Methods families use to raise funds for anorectal malformation treatment at a single public referral hospital in Southwestern Uganda.

Background: In Uganda, only two public hospitals provide pediatric surgery services. With less than 10 pediatric surgeons serving approximately 20 million children in Uganda, most patients with anorectal malformations (ARMs) must make several trips to the hospital before undergoing surgery. As a result, households borrow money, sell assets, or solicit contributions from friends and relatives to meet healthcare expenses.

Delays in Care for Children With Low Anorectal Malformations in Southwestern Uganda.

Introduction: Disparities in anorectal malformation (ARM) outcomes between high- and low-income countries may be due to delayed diagnosis in the latter setting. The Three Delays model, comprising delays in seeking, accessing, and receiving care, provides a framework for exploring these challenges. We sought to examine the frequency and nature of the preoperative delays in children presenting for surgical correction of low ARMs.

Non-symmetric cysteine stapling in native peptides and proteins.

Stapling rigidifies peptides through covalent linkages between amino acids. We introduce 2-chloromethyl-6-cyanopyridine for non-symmetric stapling of N-terminal and internal cysteines. This biocompatible method produces diverse peptide macrocycles with enhanced affinity, stability and inhibitory potency.

[Pancreatic cystic neoplasms: work-up and surveillance].

Whereas pancreatic masses are often difficult to detect with transabdominal ultrasound, cross-sectional imaging features high sensitivity for the pancreatic tumors. However, increasing availability of magnetic resonance imaging (MRI) has led to a surge in the detection of benign or precancerous pancreatic lesions. The medical history is characteristic only for two entities.

Effectiveness of primary repair for low anorectal malformations in Uganda.

Background: Anorectal malformations (ARMs) have an incidence of up to 1 in 4000 live births and can require immediate neonatal surgery due to associated intestinal blockage. Due to limited surgical access, Ugandan children present late and undergo three separate staged operations: (1) initial colostomy formation; (2) repair of the ARM (called anoplasty); and (3) colostomy closure. Three operations result in long treatment duration, potential complications with each procedure, delays in care, and stigmata associated with colostomies.

Phage-encoded bismuth bicycles enable instant access to targeted bioactive peptides.

Genetically encoded libraries play a crucial role in discovering structurally rigid, high-affinity macrocyclic peptide ligands for therapeutic applications. Bicyclic peptides with metal centres like bismuth were recently developed as a new type of constrained peptide with notable affinity, stability and membrane permeability. This study represents the genetic encoding of peptide-bismuth and peptide-arsenic bicycles in phage display.

Exploiting Hydrophobic Amino Acid Scanning to Develop Cyclic Peptide Inhibitors of the SARS-CoV-2 Main Protease with Antiviral Activity.

The development of novel antivirals is crucial not only for managing current COVID-19 infections but for addressing potential future zoonotic outbreaks. SARS-CoV-2 main protease (M) is vital for viral replication and viability and therefore serves as an attractive target for antiviral intervention. Herein, we report the optimization of a cyclic peptide inhibitor that emerged from an mRNA display selection against the SARS-CoV-2 M to enhance its cell permeability and in vitro antiviral activity.

Does Delayed Diagnosis of Hirschsprung Disease Impact Post-operative and Functional Outcomes? A Multi-Center Review From the Pediatric Colorectal and Pelvic Learning Consortium.

Background: Hirschsprung Disease (HD) is a rare cause of functional bowel obstruction in children. Patients are typically diagnosed in the neonatal period and undergo pull-through (PT) soon after diagnosis. The optimal management and post-operative outcomes of children who present in a delayed fashion are unknown.

Surgical management of complicated Crohn's disease.

Surgical management of pediatric Crohn's disease is fundamentally palliative, aiming to treat the sequalae of complicated disease while preserving intestinal length. Multidisciplinary discussion of risk factors and quality of life should take place prior to operative intervention. Though the surgical management of pediatric Crohn's disease is largely based on the adult literature, there are considerations specific to the pediatric population - notably disease and treatment effects on growth and development.

Vibrio natriegens as a superior host for the production of c-type cytochromes and difficult-to-express redox proteins.

C-type cytochromes fulfil many essential roles in both aerobic and anaerobic respiration. Their characterization requires large quantities of protein which can be obtained through heterologous production. Heterologous production of c-type cytochromes in Escherichia coli is hindered since the ccmABCDEFGH genes necessary for incorporation of heme c are only expressed under anaerobic conditions.

Electrochemical and structural characterization of recombinant respiratory proteins of the acidophilic iron oxidizer sp. PN-J47-F6 suggests adaptations to the acidic pH at protein level.

The tendency of the periplasmic redox proteins in acidophiles to have more positive redox potentials () than their homologous counterparts in neutrophiles suggests an adaptation to acidic pH at protein level, since thermodynamics of electron transfer processes are also affected by acidic pH. Since this conclusion is mainly based on the electrochemical characterization of redox proteins from extreme acidophiles of the genus , we aimed to characterize three recombinant redox proteins of the more moderate acidophile sp. PN-J47-F6.

Mapping the functional impact of non-coding regulatory elements in primary T cells through single-cell CRISPR screens.

Background: Drug targets with genetic evidence are expected to increase clinical success by at least twofold. Yet, translating disease-associated genetic variants into functional knowledge remains a fundamental challenge of drug discovery. A key issue is that the vast majority of complex disease associations cannot be cleanly mapped to a gene.

Hirschsprung disease: a cost analysis study of the direct, indirect costs and financial coping strategies for the surgical management in Western Uganda.

Background: Surgical management of Hirschsprung disease (HD) in low- and middle-income countries is typically a staged procedure, necessitating multiple hospitalizations and clinic visits increasing family financial burden. Currently, there is limited information on the costs borne by caretakers of children with Hirschsprung disease seeking surgical intervention. This study seeks to measure the costs and economic burden of surgical treatment for Hirschsprung disease in western Uganda.

The Pediatric Emergency Surgery Course: Impact on Provider Practice in Rural Uganda.

Purpose: The Pediatric Emergency Surgery Course (PESC) trains rural Ugandan providers to recognize and manage critical pediatric surgical conditions. 45 providers took PESC between 2018 and 2019. We sought to assess the impact of the course at three regional hospitals: Fort Portal, Kabale, and Kiwoko.

Does Length of Extended Resection Beyond Transition Zone Change Clinical Outcome for Hirschsprung Pull-Through?

Introduction: A proximal resection margin greater than 5 cm from the intra-operative histologically determined transition zone has been deemed necessary to minimize the risk of transition zone pull-through. This extended resection may require the sacrifice of vascular supply and even further bowel resection. The impact of extended proximal resection margin on post-operative complications and functional outcomes is unclear.

Shedding light on the electron transfer chain of a moderately acidophilic iron oxidizer: characterization of recombinant HiPIP-41, CytC-18 and CytC-78 derived from Ferrovum sp. PN-J47-F6.

Efficient electron transfer from the donor to the acceptor couple presents a necessary requirement for acidophilic and neutrophilic iron oxidizers due to the low energy yield of aerobic ferrous iron oxidation. Involved periplasmic electron carriers are very diverse in these bacteria and show adaptations to the respective thermodynamic constraints such as a more positive redox potential reported for extreme acidophilic Acidithiobacillus spp. Respiratory chain candidates of moderately acidophilic members of the genus Ferrovum share similarities with both their neutrophilic iron oxidizing relatives and the more distantly related Acidithiobacillus spp.

Double Thionated Pyrimidine Nucleobases: Molecular Tools with Tunable Photoproperties.

Sulfur-substituted nucleobases are DNA and RNA base derivatives that exhibit extremely efficient photoinduced intersystem crossing (ISC) dynamics into the lowest-energy triplet state. The long-lived and reactive triplet states of sulfur-substituted nucleobases are crucial due to their wide range of potential applications in medicine, structural biology, and the development of organic light-emitting diodes (OLEDs) and other emerging technologies. However, a comprehensive understanding of non-negligible wavelength-dependent changes in the internal conversion (IC) and ISC events is still lacking.

Glucose-stimulated insulin secretion depends on FFA1 and Gq in neonatal mouse islets.

Aims/hypothesis: After birth, the neonatal islets gradually acquire glucose-responsive insulin secretion, a process that is subjected to maternal imprinting. Although NEFA are major components of breastmilk and insulin secretagogues, their role for functional maturation of neonatal beta cells is still unclear. NEFA are the endogenous ligands of fatty acid receptor 1 (FFA1, encoded by Ffar1 in mice), a Gq-coupled receptor with stimulatory effect on insulin secretion.

delivery of miRNA induces epigenetic alterations and corrects pulmonary pathology in congenital diaphragmatic hernia.

Structural fetal diseases, such as congenital diaphragmatic hernia (CDH) can be diagnosed prenatally. Neonates with CDH are healthy as gas exchange is managed by the placenta, but impaired lung function results in critical illness from the time a baby takes its first breath. MicroRNA (miR) 200b and its downstream targets in the TGF-β pathway are critically involved in lung branching morphogenesis.