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Background: Insulin, secreted from pancreatic islets of Langerhans, is of critical importance in regulating glucose homeostasis. Defective insulin secretion and/or the inability of tissues to respond to insulin results in insulin resistance and to several metabolic and organ alterations. We have previously demonstrated that BAG3 regulates insulin secretion. Herein we explored the consequences of beta-cells specific BAG3 deficiency in an animal model. Methods: We generated a beta-cells specific BAG3 knockout mouse model. Glucose and insulin tolerance tests, proteomics, metabolomics, and immunohistochemical analysis were used to investigate the role of BAG3 in regulating insulin secretion and the effects of chronic exposure to excessive insulin release in vivo. Results: Beta-cells specific BAG3 knockout results in primary hyperinsulinism due to excessive insulin exocytosis finally leading to insulin resistance. We demonstrate that resistance is mainly muscle-dependent while the liver remains insulin sensitive. The chronically altered metabolic condition leads in time to histopathological alterations in different organs. We observe elevated glycogen and lipid accumulation in the liver reminiscent of non-alcoholic fatty liver disease as well as mesangial matrix expansion and thickening of the glomerular basement membrane, resembling the histology of chronic kidney disease. Conclusion: Altogether, this study shows that BAG3 plays a role in insulin secretion and provides a model for the study of hyperinsulinemia and insulin resistance.

Waste material classification is a challenging yet important task in waste management. The realization of low-cost waste classification systems and methods is critical to meet the ever-increasing demand for efficient waste management and recycling. In this paper, we demonstrate a simple, compact and low-cost classification system based on optical reflectance measurements in the short-wave infrared for the segregation of waste materials such as plastics, paper, glass, and aluminium. The system comprises a small set of LEDs and one single broadband photodetector. All devices are controlled through low-cost and low-power electronics, and data are gathered and managed via a computer interface. The proposed system reaches accuracy levels as high as 94.3% when considering seven distinct materials and 97.0% when excluding the most difficult to classify, thus representing a valuable proof-of-concept for future system developments.

Aim: Polydeoxyribonucleotide (PDRN) is a chain-like polymer derived from DNA. Recent in vitro and animal studies have showcased the beneficial impacts of PDRN on the process of bone mending, whether used on its own or in conjunction with other substances that aid in regeneration. This scoping review aims to synthesize the current understanding of how PDRNs influence bone healing. Materials and Methods: The studies included in the screening procedure were randomized controlled clinical trials (RCTs), both retrospective and prospective case–control studies, as well as in vitro and in vivo investigations. Articles were sourced from PubMed (MEDLINE), Scopus, EMBASE, Web of Science, and Google Scholar electronic databases using the following MeSH terms: (polydeoxyribonucleotide) and (bone) and (regeneration). Results: Initially, 228 articles were identified. Following the review process, a total of eight studies were ultimately examined. Among these, two were confined to laboratory studies, five were conducted on living organisms, and one encompassed both evaluations on living organisms and in vitro assessments. A descriptive qualitative approach was employed to present the data extracted from the studies that were included. Conclusions: PDRN has the potential to enhance the process of bone healing and the quantity of newly generated bone when combined with grafting materials. Future clinical studies are warranted to ascertain the appropriate clinical application of PDRN based on the dosage under consideration.

Interventions aiming to improve access to and retention in HIV care are optimized when they are tailored to clients' needs. This paper describes an initiative of interventions implemented by ten demonstration sites using a transnational framework to tailor services for Mexicans and Puerto Ricans living with HIV. Transnationalism describes how immigrants (and their children) exist in their "receiving" place (e.g., continental U.S.) while simultaneously maintaining connections to their country or place of origin (e.g., Mexico). We describe interventions in terms of the strategies used, the theory informing design and the tailoring, and the integration of transnationalism. We argue how applying the transnational framework may improve the quality and effectiveness of services in response to the initiative's overall goal, which is to produce innovative, robust, evidence-informed strategies that go beyond traditional tailoring approaches for HIV interventions with Latino/as populations.

This manuscript describes the experiences of three state departments of health (SDoH) that successfully launched data sharing interventions involving surveillance and/or patient data collected in clinics to improve care outcomes among people living with HIV. We examined 58 key informant interviews, gathered at two time points, to describe the development and implementation of data sharing interventions. We identified three common themes across states' experiences: creating standard practices, fostering interoperability, and negotiating the policy environment. Projects were successful when state teams adapted to changing circumstances and were committed to a consistent communication process. Once implemented, the interventions streamlined processes to promote linkage and retention in care among low-income populations living with HIV. Despite using routinely collected data, key informants emphasized the labor-intensive process to develop and sustain the interventions. Lessons learned from these three state experiences can help inform best practices for other SDoH that are considering launching similar interventions.

Ensuring continuity of and retention in care after release from prison is critical for optimizing health outcomes among people living with HIV. As part of a large federal initiative, we conducted qualitative interviews (n = 24) with individuals living with HIV and recently released from prison in four states to understand their experiences in different navigation interventions to improve access to HIV care post-release. Interventions were delivered only in prison, only in the community, or in both settings. While the interventions varied by design, overall, participants appreciated the breadth of support received from interventionists, including health system navigation, case management and social support. Even when individuals leaving prison were returning to clinics that they were familiar with, systems navigation supported continuity of care. Our findings elucidate why navigational support was instrumental, and underscore the value of a variety of types of navigation programs in facilitating continuity of care and reintegration post-prison.

With the evolution of CAD/CAM technology, custom titanium and/or zirconia abutments are increasingly being used, leading to several comparisons in the literature, both mechanical and aesthetic, to evaluate performance differences between these two types of abutments. Therefore, the aim of this comprehensive review is to present the most recent data on the latest comparisons between CAD/CAM and stock abutment applications. The PICO model was used to perform this review, through a literature search of the PubMed (MEDLINE) and Scopus electronic databases. CAD/CAM abutments allow individualization of abutment parameters with respect to soft tissue, allow increased fracture toughness, predict the failure mode, show no change in the fracture toughness over time, reduce the prosthetic steps, and reduce the functional implant prosthesis score and pain perceived by patients in the early stages. The advantages associated with the use of stock abutments mainly concern the risk of corrosion, time spent, cost, and fit, evaluated in vitro, in the implant–abutment connection. Equal conditions are present regarding the mechanical characteristics during dynamic cycles, screw loss, radiographic fit, and degree of micromotion. Further randomized controlled clinical trials should be conducted to evaluate the advantages reported to date, following in vitro studies about titanium and/or zirconia stock abutments.

Abstract Background Glycogen storage disease (GSD) type 0, VI and IX are inborn errors of metabolism involving hepatic glycogen synthesis and degradation. We performed a characterization of a large Italian cohort of 30 patients with GSD type 0a, VI, IXa, IXb and IXc. A retrospective evaluation of genetical, auxological and endocrinological data, biochemical tests, and nutritional intakes was assessed. Eventual findings of overweight/obesity and insulin-resistance were correlated with diet composition. Results Six GSD-0a, 1 GSD-VI, and 23 GSD-IX patients were enrolled, with an age of presentation from 0 to 72 months (median 14 months). Diagnosis was made at a median age of 30 months, with a median diagnostic delay of 11 months and a median follow-up of 66 months. From first to last visit, patients gained a median height of 0.6 SDS (from − 1.1 to 2.1 SDS) and a median weight of 0.5 SDS (from − 2.5 to 3.3 SDS); mean and minimal glucose values significant improved (p

Abstract Background Glycogen storage diseases (GSDs) with liver involvement are classified into types 0, I, III, IV, VI, IX and XI, depending on the affected enzyme. Hypoglycemia and hepatomegaly are hallmarks of disease, but muscular and renal tubular involvement, dyslipidemia and osteopenia can develop. Considering the paucity of literature available, herein we provide a narrative review of these latter forms of GSDs. Main body Diagnosis is based on clinical manifestations and laboratory test results, but molecular analysis is often necessary to distinguish the various forms, whose presentation can be similar. Compared to GSD type I and III, which are characterized by a more severe impact on metabolic and glycemic homeostasis, GSD type 0, VI, IX and XI are usually known to be responsive to the nutritional treatment for achieving a balanced metabolic homeostasis in the pediatric age. However, some patients can exhibit a more severe phenotype and an important progression of the liver and muscular disease. The effects of dietary adjustments in GSD type IV are encouraging, but data are limited. Conclusions Early diagnosis allows a good metabolic control, with improvement of quality of life and prognosis, therefore we underline the importance of building a proper knowledge among physicians about these rare conditions. Regular monitoring is necessary to restrain disease progression and complications.

Glycogen storage type Ib (GSDIb) is a rare inborn error of metabolism caused by glucose-6-phosphate transporter (G6PT, SLC37A4) deficiency. G6PT defect results in excessive accumulation of glycogen and fat in the liver, kidney, and intestinal mucosa and into both glycogenolysis and gluconeogenesis impairment. Clinical features include hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia, and growth retardation. Long-term complications are liver adenoma, hepatocarcinoma, nephropathy and osteoporosis. The hallmark of GSDIb is neutropenia, with impaired neutrophil function, recurrent infections and inflammatory bowel disease. Alongside classical nutritional therapy with carbohydrates supplementation and immunological therapy with granulocyte colony-stimulating factor, the emerging role of 1,5-anhydroglucitol in the pathogenesis of neutrophil dysfunction led to repurpose empagliflozin, an inhibitor of the renal glucose transporter SGLT2: the current literature of its off-label use in GSDIb patients reports beneficial effects on neutrophil dysfunction and its clinical consequences. Surprisingly, this glucose-lowering drug ameliorated the glycemic and metabolic control in GSDIb patients. Furthermore, numerous studies from big cohorts of type 2 diabetes patients showed the efficacy of empagliflozin in reducing the cardiovascular risk, the progression of kidney disease, the NAFLD and the metabolic syndrome. Beneficial effects have also been described on peripheral neuropathy in a prediabetic rat model. Increasing evidences highlight the role of empagliflozin in regulating the cellular energy sensors SIRT1/AMPK and Akt/mTOR, which leads to improvement of mitochondrial structure and function, stimulation of autophagy, decrease of oxidative stress and suppression of inflammation. Modulation of these pathways shift the oxidative metabolism from carbohydrates to lipids oxidation and results crucial in reducing insulin levels, insulin resistance, glucotoxicity and lipotoxicity. For its pleiotropic effects, empagliflozin appears to be a good candidate for drug repurposing also in other metabolic diseases presenting with hypoglycemia, organ damage, mitochondrial dysfunction and defective autophagy.

Introduction General practitioners (GPs) routinely provide care for patients with heart failure (HF); however, adherence to management guidelines, including titrating medication to optimal dose, can be challenging in this setting. This study will evaluate the effectiveness of a multifaceted intervention to support adherence to HF management guidelines in primary care.Methods and analysis We will undertake a multicentre, parallel-group, randomised controlled trial of 200 participants with HF with reduced ejection fraction. Participants will be recruited during a hospital admission due to HF. Following hospital discharge, the intervention group will have follow-up with their GP scheduled at 1 week, 4 weeks and 3 months with the provision of a medication titration plan approved by a specialist HF cardiologist. The control group will receive usual care. The primary endpoint, assessed at 6 months, will be the difference between groups in the proportion of participants being prescribed five guideline-recommended treatments; (1) ACE inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor at least 50% of target dose, (2) beta-blocker at least 50% of target dose, (3) mineralocorticoid receptor antagonist at any dose, (4) anticoagulation for patients diagnosed with atrial fibrillation, (5) referral to cardiac rehabilitation. Secondary outcomes will include functional capacity (6-minute walk test); quality of life (Kansas City Cardiomyopathy Questionnaire); depressive symptoms (Patient Health Questionnaire-2); self-care behaviour (Self-Care of Heart Failure Index). Resource utilisation will also be assessed.Ethics and dissemination Ethical approval was granted by the South Metropolitan Health Service Ethics Committee (RGS3531), with reciprocal approval at Curtin University (HRE2020-0322). Results will be disseminated via peer-reviewed publications and conferences.Trial registration number ACTRN12620001069943.

Implant rehabilitation is a daily practice in dentistry, and patients often have heightened expectations regarding both the functional and the aesthetic outcome. Implant–abutment connection (IAC) is involved in the long-term aesthetic quality of the rehabilitation. The use of one-piece implants for fixing dentures may prevent the mechanical and biological implication of the implant–abutment interface, resulting in a better quality of hard and soft tissue maintenance. In this case report, we present a novel one-piece implant in a maxillary rehabilitation with a full model-free digital approach.

Abstract Background Glycogen storage disease type XII is a rare metabolic disease resulting from Aldolase A deficiency that causes muscle glycogen accumulation, with crisis of rhabdomyolysis and hemolytic anemia. In the very few cases described, rhabdomyolysis crises are caused by fever and/or exercise and can accompany acute hemolytic anemia. Although currently there is no therapy available for this disease, the guidelines for the management of other forms of glycogen storage diseases recommend a nutritional therapy in order to avoid hypoglycemia or prevent exercise-induced rhabdomyolysis. Case presentation In this case report we describe a new phenotype of the disease in a 14-year-old boy, characterized by seizures and rhabdomyolysis. Beside an antiepileptic treatment, we propose a new therapeutic approach based on ketogenic diet in order to supply an energetic substrate for skeletal muscle and neurons. Conclusions The anti-epileptic therapy and the dietetic approach were well tolerated by the patient who showed good compliance. This led to a deceleration of the disease with no other acute episodes of seizures and rhabdomyolysis, without any side effects observed.

Objective: This study aimed to compare the relative physical recovery and symptoms after SARS-CoV-2 infection between groups confirmed positive or negative to early strains of COVID-19. Methods: A prospective, longitudinal cohort study compared outcomes of metropolitan adults polymerase chain reaction-tested for COVID-19 between March and November 2020 in Western Australia. Control matching was attempted: inpatients (gender, age) and ambulatory clinic (gender, age, asthma, chronic pulmonary disease). One-year follow-up involved three repeated measures: physical function (grip strength and 1-min sit-to-stand) and patient-reported outcomes (Fatigue Severity Scale, modified Medical Research Council dyspnoea scale and Euroqol-5D-5L). Results: Three hundred and forty-four participants were recruited (154 COVID+, age 54 ± 18 years, 75 females [49%]); 190 COVID−, age 52 ± 16 years, 67 females [35%]) prior to national vaccination roll-out. No between-group differences in physical function measures were evident at any time point. Fatigue (OR 6.62, 95% CI 2.74–15.97) and dyspnoea (OR 2.21, 95% CI 1.14–4.30) were higher in the COVID+ group at second assessment (T2). On Euroqol-5D-5L, no between-group differences were evident in the physical function domains of self-care, mobility or usual activities at any time point. However, COVID+ participants were less likely to report an absence of anxiety or depression symptoms at T2 (OR 0.41, 95% CI 0.19–0.89). Conclusions: Neither statistical nor clinically meaningful differences in physical function were evident between COVID+ and COVID− participants to 12-months after acute illness. Symptoms of fatigue, dyspnoea, anxiety or depression were more prevalent in the COVID+ group til ~8 months after illness with between-group differences no longer evident at 1 year. What is known about the topic? COVID-19 evokes multi-system sequelae including persistent physical and mental health symptoms, functional impairments and poorer quality of life. What does this paper add? A COVID+ group had equivalent physical recovery over 12 months; but higher prevalence of fatigue, dyspnoea and anxiety/depression symptoms at ~8 months compared to a COVID− group. What are the implications for practitioners? Health authorities and employers should know that while adequate physical function may return within months, post-acute sequelae of COVID-19 impair sufferers for over 6 months, likely necessitating healthcare support and workplace adjustments to optimise timely return to participation. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested an association between H. pylori and metabolic-disfunction associated fatty liver disease (MASLD). However, epidemiologic studies have yielded inconsistent results. We aim to evaluate the association of H. pylori and G-allele PNPLA3 in MASLD diagnosis, and markers of severity. Methods: A multi-center cross-sectional study was conducted. A total 224 functional dyspepsia (FD) patients cohort who underwent gastroscopy was selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, LSM by VCTE, gastric biopsies, H. pylori status, and rs738409 PNPLA3 were evaluated. A second retrospective cohort of 86 patients with biopsy-proven MASLD who underwent gastroscopy with gastric biopsies was analyzed. Results: In the FD cohort MASLD was observed in 52%, and H. pylori-positive in 51%. H. pylori infection was associated with MASLD prevalence, but in multivariate analyses adjusted for G-allele PNPLA3, it became not significant. Then in MASLD-only dyspeptic cohort, H. pylori infection was significantly linked to elevated serum AST levels and increased liver stiffness measurements, suggesting a potential role in liver injury and fibrosis. Histopathological analysis in biopsy-proven MASLD patients further supported these findings, showing a significant association between H. pylori infection and increased NAS score, fibrosis stage, and prevalence of MASH. Notably, the combination of H. pylori infection and G-allele PNPLA3 appeared to exacerbate MASLD severity beyond individual effects. Conclusions: Our results suggest that H. pylori infection may play a role in the progression of liver injury and fibrosis in patients with MASLD, especially in those with specific genetic predispositions. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusion Boxing is associated with a high risk of head injuries and increases the likelihood of chronic traumatic encephalopathy. This study explores the effects of sub‐concussive impacts on boxers by applying both linear and nonlinear analysis methods to electroencephalogram (EEG) data.Twenty‐one boxers were selected (mean ± SD, age 28.38 ± 5.5 years; weight 67.55 ± 8.90 kg; years of activity 6.76 ± 5.45; education 14.19 ± 3.08 years) and divided into ‘beginner’ and ‘advanced’ groups. The Montreal Cognitive Assessment and the Frontal Assessment Battery were administered; EEG data were collected in both eyes‐open (EO) and eyes‐closed (EC) conditions during resting states. Analyses of EEG data included normalized power spectral density (nPSD), power law exponent (PLE), detrended fluctuation analysis and multiscale entropy. Statistical analyses were used to compare the groups.Significant differences in nPSD and PLE were observed between the beginner and advanced boxers, with advanced boxers showing decreased mean nPSD and PLE (nPSD 4–7 Hz, p = 0.013; 8–13 Hz, p = 0.003; PLE frontal lobe F3 EC, p = 0.010). Multiscale entropy analysis indicated increased entropy at lower frequencies and decreased entropy at higher frequencies in advanced boxers (F3 EC, p = 0.024; occipital lobe O1 EO, p = 0.029; occipital lobe O2 EO, p = 0.036). These changes are similar to those seen in Alzheimer's disease.Nonlinear analysis of EEG data shows potential as a neurophysiological biomarker for detecting the asymptomatic phase of chronic traumatic encephalopathy in boxers. This methodology could help monitor athletes' health and reduce the risk of future neurological injuries in sports. [ABSTRACT FROM AUTHOR]

Physical activity (PA) and weight management are critical for cardiovascular disease (CVD) secondary prevention. However, PA adherence during or after cardiac rehabilitation is low. Here, we assess the feasibility and acceptability of the Australian football-themed Aussie Fans in Training (Aussie-FIT) program and associated trial procedures when adapted for men with CVD. A pragmatic randomised control trial, with waitlist control arm, and follow-up measures at 3 and 6 months. Men with a CVD diagnosis and body mass index ≥25 kg/m2 were recruited from community and clinical settings, and randomised, following baseline measures of health and health behaviours. The intervention arm attended 12 face-to-face football-themed education and PA sessions. Feasibility (recruitment, retention, attendance, and adherence to trial procedures) was assessed via mixed methods. A total of 74% (64/86) of participants expressing interest met the eligibility criteria. Of those, 49 men (mean age=61.4, standard deviation=9.5, mean body mass index=31.3, standard deviation=4.2) were randomised. Program attendance rates (87% attended ≥80% of sessions) and retention (92%) were high. Trial retention at the primary end point (3 months) was high (86%) and at the 6-month follow-ups reduced to 67%. Program and trial procedures were acceptable, except for the request to visit a pathologist for the blood draw. Using a football theme and setting may be a feasible way to engage men with CVD in health behaviour change. Given the existing pilot evidence for men at risk of CVD, and that recruitment rates were under the target, trialling a program for men with or at risk of CVD is recommended. [ABSTRACT FROM AUTHOR]

This technical note aims to present a recently developed computer-guided protocol characterized by titanium-reinforced stackable surgical guides during post-extractive implant placement and subsequent immediate loading. A full maxillary edentulism was rehabilitated with one-piece implants, starting from a pre-existing removable denture. 3D digital scans of the removable denture and upper and lower arches were performed. On this basis, a prototype with ideal esthetic and functional outcomes was realized and replicated into a custom-made radiological stent with markers. The superimposition of STL and DICOM files allowed virtual planning of one-piece implants in the ideal prosthetically driven position. The stackable guides, composed of a fixed base template and additional removable components, were then realized. The fixed template, initially secured with anchor pins to the bone, was no longer removed. The removable components, which were screwed to the base template, were used to perform implant surgery and immediate prosthetic loading. No surgical complications occurred, the implants achieved a minimum insertion torque of 35 Ncm, and immediate prosthetic loading was performed. The base template allowed for the maintenance of a fixed reference during the entire workflow, improving the transition between the digital project, the surgical procedure, and the prosthetic rehabilitation.

The extraction of impacted third molars is a common but potentially complication-prone oral surgical procedure. Wound healing plays a vital role in preventing complications. This scoping review aimed to assess the clinical and microbiological aspects of various suture materials and cyanoacrylates. Unlike existing studies, we included more articles and comprehensively compared suture materials. Articles published in languages other than English; duplicate studies; studies deemed irrelevant for the specific research questions, including those analyzing different supplementary treatments or not corresponding to the abstract’s content; ex vivo or experimental animal studies; studies lacking approval from an ethics committee; and narrative reviews, systematic reviews, or systematic and meta-analysis reviews were excluded. Thus, only 17 studies, published between 2000 and 2023, were included in the search. Suture techniques varied among surgeons, with debates on primary and secondary closure methods. A comparison of different suture materials and their effects on wound healing, infection rates, and other factors was described. Cyanoacrylate has also been used as an alternative to traditional sutures. Microbiological analysis showed varying bacterial adhesion based on the suture material, with silk sutures retaining more microbes than PTFE sutures. Clinical assessments have revealed differing inflammatory responses that affect wound healing and complications. Cyanoacrylate has emerged as a promising alternative to traditional sutures, owing to its rapid polymerization and early healing. However, the choice of suture material in impacted third molar surgery remains controversial, considering microbiological factors and clinical outcomes. More extensive randomized clinical trials are required to better understand the effect of suture materials on surgical outcomes and potential improvements. This study could enhance the safety and effectiveness of this common oral surgical procedure.

This paper proposes an equivalent 2d model incorporating translational and rotational springs to simulate constraints in the stability analysis of steel plates under in-plane patch loading. The main objective is to develop an equivalent stability analysis of these plates by accurately calibrating the level of constraint provided by the stiffeners and flanges. The calibration involves determining the spring constants of a 2d equivalent plate model to achieve the same linear elastic critical load and buckled shape as a 3d model. The paper uses the buckling coefficient as the objective function to calibrate the translational and rotational springs. The ultimate goal is to effectively replicate the constraint conditions imposed by the flanges and vertical stiffeners within the structure. The proposed simplified method yields results that closely align with those obtained from the original 3d model, incorporating finite-rigidity restraints.