all samples, and no significant differences were detected between patients with fertilization failure and donors in sequence variants or mean protein expression, or in the proportion of PAWP/WBP2NL-positive sperm. In conclusion, no clear association between PAWP/WBP2NL protein expression in sperm and fertilization outcome in ICSI were observed from this cohort., (© 2017 Wiley Periodicals, Inc.)

Extracellular matrix (ECM) "raw materials" such as demineralized bone matrix (DBM) and cartilage matrix have emerged as leading scaffolding materials for osteochondral regeneration owing to their capacity to facilitate progenitor/resident cell recruitment, infiltration, and differentiation without adding growth factors. Scaffolds comprising synthetic polymers are sturdy yet generally lack cues for guiding cell differentiation. We hypothesized that opposing gradients of decellularized cartilage (DCC) and DBM in polymeric microsphere-based scaffolds would provide superior regeneration compared to polymer-only scaffolds in vivo. Poly(D,L-lactic- co -glycolic acid) (PLGA) microsphere-based scaffolds were fabricated, either with opposing gradients of DCC and DBM encapsulated (GRADIENT) or without DCC and DBM (BLANK control), and implanted into rabbit osteochondral defects in medial femoral condyles. After 12 weeks, gross morphological evaluation showed that the repair tissue in about 30% of the implants was either slightly or significantly depressed, hinting toward rapid polymer degradation in scaffolds from both of the groups. Additionally, no differences were observed in gross morphology of the repair tissue between the BLANK and GRADIENT groups. Mechanical testing revealed no significant differences in model parameter values between the two groups. Histological observations demonstrated that the repair tissue in both of the groups was fibrous in nature with the cells demonstrating notable proliferation and matrix deposition activity. No adverse inflammatory response was observed in any of the implants from the two groups. Overall, the results emphasize the need to improve the technology in terms of altering the DBM and DCC concentrations, and tailoring the polymer degradation to these concentrations.

Objectives: California has strict firearm-related laws and is exceptional in its regulation of firearms retailers. Though evidence suggests that these laws can reduce illegal access to guns, high levels of gun violence persist in Los Angeles (LA), California. This research seeks to describe the sources of guns accessed by active offenders in LA, California and reports offenders' motivations for obtaining guns., Setting: Los Angeles County Jail (LACJ) system (four facilities)., Methods: Random sampling from a screened pool of eligible participants was used to conduct qualitative semistructured interviews with 140 incarcerated gun offenders in one of four (LACJ) facilities. Researchers collected data on firearm acquisition, experiences related to gun violence, and other topics, using a validated survey instrument. Grounded theory guided the collection and analysis of data., Results: Respondents reported possession of 77 specific guns (79.2% handguns) collectively. Social networks facilitate access to illegal guns; the majority of interviewees acquired their illegal guns through a social connection (85.7%) versus an outside broker/unregulated retailer (8.5%). Most guns were obtained through illegal purchase (n=51) or gift (n=15). A quarter of gun purchasers report engaging in a passive transaction, or one initiated by another party. Passive gun buyers were motivated by concerns for personal safety and/or economic opportunity., Conclusions: In LA's illegal gun market, where existing social relationships facilitate access to guns across a diffuse network, individuals, influenced by both fear and economic opportunity, have frequent opportunities to illegally possess firearms through passive transactions. Gun policies should better target and minimise these transactions., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Extracellular matrix materials such as decellularized cartilage (DCC) and chondroitin sulfate (CS) may be attractive chondrogenic materials for cartilage regeneration. The goal of the current study was to investigate the effects of encapsulation of DCC and CS in homogeneous microsphere-based scaffolds, and to test the hypothesis that encapsulation of these extracellular matrix materials would induce chondrogenesis of rat bone marrow stromal cells. Four different types of homogeneous scaffolds were fabricated from microspheres of poly(D,L-lactic-co-glycolic acid): Blank (poly(D,L-lactic-co-glycolic acid) only; negative control), transforming growth factor-β3 encapsulated (positive control), DCC encapsulated, and CS encapsulated. These scaffolds were then seeded with rat bone marrow stromal cells and cultured for 6 weeks. The DCC and CS encapsulation altered the morphological features of the microspheres, resulting in higher porosities in these groups. Moreover, the mechanical properties of the scaffolds were impacted due to differences in the degree of sintering, with the CS group exhibiting the highest compressive modulus. Biochemical evidence suggested a mitogenic effect of DCC and CS encapsulation on rat bone marrow stromal cells with the matrix synthesis boosted primarily by the inherently present extracellular matrix components. An important finding was that the cell seeded CS and DCC groups at week 6 had up to an order of magnitude higher glycosaminoglycan contents than their acellular counterparts. Gene expression results indicated a suppressive effect of DCC and CS encapsulation on rat bone marrow stromal cell chondrogenesis with differences in gene expression patterns existing between the DCC and CS groups. Overall, DCC and CS were easily included in microsphere-based scaffolds; however, there is a requirement to further refine their concentrations to achieve the differentiation profiles we seek in vitro., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2016.)

Bioceramic mixtures of tricalcium phosphate (TCP) and hydroxyapatite (HAp) are widely used for bone regeneration because of their excellent cytocompatibility, osteoconduction, and osteoinduction. Therefore, we hypothesized that incorporation of a mixture of TCP and HAp in microsphere-based scaffolds would enhance osteogenesis of rat bone marrow stromal cells (rBMSCs) compared to a positive control of scaffolds with encapsulated bone-morphogenic protein-2 (BMP-2). Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds encapsulating TCP and HAp mixtures in two different ratios (7:3 and 1:1) were fabricated with the same net ceramic content (30 wt%) to evaluate how incorporation of these ceramic mixtures would affect the osteogenesis in rBMSCs. Encapsulation of TCP/HAp mixtures impacted microsphere morphologies and the compressive moduli of the scaffolds. Additionally, TCP/HAp mixtures enhanced the end-point secretion of extracellular matrix components relevant to bone tissue compared to the "blank" (PLGA-only) microsphere-based scaffolds as evidenced by the biochemical, gene expression, histology, and immunohistochemical characterization. Moreover, the TCP/HAp mixture groups even surpassed the BMP-2 positive control group in some instances in terms of matrix synthesis and gene expression. Lastly, gene expression data suggested that the rBMSCs responded differently to different TCP/HAp ratios presented to them. Altogether, it can be concluded that TCP/HAp mixtures stimulated the differentiation of rBMSCs toward an osteoblastic phenotype, and therefore may be beneficial in gradient microsphere-based scaffolds for osteochondral regeneration.

Unlabelled: ECM-based materials are appealing for tissue engineering strategies because they may promote stem cell recruitment, cell infiltration, and cell differentiation without the need to supplement with additional biological factors. Cartilage ECM has recently shown potential to be chondroinductive, particularly in a hydrogel-based system, which may be revolutionary in orthopedic medicine. However, hydrogels composed of natural materials are often mechanically inferior to synthetic materials, which is a major limitation for load-bearing tissue applications. The objective was therefore to create an unprecedented hydrogel derived entirely from native cartilage ECM that was both mechanically more similar to native cartilage tissue and capable of inducing chondrogenesis. Porcine cartilage was decellularized, solubilized, and then methacrylated and UV photocrosslinked to create methacrylated solubilized decellularized cartilage (MeSDCC) gels. Methacrylated gelatin (GelMA) was employed as a control for both biomechanics and bioactivity. Rat bone marrow-derived mesenchymal stem cells were encapsulated in these networks, which were cultured in vitro for 6weeks, where chondrogenic gene expression, the compressive modulus, swelling, and histology were analyzed. One day after crosslinking, the elastic compressive modulus of the 20% MeSDCC gels was 1070±150kPa. Most notably, the stress strain profile of the 20% MeSDCC gels fell within the 95% confidence interval range of native porcine cartilage. Additionally, MeSDCC gels significantly upregulated chondrogenic genes compared to GelMA as early as day 1 and supported extensive matrix synthesis as observed histologically. Given that these gels approached the mechanics of native cartilage tissue, supported matrix synthesis, and induced chondrogenic gene expression, MeSDCC hydrogels may be promising materials for cartilage tissue engineering applications. Future efforts will focus on improving fracture mechanics as well to benefit overall biomechanical performance., Statement of Significance: Extracellular matrix (ECM)-based materials are appealing for tissue engineering strategies because they may promote stem cell recruitment, cell infiltration, and cell differentiation without the need to supplement with additional biological factors. One such ECM-based material, cartilage ECM, has recently shown potential to be chondroinductive; however, hydrogels composed of natural materials are often mechanically inferior to synthetic materials, which is a major limitation for load-bearing tissue applications. Therefore, this work is significant because we were the first to create hydrogels derived entirely from cartilage ECM that had mechanical properties similar to that of native cartilage until hydrogel failure. Furthermore, these hydrogels had a compressive modulus of 1070±150kPa, they were chondroinductive, and they supported extensive matrix synthesis. In the current study, we have shown that these new hydrogels may prove to be a promising biomaterial for cartilage tissue engineering applications., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Hydrogel precursors are liquid solutions that are prone to leaking from the defect site once implanted in vivo. Therefore, the objective of the current study was to create a hydrogel precursor that exhibited a yield stress. Additionally, devitalized cartilage extracellular matrix (DVC) was mixed with DVC that had been solubilized and methacrylated (MeSDVC) to create hydrogels that were chondroinductive. Precursors composed of 10% MeSDVC or 10% MeSDVC with 10% DVC were first evaluated rheologically, where non-Newtonian behavior was observed in all hydrogel precursors. Rat bone marrow stem cells (rBMSCs) were mixed in the precursor solutions, and the solutions were then crosslinked and cultured in vitro for 6 weeks with and without exposure to human transforming growth factor β3 (TGF-β3). The compressive modulus, gene expression, biochemical content, swelling, and histology of the gels were analyzed. The DVC-containing gels consistently outperformed the MeSDVC-only group in chondrogenic gene expression, especially at 6 weeks, where the relative collagen II expression of the DVC-containing groups with and without TGF-β3 exposure was 40- and 78-fold higher, respectively, than that of MeSDVC alone. Future work will test for chondrogenesis in vivo and overall, these two cartilage-derived components are promising materials for cartilage tissue engineering applications.

Purpose: Sperm-borne PLCζ protein induces Ca(2+) oscillations in the oocyte and is believed to play a major role during oocyte activation. However, its implication in fertilization failure following ICSI is still debated. We analyzed PLCζ gene sequence, protein expression level, and localization in both patients with previous failed fertilization by ICSI and sperm donors with proven fertility in order to assess the association of PLCζ with both sperm characteristics and ability to fertilize., Methods: Semen from 15 patients and 13 sperm donors with proven fertility was included in the study. Analysis of the PLCζ gene sequence, protein expression through Western blot, and protein localization by immunofluorescence were performed., Results: Two patients with total fertilization failure presented mutations in heterozygosis in the PLCζ gene. Comparison with donor sample sequences displayed comparable SNP allele frequency. Distribution pattern of PLCζ did not vary significantly between donor and patient samples. Levels of PLCζ protein in sperm cells showed an interindividual variability both in patient and donor samples. Several SNPs previously reported in infertile patients were also present in fertile men., Conclusion: Failed fertilization occurs even when levels and distribution of PLCζ protein are within normal range. PLCζ seems to be a necessary but not sufficient factor in determining the molecular pathway involved in oocyte activation.

Hydrogel precursors are liquid solutions that are prone to leaking after surgical placement. This problem was overcome by incorporating either decellularized cartilage (DCC) or devitalized cartilage (DVC) microparticles into traditional photocrosslinkable hydrogel precursors in an effort to achieve a paste-like hydrogel precursor. DCC and DVC were selected specifically for their potential to induce chondrogenesis of stem cells, given that materials that are chondroinductive on their own without growth factors are a revolutionary goal in orthopedic medicine. We hypothesized that DVC, lacking the additional chemical processing steps in DCC to remove cell content, would lead to a more chondroinductive hydrogel with rat bone marrow-derived mesenchymal stem cells. Hydrogels composed of methacrylated hyaluronic acid (MeHA) and either DCC or DVC microparticles were tested with and without exposure to transforming growth factor (TGF)-β3 over a 6 week culture period, where swelling, mechanical analysis, and gene expression were observed. For collagen II, Sox-9, and aggrecan expression, MeHA precursors containing DVC consistently outperformed the DCC-containing groups, even when the DCC groups were exposed to TGF-β3. DVC consistently outperformed all TGF-β3-exposed groups in aggrecan and collagen II gene expression as well. In addition, when the same concentrations of MeHA with DCC or DVC microparticles were evaluated for yield stress, the yield stress with the DVC microparticles was 2.7 times greater. Furthermore, the only MeHA-containing group that exhibited shape retention was the group containing DVC microparticles. DVC appeared to be superior to DCC in both chondroinductivity and rheological performance of hydrogel precursors, and therefore DVC microparticles may hold translational potential for cartilage regeneration.

Studies over the last two decades have revealed profound immunomodulatory aspects of vitamin D on various aspects of the immune system. This review will provide an overview of Vitamin D metabolism, a description of dendritic cell subsets, and highlight recent advances on the effects of vitamin D on dendritic cell function, maturation, cytokine production and antigen presentation. The active form of vitamin D, 1,25(OH)₂D₃, has important immunoregulatory and anti-inflammatory effects. Specifically, the 1,25(OH)₂D₃-Vitamin D₃ complex can affect the maturation and migration of many dendritic cell subsets, conferring a special immunoregulatory role as well as tolerogenic properties affecting cytokine and chemokine production. Furthermore, there have been many recent studies demonstrating the effects of Vitamin D on allergic disease and autoimmunity. A clear understanding of the effects of the various forms of Vitamin D will provide new opportunities to improve human health.

Background: Persisting psychotic-like experiences (PLEs) are associated with an increased risk of internalising symptoms in adolescence. Whether this association holds similarly for externalising symptoms, and from mid-childhood, is unclear. This prospective study investigated the extent to which PLE persistence was associated with internalising and externalising psychopathology in a community sample of children aged 9-11years at study commencement., Methods: 8099 children (mean age 10.4years) completed questionnaires assessing PLEs, externalising and internalising symptoms. A subsample of 547 children completed reassessment, on average, two years later., Results: Two-thirds (66%) of children reported PLEs at baseline. Approximately two years later, PLEs persisted in 39% of those children. After adjustment for previous psychopathology and other potential confounds, children with persisting PLEs were at higher risk for internalising (odds ratio [OR]=1.94; 95% confidence interval [CI] 1.13-3.34) and externalising (OR=1.97; 95% CI 1.19-3.26) psychopathology than children whose PLEs remitted; and, than children who never presented PLEs., Conclusions: Persistent PLEs from mid-childhood are associated with later internalising and externalising psychopathology in the general population, whereas transitory PLEs may be part of a spectrum of normative childhood development. Interventions that target persistent PLEs may contribute to a reduction in common childhood psychopathology., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Gymnodinium bloom events are of concern, since they produce toxins, which have unfavorable consequences to marine ecosystems, human health and the economy. This report describes the physico-chemical conditions that were present during the algal bloom event on May 2010 in Bahía Manzanillo and Bahía Santiago, Colima, Mexico. For this, seawater nutrient analysis, phytoplankton counts, identification, and toxicity tests were undertaken. Nutrients in seawater were determined using colorimetric techniques, the higher concentrations (8.88 microM DIN, 0.78 microM PO4 and 24.34 microM SiO2) were related with upwelling waters that promoted the algal bloom that began after registering the year lowest sea-surface temperature, favoring the rapid growth of G. catenatum (up to 1.02 x 10(7) cells/L). Phytoplankton counting was carried out using sedimentation chambers and cells enumerated on appropriated area. The bloom persisted in the bays for approximately two weeks and was associated with toxicity (determined with HPLC) in local oysters (1525.8 microg STXeq/100g), and in phytoplankton (10.9 pg STXeq/cells) samples. Strong variations in cell toxicity (1.4 to 10.9pg STXeq/cells), most likely reflected the availability of inorganic nutrients. The toxin profile of the phytoplankton samples consisted of 11 toxins and resembled those recorded for several strains of G. catenatum isolated from other coastal areas of Mexico.

This study examined 'Theory of Mind' (ToM) functioning, its association with psychometric schizotypy and with self-reported psychotic-like experiences (PLEs) and depressive symptoms, in a community sample of adolescents. Seventy-two adolescents (mean age 14.51years) from Barcelona, Spain, completed questionnaires assessing PLEs, depressive symptoms, and schizotypy. A verbal ToM task and a vocabulary test were administered. The effect of symptomatology, vocabulary ability, age, and gender on task performance was explored. Neither total score on schizotypy nor PLEs were associated with ToM performance. A significant effect of vocabulary on adolescent's performance of both ToM and control stories was found. ToM showed significant negative associations with positive schizotypy, and with one cluster of positive PLEs: first-rank experiences. Positive significant associations between ToM and persecutory delusions and the impulsive aspects of schizotypy were found. Depressive symptoms did not affect ToM performance. Positive schizotypal traits and first-rank symptoms are associated with ToM deficits in adolescents. Results support the trait-(versus state-) dependent notion of ToM impairments in schizophrenia. ToM may be a developmental impairment associated with positive schizotypy and PLEs., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

In mammals, the stress-activated protein kinase (SAPK) p38 coordinates a rapid and complex transcriptional program to adapt to sudden changes in the extracellular environment. Although a number of genes have been reported to be under the control of p38, the basic mechanisms of transcriptional regulation by this SAPK remain uncharacterized. Here we show that in response to osmotic shock, anisomycin- or TNFα-activated p38 SAPK is recruited to stress-induced genes. The MAPKK MKK6 is also found at stress-responsive promoters. The recruitment of RNA polymerase II complex to the target promoters requires p38 activity. Moreover, when tethered to DNA as a LexA fusion protein, p38 activates transcription in a stress-regulated manner. Thus, p38 activity allows for recruitment of RNA polymerase and transcription initiation. p38 directly phosphorylates and interacts with the transcription factor Elk1. p38 activity is necessary for the recruitment of Elk1 to the c-Fos promoter, and knocking down Elk1 by siRNAs compromises both p38 recruitment to the c-Fos promoter and c-Fos transcriptional up-regulation upon osmostress. In addition, p38 recruitment to the osmoinducible gene Cox2 and the TNFα target gene IL8 is mediated by the transcription factors AP1 and NFκB, respectively. Therefore, anchoring of active SAPK to target genes is mediated by transcription factors. The presence of active p38 at open reading frames also suggests the involvement of the SAPK in elongation. Taken together, SAPK recruitment to target genes appears to be a broad mechanism to regulate transcription that has been preserved from yeast to mammals.

Background: Cells have the ability to respond and adapt to environmental changes through activation of stress-activated protein kinases (SAPKs). Although p38 SAPK signalling is known to participate in the regulation of gene expression little is known on the molecular mechanisms used by this SAPK to regulate stress-responsive genes and the overall set of genes regulated by p38 in response to different stimuli., Results: Here, we report a whole genome expression analyses on mouse embryonic fibroblasts (MEFs) treated with three different p38 SAPK activating-stimuli, namely osmostress, the cytokine TNFalpha and the protein synthesis inhibitor anisomycin. We have found that the activation kinetics of p38alpha SAPK in response to these insults is different and also leads to a complex gene pattern response specific for a given stress with a restricted set of overlapping genes. In addition, we have analysed the contribution of p38alpha the major p38 family member present in MEFs, to the overall stress-induced transcriptional response by using both a chemical inhibitor (SB203580) and p38alpha deficient (p38alpha-/-) MEFs. We show here that p38 SAPK dependency ranged between 60% and 88% depending on the treatments and that there is a very good overlap between the inhibitor treatment and the ko cells. Furthermore, we have found that the dependency of SAPK varies depending on the time the cells are subjected to osmostress., Conclusions: Our genome-wide transcriptional analyses shows a selective response to specific stimuli and a restricted common response of up to 20% of the stress up-regulated early genes that involves an important set of transcription factors, which might be critical for either cell adaptation or preparation for continuous extra-cellular changes. Interestingly, up to 85% of the up-regulated genes are under the transcriptional control of p38 SAPK. Thus, activation of p38 SAPK is critical to elicit the early gene expression program required for cell adaptation to stress.

Background: The etiology and outcomes of blood-stream infections (BSI) among paediatric patients is not well described in resource-limited countries including Georgia., Methodology: Patients with positive blood cultures at the largest paediatric hospital in the country of Georgia were identified by review of the medical and laboratory records of patients who had blood for cultures drawn between January 2004 and June 2006., Results: Of 1,693 blood cultures obtained during the study period, 338 (20%) were positive; of these, 299 were included in our analysis. The median age was 14 days from a range of 2 days to 14 years of which 178 (60%) were male; 53% of the patients with a positive culture were admitted to the Neonatal Intensive Care Unit (NICU). Gram-negative bacilli (GNB) represented 165 (55%) of 299 cultures. Further speciation of 135 (82%) of 165 Gram-negative rod (GNR) was not possible because of lack of laboratory capacity. Overall, mortality was 30% (90 of 299). Among the 90 children who died, 80 (89%) were neonates and 68 (76%) had BSI caused by Gram-negative organisms. In multivariate analysis, independent risk factors for in-hospital mortality included an age of less than 30 days (OR=4.00, 95% CI 1.89-8.46) and having a positive blood culture for a Gram-negative BSI (OR = 2.38, 95% CI 1.32-4.29)., Conclusions: A high mortality rate was seen among children, particularly neonates, with positive blood cultures at the largest paediatric hospital in Georgia. Because of limited laboratory capacity, microbiological identification of common organisms known to cause BSI in children was not possible and susceptibility testing was not performed. Improving the infrastructure of diagnostic microbiology laboratories in countries with limited resources is critical in order to improve patient care and clinical outcomes, and from a public health standpoint, to improve surveillance activities.

Background and Objectives: This study's objective was to evaluate the association between health literacy and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) knowledge among patients seen at an inner-city, public hospital urgent care center (UCC)., Methods: We used a prospective survey of patients offered an HIV test by their providers during a UCC visit. We measured patients' health literacy level using the Rapid Estimate of Adult Literacy in Medicine (REALM) scale and assessed their HIV/AIDS knowledge using a 22-item questionnaire., Results: A total of 372 patients were enrolled. Among participants in this relatively young sample (55% were under the age of 40), 92 (25%) had a REALM score at or below a sixth-grade level, and 122 (33%) did not have a high school diploma. Patients' mean HIV/AIDS knowledge scores differed significantly between patients with inadequate health literacy and those with marginal or adequate health literacy. In multivariate analyses, patients' REALM scores were positively associated with patients' HIV/AIDS knowledge even after adjusting for income, education, and risk perception., Conclusions: These findings demonstrate that HIV/AIDS knowledge is strongly associated with patients' health literacy in this inner-city population. These findings reiterate the need to target HIV prevention strategies toward populations with inadequate health literacy levels and to dispel misconceptions regarding HIV/AIDS that directly influence risk-taking behaviors and health care utilization.

Despite some improvements in the health status of the world during the last few decades, major obstacles remain. Improvements in health outcomes have not been shared equally among countries and poverty is clearly the main reason. Infectious diseases, which remain the major cause of death worldwide, are an incalculable source of human misery and economic loss. In fact, 25% of all deaths and 30% of the global burden of disease are attributed to infectious diseases. Unfortunately, more than 95% of these deaths, most of which are preventable, occur in the developing world, where poverty is widespread. The 3 major infectious disease killers in these countries are HIV/AIDS, tuberculosis, and malaria. The principles of social justice and health as a human right in the developing world have been advocated as the main justification for health assistance from rich to poor countries. Although we do not disagree with this, we argue that a strategy that emphasizes the shared benefit to rich and poor countries would facilitate this process. We propose that the accomplishment of these challenging tasks should be viewed from the perspective of game theory, where the interests of the parties (in this case rich and poor countries) overlap. As the world becomes increasingly integrated, economic development in resource-poor countries will increase the opportunities for richer countries to profit from investment in the developing world. Global health has political and international security implications for the developed world, as well. In view of the current health status of the developing world, we are not playing a game but facing a matter of life and death. "When health is absent, wisdom cannot reveal itself, art cannot become manifest, strength cannot fight, wealth becomes useless, and intelligence cannot be applied" --Herophilus, 325 BCE (Physician to Alexander the Great). The purpose of this article is to address the relationship between health, poverty, and development in the context of game theory. We will focus on the link between economic inequalities and health outcomes, exclusively concentrating our analysis on the impact of infectious diseases. Subsequently, we will outline the game, the players, and the potential win-win outcomes that may potentially result.

Embryos were collected on Days 5 and 6 after breeding to investigate the effectiveness of ethylene glycol (ETG) and glycerol (GLY) as cryoprotectants of sheep morulae and blastocysts and to determine their optimum stage of development for cryopreservation. Only excellent (grade 1) and good (grade 2) embryos (196 morulae and 188 blastocysts) were incubated in increasing concentrations of GLY or ETG and submitted to a slow-freezing and quick-thawing procedure. Both cryoprotectants were removed using 0.25 M sucrose solution, and then embryos were cultured or transferred to determine their viability. Freezing medium containing ETG yielded higher in vitro survival rates (P < 0.01) than medium containing GLY (64.6% vs 16.0%); the difference between cryoprotectants was greater when morulae were used (57.9% vs 4.2%, P < 0.005) as compared with blastocysts (70.4% vs 21.5%, P < 0.05). There was a strong interaction between type of cryoprotectant and embryo stage (P < 0.005). After transfer of morphologically viable embryos, the in vivo development rate of embryos frozen with ETG was also higher than that of embryos frozen with GLY (45.5% vs 27.7%, P < 0.05). There were no significant differences in the number of lambs born among procedures and embryo stage, though the lowest lambing rate was obtained with morulae frozen with GLY (21.4%). Similar lambing rates were produced when blastocysts were frozen with either GLY or ETG (36.6% vs 43.0%). The best embryo survival after thawing was observed when blastocysts were frozen with ETG as cryoprotectant.

This study was designed to compare sleep organization at high altitude (HA) and sea level (SL) and to estimate the extent periodic breathing (PB) negatively influences arterial O2 saturation (SaO2). Six lowlanders were studied at SL and after 3 weeks spent at 3,800 m (La Paz, Bolivia). Three EEG leads, EOG, submental EMG, chest and abdominal motion, temperature of ventilated gas, and SaO2 were polygraphically recorded. Comparison of HA and SL data disclosed that: 1) Sleep organization was identical, with the same percentage of REM and stage 4. 2) PB (cycle length: 20 s; central apnea: 9 s) occurred in three subjects during all stages of sleep except REM (43-60% of total sleep). A periodic lowering in heart rate occurred during ventilatory oscillation. 3) During PB, SaO2 oscillated very regularly from 78-90%, which resulted in a mean SaO2 value calculated during oscillations similar to that of the non-periodic breathers. We conclude that lung O2 uptake during PB is preserved.

This paper presents data on hemoglobin concentration in a rural Andean sample at 3,800-3,900 m and incorporates them into a review intended to evaluate possible sources of the range of variation in mean hemoglobin concentration among samples obtained at high altitude. Between 3,400 and 4,000 m, rural Himalayan highlanders average 1.4 gm/dl lower mean hemoglobin concentration than rural Andean highlanders. With respect to potential causes of anemia, it is concluded that the relatively low values of rural Himalyan populations are not explicable by lower hypoxic stress or different techniques of obtaining and analyzing blood samples and are probably not explicable by nutritional deficiency and disease. With respect to potential causes of polycythemia within Andean populations, it is concluded that the somewhat higher values of some mining and urban samples of Andean higlanders may not be due to the mining occupation per se but may be due partly to the inclusion of European and mestizo (with at most 500 years of high-altitude ancestry) along with Amerindian highlanders (with millenia of high-altitude ancestry) as well as to the inclusion of highlanders living well above their own habitual altitudes of residence. The Andean polycythemia is probably not due to obesity, high androgen levels, or frequent intermittent hypoxemia during sleep. The effect of heavy smoking cannot be evaluated. Further work on hematological adaptation to high altitude must pay special attention to sample characteristics., (Copyright © 1990 Wiley-Liss, Inc., A Wiley Company.)

We describe 2 cases of progressive hemifacial atrophy (Parry-Romberg syndrome) with typical facial and ocular involvement. Ocular manifestations in these 2 cases include enophthalmos, due to fat atrophy, decreased corneal sensitivity, episcleritis, and band keratopathy. The slowly progressive changes were documented in one case over a 40 year period. Both cases were unilateral with limitation of the lesions at the midline.