[Hyperparathyroidism of different genesis in young patients with Turner syndrome: case series and brief review].

Hyperparathyroidism is a syndrome characterized by an excessive secretion of parathyroid hormone. Etiologically, hyperparathyroidism is subdivided into primary hyperparathyroidism, which develops as a result of parathyroid adenoma, carcinoma or hyperplasia, and secondary hyperparathyroidism, which happens as a compensatory response to a hypocalcemia caused by condition outside the parathyroid glands. Turner syndrome may also be accompanied by mineral metabolism disorders of various etiology. An association of hyperparathyroidism and Turner syndrome is interesting because of multifactorial impact on bone mineral density, but only few cases of such coexistence have been previously described in the literature. This article describes two patients with Turner syndrome and hyperparathyroidism of different etiology. Hyperparathyroidism, normocalcemia, vitamin D deficiency, osteoporosis, parathyroid tumors were found in both cases. In one case a number of assays was performed to confirm the patient's normocalcemic primary hyperparathyroidism, and surgery was performed to achieve remission. In the second case, treatment of vitamin D deficiency resulted in normalization of serum concentration of parathormone, after which the patient was prescribed antiresorptive therapy. The pathogenetic association between Turner syndrome and hyperparathyroidism requires further investigation. Comprehensive approach to the diagnosis and treatment of mineral metabolism disorders are essential for patients with coexistence of these two diseases.

The Global Burden of Early-Onset Biliary Tract Cancer: Insight From the Global Burden of Disease Study 2019.

Backgrounds/objectives: The escalating incidence of early-onset gastrointestinal cancers is becoming a primary global health concern. Biliary tract cancer (BTC) has been relatively understudied in this regard. We conducted an epidemiological study regarding the burden of this condition. Methods: We utilized data from the Global Burden of Disease Study 2019 to investigate the temporal trends in early-onset BTC (EOBTC), encompassing the estimation of frequencies and age-standardized rates (ASRs) of EOBTC incidence, mortality, and disability-adjusted life-years (DALYs), from 2010 to 2019. Results: EOBTC constituted nearly 7%of all BTC cases worldwide. The incidence rates of EOBTC decreased significantly in most regions, except in the Eastern Mediterranean (annual percentage change +1.04 %), where the incidence is rising. Stratified by the sociodemographic index (SDI), countries with low middle SDI (annual percentage change +0.5 %) show increasing incidence of EOBTC. The ASR of death and DALYs decreased in most regions. The ASR of EOBTC-related death and disability attributable to high body mass index increased in most regions, with the highest increase in Southeast Asia and low, middle SDI strata. Conclusions: There was a reduction in the burden of EOBTC globally, except for Eastern Mediterranean countries and low-middle SDI countries.

Associations of Telehealth Care Delivery with Pediatric Health Care Provider Well-Being.

BACKGROUND: The rapid, large-scale deployment of new health technologies can introduce challenges to clinicians who are already under stress. The novel coronavirus disease 19 (COVID-19) pandemic transformed health care in the United States to include a telehealth model of care delivery. Clarifying paths through which telehealth technology use is associated with change in provider well-being and interest in sustaining virtual care delivery can inform planning and optimization efforts. OBJECTIVE: This study aimed to characterize provider-reported changes in well-being and daily work associated with the pandemic-accelerated expansion of telehealth and assess the relationship of provider perceptions of telehealth effectiveness, efficiency, and work-life balance with desire for future telehealth. METHODS: A cross-sectional survey study was conducted October through November 2020, 6 months after the outbreak of COVID-19 at three children's hospitals. Factor analysis and structural equation modeling (SEM) were used to examine telehealth factors associated with reported change in well-being and desire for future telehealth. RESULTS: A total of 947 nontrainee physicians, advanced practice providers, and psychologists were surveyed. Of them, 502 (53.0%) providers responded and 467 (49.3%) met inclusion criteria of telehealth use during the study period. Of these, 325 (69.6%) were female, 301 (65.6%) were physicians, and 220 (47.1%) were medical subspecialists. Providers were 4.77 times as likely (95% confidence interval [CI]: 3.29-7.06) to report improved versus worsened well-being associated with telehealth. Also, 95.5% of providers (95% CI: 93.2-97.2%) wish to continue performing telehealth postpandemic. Our model explains 66% of the variance in telehealth-attributed provider well-being and 59% of the variance for future telehealth preference and suggests telehealth resources significantly influence provider-perceived telehealth care effectiveness which in turn significantly influences provider well-being and desire to perform telehealth. CONCLUSION: Telehealth has potential to promote provider well-being; telehealth-related changes in provider well-being are associated with both provider-perceived effectiveness of telemedicine for patients and adequacy of telehealth resources.

Rapid Development of a Telehealth Patient Satisfaction Survey Using a Multi-Stakeholder Approach.

Introduction: The COVID-19 pandemic has hastened the adoption of telehealth and the drastic shift to an unfamiliar process may impose significant impact to the quality-of-care delivery. Many providers are interested in understanding the quality of their telehealth services from the patients' experience. Materials and Methods: A telehealth patient satisfaction survey (TPSS) was developed by using an iterative stakeholder-centered design approach, incorporating elements from validated telemedicine and customer service survey instruments, and meeting the operational needs and constraints. A cross-sectional study design was employed to collect survey responses from patients and families of a large pediatric hospital. Finally, we performed exploratory factor analysis (EFA) to extract latent constructs and factor loadings of the survey items to further explain relationships. Results: A 22-item TPSS closely matched the existing in-person patient satisfaction survey and mapped to a revised SERVPERF conceptual model that was proposed by the interdisciplinary committee. Survey was implemented in the HIPAA-compliant online platform REDCap® with survey link embedded in an automated Epic MyChart (Verona, WI) visit follow-up message. In total, 2,394 survey responses were collected between July 7, 2020, and September 2, 2020. EFA revealed three constructs (with factor loadings >0.30): admission process, perceived quality of services, and telehealth satisfaction. Conclusions: We reported the development of TPSS that met the operational needs of compatibility with existing data and possible comparison to in-person survey. The survey is short and yet covers both the clinical experience and telehealth usability, with acceptable survey validity.

Identifying the Factors Influencing Patients' Telehealth Visit Satisfaction: Survey Validation Through a Structural Equation Modeling Approach.

Introduction: The COVID-19 pandemic accelerated the adoption of telehealth as an alternative to in-person hospital visits. To understand the factors impacting the quality of telehealth services, there is a need for validated survey instruments and conceptual frameworks. The objective of this study is to validate a telehealth patient satisfaction survey by structural equation modeling (SEM) and determine the relationship between the factors in the proposed telehealth patient satisfaction model (TPSM). Methods: We conducted a cross-sectional survey of pediatric patients and families receiving care from a comprehensive pediatric hospital in the Midwest between September 2020 and January 2021. In total, 2,039 usable responses were collected. We used an SEM approach by performing confirmatory factor analysis with Diagonally Weighted Least Squares modeling and Partial Least Squares-Path Modeling to establish the structural validity and examined the relationships among the constructs of "Admission Process" (AP), "Perceived Quality of Service" (PQS), and "Telehealth Satisfaction" (TS). Results: Participants were predominantly White (75%) and English-speaking (95%) parents (85%) of patients (mean age of patients was 10.2 years old). The survey responses were collected from patients visiting 43 department specialties, whereas 50% were behavioral and occupational therapy patients. The structural model showed that the admission process (AP) had a strong positive impact on perceived quality of service (PQS) (p = 0.67, t = 36.1, p < 0.001). The PQS had a strong positive impact on telehealth satisfaction (TS) (p = 0.66, t = 31.8, p < 0.001). The AP had a low positive direct impact on TS (p = 0.16, t = 7.46, p < 0.05). Overall, AP and PQS explained 61% variances (R2) of TS. Conclusions: We validated a newly proposed TS assessment model by using SEM. The TPSM will inform researchers to better understand the influencing factors in TS and help health care systems to improve telehealth patient satisfaction through a validated model.

The effects of gastric cancer interstitial fluid on tumors based on traditional Chinese medicine 'phlegm' theory and the investigation on the mechanism through microRNA-21 regulation.

This study aimed to investigate the effects of gastric cancer interstitial fluid (GCIF) on tumors and explore the possible mechanism of Xiaotan Sanjie decoction (XTSJ) on treatment of gastric cancer from the view of regulating microRNA-21 (miR-21) expression. The GCIF was extracted and identified by measuring the levels of interleukin-8 (IL-8), intercellular adhesion molecule 1 (ICAM-1) and miR-21. The effects of GCIF on the proliferation of SGC-7901 cells and tumor growing were assessed by cell counting kit-8 (CCK-8) assay and subcutaneously transplanted tumor-bearing nude mice model, respectively. Additionally, inhibition effect of XTSJ decoction on proliferation of SGC-7901 cells intervened by GCIF were assessed in vitro and anti-cancer effect of it was further assessed using orthotopic transplanted tumor-bearing nude mice model. The concentration of SGC-7901 gastric cancer cells were dependent on the concentration of the added GCIF. After 72 hours of continuous culture, the interstitial fluid had an obvious proliferative effect on the SGC-7901 tumor cells, which was the most significant in the high concentration group. XTSJ decoction could inhibit the growth-promoting effect (P < 0.01) of GCIF on gastric cancer cells. Intervention of the GCIF might promote the growth (P < 0.05) of the subcutaneously transplanted tumors in nude mice and decrease the net weight of the tumor-bearing nude mice (P < 0.05) after tumor removal. The GCIF was able to up-regulate the expression (P < 0.001) of miR-21 in the subcutaneously transplanted tumors. XTSJ decoction could downregulate the expression (P < 0.05) of miR-21 in SGC-7901 orthotopically transplanted tumors. XTSJ decoction can inhibit the multiplicative effect of GCIF on gastric cancer cells, growth of gastric tumor and promotion effect of GCIF on tumors, probably due to the down-regulating miR-21 expression in tumor tissues.

Feasibility and usability study of a pilot immersive virtual reality-based empathy training for dental providers.

PURPOSE: Social determinants of health (SDOH) significantly impact individuals' engagement with the healthcare system. To address SDOH-related oral health disparities, providers must be equipped with knowledge, skills, and attitudes (KSAs) to understand how SDOH affect patients and how to mitigate these effects. Traditional dental school curricula provide limited training on recognizing SDOH or developing empathy for those with SDOH-related access barriers. This study describes the design and evaluation of such a virtual reality (VR)-based simulation in dental training. We hypothesize the simulation will increase post-training KSAs. METHODS: We developed "MPATHI" (Making Professionals Able THrough Immersion), a scripted VR simulation where participants take the role of an English-speaking caregiver with limited socioeconomic resources seeking dental care for a child in a Spanish-speaking country. The simulation is a combination of 360° video recording and virtual scenes delivered via VR headsets. A pilot was conducted with 29 dental residents/faculty, utilizing a pre-post design to evaluate effectiveness in improving immediate and retention of KSAs toward care delivery for families facing barriers. RESULTS: MPATHI led to increased mean scores for cognitive (pre = 3.48 ± 0.80, post = 4.56 ± 0.51, p < 0.001), affective (pre = 4.20 ± 0.4, post = 4.47 ± 0.44, p < 0.001), and skill-based learning (pre = 4.00 ± 0.47, post = 4.52 ± 0.37, p < 0.001) immediately post-training. There was not a significant difference between skills measured immediately post-training and in the 1-month post-training survey (p = 0.41). Participants reported high satisfaction with the content and methods used in this training. CONCLUSIONS: This pilot study supports using VR SDOH training in dental education. VR technology provides new opportunities for innovative content design.

The role of protein restriction and interaction with antibiotics in the regulation of compensatory growth in pigs: growth performance, serum hormone concentrations, and messenger RNA levels in component tissues of the endocrine growth axis.

The present study investigated the effects of protein restriction and antibiotics on the hypothalamus-pituitary-liver growth axis during the compensatory growth of growing and finishing pigs. Growth performance, serum hormones, and messenger RNA (mRNA) levels of hormones and their receptors in growth axis tissues were recorded for analyses. A total of 64 piglets (large white × Landrace × Duroc cross) with an initial weight of 10.07 ± 0.14 kg were randomly divided into 4 treatment groups of 16 piglets per group. The dietary treatments consisted of 2 protein levels (14% and 20%) and 2 antibiotic levels (no antibiotics and 20 mg/kg colistin sulfate with 50 mg/kg kitasamycin) in a 2 × 2 factorial arrangement. The study was performed over 30 d for the first stage (S1, restriction phase) and 74 d for the second stage (S2, realimentation phase). The 4 treatment diets were maintained throughout the duration in the restriction phase. The 4 groups were fed the same diet in the realimentation phase. The trial period totaled 104 d. Protein restriction decreased BW, average daily food intake, and ADG in weaning pigs (P < 0.01) and induced compensatory growth after feeding a normal diet during the growth of finishing pigs. Average daily gain increased during the last phase of compensatory growth (P < 0.01). Protein restriction increased serum GH and leptin (LEP) and the mRNA levels of liver IGF-1 receptor (IGF-1-R; P < 0.01) but decreased serum IGF-1 (P < 0.01) and the mRNA levels of liver GH receptor (GH-R; P < 0.01) and IGF-1 (P < 0.05) in weaning piglets. Serum GH was increased, but serum IGF-1 was decreased during the realimentation phase (P < 0.05). Antibiotics increased the mRNA levels of GHRH (P < 0.05) and decreased somatostatin (P < 0.01) in the hypothalamus of weaning pigs. Protein restriction and antibiotics had no interactions across the entire trial. In conclusion, the slowing of growth caused by early protein restriction may be compensated for in the later stages of pig raising, and the mechanism of compensation is related to the regulation of GH, IGF-1, GH-R, and IGF-1-R.

Cytomegalovirus shedding in seropositive healthy women of reproductive age in Tianjin, China.

Cytomegalovirus (CMV) enters latency after primary infection and can reactivate periodically with virus excreted in body fluids which can be called shedding. CMV shedding during the early stage of pregnancy is associated with adverse pregnancy outcome. The shedding pattern in healthy seropositive women who plan to have babies has not been well characterised. Vaginal swabs, urine and blood were collected from 1262 CMV IgG-positive women who intended to have babies and tested for CMV DNA by fluorogenic quantitative PCR method. Serum IgM was also detected. The association between sociodemographic characteristics and CMV shedding prevalence was analysed. Among 1262 seropositive women, 12.8% (161/1262) were detected CMV DNA positive in at least one body fluid. CMV DNA was more frequently detected in vaginal secretion (10.5%) than in urine (3.2%) and blood (0.6%) also with higher viral loads (P < 0.00). CMV shedding was more likely detected in IgM-positive women than IgM-negative women (29.5% (13/44) vs. 12.2% (148/1218); OR 3.03, 95% CI 1.55-5.93; P = 0.001). CMV shedding in vaginal secretion was highly correlated with shedding in urine, the immune state of IgM, the adverse pregnant history and younger age. CMV shedding was more commonly detected in vaginal secretion than in urine or blood with higher viral loads among healthy seropositive women of reproductive age. Further studies are needed to figure out whether the shedding is occasional or continuous and whether it is associated with adverse pregnancy outcomes.

Effects of early protein restriction on the growth performance and gut development of pigs fed diets with or without antibiotic.

In the livestock husbandry compensatory growth may be explored as a means to improve nutrient utilization, to reduce gut health problems due to excess protein intake, to simplify feeding strategies and thus to improve production efficiencies. This study investigated the effects of early protein restriction (EPR) and early antibiotic intervention (EAI) on growth performance, intestinal morphology, colonic bacteria, metabolites and mucosal gene expressions during the restriction phase and re-alimentation phase. A total of 64 piglets (10.04 ± 0.73 kg) were randomly divided into four treatment groups according to a 2 × 2 factorial arrangement with two levels of proteins (14% v. 20%) and two levels of antibiotics (0 v. 50 mg/kg kitasamycin and 20 mg/kg colistin sulphate). After a 30-day restriction phase with four kinds of diets, all groups were fed the same diets for another 74 days. The results showed that EPR decreased BW, average daily gain (ADG), average daily feed intake in the restriction phase (P < 0.01) and increased ADG on days 66 to 104 of the late re-alimentation phase. Early protein restriction could decrease the villus height in the jejunum (P < 0.05), while shifting to the same diets restored the villus height. Meanwhile, during the re-alimentation phase, pigs in the protein restriction groups had increased concentrations of total short chain fatty acids (P < 0.05), and modified the abundances of Firmicutes and Bacteroidetes in the colon. Furthermore, the lower microbial diversity caused by EPR was improved, and gene expression analysis indicated a better barrier function in the colon. During the whole trial, EAI had no interaction with EPR and played a dispensable role in compensatory growth. Collectively, the retardation of growth caused by EPR can be compensated for in the later stages of pig raising, and accompanied by altered intestinal morphology, microbial composition.

A deep learning model for pediatric patient risk stratification.

OBJECTIVES: Current models for patient risk prediction rely on practitioner expertise and domain knowledge. This study presents a deep learning model-a type of machine learning that does not require human inputs-to analyze complex clinical and financial data for population risk stratification. STUDY DESIGN: A comparative predictive analysis of deep learning versus other popular risk prediction modeling strategies using medical claims data from a cohort of 112,641 pediatric accountable care organization members. METHODS: "Skip-Gram," an unsupervised deep learning approach that uses neural networks for prediction modeling, used data from 2014 and 2015 to predict the risk of hospitalization in 2016. The area under the curve (AUC) of the deep learning model was compared with that of both the Clinical Classifications Software and the commercial DxCG Intelligence predictive risk models, each with and without demographic and utilization features. We then calculated costs for patients in the top 1% and 5% of hospitalization risk identified by each model. RESULTS: The deep learning model performed the best across 6 predictive models, with an AUC of 75.1%. The top 1% of members selected by the deep learning model had a combined healthcare cost $5 million higher than that of the group identified by the DxCG Intelligence model. CONCLUSIONS: The deep learning model outperforms the traditional risk models in prospective hospitalization prediction. Thus, deep learning may improve the ability of managed care organizations to perform predictive modeling of financial risk, in addition to improving the accuracy of risk stratification for population health management activities.

Genetic polymorphisms of loci D18S53, D18S59, and D18S488 in fetuses from a Chinese Tianjin Han population.

We investigated the genetic polymorphisms of three short tandem repeat (STR) loci, D18S53, D18S59, and D18S488, on chromosome 18 in fetuses from a Chinese Tianjin Han population. Sixty-four villus samples and 374 amniotic fluid samples were collected from fetuses. Quantitative fluorescence polymerase chain reaction was performed to amplify the STR loci, followed by scanned electrophoresis and quantitative analysis of the fluorescence signals. Hardy-Weinberg equilibrium (HWE) analysis was performed based on the genotype distributions of the STR loci to obtain the following population genetic data: genotype frequency, heterozygosity of observation (HO), polymorphism information content (PIC), probability of discrimination power (PD), and probability of exclusion (PE). We detected 15, 13, and 15 alleles of D18S53, D18S59, and D18S488, respectively. The genotype frequencies were found to be in line with HWE. The HO values of the three loci, D18S53, D18S59, and D18S488, were 0.797, 0.847, and 0.792; the PIC values were 0.81, 0.75, and 0.73; the PD values were 0.944, 0.901, and 0.881; and the PE values were 0.593, 0.689, and 0.585, respectively. D18S53, D18S59, and D18S488 loci are good genetic markers of chromosome 18, and show potential for use in the prenatal genetic diagnosis of Edwards' syndrome.

Environmental and Genetic Activation of Hypothalamic BDNF Modulates T-cell Immunity to Exert an Anticancer Phenotype.

Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) providing complex stimuli confers an anticancer phenotype in mice mediated, in part by a specific neuroendocrine axis, with brain-derived neurotrophic factor (BDNF) as the key brain mediator. Here, we investigated how an EE modulated T-cell immunity and its role in the EE-induced anticancer effects. Our data demonstrated that CD8 T cells were required to mediate the anticancer effects of an EE in an orthotropic model of melanoma. In secondary lymphoid tissue (SLT), an EE induced early changes in the phenotype of T-cell populations, characterized by a decrease in the ratio of CD4 T helper to CD8 cytotoxic T lymphocytes (CTL). Overexpression of hypothalamic BDNF reproduced EE-induced T-cell phenotypes in SLT, whereas knockdown of hypothalamic BDNF inhibited EE-induced immune modulation in SLT. Both propranolol and mifepristone blocked the EE-associated modulation of CTLs in SLT, suggesting that both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis were involved. Our results demonstrated that enhanced anticancer effect of an EE was mediated at least in part through modulation of T-cell immunity and provided support to the emerging concept of manipulating a single gene in the brain to improve cancer immunotherapy. Cancer Immunol Res; 4(6); 488-97. ©2016 AACR.

Bilateral midshaft femoral fractures in an adolescent baseball player.

Bone disease, specifically low bone mineral density, is a common and undertreated complication that begins during childhood in patients with cystic fibrosis (CF). This case describes a male baseball player, aged 14years, with undiagnosed CF who sustained a left midshaft femoral fracture while running toward base; 8months later, he sustained a right midshaft femoral fracture under similar conditions. After the second fracture, further evaluation revealed low bone mineral density and CF. There is no previously published report of pathologic fractures occurring in the femoral shaft in an athlete with undiagnosed CF. Patients with CF have a higher fracture rate. Low-energy fractures of major bones in athletically active individuals should be viewed with suspicion for an underlying process.

RESTRUCTURING OF SKELETAL MUSCLE, LUNG AND HEART TISSUES OF RATS UNDER HYPOXIA TRAINING.

We studied some specific features of the changes in mor- pho- and stereometric characteristics of the ultrastructure of tissues of lungs, heart, and muscles, their capillarization, and the mitochondrial apparatus of cells in adult male Wistar rats under long-term physical loads. It is shown that the influence of a sustained training accompanied by the development of exercise-induced hypoxia on the structural readjustments of tissues of muscles, lungs, and myocardium can be conditionally divided into 2 groups: with destructive and compensatoryadaptive features. The changes with destructive character include, firstly, those of the ultrastructure of biological bar- riers such as, in particular, hyperhydration of barriers on the whole and their separate layers, which deteriorates the conditions of oxygen diffusion; second, the destructive changes in mitochondria (it increased the number of damaged lung organelles by 4.1 times, in the heart - at 4.5-5.5 times depending on subpopulations and in muscle - by 3.5-12.2 times also depending on the subpopulation of mitochondria), which are accompanied by a decrease in the energy potential of the mitochondrial apparatus, are observed. To the changes with compensatory-adaptive character, we refer an increase in the number of functioning capillaries (by 80% in the gastrocnemius muscle and by 60% in the myocardium), which prevents the development of secondary tissue hypoxia; intensification of pinocytosis in endotheliocytes; activation of mitochondrial morphogenesis, which was accompanied by an increase of the number of organelles at gastrocnemius muscle by 65%, in the lungs - in 4 times and in heart by 60-80% depending on the mitochondrial subpopulations; and appearance of young mitochondria and mitochondria with moderate degree of swelling, which favors the growth of the energy power of the mitochondrial apparatus of cells.

[Vascular endothelial growth factor during physical loads with different mechanism of energy's providing of muscular work].

In the article the results of investigation of vascular endothelial growth factor's (VEGF) maintenance changes at the oxidative stress caused by physical activities and associated tissue hypoxia, for the representatives of types of sport with the different mechanisms of energy providing of muscular work are presented. The highest VEGF concentration of serum was marked in sports with representatives of aerobic energy supply mechanism of muscle activity--from 122.8±3.4 to 126.2±4.1 pg·ml(-1), intermediate values in VEGF marked in a mixed mechanism energy--102.4±4.91 pg·ml(-1). Anaerobic muscle activity observed providing the lowest of VEGF value (78.5±5.2 pg·ml(-1)). Initial VEGF concentration in athletes even before the current load is higher than in the healthy untrained people. A statistically significant positive correlation between the degree of antioxidant protection and the VEGF concentration has been found. It is concluded, that angiogenesis is one of the mechanisms of adaptation to tissue hypoxia during physical activities. Scientific Institute of the National University of Physical Education and Sport of Ukraine, Kiev.

Social overcrowding as a chronic stress model that increases adiposity in mice.

Stress is a widely recognized risk factor for psychiatric and metabolic disorders. A number of animal models utilizing various stressors have been developed to facilitate our understanding in the pathophysiology of stress-related dysfunctions. The most commonly used chronic stress paradigms include the unpredictable chronic mild stress paradigm, the social defeat paradigm and the social deprivation paradigm. Here we assess the potential of social crowding as an alternative chronic stress model to study the effects on affective behaviors and metabolic disturbances. Ten-week-old male C57BL/6 mice were housed in groups of four (control) or eight (social crowding; SC) in standard cage for 9 weeks. Exploration, anxiety- and depressive-like behaviors were assessed in the open field test, the elevated T-maze, the novelty-suppressed feeding test and the forced swim test. SC mice exhibited a modest anxiety-like phenotype without change in depressive-like behaviors. Nine weeks of social crowding did not affect the body weight, but robustly increased adiposity as determined by increased mass of fat depots. Consistent with the increased fat content, serum leptin was markedly elevated in the SC mice. Specific changes in gene expression were also observed in the hypothalamus and the white adipose tissue following SC housing. Our study demonstrates the potential of social crowding as an alternative model for the study of stress-related metabolic and behavioral dysfunctions.

Blocking autophagy enhanced cytotoxicity induced by recombinant human arginase in triple-negative breast cancer cells.

Depletion of arginine by recombinant human arginase (rhArg) has proven to be an effective cancer therapeutic approach for a variety of malignant tumors. Triple-negative breast cancers (TNBCs) lack of specific therapeutic targets, resulting in poor prognosis and limited therapeutic efficacy. To explore new therapeutic approaches for TNBC we studied the cytotoxicity of rhArg in five TNBC cells. We found that rhArg could inhibit cell growth in these five TNBC cells. Intriguingly, accumulation of autophagosomes and autophagic flux was observed in rhArg-treated MDA-MB-231 cells. Inhibition of autophagy by chloroquine (CQ), 3-methyladenine (3-MA) and siRNA targeting Beclin1 significantly enhanced rhArg-induced cytotoxic effect, indicating the cytoprotective role of autophagy in rhArg-induced cell death. In addition, N-acetyl-l-cysteine (NAC), a common antioxidant, blocked autophagy induced by rhArg, suggesting that reactive oxygen species (ROS) had an essential role in the cytotoxicity of rhArg. This study provides new insights into the molecular mechanism of autophagy involved in rhArg-induced cytotoxicity in TNBC cells. Meanwhile, our results revealed that rhArg, either alone or in combination with autophagic inhibitors, might be a potential novel therapy for the treatment of TNBC.Cell Death and Disease (2014) 5, e1563; doi:10.1038/cddis.2014.503; published online 11 December 2014.

Molecular-like hierarchical self-assembly of monolayers of mixtures of particles.

We present a technique that uses an externally applied electric field to self-assemble monolayers of mixtures of particles into molecular-like hierarchical arrangements on fluid-liquid interfaces. The arrangements consist of composite particles (analogous to molecules) which are arranged in a pattern. The structure of a composite particle depends on factors such as the relative sizes of the particles and their polarizabilities, and the electric field intensity. If the particles sizes differ by a factor of two or more, the composite particle has a larger particle at its core and several smaller particles form a ring around it. The number of particles in the ring and the spacing between the composite particles depend on their polarizabilities and the electric field intensity. Approximately same sized particles form chains (analogous to polymeric molecules) in which positively and negatively polarized particles alternate.

An Immunological Approach to Increase the Brain's Resilience to Insults.

We have previously demonstrated the therapeutic potential of inducing a humoral response with autoantibodies to the N-methyl D-aspartate (NMDA) receptor using a genetic approach. In this study, we generated three recombinant proteins to different functional domains of the NMDA receptor, which is implicated in mediating brain tolerance, specifically NR1[21-375], NR1[313-619], NR1[654-800], and an intracellular scaffolding protein, Homer1a, with a similar anatomical expression pattern. All peptides showed similar antigenicity and antibody titers following systemic vaccination, and all animals thrived. Two months following vaccination, rats were administered the potent neurotoxin, kainic acid. NR1[21-375] animals showed an antiepileptic phenotype but no neuroprotection. Remarkably, despite ineffective antiepileptic activity, 6 of 7 seizing NR1[654-800] rats showed absolutely no injury with only minimal changes in the remaining animal, whereas the majority of persistently seizing rats in the other groups showed moderate to severe hippocampal injury. CREB, BDNF, and HSP70, proteins associated with preconditioning, were selectively upregulated in the hippocampus of NR1[654-800] animals, consistent with the observed neuroprotective phenotype. These results identify NR1 epitopes important in conferring anticonvulsive and neuroprotective effects and support the concept of an immunological strategy to induce a chronic state of tolerance in the brain.