Expression of Notch-1 and its ligand Jagged-1 in rat liver during liver regeneration

The Notch/Jagged signaling pathway is important for cellular differentiation and proliferation. Its dysfunction is associated with human pathologies in several tissues including liver. Point mutations in Jagged-1 gene are the cause for Alagille syndrome, associated with paucity of intrahepatic bile ducts. To determine the putative role of the trans-membrane receptor Notch and its ligand Jagged-1 in liver regeneration, we investigated the expression of Notch and Jagged-1 in rat liver following 2/3 partial hepatectomy. Immunohistochemical staining of normal rat liver showed that Notch was expressed in hepatocytes, bile duct cells and endothelial cells, whereas Jagged-1 was expressed in bile duct cells and hepatocytes. Both Notch-1 and Jagged-1 proteins were upregulated in hepatocytes after partial hepatectomy up to day 4. After partial hepatectomy, nuclear translocation of the intracellular cytoplasmic domain of Notch (NICD) increased and peaked within 15 minutes, indicating the activation of Notch. Expression of the Notch-dependent target gene (HES-1) expression increased within 30-60 minutes. Addition of recombinant Jagged-1 protein to primary cultures of hepatocytes stimulated hepatocyte DNA synthesis. Furthermore, injection of silencing RNA for Notch and Jagged-1 to livers 2 days before partial hepatectomy significantly suppressed proliferation of hepatocytes at days 2 to 4 of the regenerative response. In conclusion, Notch/Jagged signaling pathway is activated during liver regeneration and is potentially contributing to signals affecting cell growth and differentiation.     

Phenotype/Genotype Correlations in the Ultrastructure of Monogenetic Glomerular Diseases

Electron microscopy defined classic patterns of hereditary glomerular disease long before genetics revealed an underlying specific mutation. Genetic analysis is now easier to perform in clinical practice but an earlier optimism that genetics would predict disease severity and phenotype is challenged. The classic paradigm is Alport nephritis in which only a subset of mutations may predict glomerular abnormalities and disease severity. Interpretation of ultrastructural pathology of monogenetic diseases like Alport nephritis is complicated when the proband is the first family member to be diagnosed or there is discrepancy between clinical presentation and ultrastructural changes. In this review the authors have selected a dozen cases representative of common monogenetic glomerular diseases as a platform to discuss the utility of diagnostic electron microscopy in the era of molecular genetics. The emphasis is on genotype/glomerular phenotype correlations.     

Outcomes and follow-up after obstetric anal sphincter injuries

Introduction and hypothesis

To determine if the classification of obstetric anal sphincter injuries (OASIs) affected clinical and functional outcome and to assess the need for follow-up of 3a tears in secondary care

Methods

Prospective data collection in 255 patients who sustained OASIs during repair with follow-up in a specialist clinic after 6 months.

Results

One hundred and thirty-two patients (51.7 %) sustained 3a tears, 81 (31.7 %) 3b tears, 27 (10.6 %) 3c tears and 15 (5.8 %) had 4th degree tears. Twenty-three patients (9 %) reported symptoms at 6-month follow-up. Eight patients reported anal incontinence of liquid or solid stool. Among patients who sustained 3a tears, 8 patients were symptomatic: 7 had urgency and 1 had flatus incontinence. None of the patients who sustained 3a tears reported incontinence of solid/liquid stool. There appears to be no correlation with scan findings and symptoms at follow up. Most patients are asymptomatic. Urgency of faeces is the commonest symptom.

Conclusions

The vast majority of patients are asymptomatic. The necessity of seeing all these patients in secondary care for follow-up needs to be questioned. With effective primary care follow-up, there may be a place to follow up patients with 3a tears in the community during the routine 6-week postnatal check and refer the symptomatic patients to the hospital for further review.     

Challenging Case: Stones

A 40-year-old woman presents to the emergency department after a motor vehicle accident, and a CT scan revealed no injuries but incidentally notes three non-obstructing stones in the left kidney of 3, 4, and 5 mm in size. She is completely asymptomatic and has no history of urolithiasis.     

Commentary on the management of total laryngectomy patients during the COVID‐19 pandemic

The coronavirus disease‐2019 (COVID‐19) pandemic has rapidly spread across the world, placing unprecedented strain on the health care system. Health care resources including hospital beds, ICUs, as well as personal protective equipment are becoming increasingly rationed and scare commodities. In this environment, the laryngectomee (patient having previously undergone a total laryngectomy) continues to represent a unique patient with unique needs. Given their surgically altered airway, they pose a challenge to manage for the otolaryngologist within the current COVID‐19 pandemic. In this brief report, we present special considerations and best practice recommendations in the management of total laryngectomy patients. We also discuss recommendations for laryngectomy patients and minimizing community exposures.     

The Effect of Type of Femoral Component Fixation on Mortality and Morbidity after Hip Hemiarthroplasty: A Systematic Review and Meta-Analysis

HSS Journal ® - Hip hemiarthroplasty is a well-established treatment of displaced femoral neck fracture, although debate exists over whether cemented or uncemented fixation is superior....