Pathomorphological effects of Alloxan induced acute hypoglycaemia in rabbits

Alloxan is one of the frequently used beta-cytotoxic agents for the induction of Type-1 diabetes mellitus in animal models and is the drug of choice in rabbits. Its beta-cytotoxic action results in a sudden release of insulin leading to severe hypoglycaemia and even mortality if glucose therapy is not given. In the present investigation the pathological effects of alloxan induced acute hypoglycaemia were studied in rabbits. New Zealand White rabbits, 1–1.5 kg body weight, were administered alloxan @100 mg/kg b.w., as a single intravenous dose. Blood glucose levels were monitored (0 h, 20 min, 1 h, and then hourly up to 5 h) and clinical signs noted. Rabbits dead due to hypoglycaemia were necropsied and histopathology performed. Severe histopathological changes were observed especially in the brain (neuronal degeneration and necrosis), kidneys (nephrosis, nephritis) and liver (hepatosis, hepatitis) and also, other organs. Histopathological observation of beta-cytolysis was suggestive that the drug induced hypoglycaemia is insulin mediated. It was concluded that acute hypoglycaemia causes severe pathological changes and the alloxan induced immediate hypoglycaemia if not managed in time, might exacerbate the pathological effects of hyperglycaemia in the induced diabetic models.Keywords: Alloxan hypoglycaemia; Pathology; Rabbit

High glucose load and endotoxemia among overweight and obese Arab women with and without diabetes: an observational study

Dietary intake influences gut microbiota activity. Nevertheless, there is a lack of evidence available that illustrates the acute effects of high glucose meal on metabolic endotoxemia. The present study assessed the acute impact of high glucose meal on endotoxemia and other clinical parameters in Saudi females with varying degrees of glycemia. The subjects were 64 consenting pre-menopausal women, grouped into 3: control [n = 14 lean, non-T2DM, BMI = 22.2 ± 2.2 kg/m2]; overweight [n = 16, non-T2DM, BMI = 28.5 ± 1.5 kg/m2] and T2DM [n = 34, BMI = 35.2 ± 7.7 kg/m2]. After an overnight fast, all subjects were given a standardized high-glucose (75 g) meal. Anthropometrics were taken and blood samples were withdrawn at baseline and postprandial (0, 2 and 4-hours), serum glucose, endotoxin and lipid profile were quantified. At baseline, total cholesterol, LDL-cholesterol, triglycerides and serum glucose levels were significantly higher (P values <.01) whereas significantly lower HDL-cholesterol levels (P < .01) were observed in T2DM subjects compared to other groups. Baseline endotoxin levels were highest in the overweight group (3.2 ± 1.1 mmol/L) as compared to control (2.0 ± 0.5 mmol/L) and T2DM (2.7 ± 1.2 mmol/L) (P = .046). HDL-cholesterol, LDL-cholesterol and triglycerides, significantly decreased in the T2DM group after 2 hours (P values <.05), whereas unremarkable changes observed in other groups. Lastly, endotoxin levels significantly increased only in the overweight group (3.2 ± 1.1 vs 4.2 ± 1.4 mmol/L; P < .05), 4 hours postprandial. High glucose meal elevates endotoxemia only among overweight subjects and impairs dysbiosis

The Alvarado score for predicting acute appendicitis: a systematic review

Background: The Alvarado score can be used to stratify patients with symptoms of suspected appendicitis; the validity of the score in certain patient groups and at different cut points is still unclear. The aim of this study was to assess the discrimination (diagnostic accuracy) and calibration performance of the Alvarado score. Methods: A systematic search of validation studies in Medline, Embase, DARE and The Cochrane library was performed up to April 2011. We assessed the diagnostic accuracy of the score at the two cut-off points: score of 5 (1 to 4 vs. 5 to 10) and score of 7 (1 to 6 vs. 7 to 10). Calibration was analysed across low (1 to 4), intermediate (5 to 6) and high (7 to 10) risk strata. The analysis focused on three sub-groups: men, women and children. Results: Forty-two studies were included in the review. In terms of diagnostic accuracy, the cut-point of 5 was good at 'ruling out' admission for appendicitis (sensitivity 99% overall, 96% men, 99% woman, 99% children). At the cut-point of 7, recommended for 'ruling in' appendicitis and progression to surgery, the score performed poorly in each subgroup (specificity overall 81%, men 57%, woman 73%, children 76%). The Alvarado score is well calibrated in men across all risk strata (low RR 1.06, 95% CI 0.87 to 1.28; intermediate 1.09, 0.86 to 1.37 and high 1.02, 0.97 to 1.08). The score over-predicts the probability of appendicitis in children in the intermediate and high risk groups and in women across all risk strata. Conclusions: The Alvarado score is a useful diagnostic 'rule out' score at a cut point of 5 for all patient groups. The score is well calibrated in men, inconsistent in children and over-predicts the probability of appendicitis in women across all strata of risk

Primula vulgaris (primrose) genome assembly, annotation and gene expression, with comparative genomics on the heterostyly supergene

Primula vulgaris (primrose) exhibits heterostyly: plants produce self-incompatible pin- or thrum-form flowers, with anthers and stigma at reciprocal heights. Darwin concluded that this arrangement promotes insect-mediated cross-pollination; later studies revealed control by a cluster of genes, or supergene, known as the S (Style length) locus. The P. vulgaris S locus is absent from pin plants and hemizygous in thrum plants (thrum-specific); mutation of S locus genes produces self-fertile homostyle flowers with anthers and stigma at equal heights. Here, we present a 411 Mb P. vulgaris genome assembly of a homozygous inbred long homostyle, representing ~87% of the genome. We annotate over 24,000 P. vulgaris genes, and reveal more genes up-regulated in thrum than pin flowers. We show reduced genomic read coverage across the S locus in other Primula species, including P. veris, where we define the conserved structure and expression of the S locus genes in thrum. Further analysis reveals the S locus has elevated repeat content (64%) compared to the wider genome (37%). Our studies suggest conservation of S locus genetic architecture in Primula, and provide a platform for identification and evolutionary analysis of the S locus and downstream targets that regulate heterostyly in diverse heterostylous species

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Epigenetic Transitions and Knotted Solitons in Stretched Chromatin

The spreading and regulation of epigenetic marks on chromosomes is crucial to establish and maintain cellular identity. Nonetheless, the dynamical mechanism leading to the establishment and maintenance of a given, cell-line specific, epigenetic pattern is still poorly understood. In this work we propose, and investigate in silico, a possible experimental strategy to illuminate the interplay between 3D chromatin structure and epigenetic dynamics. We consider a set-up where a reconstituted chromatin fibre is stretched at its two ends (e.g., by laser tweezers), while epigenetic enzymes (writers) and chromatin-binding proteins (readers) are flooded into the system. We show that, by tuning the stretching force and the binding affinity of the readers for chromatin, the fibre undergoes a sharp transition between a stretched, epigenetically disordered, state and a crumpled, epigenetically coherent, one. We further investigate the case in which a knot is tied along the chromatin fibre, and find that the knotted segment enhances local epigenetic order, giving rise to "epigenetic solitons" which travel and diffuse along chromatin. Our results point to an intriguing coupling between 3D chromatin topology and epigenetic dynamics, which may be investigated via single molecule experiments.Comment: Accepted version; Supplementary movies can be found at http://www2.ph.ed.ac.uk/~dmichiel/KnottedSolitons.html and https://www.youtube.com/watch?v=Osghh9nEhe