Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns.

BACKGROUND: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018. METHODS: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge. RESULTS: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1-6.0%; I2, 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P<0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 [95% CI, 1.1-3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis. CONCLUSIONS: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.

Increased Butyrate Production in Clostridium saccharoperbutylacetonicum from Lignocellulose-Derived Sugars.

Butyrate is produced by chemical synthesis based on crude oil, produced by microbial fermentation, or extracted from animal fats (M. Dwidar, J.-Y. Park, R. J. Mitchell, and B.-I. Sang, The Scientific World Journal, 2012:471417, 2012, https://doi.org/10.1100/2012/471417). Butyrate production by anaerobic bacteria is highly favorable since waste or sustainable resources can be used as the substrates. For this purpose, the native hyper-butanol producer Clostridium saccharoperbutylacetonicum N1-4(HMT) was used as a chassis strain due to its broad substrate spectrum. BLASTp analysis of the predicted proteome of C. saccharoperbutylacetonicum N1-4(HMT) resulted in the identification of gene products potentially involved in acetone-butanol-ethanol (ABE) fermentation. Their participation in ABE fermentation was either confirmed or disproven by the parallel production of acids or solvents and the respective transcript levels obtained by transcriptome analysis of this strain. The genes encoding phosphotransacetylase (pta) and butyraldehyde dehydrogenase (bld) were deleted to reduce acetate and alcohol formation. The genes located in the butyryl-CoA synthesis (bcs) operon encoding crotonase, butyryl-CoA dehydrogenase with electron-transferring protein subunits α and ß, and 3-hydroxybutyryl-CoA dehydrogenase were overexpressed to channel the flux further towards butyrate formation. Thereby, the native hyper-butanol producer C. saccharoperbutylacetonicum N1-4(HMT) was converted into the hyper-butyrate producer C. saccharoperbutylacetonicum ΔbldΔpta [pMTL83151_BCS_PbgaL]. The transcription pattern following deletion and overexpression was characterized by a second transcriptomic study, revealing partial compensation for the deletion. Furthermore, this strain was characterized in pH-controlled fermentations with either glucose or Excello, a substrate yielded from spruce biomass. Butyrate was the main product, with maximum butyrate concentrations of 11.7 g·L-1 and 14.3 g·L-1, respectively. Minimal amounts of by-products were detected. IMPORTANCE Platform chemicals such as butyrate are usually produced chemically from crude oil, resulting in the carry-over of harmful compounds. The selective production of butyrate using sustainable resources or waste without harmful by-products can be achieved by bacteria such as clostridia. The hyper-butanol producer Clostridium saccharoperbutylacetonicum N1-4(HMT) was converted into a hyper-butyrate producer. Butyrate production with very small amounts of by-products was established with glucose and the sustainable lignocellulosic sugar substrate Excello extracted from spruce biomass by the biorefinery Borregaard (Sarpsborg, Norway).

We Must Do Better: Addressing High Mortality After Release from Incarceration.

People who are incarcerated have high rates of mental illness, substance use disorder, suicide attempts, and chronic medical conditions. Mortality rates are also significantly elevated following release. Additional work needs to be done to understand the risk factors for increased morbidity and mortality of people impacted by incarceration to better inform future interventions and system changes.

Does prenatal counseling for pregnancies complicated by multiple fetal abnormalities concord with postnatal outcomes?

OBJECTIVE: In pregnancies complicated by multiple fetal abnormalities, our objective was to determine the degree of concordance between prenatal prognosis and postnatal outcomes. METHOD: Retrospective cohort study of pregnancies with multiple fetal abnormalities referred to the Fetal Concerns Center of Wisconsin (FCCW) from 2015 to 2018. We reviewed records for anomalies, given prognostic severity, and postnatal outcomes. Prognostic severity was categorized as "likely mortality," "severe impairment," "moderate," and "mild" based on predetermined criteria. RESULTS: In 85 pregnancies with multiple fetal abnormalities, 48% were given a prognosis of "likely mortality," and 19% were given a prognosis of "severe impairment." In pregnancies that were continued after being counseled as "likely mortality," this outcome was concordant in all but one case, despite medical interventions. In pregnancies counseled as "severe impairment," the more common outcome was mortality or severe impairment in 88% of cases and survival with severe impairment in 33% of cases. Postnatal outcomes were concordant with prenatal severity in 68% of the cases, more severe in 20% of the cases, and less severe in fewer than 5% of cases. CONCLUSION: Prenatal predictions about severe outcomes are usually true in pregnancies complicated by multiple abnormalities. In cases of outcome discordance, outcomes tend to be more severe than predicted.

Defining Major Depressive Disorder Cohorts Using the EHR: Multiple Phenotypes Based on ICD-9 Codes and Medication Orders.

BACKGROUND: Major Depressive Disorder (MDD) is one of the most common mental illnesses and a leading cause of disability worldwide. Electronic Health Records (EHR) allow researchers to conduct unprecedented large-scale observational studies investigating MDD, its disease development and its interaction with other health outcomes. While there exist methods to classify patients as clear cases or controls, given specific data requirements, there are presently no simple, generalizable, and validated methods to classify an entire patient population into varying groups of depression likelihood and severity. METHODS: We have tested a simple, pragmatic electronic phenotype algorithm that classifies patients into one of five mutually exclusive, ordinal groups, varying in depression phenotype. Using data from an integrated health system on 278,026 patients from a 10-year study period we have tested the convergent validity of these constructs using measures of external validation, including patterns of psychiatric prescriptions, symptom severity, indicators of suicidality, comorbidity, mortality, health care utilization, and polygenic risk scores for MDD. RESULTS: We found consistent patterns of increasing morbidity and/or adverse outcomes across the five groups, providing evidence for convergent validity. LIMITATIONS: The study population is from a single rural integrated health system which is predominantly white, possibly limiting its generalizability. CONCLUSION: Our study provides initial evidence that a simple algorithm, generalizable to most EHR data sets, provides categories with meaningful face and convergent validity that can be used for stratification of an entire patient population.

Daily Pain, Physical Activity, and Home Fluid Intake in Pediatric Sickle Cell Disease.

Objectives: This study examined the temporal relationship between physical activity, fluid intake, and daily pain in children with sickle cell disease (SCD) with frequent pain. Methods: A total of 30 African American children ( M age = 13.9; 53% female; 76.3% type SS) who reported pain more than or equal to once every 2 weeks and their parents completed measures of pain and anxiety/depressive symptoms. Children then completed a daily pain diary and wore a physical activity Actiwatch for 14 days at home. Results: Contrary to physiological theory-based hypotheses, lower physical activity was associated with greater pain during the same day and the next day. Less pain was associated with greater physical activity the next day. There was no relationship between self-reported home fluid intake and daily pain ( p 's < .05). Conclusions: Results lend support for a complex bidirectional relationship between physical activity and daily pain in pediatric SCD, and identify physical activity as a target for future research.

Apo-bacteriophytochromes modulate bacterial photosynthesis in response to low light.

Bacteriophytochromes (BphPs) are light-sensing regulatory proteins encoded by photosynthetic and nonphotosynthetic bacteria. This protein class has been characterized structurally, but its biological activities remain relatively unexplored. Two BphPs in the anoxygenic photosynthetic bacterium Rhodopseudomonas palustris, designated regulatory proteins RpBphP2 and RpBphP3, are configured as light-regulated histidine kinases, which initiate a signal transduction system that controls expression of genes for the low light harvesting 4 (LH4) antenna complex. In vitro, RpBphP2 and RpBphP3 respond to light quality by reversible photoconversion, a property that requires the light-absorbing chromophore biliverdin. In vivo, RpBphP2 and RpBphP3 are both required for the expression of the LH4 antenna complex under anaerobic conditions, but biliverdin requires oxygen for its synthesis by heme oxygenase. On further investigation, we found that the apo-bacteriophytochrome forms of RpBphP2 and RpBphP3 are necessary and sufficient to control LH4 expression in response to light intensity in conjunction with other signal transduction proteins. One possibility is that the system senses a reduced quinone pool generated when light energy is absorbed by bacteriochlorophyll. The biliverdin-bound forms of the BphPs have the additional property of being able to fine-tune LH4 expression in response to light quality. These observations support the concept that some bacteriophytochromes can function with or without a chromophore and may be involved in regulating physiological processes not directly related to light sensing.

Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction.

UNLABELLED: Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacterium Ramlibacter tataouinensis RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, the R. tataouinensis bacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR from Agrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRRmon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems. IMPORTANCE: BphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of these proteins, rather than on signal transduction or the resultant phenotypes. To begin to address this knowledge gap, we solved the crystal structures of two single-domain response regulators encoded by a region immediately downstream of that encoding BphPs. We observed a previously unknown arm-in-arm dimer linkage. Monomerization via deletion of the C-terminal dimerization motif had an inhibitory effect on net response regulator phosphorylation, underlining the importance of these unusual dimers for signal transduction.

Comparing Socio-Demographics and HIV Testing and Prevention Outcomes Between Low-Income HIV-Negative Heterosexually Active Black Women and Men with Health Insurance.

OBJECTIVE: This study is to compare socio-demographic, HIV testing, and prevention factors experienced by insured low-income heterosexual Black women and men. METHODS: We examined cross-sectional data from Black women and men (n = 5837) recruited in 23 U.S. cities for National HIV Behavioral Surveillance June-December 2019. We compared socio-demographic and behavioral factors between groups using log-linked Poisson regression models, producing adjusted prevalence ratios and 95% confidence intervals. RESULTS: Black women were less likely than Black men to have private insurance (aPR 0.61, 95% CI 0.50-0.74, p < 0.0001). Black women were more likely than Black men to have incomes at or below the poverty line (aPR 1.04, 95% CI 1.01-1.07, p = 0.02), be aware of PrEP (aPR 1.20, 95% CI 1.12-1.28, p < 0.0001), and have been recently tested for HIV (aPR 1.12, 95% CI 1.04, 1.20, p < 0.01). CONCLUSIONS: Despite insured status, many Black women and men experienced suboptimal access to and utilization of HIV testing and prevention services. Understanding how social conditions produce differential access to care may help inform HIV prevention interventions.

Association of Neighborhood-Level Socioeconomic Factors With Delay to Hospital Arrival in Patients With Acute Stroke.

BACKGROUND AND OBJECTIVES: Delivery of acute ischemic stroke (AIS) therapies is contingent on the duration from last known well (LKW) to emergency department arrival time (EDAT). One reason for treatment ineligibility is delay in presentation to the hospital. We evaluate patient and neighborhood characteristics associated with time from LKW to EDAT. METHODS: This was a retrospective observational study of patients presenting to the Yale New Haven Hospital in the AIS code pathway from 2010 to 2020. Patients presenting within 4.5 hours from LKW who were recorded in the institutional Get With the Guidelines Stroke registry were classified as early while those presenting beyond 4.5 hours were designated as late. Temporal trends in late presentation were explored by univariate logistic regression. Using variables significant in univariate analysis at p < 0.05, we developed a mixed-effect logistic regression model to estimate the probability of late presentation as a function of patient-level and neighborhood (ZIP)-level characteristics (area deprivation index [ADI] derived from the Health Resources and Services Administration), adjusted for calendar year and geographic distance from the centroid of the ZIP code to the hospital. RESULTS: A total of 2,643 patients with AIS from 2010 to 2020 were included (63.4% presented late and 36.6% presented early). The frequency of late presentation increased significantly from 68% in 2010 to 71% in 2020 (p = 0.002) and only among non-White patients. Patients presenting late were more likely to be non-White (37.1% vs 26.9%, p < 0.0001), arrive by means other than emergency medical services (EMS) (32.7% vs 16.1%, p < 0.0001), have an NIHSS <6 (68.7% vs 55.2%, p < 0.0001), and present from a neighborhood with a higher ADI category (p = 0.0001) that was nearer to the hospital (median 5.8 vs 7.7 miles, p = 0.0032). In the mixed model, the ADI by units of 10 (odds ratio [OR] 1.022, 95% confidence interval [CI] 1.020-1.024), non-White race (OR 1.083, 95% CI 1.039-1.127), arrival by means other than EMS (OR 1.193, 95% CI 1.145-1.124), and an NIHSS <6 (OR 1.085, 95% CI 1.041-1.129) were associated with late presentation. DISCUSSION: In addition to patient-level factors, socioeconomic deprivation of neighborhood of residence contributes to delays in hospital presentation for AIS. These findings may provide opportunities for targeted interventions to improve presentation times in at-risk communities.

Efficacy and Impact of Peer-Led Education for Persons with Tuberculosis in Kampala, Uganda: A Pre-Post Implementation Study.

Introduction: Universal TB education and counseling (TEC) is routinely recommended for promoting knowledge and medication adherence, but the quality of delivery often varies because of inadequate clinic space, time, and health worker training. Peer-led counseling is a promising but understudied solution to these challenges. We sought to evaluate the efficacy of a peer-led TEC strategy among newly diagnosed adults initiating TB treatment in Kampala, Uganda. Methods: We conducted a longitudinal, pre-post implementation study comparing the routine, healthcare-worker-led and peer-led strategies for delivery of TEC to consecutive adult persons with TB at a large, public primary-care clinic. Trained staff administered a standardized TB knowledge survey to all persons with TB immediately following TEC. We compared TB knowledge by type of TEC received using t-tests. Results: We enrolled 161 persons with TB, 80 who received conventional TEC from health workers between June and July 2018, and 81 who received peer-led TEC between August and November 2019. The proportions of women (28% vs. 31%, p = 0.64) and persons living with HIV (36% vs 30%, p = 0.37) were similar in the pre- and post-implementation periods. Peer-led TEC was associated with a more significant increase in disease-specific (difference +21%, 95% CI +18% to + 24%, p < 0.0001) and treatment-specific TB knowledge scores (difference +14%, 95% CI + 10% to + 18%, p< 0.0001) than routine healthcare worker-delivered TEC. All TB knowledge constructs were significantly higher for those in the post-implementation period than those in the pre-implementation period. Nine participants met our threshold for adequate knowledge (score ≥ 90%) for disease-specific TB knowledge in the pre-implementation period compared to 63 (78%) in the post-implementation period (+67%, 95% CI + 55% - +78%, p < 0.001). Twenty-eight (35%) met the adequate knowledge threshold for TB treatment-specific knowledge in the pre-implementation period compared to 60 (74%) in the post-implementation period (+ 39%, 95% CI + 25 to + 53%, p < 0.0001). Finally, the proportion achieving TB treatment success (cure or completed) increased substantially from the pre-implementation period (n = 49, 68%) to the post-implementation period (n = 63, 88%), a difference of + 19% (95% CI + 6% to + 33%, p = 0.005). Conclusion: Our findings suggest that peer-led TEC is more efficacious than routine TEC at improving TB knowledge and treatment outcomes. Future studies should evaluate the implementation and effectiveness of the peer-led TEC strategy when scaled to a larger number of clinics.

Minimally invasive distal biceps tendon repair: a case series.

BACKGROUND: Distal biceps tendon repairs are commonly performed using open techniques. A minimally invasive distal biceps tendon repair technique using a speculum and hooded endoscope was developed to improve visualization, reduce soft-tissue dissection, and minimize complications. This paper describes the technique and reports the outcomes of 75 minimally invasive distal biceps tendon repairs. METHODS: The operation reports and outcomes of 75 patients who underwent distal biceps tendon repair using this technique between 2011 and 2021 were retrospectively reviewed. RESULTS: Median time to follow-up was 12 months (interquartile range [IQR], 6-56 months). Primary outcomes were function as measured by the Disabilities of Arm, Shoulder and Hand Score (DASH) questionnaire, and rate of complications. Median DASH score was 1.7 of 100 (IQR, 0-6.8). There were 2 of 75 (2.7%) re-ruptures of the distal tendon. There were no cases of vascular injury, proximal radius fracture, or posterior interosseous nerve, median, or ulnar nerve palsy. CONCLUSIONS: In this series, minimally invasive distal biceps repair was safe and effective with a low rate of major complications. Recovery of function, as indicated by low DASH scores, was satisfactory, and inconvenience during recovery was minimized. Level of evidence: IV.

Psychosocial functioning and adjustment to university settings: comparing students with chronic illnesses to healthy peers.

Purpose: College students with chronic illnesses are vulnerable to poor adjustment, but it remains unclear how these students differ from healthy peers. This study compares psychosocial adjustment and risky behavior between students with and without chronic illnesses. Participants: Participants (N = 629, 78% Caucasian, 77% Female) were recruited from universities. Methods: Participants completed measures of illness history, anxiety, depression, stressful life events, social support, and risky behavior. Results: College students with chronic illnesses demonstrated significantly greater symptoms of anxiety F(1,620) = 8.742, p < .003, depression F(1,614) = 26.947, p < .001, more stressful life events F(1,476) = 23.671, p < .001, and lower social support F(1,613) = 15.645, p < .001. No differences in risky behaviors between groups emerged F(1,601) = 3.432, p = .064. An indirect effect of health status on risk-taking behavior was observed [b = .677, 95% CI (.351, 1.072)] partially mediated by depression. Conclusion: College students with chronic illnesses demonstrated worse psychosocial outcomes than healthy students, warranting programs to support these students. Depressive symptoms partially mediated risky behavior.

Characterisation of internal tremors and vibration symptoms.

OBJECTIVES: To describe the experiences of patients who have postacute sequelae SARS-CoV-2 infection with internal vibrations and tremors as a prominent component, we leveraged the efforts by Survivor Corps, a grassroots COVID-19 patient advocacy group, to gather information from individuals belonging to its Facebook group with a history of COVID-19 suffering from vibrations and tremors. SETTING AND DESIGN: A narrative analysis was performed on 140 emails and 450 social media comments from 140 individuals collected as a response to a call to >180 000 individuals participating in Survivor Corps between 15 July and 27 July 2021. We used common coding techniques and the constant comparative method for qualitative data synthesis and categorising emails. Coded data were entered into NVivo V.12 to identify recurrent themes, theme connections and supporting quotations. Comments were analysed using Word Clouds, generated with R V.4.0.3 using quanteda, wordcloud and tm packages. MAIN OUTCOME MEASURES: Patient-reported long COVID symptom themes and domains related to internal tremors and vibration. RESULTS: The respondents' emails represented 22 themes and 7 domains pertaining to their experience with internal tremor and vibrations. These domains were as follows: (1) symptom experience, description and anatomic location; (2) initial symptom onset; (3) symptom timing; (4) symptom triggers or alleviators; (5) change from baseline health status; (6) experience with medical establishment and (7) impact on individuals' lives and livelihood. There were 22 themes in total, each corresponding to one of the broader domains. Among the responses, many described symptoms that varied in location, timing and triggers, occurred soon after their COVID-19 infection, and were markedly debilitating. There were often frustrating experiences with the healthcare system. CONCLUSIONS: This study describes key themes and experiences among a group of people reporting long COVID and having a prolonged and debilitating symptom complex that prominently features internal tremors and vibrations.

Evaluating clinical and demographic influences on health perception: A translation of the SF-12 for use with NHANES.

Improving public health depends on an intricate understanding of the factors that influence how individuals perceive and self-report their personal health. Self-perceived health is an independent predictor of future health-related outcomes, but capturing self-perception of health is complex due to the intricate relationship between clinical and perceived health. A commonly used measure of self-perceived health is the Short Form 12 (SF-12), developed in the 1990s. In this study, we aim to evaluate clinical and demographic influences on self-perceived health among American adults using the National Health and Nutrition Examination Survey (NHANES). While NHANES captures information on a number of domains of health, including clinical assessments, it does not include SF-12 items necessary to measure self-perceived health. Therefore, to assess self-perceived health for our study, we constructed and validated a novel SF-12-equivalent measure for use with NHANES using analogous items from the 2015-2016 NHANES interview questionnaires. The developed measure reflects established knowledge of population health patterns and closely parallels the behavior of the original SF-12. An analysis of the clinical and demographic influences on this novel measure of health perception revealed that both clinical and demographic factors, such as depression status and race, influence how healthy individuals perceive themselves to be. Importantly, our analysis indicated that among American adults, while controlling for clinical and demographic covariates, an increase in low-density lipoprotein (i.e., "bad") cholesterol level was associated with an improvement in self-perceived health. This study contributes significantly in two domains: it provides a novel measure of self-perceived health compatible for use with the widely used NHANES data (as well as details on how the process was developed), and it identifies a critical area in need of improved clinical education regarding the apparent confusion around cholesterol health.

The barriers and facilitators to physical activity in people with a musculoskeletal condition: A rapid review of reviews using the COM-B model to support intervention development.

Objectives: The objective of this review of reviews was to identify the potentially modifiable barriers and facilitators to physical activity in people with a musculoskeletal condition to influence intervention development. Study design: A rapid review of reviews. Methods: The Cochrane library and PubMed Central were searched for reviews using pre-defined search terms and relevant synonyms for "physical activity", "barriers" or "facilitators", and "musculoskeletal condition". The identified reviews were screened for inclusion by the principal investigator in line with recognised streamlining approaches for a rapid review. Only review papers investigating the barriers and facilitators to physical activity in adults with a musculoskeletal condition were included. A team of seven assessed the included reviews for identification of the barriers and facilitators to physical activity coded using the COM-B model of behaviour. Results: 503 reviews were identified with 12 included for analysis across a mix of conditions and designs (n = 2: qualitative; n = 6: quantitative; n = 4 mixed). A multitude of interrelated factors were identified across the COM-B components. The most prevalent factors included disease symptoms and physical function (physical capability), knowledge of the specific benefits of physical activity and knowing what to do (psychological capability), the accessibility of facilities and individualised programming (physical opportunity), tailored advice from healthcare professionals and peer support (social opportunity), beliefs about the benefits or harms of being active (reflective motivation) and having the self-efficacy to be active and experiencing positive emotions (automatic motivation). Conclusions: This review of reviews identified the complex nature of physical activity in people living with a musculoskeletal condition. The identified barriers and facilitators should be considered by intervention designers when developing behaviour change interventions for this population group.

Understanding the Patient Experience of Receiving Clinically Actionable Genetic Results from the MyCode Community Health Initiative, a Population-Based Genomic Screening Initiative.

Understanding unselected individuals' experiences receiving genetic results through population genomic screening is critical to advancing clinical utility and improving population health. We conducted qualitative interviews with individuals who received clinically actionable genetic results via the MyCode© Genomic Screening and Counseling program. We purposively sampled cohorts to seek diversity in result-related disease risk (e.g., cancer or cardiovascular) and in personal or family history of related diseases. Transcripts were analyzed using a two-step inductive coding process of broad thematic analysis followed by in-depth coding of each theme. Four thematic domains identified across all cohorts were examined: process assessment, psychosocial response, behavioral change due to the genetic result, and family communication. Coding of 63 interviews among 60 participants revealed that participants were satisfied with the results disclosure process, initially experienced a range of positive, neutral, and negative psychological reactions to results, adjusted positively to results over time, undertook clinically indicated actions in response to results, and communicated results with relatives to whom they felt emotionally close. Our findings of generally favorable responses to receiving clinically actionable genetic results via a genomic screening program may assuage fear of patient distress in such programs and guide additional biobanks, genomic screening programs, and research studies.

Restoration of PPARγ reverses lipid accumulation in alveolar macrophages of GM-CSF knockout mice.

Pulmonary alveolar proteinosis (PAP) is a lung disease characterized by a deficiency of functional granulocyte macrophage colony-stimulating factor (GM-CSF) resulting in surfactant accumulation and lipid-engorged alveolar macrophages. GM-CSF is a positive regulator of PPARγ that is constitutively expressed in healthy alveolar macrophages. We previously reported decreased PPARγ and ATP-binding cassette transporter G1 (ABCG1) levels in alveolar macrophages from PAP patients and GM-CSF knockout (KO) mice, suggesting PPARγ and ABCG1 involvement in surfactant catabolism. Because ABCG1 represents a PPARγ target, we hypothesized that PPARγ restoration would increase ABCG1 and reduce macrophage lipid accumulation. Upregulation of PPARγ was achieved using a lentivirus expression system in vivo. GM-CSF KO mice received intratracheal instillation of lentivirus (lenti)-PPARγ or control lenti-eGFP. Ten days postinstillation, 79% of harvested alveolar macrophages expressed eGFP, demonstrating transduction. Alveolar macrophages showed increased PPARγ and ABCG1 expression after lenti-PPARγ instillation, whereas PPARγ and ABCG1 levels remained unchanged in lenti-eGFP controls. Alveolar macrophages from lenti-PPARγ-treated mice also exhibited reduced intracellular phospholipids and increased cholesterol efflux to HDL, an ABCG1-mediated pathway. In vivo instillation of lenti-PPARγ results in: 1) upregulating ABCG1 and PPARγ expression of GM-CSF KO alveolar macrophages, 2) reducing intracellular lipid accumulation, and 3) increasing cholesterol efflux activity.