👤 V M Petrov

Alterations in the gut microbiome and a "leaky" gut are associated with Parkinson's disease (PD), which implies the prospect of rebalancing via dietary intervention. Here, we investigate the impact of a diet rich in resistant starch on the gut microbiome through a multi-omics approach. We conducted a randomized, controlled trial with short-term and long-term phases involving 74 PD patients of three groups: conventional diet, supplementation with resistant starch, and high-fibre diet. Our findings reveal associations between dietary patterns and changes in the gut microbiome's taxonomic composition, functional potential, metabolic activity, and host inflammatory proteome response. Resistant starch supplementation led to an increase in Faecalibacterium species and short-chain fatty acids alongside a reduction in opportunistic pathogens. Long-term supplementation also increased blood APOA4 and HSPA5 and reduced symptoms of PD. Our study highlights the potential of dietary interventions to modulate the gut microbiome and improve the quality of life for PD patients. Show less

Exchangeable apolipoproteins, including apolipoprotein C-II (apo C-II), apolipoprotein C-III (apo C-III), and apolipoprotein E (apo E), play central roles in the modulation of cardiovascular disease (CVD) risk by readily transferring between anti-atherogenic high-density lipoprotein (HDL) and pro-atherogenic triglyceride-rich lipoproteins (TRL). High intra-pancreatic fat deposition (IPFD) has also emerged as a novel risk factor for CVD. This study aimed to investigate the associations of apo C-II, apo C-III, and apo E with IPFD, as well as with TRL and HDL subclasses. Abdominal magnetic resonance imaging at 3.0 T was used to quantify IPFD. Plasma levels of apo C-II, apo C-III, and apo E were measured. TRL and HDL subclasses were analysed, with TRL categorised into very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) subclasses (IDL-C, IDL-B, and IDL-A), and HDL into HDL-large, HDL-intermediate, and HDL-small subclasses. Univariate and multivariate linear regression analyses were performed to assess these associations. A total of 128 individuals were analysed. IPFD showed a significant inverse association with both apo C-II and apo C-III, consistent across all statistical models. In the most adjusted model, each unit increase in IPFD was associated with a 0.36-unit decrease in apo C-II (p = 0.001) and a 0.31-unit decrease in apo C-III (p = 0.004). Furthermore, apo C-II and apo C-III were significantly and inversely associated with all IDL subclasses (p < 0.02), but not with VLDL, across all models. No statistically significant association between apo E and IPFD or any IDL subclass was observed in the most adjusted model. Apo C-II and apo C-III, but not apo E, contribute to the previously observed positive relationship between IPFD and IDL. Show less

Recreational sedentary screen time (rSST) is the most prevalent form of discretionary sedentary behavior and is strongly linked to poor health outcomes. However, the relationship between time spent in rSST and other 24-h behaviors is not well understood. The purpose of this study was to examine between- and within-day associations between rSST and other 24-h behaviors that include other non-rSST sedentary time (other-SED), standing (STAND), light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), and total sleep (SLEEP). Baseline data from participants randomized to the StandUPTV study, an intervention aimed to reduce rSST in adults, were included. All 24-h behaviors were assessed continuously for 7-days. The activPAL device was used to assess rSST, other-SED, STAND, LPA, and MPVA; SLEEP was assessed using a GENEactiv accelerometer. rSST was collected using Wi-Fi plugs to capture TV time and tablet app usage. A multilevel modelling approach was used to assess bidirectional associations between rSST (total, daytime, evening) and 24-h behaviors at the between-person (across persons) and within-person (across days) levels, adjusting for age, sex, chronotype, education level, and week versus weekend day. The results were scaled hourly for interpretation. On average, 8.0 ± 1.6 days of continuous daily 24-h behavior data were included from 94 participants (age [M ± SD: 42.3 ± 11.5] years; 82% female; 78% White; BMI [M ± SD: 29.8 ± 7.8] kg/m This is the first known analysis of the bidirectional relationship between rSST and 24-h behaviors. The negative association between rSST and other-SED suggests that rSST may displace rather than contribute to more cumulative sedentary time. These findings advocate that contexts of sedentary behavior should be considered as distinct behavioral targets in intervention development. Future interventions targeting rSST reduction should also include strategies to reduce total sedentary time. NCT04464993. Show less

Deficiency of 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is a rare variant of 46,XY disorders of sex development (DSD). To give clinical, hormonal and molecular genetic characteristics of cases of 46,XY DSD associated with variants in the HSD17B3 gene. The study included 310 patients with 46,XY DSD for the period from 2015 to 2019. The patients underwent a comprehensive examination, including a study of the steroid profile by high-performance liquid chromatography with tandem mass spectrometric detection, as well as a molecular genetic analysis using NGS. According to the results of molecular genetic studies, biallelic nucleotide substitutions in the HSD17B3 gene were detected in 13 cases, which accounted for 4.2% of the total number of patients with 46,XY DSD. All 13 patients with biallelic variants in the HSD17B3 gene were registered as females. The ratio of androstenedione/testosterone concentrations in the blood in this group ranged from 1.4 to 8.9. 2 variants in the HSD17B3 gene were found in several patients: c.277+4A>T (on 6 chromosomes) and c.729₇₃₅del:p.V243fs (on 9 chromosomes). 4 novel variants have been identified. Monoallelic nucleotide substitutions in the HSD17B3 gene were detected in 7 cases, which accounted for 2.3% of the total number of patients with 46,XY DSD. External genitalia in this group corresponded to Prader stages 3-4. In 1 patient, a pathogenic variant c.277+4A>T was detected in the HSD17B3 gene, in other cases variants with uncertain significance were detected. In the structure of 46,XY DSD, patients with biallelic variants in the HSD17B3 gene were identified in 4.2% of cases, with monoallelic variants - in 2.3% of cases. 4 novel variants were found in the HSD17B3 gene. Show less

Apolipoprotein E (APOE) is a component of lipid-transporting particles and a recognition ligand for receptors, which bind these particles. The APOE isoform ε2 is a risk factor for age-related macular degeneration; nevertheless, APOE absence in humans and mice does not significantly affect the retina. We found that retinal cholesterol biosynthesis and the levels of retinal cholesterol were increased in Show less