Mpox virus (MPXV) vertical transmission and fetal demise in a pregnant rhesus macaque model.

Infection with clade I Mpox virus (MPXV) results in adverse pregnancy outcomes, yet the potential for vertical transmission resulting in fetal harm with clade IIb MPXV, the clade that is currently circulating in the Western Hemisphere, remains unknown. We established a rhesus macaque model of vertical MPXV transmission with early gestation inoculation. Three pregnant rhesus macaques were inoculated intradermally with 1.5 × 10^5 plaque forming units (PFU) of clade IIb MPXV near gestational day (GD) 30 and animals were monitored for viremia and maternal and fetal well-being. Animals were euthanized to collect tissues at 5, 14, or 25 days post-inoculation (dpi). Tissues were evaluated for viral DNA (vDNA) loads, infectious virus titers, histopathology, MPXV mRNA and protein localization, as well as MPXV protein co-localization with placental cells including, Hofbauer cells, mesenchymal stromal cells, endothelial cells, and trophoblasts. vDNA was detected in maternal blood and skin lesions by 5 dpi. Lack of fetal heartbeat was observed at 14 or 25 dpi for two dams indicating fetal demise; the third dam developed significant vaginal bleeding at 5 dpi and was deemed an impending miscarriage. vDNA was detected in placental and fetal tissue in both fetal demise cases. MPXV localized to placental villi by ISH and IHC. Clade IIb MPXV infection in pregnant rhesus macaques results in vertical transmission to the fetus and adverse pregnancy outcomes, like clade I MPXV. Further studies are needed to determine whether antiviral therapy with tecovirimat will prevent vertical transmission and improve pregnancy outcomes. One Sentence Summary: Clade IIb Mpox virus infection of pregnant rhesus macaques results in vertical transmission from mother to fetus and adverse pregnancy outcomes.

Effect of Sweetened Dried Cranberry Consumption on Urinary Proteome and Fecal Microbiome in Healthy Human Subjects.

The relationship among diet, human health, and disease is an area of growing interest in biomarker research. Previous studies suggest that the consumption of cranberries (Vaccinium macrocarpon) could beneficially influence urinary and digestive health. The present study sought to determine if daily consumption of sweetened dried cranberries (SDC) changes the urinary proteome and fecal microbiome, as determined in a prospective sample of 10 healthy individuals. Baseline urine and fecal samples were collected from the subjects in the fasted (8-12 h) state. The subjects then consumed one serving (42 g) of SDC daily with lunch for 2 weeks. Urine and fecal samples were collected again the day after 2 weeks of SDC consumption. Orbitrap Q-Exactive mass spectrometry of urinary proteins showed that consumption of SDC resulted in changes to 22 urinary proteins. Multiplex sequencing of 16S ribosomal RNA genes in fecal samples indicated changes in relative abundance of several bacterial taxonomic units after consumption of SDC. There was a shift in the Firmicutes:Bacteroidetes ratio, increases in commensal bacteria, and decreases or the absence of bacteria associated with negative health effects. A decrease in uromodulin in all subjects and an increase in Akkermansia bacteria in most subjects were observed and warrant further investigation. Future larger clinical studies with multiomics and multitissue sampling designs are required to determine the effects of SDC consumption on nutrition and health.

Effect of Caloric Restriction on Metabolic Dysfunction of Young Rapacz Familial Hypercholesterolemic Swine (Sus scrofa).

The Rapacz familial hypercholesterolemic (FH) swine model is well-characterized and used for studies of both spontaneous and inducible atherosclerosis but has not been used for studies of metabolic dysfunction to date. We examined whether parameters of metabolic syndrome including weight and adiposity, serum cholesterol, and glucoregulatory function could be modulated by restriction of caloric intake in the FH swine. Three groups of FH swine (n = 6 per group) were fed without restriction (AL), 80% of AL caloric intake, or 60% of AL caloric intake for 8.8 ± 0.5 mo beginning 2 wk after weaning. Caloric intake influenced the rate and magnitude of body weight gain and change in adiposity, as determined by dual-emission X-ray absorptiometry. At the conclusion of the study, pigs in the AL group reached a total least-square mean body weight of 94.2 kg and fat mass of 31.1%, whereas those fed 80% AL were 71.6 kg and 24.3% fat, and swine fed 60% AL were 46.1 kg and 14.1% fat. Serum cholesterol was greater in AL than 60% AL pigs at the end of the study. At 10 mo of age, intravenous glucose tolerance testing, performed to assess glucoregulatory function, indicated significant differences in serum glucose clearance profiles and insulin sensitivity between the AL- and 60% AL-fed swine. The AL-fed animals showed almost 5-fold lower insulin sensitivity when compared with animals fed 60% AL caloric intake. These results highlight the value of the FH swine model to study metabolic dysfunction due to changes in caloric intake.