Emerging innovation in pain medicines.

The treatment of pain remains a critical, unmet public health challenge. According to the CDC, in 2021, an estimated 20.9% of US adults (51.6 million people) endured chronic pain, and 6.9% (17.1 million people) endured high-impact chronic pain. Additionally, the impact of the social determinants of health on pain treatment are beginning to emerge. Treating pain addresses its control and relief, enhancing patient outcomes and quality of life. However, current treatment options have limitations, creating a significant need for innovative solutions. This raises the role of innovation in identifying new pain medicines. Thus, the clinical development of novel pain medicines is an unmet need to address public health worldwide.

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Assessing the Brainstem Auditory Evoked Potentials in Subjects with Family History of Hypertension.

Background: Hypertension (HTN) has a genetic predisposition and it also impairs microcirculation, thereby, affecting the well vascularized structures like the brainstem and causing changes in Brainstem Auditory Evoked Potentials (BAEPs). Purpose: To find out the usefulness of BAEPs as a screening tool in apparently healthy individuals with a family history of HTN. Methods: One hundred and ten volunteers, aged 17 to 23 years, were enrolled in the study as participants with proper consent. After excluding the subjects with existing diseases or co-morbidities (e.g. diabetes, HTN, schizophrenia, neuropathy, etc.), those on ototoxic or neurotoxic drugs, a preliminary physical examination was performed, following which BAEPs were recorded with a proper device. Statistical analysis is done with SPSS 2016 software using the chi-square test. Results: A consistent distortion in the inter-peak latency of III-V waves is noted when a family history of HTN is present in either parent or maternal grandparents. Other statistically significant findings are present in V/I% (HTN in mother), wave I (HTN in paternal grandfather), wave III (HTN in maternal grandfather), and inter-peak latency I-V (HTN in maternal grandmother). Conclusion: BAEP may be used as a screening tool in individuals with a family history of HTN with supportive evidence from further studies in the near future.

Microbiota-Short Chain Fatty Acid Relationships and Microbial Substrate Preferences Vary Across the Spectrum of Irritable Bowel Syndrome (IBS).

Objective: Identifying microbial targets in irritable bowel syndrome (IBS) is challenged by dynamic microbiota-metabolite-host interactions. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features were related to IBS symptoms, subtypes, and endophenotypes. Design: We performed an observational study of stool microbial metagenomes, stool SCFA, and IBS traits (stool form, stool bile acids, and colonic transit) in patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and healthy controls. We analyzed associations of microbiome composition with stool SCFA to identify microbe-SCFA relationships that were shared and distinct across groups. We compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by stool characteristics. In IBS-D, we compared stool microbiomes of patients with and without bile acid malabsorption (BAM). Results: Overall stool microbiome composition and abundances of individual taxa differed between groups. Increased abundances of several bacterial species were observed in IBS-D including Dorea sp. CAG:317.. Microbes-SCFA relationships varied across groups after accounting for transit and bile acids. Significant microbe-SCFA were common in IBS-D and several SCFA-producing species were inversely correlated with SCFA. Among participants selected by stool form characteristics, functional profiling demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D with BAM. Conclusion: Microbe-SCFA associations differ across IBS subtypes and traits. Altered substrate preferences offer insights into functional microbiome traits and could be used as novel microbial IBS biomarkers. KEY MESSAGES: What is already known on this topic: The intestinal microbiota and its metabolites (e.g., short chain fatty acids [SCFA]) modulate irritable bowel syndrome (IBS) pathophysiology. What this study adds: We studied microbe-SCFA associations across IBS subtypes and endophenotypes to demonstrate (1) the intestinal microbiome plays distinct roles across IBS subtypes, (2) microbial substrate preferences vary between IBS subtypes and influences stool form, and (3) microbe-SCFA patterns may reveal key taxa that underlie shared and distinct microbial mechanisms across the IBS spectrum. How this study might affect research, practice or policy: Findings demonstrate that structural and functional features of the intestinal microbiome may represent unbiased microbial biomarkers for clinical and mechanistic IBS subtypes. Further study of these putative microbial targets as well as their interactions with diet- and host-specific traits should be pursued to develop individualized microbiome-based approached to IBS management.