The islet tissue plasminogen activator/plasmin system is upregulated with human islet amyloid polypeptide aggregation and protects beta cells from aggregation-induced toxicity.

Aims/hypothesis: Apart from its fibrinolytic activity, the tissue plasminogen activator (tPA)/plasmin system has been reported to cleave the peptide amyloid beta, attenuating brain amyloid deposition in Alzheimer's disease. As aggregation of human islet amyloid polypeptide (hIAPP) is toxic to beta cells, we sought to determine whether activation of the fibrinolytic system can also reduce islet amyloid deposition and its cytotoxic effects, which are both observed in type 2 diabetes.

Methods: The expression of Plat (encoding tPA) and plasmin activity were measured in isolated islets from amyloid-prone hIAPP transgenic mice or non-transgenic control islets expressing non-amyloidogenic mouse islet amyloid polypeptide cultured in the absence or presence of the amyloid inhibitor Congo Red.

RISING STARS: Evidence for established and emerging forms of β-cell death.

β-Cell death contributes to β-cell loss and insulin insufficiency in type 1 diabetes (T1D), and this β-cell demise has been attributed to apoptosis and necrosis. Apoptosis has been viewed as the lone form of programmed β-cell death, and evidence indicates that β-cells also undergo necrosis, regarded as an unregulated or accidental form of cell demise. More recently, studies in non-islet cell types have identified and characterized novel forms of cell death that are biochemically and morphologically distinct from apoptosis and necrosis.

RIPK3 promotes islet amyloid-induced β-cell loss and glucose intolerance in a humanized mouse model of type 2 diabetes.

Objective: Aggregation of human islet amyloid polypeptide (hIAPP), a β-cell secretory product, leads to islet amyloid deposition, islet inflammation and β-cell loss in type 2 diabetes (T2D), but the mechanisms that underlie this process are incompletely understood. Receptor interacting protein kinase 3 (RIPK3) is a pro-death signaling molecule that has recently been implicated in amyloid-associated brain pathology and β-cell cytotoxicity. Here, we evaluated the role of RIPK3 in amyloid-induced β-cell loss using a humanized mouse model of T2D that expresses hIAPP and is prone to islet amyloid formation.

Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use.

Aims: To explore the modifying effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) use on outcomes with finerenone across a wide spectrum of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the pooled analysis of FIDELIO-DKD and FIGARO-DKD.

Materials And Methods: Patients with T2D and CKD treated with optimized renin-angiotensin system blockade were randomized to finerenone or placebo. Effects of finerenone on a cardiovascular composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite outcome (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decline, or renal death), change in urine albumin-to-creatinine ratio (UACR), and safety were analysed by GLP-1RA use.

Impaired insight in schizophrenia: impact on patient-reported and physician-reported outcome measures in a randomized controlled trial.

Background: Impaired insight poses a challenge in the treatment of patients with schizophrenia because of its potential to jeopardize therapeutic engagement and medication adherence. This study explored how insight impairment, graded from none to extreme, is related to patient-reported mental health status, depression, and neurocognition in schizophrenia.

Methods: In a post hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study (NCT00014001), insight was measured using the Positive and Negative Syndrome Scale (PANSS) Item G12 (lack of insight).

RIPK1 and RIPK3 regulate TNFα-induced β-cell death in concert with caspase activity.

Objective: Type 1 diabetes (T1D) is characterized by autoimmune-associated β-cell loss, insulin insufficiency, and hyperglycemia. Although TNFα signaling is associated with β-cell loss and hyperglycemia in non-obese diabetic mice and human T1D, the molecular mechanisms of β-cell TNF receptor signaling have not been fully characterized. Based on work in other cell types, we hypothesized that receptor interacting protein kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3) regulate TNFα-induced β-cell death in concert with caspase activity.

Contrasting the Social Cognitive and Metacognitive Capacities Among Patients With Schizophrenia and Autism Spectrum Disorders Enrolled in Psychiatric Rehabilitation.

Unique deficits in synthetic metacognition have been found in schizophrenia when compared with other psychiatric conditions and community controls. Although persons with autism spectrum disorders (ASD) display similar deficits in social cognition relative to those with schizophrenia, to date no study has compared metacognitive function between these groups. We aimed to compare the metacognitive capacities of persons with schizophrenia and ASD and their associations with other outcomes (neurocognition, social cognition, depression, and quality of life).

A Pragmatic View of Disturbed Self-Reflection in Personality Disorders: Implications for Psychotherapy.

Patients with personality disorders suffer from impairment in self-reflective capacities. This is not a matter of making incorrect judgments about self-experience but reflects problems with (a) labeling internal experience consistent with the type and level of bodily arousal, (b) seeing how thoughts and feelings are connected to one another within the flow of daily life, and (c) realizing that one's own ideas about interpersonal relationships are subjective and fallible and not direct perceptions of external reality. The authors offer a discussion and definition of each of these three impairments and then offer suggestions for how to address these impairments in psychotherapy.

Colonoscopy and Colorectal Cancer Mortality in the Veterans Affairs Health Care System: A Case-Control Study.

Background: Colonoscopy is widely used in the Veterans Affairs (VA) health care system for colorectal cancer (CRC) prevention, but its effect on CRC mortality is unknown.

Objective: To determine whether colonoscopy is associated with decreased CRC mortality in veterans and whether its effect differs by anatomical location of CRC.

Design: Case-control study.

Theory of Mind in Schizophrenia: Associations With Clinical and Cognitive Insight Controlling for Levels of Psychopathology.

Poor insight in schizophrenia is a risk factor for both poor outcomes and treatment adherence. Accordingly, interest in identifying causes of poor insight has increased. This study explored whether theory of mind (ToM) impairments are linked to poor clinical and cognitive insight independent of psychopathology.

Metacognition within narratives of schizophrenia: associations with multiple domains of neurocognition.

Research has suggested many with schizophrenia experience impairments in metacognition, or difficulties apprehending their own thoughts and the thoughts of others, and that those deficits are not reducible to a single symptom or cognitive impairment. While links between metacognition and more severe levels of symptoms have emerged, less clear is whether there are consistent associations between metacognition and other neurocognitive capacities. Accordingly the current study sought to examine whether different patterns of metacognition deficits have different neurocognitive correlates.

Narrative enrichment in the psychotherapy for persons with schizophrenia: a single case study.

Recovery from schizophrenia may involve persons developing a renewed sense of their illness, identity, agency, and worth within their life stories. To explore the requirements and challenges of psychotherapy that could facilitate this, we present a case study of a person with schizophrenia enrolled in treatment for over 19 months. Observed challenges to this process include the therapist's inclinations to "fix" the client, the client's own deficits and symptoms, and discomfort within the therapeutic relationship.

Neurocognitive deficits and history of childhood abuse in schizophrenia spectrum disorders: associations with Cluster B personality traits.

Cluster B personality traits have been detected in persons with schizophrenia, at a rate exceeding that of the general population. Unclear, however, is how to account for such high rates of Cluster B traits. Accordingly, this study explored the hypothesis that the presence of these traits may be linked to impairments in neurocognition, and childhood abuse history.

Human papillomavirus type 6: classification of clinical isolates and functional analysis of E2 proteins.

Human papillomaviruses (HPVs) cause a variety of clinical manifestations, including the most prevalent viral sexually transmitted disease, genital warts. HPV-6 is found in a greater number of genital warts than any other HPV. To increase our understanding of the structural and functional relationships between HPV-6 isolates and to provide information for epidemiological studies, the sequences of the E2, E6 and E7 coding regions of HPV-6 genomes in clinical samples were determined.