Neonatal IL-4 exposure decreases adipogenesis of male rats into adulthood.

The cytokine interleukin 4 (IL-4) can increase beige adipogenesis in adult rodents. However, neonatal animals use a distinct adipocyte precursor compartment for adipogenesis as compared with adults. In this study, we address whether IL-4 can induce persistent effects on adipose tissue when administered subcutaneously in the interscapular region during the neonatal period in Sprague-Dawley rats. We injected IL-4 into neonatal male rats during postnatal days 1-6, followed by analysis of adipose tissue and adipocyte precursors at 2 wk and 10 wk of age. Adipocyte precursors were cultured and subjected to differentiation in vitro. We found that a short and transient IL-4 exposure in neonates upregulated uncoupling protein 1 (Ucp1) mRNA expression and decreased fat cell size in subcutaneous white adipose tissue (WAT). Adipocyte precursors from mature rats that had been treated with IL-4 as neonates displayed a decrease in adiponectin (Adipoq) but no change in Ucp1 expression, as compared with controls. Thus, neonatal IL-4 induces acute beige adipogenesis and decreases adipogenic differentiation capacity long term. Overall, these findings indicate that the neonatal period is critical for adipocyte development and may influence the later onset of obesity.NEW & NOTEWORTHY We used neonatal injections in rat to show that IL-4 decreases adipogenesis and increases browning of white fat. In adulthood, adipocyte precursors show persistently decreased adipogenesis but not increased browning. These studies in the neonate are the first, to our knowledge, to show that IL-4 can have long-lasting effects.

A Pilot Study of Switching Electroconvulsive Therapy for Patients With Treatment Resistant Schizophrenia or Mood Disorder.

OBJECTIVES: Switching of ECT electrode modality is commonly done in clinical practice but outcomes are unclear. We aimed to compare the clinical outcomes between ECT modality switchers and nonswitchers in a large tertiary psychiatric institution over 1 year. METHODS: Brief Psychiatric Rating Scale (BPRS), Montgomery-Åsberg Depression Rating Scale (MADRS) and Montreal Cognitive Assessment (MoCA) were used to assess symptoms and cognition. General linear regression was utilized to compare the change of BPRS or MADRS and MoCA score among switchers vs nonswitchers. RESULTS: 21.5% of 209 patients switched ECT. Baseline BPRS scores were lower among nonswitchers. Response rate in schizophrenia, depression and mania were higher for nonswitchers (69.6%, 81.35% and 84.8% respectively / 9.2 (SD 3.3) sessions) compared to switchers (53.8%, 0% and 66.7% respectively / 10.6 (SD 4.5) sessions). Most common ECT switches were Bifrontal (BF) to Bitemporal (BT) (schizophrenia), UB RUL (ultrabrief right unilateral) to BT (depression), and UB RUL to BT / BF (mania). There was no significant difference in the change of BPRS and MoCA scores between nonswitchers and switchers. However, there was significantly more improvement of MADRS scores among nonswitchers [adjusted mean ± SE: (-26.4 ± 2.8)] compared with switchers (-10.6) ±6.6). CONCLUSIONS: ECT switching was commonly done and may result in better or worse outcomes than not switching depending on diagnosis. Controlled trials are required to address this urgent clinical issue.

The Role of Adipocyte Precursors in Development and Obesity.

Maintenance of adipocyte precursors is critical for regulating metabolism and preventing obesity related disease. These precursors have been immortalized and studied in cellular models as well as-more recently-in animal models. However, little is known about adipocyte precursors from animals of different ages. Most research has focused on adipocyte precursors during obesity. This review goes over the most recent reports of adipocyte precursors during development and in adulthood. Some of these new analyses are due to new techniques such as single cell-RNA sequencing and temporally controlled lineage tracing. With these tools, we have been able to further our understanding of adipocyte precursor lineages and their different regulatory mechanisms. As we learn more about adipocyte precursor plasticity and regulation, we can hope to use this knowledge for future clinical applications.

Perceived Neighborhood Environment and Its Association with Health Screening and Exercise Participation amongst Low-Income Public Rental Flat Residents in Singapore.

Background: In Singapore, an Asian city-state, more than 80% live in public housing. While the majority (90%) own their homes, a needy minority lives in rental flats. Public rental flats are built in the same location as owner-occupied blocks. We evaluated factors associated with perceptions of the neighborhood environment and its association with exercise and health screening participation. Methods: Logistic regression was used to identify associations between perceptions of the neighborhood environment (overall perceived neighborhood disadvantage, safety, and convenience) and sociodemographic factors, as well as exercise and screening participation, amongst residents aged ≥60 years in two Singaporean public housing precincts in 2016. Results: Our response rate was 62.1% (528/800). Staying in a rental flat independently was associated with increased neighborhood disadvantage (adjusted odds ratio, aOR = 1.58, 95%CI = 1.06⁻2.35). Staying in a stand-alone block (as opposed to staying in a mixed block comprised of both rental and owner-occupied units) was associated with perceptions of a poorer physical environment (aOR = 1.81, 95%CI = 1.22⁻2.68) and lower perceived proximity to recreational areas (aOR = 1.14, 95%CI = 1.04⁻1.25). Perceptions of neighborhood disadvantage were independently associated with reduced exercise participation (aOR = 0.67, 95%CI = 0.45⁻0.98) and reduced participation in diabetes screening (aOR = 0.63, 95%CI = 0.41⁻0.95). Conclusion: Despite sharing the same built environment, differences in the perception of the neighborhood environment between low-socioeconomic status (SES) and high-SES communities persist. Perceived neighborhood disadvantage is associated with lower participation in regular exercise and diabetes screening.

Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2.

The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2Δ/Δ mutant separates biofilm formation and invasion. We found that an rhr2Δ/Δ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2Δ/Δ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population.

Use of "spare parts" in mutilated upper extremity injuries.

Management and treatment of complex mutilated upper extremity injuries often can be challenging and at times seemingly formidable. A reconstructive surgeon's ability to mobilize, transpose, and transfer tissues has allowed not only closure of complex wounds but also restoration of function and form. Use of "spare parts" from an otherwise unsalvageable limb represents the ultimate form of reconstruction that probes the creative mind and challenges the reconstructive knowledge of the surgeon. In this article, the authors review and discuss the use of various "spare parts" in the treatment of mutilating hand injuries.

Secondary procedures following mutilating hand injuries.

Mutilating hand injuries result in injury to multiple anatomic structures, which increases the possibility that secondary procedures or staged reconstruction will be necessary. Secondary procedures often are required to provide stable wound coverage, restore sensation, provide bony stability, increase range of motion, or allow prehension, all of which are performed to improve hand function. The patient, the surgeon, and the therapist must all work together to achieve the best functional result following a severe mutilating hand injury.