Caloric restriction promotes beta cell longevity and delays aging and senescence by enhancing cell identity and homeostasis mechanisms.

Caloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure and function of pancreatic beta cells over the lifetime of the animal remains unknown. Here, we used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype to transcription factors involved in beta cell identity (Mafa) and homeostasis (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more energetically competent. In fact, high-resolution light and electron microscopy indicates that CR reduces beta cell mitophagy and increases mitochondria mass, increasing mitochondrial ATP generation. Finally, we show that long-term CR delays the onset of beta cell aging and senescence to promote longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cells during aging and diabetes.

Caloric restriction promotes beta cell longevity and delays aging and senescence by enhancing cell identity and homeostasis mechanisms.

Caloric restriction (CR) extends organismal lifespan and health span by improving glucose homeostasis mechanisms. How CR affects organellar structure and function of pancreatic beta cells over the lifetime of the animal remains unknown. Here, we used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis link this transcriptional phenotype to transcription factors involved in beta cell identity (Mafa) and homeostasis (Atf6). Imaging metabolomics further demonstrates that CR beta cells are more energetically competent. In fact, high-resolution light and electron microscopy indicates that CR reduces beta cell mitophagy and increases mitochondria mass, increasing mitochondrial ATP generation. Finally, we show that long-term CR delays the onset of beta cell aging and senescence to promote longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cells during aging and diabetes.

Common calls to a poisons information centre by general practitioners.

BACKGROUND: Poisoning in the community is common and can occasionally result in serious outcomes, such as organ damage and death. Many cases of poisoning can be successfully managed in the primary care setting. OBJECTIVE: This article describes common calls the Queensland Poisons Information Centre (Qld PIC) receives from general practices and provides information on the management of poisoning in the community. DISCUSSION: Common calls to the Qld PIC from general practice include calls about exposure to paracetamol and household cleaning products, with ocular exposure to toxins common. Most cases of poisoning can be managed supportively. Decontamination, observation or antidote therapy may be required in some cases. Ocular exposure to poisons requires irrigation, examination and, occasionally, referral for specialist ophthalmological assessment. The PIC can help general practitioners (GPs) with risk assessment and management advice to ensure the best outcomes for their patients. GPs can contact the PIC on 13 11 26.

Ambulance referrals to an Australian Poisons Information Centre: a retrospective series.

INTRODUCTION: For poisoned patients, ambulance services may be the first point of contact for medical attention. With limited training in toxicology, ambulance services are encouraged to contact the Poisons Information Centre (PIC) for advice. This study aims to characterise referrals to a PIC from a state ambulance service with the purpose of improving information delivery and efficient use of these services. METHODS: This was a retrospective observational series of referrals to an Australian state PIC from ambulance staff from 1 January 2020 to 31 December 2020. Referrals were identified through the PIC Pharmhos database where the call originated from either a paramedic or emergency dispatch officer. Call reports were reviewed to extract data on patient demographics, exposure details and advice provided by the PIC. RESULTS: There were 1537 calls regarding 1420 poisoning exposures over the 12-month period, with 117 (7.6%) follow-up calls, representing 4.1% (1537/37835) of total calls to the PIC. Initial calls originated from paramedics in 999/1420 (70.4%) referrals, with dispatch officers referring 421/1420 (29.6%). Paediatric patients aged <15 years were involved in 492/1420 (34.6%) exposures with the commonest age range being 1-4 years. Most referrals involved pharmaceuticals exposures (756/1420 [53.2%]) followed by chemicals (557/1420 [39.2%]) and drugs of abuse (69/1420 [4.9%]). The commonest agents involved were paracetamol followed by quetiapine and sertraline. The PIC advised no treatment following benign exposures in 617/1420 (43.5%) calls, first aid measures in 333/1420 (23.5%) calls, supportive measures in 339/1420 (23.9%) calls and specific treatment in 32/1420 (2.3%) calls. Referral to the hospital was advised in 761/1420 (53.6%) calls, the majority of these were following deliberate self-poisonings (428/1420 [30.1%]). CONCLUSIONS: Ambulance staff commonly contact the PIC following benign exposures where no treatment is required. Ambulance referral to a PIC following suspected poisonings may have a role in preventing unnecessary transfer to hospital in poisoned patients.

Documentation in the patient medical record was associated with improved adherence to Poisons Information Centres telephone advice.

Context: There is little research examining clinician adherence to specialist toxicological phone advice. Efforts to improve adherence should be sought to optimise the management of poisoned patients. This study aimed to determine if contemporaneous documentation in the patient electronic medical record (EMR) improved adherence to Poisons Information Centre (PIC) advice.Methods: This was a prospective before and after observational study following the implementation of documented poisoning management advice by PIC staff into the patient's EMR. Advice adherence was assessed following a review of the patient medical records and designated to complete adherence, minor discrepancies not affecting patient care, major discrepancies affecting patient care and non-adherence. The primary outcome was the proportion of satisfactory (complete adherence/minor discrepancies) adherence. Secondary outcomes included the accuracy of documented telephone advice by the treating clinician, the number of case recalls and episodes of sub-optimal management.Results: A total of 980 cases (347 in the pre-intervention phase and 633 in the post-intervention phase) were included in the study, of which 350 had PIC EMR documentation performed. Documented call advice by the treating clinician was absent in 41 of 347 cases (11.8%) cases and inaccurate in 42 of 306 cases (13.7%). Following PIC documentation, satisfactory adherence improved from 304/347(87.6%) to 333/350(95.1%)(difference 7.5% [95% CI 3.1% to 11.9%]), with suboptimal management decreasing from 48/347(13.8%) to 14/350(4%)(difference - 9.8% [95% CI -5.5% to -14.4%]). Recalls were similar in both periods. The median time to enter advice into the EMR was 26 min (IQR: 14-45 min). The main reason for not documenting advice was that the PIC staff member was working a solo shift with a prohibitively heavy workload.Discussion: EMRs enable PICs to supplement verbal advice with written documentation, offering an opportunity to improve communication and enable better handover of clinical information.Conclusion: Documentation of advice by PIC staff in the patient medical record was associated with improved advice adherence and reduced sub-optimal management.

Loss of mTORC1 signaling alters pancreatic α cell mass and impairs glucagon secretion.

Glucagon plays a major role in the regulation of glucose homeostasis during fed and fasting states. However, the mechanisms responsible for the regulation of pancreatic α cell mass and function are not completely understood. In the current study, we identified mTOR complex 1 (mTORC1) as a major regulator of α cell mass and glucagon secretion. Using mice with tissue-specific deletion of the mTORC1 regulator Raptor in α cells (αRaptorKO), we showed that mTORC1 signaling is dispensable for α cell development, but essential for α cell maturation during the transition from a milk-based diet to a chow-based diet after weaning. Moreover, inhibition of mTORC1 signaling in αRaptorKO mice and in WT animals exposed to chronic rapamycin administration decreased glucagon content and glucagon secretion. In αRaptorKO mice, impaired glucagon secretion occurred in response to different secretagogues and was mediated by alterations in KATP channel subunit expression and activity. Additionally, our data identify the mTORC1/FoxA2 axis as a link between mTORC1 and transcriptional regulation of key genes responsible for α cell function. Thus, our results reveal a potential function of mTORC1 in nutrient-dependent regulation of glucagon secretion and identify a role for mTORC1 in controlling α cell-mass maintenance.

Friendship Dissolution Within Social Networks Modeled Through Multilevel Event History Analysis.

A social network perspective can bring important insight into the processes that shape human behavior. Longitudinal social network data, measuring relations between individuals over time, has become increasingly common-as have the methods available to analyze such data. A friendship duration model utilizing discrete-time multilevel survival analysis with a multiple membership random effect structure is developed and applied here to study the processes leading to undirected friendship dissolution within a larger social network. While the modeling framework is introduced in terms of understanding friendship dissolution, it can be used to understand microlevel dynamics of a social network more generally. These models can be fit with standard generalized linear mixed-model software, after transforming the data to a pair-period data set. An empirical example highlights how the model can be applied to understand the processes leading to friendship dissolution between high school students, and a simulation study is used to test the use of the modeling framework under representative conditions that would be found in social network data. Advantages of the modeling framework are highlighted, and potential limitations and future directions are discussed.

Parental and adolescent health behaviors and pathways to adulthood.

This paper examines associations among parental and adolescent health behaviors and pathways to adulthood. Using data from the National Longitudinal Study of Adolescent to Adult Health, we identify a set of latent classes describing pathways into adulthood and examine health-related predictors of these pathways. The identified pathways are consistent with prior research using other sources of data. Results also show that both adolescent and parental health behaviors differentiate pathways. Parental and adolescent smoking are associated with lowered probability of the higher education pathway and higher likelihood of the work and the work & family pathways (entry into the workforce soon after high school completion). Adolescent drinking is positively associated with the work pathway and the higher education pathway, but decreases the likelihood of the work & family pathway. Neither parental nor adolescent obesity are associated with any of the pathways to adulthood. When combined, parental/adolescent smoking and adolescent drinking are associated with displacement from the basic institutions of school, work, and family.

Delineating prototypical patterns of substance use initiations over time.

AIMS: The purpose of this paper is to discover patterns of drug use initiations over time through a multiple event process survival mixture model (MEPSUM model), a novel approach for substance use and prevention research. DESIGN: The MEPSUM model combines survival analysis and mixture modeling-specifically latent class analysis-to examine individual differences in the timing of initiation and cumulative risk of substance use over time, and is applied to cross-sectional survey data on drug initiations. SETTING: Data are drawn from the 2009 National Survey on Drug Use and Health. PARTICIPANTS: The survey includes responses from 55 772 individuals (52.05% female). MEASUREMENTS: The age of first use of nine different types of substances are examined, including alcohol, tobacco, cocaine and non-medical use of prescription drugs. FINDINGS: It is argued that six patterns parsimoniously describe the population's risk of initiating different substances over time, described colloquially as general abstainers; early, late and progressive soft drug users; and early and late hard drug users. Both gender and ethnicity significantly predict the patterns, with Caucasians and males having a higher risk for the hard drug-using patterns. The MEPSUM model produced stable results in this application, as the patterns are validated in a split-sample design. CONCLUSIONS: The MEPSUM model provides a statistical framework from which to evaluate patterns of risk for drug initiations over time and predict substance use trajectories relevant to public health interventions. The patterns that result from the model can be used as outcomes for subsequent investigations of etiological and mediating mechanisms.

A discrete-time Multiple Event Process Survival Mixture (MEPSUM) model.

Traditional survival analysis was developed to investigate the occurrence and timing of a single event, but researchers have recently begun to ask questions about the order and timing of multiple events. A multiple event process survival mixture model is developed here to analyze nonrepeatable events measured in discrete-time that may occur at the same point in time. Building on both traditional univariate survival analysis and univariate survival mixture analysis, the model approximates the underlying multivariate distribution of hazard functions via a discrete-point finite mixture in which the mixing components represent prototypical patterns of event occurrence. The model is applied in an empirical analysis concerning transitions to adulthood, where the events under study include parenthood, marriage, beginning full-time work, and obtaining a college degree. Promising opportunities, as well as possible limitations of the model and future directions for research, are discussed.

Analyzing repeated measures data on individuals nested within groups: accounting for dynamic group effects.

Researchers commonly collect repeated measures on individuals nested within groups such as students within schools, patients within treatment groups, or siblings within families. Often, it is most appropriate to conceptualize such groups as dynamic entities, potentially undergoing stochastic structural and/or functional changes over time. For instance, as a student progresses through school, more senior students matriculate while more junior students enroll, administrators and teachers may turn over, and curricular changes may be introduced. What it means to be a student within that school may thus differ from 1 year to the next. This article demonstrates how to use multilevel linear models to recover time-varying group effects when analyzing repeated measures data on individuals nested within groups that evolve over time. Two examples are provided. The 1st example examines school effects on the science achievement trajectories of students, allowing for changes in school effects over time. The 2nd example concerns dynamic family effects on individual trajectories of externalizing behavior and depression.

The association between diagnosis of plantar fasciitis and Windlass test results.

Twenty-two patients with plantar fasciitis, 23 patients with other types of foot pain, and 30 patients in a control group were evaluated with the Windlass test performed in a weightbearing and non-weightbearing position. In the non-weightbearing test, the first MP joint was maximally dorsiflexed with the ankle stabilized. The weightbearing test was performed with the toes hanging off the edge of a stool and dorsiflexion of the first MP was performed. Seven of the 22 patients in the plantar fasciitis group had a positive weightbearing Windlass test (31.8%), while only three had a positive test result in a non-weightbearing position (13.6%). None of the patients in the other foot pain group or control group had pain in the weightbearing and non-weightbearing positions. Despite its high rate of specificity, the low rate of sensitivity of the Windlass test may limit its usefulness in the clinical evaluation in patients with plantar fasciitis.