Climate Change and Health: Public Health and Legal Strategies to Reduce Reliance on Fossil Fuels, Increase Air Quality, and Improve Human Health.

Reliance upon fossil fuels and limited greenspace contribute to poor indoor and outdoor air quality and adverse health outcomes, particularly in communities of color. This article describes justice-informed public health and legal interventions to increase access to greenspace and accelerate the transitions to renewable energy and away from gas appliances.

Understanding the Interplay Between Premenstrual Dysphoric Disorder (PMDD) and Female Sexual Dysfunction (FSD).

Premenstrual dysphoric disorder (PMDD) is a severe variant of premenstrual syndrome (PMS), categorized as a mood disorder due to marked symptoms of depression and anxiety, compounded with severe physical symptoms. Female sexual dysfunction (FSD) can manifest as low libido, difficulty achieving sexual pleasure, and dyspareunia, causing functional and psychological distress. PMDD and FSD are globally prevalent conditions with postulated biological, psychological, and social associations between them. Nevertheless, sexual dysfunction in PMDD is an important aspect of women's health that has been understudied and has notable methodological limitations. In this narrative review, we summarize the existing literature on sexual function in women with PMDD and PMS, specify the distinctions between PMDD and other general symptoms of PMS, highlight the significance of understanding sexual dysfunction in the female population, and outline some available therapeutic options. Studies show that women frequently experience debilitating sexual distress during the premenstrual phase; however, there is an essential need to formulate standardized tools for definite diagnosis. Selective serotonin re-uptake inhibitors (SSRIs) and combined oral contraceptive pills (COCPs) are approved medications for PMDD, while flibanserin and bremelanotide are effective in treating FSD. However, the potential effects of these treatment modalities on the two comorbid conditions render them inconclusive. Awareness of PMDD and FSD among clinicians and society can allow the implementation of targeted interventions to alleviate the suffering of women and enhance their quality of life.

Interplay between MRI-based axon diameter and myelination estimates in macaque and human brain.

Axon diameter and myelin thickness are closely related microstructural tissue properties that affect the conduction velocity of action potentials in the nervous system. Imaging them non-invasively with MRI-based methods is thus valuable for studying brain microstructure and function. However, the relationship between MRI-based axon diameter and myelination measures has not been investigated across the brain, mainly due to methodological limitations in estimating axon diameters. In recent years, studies using ultra-high gradient strength diffusion MRI (dMRI) have demonstrated improved estimation of axon diameter across white-matter (WM) tracts in the human brain, making such investigations feasible. In this study, we aim to investigate relationships between tissue microstructure properties with MRI-based methods and compare the imaging findings to histological evidence from the literature. We collected dMRI with ultra-high gradient strength and multi-echo spin-echo MRI on ex vivo macaque and human brain samples on a preclinical scanner. From these data, we estimated axon diameter, intra-axonal signal fraction, myelin water fraction (MWF) and aggregate g-ratio and investigated their correlations. We found that the microstructural imaging parameters exhibited consistent patterns across WM tracts and species. Overall, the findings suggest that MRI-based axon geometry and myelination measures can provide complementary information about fiber morphology, and the relationships between these measures agree with prior histological evidence.

Pathways Linking Post-Traumatic Stress Disorder to Incident Ischemic Heart Disease in Women: Call to Action.

Background: Post-traumatic stress disorder (PTSD) is associated with increased rates of incident ischemic heart disease (IHD) in women. Objectives: The purpose of this study was to determine mechanisms of the PTSD-IHD association in women. Methods: In this retrospective longitudinal cohort study, data were obtained from electronic health records of all U.S. women veterans who were enrolled in Veterans Health Administration care from January 1, 2000 to December 31, 2017. Propensity score matching was used to match women with PTSD to women without PTSD on age, number of prior Veterans Health Administration visits, and presence of various traditional and nontraditional cardiovascular risk factors at index visit. Cox regression was used to model time until incident IHD diagnosis (ie, coronary artery disease, angina, or myocardial infarction) as a function of PTSD and potential mediating risk factors. Diagnoses of IHD, PTSD, and risk factors were defined by International Classification of Diseases-9th or -10th Revision, and/or Current Procedural Terminology codes. Results: PTSD was associated with elevated rates of developing each risk factor. Traditional risk factors (hypertension, hyperlipidemia, smoking, diabetes) accounted for 24.2% of the PTSD-IHD association, psychiatric risk factors (eg, depression, anxiety, substance use disorders) accounted for 33.8% of the association, and all 13 risk factors accounted for 48.5% of the association. Conclusions: Traditional IHD risk factors explained a quarter of the PTSD-IHD association in women veterans, and over half of the risk of IHD associated with PTSD remained unexplained even when adjusting for a wide range of risk factors. To be actionable, factors underlying the remaining PTSD-IHD association warrant timely investigation.

Entorhinal vessel density correlates with phosphorylated tau and TDP-43 pathology.

INTRODUCTION: The entorhinal cortex (EC) and perirhinal cortex (PC) are vulnerable to Alzheimer's disease. A triggering factor may be the interaction of vascular dysfunction and tau pathology. METHODS: We imaged post mortem human tissue at 100 µm3 with 7 T magnetic resonance imaging and manually labeled individual blood vessels (mean = 270 slices/case). Vessel density was quantified and compared per EC subfield, between EC and PC, and in relation to tau and TAR DNA-binding protein 43 (TDP-43) semiquantitative scores. RESULTS: PC was more vascularized than EC and vessel densities were higher in posterior EC subfields. Tau and TDP-43 strongly correlated with vasculature density and subregions with severe tau at the preclinical stage had significantly greater vessel density than those with low tau burden. DISCUSSION: These data impact cerebrovascular maps, quantification of subfield vasculature, and correlation of vasculature and pathology at early stages. The ordered association of vessel density, and tau or TDP-43 pathology, may be exploited in a predictive context. HIGHLIGHTS: Vessel density correlates with phosphorylated tau (p-tau) burden in entorhinal and perirhinal cortices. Perirhinal area 35 and posterior entorhinal cortex showed greatest p-tau burden but also the highest vessel density in the preclinical phase of Alzheimer's disease. We combined an ex vivo magnetic resonance imaging model and histopathology to demonstrate the 3D reconstruction of intracortical vessels and its spatial relationship to the pathology.

Infraspecific Chemical Variability and Metabolomic Profiling by Paper Spray Ionization (PSI-MS) of Averrhoa carambola from Different Brazilian Biomes.

This research focused on the molecular diversity of A. carambola collected from three Brazilian biomes (Cerrado, Amazônia, and Mata Atlântica), whose results revealed significant differences in metabolite profiles among these biomes through PSI-MS analysis. Chemometric analysis provided valuable insights into the clustering patterns and metabolic distinctions. Cerrado and Mata Atlântica biomes exhibited a 70 % similarity, indicating a notable degree of resemblance. In Cerrado, carambolaside A was notably abundant, while carambolaside M was low in Amazônia and moderate in Cerrado samples. Carambolaside B was abundant in Amazônia but relatively low in the Cerrado and Mata Atlântica. In contrast, the Amazônia biome samples appeared to be more dissimilar. In Cerrado, epicatechin, kaempferol, and procyanidin B showed lower abundance, while apigenin, quercetin, myricetin, and rutin displayed moderate levels. Mata Atlântica showed relatively higher levels of kaempferol, quercetin, and rutin. This study indicated the environmental influence on secondary metabolites production in A. carambola fruits.

Evaluation of the critical warzone experiences scale among Gulf War I-era veterans: Associations with PTSD symptoms, depressive symptoms, and suicidal thoughts and behaviors.

Prior research has established the psychometric properties of the Critical Warzone Experiences (CWE) scale among post-9/11 Iraq/Afghanistan-era veterans; however, the psychometric properties of the CWE among Gulf War I-era veterans have not yet been established. The first objective of the present study was to examine the psychometric properties of the CWE among Gulf War I-era veterans. The second objective was to test the hypothesis that the CWE would have a significant indirect effect on suicidal thoughts and behaviors via posttraumatic stress disorder (PTSD) and depressive symptoms. To test these hypotheses, a survey packet that included the CWE and measures of PTSD symptoms, depressive symptoms, and suicidal thoughts and behaviors was administered to 1,153 Gulf War I-era veterans. Consistent with prior research in post-9/11 Iraq/Afghanistan-era veterans, the CWE exhibited good internal consistency (α = .85), a unidimensional factor structure (RMSEA = .056, CFI = .959, SRMR = .033; average factor loading = .69), and good concurrent validity with PTSD (r = .47, p < .001) and depressive (r = .31, p < .001) symptoms among Gulf War I-era veterans. Additionally, as hypothesized, a significant indirect effect from the CWE to suicidal thoughts and behaviors via PTSD and depressive symptoms (ß = .35, p < .001) was also observed. Taken together, our findings provide strong support for using the CWE with Gulf War I-era veterans.

Comprehensive characterization of circulating tumor cells and cell-free DNA in patients with metastatic melanoma.

Advances in therapeutic approaches for melanoma urge the need for biomarkers that can identify patients at risk for recurrence and to guide treatment. The potential use of liquid biopsies in identifying biomarkers is increasingly being recognized. Here, we present a head-to-head comparison of several techniques to analyze circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in 20 patients with metastatic melanoma. In this study, we investigated whether diagnostic leukapheresis (DLA) combined with multimarker flow cytometry (FCM) increased the detection of CTCs in blood compared to the CellSearch platform. Additionally, we characterized cfDNA at the level of somatic mutations, extent of aneuploidy and genome-wide DNA methylation. Both CTCs and cfDNA measures were compared to tumor markers and extracranial tumor burden on radiological imaging. Compared to the CellSearch method applied on peripheral blood, DLA combined with FCM increased the proportion of patients with detectable CTCs from 35% to 70% (P = 0.06). However, the median percentage of cells that could be recovered by the DLA procedure was 29%. Alternatively, cfDNA mutation and methylation analysis detected tumor load in the majority of patients (90% and 93% of samples successfully analyzed, respectively). The aneuploidy score was positive in 35% of all patients. From all tumor measurements in blood, lactate dehydrogenase (LDH) levels were significantly correlated to variant allele frequency (P = 0.004). Furthermore, the presence of CTCs in DLA was associated with tumor burden (P < 0.001), whereas the presence of CTCs in peripheral blood was associated with number of lesions on radiological imaging (P < 0.001). In conclusion, DLA tended to increase the proportion of patients with detectable CTCs but was also associated with low recovery. Both cfDNA and CTCs were correlated with clinical parameters such as LDH levels and extracranial tumor burden.

Automatic geometry-based estimation of the locus coeruleus region on T1-weighted magnetic resonance images.

The locus coeruleus (LC) is a key brain structure implicated in cognitive function and neurodegenerative disease. Automatic segmentation of the LC is a crucial step in quantitative non-invasive analysis of the LC in large MRI cohorts. Most publicly available imaging databases for training automatic LC segmentation models take advantage of specialized contrast-enhancing (e.g., neuromelanin-sensitive) MRI. Segmentation models developed with such image contrasts, however, are not readily applicable to existing datasets with conventional MRI sequences. In this work, we evaluate the feasibility of using non-contrast neuroanatomical information to geometrically approximate the LC region from standard 3-Tesla T1-weighted images of 20 subjects from the Human Connectome Project (HCP). We employ this dataset to train and internally/externally evaluate two automatic localization methods, the Expected Label Value and the U-Net. For out-of-sample segmentation, we compare the results with atlas-based segmentation, as well as test the hypothesis that using the phase image as input can improve the robustness. We then apply our trained models to a larger subset of HCP, while exploratorily correlating LC imaging variables and structural connectivity with demographic and clinical data. This report provides an evaluation of computational methods estimating neural structure.

Global epistasis and the emergence of function in microbial consortia.

The many functions of microbial communities emerge from a complex web of interactions between organisms and their environment. This poses a significant obstacle to engineering microbial consortia, hindering our ability to harness the potential of microorganisms for biotechnological applications. In this study, we demonstrate that the collective effect of ecological interactions between microbes in a community can be captured by simple statistical models that predict how adding a new species to a community will affect its function. These predictive models mirror the patterns of global epistasis reported in genetics, and they can be quantitatively interpreted in terms of pairwise interactions between community members. Our results illuminate an unexplored path to quantitatively predicting the function of microbial consortia from their composition, paving the way to optimizing desirable community properties and bringing the tasks of predicting biological function at the genetic, organismal, and ecological scales under the same quantitative formalism.

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Lower total cholesterol and triglyceride levels in ankylosing spondylitis than non-inflammatory rheumatic disease controls in a 1978-98 study: a potential effect of increased physical energetics in manual occupations in the pre-2000 chronologic era.

OBJECTIVES: No article on serum lipids in ankylosing spondylitis (AS) and control subjects has been reported from USA. The primary aim of this study was to determine if any difference occurred in serum lipid levels in AS and control rheumatic disorders in two time periods, 1978-98 and 2000-10. The secondary aim was to investigate variables associated with lipid levels and if a difference was found between AS and control disorders. METHODS: The AS patients were compared to non-inflammatory rheumatic disorders (NIRDs) in 1978-98 and 2000-10 surveys and to rheumatoid arthritis (RA) in the 2000-10 survey. Patients were matched within 5 years of age, sex, and clinic or hospital source. RESULTS: In the 1978-98 survey, entry mean (SEM) serum cholesterol level [mg/dL] was highly (p<0.001) significantly lower in 69 AS [179.0 (4.8)] than 69 matched NIRD controls [208.0 (5.6)]. In 29 pairs of AS and NIRD subjects having manual labour occupations, mean (SEM) cholesterol level was additionally lower in AS [156.7 (5.9)] and higher in 29 NIRD controls [213.3 (8.6)] (p<0.001). In manual labour workers, mean (SEM) serum triglyceride was significantly lower (p=0.004) in 15 AS [110.3 (14.1)] than 14 NIRD controls [185.2 (19.3)]. In the 2000-10 survey, no lipid difference was found between AS vs. NIRD control patients. CONCLUSIONS: In the 1978-98 survey, AS had significantly lower mean serum cholesterol and triglyceride levels than NIRD control patients. Associated manual labour occupations may have significantly contributed to results, possibly related to increased energy expenditures from physical activity in the pre-2000 era.

No Improvement in Intention-to-treat Survival and Increasing Liver Nonutilization Rate During the MELD Era.

BACKGROUND: Although post liver transplant survival rates have significantly improved during the past 2-3 decades, the trend in intention-to-treat (ITT) survival (survival from waitlist addition) has not been well studied. METHODS: We conducted a retrospective analysis of Scientific Registry of Transplant Recipients data to determine the trend in ITT survival in liver transplant candidates. Adult (age ≧ 18 y) patients who were on the waitlist between the time period of March 1, 2002, to December 31, 2019 (n = 200 816) and deceased liver donors that were registered between the same time period (n = 152 593) were analyzed. RESULTS: We found a constant increase in posttransplant survival rates; however, the ITT survival rates showed no statistically significant improvement through the study period. We observed significant linear increase in waitlist dropout rates over time. We also observed linear increase in liver nonutilization rate in both entire cases and brain-dead cases. Donor risk index increased significantly over the years; however, it was mostly driven by increase in donation after circulatory death cases; without donation after circulatory death cases, donor risk index was stable throughout the 17 y we observed. CONCLUSIONS: The reason of the increased liver nonutilization rate is unclear; however, it is possible that reluctance to use high-risk organ to maintain better posttransplant outcomes contributed to this increase, which also could have led to increase in waitlist dropout rates and no improvements in ITT survival. Further investigation is warranted on the increased nonutilization rates to improve over all contribution of liver transplant to patient care.

Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation.

The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role and synaptic mechanisms of descending noradrenergic signaling remain unclear. Here, we establish that noradrenergic neurons of the locus coeruleus (LC) are essential for supraspinal opioid antinociception. While much previous work has emphasized the role of descending serotonergic pathways, we find that opioid antinociception is primarily driven by excitatory output from the ventrolateral periaqueductal gray (vlPAG) to the LC. Furthermore, we identify a previously unknown opioid-sensitive inhibitory input from the rostroventromedial medulla (RVM), the suppression of which disinhibits LC neurons to drive spinal noradrenergic antinociception. We describe pain-related activity throughout this circuit and report the presence of prominent bifurcating outputs from the vlPAG to the LC and the RVM. Our findings substantially revise current models of the DPMS and establish a supraspinal antinociceptive pathway that may contribute to multiple forms of descending pain modulation.

Staphylococcus aureus membrane vesicles: an evolving story.

Staphylococcus aureus is an important bacterial pathogen that causes a wide variety of human diseases in community and hospital settings. S. aureus employs a diverse array of virulence factors, both surface-associated and secreted, to promote colonization, infection, and immune evasion. Over the past decade, a growing body of research has shown that S. aureus generates extracellular membrane vesicles (MVs) that package a variety of bacterial components, many of which are virulence factors. In this review, we summarize recent advances in our understanding of S. aureus MVs and highlight their biogenesis, cargo, and potential role in the pathogenesis of staphylococcal infections. Lastly, we present some emerging questions in the field.

Demographic characteristics and epigenetic biological aging among post-9/11 veterans: Associations of DunedinPACE with sex, race, and age.

Measures of epigenetic aging derived from DNA methylation (DNAm) have enabled the assessment of biological aging in new populations and cohorts. In the present study, we used an epigenetic measure of aging, DunedinPACE, to examine rates of aging across demographic groups in a sample of 2,309 United States military veterans from the VISN 6 MIRECC's Post-Deployment Mental Health Study. As assessed by DunedinPACE, female veterans were aging faster than male veterans (ß = 0.39, 95 % CI [0.29, 0.48], p < .001), non-Hispanic Black veterans were aging faster than non-Hispanic White veterans (ß = 0.58, 95 % CI [0.50, 0.66], p < .001), and older veterans were biologically aging faster than younger veterans (ß = 0.21, 95 % CI [0.18, 0.25], p < .001). In secondary analyses, these differences in rates of aging were not explained by a variety of biopsychosocial covariates. In addition, the percentage of European genetic admixture in non-Hispanic Black veterans was not associated with DunedinPACE. Our findings suggest that female and non-Hispanic Black veterans are at greater risk of accelerated aging among post-9/11 veterans. Interventions that slow aging might provide relatively greater benefit among veterans comprising these at-risk groups.

Assessing the Reliability of Facial Feminization Content on Social Media and Its Impact on the Dissemination of Misinformation.

BACKGROUND: The surge in social media usage has transformed the dissemination and consumption of healthcare information, notably impacting plastic surgery and cosmetic specialties. This study focuses on the influence of social media, particularly Instagram and TikTok, in shaping perceptions of individuals seeking facial feminization (FF) procedures. METHODS: Using the validated DISCERN scale, we assessed the reliability and accuracy of FF content on TikTok and Instagram. The study also analyzed the relationship between content reliability on engagement metrics (likes, comments, views) and the type of content shared (educational, testimonial, promotional). RESULTS: The analysis encompassed 225 TikTok videos and 75 Instagram posts. TikTok content showed 9.33% as "very poor," 66.2% as "poor," 22.6% as "fair," and only 1.33% as "excellent." Similarly, Instagram content demonstrated 14.67% as "very poor" and 69.33% as "poor," with no content rated as "good" or "excellent." Educational content received higher reliability scores on both platforms. TikTok engagement metrics showed lower reliability ratings correlating with more views, comments, and likes. CONCLUSION: The study underscores the critical role of social media in shaping patient perspectives on FF procedures. The prevalence of inaccurate information necessitates a focus on responsible engagement by healthcare professionals, aiming to provide accurate, educational content that aligns with patients' informational needs and ultimately enhances surgical outcomes.

"The Materials Didn't Really Seem to Apply to Me": A Focus-Group Study on Young Women's Needs and Perspectives on Breast Cancer Educational Material.

Young women breast cancer survivors face unique challenges in navigating diagnosis and treatment information while also navigating their own life demands (i.e., fertility, childcare, careers). Special consideration to printed and online cancer educational materials distributed to young women should be evaluated for their suitability, but few studies have investigated the educational preferences and needs of young women cancer survivors. We sought to explore young women breast cancer survivors' needs and preferences regarding cancer educational material from diagnosis to survivorship. We used a qualitative design with convenience sampling of young women breast cancer survivors who completed active treatment at a medical center within the last 5 years to participate in semi-structured online focus groups from November 2020 to May 2021. Thirty-three young women (75.8% White, 12.1% Black, 12.1% other) participated in one of seven online focus groups, each lasting approximately 2 h. Four dominant themes emerged from the data: (1) initial interaction with online materials; (2) reasons for seeking printed and online materials; (3) disconnection of visuals; and (4) recommendations. Our findings revealed that young women were initially hesitant to seek online information, but later sought printed and online information after specific endorsement of materials. Current breast cancer materials lack content specific to young women's needs (i.e., reconstruction options), and graphics have little age and racial diversity. Oncology nurses may consider novel methods of education delivery, such as short videos to be shared easily on social media for specific content like scarring results and reconstruction options.

Primary third eyelid lymphoma with aggressive local behavior in a dog.

Lymphoma is the most common hematopoietic neoplasm in dogs. However, cases primarily involving the third eyelid are rarely reported in the species. The subtype most frequently described in this location is marginal zone lymphoma of the mucosa-associated lymphoid tissue, which has an indolent behavior. A 10-year-old intact female Poodle was presented with a 2-month history of a nodule in the left third eyelid for evaluation. This nodule was surgically excised; however, local recurrence was detected nineteen days postoperatively, with the formation of a mass that expanded and replaced the extraocular orbital tissues and infiltrated the eye. Euthanasia was elected due to the deteriorating clinical condition, and a necropsy was performed. Macroscopically, the mass infiltrated and expanded the eyelids with narrowing of the palpebral fissure, expanded into the orbital space, and infiltrated the cornea and bulbar conjunctiva. Histologically, the mass was composed of sheets of intermediate to large neoplastic lymphocytes, with frequent epitheliotropism and tingible bodies. Neoplastic lymphocytes were immunoreactive for PAX5, CD20, and CD79a and were not immunoreactive for CD3. The neoplasm was restricted to the left eyelid and orbit. A diagnosis of primary third eyelid lymphoma (extranodal) with immunophenotype B and locally aggressive behavior was made based on the macroscopic, histological, and immunohistochemical findings.