132 research outputs found

    Human 3D cellular model of hypoxic brain injury of prematurity.

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    Owing to recent medical and technological advances in neonatal care, infants born extremely premature have increased survival rates1,2. After birth, these infants are at high risk of hypoxic episodes because of lung immaturity, hypotension and lack of cerebral-flow regulation, and can develop a severe condition called encephalopathy of prematurity3. Over 80% of infants born before post-conception week 25 have moderate-to-severe long-term neurodevelopmental impairments4. The susceptible cell types in the cerebral cortex and the molecular mechanisms underlying associated gray-matter defects in premature infants remain unknown. Here we used human three-dimensional brain-region-specific organoids to study the effect of oxygen deprivation on corticogenesis. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and showed that these are related to the unfolded protein response and changes. Moreover, we verified these findings in human primary cortical tissue and demonstrated that a small-molecule modulator of the unfolded protein response pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be valuable for studying the environmental and genetic factors underlying injury in the developing human brain

    Visualizing the Influence of Social Networks on Recovery:A Mixed-Methods Social Identity Mapping Study with Recovering Adolescents

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    BackgroundSocial recovery capital (SRC) refers to resources and supports gained through relationships and is vital to adolescent addiction recovery. Much is known about how substance use relates to social networks, but little is known about how other dimensions of social networks influence recovery (e.g., network size/exposure, degree of conflict). MethodsThis mixed-methods study sampled 28 adolescents who received treatment for alcohol and other drug (AOD) use disorder (14-19 yrs.: 71% male; M=17.32 yrs., SD=1.33; White 82%): 20 were recovery high school (RHS) students. Adolescents completed a social identity map for addiction recovery (SIM-AR), survey, and interview. Qualitative data were content analyzed and the data from the SIM-AR were quantified. ResultsOn average, participants reported belonging to five having 5 distinct groups (Range, 2-9; SD=1.63; M=27.89 people, SD = 20.09) in their network. Of their social network connections, on average, 51% drank alcohol and 46% used other substances. Larger networks involved more conflict (r=0.57). Participants were more likely to spend more time with groups that had greater proportions of non-substance usinge members; these relationships were stronger for RHS than for non-RHS students. Qualitative analyses revealed that youth reported their recovery-oriented groups as supportive, yet some felt their substance-using friends also supported their recovery.DiscussionSIM-AR was a useful measurement tool, and, through qualitative interviews, we identified unique aspects of youth’s social networks important for further examination. Research with recovering youth should examine SRC-related elements within their networks including relationship quality, belonging, and conflict, in addition to the substance use behaviors of network members. <br/

    Cardiorespiratory fitness is associated with hard and light intensity physical activity but not time spent sedentary in 10–14 year old schoolchildren: the HAPPY study

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    Sedentary behaviour is a major risk factor for developing chronic diseases and is associated with low cardiorespiratory fitness in adults. It remains unclear how sedentary behaviour and different physical activity subcomponents are related to cardiorespiratory fitness in children. The purpose of this study was to assess how sedentary behaviour and different physical activity subcomponents are associated with 10–14 year-old schoolchildren's cardiorespiratory fitness

    Biochemical mutagens affect the preservation of fungi and biodiversity estimations

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    Many fungi have significant industrial applications or biosafety concerns and maintaining the original characteristics is essential. The preserved fungi have to represent the situation in nature for posterity, biodiversity estimations, and taxonomic research. However, spontaneous fungal mutations and secondary metabolites affecting producing fungi are well known. There is increasing interest in the preservation of microbes in Biological Resource Centers (BRC) to ensure that the organisms remain viable and stable genetically. It would be anathema if they contacted mutagens routinely. However, for the purpose of this discussion, there are three potential sources of biochemical mutagens when obtaining individual fungi from the environment: (a) mixtures of microorganisms are plated routinely onto growth media containing mutagenic antibiotics to control overgrowth by contaminants, (b) the microbial mixtures may contain microorganisms capable of producing mutagenic secondary metabolites, and (c) target fungi for isolation may produce “self” mutagens in pure culture. The probability that these compounds could interact with fungi undermines confidence in the preservation process and the potential effects of these biochemical mutagens are considered for the first time on strains held in BRC in this review

    Sex Differences in the Association between Serum Levels of Testosterone and Frailty in an Elderly Population: The Toledo Study for Healthy Aging

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    BACKGROUND: Age-associated decline in testosterone levels represent one of the potential mechanisms involved in the development of frailty. Although this association has been widely reported in older men, very few data are available in women. We studied the association between testosterone and frailty in women and assessed sex differences in this relationship. METHODS: We used cross-sectional data from the Toledo Study for Healthy Aging, a population-based cohort study of Spanish elderly. Frailty was defined according to Fried's approach. Multivariate odds-ratios (OR) and 95% confidence intervals (CI) associated with total (TT) and free testosterone (FT) levels were estimated using polytomous logistic regression. RESULTS: In women, there was a U-shaped relationship between FT levels and frailty (p for FT(2) = 0.03). In addition, very low levels of FT were observed in women with ≥ 4 frailty criteria (age-adjusted geometric means = 0.13 versus 0.37 in subjects with <4 components, p = 0.010). The association of FT with frailty appeared confined to obese women (p-value for interaction = 0.05).In men, the risk of frailty levels linearly decreased with testosterone (adjusted OR for frailty = 2.9 (95%CI, 1.6-5.1) and 1.6 (95%CI, 1.0-2.5), for 1 SD decrease in TT and FT, respectively). TT and FT showed association with most of frailty criteria. No interaction was found with BMI. CONCLUSION: There is a relationship between circulating levels of FT and frailty in older women. This relation seems to be modulated by BMI. The relevance and the nature of the association of FT levels and frailty are sex-specific, suggesting that different biological mechanisms may be involved

    The training needs of Turkish emergency department personnel regarding intimate partner violence

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    <p>Abstract</p> <p>Background</p> <p>Violence against females is a widespread public health problem in Turkey and the lifetime prevalence of IPV ranges between 34 and 58.7%. Health care workers (HCW) sometimes have the unique opportunity and obligation to identify, treat, and educate females who are abused. The objective of this study was to evaluate the knowledge, attitudes, and experiences of the emergency department (ED) staff regarding intimate partner violence (IPV) at a large university hospital in Turkey.</p> <p>Methods</p> <p>A cross-sectional study was conducted in a large university hospital via questionnaire. The study population consisted of all the nurses and physicians who worked in the ED during a two month period (n = 215). The questionnaire response rate was 80.5% (41 nurses and 132 physicians). The main domains of the questionnaire were knowledge regarding the definition of IPV, clinical findings in victims of IPV, legal aspects of IPV, attitudes towards IPV, knowledge about the characteristics of IPV victims and abusers, and professional and personal experiences and training with respect to IPV.</p> <p>Results</p> <p>One-half of the study group were females, 76.3% were physicians, and 89.8% had no training on IPV. The majority of the nurses (89.5%) and physicians (71.1%) declared that they were aware of the clinical appearance of IPV. The mean of the knowledge scores on clinical knowledge were 8.84 ± 1.73 (range, 0–10) for acute conditions, and 4.51 ± 3.32 for chronic conditions. The mean of the knowledge score on legal procedures and the legal rights of the victims was 4.33 ± 1.66 (range, 0–7). At least one reason to justify physical violence was accepted by 69.0% of females and 84.7% of males, but more males than females tended to justify violence (chi square = 5.96; p = 0.015). However, both genders accepted that females who experienced physical violence should seek professional medical help.</p> <p>Conclusion</p> <p>The study participants' knowledge about IPV was rather low and a training program is thus necessary on this issue. Attention must be given to the legal aspects and clinical manifestations of IPV. The training program should also include a module on gender roles in order to improve the attitudes towards IPV.</p

    Audit of therapeutic interventions in inpatient children using two scores: are they evidence-based in developing countries?

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    BACKGROUND: The evidence base of clinical interventions in paediatric hospitals of developing countries has not been formally assessed. We performed this study to determine the proportion of evidence-based therapeutic interventions in a paediatric referral hospital of a developing country METHODS: The medical records of 167 patients admitted in one-month period were revised. Primary diagnosis and primary therapeutic interventions were determined for each patient. A systematic search was performed to assess the level of evidence for each intervention. Therapeutic interventions were classified using the Ellis score and the Oxford Centre for Evidence Based Medicine Levels of Evidence RESULTS: Any dehydration due to diarrhoea (59 cases) and pneumonia (42 cases) were the most frequent diagnoses. Based on Ellis score, level I evidence supported the primary therapeutic intervention in 21%, level II in 73% and level III in 6% cases. Using the Oxford classification 16%, 8%, 1% and 75% therapeutic interventions corresponded to grades A, B, C, and D recommendations, respectively. Overall, according to Ellis score, 94% interventions were evidence based. However, out of the total, 75% interventions were based on expert opinion or basic sciences. Most children with mild to moderate dehydration (52 cases) were inappropriately treated with slow intravenous fluids, and most children with non-complicated community acquired pneumonia (42 cases) received intravenous antibiotics CONCLUSIONS: Most interventions were inappropriate, despite the availability of effective therapy for several of them. Diarrhoeal dehydration and community acquired pneumonia were the most common diagnoses and were inappropriately managed. Existing effective interventions for dehydration and pneumonia need to be put into practice at referral hospitals of developing countries. For the remaining problems, there is the need to conduct appropriate clinical studies. Caution must be taken when assigning the level of evidence supporting therapeutic interventions, as commonly used classifications may be misleadin
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