Social Determinants of Health: Underreported Heterogeneity in Systematic Reviews of Caregiver Interventions.

BACKGROUND AND OBJECTIVES:Although most people have some experience as caregivers, the nature and context of care are highly variable. Caregiving, socioeconomic factors, and health are all interrelated. For these reasons, caregiver interventions must consider these factors. This review examines the degree to which caregiver intervention research has reported and considered social determinants of health. RESEARCH DESIGN AND METHODS:We examined published systematic reviews and meta-analyses of interventions for older adults with age-related chronic conditions using the PRISMA and AMSTAR 2 checklists. From 2,707 papers meeting search criteria, we identified 197 potentially relevant systematic reviews, and selected 33 for the final analysis. RESULTS:We found scant information on the inclusion of social determinants; the papers lacked specificity regarding race/ethnicity, gender, sexual identity, socioeconomic status, and geographic location. The majority of studies focused on dementia, with other conditions common in later life vastly underrepresented. DISCUSSION AND IMPLICATIONS:Significant gaps in evidence persist, particularly for interventions targeting diverse conditions and populations. To advance health equity and improve the effectiveness of interventions, research should address caregiver heterogeneity and improve assessment, support, and instruction for diverse populations. Research must identify aspects of heterogeneity that matter in intervention design, while recognizing opportunities for common elements and strategies

Slow Diffeomorphisms of a Manifold with Two Dimensions Torus Action

The uniform norm of the differential of the n-th iteration of a diffeomorphism is called the growth sequence of the diffeomorphism. In this paper we show that there is no lower universal growth bound for volume preserving diffeomorphisms on manifolds with an effective two dimensions torus action by constructing a set of volume-preserving diffeomorphisms with arbitrarily slow growth.Comment: 12 p

Successful MRI-Guided Focused Ultrasound Uterine Fibroid Treatment Despite an Ostomy and Significant Abdominal Wall Scarring

We present a case of successful magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) of a uterine fibroid in a patient with extensive anterior abdominal wall surgical scars from two longitudinal laparotomies, a total colectomy and ileostomy. This case demonstrates that MRgFUS can be safely used in patients with an ostomy and significant abdominal wall scarring, but careful pretreatment planning and positioning during treatment is needed

Patterns of beverages consumed and risk of incident kidney disease

© 2019 by the American Society of Nephrology. Background and objectives Selected beverages, such as sugar-sweetened beverages, have been reported to influence kidney disease risk, although previous studies have been inconsistent. Further research is necessary to comprehensively evaluate all types of beverages in association with CKD risk to better inform dietary guidelines. Design, setting, participants, & measurements We conducted a prospective analysis in the Jackson Heart Study, a cohort of black men and women in Jackson, Mississippi. Beverage intake was assessed using a food frequency questionnaire administered at baseline (2000–2004). Incident CKD was defined as onset of eGFR\u3c60 ml/min per 1.73 m 2 and ≥30% eGFR decline at follow-up (2009–13) relative to baseline among those with baseline eGFR ≥60 ml/min per 1.73 m 2 . Logistic regression was used to estimate the association between the consumption of each individual beverage, beverage patterns, and incident CKD. Beverage patterns were empirically derived using principal components analysis, in which components were created on the basis of the linear combinations of beverages consumed. Results Among 3003 participants, 185 (6%) developed incident CKD over a median follow-up of 8 years. At baseline, mean age was 54 (SD 12) years, 64% were women, and mean eGFR was 98 (SD 18) ml/min per 1.73 m 2 . After adjusting for total energy intake, age, sex, education, body mass index, smoking, physical activity, hypertension, diabetes, HDL cholesterol, LDL cholesterol, history of cardiovascular disease, and baseline eGFR, a principal components analysis–derived beverage pattern consisting of higher consumption of soda, sweetened fruit drinks, and water was associated with significantly greater odds of incident CKD (odds ratio tertile 3 versus 1 =1.61; 95% confidence interval, 1.07 to 2.41). Conclusions Higher consumption of sugar-sweetened beverages was associated with an elevated risk of subsequent CKD in this community-based cohort of black Americans

Social Determinants of Health: Underreported Heterogeneity in Systematic Reviews of Caregiver Interventions

Background and Objectives: Although most people have some experience as caregivers, the nature and context of care are highly variable. Caregiving, socioeconomic factors, and health are all interrelated. For these reasons, caregiver interventions must consider these factors. This review examines the degree to which caregiver intervention research has reported and considered social determinants of health. Research Design and Methods: We examined published systematic reviews and meta-analyses of interventions for older adults with age-related chronic conditions using the PRISMA and AMSTAR 2 checklists. From 2,707 papers meeting search criteria, we identified 197 potentially relevant systematic reviews, and selected 33 for the final analysis. Results: We found scant information on the inclusion of social determinants; the papers lacked specificity regarding race/ethnicity, gender, sexual identity, socioeconomic status, and geographic location. The majority of studies focused on dementia, with other conditions common in later life vastly underrepresented. Discussion and Implications: Significant gaps in evidence persist, particularly for interventions targeting diverse conditions and populations. To advance health equity and improve the effectiveness of interventions, research should address caregiver heterogeneity and improve assessment, support, and instruction for diverse populations. Research must identify aspects of heterogeneity that matter in intervention design, while recognizing opportunities for common elements and strategies

Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling

BACKGROUND: Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown. METHODS: To understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, unc-116, at the corresponding position (Thr90Ile) by CRISPR/Cas9 editing and performed functional analysis. Next, we studied the cellular and molecular consequences of the recurrent p.Thr87Ile variant by microscopy, RNA and protein analysis in NIH3T3 cells, primary human fibroblasts and bone biopsy. RESULTS: C. elegans heterozygous for the unc-116 Thr90Ile variant displayed abnormal body length and motility phenotypes that were suppressed by additional copies of the wild type allele, consistent with a dominant negative mechanism. Time-lapse imaging of GFP-tagged mitochondria showed defective mitochondria transport in unc-116 Thr90Ile neurons providing strong evidence for disrupted kinesin motor function. Microscopy studies in human cells showed dilated endoplasmic reticulum, multiple intracellular vacuoles, and abnormal distribution of the Golgi complex, supporting an intracellular trafficking defect. RNA sequencing, proteomic analysis, and bone immunohistochemistry demonstrated down regulation of the mTOR signaling pathway that was partially rescued with leucine supplementation in patient cells. CONCLUSION: We report dominant negative variants in the KIF5B kinesin motor domain in individuals with osteogenesis imperfecta. This study expands the spectrum of kinesin-related disorders and identifies dysregulated signaling targets for KIF5B in skeletal development

All-fibre heterogeneously-integrated frequency comb generation using silicon core fibre.

Originally developed for metrology, optical frequency combs are becoming increasingly pervasive in a wider range of research topics including optical communications, spectroscopy, and radio or microwave signal processing. However, application demands in these fields can be more challenging as they require compact sources with a high tolerance to temperature variations that are capable of delivering flat comb spectra, high power per tone, narrow linewidth and high optical signal-to-noise ratio. This work reports the generation of a flat, high power frequency comb in the telecom band using a 17 mm fully-integrated silicon core fibre as a parametric mixer. Our all-fibre, cavity-free source combines the material benefits of planar waveguide structures with the advantageous properties of fibre platforms to achieve a 30 nm bandwidth comb source containing 143 tones with 30 dB OSNR over the entire spectral region

Gemfibrozil Inhibits Legionella pneumophila and Mycobacterium tuberculosis Enoyl Coenzyme A Reductases and Blocks Intracellular Growth of These Bacteria in Macrophages

We report here that gemfibrozil (GFZ) inhibits axenic and intracellular growth of Legionella pneumophila and of 27 strains of wild-type and multidrug-resistant Mycobacterium tuberculosis in bacteriological medium and in human and mouse macrophages, respectively. At a concentration of 0.4 mM, GFZ completely inhibited L. pneumophila fatty acid synthesis, while at 0.12 mM it promoted cytoplasmic accumulation of polyhydroxybutyrate. To assess the mechanism(s) of these effects, we cloned an L. pneumophila FabI enoyl reductase homolog that complemented for growth an Escherichia coli strain carrying a temperature-sensitive enoyl reductase and rendered the complemented E. coli strain sensitive to GFZ at the nonpermissive temperature. GFZ noncompetitively inhibited this L. pneumophila FabI homolog, as well as M. tuberculosis InhA and E. coli FabI

A Two-Biomarker Model Predicts Mortality in the Critically Ill with Sepsis.

RATIONALE: Improving the prospective identification of patients with systemic inflammatory response syndrome (SIRS) and sepsis at low risk for organ dysfunction and death is a major clinical challenge. OBJECTIVES: To develop and validate a multibiomarker-based prediction model for 28-day mortality in critically ill patients with SIRS and sepsis. METHODS: A derivation cohort (n = 888) and internal test cohort (n = 278) were taken from a prospective study of critically ill intensive care unit (ICU) patients meeting two of four SIRS criteria at an academic medical center for whom plasma was obtained within 24 hours. The validation cohort (n = 759) was taken from a prospective cohort enrolled at another academic medical center ICU for whom plasma was obtained within 48 hours. We measured concentrations of angiopoietin-1, angiopoietin-2, IL-6, IL-8, soluble tumor necrosis factor receptor-1, soluble vascular cell adhesion molecule-1, granulocyte colony-stimulating factor, and soluble Fas. MEASUREMENTS AND MAIN RESULTS: We identified a two-biomarker model in the derivation cohort that predicted mortality (area under the receiver operator characteristic curve [AUC], 0.79; 95% confidence interval [CI], 0.74-0.83). It performed well in the internal test cohort (AUC, 0.75; 95% CI, 0.65-0.85) and the external validation cohort (AUC, 0.77; 95% CI, 0.72-0.83). We determined a model score threshold demonstrating high negative predictive value (0.95) for death. In addition to a low risk of death, patients below this threshold had shorter ICU length of stay, lower incidence of acute kidney injury, acute respiratory distress syndrome, and need for vasopressors. CONCLUSIONS: We have developed a simple, robust biomarker-based model that identifies patients with SIRS/sepsis at low risk for death and organ dysfunction