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Phosphatidylethanol (PEth) is an alcohol derivative that has been employed as a blood-based biomarker for regular alcohol use. This study investigates the utility of phosphatidylethanol (PEth) as a biomarker for assessing alcohol consumption in post-mortem brain tissue. Using samples from the New South Wales Brain Tissue Resource Centre, we analysed PEth(16:0/18:1) levels in the cerebellum and meninges of individuals with varying histories of alcohol use, including those diagnosed with alcohol use disorder (AUD) and controls. Our findings demonstrate a significant correlation between PEth levels and blood alcohol content (BAC) at the time of death, supporting the biomarker's sensitivity to recent alcohol intake. Furthermore, this study explores the potential of PEth levels in differentiating AUD cases from controls, taking into consideration the complexities of diagnosing AUD post-mortem. The study also examined the relationship between PEth levels and liver pathology, identifying a link with the severity of liver damage. These results underscore the value of PEth as a reliable indicator of alcohol consumption and its potential contributions to post-mortem diagnostics and consequently, research into alcohol-related brain damage.

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The New South Wales Brain Tissue Resource Centre is a human brain bank that provides top-quality brain tissue for cutting-edge neuroscience research spanning various conditions from alcohol use disorder to neurodegenerative diseases. However, the conventional practice of preserving brain tissue in formalin poses challenges for immunofluorescent staining primarily due to the formalin's tendency, over time, to create cross-links between antigens, which can obscure epitopes of interest. In addition, researchers can encounter issues such as spectral bleeding, limitations in using multiple colors, autofluorescence, and cross-reactivity when working with long-term formalin-fixed brain tissue. The purpose of the study was to test chromogen-based double immunolabeling to negate the issues with immunofluorescent staining. Colocalization of antigens was explored using chromogens 3-amino-9-ethylcarbazole (AEC) and 3,3,-diaminobenzidine in a sequential staining procedure where the AEC signal was eliminated by alcohol treatment. Combinations of 2 or 3 primary antibodies from the same or different species were trialed successfully with this protocol. The colocalization of antigens was also demonstrated with pseudocoloring that mimicked immunofluorescence staining. This staining technique increases the utility of archival formalin-fixed tissue samples.

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Background: There is a great need for effective primary prevention intervention strategies to reduce and delay onset of adolescent substance use. The Icelandic Prevention Model (IPM) showed great success in Iceland over the past twenty plus years, however, evidence for the transferability of model is still somewhat limited. Using data collected in Tarragona during regional efforts to begin adoption of the IPM in Catalonia, this study tested the transferability and stability of the core risk and protective factor assumptions of the IPM overtime and examined trends of lifetime smoking, e-cigarette-use, alcohol-use, intoxication, and cannabis-use within the same time period. Methods: This study includes responses from 15- to 16-years-olds from two region-wide samples taken in 2015 and 2019 in Tarragona (N = 2,867). Survey questions assessed frequency of lifetime: smoking, e-cigarette-use, alcohol-use, intoxication, and cannabis-use, and the core model assumptions. Demographic data were also collected. Logistic regression models of main effects with and without time interaction were used to test assumptions and their stability across time. Chi-square tests and Wilcoxon-Mann-Whitney U tests were used to compare prevalence of substance use and mean scores of primary prevention variables respectively. Results: Lifetime: smoking (-7%, p < 0.001) and cannabis-use (-4%, p < 0.001) decreased, and e-cigarette-use increased (+33%, p < 0.001) in Tarragona. Lifetime intoxication (-7%, p < 0.001) decreased in a single zone exclusively. Most core model assumptions held in their hypothesised direction across time. The strongest positive association was observed between time spent with parents during weekends and reduced odds of lifetime smoking (OR: 0.62, 95%CI: 0.57-0.67) and the strongest negative association was observed between being outside after midnight and increased odds of lifetime intoxication (OR: 1.41, 95%CI: 1.32-1.51). Mean scores of primary prevention variables also changed disproportionately in Tarragona. Conclusion: This study confirms that the core IPM assumptions are similar in Tarragona as in Iceland and other contexts previously examined. They also indicate that prevalence of lifetime smoking, intoxication, and cannabis-use decreased disproportionately in Tarragona between 2015 and 2019 during the first phase of regional adoption of the model. Thus, targeting model assumptions represents a viable primary prevention strategy for communities that hope to reduce smoking, alcohol-use, intoxication, and cannabis-use among adolescents.

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Alcohol-related brain injury is characterized by cognitive deficits and brain atrophy with the prefrontal cortex particularly susceptible. White matter in the human brain is lipid rich and a major target of damage from chronic alcohol abuse; yet, there is sparse information on how these lipids are affected. Here, we used untargeted lipidomics as a discovery tool to describe these changes in the prefrontal, middle temporal, and visual cortices of human subjects with alcohol use disorder and controls. Significant changes to the lipidome, predominantly in the prefrontal and visual cortices, and differences between the white and grey matter of each brain region were identified. These effects include broad decreases to phospholipids and ceramide, decreased polyunsaturated fatty acids, decreased sphingadiene backbones, and selective decreases in cholesteryl ester fatty acid chains. Our findings show that chronic alcohol abuse results in selective changes to the neurolipidome, which likely reflects both the directs effects on the brain and concurrent effects on the liver.

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BACKGROUND: Differential effects of the coronavirus SARS-CoV-2 (COVID-19) pandemic and associated public restrictions on adolescent girls and boys are emerging but have not been elucidated. This study examined gender differences across broad indicators of adolescent well-being during the COVID-19 pandemic in Iceland, and explored potential explanations for these differences. METHODS: In total, 523 youth (56.5% girls) born in Iceland in 2004 completed measures on mental health problems (depressive symptoms, anger and suicide attempts) and measures designed for this study to assess broad indicators of adolescent well-being (e.g., day-to-day life, academic performance, family and peer relationships, and mental and physical health) and behavioral changes during the COVID-19 pandemic. Mental health problems during the pandemic were compared to expected scores based on nationwide ratings of same-aged peers in 2018. RESULTS: Although both boys and girls appeared affected, girls reported a greater negative impact across all the broad indicators of well-being and behavioral change during COVID-19 than boys, and their depressive symptoms were above and beyond the expected nationwide scores (t(1514) = 4.80, p < .001, Cohen's d = 0.315). Higher depressive symptoms were associated with increased passive social media use and decreased connecting with family members via telephone or social media among girls, and decreased sleeping and increased online gaming alone among boys. Concern about others contracting COVID-19, changes in daily and school routines, and not seeing friends in person were among the primary contributors to poor mental health identified by youth, particularly girls. CONCLUSIONS: Adolescents were broadly negatively affected by the COVID-19 pandemic and accompanying restrictions; however, this negative impact was more pronounced in girls. The findings suggest that a steady routine and remaining socially connected may help youth cope with the uncertainty and social restrictions associated with a pandemic. Moreover, healthcare providers, teachers, and other professionals should pay close attention to depressive symptoms among girls during a pandemic.

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RATIONALE: Matrix-assisted laser desorption ionisation with mass spectrometry imaging (MSI) has seen rapid development in recent years and as such is becoming an important technique for the mapping of biomolecules from the surface of tissues. One key area of development is the optimisation of analyte extraction by using modified matrices or mixes of common ones. METHODS: A series of serial sections were prepared for lipid MSI by either dry coating (sublimation) or by wet spray application of several matrices. These samples were then evaluated for analyte extraction, delocalisation and dynamic range. RESULTS: We have shown that the spraying and sublimation methods of matrix application can be used complementarily. This creates large datasets, with each preparation method applied narrowly and then interpreted as a 'fraction' of the whole. Once combined, the dynamic range is significantly increased. We have dubbed this technique 'matrix phase fractionation'. CONCLUSIONS: We have found that, by utilising matrix phase fractionation for the detection of lipids in brain tissue, it is possible to create a significantly more comprehensive dataset than would otherwise be possible with traditional 'single-run' workflows.

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Severe stress exposure causes the loss of dendritic spines on cortical pyramidal neurons and induces psychiatric-like symptoms in rodent models. These effects are strongest following early-life stress and are most persistent on apical dendrites. However, the long-term impacts and temporal effects of stress exposure on the human brain remain poorly understood. Using a novel postmortem cohort of psychiatric cases with severe stress experienced in childhood, adulthood, or no severe stress, and matched controls, we aimed to determine the impact of stress timing on pyramidal neuron structure in the human orbitofrontal cortex (OFC). We performed Golgi Cox staining and manually measured the morphology and density of over 22,000 dendritic spines on layer-specific pyramidal neuron apical dendrites. We also quantified glucocorticoid receptor mRNA and protein as a marker of stress dysregulation. Both childhood and adulthood stress were associated with large reductions in mature mushroom spine density (up to 56% loss) in both the superficial (II/III) and deeper layers (V) of the OFC. However, childhood stress caused more substantial reductions to both total and mature mushroom spines. No difference in glucocorticoid receptor mRNA and protein were seen between groups, although both negatively correlated with total spine density within the whole cohort. These findings indicate that severe stress, especially when experienced during childhood, persistently affects the fine morphological properties of neurons in the human OFC. This may impact on cell connectivity in this brain area, and at least partly explain the social and emotional symptoms that originate in the OFC in psychiatric disorders.

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Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is a well-established technique for elucidating the location and relative abundance of a range of biomolecules. More recently, research into this technique has shifted from simple discovery and demonstration of utility to application in biomedical research. Here, we describe a protocol utilizing MALDI-IMS for the spatial mapping of lipids in brain tissue from normal human brains and brains from patients with Alzheimer's disease, in the context of Alzheimer's disease. Improved accuracy calibration of the instrument from the tissue surface is emphasized, as this allows for significantly improved mass determination in time of flight (TOF)-based instruments enabling more confident preliminary lipid identification. This improved initial result allows MALDI-IMS data to be complemented with additional instrumentation, such as liquid chromatography mass spectrometry workflows or specialized non-TOF systems such as Fourier transform cyclotron resonance instruments. This method is not limited to human tissue and can be applied to virtually any lipid-rich formalin-fixed tissue. © 2019 by John Wiley & Sons, Inc.

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BACKGROUND: Binge-like ethanol (EtOH) exposure during the early rat neonatal period results in acute cell loss in specific brain regions, but such acute cell death has not been well established in the hippocampus. Binge alcohol exposure can also result in protein expression changes in the cerebellum that could alter cell fate, but this has not been reported for the hippocampal subregions. This study investigates acute apoptotic cell death in hippocampal regions CA1, CA3, and dentate gyrus (DG) following a binge EtOH exposure on postnatal day (PN) 6, PN8, or PN6 + 8 and the alteration in pro- and anti-apoptotic proteins following a single EtOH binge on PN6. METHODS: Apoptotic cell death was quantified 12 hours after EtOH binge exposure using the optical fractionator method. Western blot analysis determined expression of pro-apoptotic Bax and anti-apoptotic Bcl-2, 12, 24, and 48 hours after binge EtOH exposure on PN6. The Bcl-2:Bax ratio was used as a measure of vulnerability to apoptosis. RESULTS: Acute apoptosis increased significantly 12 hours following PN6 or 8 EtOH exposure in CA1, CA3, and DG, but the magnitude of apoptotic cell death was significantly greater in CA1 than in CA3 and DG, which did not differ. Significant cell death was not detected when a PN8 EtOH exposure was preceded by exposure on PN6. Binge EtOH exposure on PN6 resulted in a significant increase in expression of Bcl-2 and the Bcl-2:Bax ratio in the CA1/DG region at 24 hours after EtOH exposure on PN6. The Bcl-2:Bax ratio in the CA3 region was not altered. CONCLUSIONS: This study shows that repeated binge exposure does not have a cumulative effect on the magnitude of acute apoptotic cell death. This finding may be explained in part by changes in the Bcl-2:Bax ratio after a single binge EtOH exposure.

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BACKGROUND: Children with heavy prenatal alcohol exposure have well documented deficits in overall cognitive ability. Recently, attention has turned to the executive function (EF) domain in this population. Until recently, comprehensive measures of EF have not been available within one test battery. This study used a battery of tests to assess four domains of EF in alcohol-exposed children. METHODS: The Delis-Kaplan Executive Function Scale was used to evaluate EF in 18 children with heavy prenatal alcohol exposure, with and without a diagnosis of fetal alcohol syndrome (FAS), and 10 nonexposed controls. Children ranged in age from 8 to 15 years. Measures from four domains of executive functioning were analyzed: planning ability, cognitive flexibility, selective inhibition, and concept formation and reasoning. Tasks consisted of primary EF measures as well as measures of secondary component skills. RESULTS: Alcohol-exposed children were deficient on EF measures compared with nonexposed controls. Furthermore, in most cases, children with and without the FAS diagnosis did not differ from one another. These deficits were not entirely explainable by concomitant deficits on component skills. Specific impairments were identified within the domains of planning and response inhibition, with additional deficits in abstract thinking and flexibility. CONCLUSIONS: Deficits in executive functioning were observed in alcohol-exposed children with or without the diagnosis of FAS and in the absence of mental retardation. Performance on these EF tasks provides insight into the cognitive processes driving overall performance and has implications for adaptive and daily functions. These results are consistent with anecdotal and empirical reports of deficits in behavioral control and with neuroanatomical evidence of volumetric reductions in structures within the frontal-subcortical system in children with heavy prenatal alcohol exposure.

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The Mount Sinai Hospital is reengineering its inpatient services to increase the quality of patient care and achieve greater operational efficiency. The central component of this redesign has been the establishment of "care centers," which are administratively and fiscally separate "hospitals within the hospital." To promote quality and financial goals set for each care center, a novel employee incentive compensation program was created. Performance on both quality and financial indicators determines the level of bonus payments to hourly employees. The incentive compensation plan was initiated in the first quarter of 1996. By achieving two of the three performance targets, employees earned a bonus of 6% of base salary for the first two quarters. Nurses and pharmacists did not accept bonus payments because of collective bargaining agreements. The early experience of the Cardiac Care Center has been highly favorable. Changes are planned to improve the process further.

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This paper presents an exploration of the role of clinical directorate managers in facilitating evidence-based practice. It reports on a small qualitative study which explored the perceptions held by directorate managers regarding their role in facilitating evidence-based practice for their nursing teams. Insights were sought into the nature of the overt and covert behaviours which the managers used in encouraging nurses to base their practices on research evidence. The sample consisted of 10 directorate managers from two teaching hospitals in one Trust, whose characteristics were not atypical from other directorate managers. Data were collected using semi-structured, tape-recorded interviews. Interviews focused on manager's backgrounds, professional responsibilities and practices, personal research agendas and socio-political influences. Findings revealed some constraining influences on the development of evidence-based practice, such as the Clinical Managers' budget allocations, and the policies and goals of the Trust. However, in respect of the managers' own practices, whilst some facilitative behaviours were identified, the data suggested that clinical managers were behaving in a manner which actually inhibited the development of evidence-based nursing practice. It would appear that in the post-reform National Health Service (NHS) clinical managers find themselves in a difficult position which gives rise to a practical failure to use their position and organizational authority to influence the utilization of research in practice. The implications of these findings for an evidence-based health service are discussed.

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With over 500,000 individuals receiving health benefits at a cost of over $900 million, the IBM Corporation has a keen interest in the future of the U.S. health care system, the employer's role in it, and the quality of medical care its employees and retirees receive. The U.S. health care system is in the midst of undergoing a dramatic transformation, and employers and their employees need to understand this change and know how to become informed purchasers of the medical care they need.

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In its recent reengineering efforts, the Mount Sinai Hospital developed economic tools to assure that this major restructuring project would reach its predetermined financial objectives. We discuss how these tools were designed and implemented and what impact they had.

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Aim-To determine the relation of the low anticoagulant response phenotype with the Factor V Q506 (Leiden) mutation in a cohort of patients with thrombophilia.Methods-Fifty four patients with either a personal or family history of deep vein thrombosis were investigated both for their anticoagulant response by the activated protein C resistance test (APCR) and their genetic status in respect of the Leiden mutation by means of a PCR-RFLP method.Results-Low APCR ratios do not necessarily predict possession of the Leiden mutation. Conversely, normal ratios do not exclude the mutation. Of 14 individuals with low APCR ratios, the Leiden mutation was absent in five. Of the remainder, three were heterozygous and six homozygous. Of nine heterozygote individuals, only three had low APCR ratios. All patients homozygous for the defect had low APCR ratios.Conclusions-These results lend further weight to the hypothesis that the APC resistant phenotype results from more than one genetic defect and indicate the value of combined functional and molecular investigations in all patients with thrombophilia.

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Some observers feel that the federal government should play a more active leadership role in educating the medical community and in coordinating and encouraging a more rapid and effective implementation of clinically relevant applications of wide-area networking. Other people argue that the private sector is recognizing the importance of these issues and will, when the market demands it, adopt and enhance the telecommunications systems that are needed to produce effective uses of the National Information Infrastructure (NII) by the healthcare community. This debate identifies five areas for possible government involvement: convening groups for the development of standards; providing funding for research and development; ensuring the equitable distribution of resources, particularly to places and people considered by private enterprise to provide low opportunities for profit; protecting rights of privacy, intellectual property, and security; and overcoming the jurisdictional barriers to cooperation, particularly when states offer conflicting regulations. Arguments against government involvement include the likely emergence of an adequate infrastructure under free market forces, the often stifling effect of regulation, and the need to avoid a common-and-control mentality in an infrastructure that is best promoted collaboratively.

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A prospective study of injuries affecting 50 highly competitive young female gymnasts was conducted over a period of 1 year. Many of the findings of this investigation were consistent with previous studies and suggest particular injury trends in women's gymnastics. These results included injury location, injury severity, nature of onset, event, and activity at the time of injury. Some of the descriptive results, however, provided information that was heretofore unreported or inconsistent with previous investigations. These findings involved injury rate, reinjury rate, time loss, injury type, hours of practice, and incidence of physician-seen injuries. Some of these findings were disturbing and echo concerns registered in the professional literature. In particular, the reinjury rate is alarming and points to the need for complete rehabilitation before return to full participation. The results of the analytic component of the study alluded to the potential role of competitive level and maturation rate in the profile of the injury-prone gymnast. Specifically, rapid periods of growth and advanced levels of training and competition appeared to be related to injury proneness. Pursuant to the descriptive and analytic results of the investigation, recommendations for injury prevention and continued research are made.

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This paper reviews the relevant pediatric literature about blood pressure (BP) hyperreactivity to stress as a possible precursor of hypertension and coronary heart disease. Two prospective studies of children indicate that BP hyperreactivity predicts later development of hypertension. Several studies have identified correlates of BP reactivity. Race, obesity, Type A and family history of hypertension appear to be associated with BP reactivity in children. There appear to be both genetic and environmental influences, but relatively few psychosocial variables have been studied. There are significant methodological concerns in terms of defining the characteristics of the stressors and the stability and generalizability of responses to laboratory stressors. BP reactivity in children is a potentially important area of inquiry that has been understudied.

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Results showed that a Navy-sponsored weight-reduction program was relatively successful in helping participants lose weight during treatment and throughout a one-year follow-up. Of the 531 women and 155 men who reported a mean weight loss of 22 lb and 28 lb, respectively, 32 per cent of the women and 29 per cent of the men responded that no weight had been gained during treatment and follow-up. Regression analyses identified predictors of weight loss to be a self-reported improvement in health status, a history of few dieting attempts, and adult onset of obesity. Correlates of weight-loss maintenance included a change in eating behavior, a self-reported improvement in health status and feelings toward dieting, adult onset of obesity, and physical exercise participation. Such results pointed up the importance of developing an intervention program that incorporates an exercise regimen and the adoption of a long-term nutritionally-sound eating program.

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