Altered Fetal Skeletal Muscle Nutrient Metabolism Following an Adverse In Utero Environment and the Modulation of Later Life Insulin Sensitivity

The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.     

Healthcare utilization following spinal cord injury: Objective findings from a regional hospital registry

Objective: The purpose was to describe the prevalence and characteristics of healthcare utilization among individuals with spinal cord injury (SCI) from a Level I trauma center.

Design: Retrospective data analysis utilizing a local acute trauma registry for initial hospitalization and merged with the Dallas-Fort Worth Hospital Council registry to obtain subsequent health care utilization in the first post-injury year.

Setting: Dallas, TX, USA.

Participants: Six hundred and sixty four patients were admitted with an acute traumatic SCI from January 2003 through June 2014 to a Level I trauma center. Fifty five patients that expired during initial hospitalization and 18 patients with unspecified SCI (defined by ICD-9 with no etiology or level of injury specified) were not included in the analysis, leaving a final sample of 591.

Outcome Measures: Data included demographic and clinical characteristics, charges, and healthcare utilization.

Results: Mean age was 46.1?years (±18.9?years), the majority of patients were male (74%), and Caucasian (58%). Of the 591 patients, 345 (58%) had additional inpatient or emergency healthcare utilization accounting for 769 additional visits (median of 3 visits per person). Of the 769 encounters, 534 (69%) were inpatient and 235 (31%) were emergency visits not resulting in an admission. The most prevalent ICD-9 codes listed were pressure ulcer, neurogenic bowel, neurogenic bladder, urinary tract infection, fluid electrolyte imbalance, hypertension, and tobacco use.

Conclusion: Individuals with SCI experience high levels of healthcare utilization which are costly and may be preventable. Increasing our understanding of the prevalence and causes for healthcare utilization after acute SCI is important to target preventive strategies.     

Future Directions for Early Childhood Prevention of Mental Disorders: A Road Map to Mental Health,Earlier

Mental disorders are the predominant chronic diseases of youth, with substantial life span morbidity and mortality. A wealth of evidence demonstrates that the neurodevelopmental roots of common mental health problems are present in early childhood. Unfortunately, this has not been translated to systematic strategies for improving population-level mental health at this most malleable neurodevelopmental period. We lay out a translational Mental Health, Earlier road map as a key future direction for prevention of mental disorder. This paradigm shift aims to reduce population attributable risk of mental disorder emanating from early life, by preventing, attenuating, or delaying onset/course of chronic psychopathology via the promotion of self-regulation in early childhood within large-scale health care delivery systems. The Earlier Pillar rests on a “science of when to worry” that (a) optimizes clinical assessment methods for characterizing probabilistic clinical risk beginning in infancy via deliberate incorporation of neurodevelopmental heterogeneity, and (b) universal primary-care-based screening targeting patterns of dysregulated irritability as a robust transdiagnostic marker of vulnerability to life span mental health problems. The core of the Healthier Pillar is provision of low-intensity selective intervention promoting self-regulation for young children with developmentally atypical patterns of irritability within an implementation science framework in pediatric primary care to ensure highest population impact and sustainability. These Mental Health, Earlier strategies hold much promise for transforming clinical outlooks and ensuring young children’s mental health and well-being in a manner that reverberates throughout the life span.     

Nitrogen mustard gel-induced inflammation triggers lymphomatoid papulosis in patients with mycosis fungoides

Lymphomatoid papulosis (LyP) is a paraneoplastic primary cutaneous CD30⁺ lymphoproliferative disorder (LPD) that has been associated with malignant lymphomas, most commonly mycosis fungoides (MF). We observed 10 patients with MF who developed severe inflammation after using nitrogen-mustard (NM) gel from 1 to 8 months and who developed LyP. We hypothesized that NM gel produced local inflammation, which induced CD30 expression in malignant T cells in situ leading to the appearance of LyP papules. The high frequency of induction of LyP lesions in patients with severe inflammation while on treatment with NM gel suggests an association between inflammatory stimuli and development of LyP. Our observation provides insight into the pathogenesis of CD30⁺ LPD.     

Trichoblastoma,syringocystadenoma papilliferum,desmoplastic trichilemmoma and tumor of the follicular infundibulum with signet‐ring cells,all arising in nevus sebaceus

Herein, we describe a 63‐year‐old male with multiple tumors arising within a nevus sebaceus on the posterior scalp. On histopathologic examination, four distinct tumors were identified: trichoblastoma, syringocystadenoma papilliferum, desmoplastic trichilemmoma and tumor of the follicular infundibulum (TFI). Within the TFI component of the nevus sebaceus, there was intracytoplasmic accumulation of eosinophilic keratin, as shown on pancytokeratin‐stained sections, imparting a signet‐ring appearance to the cells. To our knowledge, this is the first report of signet‐ring cells arising within a TFI occurring in a nevus sebaceus. We discuss this case as well as review the literature on multiple tumors arising within nevus sebaceus and signet‐ring cell changes in primary cutaneous tumors.     

Impact of Diet Composition in Adult Offspring is Dependent on Maternal Diet during Pregnancy and Lactation in Rats

The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05). Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation.