Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma.

Meningioma, a primary brain tumor, is commonly encountered and accounts for 39% of overall CNS tumors. Despite significant progress in clinical research, conventional surgical and clinical interventions remain the primary treatment options for meningioma. Several proteomics and transcriptomics studies have identified potential markers and altered biological pathways; however, comprehensive exploration and data integration can help to achieve an in-depth understanding of the altered pathobiology. This study applied integrated meta-analysis strategies to proteomic and transcriptomic datasets comprising 48 tissue samples, identifying around 1832 common genes/proteins to explore the underlying mechanism in high-grade meningioma tumorigenesis. The in silico pathway analysis indicated the roles of extracellular matrix organization (EMO) and integrin binding cascades in regulating the apoptosis, angiogenesis, and proliferation responsible for the pathobiology. Subsequently, the expression of pathway components was validated in an independent cohort of 32 fresh frozen tissue samples using multiple reaction monitoring (MRM), confirming their expression in high-grade meningioma. Furthermore, proteome-level changes in EMO and integrin cell surface interactions were investigated in a high-grade meningioma (IOMM-Lee) cell line by inhibiting integrin-linked kinase (ILK). Inhibition of ILK by administrating Cpd22 demonstrated an anti-proliferative effect, inducing apoptosis and downregulating proteins associated with proliferation and metastasis, which provides mechanistic insight into the disease pathophysiology.

A large-scale targeted proteomics of serum and tissue shows the utility of classifying high grade and low grade meningioma tumors.

BACKGROUND: Meningiomas are the most prevalent primary brain tumors. Due to their increasing burden on healthcare, meningiomas have become a pivot of translational research globally. Despite many studies in the field of discovery proteomics, the identification of grade-specific markers for meningioma is still a paradox and requires thorough investigation. The potential of the reported markers in different studies needs further verification in large and independent sample cohorts to identify the best set of markers with a better clinical perspective. METHODS: A total of 53 fresh frozen tumor tissue and 51 serum samples were acquired from meningioma patients respectively along with healthy controls, to validate the prospect of reported differentially expressed proteins and claimed markers of Meningioma mined from numerous manuscripts and knowledgebases. A small subset of Glioma/Glioblastoma samples were also included to investigate inter-tumor segregation. Furthermore, a simple Machine Learning (ML) based analysis was performed to evaluate the classification accuracy of the list of proteins. RESULTS: A list of 15 proteins from tissue and 12 proteins from serum were found to be the best segregator using a feature selection-based machine learning strategy with an accuracy of around 80% in predicting low grade (WHO grade I) and high grade (WHO grade II and WHO grade III) meningiomas. In addition, the discriminant analysis could also unveil the complexity of meningioma grading from a segregation pattern, which leads to the understanding of transition phases between the grades. CONCLUSIONS: The identified list of validated markers could play an instrumental role in the classification of meningioma as well as provide novel clinical perspectives in regard to prognosis and therapeutic targets.

COVID-19 Booster Vaccination in the U.S. Military, August 2021-January 2022.

INTRODUCTION: A booster dose of messenger RNA vaccine protects against severe COVID-19 outcomes. This study examined the incidence of COVID-19 booster vaccination among active-duty U.S. military servicemembers between August 2021 and January 2022, factors associated with vaccination uptake, and trends over time. METHODS: This was a retrospective cohort study of active-duty military personnel using data from the Defense Medical Surveillance System. Participants were included if they served in the active component from August 2021 through January 2022 and were eligible to receive a COVID-19 booster dose by January 2022. Adjusted hazard ratio estimates of time to booster vaccination were calculated using Cox proportional hazards regression. RESULTS: Lower booster vaccine uptake was seen in the U.S. military (25%) than among the general U.S. population at the same time (45%). Booster vaccination increased with older age, with greater education, with higher income, among women, and among those stationed overseas; it decreased with previous COVID-19 infection and use of the Janssen vaccine. There were no significant racial or ethnic disparities in booster vaccination. CONCLUSIONS: In the absence of a compulsory vaccination policy, lower booster vaccine uptake was seen among servicemembers than among the general U.S. population, particularly among members who were younger, were male, Marines, and had a previous history of infection. Low vaccination rates not only increase the risk of acute and long-term health effects from COVID-19 among servicemembers, but they also degrade the overall readiness of the U.S. military.

Obesity prevalence among active component service members prior to and during the COVID-19 pandemic, January 2018-July 2021.

This study examined monthly prevalence of obesity and exercise in active component U.S. military members prior to and during the COVID-19 pandemic. Information about obesity (BMI≥30) and self-reported vigorous exercise (≥150 minutes per week) were collected from Periodic Health Assessment (PHA) data. From 1 January 2018 through 31 July 2021, there was a gradual increase in obesity and an overall decrease in vigorous exercise. Comparing the mean monthly percentage of obesity during the 12-month period prior to the pandemic to the 12 months after its start showed an overall increase in obesity (0.43%); however, no obvious spike in the obesity trend was apparent following the onset of the pandemic. The prevalence of vigorous exercise showed an abrupt decrease following the onset of the COVID-19 pandemic, but this change did not coincide with an abrupt change in the obesity trend. These results suggest that the COVID-19 pandemic had a small effect on the trend of obesity in the active component U.S. military and that obesity prevalence continues to increase.

COVID-19 and depressive symptoms among active component U.S. service members, January 2019-July 2021.

This study examined the rates of depressive symptoms in active component U.S. service members prior to and during the COVID-19 pandemic and evaluated whether SARS-CoV-2 test results (positive or negative) were associated with self-reported depressive symptoms. Depressive symptoms were measured by the Patient Health Questionnaire-2 (PHQ-2) screening instrument and were defined as positive if the total score was 3 or greater. From 1 January 2019 through 31 July 2021, 2,313,825 PHQ-2s were completed with an increase in the positive rate from 4.0% to 6.5% (absolute % difference, +2.5%; relative % change, +67.1%) from the beginning to the end of the period. While there was a gradual increase of 19.8% in the months prior to the pandemic (1.4%/month average), this increase grew to 40.4% during the pandemic (2.5%/month average). However, no association was found between a positive or negative SARS-CoV-2 test result and the PHQ-2 screening instrument result. These findings suggest that the accelerated increase in depressive symptoms is likely a function of the environment of the COVID-19 pandemic instead of the SARS-CoV-2 infection itself. Further research to better understand specific factors of the pandemic leading to depressive symptoms will improve efficient allocation of military medical resources and safeguard military medical readiness.

Repetitive Traumatic Brain Injury Among Older Adults.

OBJECTIVE: To determine the incidence of and assess risk factors for repetitive traumatic brain injury (TBI) among older adults in the United States. DESIGN: Retrospective cohort study. SETTING: Administrative claims data obtained from the Centers for Medicare & Medicaid Services' Chronic Conditions Data Warehouse. PARTICIPANTS: Individuals 65 years or older and diagnosed with TBI between July 2008 and September 2012 drawn from a 5% random sample of US Medicare beneficiaries. MAIN MEASURES: Repetitive TBI was identified as a second TBI occurring at least 90 days after the first occurrence of TBI following an 18-month TBI-free period. We identified factors associated with repetitive TBI using a log-binomial model. RESULTS: A total of 38 064 older Medicare beneficiaries experienced a TBI. Of these, 4562 (12%) beneficiaries sustained at least one subsequent TBI over up to 5 years of follow-up. The unadjusted incidence rate of repetitive TBI was 3022 (95% CI, 2935-3111) per 100 000 person-years. Epilepsy was the strongest predictor of repetitive TBI (relative risk [RR] = 1.44; 95% CI, 1.25-1.56), followed by Alzheimer disease and related dementias (RR = 1.32; 95% CI 1.20-1.45), and depression (RR = 1.30; 95% CI, 1.21-1.38). CONCLUSIONS: Injury prevention and fall-reduction interventions could be targeted to identify groups of older adults at an increased risk of repetitive head injury. Future work should focus on injury-reduction initiatives to reduce the risk of repetitive TBI as well as assessment of outcomes related to repetitive TBI.

Long-acting reversible contraceptive use, active component service women, U.S. Armed Forces, 2016-2020.

Long-acting reversible contraceptives (LARCs) are highly effective means of birth control that can improve service women's overall health and readiness. This report expands upon prior data and summarizes the annual prevalence (overall and by demographics) of LARC use from 2016 through 2020 among active component U.S. service women, compares LARC prevalence to the prevalence of short-acting reversible contraceptives (SARCs), and evaluates the probability of continued use of LARCs by type. LARC use increased from 21.9% to 23.9% from 2016 through 2019 while SARC use decreased from 28.3% to 24.9%. Both SARC and LARC use decreased in 2020 which may have been related to the coronavirus disease 2019 (COVID-19) pandemic. The prevalence of intrauterine devices (IUDs) was greater than implants, and IUDs also had a higher probability of continuation than implants. At 12 months, the continuation for IUDs was 81% compared to 73% for implants. At 24 months, the probabilities of continuation were 70% for IUDs and 54% for implants. Probabilities of continuation were similar across outsourced care and direct care settings. The increased use of LARCs along with their high frequency of continuation in U.S. service women may have a positive impact on overall health and readiness.

Disparities in COVID-19 Vaccine Initiation and Completion Among Active Component Service Members and Health Care Personnel, 11 December 2020-12 March 2021.

The objective of this study was to assess overall vaccine initiation and completion in the active component U.S. military, with a focus on racial/ethnic disparities. From 11 December 2020 through 12 March 2021, a total of 361,538 service members (27.2%) initiated a COVID-19 mRNA vaccine. Non-Hispanic Blacks were 28% less likely to initiate vaccination (95% confidence interval: 25%-29%) in comparison to non-Hispanic Whites, after adjusting for potential confounders. Increasing age, higher education levels, higher rank, and Asian/Pacific Islander race/ethnicity were also associated with increasing incidence of initiation after adjustment. When the analysis was restricted to active component health care personnel, similar patterns were seen. Overall, 93.8% of those who initiated the vaccine series completed it during the study period, and only minor differences in completion rates were noted among the demographic subgroups. This study suggests additional factors, such as vaccine hesitancy, influence COVID-19 vaccination choices in the U.S. military. Military leadership and vaccine planners should be knowledgeable about and aware of the disparities in vaccine series initiation.

Role of Visible Light on Skin Melanocytes: A Systematic Review.

In the last few years, the focus of phototherapy has shifted toward the visible (400-700 nm) part of the electromagnetic spectrum of light. Lately, it has been demonstrated that visible light (VL) can have both beneficial and detrimental effects, especially on the skin. Previously and until now, the most harmful effects on the skin are associated with ultraviolet radiation (UVR). After exposure to natural light, the most evident and immediate change is observed on skin pigmentation. Various wavelengths within the visible spectrum have been reported to alter skin pigmentation. However, the underlying mechanisms are incompletely understood so far. The article aims to shed light on the progress made in the photobiology field (photobiomodulation, PBM) to study the role of visible light on skin melanocytes.

Sepsis hospitalizations among active component service members, U.S. Armed Forces, 2011-2020.

The objective of this study was to assess the incidence and trends of sepsis hospitalizations in the active component U.S. military over the past decade. Between 1 January 2011 and 31 December 2020, there were 5,278 sepsis hospitalizations of any severity recorded among the active component. The overall incidence was 39.8 hospitalizations per 100,000 person-years (p-yrs). Annual incidence increased 64% from 2011 through 2019, then dropped considerably in 2020. Compared to their respective counterparts, rates were highest among female service members, the oldest and youngest age groups, and recruits. The gap in sepsis hospitalization rates between female and male service members increased over the surveillance period. Pneumonia was the most commonly co-occurring infection, followed by genitourinary infections. Among female service members, genitourinary infections were more commonly diagnosed compared to pneumonia. The most common non-infection co-occurring diagnoses were acute kidney failure and acute respiratory failure. This study demonstrates an apparent sex disparity in sepsis rates and further study is recommended to understand its cause.

Lesional skin in vitiligo exhibits delayed in vivo reepithelialization compared to the nonlesional skin.

Vitiligo, a common skin disorder, is characterized by the loss of functional melanocytes resulting in the depigmentation of skin. Previous studies have demonstrated molecular and architectural alterations in the epidermal keratinocytes upon loss of melanocytes. The physiological implications of these "altered" keratinocytes are yet not known. We investigated the wound healing efficiency of lesional vs nonlesional skin in 12 subjects with stable nonsegmental vitiligo using histological and ultrastructural evaluation of partial-thickness wounds. The wounds were examined 12 days postinjury, coinciding with the reepithelialization phase of healing marked primarily by keratinocyte migration and proliferation. This study demonstrated a significant difference in the reepithelialization potential between the lesional and nonlesional skin. While all 12 nonlesional wounds demonstrated considerable neoepidermis formation on the 12th day post wound, only four of the corresponding lesional samples showed comparable reepithelialization; the rest remaining in the inflammatory phase. Ultrastructural studies using transmission electron microscopy as well as immunohistochemical staining revealed a reduced number of desmosomes, shorter keratin tonofilaments and an increase in myofibroblast population in the dermis of lesional reepithelialized tissue compared to the nonlesional reepithelialized samples. This study implicates gross functional perturbations in the lesional skin during physiological wound healing in vitiligo, suggesting that the breakdown of keratinocyte-melanocyte network results in delayed wound repair kinetics in the lesional skin when compared to patient-matched nonlesional skin.