Blood microbial signatures associated with mortality in patients with sepsis: A pilot study.

Sepsis is a life-threatening illness caused by the dysregulated host response to infection. Nevertheless, our current knowledge of the microbial landscape in the blood of septic patients is still limited. Next-generation sequencing (NGS) is a sensitive method to quantitatively characterize microbiomes at various sites of the human body. In this study, we analyzed the blood microbial DNA of 22 adult patients with sepsis and 3 healthy subjects. The presence of non-human DNA was identified in both healthy and septic subjects. Septic patients had a markedly altered microbial DNA profile compared to healthy subjects over α- and ß-diversity. Unexpectedly, the patients could be further divided into two subgroups (C1 and C2) based on ß-diversity analysis. C1 patients showed much higher bacteria, viruses, fungi, and archaea abundance, and a higher level of α-diversity (Chao1, Observed and Shannon index) than both C2 patients and healthy subjects. The most striking difference was seen in the case of Streptomyces violaceusniger, Phenylobacterium sp. HYN0004, Caulobacter flavus, Streptomyces sp. 11-1-2, and Phenylobacterium zucineum, the abundance of which was the highest in the C1 group. Notably, C1 patients had a significantly poorer outcome than C2 patients. Moreover, by analyzing the patterns of microbe-microbe interactions in healthy and septic subjects, we revealed that C1 and C2 patients exhibited distinct co-occurrence and co-exclusion relationships. Together, our study uncovered two distinct microbial signatures in the blood of septic patients. Compositional and ecological analysis of blood microbial DNA may thus be useful in predicting mortality of septic patients.

Methicillin Resistance Elements in the Canine Pathogen Staphylococcus pseudintermedius and Their Association with the Peptide Toxin PSM-mec.

Staphylococcus pseudintermedius is a frequent cause of infections in dogs. Infectious isolates of this coagulase-positive staphylococcal species are often methicillin- and multidrug-resistant, which complicates therapy. In staphylococci, methicillin resistance is encoded by determinants found on mobile genetic elements called Staphylococcal Chromosome Cassette mec (SCCmec), which, in addition to methicillin resistance factors, sometimes encode additional genes, such as further resistance factors and, rarely, virulence determinants. In this study, we analyzed SCCmec in a collection of infectious methicillin-resistant S. pseudintermedius (MRSP) isolates from predominant lineages in the United States. We found that several lineages characteristically have specific types of SCCmec elements and Agr types and harbor additional factors in their SCCmec elements that may promote virulence or affect DNA uptake. All isolates had SCCmec-encoded restriction-modification (R-M) systems of types I or II, and sequence types (STs) ST84 and ST64 had one type II and one type I R-M system, although the latter lacked a complete methylation enzyme gene. ST68 isolates also had an SCCmec-encoded CRISPR system. ST71 isolates had a psm-mec gene, which, in all but apparently Agr-dysfunctional isolates, produced a PSM-mec peptide toxin, albeit at relatively small amounts. This study gives detailed insight into the composition of SCCmec elements in infectious isolates of S. pseudintermedius and lays the genetic foundation for further efforts directed at elucidating the contribution of identified accessory SCCmec factors in impacting SCCmec-encoded and thus methicillin resistance-associated virulence and resistance to DNA uptake in this leading canine pathogen.

Virulence Mechanisms of Staphylococcal Animal Pathogens.

Staphylococci are major causes of infections in mammals. Mammals are colonized by diverse staphylococcal species, often with moderate to strong host specificity, and colonization is a common source of infection. Staphylococcal infections of animals not only are of major importance for animal well-being but have considerable economic consequences, such as in the case of staphylococcal mastitis, which costs billions of dollars annually. Furthermore, pet animals can be temporary carriers of strains infectious to humans. Moreover, antimicrobial resistance is a great concern in livestock infections, as there is considerable antibiotic overuse, and resistant strains can be transferred to humans. With the number of working antibiotics continuously becoming smaller due to the concomitant spread of resistant strains, alternative approaches, such as anti-virulence, are increasingly being investigated to treat staphylococcal infections. For this, understanding the virulence mechanisms of animal staphylococcal pathogens is crucial. While many virulence factors have similar functions in humans as animals, there are increasingly frequent reports of host-specific virulence factors and mechanisms. Furthermore, we are only beginning to understand virulence mechanisms in animal-specific staphylococcal pathogens. This review gives an overview of animal infections caused by staphylococci and our knowledge about the virulence mechanisms involved.

Cyclopentenylcytosine (CPE-C): In Vitro and In Vivo Evaluation as an Antiviral against Adenoviral Ocular Infections.

Adenoviruses are the major cause of ocular viral infections worldwide. Currently, there is no approved antiviral treatment for these eye infections. Cyclopentenylcytosine (CPE-C) is an antiviral that has demonstrated activity against more than 20 viruses. The goals of the current study were to determine the in vitro and in vivo antiviral activity of CPE-C as well as its ocular toxicity. Antiviral activity was evaluated in vitro using standard plaque reduction assays to determine the 50% effective concentrations (EC50s) and in vivo in the Ad5/NZW rabbit ocular replication model. Ocular toxicity was determined in uninfected rabbit eyes following topical ocular application. The in vitro EC50s for CPE-C ranged from 0.03 to 0.059 µg/mL for nine adenovirus types that commonly infect the eye. Ocular toxicity testing determined CPE-C to be non-irritating or practically non-irritating by Draize scoring. In vivo, 3% CPE-C topically administered 4X or 2X daily for 7 days to adenovirus-infected eyes demonstrated effective antiviral activity compared with the negative control and comparable antiviral activity to the positive control, 0.5% cidofovir, topically administered twice daily for 7 days. We conclude CPE-C was relatively non-toxic to rabbit eyes and demonstrated potent anti-adenoviral activity in vitro and in vivo.

Extensive remodelling of the cell wall during the development of Staphylococcus aureus bacteraemia.

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.

Correction: Associations between healthcare utilization and access and diabetic retinopathy complications using All of Us nationwide survey data.

[This corrects the article DOI: 10.1371/journal.pone.0269231.].

Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia.

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.

A deductive thematic analysis of nurses with job-related problems who completed suicide during the early COVID-19 pandemic: A preliminary report.

BACKGROUND: Prior to the novel coronavirus (COVID-19) pandemic, nurses died by suicide more frequently than the general population. Antecedents prior to death include known job problems, such as disciplinary action; diversion of medications; inability to work due to chronic pain; and physical and mental illness. AIM: The aim of this study was to explore the suicide experience of nurses who died with known job-related problems during the early phase of the COVID-19 pandemic compared to what has been previously described. METHOD: Deductive reflexive thematic analysis was used to analyze narratives of nurses with known job problems who died by suicide from the Centers for Disease Control and Prevention's National Violent Death Reporting System. RESULTS: Forty-three nurses with known job-related problems completed suicide between March and December 2020. Factors associated with death were similar to previous findings with notable exceptions, increased prevalence of suicidal ideation and post-traumatic stress prior to the event. Pandemic-specific issues were noted including reduction in hours, fear of disease transmission, civil unrest, and grief-related trauma. LINKING EVIDENCE TO ACTION: Suicide prevention programs need to address both institutional and individual factors associated with nurse suicide. As previously recommended, transitions into retirement and job loss are vulnerable times warranting psychological support. Further, strategies to reduce the impact of stressors and increase support for nurses are needed at the organizational level. A systems level approach to hardwire coping strategies is indicated pre-licensure and throughout nurses' careers. A new focus on how to process personal and professional grief is warranted. Resources are needed for nurses traumatized by life (rape, childhood trauma) or work-related experiences.

Evaluation of Depression and Anxiety in a Diverse Population With Thyroid Eye Disease Using the Nationwide NIH All of Us Database.

PURPOSE: To evaluate the prevalence of depression and anxiety among individuals with thyroid eye disease (TED) and identify sociodemographic risk factors using the NIH All of Us database. METHODS: Three hundred ninety eight cases with TED were compared with 1,592 controls with demographics matching the 2020 US Census. Primary outcomes were diagnosed depression or anxiety; Patient Health Questionnaire-9 (PHQ-9) scores and General Anxiety Disorder-7 (GAD-7) scores were included as secondary outcomes. We performed multivariable logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between TED and depression and anxiety. RESULTS: Patients with TED were more likely to have depression (OR 2.72, 95% CI 2.08-3.56, p < 0.001) and anxiety (OR 2.82, 95% CI 2.16-3.70, p < 0.001) than controls. In patients with TED, female gender was an independent risk factor for both depression (OR 1.72; 95% CI 1.00-5.07, p = 0.05) and anxiety (OR 2.17, 95% CI 1.25-3.85, p = 0.006). Unemployment (OR 1.72, 95% CI 1.03-2.94, p = 0.04) and lower income (OR 0.88 for income as a continuous variable, 95% CI 0.79-0.99, p = 0.03) were risk factors for anxiety. Risk factors for more severe depression as assessed by PHQ-9 included lower income (OR 0.70, 95% CI 0.57-0.85, p < 0.001), and protective factors included Black race (OR 0.12, 95% CI 0.02-0.45, p = 0.002). Lower income was associated with more severe anxiety as assessed by GAD-7 (OR 0.77, 95% CI 0.64-0.94, p = 0.009). CONCLUSIONS: Patients with TED were more likely to develop depression and anxiety compared with controls. This study highlights the psychosocial impact of TED and associated socioeconomic risk factors.

Reflexive thematic analysis of job-related problems associated with pharmacist suicide, 2003-2019.

BACKGROUND: Few qualitative studies have focused on suicide and specific job-related problems associated with suicide in pharmacists. Greater knowledge of specific work-related stressors amongst pharmacists could inform suicide prevention strategies. OBJECTIVE: To identify job-related stressors associated with pharmacist suicides and compare stressors to those previously reported in physicians and nurses. METHODS: Free-text law enforcement and medical examiner data for pharmacist suicides were extracted from the National Violent Death Registry (NVDRS) for 2003-2019. Reflexive thematic analysis was deployed via a deductive approach utilizing codes and themes found in previous research on nurse and physician suicides. New codes were also identified through inductive coding. RESULTS: A total of 291,872 suicides occurred between 2003 and 2019, of which 392 were pharmacist deaths. Of these, 62 pharmacist suicides were coded with job-related problems. Almost all deductive themes/codes extracted from nurses and physicians were present in pharmacists. Common codes found in the pharmacist dataset that were also found previously in physicians and nurses were: history of mental health, substance use disorder, hopelessness impending or proceeding job loss, and access to lethal weapons and/or drugs. Novel codes were added through inductive content analysis. Codes novel to pharmacists were: verbalized suicidal ideation (SI) or intent, diversion for the purpose of suicide, and the fear of job loss. Disciplinary action at the institutional level was associated with the fear of job loss and cited as the event triggering suicide completion. CONCLUSION: Pharmacists have similar job-related stressors associated with suicide as physicians and nurses. Evaluating the process of disciplinary action is warranted. Future research is indicated to evaluate causal relationship between work-related stressors and mental health outcomes leading to suicide in pharmacists.

Exacerbation of allergic rhinitis by the commensal bacterium Streptococcus salivarius.

Allergic rhinitis (AR)-commonly called hay fever-is a widespread condition that affects the quality of life of millions of people. The pathophysiology of AR remains incompletely understood. In particular, it is unclear whether members of the colonizing nasal microbiota contribute to AR. Here, using 16S ribosomal RNA sequencing, we show that the nasal microbiome of patients with AR (n = 55) shows distinct differences compared with that from healthy individuals (n = 105), including decreased heterogeneity and the increased abundance of one species, Streptococcus salivarius. Using ex vivo and in vivo models of AR, we demonstrate that this commensal bacterium contributes to AR development, promoting inflammatory cytokine release and morphological changes in the nasal epithelium that are characteristic of AR. Our data indicate that this is due to the ability of S. salivarius to adhere to the nasal epithelium under AR conditions. Our study indicates the potential of targeted antibacterial approaches for AR therapy.

Entangled: A mixed method analysis of nurses with mental health problems who die by suicide.

Nurses die by suicide at a higher rate than the general population. Previous studies have observed mental health problems, including substance use, as a prominent antecedent before death. The purpose of this study was to explore the characteristics of nurses who died by suicide documented in the death investigation narratives from the National Violent Death Reporting System from 2003 to 2017 using thematic analysis and natural language processing. One thousand three hundred and fifty-eight subjects met these inclusion criteria. Narratives from 601 subjects were thematically analyzed and 2544 individual narratives were analyzed using natural language processing. The analyses revealed five themes: "mental health treatment," "poor general health and chronic pain," "substance use," "worsening mental health after bereavement," and "repeating a family member's suicide." Mental health/substance use, chronic illness, and chronic pain were seen to coexist in a complex, interdependent manner that appeared to be entangled in the nurses' narratives before death. These findings echo the need for reducing the stigmatization of mental health problems in nursing and removing barriers to help-seeking behaviors as early preventative interventions. Future research is needed to determine if a comprehensive healthcare integration approach to address these entangled problems would reduce suicide vulnerability in nurses and improve their quality of life.

Identification and characterization of the pathogenic potential of phenol-soluble modulin toxins in the mouse commensal Staphylococcus xylosus.

In contrast to the virulent human skin commensal Staphylococcus aureus, which secretes a plethora of toxins, other staphylococci have much reduced virulence. In these species, commonly the only toxins are those of the phenol-soluble modulin (PSM) family. PSMs are species-specific and have only been characterized in a limited number of species. S. xylosus is a usually innocuous commensal on the skin of mice and other mammals. Prompted by reports on the involvement of PSMs in atopic dermatitis (AD) and the isolation of S. xylosus from mice with AD-like symptoms, we here identified and characterized PSMs of S. xylosus with a focus on a potential involvement in AD phenotypes. We found that most clinical S. xylosus strains produce two PSMs, one of the shorter α- and one of the longer ß-type, which were responsible for almost the entire lytic and pro-inflammatory capacities of S. xylosus. Importantly, PSMα of S. xylosus caused lysis and degranulation of mast cells at degrees higher than that of S. aureus δ-toxin, the main PSM previously associated with AD. However, S. xylosus did not produce significant AD symptoms in wild-type mice as opposed to S. aureus, indicating that promotion of AD by S. xylosus likely requires a predisposed host. Our study indicates that non-specific cytolytic potency rather than specific interaction underlies PSM-mediated mast cell degranulation and suggest that the previously reported exceptional potency of δ-toxin of S. aureus is due to its high-level production. Furthermore, they suggest that species that produce cytolytic PSMs, such as S. xylosus, all have the capacity to promote AD, but a high combined level of PSM cytolytic potency is required to cause AD in a non-predisposed host.

Social Determinants of Health Data Availability for Patients with Eye Conditions.

Purpose: To quantify and characterize social determinants of health (SDoH) data coverage using single-center electronic health records (EHRs) and the National Institutes of Health All of Us research program. Design: Retrospective cohort study from June 2014 through June 2021. Participants: Adults 18 years of age or older with a diagnosis of diabetic retinopathy, glaucoma, cataracts, or age-related macular degeneration. Methods: For All of Us, research participants completed online survey forms as part of a nationwide prospective cohort study. In local EHRs, patients were selected based on diagnosis codes. Main Outcome Measures: Social determinants of health data coverage, characterized by the proportion of each disease cohort with available data regarding demographics and socioeconomic factors. Results: In All of Us, we identified 23 806 unique adult patients, of whom 2246 had a diagnosis of diabetic retinopathy, 13 448 had a diagnosis of glaucoma, 6634 had a diagnosis of cataracts, and 1478 had a diagnosis of age-related macular degeneration. Survey completion rates were high (99.5%-100%) across all cohorts for demographic information, overall health, income, education, and lifestyle. However, health care access (12.7%-29.4%), housing (0.7%-1.1%), social isolation (0.2%-0.3%), and food security (0-0.1%) showed significantly lower response rates. In local EHRs, we identified 80 548 adult patients, of whom 6616 had a diagnosis of diabetic retinopathy, 26 793 had a diagnosis of glaucoma, 40 427 had a diagnosis of cataracts, and 6712 had a diagnosis of age-related macular degeneration. High data coverage was found across all cohorts for variables related to tobacco use (82.84%-89.07%), alcohol use (77.45%-83.66%), and intravenous drug use (84.76%-93.14%). However, low data coverage (< 50% completion) was found for all other variables, including education, finances, social isolation, stress, physical activity, food insecurity, and transportation. We used chi-square testing to assess whether the data coverage varied across different disease cohorts and found that all fields varied significantly (P < 0.001). Conclusions: The limited and highly variable data coverage in both local EHRs and All of Us highlights the need for researchers and providers to develop SDoH data collection strategies and to assemble complete datasets.

Novel Association between Opioid Use and Increased Risk of Retinal Vein Occlusion Using the National Institutes of Health All of Us Research Program.

Purpose: To assess for risk factors for retinal vein occlusion (RVO) among participants in the National Institutes of Health All of Us database, particularly social risk factors that have not been well studied, including substance use. Design: Retrospective, case-control study. Participants: Data were extracted for 380 adult participants with branch retinal vein occlusion (BRVO), 311 adult participants with central retinal vein occlusion (CRVO), and 1520 controls sampled among 311 640 adult participants in the All of Us database. Methods: Data were extracted regarding demographics, comorbidities, income, housing, insurance, and substance use. Opioid use was defined by relevant diagnosis and prescription codes, with prescription use > 30 days. Controls were sampled at a 4:1 control to case ratio from a pool of individuals aged > 18 years without a diagnosis of RVO and proportionally matched to the demographic distribution of the 2019 U.S. census. Multivariable logistic regression identified medical and social determinants significantly associated with BRVO or CRVO. Statistical significance was defined as P < 0.05. Main Outcome Measure: Development of BRVO or CRVO based on diagnosis codes. Results: Among patients with BRVO, the mean (standard deviation) age was 70.1 (10.5) years. The majority (53.7%) were female. Cases were diverse; 23.7% identified as Black, and 18.4% identified as Hispanic or Latino. Medical risk factors including glaucoma (odds ratio [OR], 3.29; 95% confidence interval [CI], 2.22-4.90; P < 0.001), hypertension (OR, 2.15; 95% CI, 1.49-3.11; P < 0.001), and diabetes mellitus (OR, 1.68; 95% CI, 1.18-2.38; P = 0.004) were re-demonstrated to be associated with BRVO. Black race (OR, 2.64; 95% CI, 1.22-6.05; P = 0.017) was found to be associated with increased risk of BRVO. Past marijuana use (OR, 0.68; 95% CI, 0.50-0.92; P = 0.013) was associated with decreased risk of BRVO; however, opioid use (OR, 1.98; 95% CI, 1.41-2.78; P < 0.001) was associated with a significantly increased risk of BRVO. Similar associations were found for CRVO. Conclusions: Understanding RVO risk factors is important for primary prevention and improvement in visual outcomes. This study capitalizes on the diversity and scale of a novel nationwide database to elucidate a previously uncharacterized association between RVO and opioid use.

Thematic analysis and natural language processing of job-related problems prior to physician suicide in 2003-2018.

INTRODUCTION: Although previous studies have consistently demonstrated that physicians are more likely than non-physicians to experience work-related stressors prior to suicide, the specific nature of these stressors remains unknown. The current study aimed to better characterize job-related problems prior to physician suicide. METHODS: The study utilized a mixed methods approach combining thematic analysis and natural language processing to develop themes representing death investigation narratives of 200 physician suicides with implicated job problems in the National Violent Death Reporting System database between 2003 and 2018. RESULTS: Through thematic analysis, six overarching themes were identified: incapacity to work due to deterioration of physical health, substance use jeopardizing employment, interaction between mental health and work-related issues, relationship conflict affecting work, legal problems leading to work-related stress, and increased financial stress. Natural language processing analysis confirmed five of these themes and elucidated important subthemes. CONCLUSIONS: This is the first known study that integrated thematic analysis and natural language processing to characterize work-related stressors preceding physician suicide. The findings highlight the importance of bolstering systemic support for physicians experiencing job problems associated with their physical and mental health, substance use, relationships, legal matters, and finances in suicide prevention efforts.

Associations between healthcare utilization and access and diabetic retinopathy complications using All of Us nationwide survey data.

PURPOSE: Inadequacies in healthcare access and utilization substantially impact outcomes for diabetic patients. The All of Us database offers extensive survey data pertaining to social determinants that is not routinely available in electronic health records. This study assesses whether social determinants were associated with an increased risk of developing proliferative diabetic retinopathy or related complications (e.g. related diagnoses or procedures). METHODS: We identified 729 adult participants in the National Institutes of Health All of Us Research Program data repository with diabetic retinopathy (DR) who answered survey questions pertaining to healthcare access and utilization. Electronic health record data regarding co-morbidities, laboratory values, and procedures were extracted. Multivariable logistic regression with bi-directional stepwise variable selection was performed from a wide range of predictors. Statistical significance was defined as p<0.05. RESULTS: The mean (standard deviation) age of our cohort was 64.9 (11.4) years. 15.2% identified as Hispanic or Latino, 20.4% identified as Black, 60.6% identified as White, and 19.3% identified as Other. 10-20% of patients endorsed several reasons for avoiding or delaying care, including financial concerns and lack of access to transportation. Additional significant social determinants included race and religion discordance between healthcare provider and patient (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02-1.41, p = 0.03) and caregiver responsibilities toward others (OR 3.14, 95% CI 1.01-9.50, p = 0.04). CONCLUSIONS: Nationwide data demonstrate substantial barriers to healthcare access among DR patients. In addition to financial and social determinants, race and religion discordance between providers and patients may increase the likelihood of PDR and related complications.

Longitudinal analysis of suicides among pharmacists during 2003-2018.

BACKGROUND: Suicide is one of the leading causes of death worldwide, and estimates of suicide among health professionals are higher than the general population. High rates of suicide among physicians and nurses have been described previously, but there is a lack of data for suicides completed by pharmacists. OBJECTIVE: The purpose of this study was to quantify the incidence, means, and characteristics of pharmacist suicides in the United States. METHODS: Data were obtained from the Centers for Disease Control and Prevention's National Violent Death Reporting System (NVDRS) for the years 2003-2018. The dataset contained all suicides, coded by occupation, reported by medical examiners and law enforcement from 39 states and Washington DC and Puerto Rico. Suicide characteristics were compared between pharmacists and nonpharmacists. Age-adjusted rates were calculated for 2004, 2009, and 2014. RESULTS: During 2003-2018, the NVDRS contained 316 pharmacist suicides compared with 213,146 nonpharmacist suicides. The age-adjusted rates per 100,000 people were 19.6, 20.1, and 18.2 for 2004, 2009 and 2014, respectively. The most common means of suicide was firearm. Associated factors for suicide included job problems, current mental illness treatment, and suicide note. CONCLUSION: Suicide rates among pharmacists are higher than the general population. Future research is needed to evaluate the context of job-related problems to mitigate risk. Encouraging help-seeking behaviors to identify and treat pharmacist depression is warranted.

Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides.

Previously either regarded as insignificant or feared as potential sources of infection, the bacteria living on our skin are increasingly recognized for their role in benefitting human health. Skin commensals modulate mucosal immune defenses and directly interfere with pathogens; however, their contribution to the skin's physical integrity is less understood. Here, we show that the abundant skin commensal Staphylococcus epidermidis contributes to skin barrier integrity. S. epidermidis secretes a sphingomyelinase that acquires essential nutrients for the bacteria and assists the host in producing ceramides, the main constituent of the epithelial barrier that averts skin dehydration and aging. In mouse models, S. epidermidis significantly increases skin ceramide levels and prevents water loss of damaged skin in a fashion entirely dependent on its sphingomyelinase. Our findings reveal a symbiotic mechanism that demonstrates an important role of the skin microbiota in the maintenance of the skin's protective barrier.