Search

Older adults aged 70 and older who drive have higher crash death rates per mile driven compared to middle aged (35-54 years) adults who drive in the US. Prior studies have found that depression and or antidepressant medication use in older adults are associated with an increase in the vehicular crash rate. Using data from the prospective multi-site AAA Longitudinal Research on Aging Drivers Study, this analysis examined the independent and interdependent associations of self-reported depression and antidepressant use with driving behaviors that can increase motor vehicle crash risk such as hard braking, speeding, and night-time driving in adults over age 65. Of the 2951 participants, 6.4% reported having depression and 21.9% were on an antidepressant medication. Correcting for age, race, gender, and education level, participants on an antidepressant had increased hard braking events (1.22 [1.10-1.34]) but self-reported depression alone was not associated with changes in driving behaviors.

BACKGROUND: Dietary supplement (DS) use is common and increasing among older adults, though much data available on use frequencies are from surveys and performed cross-sectionally. This paper sought to assess the frequency and pattern of dietary supplement use among older adults over time. METHODS: A secondary analysis of data from the AAA LongROAD study, a longitudinal prospective cohort study of older adult drivers, using data from baseline and the first two years of follow up included a total of 2990 drivers aged 65-79 years recruited at five study sites across the US from July 2015 to March 2017. Participants underwent baseline and annual evaluations, which included a brown bag medication review. DS were identified and categorized according to type and key components. Prevalence and pattern of DS use over time and relationship to demographics were measured with frequency and Chi squared analyses. RESULTS: 84% of participants took at least one dietary supplement during the 2-year study period, and 55% of participants continually reported use. DS accounted for approximately 30% of the total pharmacologic-pill burden in all years. Participants who were White non-Hispanic, female, 75-79 years of age at baseline, and on more non-supplement medications took significantly more dietary supplements (P

The coronavirus disease 2019 (COVID-19) pandemic significantly impacted pharmacy students education and well-being. The primary aim of this study was to evaluate the effects of the pandemic on students perceived stress by comparing third- and fourth-year students from the pre-pandemic Class of 2019 with mid-pandemic Class of 2021 at two public institutions. Secondary aims were to evaluate the pandemic effects on students academic and professional development skills and practice readiness. The Perceived Stress Scale (PSS) and the Brief Coping Orientation to Problems Experienced (COPE) scale were used to measure student well-being. Students self-rated problem-solving, time management, and study skills were used to measure their academic and professional development; practice readiness was measured using students self-rated confidence levels. PSS scores were significantly higher in mid-pandemic than pre-pandemic students, and the Brief COPE avoidant coping subscale differed between pre-pandemic and mid-pandemic students. No differences were found in any academic and professional development skills between the pre- and mid-pandemic students, and there were significant improvements in student confidence levels for practice readiness among the mid-pandemic students. In conclusion, the pandemic appeared to affect students stress and avoidant coping mechanism but had variable effects on academic and professional development and practice readiness.

Schizophrenia (SZ) is a serious mental illness and neuropsychiatric brain disorder with behavioral symptoms that include hallucinations, delusions, disorganized behavior, and cognitive impairment. Regulation of such behaviors requires utilization of neurotransmitters released to mediate cell-cell communication which are essential to brain functions in health and disease. We hypothesized that SZ may involve dysregulation of neurotransmitters secreted from neurons. To gain an understanding of human SZ, induced neurons (iNs) were derived from SZ patients and healthy control subjects to investigate peptide neurotransmitters, known as neuropeptides, which represent the major class of transmitters. The iNs were subjected to depolarization by high KCl in the culture medium and the secreted neuropeptides were identified and quantitated by nano-LC-MS/MS tandem mass spectrometry. Several neuropeptides were identified from schizophrenia patient-derived neurons, including chromogranin B (CHGB), neurotensin, and natriuretic peptide. Focusing on the main secreted CHGB neuropeptides, results revealed differences in SZ iNs compared to control iN neurons. Lower numbers of distinct CHGB peptides were found in the SZ secretion media compared to controls. Mapping of the peptides to the CHGB precursor revealed peptides unique to either SZ or control, and peptides common to both conditions. Also, the iNs secreted neuropeptides under both KCl and basal (no KCl) conditions. These findings are consistent with reports that chromogranin B levels are reduced in the cerebrospinal fluid and specific brain regions of SZ patients. These findings suggest that iNs derived from SZ patients can model the decreased CHGB neuropeptides observed in human SZ.

INTRODUCTION: Pharmacists focusing on psychotropic medication management and practicing across a wide variety of healthcare settings have significantly improved patient-level outcomes. The Systematic Literature Review Committee of the American Association of Psychiatric Pharmacists was tasked with compiling a comprehensive database of primary literature highlighting the impact of psychiatric pharmacists on patient-level outcomes. METHODS: A systematic search of literature published from January 1, 1961, to December 31, 2022, was conducted using PubMed and search terms based on a prior American Association of Psychiatric Pharmacists literature review. Publications describing patient-level outcome results associated with pharmacist provision of care in psychiatric/neurologic settings and/or in relation to psychotropic medications were included. The search excluded articles for which there was no pharmacist intervention, no psychiatric disorder treatment, no clinical outcomes, no original research, no access to full text, and/or no English-language version. RESULTS: A total of 4270 articles were reviewed via PubMed, with 4072 articles excluded based on title, abstract, and/or full text in the initial pass and 208 articles selected for inclusion. A secondary full-text review excluded 11 additional articles, and 5 excluded articles were ultimately included based on a secondary review, for a final total of 202 articles meeting the inclusion criteria. A comprehensive database of these articles was compiled, including details on their study designs and outcomes. DISCUSSION: The articles included in the final database had a wide range of heterogeneity. While the overall impact of psychiatric pharmacists was positive, the study variability highlights the need for future publications to have more consistent, standardized outcomes with stronger study designs.

INTRODUCTION: Transgender and nonbinary (TGNB) individuals are highly stigmatized members of society and are significantly at higher risk of having mood or anxiety-related disorders compared to non-TGNB individuals. METHODS: In this retrospective cohort study, antidepressant prescribing data were collected from TGNB adults diagnosed with gender dysphoria (GD) and mood or anxiety-related disorder between January 2005 and October 2021. The primary outcome was to compare the number of active outpatient antidepressant prescriptions at the time of GD diagnosis between gender identities. The secondary outcomes were to compare antidepressant class utilization between gender identities as well as the prevalence of concurrent mood or anxiety-related disorder diagnoses between gender identities. RESULTS: Of 131 patients who met inclusion criteria, there was no significant difference in number of active antidepressant prescriptions between gender identities at the time of the GD diagnosis (p = .357). However, transgender females were prescribed bupropion at significantly higher rates than other gender identities (p = .046). Approximately 38% of patients did not have an active antidepressant prescription at the time of GD diagnosis despite concurrent mood or anxiety-related diagnoses. The prevalence of generalized anxiety disorder was significantly greater among transgender males (p = .044). DISCUSSION: Although the number of active antidepressant prescriptions between gender identities were similar in this study, we found 38% of patients were not prescribed any antidepressants at time of GD and mood or anxiety-related disorders. This serendipitous finding elucidates a potential gap in mental health care among transgender adults.

Targeted intracellular delivery via receptor-mediated endocytosis requires the delivered cargo to escape the endosome to prevent lysosomal degradation. This can in principle be achieved by membrane lysis tightly restricted to endosomal membranes upon internalization to avoid general membrane insertion and lysis. Here, we describe the design of small monomeric proteins with buried histidine containing pH-responsive hydrogen bond networks and membrane permeating amphipathic helices. Of the 30 designs that were experimentally tested, all expressed in Escherichia coli, 13 were monomeric with the expected secondary structure, and 4 designs disrupted artificial liposomes in a pH-dependent manner. Mutational analysis showed that the buried histidine hydrogen bond networks mediate pH-responsiveness and control lysis of model membranes within a very narrow range of pH (6.0-5.5) with almost no lysis occurring at neutral pH. These tightly controlled lytic monomers could help mediate endosomal escape in designed targeted delivery platforms.

Objective. The purpose of the study was to compare suicidal ideation among medical and pharmacy students and characterize related symptoms.Methods. The authors conducted a cross-sectional, retrospective study to compare suicidal ideation among medical and pharmacy students at a single public university during 2009 to 2020. Respondents' voluntary and anonymous responses to the Interactive Screening Program (ISP) Stress and Depression Questionnaire are reported.Results. The authors analyzed responses from 619 medical and 214 pharmacy students collected over 11 academic years. There was no significant difference between medical and pharmacy students who endorsed suicidal ideation (13.5% vs 17.3%, respectively). The Patient Health Questionnaire-9 (PHQ-9) scores were significantly different between medical and pharmacy students, with more pharmacy students reporting moderate to severe depression (24.3% for medical vs 35.1% for pharmacy). Compared to medical students, more pharmacy students also endorsed anhedonia, a reduced capacity for pleasure (13.4% vs 24.3%, respectively), sleep problems (29.6% vs 42.6%, respectively), and fatigue (46% vs 64.4%, respectively). Pharmacy students also reported more intense affective states such as "feeling your life is too stressful" and "feeling intensely anxious or having anxiety attacks." Relationships and physical/mental health/substance abuse were common themes that emerged from the qualitative data.Conclusion. While there was no significant difference in suicidal ideation between pharmacy and medical students, the prevalence is alarming compared to the general population. More pharmacy students endorsed symptoms of depression and intense affective states that could impair functioning. Future studies may focus on mitigation strategies for suicidal ideation among health professions students.

Faculty workload is difficult to delineate and quantify equitably because of the various factors and diverse roles that define faculty positions. This is especially true in health professions education, including pharmacy. Nonetheless, ensuring fair and transparent distribution of faculty workload is necessary for equity and engagement of the faculty workforce. While it is impossible to develop a uniform policy for all faculty, there can be a guide for how workload is developed and measured, especially for promotion or awarding of tenure, focusing on equity and transparency. Developing clear definitions of workload, setting mutually agreed expectations, and sharing transparent workload assignments and distribution within the institution may be needed. It is imperative to discuss an optimal policy for equitable and transparent workload in each institution and in academic pharmacy as a whole; a lack of this effort can create undue hardship for faculty, decrease productivity, potentially worsen faculty morale, and ultimately impair faculty retention.

Objective. The objective of this pilot study was to evaluate the attitudes and self-efficacy of advanced pharmacy practice experience (APPE) conference leaders after completing the Well-being Promotion (WelPro) training program developed at the University of California, San Francisco (UCSF) School of Pharmacy.Methods. The WelPro training program was developed to equip participants with the knowledge and tools to assist APPE students in distress and promote student wellness. After completing the WelPro training program, a 20-item survey was administered to 10 conference leaders via a web-based survey tool to assess their attitudes about burnout and self-efficacy in assisting students in distress. Descriptive statistics were used to characterize attitudes and self-efficacy.Results. Ten conference leaders participated in the training program. Of these, nine reported experiencing burnout in their careers, and all believed burnout within the pharmacy profession could be avoided. After the WelPro training program, confidence levels of the conference leaders significantly improved in the following areas: identification of students in distress, identification of resources for students, and recognition of when and how to refer students in distress.Conclusion. Increased self-efficacy of conference leaders to identify and assist students in distress could be translated into their improved ability to support students' overall well-being. The WelPro training program can serve as a model for similar wellness training programs that directors and preceptors in experiential education can implement at their institutions.

Objective. To assess in pharmacy academicians the six domains of worklife (community, control, fairness, reward, workload, values) that have been associated with burnout and poor job satisfaction.Methods. We aimed to assess the Areas of Worklife Survey (AWS) among a sample of pharmacy academicians attending a national meeting to evaluate personal, environmental, or workplace factors that may influence the worklife environment. Data were analyzed using SPSS, descriptive statistics were identified, and Kruskal-Wallis and Pearson correlations were performed.Results. The participant response rate was 40% (n=49/121 attendees). Eighty-eight percent of participants reported working more than 40 hours per week. Mean AWS scores ranged from 2.7 to 3.9 (whereby 1 indicated a strong mismatch between person and work environment and 5 indicated a strong match). The workload and fairness domains had the lowest reported scores, whereas control had the highest. Higher mean scores were reported for control and reward in those with a mentor and for fairness in those having a hobby.Conclusion. Participants gave the lowest ratings to two worklife areas, workload and fairness. Developing targeted interventions, such as in mentorship, hobbies, and transparency in the work setting, may be important for preventing burnout in pharmacy academicians. Further studies in a larger population may help to determine factors associated with the areas of worklife that received low ratings.

PurposeTo describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions.MethodsIn May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods.Results236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews.ConclusionVirtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews.

BackgroundSuicide 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.ObjectiveThe purpose of this study was to quantify the incidence, means, and characteristics of pharmacist suicides in the United States.MethodsData 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.ResultsDuring 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.ConclusionSuicide 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.

IntroductionThe American Association of Psychiatric Pharmacists (AAPP) used multiple modalities to develop and refine 28 attribute statements to describe a best practice model for outpatient psychiatric pharmacists. Before addressing implementation, assessment, and field testing, it was necessary to finalize and confirm the statements and their supporting narratives among stakeholders. The objective of this project was to confirm the attribute statements and supporting justifications for a best practice model for outpatient psychiatric pharmacists providing direct patient care.MethodsThe 4 phases that resulted in the 28 attribute statements and supporting narratives have been described and published elsewhere. As part of phase 5, the confirmation survey was distributed to pharmacists and resident members of AAPP in November 2021 for 3 weeks.ResultsThe survey respondents (n = 74; 6.1%) were licensed pharmacists for an average of 15.6 years (SD = 12.0) and had been practicing as psychiatric pharmacists for an average of 11.3 years (SD = 10.4). Slightly more than half (54.2%) of the respondents reported practicing in the outpatient setting and three-fourths (74.3%) were Board Certified Psychiatric Pharmacists. For each of the 28 statements, more than 90% of respondents either agreed or agreed with minimal reservations.DiscussionGiven the high degree of agreement on the proposed practice model statements, they will be used as the basis for the outpatient psychiatric pharmacist best practice model. Next steps in developing this model include establishing implementation guidance, determining appropriate metrics for evaluation of these statements in practice, and establishing appropriate field-testing methods.

IntroductionA 2019 survey identified significant variability of practice characteristics among outpatient psychiatric pharmacists (OPPs). No published model establishes which attributes constitute best practice for OPPs. By developing a consensus for best practice model attributes, OPPs can work toward consistent, effective patient care. This project aimed to develop attribute statements for a best practice model for OPPs providing direct patient care.MethodsBoard Certified Psychiatric Pharmacists and American Association of Psychiatric Pharmacists (AAPP) members were questioned using a 5-phase (P1-P5) survey and summit approach. The phases were: P1, broad ideation survey; P2, 10-person summit to develop draft statements; P3, survey of the draft statements for acceptance; P4, summit to resolve review feedback; and P5, survey of AAPP membership to confirm the finalized statements.ResultsP1 survey results generated a list of 143 possible attributes that informed the P2 summit, which were refined to 28 statements. P3 survey results confirmed at least 70% agreement with each statement. The P4 summit evaluated all P3 survey results and made significant modifications to 4 statements. Informal feedback was sought with other stakeholders, and supporting narratives and references were developed to provide clarity regarding the intent of each statement. Finalized statements and supporting narratives were confirmed in the P5 survey.DiscussionThe 28 attribute statements were developed over 18 months by gathering input and consensus through multiple modalities, including 3 surveys, 2 summit meetings, and numerous informal feedback requests. The agreement on the attribute statements was consistently high across all phases. The final attribute statements are presented elsewhere in this issue.

Objective: The objective of this study was to examine (1) the difference in perceived stress in first-year pharmacy students before and during the COVID-19 pandemic and (2) the difference in perceived stress among pharmacy students working different numbers of hours. Methods: Perceived Stress Scale (PSS), via an electronic survey, was administered throughout 2016-2021 using Qualtrics. End-of-year PSS scores were compared between the pre-pandemic group (2016-2018) and mid-pandemic group (2019-2021) using independent t-test and ANCOVA. All analyses were conducted using IBM SPSS Statistic Version 28.0. Results: A total of 209 first-year pharmacy students participated (response rate of 88%). No significant difference in mean PSS score was detected in the mid-pandemic cohort when compared to pre-pandemic. The mean PSS score was greater in those who worked greater than 10 h weekly compared to those who worked less. Those who did not work had an even greater mean PSS score than those who worked. Conclusions: No significant difference was observed in perceived stress between the pre-pandemic and mid-pandemic cohorts, and an increased perceived stress score was observed in pharmacy students who did not work in comparison to students who worked 1-9 h and 10-29 h.

IntroductionA comprehensive review of psychiatric pharmacy practice has never been performed in the United States. As psychiatric pharmacists become more involved in mental illness treatment, determining the current state of practice is important to help advance the specialty. The Professional Affairs Committee of the College of Psychiatric and Neurologic Pharmacists (CPNP) was charged with performing this review to define current psychiatric pharmacy practice.MethodsAn electronic survey was sent to all pharmacist members of CPNP and all nonmember Board Certified Psychiatric Pharmacists (BCPPs) in the United States in late summer 2019. The survey consisted of 36 questions across multiple domains to obtain information about respondents' education and training background, practice setting and type, and information about prescriptive authority and other areas. An initial e-mail invitation was sent along with 2 reminder e-mails over the subsequent 2 weeks.ResultsA total of 334 of 1015 pharmacists completed the survey (32.9%). Responders completed a postgraduate residency 77.8% of the time, and 88.3% were BCPP. Practice settings were split evenly between inpatient and outpatient practices or a combination of the 2. Among respondents, 46.5% reported having prescriptive authority as part of their practice, and 41.3% reported treating nonpsychiatric as well as psychiatric illnesses. Prescriptive authority was more likely in outpatient practices and in those treating nonpsychiatric illnesses.DiscussionThe current practice of psychiatric pharmacy is incredibly varied in terms of practice setting, activities performed, and services provided. Further exploration is needed to help determine the optimal role of psychiatric pharmacists.

Pharmacist-psychiatrist collaborative clinic models in specialty mental health clinics are limited, and there has been only 1 report of a clinic focused on adult attention-deficit hyperactivity disorder (ADHD). In this article, we describe the successful implementation of a pharmacist-psychiatrist collaborative practice agreement in an adult ADHD clinic at an academic medical center. Adult patients diagnosed with ADHD after a comprehensive assessment, including a full neuropsychological evaluation, were enrolled in the collaborative treatment clinic. The collaboration was a partnership between a psychiatry department and a school of pharmacy at a public university. We report the details of 58 patients and 774 patient encounters at the collaborative pharmacist-psychiatrist practice from March 2015 through June 2018. The visits were billed using traditional medical billing codes for follow-up visits. Pharmacist practice opportunities included psychiatric evaluation, medication management, counseling, and referral to auxiliary services. Challenges to the clinic's success included limited pharmacist time, prescriptive authority, and reimbursement for services from payors. A collaborative practice model targeted at adult ADHD patients may be a unique clinic setting for psychiatric pharmacists.

The objective of this study was to investigate the safety of repeated parenteral ketamine for depression. An electronic survey inquiring about the frequency of adverse events was distributed to providers of parenteral ketamine for depression. In addition, the investigators conducted a search of published studies describing six or more repeated parenteral ketamine treatments administered to individuals for depression, and extracted reported adverse events. The survey was sent to 69 providers, of which 36 responded (52% response rate); after eliminating those that were incomplete, 27 were included in the analysis. The providers in the analysis collectively reported treating 6630 patients with parenteral ketamine for depression, one-third of whom received more than 10 treatments. Only 0.7% of patients experienced an adverse effect that required discontinuation of ketamine. Psychological distress during the treatment was the most frequent cause. Other adverse events were extremely rare (such as bladder dysfunction (0.1%), cognitive decline (0.03%) and psychotic symptoms (0.03%)). Among the 20 published reports of repeated parenteral ketamine treatments, rates of significant adverse events resulting in discontinuation were low (1.2%). The rate of adverse effects reported in the survey and the published literature is low, and suggests that long-term treatment of depression with ketamine is reasonably safe.

Proton-pump inhibitors, PPIs, are considered effective therapy for stomach acid suppression due to their irreversible inhibition of the hydrogen/potassium pump in the gastric parietal cells. They are widely prescribed and are considered safe for over-the-counter use. Recent studies have shown an association between PPI use and Alzheimer dementia, while others have disputed that connection. We analyzed over ten million United States Food and Drug Administration Adverse Event Reporting System reports, including over forty thousand reports containing PPIs, and provided evidence of increased propensity for memory impairment among PPI reports when compared to histamine-2 receptor antagonist control group. Furthermore, we found significant associations of PPI use with a wide range of neurological adverse reactions including, migraine, several peripheral neuropathies, and visual and auditory neurosensory abnormalities.

INTRODUCTION:The scope of pharmacy practice has evolved over the last few decades to focus on the optimization of medication therapy. Despite this positive impact, the lack of reimbursement remains a significant barrier to the implementation of innovative pharmacist practice models. SUMMARY:We describe the successful development, implementation and outcomes of three types of pharmacist collaborative care models: (1) a pharmacist with physician oversight, (2) pharmacist-interprofessional teams and (3) physician-pharmacist teams. The outcome measurement of these pharmacist care models varied from the design phase to patient volume measurement and to comprehensive quality dashboards. All of these practice models have been successfully funded by affiliated health systems or grants. CONCLUSIONS:The expansion of pharmacist services delivered by clinical faculty has several benefits to affiliated health systems: (1) significant improvements in patient care quality, (2) access to experts in specialty areas, and (3) the dissemination of outcomes with national and international recognition, increasing the visibility of the health system.

ObjectiveThis study explored nurse suicide in the United States.MethodsCharacteristics were compared between occupations using 2014 National Violent Death Reporting System data.ResultsFemale nurse suicides were significantly higher (11.97/100,000) than in the female population (7.58/100,000) (p

The ability of naturally occurring proteins to change conformation in response to environmental changes is critical to biological function. Although there have been advances in the de novo design of stable proteins with a single, deep free-energy minimum, the design of conformational switches remains challenging. We present a general strategy to design pH-responsive protein conformational changes by precisely preorganizing histidine residues in buried hydrogen-bond networks. We design homotrimers and heterodimers that are stable above pH 6.5 but undergo cooperative, large-scale conformational changes when the pH is lowered and electrostatic and steric repulsion builds up as the network histidine residues become protonated. The transition pH and cooperativity can be controlled through the number of histidine-containing networks and the strength of the surrounding hydrophobic interactions. Upon disassembly, the designed proteins disrupt lipid membranes both in vitro and after being endocytosed in mammalian cells. Our results demonstrate that environmentally triggered conformational changes can now be programmed by de novo protein design.

Long COVID occurs in a small but important minority of patients following COVID-19, reducing quality of life and contributing to healthcare burden. Although research into underlying mechanisms is evolving, immunity is understudied. SARS-CoV-2-specific T cell responses are of key importance for viral clearance and COVID-19 recovery. However, in long COVID, the establishment and persistence of SARS-CoV-2-specific T cells are far from clear, especially beyond 12 mo postinfection and postvaccination. We defined ex vivo antigen-specific B cell and T cell responses and their T cell receptors (TCR) repertoires across 2 y postinfection in people with long COVID. Using 13 SARS-CoV-2 peptide-HLA tetramers, spanning 11 HLA allotypes, as well as spike and nucleocapsid probes, we tracked SARS-CoV-2-specific CD8+ and CD4+ T cells and B-cells in individuals from their first SARS-CoV-2 infection through primary vaccination over 24 mo. The frequencies of ORF1a-and nucleocapsid-specific T cells and B cells remained stable over 24 mo. Spike-specific CD8+ and CD4+ T cells and B cells were boosted by SARS-CoV-2 vaccination, indicating immunization, in fully recovered and people with long COVID, altered the immunodominance hierarchy of SARS-CoV-2 T cell epitopes. Meanwhile, influenza-specific CD8+ T cells were stable across 24 mo, suggesting no bystander-activation. Compared to total T cell populations, SARS-CoV-2-specific T cells were enriched for central memory phenotype, although the proportion of central memory T cells decreased following acute illness. Importantly, TCR repertoire composition was maintained throughout long COVID, including postvaccination, to 2 y postinfection. Overall, we defined ex vivo SARS-CoV-2-specific B cells and T cells to understand primary and recall responses, providing key insights into antigen-specific responses in people with long COVID. [ABSTRACT FROM AUTHOR]

Whole virion inactivated vaccine CoronaVac (C) and Spike (S) mRNA BNT162b2 (B) vaccines differ greatly in their ability to elicit neutralizing antibodies but have somewhat comparable effectiveness in protecting from severe COVID-19. We conducted further analyses for a randomized trial (Cobovax study, NCT05057169) of third dose homologous and heterologous booster vaccination, i.e. four interventions CC-C, CC-B, BB-C and BB-B. Here, we assess vaccine immunogenicity beyond neutralizing function, including S and non-S antibodies with Fc receptor (FcR) binding, antibody avidity and T cell specificity to 6 months post-vaccination. Ancestral and Omicron S-specific IgG and FcR binding are significantly higher by BNT162b2 booster than CoronaVac, regardless of first doses. Nucleocapsid (N) antibodies are only increased in homologous boosted CoronaVac participants (CC-C). CoronaVac primed participants have lower baseline S-specific CD4+ IFNγ+ cells, but are significantly increased by either CoronaVac or BNT162b2 boosters. Priming vaccine content defined T cell peptide specificity preference, with S-specific T cells dominating B primed groups and non-S structural peptides contributing more in C primed groups, regardless of booster type. S-specific CD4+ T cell responses, N-specific antibodies, and antibody effector functions via Fc receptor binding may contribute to protection and compensate for less potent neutralizing responses in CoronaVac recipients.Here the authors provide exploratory analyses of a clinical trial evaluating immunogenicity of inactivated and mRNA SARS-CoV-2 vaccines, and show that CoronaVac primed groups have disparate T cell responses and nucleocapsid specific antibodies compared to BNT162b2 that may protect in the absence of robust neutralizing antibody responses. [ABSTRACT FROM AUTHOR]

ObjectiveBeing a healthcare professional can be a uniquely rewarding calling. However, the demands of training and practice can lead to chronic distress and serious psychological, interpersonal, and personal health burdens. Although higher burnout, depression, and suicide rates have been reported in healthcare professionals, only a minority receive treatment. Concerns regarding confidentiality, stigma, potential career implications, and cost and time constraints are cited as key barriers. Web-based and mobile applications have been shown to mitigate stress, burnout, depression, and suicidal ideation among several populations and may circumvent these barriers. Here, we reviewed published data on such resources and selected a small sample that readily can be used by healthcare providers.MethodsWe searched PubMed for articles evaluating stress, burnout, depression, and suicide prevention or intervention for healthcare students or providers and identified five categories of programs with significant effectiveness: Cognitive Behavioral Therapy (online), meditation, mindfulness, breathing, and relaxation techniques. Using these categories, we searched for Web-based (through Google and beacon.anu.edu.au -a wellness resource website) and mobile applications (Apple and mobile. va.gov/appstore ) for stress, burnout, depression, and suicide prevention and identified 36 resources to further evaluate based on relevance, applicability to healthcare providers (confidentiality, convenience, and cost), and the strength of findings supporting their effectiveness.ResultsWe selected seven resources under five general categories designed to foster wellness and reduce burnout, depression, and suicide risk among healthcare workers: breathing (Breath2Relax), meditation (Headspace, guided meditation audios), Web-based Cognitive Behavioral Therapy (MoodGYM, Stress Gym), and suicide prevention apps (Stay Alive, Virtual Hope Box).ConclusionsThis list serves as a starting point to enhance coping with stressors as a healthcare student or professional in order to help mitigate burnout, depression, and suicidality. The next steps include adapting digital health strategies to specifically fit the needs of healthcare providers, with the ultimate goal of facilitating in-person care when warranted.

Currently approved monoamine modulating antidepressant and anxiolytic pharmaceutics fail in over one third of patients due to delayed and variable therapeutic effect, adverse reactions preceding the therapeutic action, and adherence issues. Even with adequate adherence to the regimen and tolerability, one third of the patients do not respond to any class of antidepressants. There is a strong correlation between treatment resistant depression and increase in inflammatory cytokines in plasma and cerebrospinal fluid. Furthermore, epidemiological studies suggest that depression and anxiety are commonly comorbid with pain and inflammation. While a link between pain, inflammation and depression has been suggested it remains unclear which anti-inflammatory treatment may be beneficial to patients with depression and anxiety due to pain. Here, we analyzed 430,783 FDA adverse effect reports of patients treated for pain to identify potential antidepressant and anxiolytic effects of various anti-inflammatory medications. Patients treated for depression or patients taking any known antidepressants were excluded. The odds ratio analysis of 139,072 NSAID reports revealed that ketoprofen was associated with decreased reports of depression by a factor of 2.32 (OR 0.43 and 95% Confidence Interval [0.31, 0.59]) and decreased reports of anxiety by a factor of 2.86 (OR 0.35 [0.22, 0.56]), diclofenac with decreased depression reports by a factor of 2.22 (OR 0.45 [0.40, 0.49]) and anxiety by a factor of 2.13 (OR 0.47 [0.41, 0.54]), while naproxen decreased depression reports by a factor of 1.92 (OR 0.52 [0.49, 0.57]) and anxiety by a factor of 1.23 (OR 0.81 [0.75, 0.88]). Other NSAIDs did not exhibit any noticeable antidepressant and/or anxiolytic effect.

BackgroundThe purpose of this study was to review to review the reported associations of depression and antidepressants with motor vehicle crashes.PurposeA literature search for material published in the English language between January, 1995, and October, 2015, in bibliographic databases was combined with a search for other relevant material referenced in the retrieved articles.MethodsRetrieved articles were systematically reviewed for inclusion criteria: 19 epidemiological studies (17 case-control and 2 cohort studies) fulfilled the inclusion criteria by estimating the crash risk associated with depression and/or psychotropic medications in naturalistic settings.ResultsThe estimates of the odds ratio (OR) of crash involvement associated with depression ranged from 1.78 to 3.99. All classes of antidepressants were reported to have side effects with the potential to affect driving safety. The majority of studies of antidepressant effects on driving reported an elevated crash risk, and ORs ranged from 1.19 to 2.03 for all crashes, and 3.19 for fatal crashes. In meta-analysis, depression was associated with approximately 2-fold increased crash risk (summary OR = 1.90; 95% CI, 1.06 to 3.39), and antidepressants were associated with approximately 40% increased crash risk (summary OR = 1.40; 95%CI, 1.18 to 1.66).ConclusionBased on the findings of the studies reviewed, depression, antidepressants or the combination of depression and antidepressants may pose a potential hazard to driving safety. More research is needed to understand the individual contributions of depression and the medications used to treat depression.