Study protocol for the Cities Changing Diabetes programme: a global mixed-methods approach

INTRODUCTION: Urban living has been shown to affect health in various ways. As the world is becoming more urbanised and almost two-thirds of people with diabetes now live in cities, research into the relationship between urban living, health and diabetes is key to improving the lives of many. The majority of people with diabetes have type 2 diabetes, a subset linked to overweight and obesity, decreased physical activity and unhealthy diets. Diabetes has significant consequences for those living with the condition as well as their families, relationships and wider society. Although care and management are improving, complications remain common, and diabetes is among the leading causes of vision loss, amputation, neuropathy and renal and cardiovascular disease worldwide. We present a research protocol for exploring the drivers of type 2 diabetes and its complications in urban settings through the Cities Changing Diabetes (CCD) partnership programme. METHODS AND ANALYSIS: A global study protocol is implemented in eight collaborating CCD partner cities. In each city, academic institutions, municipal representatives and local stakeholders collaborate to set research priorities and plan implementation of findings. Local academic teams execute the study following the global study protocol presented here. A quantitative Rule of Halves analysis obtains measures of the magnitude of the diabetes burden, the diagnosis rates in each city and the outcomes of care. A qualitative Diabetes Vulnerability Assessment explores the urban context in vulnerability to type 2 diabetes and identifies social factors and cultural determinants relevant to health, well-being and diabetes. ETHICS AND DISSEMINATION: The protocol steers the collection of primary and secondary data across the study sites. Research ethics board approval has been sought and obtained in each site. Findings from each of the local studies as well as the result from combined multisite (global) analyses will be reported in a series of core scientific journal papers

Health Care Resource Utilization and Related Costs of Patients With CKD From the United States: A Report From the DISCOVER CKD Retrospective Cohort

Introduction: It is well established that chronic kidney disease (CKD) results in a significant burden on patients’ health and health care providers. However, detailed estimates of the health care resource utilization (HCRU) of CKD are limited, particularly those which consider severity, comorbidities, and payer type. This study aimed to bridge this evidence gap by reporting contemporary HCRU and costs in patients with CKD across the US health care providers. Methods: Cost and HCRU estimates of CKD and reduced kidney function without CKD (estimated glomerular filtration rate [eGFR]: 60−75 and urine albumin-to-creatinine ratio [UACR]: <30) were derived for US patients included in the DISCOVER CKD cohort study, using linked inpatient and outpatient data from the limited claims-EMR data set (LCED) and TriNetX database. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using UACR and eGFR. Results: Overall health care costs ranged from $26,889 (A1) to$42,139 (A3), and from $28,627 (G2) to$42,902 (G5) per patient per year (PPPY), demonstrating a considerable early disease burden which continued to increase with declining kidney function. The PPPY costs of later stage CKD were particularly notable for patients with concomitant heart failure ($50,191 [A3]) and those covered by commercial payers ($55,735 [A3]). Conclusions: Health care costs and resource use associated with CKD and reduced kidney function pose a substantial burden across health care systems and payers, increasing in line with CKD progression. Early CKD screening, particularly of UACR, paired with proactive disease management may provide both an improvement to patient outcomes and a significant HCRU and cost saving to health care providers

Baseline phenotypes with preserved β-cell function and high insulin concentrations have the best improvements in glucose tolerance after weight loss: results from the prospective DEXLIFE and EGIR-RISC studies

\ua9 2024 The AuthorsBackground: Weight loss and lifestyle intervention improve glucose tolerance delaying the onset of type 2 diabetes (T2D), but individual responses are highly variable. Determining the predictive factors linked to the beneficial effects of weight loss on glucose tolerance could provide tools for individualized prevention plans. Thus, the aim was to investigate the relationship between pre-intervention values of insulin sensitivity and secretion and the improvement in glucose metabolism after weight loss. Methods: In the DEXLIFE cohort (373 individuals at high risk of T2D, assigned 3:1 to a 12-week lifestyle intervention or a control arm, Trial Registration: ISRCTN66987085), K-means clustering and logistic regression analysis were performed based on pre-intervention indices of insulin sensitivity, insulin secretion (AUC-I), and glucose-stimulated insulin response (ratio of incremental areas of insulin and glucose, iAUC I/G). The response to the intervention was evaluated in terms of reduction of OGTT-glucose concentration. Clusters\u27 validation was done in the prospective EGIR-RISC cohort (n = 1538). Results: Four replicable clusters with different glycemic and metabolomic profiles were identified. Individuals had similar weight loss, but improvement in glycemic profile and β-cell function was different among clusters, highly depending on pre-intervention insulin response to OGTT. Pre-intervention high insulin response was associated with the best improvement in AUC-G, while clusters with low AUC-I and iAUC I/G showed no beneficial effect of weight loss on glucose control, as also confirmed by the logistic regression model. Conclusions: Individuals with preserved β-cell function and high insulin concentrations at baseline have the best improvement in glucose tolerance after weight loss

Synchronous presentation of acute acalculous cholecystitis and appendicitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Acute acalculous cholecystitis is traditionally associated with elderly or critically ill patients.</p> <p>Case presentation</p> <p>We present the case of an otherwise healthy 23-year-old Caucasian man who presented with acute right-sided abdominal pain. An ultrasound examination revealed evidence of acute acalculous cholecystitis. A laparoscopy was undertaken and the dual pathologies of acute acalculous cholecystitis and acute appendicitis were discovered and a laparoscopic cholecystectomy and appendectomy were performed.</p> <p>Conclusion</p> <p>Acute acalculous cholecystitis is a rare clinical entity in young, healthy patients and this report describes the unusual association of acute acalculous cholecystitis and appendicitis. A single stage combined laparoscopic appendectomy and cholecystectomy is an effective treatment modality.</p

Prevalence of Anaplasma phagocytophilum infection and effect on lamb growth

Background: A major challenge in sheep farming during the grazing season along the coast of south-western Norway is tick-borne fever (TBF) caused by the bacteria Anaplasma phagocytophilum that is transmitted by the tick Ixodes ricinus. Methods: A study was carried out in 2007 and 2008 to examine the prevalence of A. phagocytophilum infection and effect on weaning weight in lambs. The study included 1208 lambs from farms in Sunndal Ram Circle in Møre and Romsdal County in Mid-Norway, where ticks are frequently observed. All lambs were blood sampled and serum was analyzed by an indirect fluorescent antibody assay (IFA) to determine an antibody status (positive or negative) to A. phagocytophilum infection. Weight and weight gain and possible effect of infection were analyzed using ANOVA and the MIXED procedure in SAS. Results: The overall prevalence of infection with A. phagocytophilum was 55%. A lower weaning weight of 3% (1.34 kg, p < 0.01) was estimated in lambs seropositive to an A. phagocytophilum infection compared to seronegative lambs at an average age of 137 days. Conclusions: The results show that A. phagocytophilum infection has an effect on lamb weight gain. The study also support previous findings that A. phagocytophilum infection is widespread in areas where ticks are prevalent, even in flocks treated prophylactic with acaricides

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Unique reporter-based sensor platforms to monitor signalling in cells

Introduction: In recent years much progress has been made in the development of tools for systems biology to study the levels of mRNA and protein, and their interactions within cells. However, few multiplexed methodologies are available to study cell signalling directly at the transcription factor level. &lt;p/&gt;Methods: Here we describe a sensitive, plasmid-based RNA reporter methodology to study transcription factor activation in mammalian cells, and apply this technology to profiling 60 transcription factors in parallel. The methodology uses two robust and easily accessible detection platforms; quantitative real-time PCR for quantitative analysis and DNA microarrays for parallel, higher throughput analysis. &lt;p/&gt;Findings: We test the specificity of the detection platforms with ten inducers and independently validate the transcription factor activation. &lt;p/&gt;Conclusions: We report a methodology for the multiplexed study of transcription factor activation in mammalian cells that is direct and not theoretically limited by the number of available reporters

Locked Nucleic Acid Pentamers as Universal PCR Primers for Genomic DNA Amplification

Background: Multiplexing technologies, which allow for simultaneous detection of multiple nucleic acid sequences in a single reaction, can save a lot of time, cost and labor compared to traditional single reaction detection methods. However, the multiplexing method currently used requires precise handiwork and many complicated steps, making a new, simpler technique desirable. Oligonucleotides containing locked nucleic acid residues are an attractive tool because they have strong affinities for their complementary targets, they have been used to avoid dimer formation and mismatch hybridization and to enhance efficient priming. In this study, we aimed to investigate the use of locked nucleic acid pentamers for genomic DNA amplification and multiplex genotyping. Results: We designed locked nucleic acid pentamers as universal PCR primers for genomic DNA amplification. The locked nucleic acid pentamers were able to prime amplification of the selected sequences within the investigated genomes, and the resulting products were similar in length to those obtained by restriction digest. In Real Time PCR of genomic DNA from three bacterial species, locked nucleic acid pentamers showed high priming efficiencies. Data from bias tests demonstrated that locked nucleic acid pentamers have equal affinities for each of the six genes tested from the Klebsiella pneumoniae genome. Combined with suspension array genotyping, locked nucleic acid pentamer-based PCR amplification was able to identify a total of 15 strains, including 3 species of bacteria, by gene- and species-specific probes. Among the 32 specie

Stochastically Gating Ion Channels Enable Patterned Spike Firing through Activity-Dependent Modulation of Spike Probability

The transformation of synaptic input into patterns of spike output is a fundamental operation that is determined by the particular complement of ion channels that a neuron expresses. Although it is well established that individual ion channel proteins make stochastic transitions between conducting and non-conducting states, most models of synaptic integration are deterministic, and relatively little is known about the functional consequences of interactions between stochastically gating ion channels. Here, we show that a model of stellate neurons from layer II of the medial entorhinal cortex implemented with either stochastic or deterministically gating ion channels can reproduce the resting membrane properties of stellate neurons, but only the stochastic version of the model can fully account for perithreshold membrane potential fluctuations and clustered patterns of spike output that are recorded from stellate neurons during depolarized states. We demonstrate that the stochastic model implements an example of a general mechanism for patterning of neuronal output through activity-dependent changes in the probability of spike firing. Unlike deterministic mechanisms that generate spike patterns through slow changes in the state of model parameters, this general stochastic mechanism does not require retention of information beyond the duration of a single spike and its associated afterhyperpolarization. Instead, clustered patterns of spikes emerge in the stochastic model of stellate neurons as a result of a transient increase in firing probability driven by activation of HCN channels during recovery from the spike afterhyperpolarization. Using this model, we infer conditions in which stochastic ion channel gating may influence firing patterns in vivo and predict consequences of modifications of HCN channel function for in vivo firing patterns