Case Report: Retropancreatic fascia hernia protruding into the thoracic cavity through a Bochdalek hernia

Retropancreatic fascia hernia is a novel internal hernia originating from the retropancreatic fascial defect, which subsequently expands toward the dorsal aspect of the pancreatic body and migrates into the retroperitoneal space. We encountered a rare case of concomitant retropancreatic fascia and Bochdalek hernias. Here, we describe the imaging characteristics of this hernia type and its surgical strategies

Laparoscopic restorative proctocolectomy with ileal-J-pouch anal canal anastomosis without diverting ileostomy for total colonic and extensive aganglionosis is safe and feasible with combined Lugol's iodine staining technique and indocyanine green fluorescence angiography

BackgroundWe present the surgical technique and outcomes of reduced-port laparoscopic restorative proctocolectomy with ileal-J-pouch anal canal anastomosis (IPACA) without diverting ileostomy for total colonic and extensive aganglionosis (TCA+).MethodsWe retrospectively reviewed TCA+ cases between 2014 and 2022. Preoperative ileostomy was performed when transanal bowel irrigation was ineffective. Radical surgery for TCA+ was performed at approximately 6 kg. The surgery was performed using laparoscopy through a multi-channel trocar with or without an additional 3-mm trocar and IPACA reconstruction with indocyanine green fluorescence angiography (ICG) to assess anastomotic perfusion and Lugol's iodine staining to visualize the surgical anal canal.ResultsTen patients with TCA+ were included. Ileostomy was performed in seven cases. The median operation time and blood loss were 274.5 min and 20 ml, respectively. No significant postoperative complications were found. All patients experienced frequent liquid stools and perianal excoriation in the early postoperative period, requiring anti-flatulence or codeine. The median follow-up period was 3.5 years. Three patients required irrigation management 1 year postoperatively, and the others defecated a median of 3.5 times per day. The median Kelly's clinical score was 5 in 5 patients aged >4 years.ConclusionReduced-port surgery, combined with Lugol's iodine staining and ICG, was safe, feasible, and had cosmetically and clinically acceptable mid-term outcomes

ULK1 Phosphorylates and Regulates Mineralocorticoid Receptor

Summary: Mineralocorticoid receptor (MR) signaling regulates both renal Na-Cl reabsorption and K+ excretion. We previously demonstrated that phosphorylation of S843 in the MR ligand-binding domain in renal intercalated cells is involved in the balance of these activities by regulating ligand binding and signaling. However, the kinase that phosphorylates MRS843 is unknown. Using a high-throughput screen assay of 197 kinases, we found that ULK1 is the principal kinase that is responsible for the phosphorylation of MRS843. The results were confirmed by in vitro kinase assay, mass spectrometry, and siRNA knockdown experiments. Notably, phosphorylation at MRS843 was markedly reduced in ULK1/2 double knockout mouse embryonic fibroblasts. Upstream, we show that ULK1 activity is inhibited by phosphorylation induced by angiotensin II via mTOR in cell culture and in vivo. These findings implicate mTOR and ULK1 as regulators of MR activity in intercalated cells, a pathway that is critical for maintaining electrolyte homeostasis. : Shibata et al. use a high-throughput screen assay and show that unc-51-like kinase 1 (ULK1) phosphorylates and regulates mineralocorticoid receptor (MR). Upstream, angiotensin II inhibits ULK1 and decreases MR phosphorylation via mTOR. These findings implicate mTOR and ULK1 as regulators of MR in intercalated cells. Keywords: nuclear receptor, post-translational modification, aldosterone, pendrin, Cl–/HCO3– exchange

Potassium depletion stimulates Na-Cl cotransporter via phosphorylation and inactivation of the ubiquitin ligase Kelch-like 3

AbstractKelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. Mutations in KLHL3 cause constitutively increased renal salt reabsorption and impaired K+ secretion, resulting in hypertension and hyperkalemia. Although clinical studies have shown that dietary K+ intake affects blood pressure, the mechanisms have been obscure. In this study, we demonstrate that the KLHL3 ubiquitin ligase complex is involved in the low-K+-mediated activation of Na-Cl cotransporter (NCC) in the kidney. In the distal convoluted tubules of mice eating a low-K+ diet, we found increased KLHL3 phosphorylation at S433 (KLHL3S433-P), a modification that impairs WNK binding, and also reduced total KLHL3 levels. These changes are accompanied by the accumulation of the target substrate WNK4, and activation of the downstream kinases SPAK (STE20/SPS1-related proline-alanine-rich protein kinase) and OSR1 (oxidative stress-responsive 1), resulting in NCC phosphorylation and its accumulation at the plasma membrane. Increased phosphorylation of S433 was explained by increased levels of active, phosphorylated protein kinase C (but not protein kinase A), which directly phosphorylates S433. Moreover, in HEK cells expressing KLHL3 and WNK4, we showed that the activation of protein kinase C by phorbol 12-myristate 13-acetate induces KLHL3S433-P and increases WNK4 levels by abrogating its ubiquitination. These data demonstrate the role of KLHL3 in low-K+-mediated induction of NCC; this physiologic adaptation reduces distal electrogenic Na+ reabsorption, preventing further renal K+ loss but promoting increased blood pressure

Factors associated with employment in patients undergoing hemodialysis: a mixed methods study

Abstract Background For patients undergoing hemodialysis, continuing in labor is very challenging and many patients have difficulty in current and/or previous workplaces. The objective of the present study is to clarify the determinants of being employed in hemodialysis patients by use of the mixed methods approach. Methods One hundred and forty-nine patients undergoing hemodialysis were interviewed between 2010 and 2011 using the “100-category checklists” based on the International Classification of Functioning, Disability and Health developed for hemodialysis patients. The categories with which the participants experienced difficulty at workplace were analyzed using the mixed methods approach. In quantitative data, the patients undergoing hemodialysis were divided into two groups if they experienced any difficulty in current and/or previous workplaces (i.e., “experienced” group vs. “not experienced” group). In qualitative data, responses to the open-ended questions were analyzed using a grounded theory approach. Results In total of 149 patients (male, 66%; mean age 62 years; mean hemodialysis vintage, 8.6 years), 62% had diabetes and 86% were in labor at the time of investigation. In a quantitative analysis, compared to the unexperienced group, the experienced group was more likely to show the physical problems such as fatigability and decline of physical strength and declined energy level. In a qualitative analysis, three determinants of being unemployed were emerged including hospital visits (i.e., three times a week), vascular access, and physical symptoms. In contrast, a favorable determinant for the work continuation and job opportunities was found to be a flexible dialysis shift. Conclusions Our mixed methods study suggests that patients undergoing hemodialysis frequently suffer from physical problems such as frequent hospital visits for hemodialysis, vascular access troubles, and physical distress, resulting in frequent unemployment. One solution for unemployment of the patients undergoing hemodialysis is a dialysis shift flexible for individual lifestyles