Cecal bascule presenting as internal hernia.

Cecal bascule, a rare subtype of cecal volvulus, presents diagnostic and management challenges. We report a case of cecal bascule presenting as an internal hernia in a 68-year-old male with no surgical history. Computed tomography revealed two areas of mesenteric swirling and a displaced cecum. Prompt surgical intervention included laparoscopic exploration, resection of a necrotic adhesive band, and cecopexy. This case is noteworthy because of the absence of predisposing factors like prior surgeries or inflammatory conditions. Management options for cecal bascule include resection and cecopexy, tailored to individual patient factors. Awareness among healthcare providers is crucial for the timely recognition and appropriate management of such cases. Further research is needed to refine management strategies and improve outcomes for these rare but potentially life-threatening conditions.

An Infected, Noncoronary, Bare Metal Stent Presenting as a Right Groin Abscess.

Bare metal stent infections complicating peripheral endovascular stenting are rare but can be associated with devastating morbidities. The current standard of care necessitates explantation and extra-anatomical bypass of the affected limb. We report the case of a patient presenting with a right groin abscess with draining sinuses secondary to an infected common femoral and right external iliac artery bare metal stent. In addition, a portion of the stent was explanted into the subcutaneous tissues instead of where it was placed intravascularly one year prior. The patient was not an ideal candidate for explantation and bypass due to significant medical comorbidities and underwent local debridement and long-term antibiotic management instead. His postoperative course was uncomplicated, and he had a successful outcome with management utilizing antibiotics and debridement. We aim to highlight the importance of recognizing bare metal stent infections along with their deceptive cutaneous manifestations in order to prevent the development of significant morbidity and mortality.

Thioredoxin 1 promotes autophagy through transnitrosylation of Atg7 during myocardial ischemia.

Modification of cysteine residues by oxidative and nitrosative stress affects structure and function of proteins, thereby contributing to the pathogenesis of cardiovascular disease. Although the major function of thioredoxin 1 (Trx1) is to reduce disulfide bonds, it can also act as either a denitrosylase or transnitrosylase in a context-dependent manner. Here we show that Trx1 transnitrosylates Atg7, an E1-like enzyme, thereby stimulating autophagy. During ischemia, Trx1 was oxidized at Cys32-Cys35 of the oxidoreductase catalytic center and S-nitrosylated at Cys73. Unexpectedly, Atg7 Cys545-Cys548 reduced the disulfide bond in Trx1 at Cys32-Cys35 through thiol-disulfide exchange and this then allowed NO to be released from Cys73 in Trx1 and transferred to Atg7 at Cys402. Experiments conducted with Atg7 C402S-knockin mice showed that S-nitrosylation of Atg7 at Cys402 promotes autophagy by stimulating E1-like activity, thereby protecting the heart against ischemia. These results suggest that the thiol-disulfide exchange and the NO transfer are functionally coupled, allowing oxidized Trx1 to mediate a salutary effect during myocardial ischemia through transnitrosylation of Atg7 and stimulation of autophagy.

PERM1 regulates energy metabolism in the heart via ERRα/PGC-1α axis.

Aims: PERM1 is a striated muscle-specific regulator of mitochondrial bioenergetics. We previously demonstrated that PERM1 is downregulated in the failing heart and that PERM1 positively regulates metabolic genes known as targets of the transcription factor ERRα and its coactivator PGC-1α in cultured cardiomyocytes. The aims of this study were to determine the effect of loss of PERM1 on cardiac function and energetics using newly generated Perm1-knockout (Perm1 -/-) mice and to investigate the molecular mechanisms of its transcriptional control. Methods and results: Echocardiography showed that ejection fraction and fractional shortening were lower in Perm1 -/- mice than in wild-type mice (both p < 0.05), and the phosphocreatine-to-ATP ratio was decreased in Perm1 -/- hearts (p < 0.05), indicating reduced contractile function and energy reserves of the heart. Integrated proteomic and metabolomic analyses revealed downregulation of oxidative phosphorylation and upregulation of glycolysis and polyol pathways in Perm1 -/- hearts. To examine whether PERM1 regulates energy metabolism through ERRα, we performed co-immunoprecipitation assays, which showed that PERM1 bound to ERRα in cardiomyocytes and the mouse heart. DNA binding and reporter gene assays showed that PERM1 was localized to and activated the ERR target promoters partially through ERRα. Mass spectrometry-based screening in cardiomyocytes identified BAG6 and KANK2 as potential PERM1's binding partners in transcriptional regulation. Mammalian one-hybrid assay, in which PERM1 was fused to Gal4 DNA binding domain, showed that the recruitment of PERM1 to a gene promoter was sufficient to activate transcription, which was blunted by silencing of either PGC-1α, BAG6, or KANK2. Conclusion: This study demonstrates that PERM1 is an essential regulator of cardiac energetics and function and that PERM1 is a novel transcriptional coactivator in the ERRα/PGC-1α axis that functionally interacts with BAG6 and KANK2.

A feeding jejunostomy causing an intussusception - case report and literature review.

Use of enteral nutrition has increased dramatically over the past two decades due to improved nutritional formulas, better quality feeding tubes and the ability to use less invasive endoscopic, fluoroscopic and laparoscopic techniques. Intussusception accounts for 1-5% of adult intestinal obstructions, with feeding tubes acting as a lead point in < 1% of cases. Since intussusception is rare, especially in adults, it is not always considered in the initial differential diagnosis of patients presenting with abdominal pain, nausea, vomiting or constipation. If left untreated, intussusception can eventually lead to bowel compromise, poor outcomes and even death. Therefore, prompt recognition and correction are necessary. We present a case of small bowel obstruction in an elderly male secondary to a tube-related intussusception. A review of the signs, symptoms and treatment recommendations is provided.

PERM1 regulates genes involved in fatty acid metabolism in the heart by interacting with PPARα and PGC-1α.

PERM1 (PGC-1/ERR-induced regulator in muscle 1) is a muscle-specific protein induced by PGC-1 and ERRs. Previous studies have shown that PERM1 promotes mitochondrial biogenesis and metabolism in cardiomyocytes in vitro. However, the role of endogenous PERM1 in the heart remains to be investigated with loss-of-function studies in vivo. We report the generation and characterization of systemic Perm1 knockout (KO) mice. The baseline cardiac phenotype of the homozygous Perm1 KO mice appeared normal. However, RNA-sequencing and unbiased pathway analyses showed that homozygous downregulation of PERM1 leads to downregulation of genes involved in fatty acid and carbohydrate metabolism in the heart. Transcription factor binding site analyses suggested that PPARα and PGC-1α are involved in changes in the gene expression profile. Chromatin immunoprecipitation assays showed that PERM1 interacts with the proximal regions of PPAR response elements (PPREs) in endogenous promoters of genes involved in fatty acid oxidation. Co-immunoprecipitation and reporter gene assays showed that PERM1 promoted transcription via the PPRE, partly in a PPARα and PGC-1α dependent manner. These results suggest that endogenous PERM1 is involved in the transcription of genes involved in fatty acid oxidation through physical interaction with PPARα and PGC-1α in the heart in vivo.

Machine Learning and Feature Selection Applied to SEER Data to Reliably Assess Thyroid Cancer Prognosis.

Utilizing historical clinical datasets to guide future treatment choices is beneficial for patients and physicians. Machine learning and feature selection algorithms (namely, Fisher's discriminant ratio, Kruskal-Wallis' analysis, and Relief-F) have been combined in this research to analyse a SEER database containing clinical features from de-identified thyroid cancer patients. The data covered 34 unique clinical variables such as patients' age at diagnosis or information regarding lymph nodes, which were employed to build various novel classifiers to distinguish patients that lived for over 10 years since diagnosis, from those who did not survive at least five years. By properly optimizing supervised neural networks, specifically multilayer perceptrons, using data from large groups of thyroid cancer patients (between 6,756 and 20,344 for different models), we demonstrate that unspecialized and existing medical recording can be reliably turned into power of prediction to help doctors make informed and optimized treatment decisions, as distinguishing patients in terms of prognosis has been achieved with 94.5% accuracy. We also envisage the potential of applying our machine learning strategy to other diseases and purposes such as in designing clinical trials for unmasking the maximum benefits and minimizing risks associated with new drug candidates on given populations.