Alterations in Intestinal Brush Border Membrane Functionality and Bacterial Populations Following Intra-Amniotic Administration (Gallus gallus) of Nicotinamide Riboside and Its Derivatives

Nicotinamide riboside (NR) acts as a nicotinamide adenine dinucleotide (NAD+) precursor where NR supplementation has previously been shown to be beneficial. Thus, we synthesized and characterized nicotinamide riboside tributyrate chloride (NRTBCl, water-soluble) and nicotinamide riboside trioleate chloride (NRTOCl, oil-soluble) as two new ester derivatives of nicotinamide riboside chloride (NRCl). NRCl and its derivatives were assessed in vivo, via intra-amniotic administration (Gallus gallus), with the following treatment groups: (1) non-injected (control); and injection of (2) deionized H₂O (control); (3) NRCl (30 mg/mL dose); (4) NRTBCl (30 mg/mL dose); and (5) NRTOCl (30 mg/mL dose). Post-intervention, the effects on physiological markers associated with brush border membrane morphology, intestinal bacterial populations, and duodenal gene expression of key proteins were investigated. Although no significant changes were observed in average body weights, NRTBCl exposure increased average cecum weight. NR treatment significantly increased Clostridium and NRCl treatment resulted in increased populations of Bifidobacterium, Lactobacillus, and E. coli. Duodenal gene expression analysis revealed that NRCl, NRTBCl, and NRTOCl treatments upregulated the expression of ZnT1, MUC2, and IL6 compared to the controls, suggesting alterations in brush border membrane functionality. The administration of NRCl and its derivatives appears to trigger increased expression of brush border membrane digestive proteins, with added effects on the composition and function of cecal microbial populations. Additional research is now warranted to further elucidate the effects on inflammatory biomarkers and observe changes in the specific intestinal bacterial populations post introduction of NR and its derivatives.     

Biodegradation of a Magnesium Alloy Fixation Screw Used in a Guided Bone Regeneration Model in Beagle Dogs

Nowadays, the most commonly used fixation systems are non-resorbable, but new resorbable magnesium alloy fixation screws have been introduced recently. Therefore, the aim of this study was to compare the magnesium fixation screw and the commonly used non-resorbable titanium screw in an animal model. Four 3-wall defect sites were covered with collagen membranes in the mandible of twenty beagle dogs (two sites on the left and two on the right). Each membrane was fixed with either four magnesium screws or four titanium screws. Post-operative follow-up revealed the expected observations such as transient inflammation and pain. Both groups showed a good healing response, with no differences between groups. Micro-CT analysis showed no significant difference between groups in terms of BV/TV or soft tissue volume. The void volume in the magnesium fixation screw group continued to decrease on average between the different timepoints, but not significantly. Furthermore, a gradual progression of the degradation process of the magnesium screws was observed in the same group. Magnesium screws and titanium screws showed equal performance in tissue regeneration according to GBR principles. An additional advantage of magnesium screws is their resorbable nature, which eliminates the need for a second surgical step to remove the screws.     

Infant Botulism,Israel, 2007–2021

Infant botulism (IB) is an intestinal toxemia that manifests as descending paralysis, constipation, and, in some cases, respiratory failure. Laboratory-confirmed IB cases are rare, and recent data in Israel are lacking. We conducted a national multicenter retrospective study of laboratory-confirmed IB cases reported in Israel during 2007–2021. A total of 8 cases were reported during the study period. During 2019–2021, incidence may have increased because of a cluster of 5 cases. Infant median age for diagnosis was 6.5 months, older than previously reported (3 months). Most cases occurred during March–July. Honey consumption was reported in 1 case, and possible environmental risk factors (living nearby rural or construction areas, dust exposure, and having a father who works as a farmer) were reported in 6 cases. Although IB is rare, its incidence in Israel may have increased over recent years, and its epidemiology and risk factors differ from cases reported previously in Israel.     

Intraamniotic Administration (Gallus gallus) of Genistein Alters Mineral Transport,Intestinal Morphology,and Gut Microbiota

Genistein is an isoflavone naturally present in numerous staple food crops, such as soybeans and chickpeas. This study utilized the Gallus gallus intraamniotic administration procedure to assess genistein administration effects on trace mineral status, brush border membrane (BBM) functionality, intestinal morphology, and intestinal microbiome in vivo. Eggs were divided into five groups with 1 mL injection of the following treatments: no-injection, DI H₂O, 5% inulin, and 1.25% and 2.5% genistein (n = 8 per group). Upon hatch, blood, cecum, small intestine, and liver were collected for assessment of hemoglobin, intestinal microflora alterations, intestinal morphometric assessment, and mRNA gene expression of relevant iron and zinc transporter proteins, respectively. This study demonstrated that intraamniotic administration of 2.5% genistein increased villus surface area, number of acidic goblet cells, and hemoglobin. Additionally, genistein exposure downregulated duodenal cytochrome B (DcytB) and upregulated hepcidin expression. Further, genistein exposure positively altered the composition and function of the intestinal microbiota. Our results suggest a physiological role for genistein administration in improving mineral status, favorably altering BBM functionality and development, positively modulating the intestinal microbiome, as well as improving physiological status.     

Comparing the Effects of Concord Grape (Vitis labrusca L.) Puree,Juice, and Pomace on Intestinal Morphology,Functionality, and Bacterial Populations In Vivo (Gallus gallus)

This is a preliminary study evaluating the effect of different fractions of Concord grapes (Vitis labrusca L.) on the brush border membrane (BBM) morphology, duodenal gene expression, and specific gut bacterial populations. For this study, we utilized a unique intraamniotic approach, wherein, the test substances are administered into the amnion of the Gallus gallus egg (on day 17). The embryo orally consumes the amniotic fluid along with the injected test substance before the hatch. We randomly divided ~50 fertilized eggs into 5 groups including 6% grape (juice, puree, and pomace) along with controls (no injection and diluent—H₂O). The grape juice was prepared by crushing the grapes; the grape residues were used as pomace. The grape puree included the grape skin, endocarp, mesocarp, and juice but not the seeds. On day 21, the hatch day, the blood, pectoral muscle, liver, duodenum, and large intestine were harvested. Our results showed no significant differences in blood glucose, pectoral glycogen level, or body weight. However, significant (p < 0.05) differences in duodenal and liver gene expression were observed between the treatment groups. The grape puree treatment resulted in higher Clostridium numbers and lower Bifidobacterium numbers when compared to all other groups. In summary, the dietary consumption of grape polyphenols has the potential to beneficially modulate aspects of intestinal health provided their concentration is limited.     

Cardiorespiratory Fitness Is an Independent Predictor of Cardiovascular Morbidity and Mortality and Improves Accuracy of Prediction Models

BackgroundAlthough cardiorespiratory fitness (CRF) is a strong independent predictor of adverse cardiovascular outcomes, it is not considered as a risk enhancer by current guidelines.MethodsWe evaluated asymptomatic self-referred adults aged 40 to 79 years of age, free of cardiovascular disease at baseline, who were screened annually and completed baseline exercise stress test. Baseline CRF was dichotomized into 2 groups: low (metabolic equivalents < 8) and high. The primary endpoint was the composite of death, nonfatal acute coronary syndrome, and stroke after excluding subjects diagnosed with metastatic cancer during follow-up.ResultsStudy population included 15,445 subjects with median age of 49 years (interquartile range: 44-55). During median follow-up of 8 years 1362 (9%) subjects developed the study endpoint. Kaplan-Meier survival analysis showed that both fitness and atherosclerotic cardiovascular disease (ASCVD) were associated with developing of the study endpoint (P < 0.001 for both). Cox regression model with adjustment for ASCVD risk consistently showed that lower fitness was associated with a significant 23% higher risk to develop the study endpoint (P = 0.001). Continuous net reclassification improvement analysis showed an overall improvement of 11.4% (95% confidence interval, 8%-14.6%; P value < 0.001) in the accuracy of classification when fitness was added to the ASCVD model.ConclusionsLow CRF is a strong independent predictor of the cardiovascular morbidity and mortality in asymptomatic adults. Addition of fitness to the pooled cohort ASCVD risk significantly improves the accuracy of the model.