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It has been postulated that the protective effects of lower body subcutaneous adipose tissue (LBSAT) occur via its ability to sequester surplus lipid and thus serve as a “metabolic sink.” However, the mechanisms that mediate this protective function are unknown thus this study addresses this postulate. Ad libitum, chow-fed mice underwent Sham-surgery or LBSAT removal (IngX, inguinal depot removal) and were subsequently provided chow (Chow; typical adipocyte expansion) or high fat diet (HFD; enhanced adipocyte expansion) for 5 weeks. Primary outcome measures included glucose tolerance and subsequent insulin response, muscle insulin sensitivity, liver and muscle triglycerides, adipose tissue gene expression, and circulating lipids and adipokines. In a follow up study the consequences of extended experiment length post-surgery (13 wks) or pre-existing glucose intolerance were examined. At 5 wks post-surgery IngX in HFD-fed mice reduced glucose tolerance and muscle insulin sensitivity and increased circulating insulin compared with HFD Sham. In Chow-fed mice, muscle insulin sensitivity was the only measurement reduced following IngX. At 13 wks circulating insulin concentration of HFD IngX mice continued to be higher than HFD Sham. Surgery did not induce changes in mice with pre-existing glucose intolerance. IngX also increased muscle, but not liver, triglyceride concentration in Chow- and HFD-fed mice 5 wks post-surgery, but chow group only at 13 wks. These data suggest that the presence of LBSAT protects against triglyceride accumulation in the muscle and HFD-induced glucose intolerance and muscle insulin resistance. These data suggest that lower body subcutaneous adipose tissue can function as a “metabolic sink.” [ABSTRACT FROM AUTHOR]

Objective: Malignant gliomas impose a significant symptomatic burden on patients and their families. Current guidelines recommend palliative care for patients with advanced tumors within eight weeks of diagnosis, emphasizing early integration for malignant glioma cases. However, the utilization rate of palliative care for these patients in Germany remains unquantified. This study investigates the proportion of malignant glioma patients who either died in a hospital or were transferred to hospice care from 2019 to 2022, and the prevalence of in-patient specialized palliative care interventions., Methods: In this cross-sectional, retrospective study, we analyzed data from the Institute for the Hospital Remuneration System (InEK GmbH, Siegburg, Germany), covering 2019 to 2022. We included patients with a primary or secondary diagnosis of C71 (malignant glioma) in our analysis. To refine our dataset, we identified cases with dual-coded primary and secondary diagnoses and excluded these to avoid duplication in our final tally. The data extraction process involved detailed scrutiny of hospital records to ascertain the frequency of hospital deaths, hospice transfers, and the provision of complex or specialized palliative care for patients with C71-coded diagnoses. Descriptive statistics and inferential analyses were employed to evaluate the trends and significance of the findings., Results: From 2019 to 2022, of the 101,192 hospital cases involving malignant glioma patients, 6,129 (6% of all cases) resulted in in-hospital mortality, while 2,798 (2.8%) led to hospice transfers. Among these, 10,592 cases (10.5% of total) involved the administration of complex or specialized palliative medical care. This provision rate remained unchanged throughout the COVID-19 pandemic. Notably, significantly lower frequencies of complex or specialized palliative care implementation were observed in patients below 65 years (p < 0.0001) and in male patients (p adjusted = 0.016). In cases of in-hospital mortality due to malignant gliomas, 2,479 out of 6,129 cases (40.4%) received specialized palliative care., Conclusion: Despite the poor prognosis and complex symptomatology associated with malignant gliomas, only a small proportion of affected patients received advanced palliative care. Specifically, only about 10% of hospitalized patients with malignant gliomas, and approximately 40% of those who succumb to the disease in hospital settings, were afforded complex or specialized palliative care. This discrepancy underscores an urgent need to expand palliative care access for this patient demographic. Additionally, it highlights the importance of further research to identify and address the barriers preventing wider implementation of palliative care in this context., (© 2024. The Author(s).)

Hepatic steatosis signifies onset of metabolic dysfunction-associated fatty liver disease (MAFLD) caused by disrupted metabolic homeostasis compromising liver function. Regular consumption of common beans reduces the risk of metabolic impairment, but its effective dose, the impact of biological sex, and underlying mechanisms of action are unknown. We fed female and male C57BL6/J mice with obesogenic yet isocaloric diets containing 0%, 17.5%, 35%, and 70% of total dietary protein derived from cooked whole common beans. Liver tissue was collected for histopathology, lipid quantification, and RNA-seq analyses. Beans qualitatively and quantitatively diminished hepatic fat deposition at the 35% dose in female and 70% dose in male mice. Bean-induced differentially expressed genes (DEGs) most significantly mapped to hepatic steatosis and revealed dose-responsive inhibition of de novo lipogenesis markers ( Acly , Acaca , Fasn , Elovl6 , Scd1 , etc.) and triacylglycerol biosynthesis, activation of triacylglycerol degradation, and downregulation of sterol regulatory element-binding transcription factor 1 (SREBF1) signaling. Upregulated fatty acid β-oxidation was more prominent in females, while suppression of Cd36 -mediated fatty acid uptake-in males. Sex-dependent bean effects also involved DEGs patterns downstream of peroxisome proliferator-activated receptor α (PPARα) and MLX-interacting protein-like (MLXIPL). Therefore, biological sex determines amount of common bean in the diet required to prevent hepatic lipid accumulation.

Background: Point-of-care ultrasound (POCUS) is rapidly becoming ubiquitous across healthcare specialties. This is due to several factors including its portability, immediacy of results to guide clinical decision-making, and lack of radiation exposure to patients. The recent growth of handheld ultrasound devices has improved access to ultrasound for many clinicians. Few studies have directly compared different handheld ultrasound devices among themselves or to cart-based ultrasound machines. We conducted a prospective observational study comparing four common handheld ultrasound devices for ease of use, image quality, and overall satisfaction. Twenty-four POCUS experts utilized four handheld devices (Butterfly iQ+™ by Butterfly Network Inc., Kosmos™ by EchoNous, Vscan Air™ by General Electric, and Lumify™ by Philips Healthcare) to obtain three ultrasound views on the same standardized patients using high- and low-frequency probes., Results: Data were collected from 24 POCUS experts using all 4 handheld devices. No single ultrasound device was superior in all categories. For overall ease of use, the Vscan Air™ was rated highest, followed by the Lumify™. For overall image quality, Lumify™ was rated highest, followed by Kosmos™. The Lumify™ device was rated highest for overall satisfaction, while the Vscan Air™ was rated as the most likely to be purchased personally and carried in one's coat pocket. The top 5 characteristics of handheld ultrasound devices rated as being "very important" were image quality, ease of use, portability, total costs, and availability of different probes., Conclusions: In a comparison of four common handheld ultrasound devices in the United States, no single handheld ultrasound device was perceived to have all desired characteristics. POCUS experts rated the Lumify™ highest for image quality and Vscan Air™ highest for ease of use. Overall satisfaction was highest with the Lumify™ device, while the most likely to be purchased as a pocket device was the Vscan Air™. Image quality was felt to be the most important characteristic in evaluating handheld ultrasound devices., (© 2022. The Author(s).)

Underconsumption of dietary fiber and the milieu of chemicals with which it is associated is a health concern linked to the increasing global burden of chronic diseases. The benefits of fiber are partially attributed to modulation of the gut microbiota, whose composition and function depend on the amount and quality of microbiota-accessible substrates in the diet. However, not all types of fiber are equally accessible to the gut microbiota. Phaseolus vulgaris L., or common bean, is a food type rich in fiber as well as other prebiotics posing a great potential to positively impact diet-microbiota-host interactions. To elucidate the magnitude of bean's effects on the gut microbiota, increasing doses of common bean were administered in macronutrient-matched diet formulations. The microbial communities in the ceca of female and male mice were evaluated via 16S rRNA gene sequencing. As the bean dose increased, the Bacillota:Bacteroidota ratio (formerly referred to as the Firmicutes:Bacteroidetes ratio) was reduced and α-diversity decreased, whereas the community composition was distinctly different between the diet groups according to β-diversity. These effects were more pronounced in female mice compared to male mice. Compositional analyses identified a dose-responsive bean-induced shift in microbial composition. With an increasing bean dose, Rikenellaceae, Bacteroides , and RF39, which are associated with health benefits, were enhanced. More taxa, however, were suppressed, among which were Allobaculum , Oscillospira , Dorea , and Ruminococcus , which are predominantly associated with chronic disease risk. Investigation of the origins of the dose dependent and biological sex differences in response to common bean consumption may provide insights into bean-gut microbiota-host interactions important to developing food-based precision approaches to chronic disease prevention and control.

Lipedema is a multifaceted chronic fat disorder characterized by the bilateral and disproportionate accumulation of fat predominantly in the lower body regions of females. Research strongly supports that estrogen factors likely contribute to the pathophysiology of this disease. We aim to help demonstrate this link by quantifying estrogen factor differences between women with and without lipedema. For time and lipedema adipose tissue conservation, the Protein Simple WES machine will be utilized in place of traditional western blotting. Here, we are interested in evaluating estrogen related factors, such as, but not limited to, estrogen receptors and enzymes involved in the successive conversions of cholesterol and androgens to estrogens in human subcutaneous adipose. Evaluation of these factors within adipose tissue, however, is novel for this instrument. Thus, we optimized tissue lysis and protein extraction for 11 proteins of interest. Antibodies and their working concentrations were determined based upon specific and distinguishable (signal-to-noise) peaks from electropherogram outputs across different tissue lysate concentrations. We found that overnight acetone precipitation proved to be the best procedure for extracting protein from lipid rich adipose tissue samples. Six of the eleven proteins were found to migrate to their expected molecular weights, however, five did not. For proteins that did not migrate as expected, overexpression lysates and empty vector controls were used to validate detection antibodies. Protein extract from subcutaneous adipose tissue and overexpression lysates were then combined to understand if migration was specifically altered by adipose tissue. From these results, we concluded that the lipid rich nature of adipose tissue in combination with the separation matrix designated for use with the WES were preventing the appropriate migration of some proteins rather than non-specific antibody binding or inappropriate preparation methods.

Abstract: The American Heart Association scientific statement on cardiogenic shock and the National Cardiogenic Shock Initiative have provided the impetus to advance knowledge and development of national guidelines for cardiogenic shock. We evaluate the current state of knowledge surrounding cardiogenic shock and limitations to the development of national guidelines., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Lipedema is a painful fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose tissue predominantly in the lower body. The onset of lipedema pathophysiology is thought to occur during periods of hormonal fluctuation, such as puberty, pregnancy, or menopause. Although the identification and characterization of lipedema have improved, the underlying disease etiology remains to be elucidated. Estrogen, a key regulator of adipocyte lipid and glucose metabolism, and female-associated body fat distribution are postulated to play a contributory role in the pathophysiology of lipedema. Dysregulation of adipose tissue accumulation via estrogen signaling likely occurs by two mechanisms: (1). altered adipocyte estrogen receptor distribution (ERα/ERß ratio) and subsequent metabolic signaling and/or (2). increased release of adipocyte-produced steroidogenic enzymes leading to increased paracrine estrogen release. These alterations could result in increased activation of peroxisome proliferator-activated receptor γ (PPARγ), free fatty acid entry into adipocytes, glucose uptake, and angiogenesis while decreasing lipolysis, mitochondriogenesis, and mitochondrial function. Together, these metabolic alterations would lead to increased adipogenesis and adipocyte lipid deposition, resulting in increased adipose depot mass. This review summarizes research characterizing estrogen-mediated adipose tissue metabolism and its possible relation to excessive adipose tissue accumulation associated with lipedema.

Purpose: Attitudes to surgery for paediatric thalamic tumours have evolved due to improved preoperative imaging modalities and the advent of intraoperative MRI (iMRI) as well as enhanced understanding of tumour biology. We review the developments in our local practice over the last three decades with particular attention to the impact of iMRI., Methods: We identified all paediatric patients from a prospectively maintained neuro-oncology database who received surgery for a thalamic tumour (n = 30). All children were treated in a single UK tertiary paediatric neurosurgery centre between January 1991 and June 2020. Twenty patients underwent surgical resection, the remainder (10) undergoing biopsy only. Pre-operative surgical intent (biopsy versus debulking, near-total resection, or complete resection) as well as the use of iMRI were prospectively recorded. Complications recorded in clinical documentation between postoperative days 0 and 30 were retrospectively graded using a modified version of the Clavien Dindo scale. The extent of resection with respect to the pre-determined surgical aim was also recorded. Data on patient survival and disease progression status were obtained retrospectively., Results: In our series, there were 42 procedures (25 craniotomies, 17 biopsies) performed on 30 patients (17 male, with a median age of 8 at surgery). Of the 25 surgical resections performed, complete resection was achieved in 9 (36%), near-total resection in 10 (40%), and limited debulking in 6 (24%). The predetermined surgical aim was achieved or exceeded in 91.3% of cases. The proportion of craniotomies for which substantial resection was achieved, increased from 37.5 to 94.2% with use of iMRI (p = 0.014). Surgical morbidity was not associated with greater extent of surgical resection. High-grade histology is identified as the only independent significant factor influencing overall survival as calculated by Cox proportional hazards model (p = 0.006)., Conclusion: We note a significant change in the rate and extent of attempted resection of paediatric thalamic tumours that has developed over the last 3 decades. Use of iMRI is associated with a significant increase in substantial tumour resection surgeries. This is not associated with any significant level of surgical morbidity. Improvements in pre- and intra-operative imaging alongside better understanding of tumour biology facilitate patient selection and a surgically more aggressive approach in selected cases whilst maintaining safety and avoiding operative morbidity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain-specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a pilot randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-intervention, as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an increase in anti-inflammatory immune cell populations in response to ex vivo LPS stimulation of PBMCs in the DE111 intervention group. Overall perceived gastrointestinal health, microbiota, and circulating and fecal markers of inflammation (Il-6, sIgA) and gut barrier function (plasma zonulin) were largely unaffected by DE111 intervention, although the study may have been underpowered to detect these differences. These pilot data provide information and justification to conduct an appropriately powered clinical study to further examine the immunomodulatory potential of B. subtilis DE111 in human populations.

Objective: Complications in pediatric neurooncology surgery are seldom and inconsistently reported. This study quantifies surgical morbidity after pediatric brain tumor surgery from the last decade in a single center, using existing morbidity and outcome measures., Methods: The authors identified all pediatric patients undergoing surgery for an intracranial tumor in a single tertiary pediatric neurosurgery center between January 2008 and December 2018. Complications between postoperative days 0 and 30 that had been recorded prospectively were graded using appropriate existing morbidity scales, i.e., the Clavien-Dindo (CD), Landriel, and Drake scales. The result of surgery with respect to the predetermined surgical aim was also recorded., Results: There were 477 cases (364 craniotomies and 113 biopsies) performed on 335 patients (188 males, median age 9 years). The overall 30-day mortality rate was 1.26% (n = 6), and no deaths were a direct result of surgical complication. Morbidity on the CD scale was 0 in 55.14%, 1 in 10.69%, 2 in 18.66%, 3A in 1.47%, 3B in 11.74%, and 4 in 1.05% of cases. Morbidity using the Drake classification was observed in 139 cases (29.14%). Neurological deficit that remained at 30 days was noted in 8.39%; 78% of the returns to the operative theater were for CSF diversion., Conclusions: To the authors' knowledge, this is the largest series presenting outcomes and morbidity from pediatric brain tumor surgery. The mortality rate and morbidity on the Drake classification were comparable to those of published series. An improved tool to quantify morbidity from pediatric neurooncology surgery is necessary.

Background: Microgreens are the young leafy greens of many vegetables, herbs, grains, and flowers with potential to promote human health and sustainably diversify the global food system. For successful further integration into the global food system and evaluation of their health impacts, it is critical to elucidate and optimize their nutritional quality., Objectives: We aimed to comprehensively evaluate the metabolite and mineral contents of 6 microgreen species, and the influence of maturity on their contents., Methods: Plant species evaluated were from the Brassicaceae (arugula, broccoli, and red cabbage), Amaranthaceae (red beet and red amaranth), and Fabaceae (pea) plant families. Nontargeted metabolomics and ionomics analyses were performed to examine the metabolites and minerals, respectively, in each microgreen species and its mature counterpart., Results: Nontargeted metabolomics analysis detected 3321 compounds, 1263 of which were annotated and included nutrients and bioactive compounds. Ionomics analysis detected and quantified 26 minerals including macrominerals, trace minerals, ultratrace minerals, and other metals. Principal component analysis indicated that microgreens have distinct metabolite and mineral profiles compared with one another and with their mature counterparts. Several compounds were higher ( P   < 0.05; fold change ≥2) in microgreens compared with their mature counterparts, whereas some were not different or lower. In many cases, compounds that were higher in microgreens compared with the mature counterpart were also unique to that microgreen species., Conclusions: These data provide evidence for the nutritional quality of microgreens, and can inform future research and development aimed at characterizing and optimizing microgreen nutritional quality and health impacts., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

As the severe acute respiratory syndrome coronavirus 2 virus pandemic continues to grow globally, an association is apparent between patients with underlying cardiovascular disease comorbidities and the risk of developing severe COVID-19. Furthermore, there are potential cardiac manifestations of severe acute respiratory syndrome coronavirus 2 including myocyte injury, ventricular dysfunction, coagulopathy, and electrophysiologic abnormalities. Balancing management of the infection and treatment of underlying cardiovascular disease requires further study. Addressing the increasing reports of health care worker exposure and deaths remains paramount. This review summarizes the most contemporary literature on the relationship of the cardiovascular system and COVID-19 and society statements with relevance to protection of health care workers, and provides illustrative case reports in this context., (Published by Elsevier Inc.)

The biological pathways that affect drug delivery in vivo remain poorly understood. We hypothesized that altering cell metabolism with phosphatidylinositol (3,4,5)-triphosphate (PIP3), a bioactive lipid upstream of the metabolic pathway PI3K (phosphatidylinositol 3-kinase)/AKT/ mTOR (mammalian target of rapamycin) would transiently increase protein translated by nanoparticle-delivered messenger RNA (mRNA) since these pathways increase growth and proliferation. Instead, we found that PIP3 blocked delivery of clinically-relevant lipid nanoparticles (LNPs) across multiple cell types in vitro and in vivo. PIP3-driven reductions in LNP delivery were not caused by toxicity, cell uptake, or endosomal escape. Interestingly, RNA sequencing and metabolomics analyses suggested an increase in basal metabolic rate. Higher transcriptional activity and mitochondrial expansion led us to formulate two competing hypotheses that explain the reductions in LNP-mediated mRNA delivery. First, PIP3 induced consumption of limited cellular resources, "drowning out" exogenously-delivered mRNA. Second, PIP3 triggers a catabolic response that leads to protein degradation and decreased translation., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Purpose: Accumulation of visceral, but not subcutaneous, adipose tissue is highly associated with metabolic disease. Inflammation inciting from adipose tissue is commonly associated with metabolic disease risk and comorbidities. However, constituents of the immune system, lymph nodes, embedded within these adipose depots remain under-investigated. We hypothesize that, lymph nodes are inherently distinct and differentially respond to diet-induced obesity much like the adipose depots they reside in., Methods: Adipose tissue and lymph nodes were collected from the visceral and inguinal depots of male mice fed 13 weeks of standard CHOW or high fat diet (HFD). Immune cells were isolated from tissues, counted and characterized by flow cytometry or plated for proliferative capacity following Concanavalin A stimulation. Lymph node size and fibrosis area were also characterized., Results: In HFD fed mice visceral adipose tissue accumulation was associated with significant enlargement of the lymph node encased within. The subcutaneous lymph node did not change. Compared with mice fed CHOW for 13 weeks, mice fed HFD had a decline in immune cell populations and immune cell proliferative ability, as well as, exacerbated fibrosis accumulation, within the visceral, but not subcutaneous, lymph node., Conclusions: Obesity-induced chronic low-grade inflammation is associated with impaired immunity and increased susceptibility to disease. Excessive visceral adiposity and associated inflammation driven by diet likely leads to obesity-induced immune suppression by way of lymph node/lymphatic system pathophysiology.

Microgreens are an emerging functional food crop with promise for sustainably diversifying global food systems, facilitating adaptations to urbanization and global climate change, and promoting human health. Previous work suggests microgreens have high nutritional quality, low environmental impacts, and broad consumer acceptance. For better reception into the global food system and increased per capita consumption, research is needed to elucidate consumer acceptance of various microgreens species, including factors contributing to their acceptance or lack thereof. Using a consumer panel (n = 99), this study evaluated consumer sensory perception and acceptability of six microgreens species (arugula, broccoli, bull's blood beet, red cabbage, red garnet amaranth, and tendril pea), and potential drivers and barriers to consumer acceptance. All microgreens species received high mean liking scores for acceptability by consumers (means ranged from highly acceptable to slightly acceptable), with more distinct differences across microgreens species for flavor and overall acceptability, which appeared to be driven by specific sensory properties. Data from principal component analysis demonstrated that high acceptability scores were associated with higher intent to purchase microgreens and negatively associated with food neophobia. Participants indicated that factors such as knowledge and familiarity of microgreens, cost, access/availability, freshness/shelf life, among other factors, influence their intention to purchase microgreens. These findings suggest that further integration of microgreens into the global food system will be met with high consumer acceptability, but needs to be aligned with enhanced consumer education regarding microgreens, as well as considerations of cost, availability/access, and freshness/shelf life. PRACTICAL APPLICATION: Researchers investigated consumer sensory perception and acceptability of six microgreens species (arugula, broccoli, bull's blood beet, red cabbage, red garnet amaranth, and tendril pea), and potential drivers and barriers to consumer acceptance. All microgreens tested had high consumer acceptability, but certain factors such as sensory perception and food neophobia impacted their acceptability. Additionally, participants indicated that factors such as knowledge, access and availability, cost, freshness, and shelf life may impact the purchasing of microgreens and thus are important factors to consider for further integration of this emerging functional food crop into the global food system., (© 2020 Institute of Food Technologists®.)

Preclinical and clinical findings indicate that glucocorticoids (GC) induce lipid accumulation in visceral depots, while inhibiting lipid stores from subcutaneous depots. Whereas some suggest that this is due to adipose depot specific concentration of glucocorticoid receptors (GR) or 11beta-hydroxysteroid dehydrogenase 1 (11β-HSD1), others demonstrate these events emerge from increases in interleukin-1 beta (IL-1β) from macrophages within distinct depots. Regardless of the mechanisms, most of these studies occur in males and thus lack evaluation of sex differences. Here, we examined the impact of 2-week corticosterone (CORT) (3 mg/kg/day) or saline treatment on GR, 11β-HSD1 and IL-1β protein concentration in intra-abdominal (epididymal/parametrial, and visceral) and subcutaneous (inguinal) depots in male and female Sprague Dawley rats. The objective was to examine if factors that regulate GC-induced adipose depot metabolism and distribution, differ between males and females. CORT inhibited, but did not decrease, body weight gain in both sexes. 11β-HSD1 was similar between the sexes in all adipose depots. CORT increased IL-1β in both sexes only in gonadal adipose tissue. Overall, males had greater GR protein concentration in all adipose depots, whereas females had more IL-1β in intra-abdominal adipose depots. Given the male-biased increase in intra-abdominal GR protein concentration, the data suggest that males may be more prone to CORT-induced increases in visceral obesity, which may have implications for increased risk for metabolic diseases. Overall, the data suggest that the effects of GC signaling in adipose tissue are multifaceted, dependent on sex, and the inherent adipocyte characteristics.Lay summaryResearch supports that glucocorticoids (GC) induce visceral adipose tissue accumulation, however few studies have examined if these GC-mediated outcomes are similar between males and females. This study investigates if female rats differentially respond to corticosterone treatment. Results indicate that male rats may have an increased susceptibility to CORT-induced accumulation of visceral adipose tissue compared with females, which may have implication for sex-specific risk for metabolic diseases.

Objective: Children with posterior fossa tumors (PFTs) may present with hydrocephalus. Persistent (or new) hydrocephalus is common after PFT resection. Endoscopic third ventriculostomy (ETV) is sometimes performed prior to resection to 1) temporize hydrocephalus prior to resection and 2) prophylactically treat post-resection hydrocephalus. The objective of this study was to establish, in a historical cohort study of pediatric patients who underwent primary craniotomy for PFT resection, whether or not pre-resection ETV prevents the need for post-resection CSF diversion to manage hydrocephalus., Methods: The authors interrogated their prospectively maintained surgical neuro-oncology database to find all primary PFT resections from a single tertiary pediatric neurosurgery unit. These data were reviewed and supplemented with data from case notes and radiological review. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) score was retrospectively calculated for all patients. The primary outcome was the need for any form of postoperative CSF diversion within 6 months of PFT resection (including ventriculoperitoneal shunting, ETV, external ventricular drainage [EVD], and lumbar drainage [LD]). This was considered an ETV failure in the ETV group. The secondary outcomes were time to CSF diversion, shunt dependence at 6 months, and complications of ETV. Statistical analysis was done in RStudio, with significance defined as p < 0.05., Results: A total of 95 patients were included in the study. There were 28 patients in the ETV group and 67 in the non-ETV group. Patients in the ETV group were younger (median age 5 vs 7 years, p = 0.04) and had more severe preoperative hydrocephalus (mean frontal-occipital horn ratio 0.45 vs 0.41 in the non-ETV group, p = 0.003) and higher mCPPRH scores (mean 4.42 vs 2.66, p < 0.001). The groups were similar in terms of sex and tumor histology. The overall rate of post-resection CSF diversion of any kind (shunt, repeat ETV, LD, or EVD) in the entire cohort was 25.26%. Post-resection CSF diversion was needed in 32% of patients in the ETV group and in 22% of the patients in the non-ETV group (p > 0.05). Shunt dependence at 6 months was seen in 21% of the ETV group and 16% of the non-ETV group (p > 0.05). The median time to ETV failure was 9 days. ETV failure correlated with patients with ependymoma (p = 0.02). Children who had ETV failure had higher mCPPRH scores than the ETV success group (5.67 vs 3.84, p = 0.04)., Conclusions: Pre-resection ETV did not reliably prevent the need for post-resection CSF diversion. ETV was more likely to fail in children with ependymoma and those with higher mCPPRH scores. Based on the findings of this study, the authors will change the practice at their institution; pre-resection ETV will now be performed based on a newly defined protocol.

Clinical studies indicate that eating common bean, Phaseolus vulgaris L., plays a role in body weight regulation but mechanisms have yet to be elucidated. Here, we investigated the anti-obesogenic activity of white kidney bean in a mouse model of dietary-induced obesity. Bean consumption reduced the accumulation of adipose tissue in male and female C57BL6 mice. The anti-obesogenic effect of white kidney bean was not due to alterations in energy intake, energy excreted in the feces, or feed efficiency ratio. While bean consumption increased the mass of the intestine, no marked differences were consistently observed in crypt height, mucin content of goblet cells, proliferation index or zone of proliferation. However, significantly higher concentrations of total bacteria and of Akkermansia muciniphila were detected in cecal content of bean-fed mice, and the ratio of Firmicutes to Bacteroidetes was reduced. Bile acid content was higher in the ileum of bean-fed mice, but transcript levels of farnesoid X receptor were not significantly affected. Whether changes in bile-acid-mediated cell signaling play a role in bean-related differences in fat accumulation and/or overall metabolic health requires further investigation.

Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and have no relevant interests to declare.

Purpose: To evaluate safety and effectiveness of the iCAST Covered Stent for treatment of iliac artery atherosclerotic lesions., Materials and Methods: The iCARUS trial (ClinicalTrials.gov Identifier: NCT00593385) was a single-arm, prospective, multicenter study that enrolled 152 per protocol subjects at 25 sites in the United States and Germany. Subjects with multiple lesions and/or stents were eligible. The primary endpoint was the composite rate of death within 30 days, target lesion revascularization (TLR) within 9 months, or restenosis at 9 months after procedure. Secondary endpoints included major adverse vascular events (MAVEs), primary patency, freedom from TLR, and clinical success., Results: Device and acute procedural success were achieved in 98.7% and 92.7% of cases, respectively. MAVE rate was 4.6% at 30 days. The 9-month primary composite endpoint rate was 8.1% (10/123), which was below the performance goal of 16.57%. Nine-month primary patency, defined as continuous flow without revascularization, bypass, or target limb amputation, was 96.4%. Freedom from TLR at 9 months and 3 years was 97.2% and 86.6%, respectively. Early clinical success was seen in 88.7% of subjects at 30 days with sustained clinical benefit in 72.4% of subjects at 3 years., Conclusions: The iCARUS study demonstrated that the iCAST Covered Stent was safe and effective for treatment of atherosclerotic iliac artery lesions with sustained clinical benefit out to 3 years., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

On January 26, 2018, the 23rd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado. The meeting consisted of plenary sessions with oral presentations and a poster presentation session. There were four plenary sessions that covered a wide range of topics relating to alcohol use: Alcohol and Liver Disease; Alcohol, Inflammation and Immune Response; Alcohol and Organ Injury; Heath Consequences and Alcohol Drinking. The meeting provided a forum for the presentation and discussion of novel research findings regarding alcohol use and immunology., (Copyright © 2018. Published by Elsevier Inc.)

Background Inflammation, induced by excessive adiposity, links obesity to disease risk yet little attention has been devoted to the lymphoid tissues embedded within adipose tissue depots. Lymph nodes are the primary site for the development of protective immunity, hence any disease process that affects these tissues will also directly impact immunity. Here we examined how obesity alters secondary lymphatic tissue structure and encapsulated immune cells. Materials and methods Four-month-old C57BL/6 male mice were fed standard rodent chow or a Western high fat diet (HFD) for 6 months. Center regions of visceral and subcutaneous lymph nodes (SQLNS) were observed via transmission electron microscopy (TEM). Results Compared with chow, HFD-induced obesity deleteriously modified the structural microarchitecture and immune cell morphology of visceral and SQLNs. In HFD mice, fibroblastic reticular cells (FRCs) were dysregulated while laying among excessive amounts of disorganized collagen (C). In addition HFD lymph nodes contained a disproportionate amount of cellular debris from damaged or dead cells, increased sinus spacing and decreased immune cell interactions. Specifically, dendritic cells (DCs) that are necessary for adaptive immune response where embedded among extracellular debris with decreased pseudopodia. Similarly, the extraneous fibrous extracellular matrix (ECM) in HFD mice limited contact between lymphocytes (LCs) causing their microvilli extensions to decrease. Discussion Overall, excessive C production within lymph nodes, driven by diet-induced obesity, creates a physical barrier that impedes proper lymph flow and cellular communication. Obesity-induced disorganization of the immune cell guidance network interrupts immune cell adhesion and consequently inhibits travel within cortex regions needed for cell interactions, survival and proliferation.

Background: The authors report a case with interesting clinical and radiological outcomes following complete anatomical hemispherectomy., Methods: A seven-year-old female with medically refractory epilepsy secondary to Rasmussen's encephalitis was treated with a complete right-sided anatomical hemispherectomy., Results: Surgical intervention provided seizure relief, and at eleven-years post-operatively she was independently mobile, with spasticity of the upper limb. She had normal intellect and was pursuing higher education. Functional MRI found re-location of left-sided motor control to the remaining left hemisphere, alongside the existing motor cortex., Conclusion: This interesting case is a good example of effective neuroplasticity; motor functionality relocated an area in the contralateral hemisphere that already contained the prerequisite cellular architecture and white matter connectivity required to control movement.

Aim: The choice between anterior cervical discectomy & fusion (ACD) or posterior cervical foraminotomy (PCF) for the treatment of cervical brachialgia is controversial. This study aimes to compare clinical outcomes between these two operative inteventions for brachialgia., Methods: Retrospective review of prospectively collected data was performed. Patients receiving a primary ACD or PCF to treat brachialgia, in a single tertiary neurosurgical unit were included. Surgical details, and patient reported outcomes (COMI-Neck questionnaire) were extracted from a prospectively maintained spinal procedure database. Minimum clinically important difference (MCID) was defined as a change in COMI score of -2 at 12 months. The student t-test, Chi-square test, and linear regression were used to compare groups., Results: Between June 2011 ad February 2016 there were 634 ACD procedures (Median age 49; 321 Male), and 54 PCF procedures (Median age 50; 37 Male) perfomed for brachialgia. Age, ASA and pre-operative COMI were similar between the groups (p > .05). Complete outcome data was recorded at twelve months in 312 ACD and 36 PCF patients. Both ACD and PCF were associated with an improvement in COMI at 3 and 12 months (all p < .01). Mean change in COMI at 3 months was -2.38 for ACD, versus -2.31 for PCF (p = .88); at twelve months it was -2.94 for ACD, versus -2.67 for PCF (p = .55). MCID was seen in 59% of ACD cases, versus 58% of PCF cases at twelve months (p = .91)., Conclusion: There was no significant difference between outcomes in the ACD and PCF groups. This is supportive of published literature. The proposed multicenter RCTs may inform further.

This study examined whether trained variability would generalize across dimensions of the target response. Two experiments used a computerized rectangle drawing task that required participants to click and drag a mouse cursor to create rectangles on a computer screen. In Experiment 1, one group received points when successive rectangles varied in their size, shape and location (VAR), another group were yoked to the VAR group and received points that were allocated to them using a yoking procedure (YOKE), regardless of the variability in the size, shape or location of the rectangle drawn. Variability was higher for a dimension when variability on that dimension was directly reinforced. In Experiment 2, three groups of participants received points when rectangles varied on two dimensions; each group differed in the two dimensions that required variation. Variability was again higher for the reinforced dimensions for two of the three groups. Comparison with the YOKE group showed that the variability on those dimensions where variability was not directly reinforced was affected by reinforcement for variability on the other dimensions. Specifically, the variability in Shape and Location was significantly higher when these two dimensions occurred with other dimensions where variability was reinforced (as in Experiment 2) compared to when they were not required to vary (as in the YOKE group). This suggests that, for these two groups, the reinforced variability on the other two dimensions generalized to the third dimension. Implications of this finding to our understanding of factors that promote behavioral variability are discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Pediatric neuro-oncology surgery continues to progress in sophistication, largely driven by advances in technology used to aid the following aspects of surgery: operative planning (advanced MRI techniques including fMRI and DTI), intraoperative navigation [preoperative MRI, intra-operative MRI (ioMRI) and intra-operative ultrasound (ioUS)], tumor visualization (microscopy, endoscopy, fluorescence), tumor resection techniques (ultrasonic aspirator, micro-instruments, micro-endoscopic instruments), delineation of the resection extent (ioMRI, ioUS, and fluorescence), and intraoperative safety (neurophysiological monitoring, ioMRI). This article discusses the aforementioned technological advances, and their multimodal use to optimize safe pediatric neuro-oncology surgery.

Obesity-related adverse health consequences occur predominately in individuals with upper body fat distribution commonly associated with increased central adiposity. Visceral adipose tissue accumulation is described to be the greatest driver of obesity-induced inflammation, however evidence also supports that the intestines fundamentally contribute to the development of obesity-induced metabolic disease. The visceral adipose depot shares the same vasculature and lymph drainage as the small intestine. We hypothesize that the visceral lymph node, which drains adipose tissue and the gastrointestinal tract, is central to the exacerbation of systemic pro-inflammation. Male C57BL/6 mice were fed CHOW or high fat diet (HFD) for 7 weeks. At termination the mesenteric depot, visceral lymph node and ileum, jejunum and Peyer's patches were collected. Cytokine concentration was determined in adipose tissue whereas immune cell populations where investigated in the visceral lymph node and intestinal segments by flow cytometry. Visceral adipose tissue and the gastrointestinal tract mutually influence immune cells enclosed within the visceral lymph node. HFD increased visceral lymph node immune cell number. This likely resulted from 1.) an increase in immune cells migration from the small intestines likely from activated dendritic cells that travel to the lymph node and 2.) cytokine effluent from visceral adipose tissue that promoted expansion, survival and retention of pro-inflammatory immune cells. Overall, the visceral lymph node, the immune nexus of visceral adipose tissue and the small intestines, likely plays a fundamental role in exacerbation of systemic pro-inflammation by HFD-induced obesity. The research of Tim Bartness greatly enhanced the understanding of adipose tissue regulation. Studies from his laboratory significantly contributed to our awareness of extrinsic factors that influence body fatness levels. Specifically, the work he produced eloquently demonstrated that adipose tissue was more complex than an insulating storage center; it was connected to our brains via the sympathetic and sensory nervous system. Mapping studies demonstrated that adipose tissue both receives and sends information to the brain. Further, his lab demonstrated that nervous system connections contributed to lipolysis, thermogenesis and adipocyte proliferation and growth. The work of Tim Bartness will continue to influence adipose tissue research. As such, Tim Bartness directly inspired the following research. Adipose tissue extrinsic factors are not limited to the peripheral nervous system. The lymphatic system is an additional extrinsic factor that cross talks with adipose tissue, however its role in this context is under emphasized. Here we begin to elucidate how the lymphatic system may contribute to the comorbidities associated with visceral adipose tissue accumulation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Obesity and associated metabolic co-morbidities are a worldwide public health problem. Negative health outcomes associated with obesity, however, do not arise from excessive adiposity alone. Rather, deleterious outcomes of adipose tissue accumulation are a result of how adipocytes are distributed to individual regions in the body. Due to our increased understanding of the dynamic relationship that exists between specific adipose depots and disease risk, an accurate characterization of total body adiposity as well as location is required to properly evaluate a population's disease risk. Specifically, distinctive tissue depots within the body include the lower body, upper body and abdominal (deep and superficial) subcutaneous regions, as well as visceral (mesenteric and omental) regions. Upper body and visceral adipose tissues are highly associated with metabolic dysfunction and chronic disease development, whereas lower body gluteofemoral subcutaneous adipose tissue imparts protection against diet-induced metabolic derangement. Each adipose depot functions distinctly as an endocrine organ hence it has a different level of impact on health outcomes. Effluent from adipose tissue can modulate the functions of other tissues, whilst receiving differential communication from the rest of the body via central nervous system innervation, metabolites and other signaling molecules. More so, adipose depots contain a diverse reservoir of tissue-resident immune cells that play an integral part in both maintaining tissue homeostasis, as well as propagating metabolically-induced inflammation. Overall, the conceptualization of obesity and associated risks needs updating to reflect the complexities of obesity. We review adipose tissue characteristics that are linked to deleterious or beneficial adipose tissue distributions.

The protective effects of lower body subcutaneous adiposity are linked to the depot functioning as a "metabolic sink" receiving and sequestering excess lipid. This postulate, however, is based on indirect evidence. Mechanisms that mediate this protection are unknown. Here we directly examined this with progressive subcutaneous adipose tissue removal. Ad libitum chow fed mice underwent sham surgery, unilateral or bilateral removal of inguinal adipose tissue or bilateral removal of both inguinal and dorsal adipose tissue. Subsequently mice were separated into 5 week chow or 5 or 13 week HFD groups (N = 10 per group). Primary outcome measures included adipocyte distribution, muscle and liver triglycerides, glucose tolerance, circulating adipocytokines and muscle insulin sensitivity. Subcutaneous adipose tissue removal caused lipid accumulation in femoral muscle proximal to excision, however, lipid accumulation was not proportionally inverse to adipose tissue quantity excised. Accumulative adipose removal was associated with an incremental reduction in systemic glucose tolerance in 13 week HFD mice. Although insulin-stimulated pAkt/Akt did not progressively decrease among surgery groups following 13 weeks of HFD, there was a suppressed pAkt/Akt response in the non-insulin stimulated (saline-injected) 13 week HFD mice. Hence, increases in lower body subcutaneous adipose removal resulted in incremental decreases in the effectiveness of basal insulin sensitivity of femoral muscle. The current data supports that the subcutaneous depot protects systemic glucose homeostasis while also protecting proximal muscle from metabolic dysregulation and lipid accumulation. Removal of the "metabolic sink" likely leads to glucose intolerance because of decreased storage space for glucose and/or lipids.

Exercise training has robust effects on subcutaneous inguinal white adipose tissue (iWAT), characterized by a shift to a brown adipose tissue (BAT)-like phenotype. Consistent with this, transplantation of exercise-trained iWAT into sedentary rodents activates thermogenesis and improves glucose homeostasis, suggesting that iWAT metabolism may contribute to the beneficial effects of exercise. However, it is yet to be determined if adaptations in iWAT are necessary for the beneficial systemic effects of exercise. To test this, male C57BL/6 mice were provided access to voluntary wheel running (VWR) or remained as a cage control (SED) for 11 nights after iWAT removal via lipectomy (LIPX) or SHAM surgery. We found that SHAM and LIPX mice with access to VWR ran similar distances and had comparable reductions in body mass, increased food intake, and increased respiratory exchange ratio (RER). Further, VWR improved indexes of glucose homeostasis and insulin tolerance in both SHAM and LIPX mice. The lack of effect of LIPX in the response to VWR was not explained by compensatory increases in markers of mitochondrial biogenesis and thermogenesis in skeletal muscle, epididymal white adipose tissue, or interscapular brown adipose tissue. Together, these data demonstrate that mice with and without iWAT have comparable adaptations to VWR, suggesting that iWAT may be dispensable for the metabolic health benefits of exercise.

Background: Two distinct categories of aneurysms are described in relation to the posterior inferior cerebellar artery (PICA) and vertebral artery (VA): saccular (SA) and dissecting (DA) types. This distinction is often unrecognized because abnormalities here are uncommon and most studies are small., Objective: To determine if there are any differences in the clinical presentation, in-hospital course, or outcomes in patients with DA vs SA of the PICA or VA., Methods: Thirty-eight patients with a VA or PICA aneurysm were identified from a departmental subarachnoid hemorrhage database and categorized into DA or SA types. Prospectively collected demographic and outcome data (length of stay, discharge Glasgow Outcome Score) were supplemented by abstracting records for procedural data (extraventricular drain [EVD], ventriculoperitoneal [VP] shunt, tracheostomy, and nasogastric feeding). Univariate, binary logistic regression, and Cox regression analysis was used to compare patients with SA vs DA., Results: Three aneurysms related to arteriovenous malformation were excluded. Five patients were conservatively managed. Of the 30 treated cases, more patients with a DA presented in poor grade (6/13 vs 2/17 SA; P = .035). More DA patients required an EVD (85% vs 29%; P = .003), VP shunt (54% vs 6%; P = .003), tracheostomy (46% vs 6%; P < .01), and nasogastric feeding (85% vs 35%; P = .007). The median length of stay (41 vs 17 d, P < .001) was longer, and the age and injury severity adjusted odds of discharge home were significantly lower in the DA group (P = .008). Thirty-day mortality was not significantly different (23% of DA vs 24% of SA; P = .2)., Conclusion: The presentation, clinical course, and outcomes differ in patients with DA vs SA of the PICA and VA., (Copyright © 2017 by the Congress of Neurological Surgeons)

Significant progress has been made in the percutaneous coronary intervention technique from the days of balloon angioplasty to modern-day metallic drug-eluting stents (DES). Although metallic stents solve a temporary problem of acute recoil following balloon angioplasty, they leave behind a permanent problem implicated in very late events (in addition to neoatherosclerosis). BRS were developed as a potential solution to this permanent problem, but the promise of these devices has been tempered by clinical trials showing increased risk of safety outcomes, both early and late. This is not too dissimilar to the challenges seen with first-generation DES in which refinement of deployment technique, prolongation of dual antiplatelet therapy, and technical iteration mitigated excess risk of very late stent thrombosis, making DES the treatment of choice for coronary artery disease. This white paper discusses the factors potentially implicated in the excess risks, including the scaffold consideration and deployment technique, and outlines patient and lesion selection, implantation technique, and dual antiplatelet therapy considerations to potentially mitigate this excess risk with the first-generation thick strut Absorb scaffold (Abbott Vascular, Abbott Park, Illinois). It remains to be seen whether these considerations together with technical iterations will ultimately close the gap between scaffolds and metal stents for short-term events while at the same time preserving options for future revascularization once the scaffold bioresorbs., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We report a new multiplexed strategy for the electrochemical detection of regional DNA methylation across multiple regions. Using the sequence dependent affinity of bisulfite treated DNA towards gold surfaces, the method integrates the high sensitivity of a micro-fabricated multiplex device comprising a microarray of gold electrodes, with the powerful multiplexing capability of multiplex-PCR. The synergy of this combination enables the monitoring of the methylation changes across several genomic regions simultaneously from as low as 500 pg μl -1 of DNA with no sequencing requirement.

Objectives: The spatial proximity of adipose depots to secondary lymph nodes allows a unique relation between the two systems. Obesity, predominately visceral adiposity, links to numerous diseases; hence, we postulate that secondary lymphatics within this region contributes to disease risk., Material and Methods: Male C57BL/6 mice were fed standard CHOW (18% kcal fat) or Western diet (45% kcal fat) for 7 weeks. Visceral and subcutaneous lymph nodes and associated adipose depots they occupy were excised. Lymph node morphology and resident immune cell populations were characterized via histopathology, immunofluorescence and flow cytometry. Adipose tissue immune cell populations were also characterized., Results: Obesity caused lymph node expansion, increased viable cell number and deviations in immune cell populations. These alterations were exclusive to visceral lymph nodes. Notably, pro-inflammatory antigen presenting cells and regulatory T cells increased in number in the visceral lymph node. Obesity, however, reduced T regulatory cells in visceral lymph nodes. The visceral adipose depot also had greater reactivity towards HFD than subcutaneous, with a greater percent of macrophages, dendritic and CD8 + T cells. Immune cell number, in both the visceral and subcutaneous, however decreased as adipose depots enlarged., Conclusion: Overall, HFD has a greater influence on visceral cavity than the subcutaneous. In the visceral lymph node, but not subcutaneous, HFD-induced obesity decreased cell populations that suppressed immune function while increasing those that regulate/activate immune response., (© 2017 John Wiley & Sons Ltd.)

The visible borrow system (VBS) simulates a natural rodent habitat that supports genuine stress provoking social interactions. This model allows investigation of behavioral, neural and endocrine alterations caused by chronic stress. The Sakai lab further used this model to investigate metabolic outcomes of stress in relation to dominance hierarchies formed within the VBS. Communal social conflict occurs among all VBS rats, but only the SUB rats succumb to the redistribution of lipids in the visceral cavity and consequent metabolic dysregulation, such as hyper-insulinemia. These increases in visceral adipose tissue occur after two cycles of VBS stress and recovery bouts and are associated with decreases in subcutaneous adipose tissue. Traditionally, distribution shift in lipid deposition is predominately thought to occur by characteristics specific to the visceral depot, but evidence supports that decreased subcutaneous adipose tissue deposition may be linked to enhanced visceral adipose expansion. This review will discuss VBS stress and redirection of adipose tissue in SUB rats. There will be specific focus on the enhanced adipogenic capacity of visceral adipose tissue as driven by glucocorticoid receptor density, 11-hydroxysteroid dehydrogenase type 1 (11-HSD1) and lipoprotein lipase (LPL). Additionally, the proposed contribution of decreased subcutaneous adipose expansion via stress-induced inhibition of lipid uptake, storage and cellularity will be discussed. Overall, this review will summarize how stress-induced visceral obesity may result from a combination of maladaptive responses within the visceral and subcutaneous depot., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Mood disorders such as major depressive disorder (MDD) affect a significant proportion of the population. Although progress has been made in the development of therapeutics, a large number of individuals do not attain full remission of symptoms and adverse side effects affect treatment compliance for some. In order to develop new therapies, there is a push for new models that better reflect the multiple risk factors that likely contribute to the development of depressive illness. We hypothesized that early life stress would exacerbate the depressive-like phenotype that we have previously observed in socially subordinate (SUB) adult male rats in the visible burrow system (VBS), a semi-natural, ethologically relevant environment in which males in a colony form a dominance hierarchy. Dams were exposed to chronic variable stress (CVS) during the last week of gestation, resulting in a robust and non-habituating glucocorticoid response that did not alter maternal food intake, body weight or litter size and weight. As adults, one prenatal CVS (PCVS) and one non-stressed (NS) male were housed in the VBS with adult females. Although there were no overt differences between PCVS and NS male offspring prior to VBS housing, a greater percentage of PCVS males became SUB. However, the depressive-like phenotype of SUB males was not exacerbated in PCVS males; rather, they appeared to better cope with SUB status than NS SUB males. They had lower basal plasma corticosterone than NS SUB males at the end of VBS housing. In situ hybridization for CRH in the PVN and CeA did not reveal any prenatal treatment or status effects, while NPY expression was higher within the MeA of dominant and subordinate males exposed to the VBS in comparison with controls, but with no effect of prenatal treatment. These data suggest that prenatal chronic variable stress may confer resilience to offspring when exposed to social stress in adulthood., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To validate 3 angiographic scoring systems for peripheral artery calcification using intravascular ultrasound (IVUS) as the gold standard., Methods: The study employed preprocedure angiography and IVUS data from 47 patients (median age 72 years; 34 men) in the 55-patient JetStream G3 Calcium Study ( ClinicalTrials.gov identifier NCT01273623) to validate the 3 angiographic scoring systems [Peripheral Academic Research Consortium (PARC), Peripheral Arterial Calcium Scoring System (PACSS), and the DEFINITIVE Ca ++ trial]. Preprocedure angiograms were analyzed using conventional quantitative vessel analysis software in 2 orthogonal views. Calcium length was evaluated by markers placed beside the artery during the procedure; calcium deposit(s) were assessed as being on one or both sides of the vessel wall. The 3 calcium scoring systems used these 2 basic angiographic elements to evaluate calcium severity. Based on these criteria, calcium severity varied from none to focal, mild, moderate, or severe in PARC; grade 0 to 4 in PACSS; and none, moderate, or severe in the DEFINITIVE Ca ++ system. Calcium location on IVUS was classified as superficial, deep, or mixed. Lesion length was the segment between the most normal looking proximal and distal reference sites. Superficial, deep, and calcium length were based on motorized IVUS pullback., Results: IVUS detected calcium in 44/47 (93.6%) lesions, and angiography detected calcium in 26/47 (55.3%) lesions (p<0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of angiography relative to IVUS were 59%, 100%, 100%, and 14%, respectively. With increasing severity of angiographic calcium, there was a stepwise increase in the prevalence of IVUS superficial calcium and the maximum arc and length of superficial calcium. Using PARC criteria, with increasing severity of calcification, IVUS maximum calcium arc increased from 120° for none to 305° for severe (p<0.001); the length of calcium increased from 7 to 68 mm (p<0.001). Though a similar trend was seen in IVUS superficial calcium, it was not observed in IVUS deep calcium. Similar observations were seen when using the PACSS and DEFINITIVE Ca ++ scoring systems., Conclusion: IVUS confirmed that the PARC, PACSS, and DEFINITIVE Ca ++ calcium scoring systems can be used to classify the degree of calcium in peripheral artery disease, especially superficial calcium.

An imbalance between energy intake and expenditure leads to obesity. Adiposity associated with obesity progressively causes inflammation, type 2 diabetes, hypertension, hyperlipidemia and cardiovascular disease. Excessive dietary intake of fat results in its accumulation and storage in the white adipose tissue (WAT), whereas energy expenditure by fat utilization and oxidation predominately occurs in the brown adipose tissue (BAT). Recently, the presence of a third type of fat, referred to as beige or brite (brown in white), has been recognized in certain kinds of WAT depots. It has been suggested that WAT can undergo the process of browning in response to stimuli that induce and enhance the expression of thermogenes characteristic of those typically associated with brown fat. The resultant beige or brite cells enhance energy expenditure by reducing lipids stored within adipose tissue. This has created significant excitement towards the development of a promising strategy to induce browning/beiging in WAT to combat the growing epidemic of obesity. This review systematically describes differential locations and functions of WAT and BAT, mechanisms of beiging of WAT and a concise analysis of drug molecules and natural products that activate the browning phenomenon in vitro and in vivo. This review also discusses potential approaches for targeting WAT with compounds for site-specific beiging induction. Overall, there are numerous mechanisms that govern browning of WAT. There are a variety of newly identified targets whereby potential molecules can promote beiging of WAT and thereby combat obesity.

Objectives: Adipose tissue plays a fundamental role in glucose homeostasis. For example, fat removal (lipectomy, LipX) in lean mice, resulting in a compensatory 50% increase in total fat mass, is associated with significant improvement in glucose tolerance. This study was designed to further examine the link between fat removal, adipose tissue compensation and glucose homeostasis using a peroxisome proliferator-activated receptor γ (PPAR γ; activator of adipogenesis) knockout mouse., Material and Methods: The study involved PPARγ knockout (FKOγ) or control mice (CON), subdivided into groups that received LipX or Sham surgery. We reasoned that as the ability of adipose tissue to expand in response to LipX would be compromised in FKOγ mice, so would improvements in glucose homeostasis., Results: In CON mice, LipX increased total adipose depot mass (~60%), adipocyte number (~45%) and changed adipocyte distribution to smaller cells. Glucose tolerance was improved (~30%) in LipX CON mice compared to Shams. In FKOγ mice, LipX did not result in any significant changes in adipose depot mass, adipocyte number or distribution. LipX FKOγ mice were also characterized by reduction of glucose tolerance (~30%) compared to shams., Conclusions: Inhibition of adipose tissue PPARγ prevented LipX-induced increases in adipocyte expansion and produced a glucose-intolerant phenotype. These data support the notion that adipose tissue expansion is critical to maintain and/or improvement in glucose homeostasis., (© 2016 John Wiley & Sons Ltd.)

Objectives: The aim of this study was to examine the effects of a Western diet (WD) and supplementation with Fuzhuan tea on large artery stiffness, as determined by aortic pulse wave velocity (aPWV)., Methods: Mice were subjected to a standard diet (SD; n = 12) or WD (n = 10) for 7 mo, and were then separated to receive nonsupplemented drinking water (SD-W and WD-W) or water supplemented with Fuzhuan tea (SD-T and WD-T) (200 mg/kg daily); mice were then maintained on their respective diets for an additional 2 mo., Results: After the initial 7-mo feeding period, WD elicited a modest and significantly greater increase in body weight than did SD (39.6 ± 0.71 versus 34.5 ± 1.16 g; P < 0.01). PWV was significantly elevated in WD but not in SD (459.3 ± 4.8 versus 422.4 ± 6.4 cm/s; P < 0.001). Following an additional 2 mo, PWV continued to increase in WD-W, but returned to control levels in WD-T (WD-W: 519.8 ± 12.8; WD-T: 426.5 ± 18.6; SD-W: 429.7 ± 8.6; SD-T: 429.1 ± 6.1 cm/s; P < 0.001, WD-W versus all groups). The increase in PWV in WD-W was accompanied by an increase in aortic collagen (WD-W: 38.8 ± 4.6 versus SD-W: 17.5 ± 5.1 percent cross-sectional area; P < 0.05)., Conclusion: The results of the present study suggest that the increase in arterial stiffness after modest, diet-induced weight gain can be reversed by supplementation with Fuzhuan tea., (Copyright © 2016 Elsevier Inc. All rights reserved.)