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Irritable Bowel Syndrome (IBS) is a chronic, one of the commonest and persistent gastrointestinal (GI) disorder. Previously, the management plan for IBS-D included enhancing awareness; first line treatment included an increased dietary fiber intake, opioids for diarrhea and antispasmodics for pain management. A recent treatment guideline by the American Gastroenterology Association (AGA) suggests a modified approach to treating patients with IBS-D. Eight drug recommendations were made, and a set of instructions on when to employ which medication was devised. With the incorporation of these structured guidelines, a more tailored and focused approach to IBS management may become plausible.

With the advancement in reusable rocket propulsion technology, space tourist trips into outer space are now becoming a possibility at a cost-effective rate. As such, astronauts will face a host of health-related challenges, particularly on long-duration space missions where maintaining a balanced healthy microbiome is going to be vital for human survival in space exploration as well as mission success. The human microbiome involves a whole list of micro-organisms that reside in and on the human host, and plays an integral role in keeping the human host healthy. However, imbalances in the microbiome have been directly linked to many human diseases. Research findings have clearly shown that the outer space environment can directly affect the normal microbiome of astronauts when the astronaut is exposed to the microgravity environment. In this study, we show that the simulation of microgravity on earth can mimic the outer space microgravity environment. Staphylococus aureus (S. aureus) was chosen for this study as it is an opportunistic pathogen, which is part of the normal human skin microflora and the nasal passages. This study’s results show that S. aureus proliferation was significantly increased under a microgravity environment compared to Earth’s gravity conditions, which complements previous work performed on bacteria in the outer space environment in the International Space Station (ISS). This demonstrates that this technology can be utilised here on Earth to mimic the outer space environment and to study challenging health-related questions. This in return saves us the cost on conducting experiments in the ISS and can help advance knowledge at a faster rate and produce countermeasures to mitigate the negative side effects of the hostile outer space environment on humans.

Background: Enthusiasm for using polygenic risk scores (PRSs) in clinical practice is tempered by concerns about their portability to diverse ancestry groups, thus motivating genome-wide association studies in non-European ancestry cohorts. Methods: We conducted a genome-wide association study for coronary heart disease in a Middle Eastern cohort using whole genome sequencing and assessed the performance of 6 PRSs developed with methods including LDpred (PGS000296), metaGRS (PGS000018), Pruning and Thresholding (PGS000337), and an EnsemblePRS we developed. Additionally, we evaluated the burden of rare variants in lipid genes in cases and controls. Whole genome sequencing at 30× coverage was performed in 1067 coronary heart disease cases (mean age=59 years; 70.3% males) and 6170 controls (mean age=40 years; 43.5% males). Results: The majority of PRSs performed well; odds ratio (OR) per 1 SD increase (OR 1sd ) was highest for PGS000337 (OR 1sd =1.81, 95% CI [1.66–1.98], P =3.07×10 −41 ). EnsemblePRS performed better than individual PRSs (OR 1sd =1.8, 95% CI [1.66–1.96], P =5.89×10 −44 ). The OR for the 10th decile versus the remaining deciles was >3.2 for PGS000337, PGS000296, PGS000018, and reached 4.58 for EnsemblePRS. Of 400 known genome-wide significant loci, 33 replicated at P <10 −4 . However, the 9p21 locus did not replicate. Six suggestive ( P <10 −5 ) new loci/genes with plausible biological function were identified (eg, CORO7 , RBM47 , PDE4D ). The burden of rare functional variants in LDLR , APOB , PCSK9 , and ANGPTL4 was greater in cases than controls. Conclusions: Overall, we demonstrate that PRSs derived from European ancestry genome-wide association studies performed well in a Middle Eastern cohort, suggesting these could be used in the clinical setting while ancestry-specific PRSs are developed.

Introduction: The potential use of polygenic risk scores (PRSs) in clinical practice is tempered by concern about their portability among diverse populations. To prevent disparities in genomic medicine, there is an urgent need to conduct genome-wide association studies in non-European ancestry cohorts. Methods: We conducted whole genome sequencing (WGS) with 30x coverage on coronary heart disease patients (n=1,067, mean age ± SD = 59.96 years ± 10.99; 70.32% males) and controls (n=6,170, mean age ± SD = 40.02 years ± 12.56; 43.45% males) in a Middle Eastern cohort to compare the performance of available PRSs for CHD (LDpred, metaGRS, lassosum, and P+T) and identify common variants associated with CHD (via generalized linear mixed models). Results: Excepting lassosum, all PRSs performed well. LDpred and metaGRS performed similarly (AUC= ~0.685) and outperformed P+T (AUC=0.667). Based on the OR per 1 SD increase (OR 1sd ), P+T (OR 1sd =1.85 [1.69-2.02], P =3.69x10 -41 ) outperformed other PRSs (OR 1sd =1.61 [1.48-1.74], P =3.02x10 -31 for LDpred and OR 1sd =1.61 [1.49-1.75], P =9.47x10 -31 for metaGRS). After binning PRSs into 10 deciles, the odds of CHD in the top decile compared to all others was highest for metaGRS (3.87 [3.07-4.88]) and LDpred (3.45 [2.74-4.341]). Thirty-two known GWAS loci (e.g., ABCG8 , CELSR2 , and SLC22A4 ) were replicated in our analysis with P <0.05. Seven suggestive new loci/genes ( P <10 -6 ) with relevant biological function were identified (e.g., CORO7 , RBM47 , and PDE4D ). The well-established 9p21 locus was not replicated. Conclusions: Genome-wide PRSs derived from European ancestry cohorts performed well in a Middle Eastern cohort. Further studies are needed to develop and validate an ancestry specific PRS and to confirm the suggestive loci/genes.

Abstract The purpose of this pilot study was to explore the efficacy, safety, and tolerability of vidofludimus calcium (VC) in the treatment of primary sclerosing cholangitis (PSC). This was a single‐arm open‐label pilot study with a cohort of 18 patients with PSC. Study patients received VC for a period of 6 months. The study was undertaken at two sites, Mayo Clinic, Rochester, MN, and Mayo Clinic, Phoenix, AZ. The primary endpoint of the study was improvement of serum alkaline phosphatase (ALP) at the end of the study. Secondary endpoints included assessment of other liver biomarkers (bilirubin, alanine aminotransferase, and aspartate aminotransferase). Of 18 patients enrolled, 11 completed the 6 months of study treatment. Patients who completed treatment versus those who did not were similar other than a significantly higher direct bilirubin at baseline in the group that completed treatment (mean ± SD, 0.4 ± 0.3 versus 0.1 ± 0.1, p = 0.04). By intent to treat analysis, the primary outcome was met in 16.7% (3/18) of patients. By per‐protocol analysis, including only patients who completed treatment, normalization of ALP occurred in 27.7% (3/11) at week 24 (95% confidence interval, 6.0% to 61.0%). VC was well tolerated with no drug‐related serious adverse events. Conclusion: This proof of concept study provides support for further exploration of VC in patients with PSC.