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Background Compared with peers, young sexual and gender minorities (SGM) are at a four to seven-fold increased risk of attempting suicide. Prior epidemiological studies, mainly focusing on monomorbid inequalities and without conducting diagnostic clinical interviews, have been unable to report robust data on psychiatric comorbidities among those who attempted suicide. The purpose of this presentation is to describe the presence of current psychiatric comorbidities among SGM youth and young adults at elevated risk for repeat suicide attempts. Methods A diverse convenience sample of SGM youth and young adults with a lifetime history of suicide attempts and current suicidal ideation was recruited for an open-phase suicide prevention trial in San Diego, CA. At baseline, participants underwent a 15-module DIAMOND interview for adults or computerized K-SADS for minors, and a battery of self-report questionnaires. Results Among the 31 participants (Mage = 22 years [Range: 16, 29]; 100% sexual, 52% gender, and 61% racial/ethnic minority), 27 (87%) participants met criteria for any mood disorder, 24 (77%) for any anxiety disorder, 16 (52%) for any trauma or stress disorder, and 2 (6%) for any psychotic disorder. One (3%) participant did not meet criteria for any psychiatric diagnoses, while five (16%) met criteria for a single and 25 (81%) for multiple diagnoses. The average number of diagnoses was 3.2 (Range: 0, 7). Additionally, 20 (65%) participants met the cut-off for likely ADHD, 20 (65%) for possible borderline personality disorder, and 21 (68%) for likely body dysmorphic disorder, with 11 (35%) within the 90th percentile for reference eating disorder severity. Conclusions The degree of psychiatric comorbidities in the sample of SGM youth and young adults at elevated risk for suicide was high. Beside direct suicide risk mitigation efforts, suicide prevention programs that target young SGM with a history of attempts should screen for untreated psychiatric disorders. Key messages • LGBTQ+ youth and young adults at elevated risk for repeat suicide attempts experience a high degree of psychiatric comorbity. • Beyond suicide risk mitigation, LGBTQ+ youth suicide prevention programs should focus on untreated psychiatric comorbidities.

We analyzed results from semi-structured interviews and participant observation with educators, clinical staff, and administrators who worked at nearly 100 different correctional facilities centrally managed by eight separate state prison systems to understand how the beliefs they hold about the life experiences and future trajectories of incarcerated people influence prison social climate. We found that staff who regard incarcerated people as past and/or future neighbors are more likely to foster a safe, mutually respectful prison social climate conducive to positive personal transformation. Envisioning prison social climate as a product of the relationship between staff and incarcerated people demonstrates how prisons and communities interact with each other to shape the past and future possibilities for people who are incarcerated. Our results offer six policy implications, to (1) mandate administrative-institutional commitment to creating a positive prison social climate in which correctional staff and incarcerated people are partners in rehabilitation; (2) expand existing program opportunities in prison to ensure widespread availability of educational, vocational, and therapeutic treatment programs; (3) increase representation of staff who share experiential and demographic characteristics with incarcerated people to reduce or eliminate unconscious bias; (4) generate public awareness of, and support for, rehabilitative measures proven to better prepare incarcerated people for release from prison; (5) increase community engagement by publicizing graduation and other positive events; and (6) foster a mutually supportive work environment among educational, clinical, and administrative staff.

Background Medication safety issues have detrimental implications on long-term outcomes in the high-risk kidney transplant (KTX) population. Medication errors, adverse drug events, and medication nonadherence are important and modifiable mechanisms of graft loss. Objective To describe the frequency and types of interventions made during a pharmacist-led, mobile health–based intervention in KTX recipients and the impact on patient risk levels. Methods This was a secondary analysis of data collected during a 12-month, parallel-arm, 1:1 randomized clinical controlled trial including 136 KTX recipients. Participants were randomized to receive either usual care or supplemental, pharmacist-driven medication therapy monitoring and management using a smartphone-enabled app integrated with telemonitoring of blood pressure and glucose (when applicable) and risk-based televisits. The primary outcome was pharmacist intervention type. Secondary outcomes included frequency of interventions and changes in risk levels. Results A total of 68 patients were randomized to the intervention and included in this analysis. The mean age at baseline was 50.2 years; 51.5% of participants were male, and 58.8% were black. Primary pharmacist intervention types were medication reconciliation and patient education, followed by medication changes. Medication reconciliation remained high throughout the study period, whereas education and medication changes trended downward. From baseline to month 12, we observed an approximately 15% decrease in high-risk patients and a corresponding 15% increase in medium- or low-risk patients. Conclusion and Relevance A pharmacist-led mHealth intervention may enhance opportunities for pharmacological and nonpharmacological interventions and mitigate risk levels in KTX recipients.

For many years, it was believed that the aging process was inevitable and that age-related diseases could not be prevented or reversed. The geroscience hypothesis, however, posits that aging is, in fact, malleable and, by targeting the hallmarks of biological aging, it is indeed possible to alleviate age-related diseases and dysfunction and extend longevity. This field of geroscience thus aims to prevent the development of multiple disorders with age, thereby extending healthspan, with the reduction of morbidity toward the end of life. Experts in the field have made remarkable advancements in understanding the mechanisms underlying biological aging and identified ways to target aging pathways using both novel agents and repurposed therapies. While geroscience researchers currently face significant barriers in bringing therapies through clinical development, proof-of-concept studies, as well as early-stage clinical trials, are underway to assess the feasibility of drug evaluation and lay a regulatory foundation for future FDA approvals in the future.

Background: An association between chronic infectious diseases and development of dementia has been suspected for decades, based on the finding of pathogens in postmortem brain tissue and on serological evidence. However, questions remain regarding confounders, reverse causality, and how accurate, reproducible and generalizable those findings are. Objective: Investigate whether exposure to Herpes simplex (manifested as herpes labialis), Chlamydophila pneumoniae (C. pneumoniae), Helicobacter pylori (H. pylori), and cytomegalovirus (CMV) modifies the risk of dementia in a populational cohort. Methods: Questionnaires regarding incidence of herpes infections were administered to Original Framingham Study participants (n = 2,632). Serologies for C. pneumoniae, H. pylori, and CMV were obtained in Original (n = 2,351) and Offspring cohort (n = 3,687) participants. Participants are under continuous dementia surveillance. Brain MRI and neuropsychological batteries were administered to Offspring participants from 1999–2005. The association between each infection and incident dementia was tested with Cox models. Linear models were used to investigate associations between MRI or neuropsychological parameters and serologies. Results: There was no association between infection serologies and dementia incidence, total brain volume, and white matter hyperintensities. Herpes labialis was associated with reduced 10-year dementia risk (HR 0.66, CI 0.46–0.97), but not for the duration of follow-up. H. pylori antibodies were associated with worse global cognition (β –0.14, CI –0.22, –0.05). Conclusion: We found no association between measures of chronic infection and incident dementia, except for a reduction in 10-year dementia risk for patients with herpes labialis. This unexpected result requires confirmation and further characterization, concerning antiviral treatment effects and capture of episodes.

Background: Depressive symptoms predict increased risk for dementia decades before the emergence of cognitive symptoms. Studies in older adults provide preliminary evidence for an association between depressive symptoms and amyloid-β (Aβ) and tau accumulation. It is unknown if similar alterations are observed in midlife when preventive strategies may be most effective. Objective: The study aim was to evaluate the association between depressive symptoms and cerebral Aβ and tau in a predominately middle-aged cohort with examination of the apolipoprotein (APOE) ɛ4 allele as a moderator. Methods: Participants included 201 adults (mean age 53±8 years) who underwent 11C-Pittsburgh Compound B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging. Depressive symptoms were evaluated with the Center for Epidemiological Studies Depression Scale (CES-D) at the time of PET imaging, as well as eight years prior. Associations between depressive symptoms at both timepoints, as well as depression (CES-D≥16), with regional Aβ and tau PET retention were evaluated with linear regression adjusting for age and sex. Interactions with the APOE ɛ4 allele were explored. Results: Depressive symptoms and depression were not associated with PET outcomes in the overall sample. However, among APOE ɛ4 allele carriers, there was a significant cross-sectional association between depressive symptoms and increased tau PET uptake in the entorhinal cortex (β= 0.446, SE = 0.155, p = 0.006) and amygdala (β= 0.350, SE = 0.133, p = 0.012). Conclusion: Although longitudinal studies are necessary, the results suggest that APOE ɛ4 carriers with depressive symptoms may present with higher susceptibility to early tau accumulation in regions integral to affective regulation and memory consolidation.

Objectives Early posttransplant, the administration of oral or enteral medications in pancreas transplant is challenging because of the management of postoperative ileus and gastroparesis. The use of sublingual tacrolimus may offer a promising alternative. The objective of this study was to compare the pharmacokinetics and perioperative outcomes between oral and sublingual tacrolimus in pancreas transplant. Materials and methods This was a single-center, retrospective study of pancreas transplants between January 1, 2011, and July 1, 2018. We transitioned our tacrolimus protocol from oral to sublingual dosing in pancreas transplant patients beginning January 1, 2017. Results This analysis included 54 pancreas transplant recipients, with 17 patients on sublingual tacrolimus matched to 37 patients on oral tacrolimus. Within the sublingual group, it took a mean of 3.2 days to achieve a therapeutic tacrolimus trough level (≥8 ng/mL) compared with a mean of 3.8 days in the oral group (P = .175). There was no difference in the incidence of hyperkalemia and supratherapeutic tacrolimus levels between groups. The conversion factor from sublingual to oral in this patient population was 0.67, which was different than what has been reported in other populations. Clinical outcomes were similar between groups. Conclusions Sublingual tacrolimus use in pancreas transplant patients appears to be a safe and effective strategy to avoid oral or intravenous therapy in the perioperative period and may reduce the time to achieve therapeutic levels.

In 2016, with the support of a three-year National Endowment for the Humanities (NEH) Collaborative Research Grant to research and write a precolonial African history of family, generations, and gender, we began building the Bantu Ancestral Roots Database (BARD). BARD is a digital repository of word-roots related to gender and life stage practices from over sixty Bantu languages. We developed it to assist us in our analysis of this large corpus of data that we used to write histories of people’s material and ideological inventions that cover the longue durée across multiple regions. BARD allows researchers with internet access to search for terms by entering at least three consecutive phonemes. If phonemes exist in that sequence in any of the 64 Bantu languages that BARD holds, those words and their meanings appear as results. In this article, we discuss the usefulness and complexities of Digital Humanities (DH) as research tools. We explain our methodology and research process using three reconstructed word-roots pertinent to our research on family and generations. The three word-roots we examine invite scholars to probe how to recover deep connections and linkages between people’s pasts in Africa and its Diasporas, particularly in ways that move beyond histories of the slave trade and enslavement. As we developed our open-access website African Social History and Data Across Bantu Matrilineal Communities (ASH-DABMC) and our database, BARD, we gained greater insight into the meanings encoded in our data even as we faced challenges. We hope the discussion of our experiences will provide an intellectual framework and inspire others considering digital projects.

Background and objectives Medication safety events are predominant contributors to suboptimal graft outcomes in kidney transplant recipients. The goal of this study was to examine the efficacy of improving medication safety through a pharmacist-led, mobile health–based intervention. Design, setting, participants, & measurements This was a 12-month, single-center, prospective, parallel, two-arm, single-blind, randomized controlled trial. Adult kidney recipients 6–36 months post-transplant were eligible. Participants randomized to intervention received supplemental clinical pharmacist–led medication therapy monitoring and management via a mobile health–based application, integrated with risk-guided televisits and home-based BP and glucose monitoring. The application provided an accurate medication regimen, timely reminders, and side effect surveys. Both the control and intervention arms received usual care, including serial laboratory monitoring and regular clinic visits. The coprimary outcomes were to assess the incidence and severity of medication errors and adverse events. Results In total, 136 kidney transplant recipients were included, 68 in each arm. The mean age was 51 years, 57% were male, and 64% were Black individuals. Participants receiving the intervention experienced a significant reduction in medication errors (61% reduction in the risk rate; incident risk ratio, 0.39; 95% confidence interval, 0.28 to 0.55; P Conclusions We demonstrated a significant reduction in medication errors, adverse events, and hospitalizations using a pharmacist-led, mobile health–based intervention.

Plasmodium falciparum merozoite surface protein (PfMSP)2 is a target of parasite-neutralizing Abs. Inclusion of recombinant PfMSP2 (rPfMSP2) as a component of a multivalent malaria vaccine is of interest, but presents challenges. Previously, we used the highly immunogenic PfMSP8 as a carrier to enhance production and/or immunogenicity of malaria vaccine targets. In this study, we exploited the benefits of rPfMSP8 as a carrier to optimize a rPfMSP2-based subunit vaccine. rPfMSP2 and chimeric rPfMSP2/8 vaccines produced in Escherichia coli were evaluated in comparative immunogenicity studies in inbred (CB6F1/J) and outbred (CD1) mice, varying the dose and adjuvant. Immunization of mice with both rPfMSP2-based vaccines elicited high-titer anti-PfMSP2 Abs that recognized the major allelic variants of PfMSP2. Vaccine-induced T cells recognized epitopes present in both PfMSP2 and the PfMSP8 carrier. Competition assays revealed differences in Ab specificities induced by the two rPfMSP2-based vaccines, with evidence of epitope masking by rPfMSP2-associated fibrils. In contrast to aluminum hydroxide (Alum) as adjuvant, formulation of rPfMSP2 vaccines with glucopyranosyl lipid adjuvant–stable emulsion, a synthetic TLR4 agonist, elicited Th1-associated cytokines, shifting production of Abs to cytophilic IgG subclasses. The rPfMSP2/8 + glucopyranosyl lipid adjuvant–stable emulsion formulation induced significantly higher Ab titers with superior durability and capacity to opsonize P. falciparum merozoites for phagocytosis. Immunization with a trivalent vaccine including PfMSP2/8, PfMSP1/8, and the P. falciparum 25 kDa sexual stage antigen fused to PfMSP8 (Pfs25/8) induced high levels of Abs specific for epitopes in each targeted domain, with no evidence of antigenic competition. These results are highly encouraging for the addition of rPfMSP2/8 as a component of an efficacious, multivalent, multistage malaria vaccine.

Carotenoid pigments serve many endogenous functions in organisms, but some of the more fascinating are the external displays of carotenoids in the colorful red, orange and yellow plumages of birds. Since Darwin, biologists have been curious about the selective advantages (e.g., mate attraction) of having such ornate features, and, more recently, advances in biochemical methods have permitted researchers to explore the composition and characteristics of carotenoid pigments in feathers. Here we review contemporary methods for extracting and analyzing carotenoids in bird feathers, with special attention to the difficulties of removal from the feather keratin matrix, the possibility of feather carotenoid esterification and the strengths and challenges of different analytical methods like high-performance liquid chromatography and Raman spectroscopy. We also add an experimental test of current common extraction methods (e.g., mechanical, thermochemical) and find significant differences in the recovery of specific classes of carotenoids, suggesting that no single approach is best for all pigment or feather types.

Se llama hidrotórax a una efusión pleural primaria que ocurre durante la vida prenatal (denominado ‘quilotórax primario’ después del nacimiento). En ciertos casos, esta efusión es severa y produce compresión pulmonar y cardiaca, por lo cual, la mortalidad perinatal sigue siendo alta. Los recién nacidos con hidrotórax requieren, muchas veces, de drenaje, nutrición parenteral total y medicación específica para su recuperación. Sin embargo, las intervenciones prenatales, principalmente con derivaciones toraco-amnióticas, pueden mejorar estos resultados. Reportamos el caso de un feto con hidrotórax severo a quien se le realizó una toracocentesis y revisamos la literatura acerca de su rol en el tratamiento prenatal actual.

Dyslipidemia is a cardiovascular risk factor that is increasing in prevalence in the country. The need to treat and manage elevated cholesterol levels, both pharmacologic and non-pharmacologic, is of utmost importance. Different medical societies and groups bonded together to formulate the 2020 Philippine Clinical Practice Guidelines for dyslipidemia. The group raised nine clinical questions that are important in dyslipidemia management. A technical working group analyzed the clinical questions dealing with non-pharmacologic management, primary prevention for both non-diabetic and individuals with diabetes, familial hypercholesterolemia, secondary prevention, adverse events of statins and the use of other lipid parameters as measurement of risk for cardiovascular disease. Randomized controlled trials and meta-analyses were included in the GRADE-PRO analysis to come up with the statements answering the clinical questions. The statements were presented to a panel consisting of government agencies, members of the different medical societies, and private institutions, and the statements were voted upon to come up with the final statements of the 2020 practice guidelines. The 2020 CPG is aimed for the Filipino physician to confidently care for the individual with dyslipidemia and eventually lower his risk for cardiovascular disease.

Visual impairment (VI) may lead to worsening functional status and disability. Although disability is very difficult to reverse, it is usually preceded by frailty that may be reverted more easily. It is possible that VI is also related to frailty. To assess the relationship between VI and worsening of the frailty status. Data were taken from the Toledo Study for Healthy Aging (TSHA), a cohort study of community-dwelling people older than 65 years living in one Spanish province who were followed for 5 years. 1181 participants were included. VI was self-reported and frailty was operationalized using the Fried’s phenotype adapted to a Spanish population. Models of multivariate logistic regression were built to assess the associations. The mean age was 73.9 (Standard Deviation (SD) = 5 years) and 58.5% were females. Pre-frailty/frailty prevalence at baseline and follow-up were 41.2/5% and 36.2/12.5%, respectively, and VI was reported by 14.1%. After adjusting for age, gender, education level, tobacco consumption, type 2 diabetes mellitus, high blood pressure, cardiovascular disease, depressive symptoms and cognitive status, odds ratios for the development of frailty by VI were 2.5 (95% Confidence Interval (CI) 1.5–4.4) for non-frail, 2.7 (95% CI 1.3–5.7) for pre-frail and 1.9 (CI 0.6–6.00) for robust participants. The frailty domains whose appearance was most increased by VI were slowness, low energy, low physical activity and weakness. Our findings support that VI worsens frailty in the early stages of its development (pre-frailty). VI impairs several frailty items at the same time. Our study highlights the need to assess both VI and frailty for the prevention of frailty and disability in older people.

PurposeSchool improvement planning and implementation is one organizational process by which principals may positively impact school and student outcomes. Limited research, however, has explored how principal preparation programs prepare aspiring leaders for this common school leadership activity. This study examined aspiring principals engaged in the school improvement process by evaluating what they included in their school improvement plans (SIPs) that were developed as part of their field experience.Design/methodology/approachThe authors examined SIPs aspiring principals collaboratively developed as part of their field experience. Using an abductive analysis method, combining both deductive and inductive coding methods, authors examined 77 SIPs in which aspiring principals used school level data in planning.FindingsEach aspiring principal's SIP was contextually specific. No two plans were identical relative to who was targeted for improvement and how the plan was to be implemented, indicating aspiring principals can apply course-based learning and implement important data-driven decision-making skills in field-based school improvement projects.Research limitations/implicationsFindings are exploratory and limited to SIPs developed by aspiring principals in one university program in one large urban school district context. The findings that specific requirements and program structures affected the aspiring principal's school improvement planning process as did the overall school context adds to current understandings of how course-based learning is applied. However, further investigations are needed.Practical implicationsFindings provide evidence of how school leadership preparation programs may impact leadership development relative to skills associated with school improvement planning. The findings also suggest the importance of detailed analysis of aspiring principals school improvement planning as a program evaluation process.Originality/valueThis study was the first to document the content of aspiring principals' field-based SIPS and how skills in data-driven decision-making were applied in a SIP field-based activity.

Over the past decade, there has been an increase of 1:1 laptop schools across the United States. Yet, minimal research exists which examines the experiences of school site administrators as they le...

As a response to the COVID-19 pandemic, many school administrators are forced to transform traditional schooling into an online distance learning environment. This commentary addresses how some of the challenges and implications of our research in leadership and instruction of one-to-one laptop schools are applicable to establishing a distance learning environment alongside current standards for instruction. School administrators are strongly encouraged to collaborate with teachers as soon as teachers report for the school year to help create a shared vision of effective online instruction and implement supplemental frameworks that will guide evaluation of teaching and learning online.

This study examines what aspiring principal candidates in one university-based preparation program learned as a result of developing and implementing a school improvement plan. A case study approach was used to examine 53 aspiring principals’ reports of what they learned from implementing school improvement plans. Findings revealed three significant themes: (1) the importance of collaboratively engaging the participants of the school improvement plan; (2) the essential need of establishing relationships; and (3) understanding the significance and impact of data-driven decisions. Findings can inform leadership preparation programs to redirect coursework that will help aspiring principals improve leadership skills.

Tacrolimus (Tac) is widely used to prevent rejection and graft loss in solid organ transplantation. A limiting characteristic of Tac is the high intra and interpatient variability associated with its use. Routine therapeutic drug monitoring (TDM) is necessary to facilitate Tac management and to avoid undesirable clinical outcomes. However, whole blood trough concentrations commonly utilized in TDM are not strong predictors of the detrimental clinical outcomes of interest. Recently, researchers have focused on Tac intrapatient variability (Tac IPV) as a novel marker to better assess patient risk. Higher Tac IPV has been associated with a number of mechanisms leading to shortened graft survival. Medication nonadherence (MNA) is considered to be the primary determinant of high Tac IPV and perhaps the most modifiable risk factor. An understanding of the methodology behind Tac IPV is imperative to its recognition as an important prognostic measure and integration into clinical practice. Therapeutic interventions targeting MNA and reducing Tac IPV are crucial to improving long-term graft survival.

Nutritionally adequate and safe complementary feeding starting from the age of 6 months up to 59 months is one of the effective intervention to reduce infant and child morbidity and malnutrition. This study aims to determine the nutritional status of children ages 6-59 months and their caregiver’s infant and young child feeding (IYCF) practices of the Buhid community in Rizal, Occidental Mindoro. The design used in this study was a descriptive cross-sectional carried out between December 2016-February 2017. A survey questionnaire was utilized as an instrument in this study. It includes an anthropometric survey of 6-59 months old and infant and young child feeding practices using WHO and UNICEF IYCF indicators. Vaccination, vitamin A supplementation and deworming coverage were also measured. Findings revealed a prevalence of global acute malnutrition (GAM) at a critical level. There is a low but significant prevalence of stunting and underweight among children. There is a good infant and young feeding practice in the community except for the minimum acceptable diet during complementary feeding. Lastly, there is low BCG and measles vaccination coverage in the community that could be a threat to the impending disease outbreak.

Experiential avoidance is a common psychological process, a core component of third-wave behavioral therapies, and a robust predictor of general psychopathology. The Acceptance and Action Questionnaire (AAQ version II [AAQ – II]; Bond et al. 2011) is a popular and widely used measure of experiential avoidance. However, studies examining the measurement and function of the AAQ-II across cultures are largely relegated to translational investigations across different languages, thus providing little information about measurement equivalence among English speaking populations from different racial/ethnic backgrounds. The present study examined data from the 2016–2017 National Healthy Minds Study (HMS; N = 24,439) and tested the measurement invariance of the AAQ – II across White, Black, Latinx, Asian American, and Middle Eastern college students. We then examined how racial/ethnic group moderated experiential avoidance as a concurrent predictor of anxiety and depression. Multigroup structural equation modeling indicated support for configural but not metric measurement invariance across all groups. The effect size of the non-invariance was small in magnitude. The AAQ – II functioned as a strong positive correlate of anxiety and depression measures across racial/ethnic groups. Moderation analyses further indicated that the AAQ-II was a significantly stronger predictor of anxiety and depression for White participants (β′s = .717, .738 respectively) compared to Asian American participants (β′s = 0.671, 0.665 respectively) and was a significantly stronger predictor of anxiety for White participants compared to Latinx respondents (β = 0.662). Implications for research, theory, and clinical practice are discussed, with specific recommendations for culturally informed adaptations to the AAQ – II.

BACKGROUND Erasmus syndrome is a rare disease entity characterized by the development of systemic sclerosis (SSc) in a background of silica exposure or silicosis. CASE REPORT We report the case of a 40-year-old Filipino man who previously worked in a silica grind mill for 10 years and eventually developed Erasmus syndrome. The patient initially presented with chronic back pain in 2018 associated with findings of pulmonary tuberculosis on chest X-ray, with notable improvement after 6 months of anti-tuberculosis treatment. However, his back pain recurred in 2021; this time with arthralgia, Raynaud's phenomenon, thickening of both hands, skin hypopigmentation on the chest, back, and forehead, and exertional dyspnea. Physical examination revealed salt-and-pepper dermopathy and skin tightening over the back, chest, and extremities. Mobility of his hands was limited, associated with sclerodactyly and digital pitting. Antinuclear antibody-immunofluorescence and anti-scleroderma-70 antibodies were strongly positive, confirming the diagnosis of SSc. Chest computed tomography illustrated multiple subcentimeter nodules and enlarged mediastinal lymph nodes with eggshell calcifications, consistent with silicosis. Spirometry with body plethysmography was normal but diffusing capacity for carbon monoxide was severely reduced. Histopathology of the skin showed markedly thickened collagen bundles in the dermis. CONCLUSIONS Chronic silica exposure is a risk factor for the development of silicosis. The clinical course of patients with silicosis may be complicated by SSc. Maintaining a high index of suspicion is key to the diagnosis of Erasmus syndrome. The present report emphasizes the importance of preventive measures and surveillance among those with occupational exposure to silica. To our knowledge, this is the first documented case of Erasmus syndrome in the Philippines.

Tibial stress fracture (TSF) is an overuse running injury with a long recovery period. While many running studies refer to biomechanical risk factors for TSF, only a few have compared biomechanics in runners with TSF to controls. The aim of this systematic review and meta-analysis was to evaluate biomechanics in runners with TSF compared to controls.Electronic databases PubMed, Web of Science, SPORTDiscus, Scopus, Cochrane, and CINAHL were searched. Risk of bias was assessed and meta-analysis conducted for variables reported in 3 or more studies.The search retrieved 359 unique records, but only the 14 that compared runners with TSF to controls were included in the review. Most studies were retrospective, 2 were prospective, and most had a small sample size (5-30 per group). Many variables were not significantly different between groups. Meta-analysis of peak impact, active, and braking ground reaction forces found no significant differences between groups. Individual studies found larger tibial peak anterior tensile stress, peak posterior compressive stress, peak axial acceleration, peak rearfoot eversion and hip adduction in the TSF group.Meta-analysis indicated that discrete ground reaction force variables were not statistically significantly different in runners with TSF compared to controls. In individual included studies, many biomechanical variables were not statistically significantly different between groups. However, many were reported by only a single study, and sample sizes were small. We encourage additional studies with larger sample sizes of runners with TSF and controls and adequate statistical power to confirm or refute these findings.

An inadvertent consequence of advances in stem cell research, neuroscience, and resuscitation science has been to enable scientific insights regarding what happens to the human brain in relation to death. The scientific exploration of death is in large part possible due to the recognition that brain cells are more resilient to the effects of anoxia than assumed. Hence, brain cells become irreversibly damaged and "die" over hours to days postmortem. Resuscitation science has enabled life to be restored to millions of people after their hearts had stopped. These survivors have described a unique set of recollections in relation to death that appear universal. We review the literature, with a focus on death, the recalled experiences in relation to cardiac arrest, post-intensive care syndrome, and related phenomena that provide insights into potential mechanisms, ethical implications, and methodologic considerations for systematic investigation. We also identify issues and controversies related to the study of consciousness and the recalled experience of cardiac arrest and death in subjects who have been in a coma, with a view to standardize and facilitate future research.

In the absence of adequate measurement efforts, expansive gender and sexual identities will remain underexplored in quantitative social science and health research. We use primary survey data (N = 309) to identify factors associated with U.S.based social and health science faculty's attitudes toward inclusive gender and sexuality measures in participant-based research. Results suggest that political science faculty rated expansive gender and sexuality measures as less important to their own research, relative to psychology, sociology, and health sciences faculty. In addition, cisgender/heterosexual women and LGBTQ+ identifying faculty rate and apply these measures more positively compared to faculy who identify as cisgender/heterosexual men. Finally, faculty engaging in predominantly quantitative research, or in teaching-focused positions, had lower ratings of the importance of gender expansive measurement. Results suggest that while individual characteristics shape faculty's attitudes toward and use of inclusive gender and sexuality measures, disciplinary and academic contexts also matter.

Background and ObjectivesLoneliness is common, and its prevalence is rising. The relationship of loneliness with subsequent dementia and the early preclinical course of Alzheimer disease and related dementia (ADRD) remains unclear. Thus, the primary objective of this study was to determine the association of loneliness with 10-year all-cause dementia risk and early cognitive and neuroanatomic imaging markers of ADRD vulnerability.MethodsThis was a retrospective analysis of prospectively collected data from the population-based Framingham Study cohorts (September 9, 1948–December 31, 2018). Eligible participants had loneliness assessed and were dementia-free at baseline. Loneliness was recorded with the Center for Epidemiologic Studies Depression Scale, defined conservatively as feeling lonely ≥3 days in the past week. The main outcomes were incident dementia over a 10-year period, cognition, and MRI brain volumes and white matter injury.ResultsOf 2,308 participants (mean age 73 [SD 9] years, 56% women) who met eligibility in the dementia sample, 14% (329 of 2,308) developed dementia and 6% (144 of 2,308) were lonely. Lonely (versus not lonely) adults had higher 10-year dementia risk (age-, sex-, and education-adjusted hazard ratio 1.54, 95% CI 1.06–2.24). Lonely participants APOE ε4 alleles had a 3-fold greater risk (adjusted hazard ratio 3.03, 95% CI, 1.63–5.62). Among 1,875 persons without dementia who met eligibility in the cognition sample (mean age 62 [SD 9] years, 54% women), loneliness associated with poorer executive function, lower total cerebral volume, and greater white matter injury.DiscussionOver 10 years of close clinical dementia surveillance in this cohort study, loneliness was associated with increased dementia risk; this tripled in adults whose baseline risk would otherwise be relatively low on the basis of age and genetic risk, representing a majority of the US population. Loneliness was also associated with worse neurocognitive markers of ADRD vulnerability, suggesting an early pathogenic role. These findings may have important clinical and public health implications given observed loneliness trends.Classification of EvidenceThis study provides Class I evidence that loneliness increases the 10-year risk of developing dementia.

Preclinical studies indicate an age-associated accumulation of senescent cells across multiple organ systems. Emerging evidence suggests that tau protein accumulation, which closely correlates with cognitive decline in Alzheimer’s disease and other tauopathies, drives cellular senescence in the brain. Pharmacologically clearing senescent cells in mouse models of tauopathy reduced brain pathogenesis. Compared to vehicle treated mice, intermittent senolytic administration reduced tau accumulation and neuroinflammation, preserved neuronal and synaptic density, restored aberrant cerebral blood flow, and reduced ventricular enlargement. Intermittent dosing of the senolytics, dasatinib plus quercetin, has shown an acceptable safety profile in clinical studies for other senescence-associated conditions. With these data, we proposed and herein describe the objectives and methods for a clinical vanguard study. This initial open-label clinical trial pilots an intermittent senolytic combination therapy of dasatinib plus quercetin in five older adults with early-stage Alzheimer’s disease. The primary objective is to evaluate the central nervous system penetration of dasatinib and quercetin through analysis of cerebrospinal fluid collected at baseline and after 12 weeks of treatment. Further, through a series of secondary outcome measures to assess target engagement of the senolytic compounds and Alzheimer’s disease-relevant cognitive, functional, and physical outcomes, we will collect preliminary data on safety, feasibility, and efficacy. The results of this study will be used to inform the development of a randomized, double-blind, placebo-controlled multicenter phase II trial to further explore of the safety, feasibility, and efficacy of senolytics for modulating the progression of Alzheimer’s disease. Clinicaltrials.gov registration number and date: NCT04063124 (08/21/2019).

Background: Apathy is among the most frequent neuropsychiatric syndromes in Alzheimer’s disease (AD). Objective: To determine the prevalence of apathy and the associated clinical and laboratorial parameters (focus on inflammatory biomarkers) in patients with dementia enrolled at the Texas Alzheimer’s Research and Care Consortium (TARCC) study. Methods: This is a cross-sectional analysis of TARCC baseline. Participants were evaluated through different clinical tools, including the Mini-Mental State Examination (MMSE) and the Lawton-Brody Instrumental Activities of Daily Life (IADL)/Physical Self-Maintenance Scale (PSMS). Apathy was defined by a positive response to the respective item in the Neuropsychiatric Inventory–Questionnaire applied to caregivers. Serum levels of 16 biomarkers were determined by HumanMap multiplex immunoassay. Comparisons between apathy versus non-apathy groups were carried out with non-parametric tests. Logistic regression and the least absolute shrinkage and selection operator (LASSO) were used to separately model apathy as a function of each biomarker, adjusted for the potential confounders. Results: From 1,319 patients with AD (M/F: 579/740, mean age ± SD: 75.3 ± 8.4), 373 (28.3%) exhibited apathy. When categorized according to the presence of apathy, the groups had significant differences in sex, diabetes diagnosis, and tobacco use. The apathy group also had worse cognitive performance and daily functioning than the non-apathy group as assessed, respectively, by MMSE and IADL/PSMS. Higher levels of interleukin-6, interleukin-10, and leptin were associated with higher odds of apathy. Conclusion: Apathy is associated with cognitive and functional status in AD. The association between apathy and peripheral inflammatory mediators deserves further investigation.

Pragmatic biomarkers of preclinical dementia would allow for easy and large-scale screening of risk in populations. Physical function measures like grip strength and gait speed are potential predictive biomarkers but their relationship with plasma markers of Alzheimer's Disease and neurodegeneration have not been elucidated.To examine association between physical function measures and plasma markers of Alzheimer's Disease (AD) and neurodegeneration.Cross-sectional and longitudinal analyses.Community-based cohort in the city of Framingham, Massachusetts.2336 participants of the Framingham Heart Study Offspring cohort with an average age of 61.Plasma Aβ40 and Aβ42 were measured in 1998-2001 (Exam-7) and plasma total tau measured 5 years later (Exam-8). Grip strength, fast walk speed and chair stand speed were measured at both exams. Quantification of Aβ isoforms in plasma was performed using INNO-BIA assays and plasma total-tau was measured using Quanterix Simoa HD-1 assay. Confounder-adjusted linear regression models examined associations between physical function and plasma markers, Results: Grip strength at Exam-7 was associated with plasma Aβ40 (β -0.006, p-value 0.032) at Exam-7 and plasma total-tau (β -0.010, p-value 0.001) at Exam-8. Grip strength and fast walk speed at Exam-8 were associated with plasma total-tau at Exam-8 (GS: β -0.009, p 0.0005; FWS: β -0.226, p-value0.0001). Chair stand speed was not associated with plasma markers; Aβ42 was not associated with function.Grip strength and fast walk speed are associated with plasma markers of neurodegeneration in dementia-free middle aged and older individuals. Both these measures could be used as potential screening tools for identifying individuals at a higher risk for AD and related dementias alongside other validated markers.

PSR J1023+0038 is the first millisecond pulsar that was ever observed as an optical and UV pulsar. So far, it is the only optical transitional millisecond pulsar. The rotation- and accretion-powered emission mechanisms hardly individually explain the observed characteristics of optical pulsations. A synergistic model, combining these standard emission processes, was proposed to explain the origin of the X-ray/UV/optical pulsations. We study the phase lag between the pulses in the optical and X-ray bands to gain insight into the physical mechanisms that cause it. We performed a detailed timing analysis of simultaneous or quasi-simultaneous observations in the X-ray band, acquired with the XMM-Newton and NICER satellites, and in the optical band, with the fast photometers SiFAP2 (mounted at the 3.6 m Telescopio Nazionale Galileo) and Aqueye+ (mounted at the 1.8 m Copernicus Telescope). We estimated the time lag of the optical pulsation with respect to that in the X-rays by modeling the folded pulse profiles with two harmonic components. Optical pulses lag the X-ray pulses by $\sim$ 150 $\mu$s in observations acquired with instruments (NICER and Aqueye+) whose absolute timing uncertainty is much smaller than the measured lag. We also show that the phase lag between optical and X-ray pulsations lies in a limited range of values, $\delta \phi \in$ (0 $-$ 0.15), which is maintained over timescales of about five years. This indicates that both pulsations originate from the same region, and it supports the hypothesis of a common emission mechanism. Our results are interpreted in the shock-driven mini pulsar nebula scenario. This scenario suggests that optical and X-ray pulses are produced by synchrotron emission from the shock that formed within a few light cylinder radii away ($\sim$ 100 km) from the pulsar, where its striped wind encounters the accretion disk inflow., Comment: 13 pages, 6 figures, 5 tables, accepted for publication in A&A

Increasing patient age has been associated with worse outcomes after pituitary adenoma resection in previous studies, but the prognostic value of frailty compared with advancing age on pituitary adenoma resection outcomes has not been clearly evaluated.The National Surgical Quality Improvement Program from 2015 to 2019 was queried for data for patients aged18 years who underwent pituitary adenoma resection (n = 1454 identified patients). Univariate and multivariate analyses of age and frailty (5-factor modified frailty index [mFI-5]) were performed on 30-day mortality, major complications, extended length of stay (eLOS), discharge destination, and readmission and reoperation. The receiver operating characteristic curve analysis was performed to compare effect of age and mFI-5.On univariate analysis, increasing frailty was significantly associated with greater risk of unplanned readmission (frail: odds ratio [OR], 1.9; 95% confidence interval [CI], 1.2-3.2; severely frail: OR, 6.9; 95% CI, 2.4-19.8) and a major complication (frail: OR, 3.6; 95% CI, 2.1-6.1). Severe frailty was also associated with nonhome discharge (OR, 10.6; 95% CI, 3.2-35.8) and eLOS (OR, 4.5; 95% CI, 1.5-13.4). Increasing age was not associated with any of these outcome measures. Multivariate analysis also demonstrated similar trends. In receiver operating characteristic curve analysis, the mFI-5 score showed higher discrimination for major complications compared with age (area under the curve: 0.624 vs. 0.503; P0.001).Increasing frailty, and not advancing age, was an independent predictor for major complications, unplanned readmissions, eLOS, and nonhome discharge after pituitary adenoma resection, suggesting frailty to be superior to age in preoperative risk stratification in this patient population.

The COVID-19 pandemic has affected medical residency (MR) programs worldwide. However, few reports have focused on the MR of Physical Medicine and Rehabilitation (PMR). Therefore, our objective was to describe the perceptions of PMR residents in Peru about their MR during the COVID-19 pandemic.Cross-sectional study. During June 2021, we sought to address all PMR residents in Peru, using a virtual, anonymous and voluntary survey of 13 questions elaborated in Google Forms, which addressed their perception of RM.Of 142 PMR residents in Peru, 60 (42.3%) responded to the survey. Among these, 21.7% considered that their residency training site (RTS) met little or nothing with the minimum requirements to be one, 50% that their RTS cared little or notthing for him/her since the start of the COVID-19 pandemic, 35% that the physicians attending their RTS cared little or nothing about academics, and 71.7% that the lack of subspecialist physicians in PMR greatly affects their training. In addition, 71.7% and 81.7% reported having learned little or nothing about musculoskeletal ultrasound and electrodiagnostic studies, respectively. Finally, 18.3% reported regretting to have chosen the specialty.We found an important negative perception about MR and a low self-perception of having learned about musculoskeletal ultrasound and electrodiagnostic studies. It is important to delve into the causes and look for alternatives to improve the training of PMR residents.