Single cell transcriptomic analysis of SGLT2 expression supports an indirect or off-target role for the cardioprotective benefits of empagliflozin in heart failure.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), such as empagliflozin, have shown remarkable benefits in reducing cardiovascular events and mortality in patients with heart failure irrespective of diabetes. Because of the magnitude of the benefits and broad application in both heart failure with reduced and preserved ejection fraction, there have been concerted efforts to identify a mechanism for the observed benefits. One hypothesis is that SGLT2i act directly on the heart.

High glucose heightens vulnerability to infection in human macrophages by hampering the production of reactive oxygen species through TLR2 and TLR4.

Diabetes increases susceptibility to infections, including (). Our group previously demonstrated that diabetic patients with cutaneous leishmaniasis (CL) take longer to heal lesions compared to non-diabetics. Since macrophages play a critical role in CL pathogenesis, we investigated how high glucose levels impact their response during infection.

Microvessel co-transplantation improves poor remuscularization by hiPSC-cardiomyocytes in a complex disease model of myocardial infarction and type 2 diabetes.

People with type 2 diabetes (T2D) are at a higher risk for myocardial infarction (MI) than age-matched healthy individuals. Here, we studied cell-based cardiac regeneration post MI in T2D rats modeling the co-morbid conditions in patients with MI. We recapitulated the T2D hallmarks and clinical aspects of diabetic cardiomyopathy using high-fat diet and streptozotocin in athymic rats, which were then subjected to MI and intramyocardial implantation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with or without rat adipose-derived microvessels (MVs).

Pharmacological inhibition of key metabolic pathways attenuates Leishmania spp infection in macrophages.

Macrophages represent a fundamental component of the innate immune system that play a critical role in detecting and responding to pathogens as well as danger signals. Leishmania spp. infections lead to a notable alteration in macrophage metabolism, whereby infected cells display heightened energy metabolism that is linked to the integrity of host mitochondria.

Impact of fraud in Europe: Causes and effects.

This research aims to explore the impact of fraud on society, in general, and in the European Union, in particular. Methodologically, this research is divided into two analyses. Firstly, a theoretical analysis based on a systematic literature review of fraud and its impact on society and the economy.

Rare Genetic Variants of NLRP12 in Admixed Latino-American Children With SARS-CoV-2-Related Multisystem Inflammatory Syndrome.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients.

Epidural Hematoma in Minor Hepatic Metastasectomy.

Liver resection poses many challenges for the anesthesiologist, including intraoperative hemodynamic instability, postoperative pain, and risk of coagulopathy. We report a case of epidural hematoma after epidural catheter removal, following a minor liver single metastasectomy. The main purpose of this case report is to bring to light the false security provided by traditional coagulation parameters and whether further investigation should be considered in selected cases, before handling neuraxial catheters.

An Overview of Biosimilars-Development, Quality, Regulatory Issues, and Management in Healthcare.

Biological therapies have transformed high-burden treatments. As the patent and exclusivity period for biological medicines draws to a close, there is a possibility for the development and authorization of biosimilars. These products boast comparable levels of safety, quality, and effectiveness to their precursor reference products.

Effect of Blueberry Supplementation on a Diet-Induced Rat Model of Prediabetes-Focus on Hepatic Lipid Deposition, Endoplasmic Stress Response and Autophagy.

Blueberries, red fruits enriched in polyphenols and fibers, are envisaged as a promising nutraceutical intervention in a plethora of metabolic diseases. Prediabetes, an intermediate state between normal glucose tolerance and type 2 diabetes, fuels the development of complications, including hepatic steatosis. In previous work, we have demonstrated that blueberry juice (BJ) supplementation benefits glycemic control and lipid profile, which was accompanied by an amelioration of hepatic mitochondrial bioenergetics.

Addiction interprofessional experiences of care: Stress, coping and transformation.

This study aimed to explore healthcare professionals' attribution of meaning to the concept of addiction, treatment and recovery. The study was conducted through semi-structured interviews with 18 healthcare professionals in the field of addiction: nine nurses, six psychologists, a psychiatrist, a social worker and a psychosocial technician. Based on a qualitative methodology, a thematic analysis was performed using the NVivo software.

Antisenescence Therapy Improves Function in a Human Model of Cardiac Fibrosis-on-a-Chip.

Cardiac fibrosis is a significant contributor to heart failure and is characterized by abnormal ECM deposition and impaired contractile function. We have previously developed a model of cardiac fibrosis via TGF-β treatment of engineered microtissues using heart-on-a-chip technology which incorporates human induced pluripotent stem cell-derived cardiomyocytes and cardiac fibroblasts. Here, we describe that these cardiac fibrotic tissues expressed markers associated with cellular senescence via transcriptomic analysis.

Transcriptome Analysis Identifies the Crosstalk between Dendritic and Natural Killer Cells in Human Cutaneous Leishmaniasis.

Skin ulcers of cutaneous leishmaniasis (CL) are characterized by a localized inflammatory response mediated by innate and adaptive immune cells, including dendritic cells (DC) and natural killer (NK) cells. Bidirectional interactions between DCs and NK cells contribute to tailor leishmaniasis outcome. Despite advances in the biology field in recent decades, the mechanisms involved in DC/NK-mediated control of sp.

Adhesive Capsulitis' Patients Report Improvement in Functionality Trough International Classification of Functioning, Disability and Health Checklist and Dash After Suprascapular Nerve Blocks.

 To evaluate the functionality in patients with adhesive capsulitis undergoing suprascapular nerve block (SSNB).  A before-and-after clinical prospective study in a single center was conducted with patients with secondary adhesive capsulitis treated with four nerve blocks based on anatomical limits. The sample was non-probabilistic, and it was obtained after a routine appointment at a specialized outpatient clinic.

Modeling Heart Diseases on a Chip: Advantages and Future Opportunities.

Heart disease is a significant burden on global health care systems and is a leading cause of death each year. To improve our understanding of heart disease, high quality disease models are needed. These will facilitate the discovery and development of new treatments for heart disease.

Isolation of ready-made rat microvessels and its applications in effective in vivo vascularization and in angiogenic studies in vitro.

Despite recent advances in the differentiation of human pluripotent stem cells into multiple cell types for application in replacement therapies, tissue vascularization remains a bottleneck for regenerative medicine. Fragments of primary microvessels (MVs) harvested from adipose tissue retain endothelialized lumens and perivascular cell coverage. We have used these MVs to support the survival and engraftment of transplanted human pluripotent stem cell-derived cardiomyocytes, pancreatic progenitors or primary human islets.

A human model of arteriovenous malformation (AVM)-on-a-chip reproduces key disease hallmarks and enables drug testing in perfused human vessel networks.

Brain arteriovenous malformations (AVMs) are a disorder wherein abnormal, enlarged blood vessels connect arteries directly to veins, without an intervening capillary bed. AVMs are one of the leading causes of hemorrhagic stroke in children and young adults. Most human sporadic brain AVMs are associated with genetic activating mutations in the KRAS gene.

Prediabetes Induces More Severe Acute COVID-19 Associated With IL-6 Production Without Worsening Long-Term Symptoms.

Aims: Pre-existing conditions, such as age, hypertension, obesity, and diabetes, constitute known risk factors for severe COVID-19. However, the impact of prediabetes mellitus (PDM) on COVID-19 severity is less clear. This study aimed to evaluate the influence of PDM in the acute and long-term phases of COVID-19.

A three-dimensional human adipocyte model of fatty acid-induced obesity.

Obesity prevalence has reached pandemic proportions, leaving individuals at high risk for the development of diseases such as cancer and type 2 diabetes. In obesity, to accommodate excess lipid storage, adipocytes become hypertrophic, which is associated with an increased pro-inflammatory cytokine secretion and dysfunction of metabolic processes such as insulin signaling and lipolysis. Targeting adipocyte dysfunction is an important strategy to prevent the development of obesity-associated disease.

Effects of social distancing caused by the COVID-19 pandemic on physical activity level, sitting time, and binge eating: a comparison between overweight/obese and normal-weight adults.

Purpose: To compare changes in physical activity level (PAL), sitting time (ST), and binge eating disorder (BED) in overweight/obese adults vs. those normal weight during social distancing caused by the COVID-19 pandemic.

Methods: A cross-sectional and retrospective study was carried out with adults of both sexes, aged 18-60 years, which assessed, through an online form, the PAL, ST, and BED pre (PSD) and during social distancing (DSD) caused by the COVID-19 pandemic.

Microvascular Dysfunction in Skeletal Muscle Precedes Myocardial Vascular Changes in Diabetic Cardiomyopathy: Sex-Dependent Differences.

Aim: To uncover sex-related microvascular abnormalities that underlie the early presentation of reduced perfusion in leg skeletal muscle in a type II rat model of diabetic cardiomyopathy.

Methods And Results: Diabetes was induced using a non-obese, diet-based, low-dose streptozotocin model in adult female (18 diabetic, 9 control) and male rats (29 diabetic, 11 control). Time-course monitoring over 12 months following diabetes induction was performed using echocardiography, treadmill exercise, photoacoustic imaging, flow-mediated dilation (FMD), histopathology, and immunohistochemistry.

GP2-enriched pancreatic progenitors give rise to functional beta cells in vivo and eliminate the risk of teratoma formation.

Human pluripotent stem cell (hPSC)-derived pancreatic progenitors (PPs) can be differentiated into beta-like cells in vitro and in vivo and therefore have therapeutic potential for type 1 diabetes (T1D) treatment. However, the purity of PPs varies across different hPSC lines, differentiation protocols, and laboratories. The uncommitted cells may give rise to non-pancreatic endodermal, mesodermal, or ectodermal derivatives in vivo, hampering the safety of hPSC-derived PPs for clinical applications and their differentiation efficiency in research settings.

Trophic niche changes associated with the eradication of invasive mammals in an insular lizard: an assessment using isotopes.

Invasive species are a major threat to island biodiversity, and their eradications have substantially contributed to the conservation of island endemics. However, the consequences of eradications on the trophic ecology of native taxa are largely unexplored. Here, we used the eradication of invasive black rats and European rabbits from the Berlenga Island, in the western coast of Portugal, as a whole-ecosystem experiment to investigate the effects of the eradication of invasive mammals on the trophic niche and body dimensions of the island-restricted Berlenga wall lizard over a 2-year period.

Cerebrospinal fluid fistula after combined spinal-epidural block.

Neuraxial anaesthesia is an essential technique in obstetric anaesthesia practice. Cerebrospinal fluid (CSF) fistula is a rare complication and there is no consensus about its clinical approach. We present a case of a 28-year-old nulliparous woman that developed a cutaneous CSF fistula following combined spinal and epidural block for caesarean delivery.