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Objective:Our aim was to evaluate the safety of a silver-alginate-containing dressing to reduce peripherally inserted central catheter (PICC) infections in neonatal intensive care unit (NICU) patients.Study Design:Patients were randomized 3:1 to receive a patch containing silver, alginate and maltodextrin or standard of care. Patches were placed under the regular transparent retention dressing at the PICC exit site at insertion and were replaced with every dressing change at least every 2 weeks until PICC discontinuation. All study infants were monitored for adverse skin reactions.Result:A total of 100 infants were followed up for 1922 person-days, including 75 subjects with 89 PICCs who received the patch. The median birth weight (1330 g) and median gestational age (30 weeks) was lower in the patch group when compared with the controls (P=0.001 and 0.005, respectively). Study patients received the patch with their PICC at a median age of 5 days; the patch stayed in place for a median of 13 days. We noted no adverse skin reactions and found no evidence that the patch alters the microbiology of PICC-associated infections.Conclusion:This pilot trial suggests that silver-alginate-coated dressings are skin safe and their inclusion in future trials aimed at reduction of PICC-associated bloodstream infections in the NICU should be considered. [ABSTRACT FROM AUTHOR]

Making a measurement over millions of nanoparticles or exposed crystal facets seldom reports on reactivity of a single nanoparticle or facet, which may depart drastically from ensemble measurements. Within the past 30 years, science has moved toward studying the reactivity of single atoms, molecules, and nanoparticles, one at a time. This shift has been fueled by the realization that everything changes at the nanoscale, especially important industrially relevant properties like those important to electrocatalysis. Studying single nanoscale entities, however, is not trivial and has required the development of new measurement tools. This review explores a tale of the clever use of old and new measurement tools to study electrocatalysis at the single entity level. We explore in detail the complex interrelationship between measurement method, electrocatalytic material, and reaction of interest (e.g., carbon dioxide reduction, oxygen reduction, hydrazine oxidation, etc.). We end with our perspective on the future of single entity electrocatalysis with a key focus on what types of measurements present the greatest opportunity for fundamental discovery.

Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle's branches. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 'Kraken' RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection., (© 2024. The Author(s).)

Introduction: Oral cannabidiol (CBD) product use is increasingly growing among women; however, there is a lack of data on sex differences in the pharmacokinetics (PKs) of CBD and its primary metabolites, 7-hydroxy-CBD (7-OH-CBD) and 7-carboxy-CBD (7-COOH-CBD), after repeated doses. Materials and Methods: The present study is a secondary analysis of data from a randomized, double-blind, placebo-controlled multiple-dose trial of a commercially available, CBD-dominant oral cannabis product. Healthy participants ( n =17 males and 15 females) were randomized to receive 120 to 480 mg of CBD daily for 7 days. Dosing groups were pooled for all analyses due to sample size limitations. Analyses compared plasma PK parameters by sex, day, and sex×day. Results: For raw PK parameters for CBD and metabolites, there were no statistically significant effects of sex×day or sex (all p -values >0.05). For metabolite-to-parent ratios (MPRs) of AUC 0-t , there were significant effects of the sex×day interactions for 7-OH-CBD ( F =6.89, p =0.016) and 7-COOH-CBD ( F =5.96, p =0.021). For 7-OH-CBD, follow-up analyses showed significant simple effects of day within females ( t =4.13, p <0.001), but not within males ( t =0.34, p =0.73), such that 7-OH-CBD MPRs increased significantly from day 1 to 7 for females, but not for males. For 7-COOH-CBD, follow-up analyses revealed significant simple effects of day within females ( t =8.24, p <0.001) and males ( t =5.20, p <0.001), therefore 7-COOH-CBD MPRs increased significantly from day 1 to 7 in both sexes, but the increase was significantly greater among females than among males. Within dosing days, there were no statistically significant simple effects of sex on MPRs of 7-OH-CBD or 7-COOH-CBD. Conclusions: Females exhibited greater relative exposure to CBD metabolites in plasma over time, which may reflect sex differences in CBD metabolism or elimination. Further research assessing the safety implications of higher relative exposure to CBD metabolites over longer periods of time is warranted to mirror typical consumer use patterns.

Background: Unsafe storage of firearms is associated with increased risk of suicide.. However, contemporary population-based data on the prevalence and correlates of firearm storage practices among veterans are limited., Methods: Data were from the 2022 National Health and Resilience in Veterans Study, a nationally representative sample of 2441 veterans. Analyses examined: (1) the prevalence of firearm storage practices; (2) sociodemographic, psychiatric, and clinical characteristics associated with storing firearms loaded and/or in non-secure location; and (3) associations between types of potentially traumatic events and storage practices., Results: More than half of veterans reported owning one or more personal firearms (50.9%). Among firearm owners, 52.9% reported some form of unsafe firearm storage practice (i.e., loaded and/or non-secure location), with 39.9% reporting that they stored one or more firearms loaded. After adjusting for sociodemographic characteristics, major depressive, alcohol and drug use disorders, direct trauma exposures, future suicidal intent, and traumatic brain injury were associated with storing firearms loaded and/or in a non-secure location (ORs = 1.09-7.16). Veterans with a history of specific forms of direct trauma exposure (e.g., physical assault) were more likely to store firearms unsafely., Limitations: Cross-sectional design precludes causal inference., Conclusions: Half of U.S. veterans who own firearms store at least one personal firearm loaded and/or in a non-secure location, with approximately four-in-ten keeping a loaded firearm in the home. These high rates underscore the importance of nationwide training initiatives to promote safe firearm storage for all service members and veterans, regardless of risk status, as well as for healthcare professionals working with veterans., Competing Interests: Declaration of competing interest MLH has served as a paid consultant for Spectrum Therapeutics in the past two years. No other authors have any disclosures., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glioblastoma is one of the most aggressive and invasive types of brain cancer with a 5-year survival rate of 6.8%. With limited options, patients often have poor quality of life and are moved to palliative care after diagnosis. As a result, there is an extreme need for a novel theranostic method that allows for early diagnosis and noninvasive treatment as current peptide-based delivery standards may have off-target effects. Prussian Blue nanoparticles (PBNPs) have recently been investigated as photoacoustic imaging (PAI) and photothermal ablation agents. However, due to their inability to cross the blood-brain barrier (BBB), their use in glioblastoma treatment is limited. By utilizing a hybrid, biomimetic nanoparticle composed of a PBNP interior and a U-87 cancer cell-derived exosome coating (Exo:PB), we show tumor-specific targeting within the brain and selective thermal therapy potential due to the strong photoconversion abilities. Particle characterization was carried out and showed a complete coating around the PBNPs that contains exosome markers. In vitro cellular uptake patterns are similar to native U-87 exosomes and when exposed to an 808 nm laser, show localized cell death within the specified region. After intravenous injection of Exo:PB into subcutaneously implanted glioblastoma mice, they have shown effective targeting and eradication of tumor volume compared to PEG-coated PBNPs (PEG:PB). Through systemic administration of Exo:PB particles into orthotopic glioblastoma-bearing mice, the PBNP signal was detected in the brain tumor region through PAI. It was seen that Exo:PB had preferential tumor accumulation with less off-targeting compared to the RGD:PB control. Ex vivo analysis validated specific targeting with a direct overlay of Exo:PB with the tumor by both H&E staining and Ki67 labeling. Overall, we have developed a novel biomimetic material that can naturally cross the BBB and act as a theranostic agent for systemic targeting of glioblastoma tissue and photothermal therapeutic effect.

Colorectal cancer (CRC) is the third leading cause of cancer death in the U.S., and early detection and diagnosis are essential for effective treatment. Current methods are inadequate for rapid detection of early disease, revealing flat lesions, and delineating tumor margins with accuracy and molecular specificity. Fluorescence endoscopy can generate wide field-of-view images enabling detection of CRC lesions and margins; increased signal intensity and improved signal-to-noise ratios can increase both speed and sensitivity of cancer detection. For this purpose, we developed targeted near-infrared (NIR) fluorescent silica nanoparticles (FSNs). We tuned their size to 50-200 nm and conjugated their surface with an antibody to carcinoembryonic antigen (CEA) to prepare CEA-FSNs. The physicochemical properties and biodegradable profiles of CEA-FSN were characterized, and molecular targeting was verified in culture using HT29 (CEA positive) and HCT116 (CEA negative) cells. CEA-FSNs bound to the HT29 cells to a greater extent than to the HCT116 cells, and smaller CEA-FSNs were internalized into HT29 cells more efficiently than larger CEA-FSNs. After intravenous administration of CEA-FSNs, a significantly greater signal was observed from the CEA-positive HT29 than the CEA-negative HCT116 tumors in xenografted mice. In F344-PIRC rats, polyps in the intestine were detected by white-light endoscopy, and NIR fluorescent signals were found in the excised intestinal tissue after topical application of CEA-FSNs. Immunofluorescence imaging of excised tissue sections demonstrated that the particle signals coregistered with signals for both CRC and CEA. These results indicate that CEA-FSNs have potential as a molecular imaging marker for early diagnosis of CRC.

Background: Military sexual trauma (MST) and moral injury (MI) are associated with adverse psychiatric and health outcomes among military veterans. However, no known population-based studies have examined the incremental burden associated with the co-occurrence of these experiences relative to either alone., Method: Cross-sectional data were analyzed from the National Health and Resilience in Veterans Study, a nationally representative sample of 1330 U.S. combat veterans. Veterans reported on history of exposure to MST and potentially morally injurious events (PMIEs). Analyses estimated the lifetime prevalence of MST only, PMIEs only, and co-occurring MST and PMIEs; and examined associations between MST/PMIEs status and psychiatric and physical health comorbidities, functioning, and suicidality., Results: The lifetime weighted prevalence of exposure to MST only, PMIEs only, and co-occurring MST and PMIEs were 2.7%, 32.3%, and 4.5%, respectively. Compared with all other groups, the co-occurring MST + PMIEs group reported greater severity of posttraumatic stress, depression, generalized anxiety, and insomnia symptoms. They also scored lower on measures of physical, mental, and psychosocial functioning, and reported a greater number of chronic medical conditions and somatic complaints. Veterans with co-occurring MST + PMIEs were more than twice as likely as those with MST only to report past-year suicidal ideation., Conclusions: The co-occurrence of MST and MI is associated with a greater psychiatric and health burden among combat veterans than either experience alone. Results underscore the importance of assessing and treating MST and MI in this population. Findings underscore the importance for future work to parse overlap between morally salient aspects of MST and the concept of moral injury., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

High rates of cannabis use among people with posttraumatic stress disorder (PTSD) have raised questions about the efficacy of evidence-based PTSD treatments for individuals reporting cannabis use, particularly those with co-occurring alcohol or other substance use disorders (SUDs). Using a subset of four randomized clinical trials (RCTs) included in Project Harmony, an individual patient meta-analysis of 36 RCTs (total N = 4046) of treatments for co-occurring PTSD+SUD, we examined differences in trauma-focused (TF) and non-trauma-focused (non-TF) treatment outcomes for individuals who did and did not endorse baseline cannabis use (N = 410; 70% male; 33.2% endorsed cannabis use). Propensity score-weighted mixed effects modeling evaluated main and interactive effects of treatment assignment (TF versus non-TF) and baseline cannabis use (yes/no) on attendance rates and within-treatment changes in PTSD, alcohol, and non-cannabis drug use severity. Results revealed significant improvements across outcomes among participants in all conditions, with larger PTSD symptom reductions but lower attendance among individuals receiving TF versus non-TF treatment in both cannabis groups. Participants achieved similar reductions in alcohol and drug use across all conditions. TF outperformed non-TF treatments regardless of recent cannabis use, underscoring the importance of reducing barriers to accessing TF treatments for individuals reporting cannabis use., Competing Interests: Declaration of Competing Interest Drs. Back and Therese Killeen are authors on the COPE therapy manuals published by Oxford University Press. Dr. Back has received compensation from UpToDate. Dr. Norman has received compensation from UpToDate and royalties from Elsevier Press. Dr. Hill has been a paid consultant for Canopy Growth Corporation in the past two years. The other authors report no financial relationships with commercial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Cannabidiol (CBD) has been shown to maintain bone integrity in pre-clinical models, but little is known about the effects of delta-9-tetrahydrocannabinol (THC) on bone turnover. In this study we explored the effects of two oral medical cannabis products on normal bone homeostasis through evaluation of markers of bone resorption (carboxyl-terminal collagen crosslinks, CTx) and bone formation (procollagen type 1 N-terminal propeptide, P1NP; alkaline phosphatase, ALP). Methods: This study is an analysis of secondary data from two Phase 1 double-blind, placebo-controlled trials of Spectrum Yellow (0.9 mg THC, 20 mg CBD/mL of oil) and Spectrum Red (2.5 mg THC, 0.3 mg CBD/softgel). Healthy participants ( n =38 men, 45 women) were randomized to receive 5-20 mg THC (CBD levels varied as a function of administered product) or placebo daily (BID) for 7 days. Bone markers were assessed at baseline, upon completion of product administration (day 8), and after a 5-day washout (day 13). Results: All bone markers were significantly higher in men at baseline ( p ≤0.008). For CTx, there was a significant day×group interaction ( F =3.23, p =0.04); CTx levels were significantly lower in participants treated with Spectrum Red ( b =-164.28; 95% confidence interval [CI], -328 to -0.29; p =0.04) and marginally lower in participants treated with Spectrum Yellow ( b =-157.31; 95% CI, -323 to 8.68; p =0.06) versus placebo on day 8. For P1NP and ALP, there were no significant differences between treatments across study days. Bone marker values outside the reference range (RR) were observed; CTx > RR ( n =71) was predominantly (85.9%) observed in male participants, whereas P1NP > RR ( n =100) was more evenly distributed between sexes (53.0% in men). These were not considered clinically significant and did not differ between treatment groups. Conclusions: These are the first interventional human data on the effect of cannabinoids on biomarkers of bone turnover. Short-term treatment with CBD- or THC-dominant medical cannabis products resulted in attenuation of a marker of bone resorption. Although the attenuation was not clinically significant, this finding may be indicative of protective properties of cannabinoids in bone. Further research over longer dosing durations in individuals exhibiting bone-specific conditions (e.g., osteoporosis) is warranted. ClinicalTrials.gov IDs: ACTRN12619001723178 and ACTRN12619001450101.

Currently, there are multiple breast dosimetry estimation methods for mammography and its variants in use throughout the world. This fact alone introduces uncertainty, since it is often impossible to distinguish which model is internally used by a specific imaging system. In addition, all current models are hampered by various limitations, in terms of overly simplified models of the breast and its composition, as well as simplistic models of the imaging system. Many of these simplifications were necessary, for the most part, due to the need to limit the computational cost of obtaining the required dose conversion coefficients decades ago, when these models were first implemented. With the advancements in computational power, and to address most of the known limitations of previous breast dosimetry methods, a new breast dosimetry method, based on new breast models, has been developed, implemented, and tested. This model, developed jointly by the American Association of Physicists in Medicine and the European Federation for Organizations of Medical Physics, is applicable to standard mammography, digital breast tomosynthesis, and their contrast-enhanced variants. In addition, it includes models of the breast in both the cranio-caudal and the medio-lateral oblique views. Special emphasis was placed on the breast and system models used being based on evidence, either by analysis of large sets of patient data or by performing measurements on imaging devices from a range of manufacturers. Due to the vast number of dose conversion coefficients resulting from the developed model, and the relative complexity of the calculations needed to apply it, a software program has been made available for download or online use, free of charge, to apply the developed breast dosimetry method. The program is available for download or it can be used directly online. A separate User's Guide is provided with the software., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

The coronavirus disease 2019 (COVID-19) pandemic has claimed over 7 million lives worldwide, providing a stark reminder of the importance of pandemic preparedness. Due to the lack of approved antiviral drugs effective against coronaviruses at the start of the pandemic, the world largely relied on repurposed efforts. Here, we summarise results from randomised controlled trials to date, as well as selected in vitro data of directly acting antivirals, host-targeting antivirals, and immunomodulatory drugs. Overall, repurposing efforts evaluating directly acting antivirals targeting other viral families were largely unsuccessful, whereas several immunomodulatory drugs led to clinical improvement in hospitalised patients with severe disease. In addition, accelerated drug discovery efforts during the pandemic progressed to multiple novel directly acting antivirals with clinical efficacy, including small molecule inhibitors and monoclonal antibodies. We argue that large-scale investment is required to prepare for future pandemics; both to develop an arsenal of broad-spectrum antivirals beyond coronaviruses and build worldwide clinical trial networks that can be rapidly utilised.

Introduction: This study aimed to identify the prevalence and correlates of firearm ownership in a large, contemporary, nationally representative sample of U.S. military veterans., Methods: Data were analyzed from the 2022 National Health and Resilience in Veterans Study (N=2,326; mean age=60.2 years). Weighted independent-sample t-tests and chi-square analyses were conducted to compare veterans who did with those who did not report firearm ownership on sociodemographic, military, and psychiatric variables. A multivariable logistic regression analysis using backward elimination was conducted to identify the characteristics independently associated with firearm ownership, and a relative importance analysis was conducted to quantify the relative variance in firearm ownership that was explained by each of the statistically significant main effects., Results: Of the total 2,326 veterans, 1,217 (weighted 50.9%, 95% CI=48.0%, 53.9%) reported owning any firearms. Male sex, conservative political ideology, living in rural area, home ownership, cumulative trauma burden, and lifetime history of alcohol use disorder were most strongly associated with firearm ownership., Conclusions: This study provides an updated characterization of the prevalence and correlates of firearm ownership among the U.S. veterans. Results of this nationally representative study suggest that firearm ownership in this group may be higher than previously reported and underscore the importance of targeted suicide prevention efforts promoting firearm safety among vulnerable segments of this population., (Published by Elsevier Inc.)

Background: Little is known about environmental factors that may influence associations between genetic liability to suicidality and suicidal behavior., Methods: This study examined whether a suicidality polygenic risk score (PRS) derived from a large genome-wide association study ( N = 122,935) was associated with suicide attempts in a population-based sample of European-American US military veterans ( N = 1664; 92.5% male), and whether cumulative lifetime trauma exposure moderated this association., Results: Eighty-five veterans (weighted 6.3%) reported a history of suicide attempt. After adjusting for sociodemographic and psychiatric characteristics, suicidality PRS was associated with lifetime suicide attempt (odds ratio 2.65; 95% CI 1.37-5.11). A significant suicidality PRS-by-trauma exposure interaction emerged, such that veterans with higher levels of suicidality PRS and greater trauma burden had the highest probability of lifetime suicide attempt (16.6%), whereas the probability of attempts was substantially lower among those with high suicidality PRS and low trauma exposure (1.4%). The PRS-by-trauma interaction effect was enriched for genes implicated in cellular and developmental processes, and nervous system development, with variants annotated to the DAB2 and SPNS2 genes, which are implicated in inflammatory processes. Drug repurposing analyses revealed upregulation of suicide gene-sets in the context of medrysone, a drug targeting chronic inflammation, and clofibrate, a triacylglyceride level lowering agent., Conclusion: Results suggest that genetic liability to suicidality is associated with increased risk of suicide attempt among veterans, particularly in the presence of high levels of cumulative trauma exposure. Additional research is warranted to investigate whether incorporation of genomic information may improve suicide prediction models.

Europium ion-activated calcium silicate phosphors (Ca 2 SiO 4 :Eu 3+ ) with sharp red-light emission were fabricated via the hydrothermal method. The size of Ca 2 SiO 4 :Eu 3+ phosphors was controlled between 20 and 200 nm by precursor silicate particle sizes. Systematic studies to determine morphology, crystal phase, and photoluminescence (PL) were carried out for all the phosphors, and their optical efficiencies were compared. We found that the luminescence intensity and emission wavelength of Ca 2 SiO 4 :Eu 3+ phosphors depend on their particle sizes. Particularly, the Ca 2 SiO 4 :Eu 3+ synthesized with 20 nm silica seed contains the most intense red emission, high color purity, and high PL quantum yield. For the 20 nm-sized Ca 2 SiO 4 :Eu 3+ phosphor, PL quantum yields are measured to be above 87.95% and high color purity of 99.8%. The unusually high intensity of 5 D 0 → 7 F 4 emission (712 nm) is explained by structural distortion arising from silicate particle size reductions. We show that the obtained phosphor is a suitable candidate for solid-state lighting as a red component through CIE chromaticity coordinate and color purity measurements. Furthermore, the Ca 2 SiO 4 :Eu 3+ particles are examined for their validity as promising bio-imaging probes through cell labeling and imaging experiments and biodegradability studies., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Childhood sexual abuse (CSA) and military sexual trauma (MST) are prevalent among veterans. Such exposures are associated with adverse mental-health sequelae, including elevated risk for suicidal thoughts and behaviors. Nonetheless, prior studies have largely focused upon discrete experiences of CSA or MST in circumscribed samples. In the current study, we analyzed data from a large, nationally representative sample of 4,069 US military veterans to examine main and interactive effects of CSA and MST in relation to suicidal thoughts and behaviors. After accounting for sociodemographics, psychiatric comorbidity, and trauma-related characteristics, we detected a significant interaction between MST and CSA as it related to report of past-year suicidal ideation, lifetime suicide attempt, and risk for future suicide attempt. These findings underscore the impact of sexual trauma throughout the lifespan, highlighting the continued importance of screening for trauma exposure and connecting veterans to appropriate, evidence-based treatment to decrease their risk for suicidal thoughts and behaviors.

Background: The coronavirus disease-2019 (COVID-19) pandemic has caused myriad health, social, and economic stressors. To date, however, no known study has examined changes in mental health during the pandemic in the U.S. military veteran population., Methods: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative, prospective cohort survey of 3078 veterans. Pre-to-peri-pandemic changes in psychiatric symptoms were evaluated, as well as pre-pandemic risk and protective factors and pandemic-related correlates of increased psychiatric distress., Results: The prevalence of generalized anxiety disorder (GAD) positive screens increased from pre- to peri-pandemic (7.1% to 9.4%; p < 0.001) and was driven by an increase among veterans aged 45-64 years (8.2% to 13.5%; p < 0.001), but the prevalence of major depressive disorder and posttraumatic stress disorder positive screens remained stable. Using a continuous measure of psychiatric distress, an estimated 13.2% of veterans reported a clinically meaningful pre-to-peri-pandemic increase in distress (mean = 1.1 standard deviation). Veterans with a larger pre-pandemic social network size and secure attachment style were less likely to experience increased distress, whereas veterans reporting more pre-pandemic loneliness were more likely to experience increased distress. Concerns about pandemic-related social losses, mental health COVID-19 effects, and housing stability during the pandemic were associated with increased distress, over-and-above pre-pandemic factors., Conclusions: Although most U.S. veterans showed resilience to mental health problems nearly 1 year into the pandemic, the prevalence of GAD positive screens increased, particularly among middle-aged veterans, and one of seven veterans experienced increased distress. Clinical implications of these findings are discussed.

The COVID-19 pandemic stemmed a parallel upsurge in the scientific literature about SARS-CoV-2 infection and its health burden. The Rat Genome Database (RGD) created a COVID-19 Disease Portal to leverage information from the scientific literature. In the COVID-19 Portal, gene-disease associations are established by manual curation of PubMed literature. The portal contains data for nine ontologies related to COVID-19, an embedded enrichment analysis tool, as well as links to a toolkit. Using these information and tools, we performed analyses on the curated COVID-19 disease genes. As expected, Disease Ontology enrichment analysis showed that the COVID-19 gene set is highly enriched with coronavirus infectious disease and related diseases. However, other less related diseases were also highly enriched, such as liver and rheumatic diseases. Using the comparison heatmap tool, we found nearly 60 percent of the COVID-19 genes were associated with nervous system disease and 40 percent were associated with gastrointestinal disease. Our analysis confirms the role of the immune system in COVID-19 pathogenesis as shown by substantial enrichment of immune system related Gene Ontology terms. The information in RGD's COVID-19 disease portal can generate new hypotheses to potentiate novel therapies and prevention of acute and long-term complications of COVID-19.

Objective: Suicidal intent is a risk factor for engagement in suicidal behavior, use of violent means, and suicide mortality. Yet, scarce research has examined factors associated with suicidal intent among U.S. military veterans, a population at high risk for suicide. This study examined vulnerability factors associated with suicidal intent in a population-based sample of U.S. veterans., Methods: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a representative sample of 4069 U.S. veterans. Analyses estimated the prevalence of current suicidal intent (i.e., veterans' report that they would likely attempt suicide in the future) and examined factors most strongly associated with suicidal intent., Results: Forty-nine veterans (1.4%; 95% confidence interval = 1.0-1.8%) reported suicidal intent. Recurrent past-year suicidal ideation (≥2 times), low dispositional gratitude, current depression, current insomnia, childhood sexual abuse, and a prior suicide attempt were most strongly associated with suicidal intent (7.1-50.1% of the total explained variance). Veterans with several of these co-occurring factors were at highest risk for suicidal intent; of veterans with 0, ≥1, ≥2, ≥3, and ≥4 of these factors, 0.1%, 4.4%, 10.8%, 19.5%, and 28.1% reported suicidal intent, respectively., Discussion: Specific vulnerability factors, particularly when co-occurring, may increase veterans' intention of attempting suicide. Findings underscore the importance for clinicians to continuously assess suicidal intent when working with this population, particularly as veterans' reports of suicidal thinking increases., (Copyright © 2022. Published by Elsevier Ltd.)

Cannabis use is common among individuals with posttraumatic stress disorder (PTSD) symptoms, but its impact on psychiatric symptoms and functioning in this population is unclear. To clarify the clinical and functional correlates of cannabis use in individuals with PTSD symptoms, we analyzed data from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative survey of U.S. military veterans. Participants with current subthreshold or full PTSD (N = 608) reported on their past-6-month cannabis use and current psychiatric symptoms, functioning, treatment utilization, and PTSD symptom management strategies. Veterans with subthreshold/full PTSD who used cannabis more than weekly were more likely to screen positive for co-occurring depression, anxiety, and suicidal ideation than those who did not use cannabis, ORs = 3.4-3.8, or used cannabis less than weekly, ORs = 2.7-3.7. Veterans who used cannabis more than weekly also scored lower in cognitive functioning than veterans with no use, d = 0.25, or infrequent use, d = 0.71, and were substantially more likely to endorse avoidance coping strategies, ORs = 8.2-12.2, including substance use, OR = 4.4, and behavioral disengagement, ORs = 2.7-9.1, to manage PTSD symptoms. Despite more psychiatric and functional problems, veterans with frequent cannabis use were not more likely to engage in mental health treatment, ORs = 0.87-0.99. The results suggest enhanced cannabis use screening, interventions targeting risky use, and strategies promoting treatment engagement may help ameliorate more severe clinical presentations associated with frequent cannabis use among veterans with subthreshold/full PTSD., (© 2022 International Society for Traumatic Stress Studies.)

Background: The reported prevalence of military sexual trauma (MST) has increased over the past decades in the United States, yet scarce population-based studies have examined the prevalence, correlates, and health burden of MST in the general veteran population., Methods: Data were from the 2019-2020 National Health and Resilience in Veterans Study, a population-based survey of veterans (n = 4069)., Analyses: (1) estimated the prevalence of MST; (2) identified sex-stratified sociodemographic, military, and trauma characteristics associated with MST; and (3) examined sex-stratified associations between MST and psychiatric comorbidities, functioning, disability, and treatment utilization., Results: Female veterans reported substantially higher rates of MST (44.2%) than male veterans (3.5%). Relative to male veterans without MST histories, male veterans with MST histories had nearly 3-fold increased odds of reporting future suicidal intent, 2-to-3-fold greater odds of screening positive for current posttraumatic stress disorder (PTSD), depression, and generalized anxiety disorder; and nearly 2-fold increased odds of being disabled. Male veterans with MST histories also scored lower on mental, physical, cognitive, and psychosocial functioning (d's = 0.16-0.29). Relative to female veterans without MST histories, female veterans with MST histories had 5-fold greater odds of current PTSD, 2-fold greater odds of engaging in mental health treatment, and scored lower on psychosocial functioning and higher on somatic symptoms (both d's = 0.25)., Limitations: Cross-sectional design precludes causal inference., Conclusions: A substantial proportion of veterans in the U.S. experience sexual trauma during their military service, and these experiences are associated with an elevated health burden., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Suicide is a major public health problem in U.S. military veterans, but little is known about factors associated with remission from suicide attempts in this population. We aimed to identify risk and protective correlates of remission from suicidal thoughts and behavior (STB) in U.S. veterans with a prior suicide attempt. Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study survey. A broad range of sociodemographic, military, physical and mental health, and psychosocial variable were assessed. Purpose in life, dispositional gratitude, and conscientiousness emerged as independent correlates of STB remission (24.3%-40.3% of explained variance), even after accounting for other relevant risk and protective factors. While the cross-sectional nature of the study precludes the ability to determine whether the identified protective factors are causally related to STB remission, results suggest three potentially modifiable targets for suicide prevention efforts in veterans. Longitudinal studies are needed to better understand the role of purpose in life, dispositional gratitude, and conscientiousness in promoting remission from STBs in veterans and other populations at risk for suicide., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Biological interpretation of a large amount of gene or protein data is complex. Ontology analysis tools are imperative in finding functional similarities through overrepresentation or enrichment of terms associated with the input gene or protein lists. However, most tools are limited by their ability to do ontology-specific and species-limited analyses. Furthermore, some enrichment tools are not updated frequently with recent information from databases, thus giving users inaccurate, outdated or uninformative data. Here, we present MOET or the Multi-Ontology Enrichment Tool (v.1 released in April 2019 and v.2 released in May 2021), an ontology analysis tool leveraging data that the Rat Genome Database (RGD) integrated from in-house expert curation and external databases including the National Center for Biotechnology Information (NCBI), Mouse Genome Informatics (MGI), The Kyoto Encyclopedia of Genes and Genomes (KEGG), The Gene Ontology Resource, UniProt-GOA, and others. Given a gene or protein list, MOET analysis identifies significantly overrepresented ontology terms using a hypergeometric test and provides nominal and Bonferroni corrected P-values and odds ratios for the overrepresented terms. The results are shown as a downloadable list of terms with and without Bonferroni correction, and a graph of the P-values and number of annotated genes for each term in the list. MOET can be accessed freely from https://rgd.mcw.edu/rgdweb/enrichment/start.html., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Background: Population-based data on risk factors for suicide attempts among veterans remains limited., Methods: A national probability sample of 2307 veterans was followed over the course of four timepoints spanning seven years to examine how a range of baseline risk factors predict incident suicide attempt. Suicide attempt data were aggregated into a single follow-up timepoint., Results: Sixty-two veterans (3.1%) reported attempting suicide during the 7-year period. The strongest risk factors for suicide attempts were higher baseline levels of loneliness, lower baseline levels of adaptive psychosocial traits (e.g., dispositional gratitude), baseline thoughts of self-harm, and greater post-baseline trauma exposures (12.3%-41.3% of explained variance). Veterans with multiple co-occurring risk factors were at greatest risk for attempts; of veterans with 0, 1, 2, 3, and all 4 of these factors, the predicted probability of suicide attempt was 2.0%, 5.3%, 13.5%, 30.4%, and 55.0%, respectively., Conclusions: Baseline loneliness, dispositional gratitude, thoughts of self-harm, and new-onset traumas emerged as the strongest risk factors for suicide attempts among veterans, underscoring the potential importance of targeting these factors in prevention efforts. Veterans with multiple co-occurring risk factors have substantially greater risk for suicide attempts, suggesting that examination of multiple coinciding vulnerability factors may help improve suicide risk prediction models., (© 2021 The American Association of Suicidology.)

Model organism research is essential for discovering the mechanisms of human diseases by defining biologically meaningful gene to disease relationships. The Rat Genome Database (RGD, ( https://rgd.mcw.edu )) is a cross-species knowledgebase and the premier online resource for rat genetic and physiologic data. This rich resource is enhanced by the inclusion and integration of comparative data for human and mouse, as well as other human disease models including chinchilla, dog, bonobo, pig, 13-lined ground squirrel, green monkey, and naked mole-rat. Functional information has been added to records via the assignment of annotations based on sequence similarity to human, rat, and mouse genes. RGD has also imported well-supported cross-species data from external resources. To enable use of these data, RGD has developed a robust infrastructure of standardized ontologies, data formats, and disease- and species-centric portals, complemented with a suite of innovative tools for discovery and analysis. Using examples of single-gene and polygenic human diseases, we illustrate how data from multiple species can help to identify or confirm a gene as involved in a disease and to identify model organisms that can be studied to understand the pathophysiology of a gene or pathway. The ultimate aim of this report is to demonstrate the utility of RGD not only as the core resource for the rat research community but also as a source of bioinformatic tools to support a wider audience, empowering the search for appropriate models for human afflictions., (© 2021. The Author(s).)

Purpose: Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities., Methods: Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t -tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t -test., Results: Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups., Conclusion: Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors., Competing Interests: Debra L. BartonResearch Funding: Merck Stephanie L. PughResearch Funding: Pfizer (Inst), Millennium (Inst) Patricia A. GanzLeadership: Intrinsic LifeSciences (I)Stock and Other Ownership Interests: Xenon Pharma (I), Intrinsic LifeSciences (I), Teva, Novartis, Merck, Johnson & Johnson, Pfizer, GlaxoSmithKline, Abbott LaboratoriesConsulting or Advisory Role: InformedDNA, Vifor Pharma (I), Ambys Medicines (I), Global Blood Therapeutics (I), GlaxoSmithKline (I), Ionis Pharmaceuticals (I), Protagonist Therapeutics (I), Akebia Therapeutics (I), Regeneron (I), Sierra Oncology (I), Rockwell Medical Technologies Inc (I), Astellas Pharma (I), Gossamer Bio (I), American Regent (I), Disc Medicine (I), Blue Note Therapeutics (I), Grail (I)Research Funding: Blue Note Therapeutics (Inst)Patents, Royalties, Other Intellectual Property: Related to iron metabolism and the anemia of chronic disease, UpToDate royalties for section editor on survivorshipTravel, Accommodations, Expenses: Intrinsic LifeSciences (I) Steven C. PlaxeStock and Other Ownership Interests: Pfizer, Merck, Zimmer Biomet, GlaxoSmithKline, AstraZeneca, Bristol Myers Squibb/Pfizer, Johnson & Johnson/JanssenResearch Funding: Endocyte, Incyte, MedImmune, Novartis, Pfizer, Janssen Oncology, BIND Therapeutics, PharmaMar, AstraZeneca, Kevelt, Millennium, Tesaro Bridget F. KoontzEmployment: GenesisCareLeadership: GenesisCareConsulting or Advisory Role: Blue Earth Diagnostics, Myovant Sciences, Rythera TherapeuticsResearch Funding: Janssen, Merck, Blue Earth DiagnosticsPatents, Royalties, Other Intellectual Property: Demos Publishing Matthew L. HillStock and Other Ownership Interests: AstraZeneca, Newlink Genetics, Kazia Therapeutics, Leap Therapeutics, OncoSec, MEI Pharma, PLx Pharma, Radius Health, Crispr Therapeutics, Cassava SciencesOpen Payments Link: https://openpaymentsdata.cms.gov/physician/820072 Carolyn Y. MullerResearch Funding: AstraZeneca, Genmab, VBL Therapeutics, Roche/Genentech, TapImmune Inc, Linnaeus Therapeutics, Agenus, Incyte, MerckPatents, Royalties, Other Intellectual Property: Have a pending patent on the cancer use for R-ketorolac—not yet its own new drugOther Relationship: NCI, Department of Defense Lisa A. KachnicConsulting or Advisory Role: New B InnovationResearch Funding: Varian Medical SystemsPatents, Royalties, Other Intellectual Property: UpToDateNo other potential conflicts of interest were reported.

Most enveloped viruses rely on the host cell endoplasmic reticulum (ER) quality control (QC) machinery for proper folding of glycoproteins. The key ER α-glucosidases (α-Glu) I and II of the ERQC machinery are attractive targets for developing broad-spectrum antivirals. Iminosugars based on deoxynojirimycin have been extensively studied as ER α-glucosidase inhibitors; however, other glycomimetic compounds are less established. Accordingly, we synthesized a series of N-substituted derivatives of valiolamine, the iminosugar scaffold of type 2 diabetes drug voglibose. To understand the basis for up to 100,000-fold improved inhibitory potency, we determined high-resolution crystal structures of mouse ER α-GluII in complex with valiolamine and 10 derivatives. The structures revealed extensive interactions with all four α-GluII subsites. We further showed that N-substituted valiolamines were active against dengue virus and SARS-CoV-2 in vitro . This study introduces valiolamine-based inhibitors of the ERQC machinery as candidates for developing potential broad-spectrum therapeutics against the existing and emerging viruses.

Purpose: Contrast-Enhanced Mammography (CEM) produces a dual-energy subtracted (DES) image that demonstrates iodine uptake (neovascularity) in breast tissue. We aim to review a range of artifacts on DES images produced using equipment from two different vendors and compare their incidence and subjective severity., Methods: We retrospectively reviewed CEM studies performed between September 2013 and March 2017 using GE Senographe Essential (n = 100) and Hologic Selenia Dimensions (n = 100) equipment. Artifacts were categorized and graded in severity by a subspecialist breast radiologist and one of two medical imaging technologists in consensus. The incidence of artifacts between vendors was compared by calculating the relative risk, and the severity gradings were compared using a Wilcoxon rank-sum test., Results: Elephant rind, corrugations and the black line on chest wall artifact were seen exclusively in Hologic images. Artifacts such as cloudy fat, negative rim around lesion and white line on pectoral muscle were seen in significantly more Hologic images (p < 0.05) whilst halo, ripple, skin line enhancement, black line on pectoral muscle, bright pectorals, chest wall high-lighting and air gap were seen in significantly more GE images (p < 0.05). The severity gradings for cloudy fat had a significantly higher mean rank in Hologic images (p < 0.001) whilst halo and ripple artifacts had a significantly higher mean rank in GE images (p < 0.001 and p = 0.028 respectively)., Conclusion: The type, incidence and subjective severity of CEM-specific artifacts differ between vendors. Further research is needed, but differences in algorithms used to produce the DE image are postulated to be a significant contributor., (Copyright © 2021. Published by Elsevier Inc.)

Background: Substance use is a strong risk factor for suicidal behavior. To date, however, no known study has evaluated optimal cut-off scores on substance use severity measures to identify individuals who may be at elevated risk for suicide., Methods: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 4069 U.S. veterans. Receiver operating characteristic curve analyses were conducted to identify cut-off scores on the Alcohol Use Disorders Identification Test (AUDIT) and Screen of Drug Use (SDU) that optimally differentiated veterans with and without past-year suicidal ideation (SI) in the full sample, as well a high-risk subsample with histories of major depressive disorder (MDD) and/or posttraumatic stress disorder (PTSD)., Results: The prevalence of past-year SI was 11.7% (n = 387); A total of 10.5% (n = 360) of the sample screened positive for past-year alcohol use disorder, 9.1% (n = 314) for past-year drug use disorder, and 22.4% (n = 833) for lifetime MDD/PTSD. The optimal AUDIT cut-off score that differentiated suicide ideators and non-ideators was ≥14 in the full sample, and ≥18 in the high-risk subsample; these scores are indicative of moderate-to-severe alcohol use disorder. The optimal SDU cut-off score was ≥1 for both the full sample and high-risk subsample, which is lower than the recommend cut-off score for probable drug use disorder (≥7)., Conclusions: Results identify high-specificity thresholds on the AUDIT and SDU that may have clinical utility in suicide risk assessment in veterans. Veterans with moderate-to-severe alcohol use disorder or who use non-prescription drugs may warrant further suicide risk assessment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Sepsis is a life-threatening condition involving a dysregulated immune response to infectious agents that cause injury to host tissues and organs. Current treatments are limited to early administration of antibiotics and supportive care. While appealing, the strategy of targeted inhibition of individual molecules in the inflammatory cascade has not proved beneficial. Non-targeted, systemic immunosuppression with steroids has shown limited efficacy and raises concern for secondary infection. Iminosugars are a class of small molecule glycomimetics with distinct inhibition profiles for glycan processing enzymes based on stereochemistry. Inhibition of host endoplasmic reticulum resident glycoprotein processing enzymes has demonstrated efficacy as a broad-spectrum antiviral strategy, but limited consideration has been given to the effects on host glycoprotein production and consequent disruption of signalling cascades. This work demonstrates that iminosugars inhibit dengue virus, bacterial lipopolysaccharide and fungal antigen-stimulated cytokine responses in human macrophages. In spite of decreased inflammatory mediator production, viral replication is suppressed in the presence of iminosugar. Transcriptome analysis reveals the key interaction of pathogen-induced endoplasmic reticulum stress, the resulting unfolded protein response and inflammation. Our work shows that iminosugars modulate these interactions. Based on these findings, we propose a new therapeutic role for iminosugars as treatment for sepsis-related inflammatory disorders associated with excess cytokine secretion., (© 2021 The Authors. Immunology published by John Wiley & Sons Ltd.)

Importance: The COVID-19 pandemic has raised considerable concerns about increased risk for suicidal behavior among US military veterans, who already had elevated rates of suicide before the pandemic., Objective: To examine longitudinal changes in suicidal behavior from before the COVID-19 pandemic to nearly 10 months into the pandemic and identify risk factors and COVID-related variables associated with new-onset suicide ideation (SI)., Design, Setting, and Participants: This population-based prospective cohort study used data from the first and second wave of the National Health and Resilience in Veterans Study, conducted from November 18, 2019, to December 19, 2020. Median dates of data collection for the prepandemic and peripandemic assessments were November 21, 2019, and November 14, 2020, nearly 10 months after the start of the COVID-19 public health emergency in the US. A total of 3078 US military veterans aged 22 to 99 years were included in the study., Main Outcomes and Measures: Past-year SI and suicide attempts., Results: In this cohort study of 3078 US veterans (mean [SD] age, 63.2 [14.7] years; 91.6% men; 79.3% non-Hispanic White veterans, 10.3% non-Hispanic Black veterans, and 6.0% Hispanic veterans), 233 (7.8%) reported past-year SI, and 8 (0.3%) reported suicide attempts at the peripandemic assessment. Past-year SI decreased from 10.6% prepandemic (95% CI, 9.6%-11.8%) to 7.8% peripandemic (95% CI, 6.9%-8.8%). A total of 82 veterans (2.6%) developed new-onset SI over the follow-up period. After adjusting for sociodemographic and military characteristics, the strongest risk factors and COVID-19-related variables for new-onset SI were low social support (odds ratio [OR], 2.77; 95% CI, 1.46-5.28), suicide attempt history (OR, 6.31; 95% CI, 2.71-14.67), lifetime posttraumatic stress disorder and/or depression (OR, 2.25; 95% CI, 1.16-4.35), past-year alcohol use disorder severity (OR, 1.06; 95% CI, 1.01-1.12), COVID-19 infection (OR, 2.41; 95% CI, 1.41-5.01), and worsening of social relationships during the pandemic (OR, 1.47; 95% CI, 1.16-1.88)., Conclusions and Relevance: The results of this cohort study suggest that despite grim forecasts that the COVID-19 pandemic would exacerbate suicidality among US military veterans, the rate of SI decreased at the population level nearly 10 months into the pandemic. Veterans who were infected with COVID-19 were more than twice as likely to report SI, which suggests the need for future research to examine the potential link between COVID-19 infection and suicidal behavior.

Objective: Several vulnerability factors for suicidal behavior in U.S. veterans have been identified. However, little is known about factors that differentiate veterans who contemplate suicide from those who attempt suicide. This study examined sociodemographic and clinical characteristics that distinguish veterans who think about suicide from those who attempt suicide., Method: Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a population-based sample of 4069 veterans. Analyses estimated the lifetime prevalence of suicide ideation (SI) and suicide attempts (SA); and examined differences between veterans with a history of attempt(s), and SI without a history of attempt(s)., Results: A total 25.9% of U.S. veterans reported lifetime SI and 3.9% reported a SA. Several factors distinguished veterans with a history of SA from those with SI only: the strongest were younger age (odds ratio [OR] = 0.97, 95% CI = 0.95-0.98), nonsuicidal self-injury (OR = 1.81, 95% CI = 1.11-3.03), adverse childhood experiences (OR = 1.14; 95% CI = 1.06-1.23), alcohol use disorder (OR = 1.99; 95% CI = 1.28-3.12), lower household income (OR = 0.62; 95% CI = 0.40-0.95), and physical disability (OR = 1.69; 95% CI = 1.07-2.70)., Conclusions: Although a quarter of U.S. veterans contemplate suicide in their lifetimes, the majority do not attempt suicide. Specific sociodemographic and clinical features may differentiate veterans who contemplate versus attempt suicide., (Copyright © 2021 Elsevier Inc. All rights reserved.)

More than half of U.S. states legalized medical or recreational sale and possession of cannabis since the prevalence of cannabis use was last estimated among U.S. military veterans in 2014. To provide updated estimates of the prevalence and correlates of cannabis use, cannabis use disorder (CUD), and medical cannabis card possession in this population, data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative survey of 4,069 veterans ages 22-99 years who reported on their past-6-month cannabis use, CUD symptoms, and possession of a medical cannabis card. An estimated 11.9% [95% confidence interval (CI) = 10.9-12.9%)] of veterans reported using cannabis, 2.7% (95% CI = 2.3-3.3%) screened positive for CUD, and 1.5% (95% CI = 1.2-2.0%) reported possessing a medical card. Prevalence of cannabis use, CUD, and card possession were higher among younger veterans (use: 20.2%, CUD: 5.6%, card: 2.1%) and those with psychiatric conditions (use: 24.0%-30.0%, CUD: 8.9%-13.0%, card: 3.1%-4.0%). Younger age, alcohol use disorder, and childhood adversity explained a large proportion of variance in cannabis use and CUD, and depression was independently associated with CUD (odds ratio [OR] = 2.76). Physical disability (OR = 3.59), combat veteran status (OR = 2.84), and non-Hispanic black (OR = 0.23) relative to white race/ethnicity most strongly predicted using cannabis with a medical card. The estimated prevalence of cannabis use in veterans-nearly 12%-is higher than the most recently reported estimate (9% in 2014). Veteran cannabis use may be increasing and is particularly prevalent among veterans with psychiatric conditions., (Copyright © 2021. Published by Elsevier Ltd.)

Basigin, or CD147, has been reported as a coreceptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to invade host cells. Basigin also has a well-established role in Plasmodium falciparum malaria infection of human erythrocytes, where it is bound by one of the parasite's invasion ligands, reticulocyte binding protein homolog 5 (RH5). Here, we sought to validate the claim that the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein can form a complex with basigin, using RH5-basigin as a positive control. Using recombinantly expressed proteins, size exclusion chromatography and surface plasmon resonance, we show that neither RBD nor full-length spike glycoprotein bind to recombinant human basigin (expressed in either Escherichia coli or mammalian cells). Further, polyclonal anti-basigin IgG did not block SARS-CoV-2 infection of Vero E6 cells. Given the immense interest in SARS-CoV-2 therapeutic targets to improve treatment options for those who become seriously ill with coronavirus disease 2019 (COVID-19), we would caution the inclusion of basigin in this list on the basis of its reported direct interaction with SARS-CoV-2 spike glycoprotein. IMPORTANCE Reducing the mortality and morbidity associated with COVID-19 remains a global health priority. Vaccines have proven highly effective at preventing infection and hospitalization, but efforts must continue to improve treatment options for those who still become seriously ill. Critical to these efforts is the identification of host factors that are essential to viral entry and replication. Basigin, or CD147, was previously identified as a possible therapeutic target based on the observation that it may act as a coreceptor for SARS-CoV-2, binding to the receptor binding domain of the spike protein. Here, we show that there is no direct interaction between the RBD and basigin, casting doubt on its role as a coreceptor and plausibility as a therapeutic target.

Objective: US military veterans have high rates of suicide relative to civilians. However, little is known about the prevalence and correlates of suicidal behaviors in the general US veteran population., Methods: Data were from the National Health and Resilience in Veterans Study, a representative survey of US veterans conducted in 2019-2020 (n = 4,069). Analyses (1) estimated the prevalence of current suicidal ideation, lifetime suicide plans, and lifetime suicide attempts; (2) identified associated sociodemographic, military, DSM-5 psychiatric, and other risk correlates; and (3) examined mental health treatment utilization among veterans with suicidal ideation, suicide plans, or suicide attempts., Results: The prevalence of current suicidal ideation, lifetime suicide plans, and lifetime suicide attempts was 9.0%, 7.3%, and 3.9%, respectively. Suicidal behaviors were most prevalent among veterans aged 18-44 years, with 18.2%, 19.3%, and 11.1%, respectively, endorsing suicidal ideation, suicide plans, and suicide attempts. Major depressive disorder (MDD), age, posttraumatic stress disorder, and adverse childhood experiences (ACEs) emerged as the strongest correlates of suicidal ideation and suicide plans, while MDD, age, alcohol use disorder, and ACEs were the strongest correlates of suicide attempts. Only 35.5% of veterans with current suicidal ideation were engaged in mental health treatment, with veterans who used the US Veterans Administration (VA) as their primary source of health care more than twice as likely as VA non-users to be engaged in such treatment (54.7% vs 23.8%)., Conclusions: Suicidal behaviors are highly prevalent among US veterans, particularly among young veterans. Results suggest that nearly two-thirds of veterans with current suicidal ideation are not engaged in mental health treatment, signaling the need for enhanced suicide prevention and outreach efforts., (© Copyright 2021 Physicians Postgraduate Press, Inc.)