A dissociated glucocorticoid receptor modulator mitigates glucolipotoxicity in the endocrine pancreas and peripheral tissues: Preclinical data from a mouse model of diet-induced type 2 diabetes.

Aims: Type 2 diabetes (T2D) is a prevalent metabolic disease linked to obesity and metabolic syndrome (MS). The glucolipotoxic environment (GLT) impacts tissues causing low-grade inflammation, insulin resistance and the gradual loss of pancreatic β-cell function, leading to hyperglycemia. We have previously shown that Compound A (CpdA), a plant-derived dissociative glucocorticoid receptor-modulator with inflammation-suppressive activity, displays protective effects on β-cells in type 1 diabetes murine models.

Cotransplantation of marginal mass allogeneic islets with 3D culture-derived adult human skin cells improves glycemia in diabetic mice.

Islet transplantation represents a therapeutic option for type 1 diabetes (T1D). Long-term viability of transplanted islets requires improvement. Mesenchymal stromal cells (MSCs) have been proposed as adjuvants for islet transplantation facilitating grafting and functionality.

We Still Have a Lot to Learn.

Use of contingent electric skin shock in the treatment of severe problem behavior has been criticized on the grounds that (a) it is not necessary because function-based procedures using positive reinforcement are just as effective; (b) it violates contemporary ethical standards; and (c) it lacks social validity. There are good reasons to challenge these claims. The meaning of "severe problem behavior" is imprecise and we should be cautious in our claims about how to treat it.

Report of the ABAI Task Force on Contingent Electric Skin Shock.

As a task force appointed by the Executive Council of the Association for Behavior Analysis International (ABAI), we investigated the clinical use of contingent electric skin shock (CESS) in behavior analytic treatments for severe problem behavior. We studied how CESS is used in contemporary behavior analysis, reinforcement-based alternatives to CESS, and current ethical and professional guidelines for applied behavior analysts. We recommended that ABAI uphold clients' right to receive CESS when it is restricted to extreme cases and used under rigorous professional and legal oversight.

Rich-lean transitions produced by stimuli associated with accurate and inaccurate responding by pigeons.

Discriminable transitions from relatively favorable schedules of reinforcement to unfavorable schedules (rich-lean transitions) can produce disruptions in operant behavior. A prior evaluation in our laboratory (Toegel et al., 2021) found that placing a border around a key displayed on a resistive touchscreen increased pigeons' response accuracy relative to conditions without the border.

A case of descending necrotizing mediastinitis: Extra-pleural treatment.

Aim: Descending necrotising mediastinitis (DNM) is a rare but life-threatening condition. Diagnosis is challenging and prompt treatment is essential. We report a case of DNM in a 44-year-old man.

FK506-Binding Protein 2 Participates in Proinsulin Folding.

Apart from chaperoning, disulfide bond formation, and downstream processing, the molecular sequence of proinsulin folding is not completely understood. Proinsulin requires proline isomerization for correct folding. Since FK506-binding protein 2 (FKBP2) is an ER-resident proline isomerase, we hypothesized that FKBP2 contributes to proinsulin folding.

Compound A attenuates proinflammatory cytokine-induced endoplasmic reticulum stress in beta cells and displays beneficial therapeutic effects in a mouse model of autoimmune diabetes.

Type 1 diabetes (T1D) is characterized by an immune-mediated progressive destruction of the insulin-producing β-cells. Proinflammatory cytokines trigger endoplasmic reticulum (ER) stress and subsequent insulin secretory deficiency in cultured β-cells, mimicking the islet microenvironment in T1D. β-cells undergo physiologic ER stress due to the high rate of insulin production and secretion under stimulated conditions.

The aversiveness of timeout from response-dependent and response-independent food deliveries as a function of delivery rate.

Seven experiments with rats assessed the aversiveness of timeout using punishment and avoidance procedures. Experiments 1 and 2 considered the contributions of stimulus change, suspending the response-reinforcer contingency, response prevention, the general disruption in the reinforcement schedule during time-in, and overall decreases in reinforcement. Results support the conclusion that response-contingent timeouts punish behavior because they are signaled periods during which an ongoing schedule of positive reinforcement is suspended.

Effects of advance notice on transition-related pausing in pigeons.

Transitions between tasks can produce behavioral disruptions that are characterized as problematic. Advance notice, a procedure designed to reduce disruptions, involves presenting a stimulus to warn of the end of the ongoing activity and the nature of the upcoming activity. Clinical evaluations of advance notice have produced mixed results.

Design and evaluation of a touchscreen apparatus for operant research with pigeons.

We developed a touchscreen apparatus for pigeons and conducted a series of experiments that assessed its utility for free-operant procedures. The apparatus incorporated an on-board Windows computer, an electromechanical interface, an amplified speaker, and the touchscreen. We found that merely projecting a virtual key on the screen was insufficient; too many pecks missed the key.

Coffee intake during pregnancy and neonatal low birth weight: data from a multicenter Italian cross sectional study.

Coffee intake is common during pregnancy. However, the influence of coffee and caffeine on pregnancy has not yet been fully determined. Some studies show that high coffee intake could cause miscarriage, preterm birth or reduction of fetal growth, but other studies do not support these findings.

The Lysine Demethylase KDM5B Regulates Islet Function and Glucose Homeostasis.

Aims: Posttranslational modifications of histones and transcription factors regulate gene expression and are implicated in beta-cell failure and diabetes. We have recently shown that preserving H3K27 and H3K4 methylation using the lysine demethylase inhibitor GSK-J4 reduces cytokine-induced destruction of beta-cells and improves beta-cell function. Here, we investigate the therapeutic potential of GSK-J4 to prevent diabetes development and examine the importance of H3K4 methylation for islet function.

Endoplasmic Reticulum Chaperone Glucose-Regulated Protein 94 Is Essential for Proinsulin Handling.

Although endoplasmic reticulum (ER) chaperone binding to mutant proinsulin has been reported, the role of protein chaperones in the handling of wild-type proinsulin is underinvestigated. Here, we have explored the importance of glucose-regulated protein 94 (GRP94), a prominent ER chaperone known to fold insulin-like growth factors, in proinsulin handling within β-cells. We found that GRP94 coimmunoprecipitated with proinsulin and that inhibition of GRP94 function and/or expression reduced glucose-dependent insulin secretion, shortened proinsulin half-life, and lowered intracellular proinsulin and insulin levels.

SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice.

Obesity, metabolic syndrome, and type 2 diabetes, three strongly interrelated diseases, are associated to increased morbidity and mortality worldwide. The pathogenesis of obesity-associated disorders is still under study. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein expressed in many cell types including adipocytes, parenchymal, and non-parenchymal hepatic cells and pancreatic cells.

Immunomodulatory Properties and Potential Therapeutic Benefits of Muse Cells Administration in Diabetes.

It is well established the link between inflammation and the development of insulin resistance and pathogenesis of type 2 diabetes. Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β cells mediated by autoreactive T lymphocytes and pro-inflammatory agents. Therefore, developing new strategies to efficiently control dysregulated inflammation could have substantial benefits in the treatment of diabetes.

Interactions Between the Neuroendocrine System and T Lymphocytes in Diabetes.

It is well established that there is a fine-tuned bidirectional communication between the immune and neuroendocrine tissues in maintaining homeostasis. Several types of immune cells, hormones, and neurotransmitters of different chemical nature are involved as communicators between organs. Apart of being key players of the adaptive arm of the immune system, it has been recently described that T lymphocytes are involved in the modulation of metabolism of several tissues in health and disease.

How I Learned to Stop Worrying and Love Replication Failures.

Worries about the reproducibility of experiments in the behavioral and social sciences arise from evidence that many published reports contain false positive results. Misunderstanding and misuse of statistical procedures are key sources of false positives. In behavior analysis, however, statistical procedures have not been used much.

Pluripotent nontumorigenic multilineage differentiating stress enduring cells (Muse cells): a seven-year retrospective.

Multilineage differentiating stress enduring (Muse) cells, discovered in the spring of 2010 at Tohoku University in Sendai, Japan, were quickly recognized by scientists as a possible source of pluripotent cells naturally present within mesenchymal tissues. Muse cells normally exist in a quiescent state, singularly activated by severe cellular stress in vitro and in vivo. Muse cells have the capacity for self-renewal while maintaining pluripotent cell characteristics indicated by the expression of pluripotent stem cell markers.

Vigilance on use of drugs, herbal products, and food supplements during pregnancy: focus on fosfomycin.

Purpose: Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteremia, sepsis, pyelonephritis, and kidney dysfunction with a mortality rates reported of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them require antimicrobials treatment for at least one episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes.

Pluripotent Nontumorigenic Adipose Tissue-Derived Muse Cells have Immunomodulatory Capacity Mediated by Transforming Growth Factor-β1.

Adult mesenchymal stromal cell-based interventions have shown promising results in a broad range of diseases. However, their use has faced limited effectiveness owing to the low survival rates and susceptibility to environmental stress on transplantation. We describe the cellular and molecular characteristics of multilineage-differentiating stress-enduring (Muse) cells derived from adipose tissue (AT), a subpopulation of pluripotent stem cells isolated from human lipoaspirates.

GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A.

Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties.

Effect of TGF-β1 Stimulation on the Secretome of Human Adipose-Derived Mesenchymal Stromal Cells.

Adipose tissue is an attractive source of mesenchymal stromal cells (MSCs) owing to the relative ease of obtaining large volumes with more MSC abundance compared with other sources. Increasing evidence supports the fact that trophic factors secreted by MSCs play a pivotal therapeutic role. Several strategies in regenerative medicine use MSCs, mainly exploiting their immunosuppressive effect and homing capacity to sites of damage.