Death Associated Protein Kinase (DAPK) -mediated neurodegenerative mechanisms in nematode excitotoxicity

Background: Excitotoxicity (the toxic overstimulation of neurons by the excitatory transmitter Glutamate) is a central process in widespread neurodegenerative conditions such as brain ischemia and chronic neurological diseases. Many mechanisms have been suggested to mediate excitotoxicity, but their significance across diverse excitotoxic scenarios remains unclear. Death Associated Protein Kinase (DAPK), a critical molecular switch that controls a range of key signaling and cell death pathways, has been suggested to have an important role in excitotoxicity. However, the molecular mechanism by which DAPK exerts its effect is controversial. A few distinct mechanisms have been suggested by single (sometimes contradicting) studies, and a larger array of potential mechanisms is implicated by the extensive interactome of DAPK. Results: Here we analyze a well-characterized model of excitotoxicity in the nematode C. elegans to show that DAPK is an important mediator of excitotoxic neurodegeneration across a large evolutionary distance. We further show that some proposed mechanisms of DAPK’s action (modulation of synaptic strength, involvement of the DANGER-related protein MAB-21, and autophagy) do not have a major role in nematode excitotoxicity. In contrast, Pin1/PINN-1 (a DAPK interaction-partner and a peptidyl-prolyl isomerase involved in chronic neurodegenerative conditions) suppresses neurodegeneration in our excitotoxicity model. Conclusions: Our studies highlight the prominence of DAPK and Pin1/PINN-1 as conserved mediators of cell death processes in diverse scenarios of neurodegeneration

Defining levels of care in cardiogenic shock

BackgroundExpert opinion and professional society statements have called for multi-tier care systems for the management of cardiogenic shock (CS). However, little is known about how to pragmatically define centers with different levels of care (LOC) for CS.MethodsEleven of 23 hospitals within our healthcare system sharing a common electronic health record were classified as different LOC according to their highest mechanical circulatory support (MCS) capabilities: Level 1 (L-1)—durable left ventricular assist device, Level 1A (L-1A)—extracorporeal membrane oxygenation, Level 2 (L-2)—intra-aortic balloon pump and percutaneous ventricular assist device; and Level 3 (L-3)—no MCS. All adult patients treated for CS (International Classification of Diseases, ICD-10 code R57.0) between 2016 and 2022 were included. Etiologies of CS were identified using associated diagnostic codes. Management strategies and outcomes across LOC were compared.ResultsHigher LOC centers had higher volumes: L-1 (n = 1): 2,831 patients, L-1A (n = 4): 3,452, L-2 (n = 1): 340, and L-3 (n = 5): 780. Emergency room admissions were more common in lower LOC (96% at L-3 vs. 46% L-1; p < 0.001), while hospital transfers were predominant at higher LOC (40% at L-1 vs. 2.7% at L-3; p < 0.001). Men comprised 61% of the cohort. Patients were younger in the higher LOC [69 (60–78) years at L-1 vs. 77 (67–85) years at L-3; p < 0.001]. Patients with acute myocardial infarction (AMI)-CS and acute heart failure (AHF)-CS were concentrated in higher LOC centers while other etiologies of CS were more common in L-2 and L-3 (p < 0.001). Cardiac arrest on admission was more prevalent in lower LOC centers (L-1: 2.8% vs. L-3: 12.1%; p < 0.001). Patients with AMI-CS received more percutaneous coronary intervention in lower LOC (51% L-2 vs. 29% L-1; p < 0.01) but more coronary arterial bypass graft surgery at higher LOC (L-1: 42% vs. L-1A: 23%; p < 0.001). MCS use was consistent across levels for AMI-CS but was more frequent in higher LOC for AHF-CS patients (L-1: 28% vs. L-2: 10%; p < 0.001). Despite increasing in-hospital mortality with decreasing LOC, no significant difference was seen after multivariable adjustment.ConclusionThis is the first report describing a pragmatic classification of LOC for CS which, based on MCS capabilities, can discriminate between centers with distinct demographics, practice patterns, and outcomes. This classification may serve as the basis for future research and the creation of CS systems of care

Comparative non-metric and morphometric analyses of rats at residential halls of the University of Benin campus, Nigeria

Background: In mammals and across rat species, the variation in conformation is markedly observed in the head and the variation in the shape of the head is mostly determined by the shape of the skull. Hence comparative topographic analysis and morphometry is a veritable tool in precise categorization of peri-domestic rats and species identification. Methods: Killed rodents around residential dwellings of students on campus were collected and measurements taken of external morphology. Thirty-one external head and corporal parameters; and 40 cranial measurements respectively were obtained. Topographic features and specific anatomical landmarks measured were matched using congruent anatomical landmarks and compared to referenced standard measurements. Results: External morphometry suggests that all retrieved samples were more closely related to the species Rattus rattus. However, craniodental analysis of captured rats reveals variations from the mean of typical R. rattus. In comparison with Mastomys natalensis, the mean averages of the rat species were perceptibly different for only two of the parameters viz palatine fissure length (PL) (p = 0.039) and distance between interparietal bone (DP) (p = 0.06). In contrast, the mean of whole length of skull (WL), length of diastema (PI), length of nasal bone (NL), length of frontal bone (LF) and occipital width (OH) were significantly different from that of R. rattus with p values of 0.047, 0.036, 0.048, 0.032 and 0.034 respectively. Conclusion: This study focuses on peridomestic rat’s identification within the University campus based on morphometry, providing unique landmarks for differentiation between Mastomys, Mus, Rattus and other rat species with emphasis on the need for more comprehensive investigation, categorization and morphometric profiling of rat population in Nigeria. Metric data generated for rat profiling in Nigeria is pivotal for a more comprehensive strategy for prevention of Lassa fever. Keywords: External morphometry, Craniodental morphometry, Lassa fever, Peridomestic rat, Mastomy

Insulin-secreting β-cell neoplasia in a 7-year-old female dog, case report and review

A 7-year-old female dog presented with intermittent episodes of urinary incontinence, tremors, intermittent episodes of pelvic limb weakness and collapse, and lethargy were noticed over a period of two months. Hypoglycaemia, secondary to an insulin-secreting β-cell tumour, was suspected on the basis of clinical signs, ultrasound and serum biochemistry. A laparotomy was then performed to remove the tumour mass. Post-surgical pancreatitis was a major complication. Histology revealed a malignant neuroendocrine neoplasia of the β-cells of the pancreas. This case review is reported to keep clinicians abreast of the canine insulinoma disorder and the complications surrounding its diagnosis and treatment