Matrix-free calcium in isolated chromaffin vesicles

Isolated secretory vesicles from bovine adrenal medulla contain 80 nmol of Ca2+ and 25 nmol of Mg2+ per milligram of protein. As determined with a Ca2+-selective electrode, a further accumulation of about 160 nmol of Ca2+/mg of protein can be attained upon addition of the Ca2+ ionophore A23187. During this process protons are released from the vesicles, in exchange for Ca2+ ions, as indicated by the decrease of the pH in the incubation medium or the release of 9-aminoacridine previously taken up by the vesicles. Intravesicular Mg2+ is not released from the vesicles by A23 187, as determined by atomic emission spectroscopy. In the presence of N H Q , which causes the collapse of the secretory vesicle transmembrane proton gradient (ApH), Ca2+ uptake decreases. Under these conditions A23 187-mediated influx of Ca2+ and efflux of H+ cease at Ca2+ concentrations of about 4 pM. Below this concentration Ca2+ is even released from the vesicles. At the Ca2+ concentration at which no net flux of ions occurs the intravesicular matrix free Ca2+ equals the extravesicular free Ca2+. In the absence of NH4C1 we determined an intravesicular pH of 6.2. Under these conditions the Ca2+ influx ceases around 0.15 pM. From this value and the known pH across the vesicular membrane an intravesicular matrix free Ca2+ concentration of about 24 pM was calculated. This is within the same order of magnitude as the concentration of free Ca2+ in the vesicles determined in the presence of NH4C1. Calculation of the total Ca2+ present in the secretory vesicles gives an apparent intravesicular Ca2+ concentration of 40 mM, which is a factor of lo4 higher than the free intravesicular concentration of Ca2+. It can be concluded, therefore, that the concentration gradient of free Ca2+ across the secretory vesicle membrane in the intact chromaffin cells is probably small, which implies that less energy is required to accumulate and maintain Ca2+ within the vesicles than was previously anticipated

A prospective longitudinal study of Pasireotide in Nelson's syndrome

PURPOSE: Nelson's syndrome is a challenging condition that can develop following bilateral adrenalectomy for Cushing's disease, with high circulating ACTH levels, pigmentation and an invasive pituitary tumor. There is no established medical therapy. The aim of the study was to assess the effects of pasireotide on plasma ACTH and tumor volume in Nelson's syndrome. METHODS: Open labeled multicenter longitudinal trial in three steps: (1) a placebo-controlled acute response test; (2) 1 month pasireotide 300-600 μg s.c. twice-daily; (3) 6 months pasireotide long-acting-release (LAR) 40-60 mg monthly. RESULTS: Seven patients had s.c. treatment and 5 proceeded to LAR treatment. There was a significant reduction in morning plasma ACTH during treatment (mean ± SD; 1823 ± 1286 ng/l vs. 888.0 ± 812.8 ng/l during the s.c. phase vs. 829.0 ± 1171 ng/l during the LAR phase, p < 0.0001). Analysis of ACTH levels using a random intercept linear mixed-random effects longitudinal model showed that ACTH (before the morning dose of glucocorticoids) declined significantly by 26.1 ng/l per week during the 28-week of treatment (95% CI - 45.2 to - 7.1, p < 0.01). An acute response to a test dose predicted outcome in 4/5 patients. Overall, there was no significant change in tumor volumes (1.4 ± 0.9 vs. 1.3 ± 1.0, p = 0.86). Four patients withdrew during the study. Hyperglycemia occurred in 6 patients. CONCLUSIONS: Pasireotide lowers plasma ACTH levels in patients with Nelson's syndrome. A longer period of treatment may be needed to assess the effects of pasireotide on tumor volume. TRIAL REGISTRATION: Clinical Trials.gov ID, NCT01617733

The Impact of Food-Shaping Techniques on Nutrition, Mealtime Experiences, and Quality of Life for Older Adults in Aged Care Settings: A Systematic Review

OBJECTIVE: Food-shaping methods, particularly for texture-modified foods, present numerous opportunities to improve the visual appeal of food and potentially the nutrition of older people with dysphagia (swallowing difficulty). This review appraises and synthesizes the evidence on the use of food-shaping methods to enhance nutrition in older adults with swallowing difficulties. METHODS: In August 2022, five electronic databases (PubMed, CINAHL, Scopus, Cochrane Library, and Web of Science) were searched for original research related to the intersection of nutrition, food shaping, and older adults with swallowing difficulties. Characteristics of included studies were described and data from results and findings extracted for analysis across studies. RESULTS: Eighteen studies met the inclusion criteria and encompassed a variety of settings, including aged care settings (n = 15) and food science laboratories (n = 3). Qualitative and quantitative findings demonstrated a variety of impacts of food shaping for the older adult with swallowing difficulty, including enhanced nutrition and wellbeing. The content themes identified across studies were: links between food shaping and nutrition, shaping food for individual choice, food shaping for enjoyment, a combination of supporting factors, collaborative inter-disciplinary teams and roles, and implementation aligns with local contexts. CONCLUSION: With recent growth in research on food shaping, the body of studies reviewed identified an influence of food-shaping methods on the nutritional status of older adults with swallowing difficulties. Given the identified potential benefit of food shaping and attention to the visual appeal of food for older people, further research examining links between food shaping and nutrition are warranted

Perceptions and willingness concerning the collection of sexual orientation and gender identity data in Australian healthcare services

Background Despite growing recognition of the importance of collecting sexual orientation and gender identity (SOGI) data to improve healthcare access and equity for LGBTQA+ populations, uncertainty remains around how these data are collected, their perceived importance and individuals' willingness to disclose such information in healthcare settings. The aim of this study was to understand perceptions of the collection of data on sexual orientation and gender identity in healthcare settings across Australia, and individuals' willingness to provide this data. Methods A cross-sectional online survey of 657 Australian residents was conducted to assess participants' attitudes towards SOGI data in healthcare settings, along with preferences for methods to collect these data. Statistical analyses included ANCOVA, Chi-squared tests and Wilcoxon signed-rank tests. Results Participants generally recognised the importance of the collection of basic demographic data to support the provision of health services. Willingness to share SOGI data varied, with significant differences noted across gender, sexual orientation and cultural backgrounds. LGBTQA+ participants expressed greater willingness to provide SOGI data, but only in contextually appropriate situations, and preferred more inclusive data collection methods. Conclusions The study shows a context-dependent willingness to provide SOGI data in health care, underscoring the need for sensitive data collection methods. Insights into SOGI data collection attitudes are vital for developing inclusive and respectful healthcare practices. Improved SOGI data collection can enrich healthcare outcomes for diverse groups, informing public health policies and practices tailored to LGBTQA+ needs

A review of wearable motion tracking systems used in rehabilitation following hip and knee replacement

Clinical teams are under increasing pressure to facilitate early hospital discharge for total hip replacement and total knee replacement patients following surgery. A wide variety of wearable devices are being marketed to assist with rehabilitation following surgery. A review of wearable devices was undertaken to assess the evidence supporting their efficacy in assisting rehabilitation following total hip replacement and total knee replacement. A search was conducted using the electronic databases including Medline, CINAHL, Cochrane, PsycARTICLES, and PubMed of studies from January 2000 to October 2017. Five studies met the eligibility criteria, and all used an accelerometer and a gyroscope for their technology. A review of the studies found very little evidence to support the efficacy of the technology, although they show that the use of the technology is feasible. Future work should establish which wearable technology is most valuable to patients, which ones improve patient outcomes, and the most economical model for deploying the technolog

Application pratique de la méthode d’estimation de l’âge au décès de Schmitt et Broqua (2000)

Cette étude tend à confronter la méthode d’estimation de l’âge au décès proposée par Schmitt et Broqua (2000) à la réalité archéologique de la population d’une nécropole historique. Le grand nombre de bassins étudiés (940) permet une approche statistique de l’estimation d’âge proposée, en particulier sur la conservation des os coxaux et sur les différences d’estimation entre les côtés droit et gauche. Finalement, la méthode semble assez bien adaptée à l’étude d’une population archéologique bien que les différences entre les côtés ne soient pas négligeables

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

Coproducing Knowledge of the Implementation of Complex Digital Health Interventions for Adults with Acquired Brain Injury and their Communication Partners: Protocol for a Mixed Methods Study.

BACKGROUND: The Social Brain Toolkit, conceived and developed in partnership with stakeholders, is a novel suite of web-based communication interventions for people with brain injury and their communication partners. To support effective implementation, the developers of the Social Brain Toolkit have collaborated with people with brain injury, communication partners, clinicians, and individuals with digital health implementation experience to coproduce new implementation knowledge. In recognition of the equal value of experiential and academic knowledge, both types of knowledge are included in this study protocol, with input from stakeholder coauthors. OBJECTIVE: This study aims to collaborate with stakeholders to prioritize theoretically based implementation targets for the Social Brain Toolkit, understand the nature of these priorities, and develop targeted implementation strategies to address these priorities, in order to support the Social Brain Toolkit's implementation. METHODS: Theoretically underpinned by the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework of digital health implementation, a maximum variation sample (N=35) of stakeholders coproduced knowledge of the implementation of the Social Brain Toolkit. People with brain injury (n=10), communication partners (n=11), and clinicians (n=5) participated in an initial web-based prioritization survey based on the NASSS framework. Survey completion was facilitated by plain English explanations and accessible captioned videos developed through 3 rounds of piloting. A speech-language pathologist also assisted stakeholders with brain injury to participate in the survey via video teleconference. Participants subsequently elaborated on their identified priorities via 7 web-based focus groups, in which researchers and stakeholders exchanged stakeholder perspectives and research evidence from a concurrent systematic review. Stakeholders were supported to engage in focus groups through the use of visual supports and plain English explanations. Additionally, individuals with experience in digital health implementation (n=9) responded to the prioritization survey questions via individual interview. The results will be deductively analyzed in relation to the NASSS framework in a coauthorship process with people with brain injury, communication partners, and clinicians. RESULTS: Ethical approval was received from the University of Technology Sydney Health and Medical Research Ethics Committee (ETH20-5466) on December 15, 2020. Data were collected from April 13 to November 18, 2021. Data analysis is currently underway, with results expected for publication in mid-2022. CONCLUSIONS: In this study, researchers supported individuals with living experience of acquired brain injury, of communicating with or clinically supporting someone post injury, and of digital health implementation, to directly access and leverage the latest implementation research evidence and theory. With this support, stakeholders were able to prioritize implementation research targets, develop targeted implementation solutions, and coauthor and publish new implementation findings. The results will be used to optimize the implementation of 3 real-world, evidence-based interventions and thus improve the outcomes of people with brain injury and their communication partners. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35080

Comparative and Functional Genomics of Rhodococcus opacus PD630 for Biofuels Development

The Actinomycetales bacteria Rhodococcus opacus PD630 and Rhodococcus jostii RHA1 bioconvert a diverse range of organic substrates through lipid biosynthesis into large quantities of energy-rich triacylglycerols (TAGs). To describe the genetic basis of the Rhodococcus oleaginous metabolism, we sequenced and performed comparative analysis of the 9.27 Mb R. opacus PD630 genome. Metabolic-reconstruction assigned 2017 enzymatic reactions to the 8632 R. opacus PD630 genes we identified. Of these, 261 genes were implicated in the R. opacus PD630 TAGs cycle by metabolic reconstruction and gene family analysis. Rhodococcus synthesizes uncommon straight-chain odd-carbon fatty acids in high abundance and stores them as TAGs. We have identified these to be pentadecanoic, heptadecanoic, and cis-heptadecenoic acids. To identify bioconversion pathways, we screened R. opacus PD630, R. jostii RHA1, Ralstonia eutropha H16, and C. glutamicum 13032 for growth on 190 compounds. The results of the catabolic screen, phylogenetic analysis of the TAGs cycle enzymes, and metabolic product characterizations were integrated into a working model of prokaryotic oleaginy.Cambridge-MIT InstituteMassachusetts Institute of Technology. (Seed Grant program)Shell Oil CompanyNational Institute of Allergy and Infectious Diseases (U.S.)United States. National Institutes of HealthNational Institutes of Health. Department of Health and Human Services (Contract No. HHSN272200900006C