Transgender people in clinical trials of drugs and biologics: An analysis of ClinicalTrials.gov from 2007 to 2023.

AIMS: Transgender people have unmet health needs related to chronic conditions such as dementia, osteoporosis and hypertension. Community-driven advocacy increased transgender representation in phase III trials for pharmacological prevention of HIV, but the extent to which drug trials for other conditions have included transgender people is unknown. We investigated the extent to which trials of drugs and biologics represented transgender people across therapeutic areas on ClinicalTrials.gov. METHODS: Cross-sectional analysis of trials of drugs and biologics registered on ClinicalTrials.gov from 2007-2023. We included efficacy and effectiveness trials (phase II-IV) with transgender-related terms (e.g. 'transgend*'). We labelled trials as Inclusive or Exclusive of transgender people using the trial eligibility criteria. We compared trials (therapeutic area, trial design, enrolment), summarized trials registered from 2008 onward and characterized participant enrolment for Inclusive trials with primary trial publications. We summarized continuous data using median (range), categorical data using frequencies and percentages and compared trial characteristics using Fisher's exact test. RESULTS: Ninety-seven trials represented transgender people. Characteristics were similar between 85 Inclusive and 12 Exclusive trials. Among Inclusive trials, 58% focused on infectious diseases (e.g. treatment or prevention of HIV and COVID-19), 15% on mental health (e.g. post-traumatic stress disorder, substance use-related disorders), and the remainder focused on endocrine (9%), pain (5%), digestive system disorders (1%) and neoplasms (1%). Twenty (of 25) trials reported enrolment of transgender participants in primary trial publications or reported results. CONCLUSION: Transgender-inclusive trials have increased since 2008. Most trials focused on infectious diseases and mental health. Investigators should increase opportunities to include of transgender people in trials of drugs and biologics for chronic diseases.

Electrophysiological Mechanisms and Validation of Ferritin-Based Magnetogenetics for Remote Control of Neurons.

Magnetogenetics was developed to remotely control genetically targeted neurons. A variant of magnetogenetics uses magnetic fields to activate transient receptor potential vanilloid (TRPV) channels when coupled with ferritin. Stimulation with static or radiofrequency (RF) magnetic fields of neurons expressing these channels induces Ca2+ transients and modulates behavior. However, the validity of ferritin-based magnetogenetics has been questioned due to controversies surrounding the underlying mechanisms and deficits in reproducibility. Here, we validated the magnetogenetic approach FeRIC using electrophysiological and imaging techniques. Previously, interference from RF stimulation rendered patch-clamp recordings inaccessible for magnetogenetics. We solved this limitation for FeRIC, and we studied the bioelectrical properties of neurons expressing TRPV4 (non-selective cation channel) and TMEM16A (chloride permeable channel) coupled to ferritin (FeRIC channels) under RF stimulation. We used cultured neurons obtained from rat hippocampus of either sex. We show that RF decreases the membrane resistance and depolarizes the membrane potential in neurons expressing TRPV4FeRIC RF does not directly trigger action potential firing but increases the neuronal basal spiking frequency. In neurons expressing TMEM16AFeRIC, RF decreases the membrane resistance, hyperpolarizes the membrane potential, and decreases the spiking frequency. Additionally, we corroborated the previously described biochemical mechanism responsible for RF-induced activation of ferritin-coupled ion channels. We solved an enduring problem for ferritin-based magnetogenetics, obtaining direct electrophysiological evidence of RF-induced activation of ferritin-coupled ion channels. We found that RF does not yield instantaneous changes in neuronal membrane potentials. Instead, RF produces responses that are long-lasting and moderate, but effective in controlling the bioelectrical properties of neurons.Significance statement Cell-specific and non-invasive stimulation can be a powerful tool for modulating neuronal circuits and functions. Magnetogenetic techniques that are fully genetically encoded provide such tools. However, there have been significant controversies surrounding the efficacy and underlying mechanisms of magnetogenetics. Here, we demonstrate that by employing a fully genetically encoded magnetogenetic approach called FeRIC, we can modulate neuronal voltage, inducing either depolarization or hyperpolarization through the activation of ion channels with magnetic fields; we validate this modulation mechanism with the gold-standard patch-clamp technique. We further discover that this neuronal modulation is not achieved by instantaneously triggering action potentials as previously assumed, but by modulating neuronal excitability.

Targeting IGF2BP3 enhances antileukemic effects of menin-MLL inhibition in MLL-AF4 leukemia.

ABSTRACT: RNA-binding proteins (RBPs) are emerging as a novel class of therapeutic targets in cancer, including in leukemia, given their important role in posttranscriptional gene regulation, and have the unexplored potential to be combined with existing therapies. The RBP insulin-like growth factor 2 messenger RNA-binding protein 3 (IGF2BP3) has been found to be a critical regulator of MLL-AF4 leukemogenesis and represents a promising therapeutic target. Here, we study the combined effects of targeting IGF2BP3 and menin-MLL interaction in MLL-AF4-driven leukemia in vitro and in vivo, using genetic inhibition with CRISPR-Cas9-mediated deletion of Igf2bp3 and pharmacologic inhibition of the menin-MLL interaction with multiple commercially available inhibitors. Depletion of Igf2bp3 sensitized MLL-AF4 leukemia to the effects of menin-MLL inhibition on cell growth and leukemic initiating cells in vitro. Mechanistically, we found that both Igf2bp3 depletion and menin-MLL inhibition led to increased differentiation in vitro and in vivo, seen in functional readouts and by gene expression analyses. IGF2BP3 knockdown had a greater effect on increasing survival and attenuating disease than pharmacologic menin-MLL inhibition with small molecule MI-503 alone and showed enhanced antileukemic effects in combination. Our work shows that IGF2BP3 is an oncogenic amplifier of MLL-AF4-mediated leukemogenesis and a potent therapeutic target, providing a paradigm for targeting leukemia at both the transcriptional and posttranscriptional level.

Engineered Glucose Oxidase-Carbon Nanotube Conjugates for Tissue-Translatable Glucose Nanosensors.

Continuous and non-invasive glucose monitoring and imaging is important for disease diagnosis, treatment, and management. However, glucose monitoring remains a technical challenge owing to the dearth of tissue-transparent glucose sensors. In this study, we present the development of near-infrared fluorescent single-walled carbon nanotube (SWCNT) based nanosensors directly functionalized with glucose oxidase (GOx) capable of immediate and reversible glucose imaging in biological fluids and tissues. We prepared GOx-SWCNT nanosensors by facile sonication of SWCNT with GOx in a manner that-surprisingly-does not compromise the ability of GOx to detect glucose. Importantly, we find by using denatured GOx that the fluorescence modulation of GOx-SWCNT is not associated with the catalytic oxidation of glucose but rather triggered by glucose-GOx binding. Leveraging the unique response mechanism of GOx-SWCNT nanosensors, we developed catalytically inactive apo-GOx-SWCNT that enables both sensitive and reversible glucose imaging, exhibiting a ΔF/F0 of up to 40 % within 1 s of exposure to glucose without consuming the glucose analyte. We finally demonstrate the potential applicability of apo-GOx-SWCNT in biomedical applications by glucose quantification in human plasma and glucose imaging in mouse brain slices.

RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric hematological malignancy, with ETV6::RUNX1 being the most prevalent translocation whose exact pathogenesis remains unclear. IGF2BP1 (Insulin-like Growth Factor 2 Binding Protein 1) is an oncofetal RNA binding protein seen to be specifically overexpressed in ETV6::RUNX1 positive B-ALL. In this study, we have studied the mechanistic role of IGF2BP1 in leukemogenesis and its synergism with the ETV6::RUNX1 fusion protein. METHODS: Gene expression was analyzed from patient bone marrow RNA using Real Time RT-qPCR. Knockout cell lines were created using CRISPR-Cas9 based lentiviral vectors. RNA-Seq and RNA Immunoprecipitation sequencing (RIP-Seq) after IGF2BP1 pulldown were performed using the Illumina platform. Mouse experiments were done by retroviral overexpression of donor HSCs followed by lethal irradiation of recipients using a bone marrow transplant model. RESULTS: We observed specific overexpression of IGF2BP1 in ETV6::RUNX1 positive patients in an Indian cohort of pediatric ALL (n=167) with a positive correlation with prednisolone resistance. IGF2BP1 expression was essential for tumor cell survival in multiple ETV6::RUNX1 positive B-ALL cell lines. Integrated analysis of transcriptome sequencing after IGF2BP1 knockout and RIP-Seq after IGF2BP1 pulldown in Reh cell line revealed that IGF2BP1 targets encompass multiple pro-oncogenic signalling pathways including TNFα/NFκB and PI3K-Akt pathways. These pathways were also dysregulated in primary ETV6::RUNX1 positive B-ALL patient samples from our center as well as in public B-ALL patient datasets. IGF2BP1 showed binding and stabilization of the ETV6::RUNX1 fusion transcript itself. This positive feedback loop led to constitutive dysregulation of several oncogenic pathways. Enforced co-expression of ETV6::RUNX1 and IGF2BP1 in mouse bone marrow resulted in marrow hypercellularity which was characterized by multi-lineage progenitor expansion and strong Ki67 positivity. This pre-leukemic phenotype confirmed their synergism in-vivo. Clonal expansion of cells overexpressing both ETV6::RUNX1 and IGF2BP1 was clearly observed. These mice also developed splenomegaly indicating extramedullary hematopoiesis. CONCLUSION: Our data suggest a combined impact of the ETV6::RUNX1 fusion protein and RNA binding protein, IGF2BP1 in activating multiple oncogenic pathways in B-ALL which makes IGF2BP1 and these pathways as attractive therapeutic targets and biomarkers.

The Diabetic Foot-Pain-Depression Cycle.

BACKGROUND: More than 86,000 Americans with type 2 diabetes mellitus (T2DM) undergo nontraumatic lower-extremity amputations annually. The opioid-prescribing practice of podiatric surgeons remains understudied. We hypothesized that patients with T2DM who undergo any forefoot amputation while using antidepressant medication will have reduced odds of using opioids beyond 7 days. METHODS: We completed a retrospective cohort study examining patients with T2DM who underwent forefoot amputation (toe, ray, transmetatarsal). Data were restricted to patients with a hemoglobin A1c level less than 8.0% and an ankle-brachial index greater than 0.8. The outcome was use of postoperative opioids beyond 7 days. Patients received an initial opioid prescription of 7 days or less. We developed simple logistic regression models to identify the odds of a patient using opioids beyond 7 days by patient variables: age, race, sex, amputation level, body mass index, antidepressant medication use, and marital status. Variables with P < .1 in the univariate analysis were included in the multiple logistic regression model. RESULTS: Fifty patients met the inclusion criteria. Antidepressant use and marital status were the only statistically significant variables. Adjusting for marital status, patients with antidepressant use had decreased odds (odds ratio, 0.018; 95% confidence interval, 0.001-0.229; P = .002) of using opioids beyond 7 days after a diabetic forefoot amputation. CONCLUSIONS: Patients with T2DM who used antidepressants had significantly reduced odds of using opioids beyond 1 week after forefoot amputations compared with those without antidepressant use. We proposed an underlying diabetic foot-pain-depression cycle. To break the cycle, podiatric surgeons should screen this population for depression preoperatively and postoperatively and not hesitate to make a mental health referral if warranted. Nontraumatic amputations can be a traumatic experience for patients; psychiatrists and other mental health providers should be members of limb preservation teams.

Epidemiology of SARS-CoV-2 transmission and superspreading in Salt Lake County, Utah, March-May 2020.

BACKGROUND: Understanding the drivers of SARS-CoV-2 transmission can inform the development of interventions. We evaluated transmission identified by contact tracing investigations between March-May 2020 in Salt Lake County, Utah, to quantify the impact of this intervention and identify risk factors for transmission. METHODS: RT-PCR positive and untested symptomatic contacts were classified as confirmed and probable secondary case-patients, respectively. We compared the number of case-patients and close contacts generated by different groups, and used logistic regression to evaluate factors associated with transmission. RESULTS: Data were collected on 184 index case-patients and up to six generations of contacts. Of 1,499 close contacts, 374 (25%) were classified as secondary case-patients. Decreased transmission odds were observed for contacts aged <18 years (OR = 0.55 [95% CI: 0.38-0.79]), versus 18-44 years, and for workplace (OR = 0.36 [95% CI: 0.23-0.55]) and social (OR = 0.44 [95% CI: 0.28-0.66]) contacts, versus household contacts. Higher transmission odds were observed for case-patient's spouses than other household contacts (OR = 2.25 [95% CI: 1.52-3.35]). Compared to index case-patients identified in the community, secondary case-patients identified through contract-tracing generated significantly fewer close contacts and secondary case-patients of their own. Transmission was heterogeneous, with 41% of index case-patients generating 81% of directly-linked secondary case-patients. CONCLUSIONS: Given sufficient resources and complementary public health measures, contact tracing can contain known chains of SARS-CoV-2 transmission. Transmission is associated with age and exposure setting, and can be highly variable, with a few infections generating a disproportionately high share of onward transmission.

Intraindividual phenotyping of depression in high-risk youth: An application of a multilevel hidden Markov model.

BACKGROUND: Traditionally, depression phenotypes have been defined based on interindividual differences that distinguish between subgroups of individuals expressing distinct depressive symptoms often from cross-sectional data. Alternatively, depression phenotypes can be defined based on intraindividual differences, differentiating between transitory states of distinct symptoms profiles that a person transitions into or out of over time. Such within-person phenotypic states are less examined, despite their potential significance for understanding and treating depression. METHODS: The current study used intensive longitudinal data of youths (N = 120) at risk for depression. Clinical interviews (at baseline, 4, 10, 16, and 22 months) yielded 90 weekly assessments. We applied a multilevel hidden Markov model to identify intraindividual phenotypes of weekly depressive symptoms for at-risk youth. RESULTS: Three intraindividual phenotypes emerged: a low-depression state, an elevated-depression state, and a cognitive-physical-symptom state. Youth had a high probability of remaining in the same state over time. Furthermore, probabilities of transitioning from one state to another did not differ by age or ethnoracial minority status; girls were more likely than boys to transition from a low-depression state to either the elevated-depression state or the cognitive-physical symptom state. Finally, these intraindividual phenotypes and their dynamics were associated with comorbid externalizing symptoms. CONCLUSION: Identifying these states as well as the transitions between them characterizes how symptoms of depression change over time and provide potential directions for intervention efforts.

Distinct oncogenic phenotypes in hematopoietic specific deletions of Trp53.

Loss of function in the tumor suppressor gene TP53 is the most common alteration seen in human cancer. In mice, P53 deletion in all cells leads predominantly to the development of T-cell lymphomas, followed by B-cell lymphomas, sarcomas and teratomas. In order to dissect the role of P53 in the hematopoietic system, we generated and analyzed two different mouse models deficient for P53. A pan-hematopoietic P53 deletion mouse was created using Vav1-Cre based deletion; and a B-cell-specific deletion mouse was created using a CD19-Cre based deletion. The Vav1-P53CKO mice predominantly developed T-cell malignancies in younger mice, and myeloid malignancies in older mice. In T-cell malignancies, there was accelerated thymic cell maturation with overexpression of Notch1 and its downstream effectors. CD19-P53CKO mice developed marginal zone expansion in the spleen, followed by marginal zone lymphoma, some of which progressed to diffuse large B-cell lymphomas. Interestingly, marginal zone and diffuse large B-cell lymphomas had a unique gene expression signature characterized by activation of the PI3K pathway, compared with wild type marginal zone or follicular cells of the spleen. This study demonstrates lineage specific P53 deletion leading to distinct phenotypes secondary to unique gene expression programs set in motion.

Nighttime Sleep Quality and Daytime Sleepiness Predicts Suicide Risk in Adults Admitted to an Inpatient Psychiatric Hospital.

As sleep problems have been identified as an important, yet understudied, predictor of suicide risk, the present study analyzed the relationship between daytime sleepiness and nighttime sleep disturbance in a high-risk population of adults admitted to an inpatient psychiatric hospital. Objectives were to (1) examine the time course of subjective daytime sleepiness, nighttime sleep disturbance, and suicide risk throughout inpatient psychiatric treatment, (2) examine pre- to post-treatment changes in sleep disturbance with treatment as usual in an inpatient psychiatric setting, and (3) investigate whether daytime sleepiness and nighttime sleep disturbance predicted suicide risk above and beyond anxiety and depression. Participants were 500 consecutively admitted adults admitted to an intermediate length of stay (4-6 weeks) inpatient psychiatric hospital (47% female; 18-87 years of age). Measures of sleep, suicide risk, depression, and anxiety were completed at admission, weeks 1 through 4, and at discharge. Latent growth curve modeling (LGM) and hierarchal linear modeling (HLM) were conducted. The LGM analysis demonstrated that daytime sleepiness, nighttime sleep disturbance, and suicide risk all improved throughout inpatient treatment. Further, HLM showed that daytime sleepiness predicted suicide risk above and beyond symptoms of anxiety, depression, major sleep medications, and prior suicidal ideation and attempts, while nighttime sleep disturbance predicted suicide risk above and beyond symptoms of anxiety, major sleep medications, and prior suicidal ideation and attempts. Findings indicate the need to reevaluate safety protocols that may impact sleep, particularly that may increase daytime sleepiness, and to develop evidence-based sleep interventions for individuals admitted to inpatient psychiatric hospitals.

Dissecting the depressed mood criterion in adult depression: The heterogeneity of mood disturbances in major depressive episodes.

BACKGROUND: Mood disturbances have historically remained a core criterion in diagnosing major depressive episode. DSMs have illustrated this criterion with depressed, hopeless, discouraged, cheerless, and irritable mood, suggesting interchangeability. Extant research has examined individual forms of mood disturbance to depression severity. Less examined is the heterogeneity in mood disturbances and its implication to their association to depression presentations and outcomes. METHOD: The current study used a nationally representative sample of U.S. adults with unipolar major depressive disorder to study the association between specific forms of mood disturbances to depression severity, chronicity, or symptoms, above and beyond other forms, as well as their relations to functional impairment, suicidal outcomes, and psychiatric comorbidity via generalized linear models. RESULTS: Cheerless and hopeless mood were associated with depression severity. Hopeless and irritable mood were associated with depression chronicity. Different forms of mood disturbance showed differential relations to depressive symptoms. Cheerless, hopeless, and irritable mood were associated with depression-specific functional interference, incremental to depression severity. Cheerless, hopeless, and discouraged mood were associated with passive suicidal ideation. Hopeless mood was associated with active suicidal ideation. Hopeless and irritable mood were associated with both suicide plan and suicide attempt. Different forms of mood disturbance demonstrated differential associations to comorbid psychiatric conditions. DISCUSSION: The relations between different forms of mood disturbances and various aspects of depression are nuanced. Theoretically, these relations highlight the potential utility in acknowledging the complexity and heterogeneity in mood disturbances. Clinically, our results suggest potential utility in routinely monitoring mood disturbances.

Prospective and Contemporaneous Relations of Self-Esteem and Depressed Affect in the Context of Parent-Child Closeness during Adolescence: A Random-Intercept Cross-Lagged Panel Model.

Adolescent self-esteem and depression are influenced by important psychosocial factors such as parental relationships, yet it is unclear how these within-person relations present over time. The current study investigates the longitudinal relations between self-esteem, depressed affect, and parent-adolescent closeness during middle adolescence. Adolescents (n = 562; mean age = 14.73, SD = 0.82; 52% female; 72% White, 28% Racial Minority) were surveyed annually over four years (1988-1991). A random-intercept cross-lagged panel model was applied to disaggregate between- and within-person associations. Consistent with the scar model, adolescents experiencing heightened depressed affect were likely to have lower self-esteem. Furthermore, perceived mother-adolescent, but not father-adolescent, closeness positively predicted adolescent self-esteem. The results highlight the importance of considering interpersonal relationships and age in developmental models of self-esteem and depression.

Toenail Dust as a Potential Occupational Hazard in Podiatric Medicine: A Comprehensive Literature Review.

BACKGROUND: Debridement of toenails is a common procedure that leads to the production of nail dust aerosols in the work environment. Previous studies indicate that inhaled nail dust can cause respiratory distress and eye irritation. This comprehensive review aimed to assess the available literature on the effect of nail dust exposure and to evaluate nail dust as a potential occupational hazard for podiatric physicians. METHODS: A comprehensive literature search was conducted via PubMed, Google Scholar, CINAHL, Cochrane Library, and ClinicalTrials.gov. Risks of bias of the collected studies were evaluated using various assessment tools to match the type of study design. A qualitative analysis of the included studies was performed, from which primary and secondary outcome measures were extracted: prevalence of symptoms and specific microorganisms in nail dust. RESULTS: Of 403 articles screened, eight met the inclusion criteria. The primary outcome measure resulted in a pooled prevalence of eye-related symptoms being the most consistent symptom reported (41%-48%). The secondary outcome measure resulted in a pooled prevalence of Trichophyton rubrum (9.52%-38%) and Aspergillus (11.11%-35.48%) as the most common microorganisms present in nail dust. CONCLUSIONS: From the included eight articles, we found that nail dust is a potential occupational hazard, especially for those exposed more often. Aspergillus and T rubrum are most commonly associated with nail dust leading to development of respiratory illness. It is important to take preventive measures in podiatric medical clinics by using improved and efficient personal protective equipment for workers exposed to nail dust. Detailed health safety guidelines can be developed to decrease respiratory symptoms and diseases from nail dust exposure.

Temperature Changes during Implant Osteotomy Preparations in Human Cadaver Tibiae Comparing MIS® Straight Drills with Densah® Burs.

(1) Background: Several studies showed a sustained temperature of 47 °C or 50 °C for one minute resulted in vascular stasis and bone resorption with only limited bone regrowth over a 3-4-week healing period. The purpose of the present study was to evaluate the temperature changes (ΔΤ) that occur during the preparation of dental implant osteotomies using MIS® straight drills versus Densah® burs in a clockwise (cutting) drilling protocol. (2) Methods: Two hundred forty (240) osteotomies of two different systems' drills were prepared at 6 mm depth at 800, 1000, and 1200 revolutions per minute (RPM), in fresh, unembalmed tibiae, obtained by a female cadaver. ΔΤ was calculated by subtracting the baseline temperature on the tibial surface, from the maximum temperature-inside the osteotomy (ΔT = Tmax - Tbase). The variables were evaluated both for their individual and for their synergistic effect on ΔΤ with the use of one-, two-, three- and four-way interactions; (3) Results: An independent and a three-way interaction (drill design, drill width, and RPM) was found in all three RPM for the Densah® burs and at 1000 RPM for the MIS® straight drills. As Densah® burs diameter increased, ΔΤ decreased. The aforementioned pattern was seen only at 1000 RPM for the MIS® straight drills. The usage of drills 20 times more than the implant manufacturers' recommendation did not significantly affect the ΔΤ. A stereoscopic examination of the specimens confirmed the findings. (4) Conclusions: The independent and synergistic effect of drills' diameter, design and RPM had a significant effect on ΔΤ in human tibiae, which never exceeded the critical threshold of 47 °C.

RNA binding proteins in MLL-rearranged leukemia.

RNA binding proteins (RBPs) have recently emerged as important post-transcriptional gene expression regulators in both normal development and disease. RBPs influence the fate of mRNAs through multiple mechanisms of action such as RNA modifications, alternative splicing, and miR-mediated regulation. This complex and, often, combinatorial regulation by RBPs critically impacts the expression of oncogenic transcripts and, thus, the activation of pathways that drive oncogenesis. Here, we focus on the major features of RBPs, their mechanisms of action, and discuss the current progress in investigating the function of important RBPs in MLL-rearranged leukemia.

Regulation of T-independent B-cell responses by microRNA-146a.

The microRNA, miR-146a, is a negative feedback regulator of the central immune transcription factor, nuclear factor kappa B (NFkB). MiR-146a plays important roles in the immune system, and miR-146a deficient mice show a complex phenotype with features of chronic inflammation and autoimmune disease. In this study, we examined the role of miR-146a in extrafollicular B-cell responses, finding that miR-146a suppresses cellular responses in vivo and in vitro. Gene expression profiling revealed that miR-146a-deficient B-cells showed upregulation of interferon pathway genes, including Traf6, a known miR-146a target. We next interrogated the role of TRAF6 in these B-cell responses, finding that TRAF6 is required for proliferation by genetic and pharmacologic inhibition. Together, our findings demonstrate a novel role for miR-146a and TRAF6 in the extrafollicular B-cell responses, which have recently been tied to autoimmune disease pathogenesis. Our work highlights the pathogenetic role of miR-146a and the potential of pharmacologic inhibition of TRAF6 in autoimmune diseases in which miR-146a is deregulated.

A Culturally and Linguistically Appropriate Telephone Support Intervention for Diverse Family Caregivers of Persons With Dementia During the COVID-19 Pandemic.

Caregivers of persons with dementia (PWDs) were socially isolated with little support during the COVID-19 pandemic "Stay-At-Home" order in the United States. To enhance social and emotional connection for diverse caregivers, a culturally/linguistically appropriate telephone intervention provided compassionate listening, mindful breathing, and COVID-19 safety education. The study purpose was to understand caregiving challenges and to evaluate the intervention for caregivers during the early pandemic using a qualitative approach. Twenty-three caregivers participated in the intervention provided by bilingual research assistants for 3 months. Call logs were used to describe the caregivers' dialogue. Thematic analysis identified (a) the challenges, including fear of coronavirus disease, providing around-the-clock care, and forced isolation and negative emotions; and (b) caregivers' experience with the intervention, including connecting with the outside, relief from emotional stress, reliable COVID-19 information, and reinformed caregiving skills. Results suggest that the telephone support was of benefit to diverse caregivers of PWDs during the pandemic by promoting social connection and reducing emotional distress.

The cross-sectional, longitudinal, and transitional associations between perceived support and suicidal ideation and behavior in late adolescence and emerging adulthood: Adjacent-category logit models.

INTRODUCTION: Suicidal ideation (SI) and attempts (SA) are prevalent in late adolescence and emerging adulthood. Prior research has identified perceived support as a correlate of SI and SA. Less is known, though, about the role of perceived support in differentiating among suicidal outcomes and between the incremental escalation of suicidal outcomes from SI to SA to serious suicide attempts (SSA). METHOD: Using ordinal regression, we used Wave 1 and 2 data from the National Longitudinal Study of Adolescent to Adult Health (N = 4500; 53% female; Mage  = 16.6; 12% Hispanic) to examine cross-sectional, longitudinal, and transitional models of perceived support and suicidality. RESULTS: Cross-sectional results indicated that youths with higher perceived support were less likely to have suicidal ideation. Longitudinal results showed that youths with higher perceived support at Wave 1 were less likely to have suicidal ideation or serious suicide attempts at Wave 2. Transitional model results revealed that higher perceived support at Wave 1 was negatively associated with escalation in suicidal outcomes from Wave 1 to 2. CONCLUSION: We discuss findings in the context of theories of suicide and discuss implications for suicide risk identification, intervention, and prevention efforts in late adolescence and emerging adulthood.

Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies in the Mozambican Population: A Cross-Sectional Serologic Study in 3 Cities, July-August 2020.

BACKGROUND: The extent of population exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was uncertain in many African countries during the onset of the pandemic. METHODS: We conducted a cross-sectional study and randomly selected and surveyed general population and occupational groups from 6 July to 24 August 2020, in 3 cities in Mozambique. Anti-SARS-CoV-2-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies were measured using a point-of-care rapid test. The prevalence was weighted for population (by age, sex, and city) and adjusted for test sensitivity and specificity. RESULTS: A total of 21 183 participants, including 11 143 from the general population and 10 040 from occupational groups, were included across all 3 cities. General population seropositivity (IgM or IgG) prevalence was 3.0% (95% confidence interval [CI], 1.0%-6.6%) in Pemba, 2.1% (95% CI, 1.2%-3.3%) in Maputo City, and 0.9% (95% CI, .1%-1.9%) in Quelimane. The prevalence in occupational groups ranged from 2.8% (95% CI, 1.3%-5.2%) to 5.9% (95% CI, 4.3%-8.0%) in Pemba, 0.3% (95% CI, .0%-2.2%) to 4.0% (95% CI, 2.6%-5.7%) in Maputo City, and 0.0% (95% CI, .0%-.7%) to 6.6% (95% CI, 3.8%-10.5%) in Quelimane, and showed variations between the groups tested. CONCLUSIONS: In the first representative COVID-19 serosurveys in Mozambique, in mid-2020, weighted and assay-adjusted seroprevalence in 3 provincial capitals of anti-SARS-CoV-2 ranged from 0.9% to 3.0%, whereas adjusted prevalence in occupational groups ranged from 0.0% to 6.6% with variation between groups. Exposure to SARS-CoV-2 was extensive during the first pandemic wave, and transmission may have been more intense among occupational groups. These data have been of utmost importance to inform public health intervention to control and respond to the pandemic in Mozambique.

Impact of War and Resettlement on Vietnamese Families Facing Dementia: A Qualitative Study.

OBJECTIVES: Most Vietnamese immigrants in the U.S. today arrived as political refugees due to the Vietnam War in the late 20th century. Refugees are disproportionally affected by health and mental health disparities as a result of experiencing distress and potentially traumatic experiences before, during, and after their migration processes. This study involved Vietnamese families facing dementia and used a qualitative approach to investigate participants' experiences before, during, and right after their resettlement in the U.S. METHODS: In-person interviews were conducted with 11 Vietnamese adults who cared for their family member with dementia. A descriptive analysis approach was used. RESULTS: Five major themes emerged from the interviews:1) immigrating separately from family members, 2) difficult and unsafe journeys, 3) experiences of loss, 4) lack of support systems in the U.S., and 5) feelings of unhappiness, sadness, or signs of depression. CONCLUSIONS: This study provides a close examination of Vietnamese refugees' unique backgrounds and how individuals with dementia and their caregivers from this population may be disproportionally impacted by stress. CLINICAL IMPLICATIONS: To reduce health disparities, we recommend that providers and policymakers allocate more resources for culturally appropriate routine assessment, treatment, and referrals of those with dementia and their caregivers.