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Background: Previous epidemiological research has linked posttraumatic stress disorder (PTSD) with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records provide an opportunity to overcome clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex., Methods: PTSD was defined among biobank participants ( N  = 145,959) in 3 major healthcare systems using 2 ICD code-based definitions: broad (≥1 PTSD or acute stress codes vs. 0; n cases  = 16,706) and narrow (≥2 PTSD codes vs. 0; n cases  = 3325). Using a phenome-wide association study design, we tested associations between each PTSD definition and all prevalent disease umbrella categories, i.e., phecodes. We also conducted sex-stratified phenome-wide association study analyses including a sex × diagnosis interaction term in each logistic regression., Results: A substantial number of phecodes were significantly associated with PTSD Narrow (61%) and PTSD Broad (83%). While the strongest associations were shared between the 2 definitions, PTSD Broad captured 334 additional phecodes not significantly associated with PTSD Narrow and exhibited a wider range of significantly associated phecodes across various categories, including respiratory, genitourinary, and circulatory conditions. Sex differences were observed in that PTSD Broad was more strongly associated with osteoporosis, respiratory failure, hemorrhage, and pulmonary heart disease among male patients and with urinary tract infection, acute pharyngitis, respiratory infections, and overweight among female patients., Conclusions: This study provides valuable insights into a diverse range of comorbidities associated with PTSD, including both known and novel associations, while highlighting the influence of sex differences and the impact of defining PTSD using electronic health records., (© 2024 The Authors.)

Opioid use disorder (OUD) looms as one of the most severe medical crises facing society. More effective therapeutics will require a deeper understanding of molecular changes supporting drug-taking and relapse. Here, we develop a brain reward circuit-wide atlas of opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) and heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute heroin exposure, chronic heroin intake, context-induced drug-seeking following abstinence, and relapse. Bioinformatics analysis of this rich dataset identified numerous patterns of transcriptional regulation, with both region-specific and pan-circuit biological domains affected by heroin. Integration of RNA-seq data with OUD-relevant behavioral outcomes uncovered region-specific molecular changes and biological processes that predispose to OUD vulnerability. Comparisons with human OUD RNA-seq and genome-wide association study data revealed convergent molecular abnormalities and gene candidates with high therapeutic potential. These studies outline molecular reprogramming underlying OUD and provide a foundational resource for future investigations into mechanisms and treatment strategies.

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric syndrome with genetic and environmental influences. In addition to neuroanatomical and circuit-level disturbances, dysregulation of the brain transcriptome is a key phenotypic signature of MDD. Postmortem brain gene expression data are uniquely valuable resources for identifying this signature and key genomic drivers in human depression; however, the scarcity of brain tissue limits our capacity to observe the dynamic transcriptional landscape of MDD. It is therefore crucial to explore and integrate depression and stress transcriptomic data from numerous, complementary perspectives to construct a richer understanding of the pathophysiology of depression. In this review, we discuss multiple approaches for exploring the brain transcriptome reflecting dynamic stages of MDD: predisposition, onset, and illness. We next highlight bioinformatic approaches for hypothesis-free, genome-wide analyses of genomic and transcriptomic data and their integration. Last, we summarize the findings of recent genetic and transcriptomic studies within this conceptual framework., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from men suffering from CUD and matched controls. Weighted gene coexpression analyses identified CUD-specific gene networks enriched in ionotropic receptors and linked to lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity.

Regions of hypoxia are common in solid tumors and drive changes in gene expression that increase risk of cancer metastasis. Tumor cells must respond to the stress of hypoxia by activating genes to modify cell metabolism and antioxidant response to improve survival. The goal of the current study was to determine the effect of hypoxia on cell metabolism and markers of oxidative stress in metastatic (metM-Wnt lung ) compared with nonmetastatic (M-Wnt) murine mammary cancer cell lines. We show that hypoxia induced a greater suppression of glutamine to glutamate conversion in metastatic cells (13% in metastatic cells compared to 7% in nonmetastatic cells). We also show that hypoxia increased expression of genes involved in antioxidant response in metastatic compared to nonmetastatic cells, including glutamate cysteine ligase catalytic and modifier subunits and malic enzyme 1. Interestingly, hypoxia increased the mRNA level of the transaminase glutamic pyruvic transaminase 2 (Gpt2, 7.7-fold) only in metM-Wnt lung cells. The change in Gpt2 expression was accompanied by transcriptional (4.2-fold) and translational (6.5-fold) induction of the integrated stress response effector protein activating transcription factor 4 (ATF4). Genetic depletion ATF4 demonstrated importance of this molecule for survival of hypoxic metastatic cells in detached conditions. These findings indicate that more aggressive, metastatic cancer cells utilize hypoxia for metabolic reprogramming and induction of antioxidant defense, including activation of ATF4, for survival in detached conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kiesel, Sheeley, Hicks, Andolino, Donkin, Wendt, Hursting and Teegarden.)

The disparity between kidney transplant candidates and donors necessitates innovations to increase organ availability. Transporting kidneys allows for living donors and recipients to undergo surgery with a familiar transplant team, city, friends, and family. The effect of shipping kidneys and prolonged cold ischemia time (CIT) with living donor transplantation outcomes is not clearly known. This retrospective matched (age, gender, race, and year of procedure) cohort study compared allograft outcomes for shipped live donor kidney transplants and nonshipped living donor kidney transplants. Fifty-seven shipped live donor kidneys were transplanted from 31 institutions in 26 cities. The mean shipping distance was 1634 miles (range 123-2811) with mean CIT of 12.1 ± 2.8 h. The incidence of delayed graft function in the shipped cohort was 1.8% (1/57) compared to 0% (0/57) in the nonshipped cohort. The 1-year allograft survival was 98% in both cohorts. There were no significant differences between the mean serum creatinine values or the rates of serum creatinine decline in the immediate postoperative period even after adjusted for gender and differences in recipient and donor BMI. Despite prolonged CITs, outcomes for shipped live donor kidney transplants were similar when compared to matched nonshipped living donor kidney transplants., (© 2014 Steunstichting ESOT.)

In this work, a detailed and systematic study of the plasmonic properties of a novel film over nanowell surface is investigated. These nanostructures are fabricated using nanosphere lithography and reactive ion etching and structurally characterized by AFM and SEM. The resulting structures show remarkably narrow plasmon bands in reflectance spectra (as little as 0.10 eV) and greater sensitivity to external dielectric environment than has been seen in other nanoparticle systems, resulting in an improvement in the figure of merit (FOM = refractive index sensitivity (eV.RIU(-1))/full width at half-maximum (eV)) for refractive index sensing. Theoretical modeling for the plasmon spectra of these nanostructures is done using discrete dipole approximation code under periodic boundary conditions. The modeling results match the measurements accurately in aspects of the variation of the plasmon line shape with altering internanowell distance and dielectric environment.

Frequency-scanned excitation profiles of coherent second harmonic generation (SHG) were measured for silver nanoparticle arrays prepared by nanosphere lithography. The frequency of the fundamental beam did not coincide with the localized surface plasmon resonance (LSPR) of the nanoparticles and was tuned so that the coherent second harmonic (SH) emission was in the region of the LSPR at 720-750 nm. The SH emission from the arrays was compared with a smooth silver film to identify an enhancement of SH emission efficiency that peaks near approximately 650 nm for nanoparticles 50 nm in height. The polarization and orientation dependence of this enhancement suggests that it is related to a dipolar LSPR mode polarized normal to the plane of the substrate. Linear extinction spectra are dominated by in-plane dipoles and do not show this weak out-of-plane LSPR mode. The nanoparticle arrays are truncated tetrahedrons symmetrically oriented by nanosphere lithography to cancel SH from in-plane dipoles which allows observation of the weak out-of-plane component.

Seventy-five families of children with intractable epilepsy but without a severe learning disability (mean age 7 years 1 month, SD 2 years 6 months; range 2 to 12 years) who attended a regional paediatric neurology service, were surveyed. A postal questionnaire was used which included standardized measures of child and family adjustment; forty-eight families responded (64%; 31 males, 17 females). There was no significant difference between responders and non-responders in terms of age, sex, number of other chronic illnesses and disabilities, age at epilepsy diagnosis, seizure type, nor number of antiepileptic drugs currently prescribed (p > 0.05). The importance of including multidimensional measures of outcome was highlighted by the finding that epilepsy, pharmacological, and psychosocial factors were differentially associated with specific adjustment difficulties. Two factors appeared to be most pervasively implicated across a range of adjustment problems: frequency of rectal diazepam administration and family patterns of relating to each other (p < 0.05). It appeared that duration of seizures (as indicated by frequency of rectal diazepam administration), rather than the frequency of seizures per se, was more pernicious in terms of poor adjustment. Intrafamilial relations (degree of conflict/cohesion and soon) were not only associated with adjustment difficulties in the child, but also with the frequency of seizures themselves. Implications for psychological interventions in intractable epilepsy in childhood are highlighted.

Psychological interventions aimed at seizure management are described with a 14-year-old boy with a learning disability and intractable epilepsy. Baseline records suggested that a majority of tonic seizures and 'drop attacks' were associated with going off to sleep and by environmental 'startles'. Psychological formulation implicated sudden changes in arousal levels as an underlying mechanism of action. Cognitive-behavioural countermeasures were employed to alter arousal levels and processes in different ways in different 'at-risk' situations. A multiple baseline design was used to control for non-specific effects of interventions on non-targeted seizures. Results suggested significant declines in the number of sleep onset and startle-response seizures were attained by these methods. Gains were maintained at 2-month follow-up., (Copyright 1999 BEA Trading Ltd.)

In the cystic fibrosis (CF) patient, lung function decreases throughout life as a result of continuous cycles of infection, particularly with Pseudomonas aeruginosa and Staphylococcus aureus. The mechanism underlying the pathophysiology of the disease in humans has not been established. However, it has been suggested that abnormal, tenacious mucus, resulting perhaps from improper hydration from loss of Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) protein, impairs clearance of bacteria from the CF airway and provides an environment favorable to bacterial growth. If this hypothesis is correct, it could explain the absence of respiratory disease in CFTR-deficient mice, since mice have only a single submucosal gland and display few goblet cells in their lower airways, even when exposed to bacteria. To test this hypothesis further, we induced allergic airway disease in CFTR-deficient mice. We found that induction of allergic airway disease in mice, unlike bacterial infection, results in an inflammatory response characterized by goblet cell hyperplasia, increased mucin gene expression, and increased production of mucus. However, we also found that disease progression and resolution is identical in Cftr-/- mice and control animals. Furthermore, we show that the presence of mucus in the Cftr-/- airway does not lead to chronic airway disease, even upon direct inoculation with S. aureus and P. aeruginosa. Therefore, factors in addition to the absence of high levels of mucus secretion protect the mouse from the airway disease seen in human CF patients.

Direct measurements of arterial blood pressure and intracranial pressure were recorded in 39 patients aged 3.6 months to 5 years 11 months with Reye's syndrome judged to be stage 2 or beyond. Of 33 patients who survived, 27 made a full recovery and six were severely handicapped. Measurement of cerebral perfusion pressure, which is greatly reduced in the more severe forms of Reye's syndrome, was a better guide to prognosis and management than intracranial pressure alone. The findings emphasise that maintenance of cerebral perfusion pressure is essential if mortality and morbidity are to be reduced. Intracranial monitoring is mandatory in all but the mildest cases of Reye's syndrome.

A family of synthetic elastic fibers, designated spandex fibers, has been developed, providing new degrees of sheerness and effective "power" in elastic fabrics. These fibers have segmented polyurethane structures. They are durable, they are white and accept dye readily, and they can be set by heat. The development of these fibers has led to new textile technology and to new uses for elastic fabrics.