Improved design of nasogastric feeding tubes

Disappointed with the overall performance of weighted and unweighted nasogastric feeding tubes, a design programme was initiated which resulted in the development of two new nasogastric tubes, one weighted and one unweighted. The tubes were manufactured with polyurethane rather than polyvinylchloride (PVC) which permitted an increase in diameter of the internal lumen which in turn was coated with water activated lubricant to ease removal of the introducer wire. A specially modelled outflow port was incorporated into the tips of both tubes. The performance of the two new polyurethane nasogastric feeding tubes was assessed under controlled trial condition using as a reference a widely used PVC unweighted open ended tube. While intubation times were similar in patients without concurrent endotracheal intubation, it took a significantly shorter time to intubate patients with concurrent endotracheal intubation with the new weighted tube. Following tube intubation, it was possible to aspirate gastric contents significantly more often through the new polyurethane tubes (p < 0.001) than through the PVC tube, and the unweighted polyurethane tube stayed in situ longer (p < 0.05) than the PVC tube. The newly designed polyurethane nasogastric feeding tubes are the first tubes that have been shown to have advantages over the simpler type of open ended, unweighted PVC nasogastric feeding tubes.     

Spongian diterpenes with thyrotropin releasing hormone receptor 2 binding affinity from Spongia sp

High-throughput screening of a plant and marine invertebrate extract library to find natural products with rat thyrotropin releasing hormorne (TRH) receptor 2 binding affinity led to the isolation of four new (1-4) and one known (5) spongian diterpene from the sponge Spongia sp. The structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. The absolute configurations of 1-4 were proposed on the basis of analysis of their CD spectra. Diterpenes 1-5 showed rat TRH receptor 2 binding affinity with IC(50) values of 23 microM, 70 microM, 400 microM, 600 microM, and 1 mM, respectively.     

Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth,Tolerability, Safety,and Gut Microbiome in Infants with Cow’s Milk Protein Allergy

This open-label, non-randomized, multicenter trial (Registration: {"type":"clinical-trial","attrs":{"text":"NCT 03661736","term_id":"NCT03661736"}}NCT 03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow’s milk protein allergy (CMPA). Term infants aged 1–8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from –0.31 at the baseline to +0.28 at the 4-months’ follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.     

Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy

Background: HIV infection results in immunometabolic reprogramming. While we are beginning to understand how this metabolic reprogramming regulates the immune response to HIV infection, we do not currently understand the impact of ART on immunometabolism in people with HIV (PWH). Methods: Serum obtained from HIV-infected (n = 278) and geographically matched HIV seronegative control subjects (n = 300) from Rakai Uganda were used in this study. Serum was obtained before and ~2 years following the initiation of ART from HIV-infected individuals. We conducted metabolomics profiling of the serum and focused our analysis on metabolic substrates and pathways assocaited with immunometabolism. Results: HIV infection was associated with metabolic adaptations that implicated hyperactive glycolysis, enhanced formation of lactate, increased activity of the pentose phosphate pathway (PPP), decreased β-oxidation of long-chain fatty acids, increased utilization of medium-chain fatty acids, and enhanced amino acid catabolism. Following ART, serum levels of ketone bodies, carnitine, and amino acid metabolism were normalized, however glycolysis, PPP, lactate production, and β-oxidation of long-chain fatty acids remained abnormal. Conclusion: Our findings suggest that HIV infection is associated with an increased immunometabolic demand that is satisfied through the utilization of alternative energetic substrates, including fatty acids and amino acids. ART alone was insufficient to completely restore this metabolic reprogramming to HIV infection, suggesting that a sustained impairment of immunometabolism may contribute to chronic immune activation and comorbid conditions in virally suppressed PWH.     

Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer

Background To understand the relationship between key non-canonical NF-κB kinase IKK-alpha(α), tumour mutational profile and survival in primary colorectal cancer.Methods Immunohistochemical expression of IKKα was assessed in a cohort of 1030 patients who had undergone surgery for colorectal cancer using immunohistochemistry. Mutational tumour profile was examined using a customised gene panel. Immunofluorescence was used to identify the cellular location of punctate IKKα expression.Results Two patterns of IKKα expression were observed; firstly, in the tumour cell cytoplasm and secondly as discrete ‘punctate’ areas in a juxtanuclear position. Although cytoplasmic expression of IKKα was not associated with survival, high ‘punctate’ IKKα expression was associated with significantly reduced cancer-specific survival on multivariate analysis. High punctate expression of IKKα was associated with mutations in KRAS and PDGFRA. Dual immunofluorescence suggested punctate IKKα expression was co-located with the Golgi apparatus.Conclusions These results suggest the spatial expression of IKKα is a potential biomarker in colorectal cancer. This is associated with a differential mutational profile highlighting possible distinct signalling roles for IKKα in the context of colorectal cancer as well as potential implications for future treatment strategies using IKKα inhibitors.Subject terms: Prognostic markers, Colorectal cancer     

Heated Allergens and Induction of Tolerance in Food Allergic Children

Food allergies are one of the first manifestations of allergic disease and have been shown to significantly impact on general health perception, parental emotional distress and family activities. It is estimated that in the Western world, almost one in ten children have an IgE-mediated allergy. Cow’s milk and egg allergy are common childhood allergies. Until recently, children with food allergy were advised to avoid all dietary exposure to the allergen to which they were sensitive, in the thought that consumption would exacerbate their allergy. However, recent publications indicate that up to 70% of children with egg allergy can tolerate egg baked in a cake or muffin without apparent reaction. Likewise, up to 75% of children can tolerate baked goods containing cow’s milk, and these children demonstrate IgE and IgG4 profiles indicative of tolerance development. This article will review the current literature regarding the use of heated food allergens as immunotherapy for children with cow’s milk and egg allergy.     

Additional mechanisms of hiatal hernia recurrence and its prevention

Summary The conventional hiatal hernia repair is a tension repair. Large defects such as those associated with an intrathoracic stomach can have a high rate of recurrence resulting in esophageal symptoms and in some instances gastric strangulation. Numerous additive procedures are used to secure the stomach in the abdominal cavity including mesh buttressing, fundoplication, anterior abdominal wall gastropexy and fundus diaphragmatic suture fixation. The optimal repair is unknown primarily because crura closure failure is poorly understood. A literature review was used to determine the proven causes of hiatal hernia recurrence. Early postoperative vomiting, surgeon inexperience, short esophagus and no crus closure are documented causes. In a series of 19 hiatal hernia recurrence repairs from our institution, additional causes such as suture pull-out and trauma have been established as additional mechanisms of recurrence. Increased intra-abdominal pressure associated with motor vehicle accidents was the precipitating factor in 2/19 patients. Suggested methods for prevention of hiatal disruption and resultant hernia are proposed which include: a postoperative antiemetic regimen, restricted activity in the early postoperative period, an assessment technique for the short esophagus when utilizing a laparoscopic approach, crus closure calibration and inclusion of the diaphragmatic fascia when performing hiatal closure for large paraesophageal hernias and the short esophagus.