Identify determinants of weight gain in people with type 2 diabetes mellitus (T2DM) allocated to intensive versus standard glycemic control in the Action to Control Cardiovascular Risk in Diabetes ...(ACCORD) trial.
We studied determinants of weight gain over 2 years in 8,929 participants (4,425 intensive arm and 4,504 standard arm) with T2DM in the ACCORD trial. We used general linear models to examine the association between each baseline characteristic and weight change at the 2-year visit. We fit a linear regression of change in weight and A1C and used general linear models to examine the association between each medication at baseline and weight change at the 2-year visit, stratified by glycemia allocation.
There was significantly more weight gain in the intensive glycemia arm of the trial compared with the standard arm (3.0 ± 7.0 vs. 0.3 ± 6.3 kg). On multivariate analysis, younger age, male sex, Asian race, no smoking history, high A1C, baseline BMI of 25-35, high waist circumference, baseline insulin use, and baseline metformin use were independently associated with weight gain over 2 years. Reduction of A1C from baseline was consistently associated with weight gain only when baseline A1C was elevated. Medication usage accounted for <15% of the variability of weight change, with initiation of thiazolidinedione (TZD) use the most prominent factor. Intensive participants who never took insulin or a TZD had an average weight loss of 2.9 kg during the first 2 years of the trial. In contrast, intensive participants who had never previously used insulin or TZD but began this combination after enrolling in the ACCORD trial had a weight gain of 4.6-5.3 kg at 2 years.
Weight gain in ACCORD was greater with intensive than with standard treatment and generally associated with reduction of A1C from elevated baseline values. Initiation of TZD and/or insulin therapy was the most important medication-related factor associated with weight gain.
To study the biodistribution of MSCs, we labeled adult murine C57BL/6 MSCs with firefly luciferase and DsRed2 fluorescent protein using nonviral Sleeping Beauty transposons and coinfused labeled MSCs ...with bone marrow into irradiated allogeneic recipients. Using in vivo whole‐body imaging, luciferase signals were shown to be increased between weeks 3 and 12. Unexpectedly, some mice with the highest luciferase signals died and all surviving mice developed foci of sarcoma in their lungs. Two mice also developed sarcomas in their extremities. Common cytogenetic abnormalities were identified in tumor cells isolated from different animals. Original MSC cultures not labeled with transposons, as well as independently isolated cultured MSCs, were found to be cytogenetically abnormal. Moreover, primary MSCs derived from the bone marrow of both BALB/c and C57BL/6 mice showed cytogenetic aberrations after several passages in vitro, showing that transformation was not a strain‐specific nor rare event. Clonal evolution was observed in vivo, suggesting that the critical transformation event(s) occurred before infusion. Mapping of the transposition insertion sites did not identify an obvious transposon‐related genetic abnormality, and p53 was not overexpressed. Infusion of MSC‐derived sarcoma cells resulted in malignant lesions in secondary recipients. This new sarcoma cell line, S1, is unique in having a cytogenetic profile similar to human sarcoma and contains bioluminescent and fluorescent genes, making it useful for investigations of cellular biodistribution and tumor response to therapy in vivo. More importantly, our study indicates that sarcoma can evolve from MSC cultures.
Clostridium difficile infection (CDI) is becoming more common worldwide. The morbidity and mortality associated with C difficile is also increasing at an alarming rate. Critically ill patients are at ...particularly high risk for CDI because of the prevalence of multiple risk factors in this patient population. Treatment of C difficile continues to be a difficult problem in patients with severe or recurrent disease. This article seeks to provide a broad understanding of CDI in the intensive care unit, with special emphasis on risk factor identification, treatment options, and disease prevention.
To initiate a system-level analysis of
C. elegans DAF-7/TGF-β signaling, we combined interactome mapping with single and double genetic perturbations. Yeast two-hybrid (Y2H) screens starting with ...known DAF-7/TGF-β pathway components defined a network of 71 interactions among 59 proteins. Coaffinity purification (co-AP) assays in mammalian cells confirmed the overall quality of this network. Systematic perturbations of the network using RNAi, both in wild-type and
daf-7/TGF-β pathway mutant animals, identified nine DAF-7/TGF-β signaling modifiers, seven of which are conserved in humans. We show that one of these has functional homology to human SNO/SKI oncoproteins and that mutations at the corresponding genetic locus
daf-5 confer defects in DAF-7/TGF-β signaling. Our results reveal substantial molecular complexity in DAF-7/TGF-β signal transduction. Integrating interactome maps with systematic genetic perturbations may be useful for developing a systems biology approach to this and other signaling modules.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Enhancing health equity is endorsed in the Sustainable Development Goals. The failure of systematic reviews to consider potential differences in effects across equity factors is cited by ...decision‐makers as a limitation to their ability to inform policy and program decisions.
Objectives
To explore what methods systematic reviewers use to consider health equity in systematic reviews of effectiveness.
Search methods
We searched the following databases up to 26 February 2021: MEDLINE, PsycINFO, the Cochrane Methodology Register, CINAHL, Education Resources Information Center, Education s, Criminal Justice s, Hein Index to Foreign Legal Periodicals, PAIS International, Social Services s, Sociological s, Digital Dissertations and the Health Technology Assessment Database. We searched SCOPUS to identify articles that cited any of the included studies on 10 June 10 2021. We contacted authors and searched the reference lists of included studies to identify additional potentially relevant studies.
Selection criteria
We included empirical studies of cohorts of systematic reviews that assessed methods for measuring effects on health inequalities. We define health inequalities as unfair and avoidable differences across socially stratifying factors that limit opportunities for health. We operationalised this by assessing studies which evaluated differences in health across any component of the PROGRESS‐Plus acronym, which stands for Place of residence, Race/ethnicity/culture/language, Occupation, Gender or sex, Religion, Education, Socioeconomic status, Social capital. "Plus" stands for other factors associated with discrimination, exclusion, marginalisation or vulnerability such as personal characteristics (e.g. age, disability), relationships that limit opportunities for health (e.g. children in a household with parents who smoke) or environmental situations which provide limited control of opportunities for health (e.g. school food environment).
Data collection and analysis
Two review authors independently extracted data using a pre‐tested form. Risk of bias was appraised for included studies according to the potential for bias in selection and detection of systematic reviews.
Main results
In total, 48,814 studies were identified and the titles and s were screened in duplicate. In this updated review, we identified an additional 124 methodological studies published in the 10 years since the first version of this review, which included 34 studies. Thus, 158 methodological studies met our criteria for inclusion. The methods used by these studies focused on evidence relevant to populations experiencing health inequity (108 out of 158 studies), assess subgroup analysis across PROGRESS‐Plus (26 out of 158 studies), assess analysis of a gradient in effect across PROGRESS‐Plus (2 out of 158 studies) or use a combination of subgroup analysis and focused approaches (20 out of 158 studies). The most common PROGRESS‐Plus factors assessed were age (43 studies), socioeconomic status in 35 studies, low‐ and middle‐income countries in 24 studies, gender or sex in 22 studies, race or ethnicity in 17 studies, and four studies assessed multiple factors across which health inequity may exist.
Only 16 studies provided a definition of health inequity. Five methodological approaches to consider health equity in systematic reviews of effectiveness were identified: 1) descriptive assessment of reporting and analysis in systematic reviews (140 of 158 studies used a type of descriptive method); 2) descriptive assessment of reporting and analysis in original trials (50 studies); 3) analytic approaches which assessed differential effects across one or more PROGRESS‐Plus factors (16 studies); 4) applicability assessment (25 studies) and 5) stakeholder engagement (28 studies), which is a new finding in this update and examines the appraisal of whether relevant stakeholders with lived experience of health inequity were included in the design of systematic reviews or design and delivery of interventions. Reporting for both approaches (analytic and applicability) lacked transparency and was insufficiently detailed to enable the assessment of credibility.
Authors' conclusions
There is a need for improvement in conceptual clarity about the definition of health equity, describing sufficient detail about analytic approaches (including subgroup analyses) and transparent reporting of judgments required for applicability assessments in order to consider health equity in systematic reviews of effectiveness.
Multiple articles and surveys in the literature suggest that medical students find a career in pathology undesirable and believe it is disproportionately focused primarily on the autopsy.
To measure ...the effect of applied interventions on medical student attitudes about the field of pathology.
This prospective study involving medical students from first through fourth year was conducted as a pilot study in 2 medical schools in the United States. A 2-part anonymous survey regarding interest in pathology as a career and familiarity with the specialty using a 10-point scale was given to first- and second-year medical students before and after they listened to a 10-minute pathology career presentation. The same survey was given to third- and fourth-year medical students before and after a 4-week pathology elective.
A total of 121 and 83 students responded to the survey before and after the intervention, respectively. Of the 121 students who responded to the survey before the intervention, 106 (87.6%) had not spent significant time in a pathology laboratory before the intervention. The majority of responses in interest in career, job responsibilities, and features of pathologists before and after the intervention demonstrated a statistically significant difference (P < .001). We compared survey scores of presentation versus 4-week rotation groups before and after the intervention. Students who experienced the presentation did not differ from students who experienced the rotation in the majority of questions related to interest in career, job responsibilities, and features of pathologists.
Our study suggests that pathology exposure strategies can have a beneficial effect on student perceptions of the field and consideration of a career in pathology. Overall, the presentation intervention seemed to have the greatest effect on the first- and second-year students.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Introduction: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in travelers as well as for children living in low- to middle-income countries. ETEC adhere to intestinal epithelium via ...colonization factors (CFs). CFA/I, a common CF, is composed of a polymeric stalk and a tip-localized minor adhesive subunit, CfaE. Vaccine delivery by the transcutaneous immunization of dscCfaE was safe but was poorly immunogenic in a phase 1 trial when administered to volunteers with LTR(192G) and mLT. To potentially enhance the immunogenicity of CfaE while still delivering via a cutaneous route, we evaluated the safety and immunogenicity of two CfaE constructs administered intradermally (ID) with or without mLT. Methods: CfaE was evaluated as a donor strand-complemented construct (dscCfaE) and as a chimeric construct (Chimera) in which dscCfaE replaces the A1 domain of the cholera toxin A subunit and assembles non-covalently with the pentamer of heat-labile toxin B (LTB). Subjects received three ID vaccinations three weeks apart with either dscCfaE (1, 5, and 25 µg) or Chimera (2.6 and 12.9 µg) with and without 0.1 µg of mLT. Subjects were monitored for local and systemic adverse events. Immunogenicity was evaluated by serum and antibody-secreting cell (ASC) responses. Results. The vaccine was well-tolerated with predominantly mild and moderate local vaccine site reactions characterized by erythema, induration and post-inflammatory hyperpigmentation. High rates of serologic and ASC responses were seen across study groups with the most robust responses observed in subjects receiving 25 µg of dscCfaE with 0.1 mcg of LT(R192G). Conclusion: Both ETEC adhesin vaccine prototypes were safe and immunogenic when co-administered with mLT by the ID route. The observed immune responses induced with the high dose of dscCfaE and mLT warrant further assessment in a controlled human infection model.
The chemical composition of stars hosting small exoplanets (with radii less than four Earth radii) appears to be more diverse than that of gas-giant hosts, which tend to be metal-rich. This implies ...that small, including Earth-size, planets may have readily formed at earlier epochs in the universe's history when metals were more scarce. We report Kepler spacecraft observations of Kepler-444, a metal-poor Sun-like star from the old population of the Galactic thick disk and the host to a compact system of five transiting planets with sizes between those of Mercury and Venus. We validate this system as a true five-planet system orbiting the target star and provide a detailed characterization of its planetary and orbital parameters based on an analysis of the transit photometry. Kepler-444 is the densest star with detected solar-like oscillations. We use asteroseismology to directly measure a precise age of 11.2 + or - 1.0 Gyr for the host star, indicating that Kepler-444 formed when the universe was less than 20% of its current age and making it the oldest known system of terrestrial-size planets. We thus show that Earth-size planets have formed throughout most of the universe's 13.8 billion year history, leaving open the possibility for the existence of ancient life in the Galaxy. The age of Kepler-444 not only suggests that thick-disk stars were among the hosts to the first Galactic planets, but may also help to pinpoint the beginning of the era of planet formation.
We report on a 3 yr spectroscopic monitoring program of the Ha emission in the massive X-ray binary LS I +65 010 = 2S 0114+650, which consists of a B supergiant and a slowly rotating X-ray pulsar. We ...present revised orbital elements that yield a period of P = 11.5983 c 0.0006 days and confirm that the orbit has a nonzero eccentricity e = 0.18 c 0.05. The Ha emission profile is formed in the base of the wind of the B supergiant primary, and we show how this spectral feature varies on timescales that are probably related to the rotational period of the B supergiant. We also examine the X-ray fluxes from the Rossi X-ray Timing Explorer All-Sky Monitor instrument, and we show that the X-ray orbital light curve has a maximum at periastron and a minimum at the inferior conjunction of the B supergiant. We also show that the wind emission strength and the high-energy X-ray flux appear to vary in tandem on timescales of approximately 1 yr.
PDF
