A new approach to the chronology of caves 268/272/275 in the Dunhuang Mogao Grottoes: combining radiocarbon dates and archaeological information within a Bayesian statistical framework

The construction chronology of three of the earliest Dunhuang Mogao Grottoes (Caves 268, 272, and 275) has been the subject of ongoing debate for over half a century. This chronology is a crucial topic in terms of further understanding of the establishment of the Dunhuang Mogao Grottoes, early Buddhism in the Gansu corridor, and its relationship with Buddhism developed in the Central Plains. Building upon archaeological, art historical and radiocarbon (14C) dating studies, we integrate new 14C data with these previously published findings utilizing Bayesian statistical modeling to improve the chronological resolution of this issue. Thus, we determine that all three of these caves were constructed around AD 410–440, suggesting coeval rather than sequential construction

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl--dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4-]2- and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3-]-. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states

Tratamiento psicosocial Matrix para la adicción a cocaína: componentes de un tratamiento efectivo

España, uno de los países europeos con mayor prevalencia de consumo de cocaína entre población joven, tiene una necesidad de transferencia de modelos empíricos de tratamiento llegados de otros países. El instituto Norteamericano NIDA recomienda Matrix como un modelo efectivo de tratamiento en adicciones a estimulantes. Los objetivos de este estudio teórico-descriptivo del modelo son describir con detalle: 1) el desarrollo histórico y repercusión del modelo, 2) la fi losofía y base teórica, 3) los constructos centrales; 4) la estructura y organización, y 5) los recursos materiales, humanos e infraestructura necesarios para implementarlo. La metodología incluye una revisión bibliográfi ca exhaustiva, la formación y experiencia clínica directa con el modelo. Los resultados muestran que Matrix está basado en teorías psicológicas consideradas efi caces para el tratamiento de las adicciones y comunes a las utilizadas por los psicólogos a nivel internacional (cognitivo-conductuales, psico-educativas, motivacionales, manejo de contingencias, monitorización del consumo, apoyo social). Consiste en una intervención intensiva inicial de 62 sesiones mínimas repartidas en 4 meses, seguida de un tratamiento de continuación indefi nido. Conclusiones: el modelo en su conjunto cumple los principios de buenas prácticas de NIDA. Su estandarización y materiales lo hacen fácil de implementar a nivel internacional.Evidence-Based Models for the psychosocial treatment drug addiction are in need in Spain, currently one of the European countries with highest prevalence on cocaine use among youth. This article describes in detail the Matrix model, one of the EBM recommended by NIDA as effective treatments for stimulant drugs. The goals are to describe: 1) the history and impact of this model, 2) philosophy and basic psychosocial theories, 3) core constructs, 4) structure of the model and 5) infrastructure and needed resources. Methods include a comprehensive literature review of the model descriptive publications, collaboration with the model authors, on-site training and direct experience utilizing the model sessions. Results showed that Matrix is based on psychological theories known and used by Spanish psychologists (cognitive-behavioral therapy, motivational strategies, relapse prevention, contingency management, monitoring drug-use, social support). It consists on 62 multivariate sessions along 4 months of intensive treatment followed by continuous support group sessions. The model follows the NIDA principles of Drugaddiction Treatment. Its standardization, structure and writing materials make possible to easily transfer this model to multiple communities and countries

The Substance Abuse Treatment Workforce of South Africa

The purpose of this paper is to describe characteristics of substance abuse treatment counselors in the Republic of South Africa, including demographics, education, training, and job duties. Counselors recruited from 24 treatment centers completed a survey after signing informed consent. Counselors were primarily female (75%), racially diverse (36.4% White, 30.8% Black, 18.9% Coloured, 12.6% Indian or Asian, and 1.4% Cape Malay), and were 38 years old on average. The majority (62.3%) held at least an equivalent of a bachelor’s degree, and just under half (49%) were registered social workers. Counselors had a mean of 5.3 years’ experience in substance abuse treatment. The substance abuse treatment workforce of South Africa appears to be young and educated, yet only one third of the counselors had any formal training in Cognitive Behavioral Therapy. South African counselors could benefit from more training in evidence-based techniques

A Bioinformatics-Assisted Review on Iron Metabolism and Immune System to Identify Potential Biomarkers of Exercise Stress-Induced Immunosuppression

The immune function is closely related to iron (Fe) homeostasis and allostasis. The aim of this bioinformatics-assisted review was twofold; (i) to update the current knowledge of Fe metabolism and its relationship to the immune system, and (ii) to perform a prediction analysis of regulatory network hubs that might serve as potential biomarkers during stress-induced immunosuppression. Several literature and bioinformatics databases/repositories were utilized to review Fe metabolism and complement the molecular description of prioritized proteins. The Search Tool for the Retrieval of Interacting Genes (STRING) was used to build a protein-protein interactions network for subsequent network topology analysis. Importantly, Fe is a sensitive double-edged sword where two extremes of its nutritional status may have harmful effects on innate and adaptive immunity. We identified clearly connected important hubs that belong to two clusters: (i) presentation of peptide antigens to the immune system with the involvement of redox reactions of Fe, heme, and Fe trafficking/transport; and (ii) ubiquitination, endocytosis, and degradation processes of proteins related to Fe metabolism in immune cells (e.g., macrophages). The identified potential biomarkers were in agreement with the current experimental evidence, are included in several immunological/biomarkers databases, and/or are emerging genetic markers for different stressful conditions. Although further validation is warranted, this hybrid method (human-machine collaboration) to extract meaningful biological applications using available data in literature and bioinformatics tools should be highlighted.The ‘Bioinformatics-assisted Review’ is a project developed and supported by the Research Division at the Dynamical Business and Science Society—DBSS International SAS. The APC was funded by the Exercise & Sport Nutrition Laboratory (ESNL) at Texas A&M University, the POWER LAB at University of Central Florida and the Sport Genomics Research Group at University of the Basque Country UPV/EHU

Bridging the Gap Between Practice Guidelines and the Therapy Room: Community-Derived Practice Adaptations for Psychological Services with Transgender and Gender Diverse Adults in the Central United States

Individuals who identify as transgender and gender diverse (TGD) are presenting at mental health clinicians’ offices with increasing frequency. Many TGD clients are seeking care related to affirming their gender identity but also may present with anxiety, depression, trauma, substance abuse, or other problems forwhich a clinician may commonly provide services. Some clinicians may hesitate to accept TGD clients into their practice if they have little specialized training to work with this population in an affirming manner, especially in more underserved areas where a generalist practice is the norm. Numerous professional associations and experts have developed guidelines for affirmative behavioral health care for TGDpeople.However, what is needed are community-informed recommendations to bridge from the official guidelines to clinicians’ in-session activities. The Trans Collaborations Practice Adaptations for Psychological Interventions for Transgender and Gender Diverse Adults are derived from iterative interviews with TGD community members and affirming mental health clinicians in the Central United States. The 12 practice adaptations are intended to guide clinicians to adapt their usual treatment approach to be TGD affirming, especially in underserved and rural areas. The practice adaptations cover numerous aspects of practice including the office setting and paperwork, understanding gender identity and incorporating it into the case conceptualization, therapist’s self-awareness, and referrals. The Trans Collaborations Practice Adaptations will help clinicians work confidently and competently with adult TGD clients, regardless of the presenting problem, to ensure TGD communities receive the best interventions for their behavioral health concerns

Closed-loop control of continuous piperacillin delivery: An in silico study

Background and objective: Sub-therapeutic dosing of piperacillin-tazobactam in critically-ill patients is associated with poor clinical outcomes and may promote the emergence of drug-resistant infections. In this paper, an in silico investigation of whether closed-loop control can improve pharmacokinetic-pharmacodynamic (PK-PD) target attainment is described. Method: An in silico platform was developed using PK data from 20 critically-ill patients receiving piperacillin-tazobactam where serum and tissue interstitial fluid (ISF) PK were defined. Intra-day variability on renal clearance, ISF sensor error, and infusion constraints were taken into account. Proportional-integral-derivative (PID) control was selected for drug delivery modulation. Dose adjustment was made based on ISF sensor data with a 30-min sampling period, targeting a serum piperacillin concentration between 32 and 64 mg/L. A single tuning parameter set was employed across the virtual population. The PID controller was compared to standard therapy, including bolus and continuous infusion of piperacillin-tazobactam. Results: Despite significant inter-subject and simulated intra-day PK variability and sensor error, PID demonstrated a significant improvement in target attainment compared to traditional bolus and continuous infusion approaches. Conclusion: A PID controller driven by ISF drug concentration measurements has the potential to precisely deliver piperacillin-tazobactam in critically-ill patients undergoing treatment for sepsis

Glucocorticoid signaling enhances expression of glucose-sensing molecules in immature pancreatic beta-like cells derived from murine embryonic stem cells in vitro

Pluripotent stem cells may serve as an alternative source of beta-like cells for replacement therapy of type 1 diabetes; however, the beta-like cells generated in many differentiation protocols are immature. The maturation of endogenous beta cells involves an increase in insulin expression starting in late gestation and a gradual acquisition of the abilities to sense glucose and secrete insulin by week 2 after birth in mice; however, what molecules regulate these maturation processes are incompletely known. Here, we aim to identify small molecules that affect immature beta cells. A cell-based assay, employing pancreatic beta-like cells derived from murine embryonic stem (ES) cells harboring a transgene containing an Insulin 1-promoter driven enhanced green fluorescent protein reporter, was used to screen a compound library (NIH Clinical Collection-003). Cortisone, a glucocorticoid, was among five positive hit compounds. Quantitative RT-PCR analysis revealed that glucocorticoids enhance the gene expression of not only insulin 1 but also glucose transporter-2 (Glut2; Slc2a2) and glucokinase (Gck), two molecules important for glucose sensing. Mifepristone, a pharmacological inhibitor of glucocorticoid receptor (GR) signaling, reduced the effects of glucocorticoids on Glut2 and Gck expression. The effects of glucocorticoids on ES-derived cells were further validated in immature primary islets. Isolated islets from 1-week-old mice had an increased Glut2 and Gck expression in response to a 4-day treatment of exogenous hydrocortisone in vitro. Gene deletion of GR in beta cells using rat insulin 2 promoter-driven Cre crossed with GRflox/flox mice resulted in a reduced gene expression of Glut2, but not Gck, and an abrogation of insulin secretion when islets were incubated in 0.5 mM D-glucose and stimulated by 17 mM D-glucose in vitro. These results demonstrate that glucocorticoids positively regulate glucose sensors in immature murine beta-like cells

multifunctional bioinstructive 3d architectures to modulate cellular behavior

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