Collagen and bone morphogenetic protein-2 functionalized hydroxyapatite scaffolds induce osteogenic differentiation in human adipose-derived stem cells

Surface modification is one important way to fabricate successful biocompatible materials in bone tissue engineering. Hydroxyapatite (HAp) materials have received considerable attention as suitable bioceramics for manufacturing osseous implants because of their similarity to bone mineral in terms of chemical composition. In this study, the surface of porous HAp scaffold was modified by collagen treatment and bone morphogenetic protein‐2 (BMP‐2) conjugation. The surface modification did not affect the HAp scaffold's bulk properties. No significant difference in compressive strength was found among different scaffolds, with HAp, collagen modified HAp, and collagen–BMP‐2‐functionalized HAp having compressive strengths of 45.8 ± 3.12, 51.2 ± 4.09, and 50.7 ± 3.98 MPa, respectively. In vitro studies were performed to compare adhesion and osteogenic differentiation between human adipose‐derived stem cells (hADSCs) with modified surfaces and those unmodified HAp surfaces. Collagen or BMP‐2 alone was insufficient and that both collagen and BMP‐2 are necessary to get the desired results. The findings suggest the possibility of using three‐dimensional HAp scaffold treated with gold‐standard collagen coating and highly researched BMP‐2 growth factor as a platform to deliver hADSCs. Results of this study could be used to develop treatment strategy for regenerating completely transected models using more synergistic approaches

An AI-Based Framework for Translating American Sign Language to English and Vice Versa

Abstract: In this paper, we propose a framework to convert American Sign Language (ASL) to English and English to ASL. Within this framework, we use a deep learning model along with the rolling average prediction that captures image frames from videos and classifies the signs from the image frames. The classified frames are then used to construct ASL words and sentences to support people with hearing impairments. We also use the same deep learning model to capture signs from the people with deaf symptoms and convert them into ASL words and English sentences. Based on this framework, we developed a web-based tool to use in real-life application and we also present the tool as a proof of concept. With the evaluation, we found that the deep learning model converts the image signs into ASL words and sentences with high accuracy. The tool was also found to be very useful for people with hearing impairment and deaf symptoms. The main contribution of this work is the design of a system to convert ASL to English and vice versa

Gender dimorphism and age of onset in malignant peripheral nerve sheath tumor preclinical models and human patients.

BackgroundGender-based differences in disease onset in murine models of malignant peripheral nerve sheath tumor (MPNST) and in patients with Neurofibromatosis type-1-(NF-1)-associated or spontaneous MPNST has not been well studied.MethodsForty-three mGFAP-Cre+;Ptenloxp/+;LSL-K-rasG12D/+ mice were observed for tumor development and evaluated for gender disparity in age of MPNST onset. Patient data from the prospectively collected UCLA sarcoma database (1974-2011, n = 113 MPNST patients) and 39 published studies on MPNST patients (n = 916) were analyzed for age of onset differences between sexes and between NF-1 and spontaneous MPNST patients.ResultsOur murine model showed gender-based differences in MPNST onset, with males developing MPNST significantly earlier than females (142 vs. 162 days, p = 0.015). In the UCLA patient population, males also developed MPNST earlier than females (median age 35 vs. 39.5 years, p = 0.048). Patients with NF-1-associated MPNST had significantly earlier age of onset compared to spontaneous MPNST (median age 33 vs. 39 years, p = 0.007). However, expanded analysis of 916 published MPNST cases revealed no significant age difference in MPNST onset between males and females. Similar to the UCLA dataset, patients with NF-1 developed MPNST at a significantly younger age than spontaneous MPNST patients (p < 0.0001, median age 28 vs. 41 years) and this disparity was maintained across North American, European, and Asian populations.ConclusionsAlthough our preclinical model and single-institution patient cohort show gender dimorphism in MPNST onset, no significant gender disparity was detected in the larger MPNST patient meta-dataset. NF-1 patients develop MPNST 13 years earlier than patients with spontaneous MPNST, with little geographical variance

Investigation of the ground-state spin inversion in the neutron-rich 47,49Cl isotopes

A first γ -ray study of 47,49Cl spectroscopy was performed at the Radioactive Isotope Beam Factory with 50Ar projectiles at 217 MeV/nucleon, impinging on the liquid hydrogen target of the MINOS device. Prompt deexcitation γ rays were measured with the NaI(Tl) array DALI2+. Through the one-proton knockout reaction 50Ar(p, 2p), a spin assignment could be determined for the low-lying states of 49Cl from the momentum distribution obtained with the SAMURAI spectrometer. A spin-parity Jπ = 3/2+ is deduced for the ground state of 49Cl, similar to the recently studied N = 32 isotope 51K. The evolution of the energy difference E(1/2+ 1 ) − E(3/2+ 1 ) is compared to state-of-the-art theoretical predictions.Ministerio de Ciencia de España, Innovación y Universidades y fondos FEDER. FIS2017-88410-PFondo Nacional de Investigación, Desarrollo e Innovación de Hungría. Proyecto No. K128947.The Office of Nuclear Physics, U.S. Department of Energy. De-sc0018223The United Kingdom Science and Technology Facilities Council (STFC). ST/L005816/1Natural Sciences and Engineering Research Council of Canada (NSERC). SAPIN-2016-00033, SAPIN-2018- 00027 y RGPAS-2018-522453

Melanocortin 4 Receptors Reciprocally Regulate Sympathetic and Parasympathetic Preganglionic Neurons

Melanocortin 4 receptors (MC4Rs) in the central nervous system are key regulators of energy and glucose homeostasis. Notably, obese patients with MC4R mutations are hyperinsulinemic and resistant to obesity-induced hypertension. Although these effects are likely dependent upon the activity of the autonomic nervous system, the cellular effects of MC4Rs on parasympathetic and sympathetic neurons remain undefined. Here, we show that MC4R agonists inhibit parasympathetic preganglionic neurons in the brainstem. In contrast, MC4R agonists activate sympathetic preganglionic neurons in the spinal cord. Deletion of MC4Rs in cholinergic neurons resulted in elevated levels of insulin. Furthermore, re-expression of MC4Rs specifically in cholinergic neurons (including sympathetic preganglionic neurons) restores obesity-associated hypertension in MC4R null mice. These findings provide a cellular correlate of the autonomic side effects associated with MC4R agonists and demonstrate a role for MC4Rs expressed in cholinergic neurons in the regulation of insulin levels and in the development of obesity-induced hypertension

Prevalence and Factors Associated With Mental Health Symptoms in Adults Undergoing Covid-19 Testing

BACKGROUND AND OBJECTIVE: Understanding the mental health impact of the COVID-19 pandemic on persons receiving COVID-19 testing will help guide mental health interventions. We aimed to determine the association between sociodemographic factors and mental health symptoms at 8 weeks (baseline) after a COVID-19 test, and compare prevalence of mental health symptoms at baseline to those at 16-week follow-up. MATERIALS AND METHODS: Prospective cohort study of adults who received outpatient COVID-19 testing at primary care clinics. Logistic regression analyses were used to assess the association between sociodemographic characteristics and COVID-19 test results with mental health symptoms. Mental health symptoms reported at baseline were compared to symptoms at 16 weeks follow-up using conditional logistic regression analyses. RESULTS: At baseline, a total of 124 (47.51%) participants reported at least mild depressive symptoms, 110 (42.15%) participants endorsed at least mild anxiety symptoms, and 94 participants (35.21%) endorsed hazardous use of alcohol. Females compared to males were at increased risk of at least mild depressive symptoms at baseline (Adjusted Odds Ratio (AOR): 2.08; 95% CI: 1.14-3.79). The odds of at least mild depressive symptoms was significantly lower among those residing in zip codes within the highest quartile compared to lowest quartile of household income (AOR: 0.37; 95% CI: 0.17-0.81). Also, non-Hispanic Whites had significantly higher odds of reporting hazardous alcohol use compared to non-Whites at baseline (AOR: 1.94; 95% CI: 1.05-3.57). The prevalence of mental health symptoms remained elevated after 16 weeks. CONCLUSION AND RELEVANCE: We found a high burden of symptoms of depression and anxiety as well as hazardous alcohol use in a diverse population who received testing for COVID-19 in the primary care setting. Primary care providers need to remain vigilant in screening for symptoms of mental health disorders in patients tested for COVID-19 well after initial testing

Novel Dedifferentiated Liposarcoma Xenograft Models Reveal PTEN Down-Regulation as a Malignant Signature and Response to PI3K Pathway Inhibition

Liposarcoma is a type of soft tissue sarcoma that exhibits poor survival and a high recurrence rate. Treatment is generally limited to surgery and radiation, which emphasizes the need for better understanding of this disease. Because very few in vivo and in vitro models can reproducibly recapitulate the human disease, we generated several xenograft models from surgically resected human dedifferentiated liposarcoma. All xenografts recapitulated morphological and gene expression characteristics of the patient tumors after continuous in vivo passages. Importantly, xenograftability was directly correlated with disease-specific survival of liposarcoma patients. Thus, the ability for the tumor of a patient to engraft may help identify those patients who will benefit from more aggressive treatment regimens. Gene expression analyses highlighted the association between xenograftability and a unique gene expression signature, including down-regulated PTEN tumor-suppressor gene expression and a progenitor-like phenotype. When treated with the PI3K/AKT/mTOR pathway inhibitor rapamycin alone or in combination with the multikinase inhibitor sorafenib, all xenografts responded with increased lipid content and a more differentiated gene expression profile. These human xenograft models may facilitate liposarcoma research and accelerate the generation of readily translatable preclinical data that could ultimately influence patient care

A Novel Excitatory Paraventricular Nucleus to AgRP Neuron Circuit that Drives Hunger

Summary Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to its control. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake1-5. Consistent with their obligatory role in regulating appetite, genetic ablation or pharmacogenetic inhibition of AgRP neurons decreases feeding3,6,7. Excitatory input to AgRP neurons is key in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric state-dependent synaptic plasticity8-10. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing Thyrotropin-releasing hormone (TRH) and Pituitary adenylate cyclase-activating polypeptide (PACAP). Pharmaco-genetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated

Building operational research capacity in the Pacific

Operational research (OR) in public health aims to investigate strategies, interventions, tools or knowledge that can enhance the quality, coverage, effectiveness or performance of health systems. Attention has recently been drawn to the lack of OR capacity in public health programmes throughout the Pacific Islands, despite considerable investment in implementation. This lack of ongoing and critical reflection may prevent health programme staff from understanding why programme objectives are not being fully achieved, and hinder long-term gains in public health. The International Union Against Tuberculosis and Lung Disease (The Union) has been collaborating with Pacific agencies to conduct OR courses based on the training model developed by The Union and Médecins Sans Frontières Brussels-Luxembourg in 2009. The first of these commenced in 2011 in collaboration with the Fiji National University, the Fiji Ministry of Health, the World Health Organization and other partners. The Union and the Secretariat of the Pacific Community organised a second course for participants from other Pacific Island countries and territories in 2012, and an additional course for Fijian participants commenced in 2013. Twelve participants enrolled in each of the three courses. Of the two courses completed by end 2013, 18 of 24 participants completed their OR and submitted papers by the course deadline, and 17 papers have been published to date. This article describes the context, process and outputs of the Pacific courses, as well as innovations, adaptations and challenges