The gut mucin-microbiota interactions: a missing key to optimizing endurance performance.

Endurance athletes offer unique physiology and metabolism compared to sedentary individuals. Athletes training at high intensities for prolonged periods are at risk for gastrointestinal disturbances. An important factor in endurance performance is the integrity and function of the gut barrier, which primarily depends on heavily O-glycosylated mucins. Emerging evidence shows a complex bidirectional dialogue between glycans on mucins and gut microorganisms. This review emphasizes the importance of the crosstalk between the gut microbiome and host mucus mucins and some of the mechanisms underlying this symbiosis. The contribution of mucin glycans to the composition and functionality of the gut microbiome is discussed, as well as the persuasive impact of the gut microbiome on mucin composition, thickness, and immune and metabolic functions. Lastly, we propose natural and synthetic glycans supplements to improve intestinal mucus production and barrier function, offering new opportunities to enhance endurance athletes' performance and gut health.

Point-of-care Ultrasound Identification of Tension Hydrothorax in the Emergency Department: A Case Series.

INTRODUCTION: Tension hydrothorax is an uncommon emergent condition in which hemodynamic instability and respiratory compromise may occur. Emergency physicians may diagnose tension hydrothorax by point-of-care ultrasound. CASE SERIES: We discuss the key sonographic features assisting in identification. Four patients with history of malignancy who were found to have tension hydrothorax exhibited the following common ultrasound findings: massive, left-sided pleural effusion; complete, compressive atelectasis; and shift of cardiac structures into the right hemithorax, resulting in right-sided probe placement to obtain cardiac views. CONCLUSION: This is the first instance to our knowledge of point-of-care ultrasound findings in tension hydrothorax to be described in the literature.

Evaluation of a viral transcriptome Next Generation Sequencing assay as an alternative to animal assays for viral safety testing of cell substrates.

The viral safety of biological products is ensured by tests throughout the production chain, and, for certain products, by steps in the manufacturing process enabling the elimination or inactivation of viruses. Current testing programs include sample inoculation in animals and embryonic eggs. Following the 3Rs principles of replacement, reduction, and refinement of animal-use methods, such techniques are intended to be replaced not only for ethical reasons but also because of their inherent technical limitations, their long turnaround times, and their limits in virus detection. Therefore, we have compared the limit and range of sensitivity of in vivo tests used for viral testing of cells with a transcriptomic assay based on Next Generation Sequencing (NGS). Cell cultures were infected with a panel of nine (9) viruses, among them only five (5) were detected, with variable sensitivity, by in vivo tests. The transcriptomic assay was able to detect one (1) infected cell among 103 to 107 non-infected cells for all viruses assessed, including those not detected by the conventional in vivo tests. Here we show that NGS extends the breath of detection of viral contaminants compared to traditional testing. Collectively, these results support the replacement of the conventional in vivo tests by an NGS-based transcriptomic assay for virus safety testing of cell substrates.

Students' Perceptions of Their Student-Operated Restaurant Experience: A Qualitative Study.

As there is a rapid increase in the consumption of food outside the home, it is essential that future foodservice managers are well prepared for their critical role in menu creation and nutrition care planning in a variety of foodservice establishments. Student-operated restaurants (SORs) are one method of experiential learning used to educate future foodservice managers. This study aimed to explore the students' perceptions of their SOR experience and the extent to which nutrition concepts were incorporated in their program. This is a research area that has not been explored previously. For this study, a total of eighteen students from four universities were recruited via email to participate in interviews. Results from the qualitative thematic analysis of interview data revealed the following three overarching themes related to students' SOR experience: (1) Interpersonal Relationships and Mentoring, (2) Assessment of Immediate Experience, and (3) Moving Forward, Added Value, and Growth. Regarding nutrition, while some students felt that nutrition principles were effectively addressed during their SOR experience, other students acknowledged a lack of nutritional emphasis in their SOR and expressed a desire for a greater application of the nutritional principles learned in other classes. The SOR experience described by students was rich as they developed a variety of relationships and skills.

Genomic profiling and precision medicine in complex ameloblastoma.

BACKGROUND: Ameloblastoma may present a significant treatment challenge in the locally advanced, recurrent and metastatic setting. Comprehensive genomic profiling (CGP) can identify targetable genomic alterations to aid in treatment. METHODS: Ameloblastoma samples were sequenced using hybrid-capture based sequencing. A systematic literature review was performed to examine outcomes in studies employing targeted treatment in ameloblastoma. RESULTS: We reviewed 14 cases of Ameloblastoma using CGP. There were six patients with activating BRAF mutations, five with PIK3CA, five with SMO, four with FGFR2, one with EGFR, and one with ROS1. All cases were MSI stable and the median TMB was 2.5 mutations/Mb. A separate literature review of clinical outcomes in ameloblastoma showed a predominance of at least partial response to targeted treatment (7/12 cases). CONCLUSION: CGP is helpful in identifying specific driver mutations in patients with complex ameloblastoma. Targeted treatment has been employed with success in achieving treatment response.

Relationships of self-awareness and facial affect recognition to social communication ability in persons with traumatic brain injury.

Traumatic brain injury (TBI) can cause changes to the injured person's physical ability, cognitive functioning, and social interactions. Since these attributes largely determine a person's concept of who they are, TBI poses a threat to sense of self. Due to the importance of social communication skills for community integration, impairment of these skills is a particular threat to sense of self. The present investigation sought to explore characteristics that influence social communication abilities. We hypothesized that both ability to interpret facial affect and self-awareness would be associated with communication ability. We also expected that facial affect recognition would influence self-awareness and that the effect of facial affect recognition on social communication would be partially mediated by self-awareness. For this prospective cohort study, participants were 77 individuals with documented TBI. Of these, 65% were male and 83% sustained severe injuries. The hypothesized association of facial affect recognition with social communication was demonstrated with path analysis as was the effect of facial affect recognition on self-awareness. However, the effect of facial affect recognition on social communication was not mediated by self-awareness. In addition, social communication was associated with employment, social integration, and loneliness. Findings highlighted the importance of social communication after TBI.

Predictors of Missed Follow-up Visits in the National Traumatic Brain Injury Model Systems Cohort Study.

OBJECTIVE: To identify key variables that could predict risk of loss to follow-up (LTFU) in a nationally funded longitudinal database of persons with traumatic brain injury. DESIGN: Secondary analysis of a prospective longitudinal cohort study. SETTING: Traumatic Brain Injury Model System (TBIMS) Centers in the US. PARTICIPANTS: A total of 17,956 TBIMS participants (N=17,956) with interview status data available were included if eligible for 1-, 2-, 5-, 10-, 15-, or 20-year follow-ups between October 31, 1989, and September 30, 2020. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Follow-up data collection completion status at years 1, 2, 5, 10, 15, and 20. RESULTS: Information relevant to participants' history, injury characteristics, rehabilitation stay, and patterns of follow-up across 20 years were considered using a series of logistic regression models. Overall, LTFU rates were low (consistently <20%). The most robust predictors of LTFU across models were missed earlier follow-ups and demographic factors including Hispanic ethnicity, lower education, and lack of private health insurance. CONCLUSIONS: Efforts to retain participants in such social disadvantaged or minority groups are encouraged given their disproportionate rate of LTFU. Repeated attempts to reach participants after a previously missed assessment are beneficial because many participants that missed 1 or more follow-ups were later recovered.

Analysis of Airway Management for Cesarean Delivery: Use of Risk and Proportion Differences.

OBJECTIVES: Securing the parturient airway is essential during general anesthesia for cesarean delivery. The purpose of this study was to compare inferior airway views provided by the use of three commonly available laryngoscopy blades-Macintosh, Miller, or Glidescope Mac-Style-to the incidence of difficult orotracheal intubation. METHODS: Following institutional review board approval, data from 449 electronic medical records in parturients undergoing general anesthesia for cesarean delivery were extracted during a 6-year period. The association of these blades with difficult orotracheal intubation was analyzed with risk and proportion differences measures of effect size. RESULTS: The overall incidence of difficult orotracheal intubation was 4.2% (95% confidence interval 2.7 - 6.5%), with 6 failed orotracheal intubations (5 laryngeal mask airways rescues and 1 mask rescue). Clinically important increases in risk differences for difficult orotracheal intubation were observed in parturients with restricted mouth openings, modified Mallampati III and IV views, and reduced thyromental distances. When modified Cormack-Lehane views were grouped into III and IV versus I and II cohorts; proportion differences for difficult orotracheal intubation were dependent upon the type of blade used, with the Miller blade providing the lowest proportion difference. CONCLUSIONS: Miller blade laryngoscopy provided the lowest proportion difference for difficult orotracheal intubation during general anesthesia for cesarean delivery. Miller blade laryngoscopy provides effective procurement of the parturient airway.

Brain-Immune Interactions as the Basis of Gulf War Illness: Clinical Assessment and Deployment Profile of 1990-1991 Gulf War Veterans in the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study.

The Boston University-based Gulf War Illness Consortium (GWIC) is a multidisciplinary initiative developed to provide detailed understanding of brain and immune alterations that underlie Gulf War illness (GWI), the persistent multisymptom disorder associated with military service in the 1990-1991 Gulf War. The core GWIC case-control clinical study conducted in-depth brain and immune evaluation of 269 Gulf War veterans (223 GWI cases, 46 controls) at three U.S. sites that included clinical assessments, brain imaging, neuropsychological testing, and analyses of a broad range of immune and immunogenetic parameters. GWI cases were similar to controls on most demographic, military, and deployment characteristics although on average were two years younger, with a higher proportion of enlisted personnel vs. officers. Results of physical evaluation and routine clinical lab tests were largely normal, with few differences between GWI cases and healthy controls. However, veterans with GWI scored significantly worse than controls on standardized assessments of general health, pain, fatigue, and sleep quality and had higher rates of diagnosed conditions that included hypertension, respiratory and sinus conditions, gastrointestinal conditions, and current or lifetime depression and post-traumatic stress disorder. Among multiple deployment experiences/exposures reported by veterans, multivariable logistic regression identified just two significant GWI risk factors: extended use of skin pesticides in theater (adjusted OR = 3.25, p = 0.005) and experiencing mild traumatic brain injury during deployment (OR = 7.39, p = 0.009). Gulf War experiences associated with intense stress or trauma (e.g., participation in ground combat) were not associated with GWI. Data and samples from the GWIC project are now stored in a repository for use by GWI researchers. Future reports will present detailed findings on brain structure and function, immune function, and association of neuroimmune measures with characteristics of GWI and Gulf War service.

BRCA1 binds TERRA RNA and suppresses R-Loop-based telomeric DNA damage.

R-loop structures act as modulators of physiological processes such as transcription termination, gene regulation, and DNA repair. However, they can cause transcription-replication conflicts and give rise to genomic instability, particularly at telomeres, which are prone to forming DNA secondary structures. Here, we demonstrate that BRCA1 binds TERRA RNA, directly and physically via its N-terminal nuclear localization sequence, as well as telomere-specific shelterin proteins in an R-loop-, and a cell cycle-dependent manner. R-loop-driven BRCA1 binding to CpG-rich TERRA promoters represses TERRA transcription, prevents TERRA R-loop-associated damage, and promotes its repair, likely in association with SETX and XRN2. BRCA1 depletion upregulates TERRA expression, leading to overly abundant TERRA R-loops, telomeric replication stress, and signs of telomeric aberrancy. Moreover, BRCA1 mutations within the TERRA-binding region lead to an excess of TERRA-associated R-loops and telomeric abnormalities. Thus, normal BRCA1/TERRA binding suppresses telomere-centered genome instability.

Arsenic and mercury contamination and complex aquatic bioindicator responses to historical gold mining and modern watershed stressors in urban Nova Scotia, Canada.

Beginning in the late-1800s, gold mining activities throughout Nova Scotia, eastern Canada, released contaminants, notably geogenic arsenic from milled ore and anthropogenic mercury from amalgamation, to local environments via surface water flows through tailings fields. We investigated recovery from and legacy effects of the tailings field at the Montague Gold District (~1863-1940) on nearby urban lake ecosystems using geochemical measures and zooplankton remains archived in dated sediment cores from an impact (Lake Charles) and a reference (Loon Lake) lake. Sedimentary levels of total arsenic and total mercury were used to assess mining-related inputs. Arsenic concentrations remain elevated at nearly 300 times above sediment guidelines in Lake Charles surface sediments, due to its upward mobilization from enriched sediment intervals and sequestration by iron oxyhydroxides in surficial sediments. Peak mercury concentrations at Lake Charles were eight times above sediment guidelines during the mining period, and since ~1990 have recovered to levels observed before mining began. Legacy mining impacts at Lake Charles and non-mining related environmental changes in the post-1950 sediments at both lakes have thus combined to structure assemblage compositions of primary consumers. At both lakes, assemblages of pelagic-dominated Cladocera differed (p ≤ 0.05) during the mining period compared to periods before and after mining. Taxon richness differed (p ≤ 0.01) only between the pre- and post-mining periods at mining-impacted Lake Charles and reflects long-term declines of substrate-dwelling littoral taxa. Geochemical and biological recovery have not completely occurred at Lake Charles despite the mine district's closure ~80 years ago. Our findings demonstrate that impacts of ore processing and amalgamation from historical gold mining, combined with recent watershed stressors, continue to affect sedimentary arsenic geochemistry and intermediate trophic levels of nearby, downstream aquatic habitats.

A randomized controlled trial of acceptance and commitment therapy for psychological distress among persons with traumatic brain injury.

Psychological distress is common in persons with traumatic brain injury (TBI) but treatments remain underdeveloped. This randomized controlled trial of Acceptance and Commitment Therapy (ACT) was designed to address this gap. Ninety-three persons with medically-documented complicated mild to severe TBI, normal-to-mildly impaired memory, and clinically significant psychological distress in the chronic phase of recovery were randomized to receive eight weeks of ACT (manualized with adaptations to address TBI-related cognitive impairments) or a single session of needs assessment, brief counseling/education, and referral. The ACT group showed significantly greater reduction of psychological distress (Brief Symptom Inventory 18) and demonstrated improvements in psychological flexibility and commitment to action (Acceptance and Action Questionnaire-II (AAQ-II) scores). The number of treatment responders (post-treatment BSI 18 GSI T scores <63) was larger in the ACT group than in the control group. Entry of AAQ-II scores into the model of between-group differences in BSI 18 GSI T scores indicated that core ACT processes explained the variance in treatment group outcomes. Provision of ACT reduces psychological distress in persons with TBI in the chronic phase of recovery when adaptations are made to accommodate TBI-related cognitive impairments. Additional clinical trials with a structurally equivalent control group are needed.

Publisher Correction: Unraveling the effects of the gut microbiota composition and function on horse endurance physiology.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Priming for welfare: gut microbiota is associated with equitation conditions and behavior in horse athletes.

We simultaneously measured the fecal microbiota and multiple environmental and host-related variables in a cohort of 185 healthy horses reared in similar conditions during a period of eight months. The pattern of rare bacteria varied from host to host and was largely different between two time points. Among a suite of variables examined, equitation factors were highly associated with the gut microbiota variability, evoking a relationship between gut microbiota and high levels of physical and mental stressors. Behavioral indicators that pointed toward a compromised welfare state (e.g. stereotypies, hypervigilance and aggressiveness) were also associated with the gut microbiota, reinforcing the notion for the existence of the microbiota-gut-brain axis. These observations were consistent with the microbiability of behaviour traits (> 15%), illustrating the importance of gut microbial composition to animal behaviour. As more elite athletes suffer from stress, targeting the microbiota offers a new opportunity to investigate the bidirectional interactions within the brain gut microbiota axis.

Mucosal microbial load in Crohn's disease: A potential predictor of response to faecal microbiota transplantation.

BACKGROUND: The remission of Crohn's disease (CD) can be accomplished by faecal microbiota transplantation (FMT). However, this procedure has a low success rate, which could be attributed to mis-communication between recipient intestinal mucosa and donor microbiota. METHODS: Here we used a human explant tissue model and an in vivo mouse model to examine changes in recipient intestinal mucosa upon contact with a faecal suspension (FS) obtained from a healthy donor. CD patients provided resected inflamed and non-inflamed mucosal tissues, whereas control colonic mucosa samples were collected from colorectal cancer patients. For the models, mucosal microbiome composition and tissue response were evaluated. FINDINGS: We show that cytokine release and tissue damage were significantly greater in inflamed compared to non-inflamed CD tissues. Moreover, mucosal samples harbouring an initial low microbial load presented a shift in composition towards that of the FS, an increase in the relative count of Faecalibacterium prausnitzii, and a higher secretion of anti-inflammatory cytokine IL-10 compared to those with a high microbial load. INTERPRETATION: Our results indicate that FMT during active inflammatory disease can compromise treatment outcome. We recommend the stratification of FMT recipients on the basis of tissue microbial load as a strategy to ensure successful colonization. FUNDING: This study was supported by grants from the Instituto de Salud Carlos III/FEDER (PI17/00614), the European Commission: (INCOMED-267128) and PERIS (SLT002/16). K.M. is a postdoctoral fellow and S.V. a senior clinical investigator of the Fund for Scientific Research Flanders, Belgium (FWO-Vlaanderen).

Nitrous Oxide for Labor Analgesia: What We Know to Date.

Background: Although nitrous oxide (N2O) has been used since the 1880s for labor analgesia, its popularity has only recently increased in the United States. In 2011, only 3 centers in the country offered N2O, but as of 2020, several hundred labor units have adopted its use. Methods: We reviewed the literature and summarize the mechanism of action, clinical uses, and efficacy of N2O for labor analgesia, as well as patient satisfaction related to its use. Results: N2O has several proposed mechanisms of action that make it a viable option for all 3 stages of labor and postpartum procedures. N2O has been shown to be a safe option for both mom and baby during labor and delivery. Studies support N2O as an analgesic for laboring. Even though 40% to 60% of women who use N2O convert to a labor epidural analgesia, satisfaction surveys indicate that analgesia is not the only factor contributing to the use of N2O during labor. Conclusion: The use of N2O has increased in labor and delivery units across the United States since 2011. Despite inferior analgesic properties compared to epidural analgesia, N2O offers a safe alternative for many parturients who want a greater sense of control and mobility.

Inter-breed diversity and temporal dynamics of the faecal microbiota in healthy horses.

Understanding gut microbiota similarities and differences across breeds in horses has the potential to advance approaches aimed at personalized microbial modifications, particularly those involved in improving sport athletic performance. Here, we explore whether faecal microbiota composition based on faecal 16S ribosomal RNA gene sequencing varies across six different sport breeds at two time points 8 months apart within a cohort of 189 healthy horses cared for under similar conditions. Lusitano horses presented the smallest and Hanoverians the greatest bacterial diversity. We found subtle but significant differences in ß-diversity between Lusitano, Anglo Arabian and the central European breeds, and we reproduced these results across the two time points. Repeat sampling of subjects showed community to be temporally more stable in Lusitano and Anglo Arabian breeds. Additionally, we found that 27 genera significantly varied in abundance across breeds. Overall, 33% of these taxa overlapped with previously identified taxa that were associated with genetic variation in humans or other species. However, a non-significant correlation was observed between microbial composition and the host pedigree-based kinship. Despite a notable variation in the diversity and composition of the faecal microbiota, breed exerted limited effects on the equine faecal microbiota.

Unraveling the effects of the gut microbiota composition and function on horse endurance physiology.

An integrated analysis of gut microbiota, blood biochemical and metabolome in 52 endurance horses was performed. Clustering by gut microbiota revealed the existence of two communities mainly driven by diet as host properties showed little effect. Community 1 presented lower richness and diversity, but higher dominance and rarity of species, including some pathobionts. Moreover, its microbiota composition was tightly linked to host blood metabolites related to lipid metabolism and glycolysis at basal time. Despite the lower fiber intake, community type 1 appeared more specialized to produce acetate as a mean of maintaining the energy supply as glucose concentrations fell during the race. On the other hand, community type 2 showed an enrichment of fibrolytic and cellulolytic bacteria as well as anaerobic fungi, coupled to a higher production of propionate and butyrate. The higher butyrate proportion in community 2 was not associated with protective effects on telomere lengths but could have ameliorated mucosal inflammation and oxidative status. The gut microbiota was neither associated with the blood biochemical markers nor metabolome during the endurance race, and did not provide a biomarker for race ranking or risk of failure to finish the race.

Inadequate DNA Damage Repair Promotes Mammary Transdifferentiation, Leading to BRCA1 Breast Cancer.

Loss of BRCA1 p220 function often results in basal-like breast cancer (BLBC), but the underlying disease mechanism is largely opaque. In mammary epithelial cells (MECs), BRCA1 interacts with multiple proteins, including NUMB and HES1, to form complexes that participate in interstrand crosslink (ICL) DNA repair and MEC differentiation control. Unrepaired ICL damage results in aberrant transdifferentiation to a mesenchymal state of cultured, human basal-like MECs and to a basal/mesenchymal state in primary mouse luminal MECs. Loss of BRCA1, NUMB, or HES1 or chemically induced ICL damage in primary murine luminal MECs results in persistent DNA damage that triggers luminal to basal/mesenchymal transdifferentiation. In vivo single-cell analysis revealed a time-dependent evolution from normal luminal MECs to luminal progenitor-like tumor cells with basal/mesenchymal transdifferentiation during murine BRCA1 BLBC development. Growing DNA damage accompanied this malignant transformation.

Evaluation of an Integrative Post-Traumatic Stress Disorder Treatment Program.

OBJECTIVES: Post-traumatic stress disorder (PTSD) and combat-related stress can be refractory, pervasive, and have a devastating impact on those affected, their families, and society at large. Challenges dealing with symptoms may in turn make a servicemember more susceptible to problems, including alcohol abuse, interpersonal conflict, and occupational problems. An effective treatment strategy will address multifactorial issues by using a holistic multimodal approach. Back on Track is an intensive outpatient program utilizing a holistic philosophy and multimodal treatments to provide a whole systems approach for the treatment of combat-related stress reactions and PTSD in active duty servicemembers. DESIGN/SETTING/SUBJECTS: An explanatory, sequential, mixed-methods program evaluation was conducted to assess the effectiveness of a PTSD and combat stress treatment program. Quantitative outcomes were collected and analyzed on 595 participants at pre- and postinterventions and 6-week follow-up and qualitative data were gathered through participant interviews. INTERVENTION: The manualized program uses a multimodal, psychoeducational group therapy format with a holistic approach for treating combat stress, increasing resiliency, and assisting with reintegration. Rotating providers visit from other programs and services to deliver content in bio-psycho-social-spiritual domains, including didactic lectures on mindfulness and the relaxation response and daily sessions of yoga nidra and meditation. OUTCOME MEASURES: The primary outcome measure was PTSD symptom severity assessed with the PTSD Checklist-Military Version (PCL-M). Secondary outcomes included self-efficacy, knowledge, use, and satisfaction. Quantitative data were contextualized with interview data. RESULTS: Results demonstrated a highly statistically significant effect of the program when comparing within-subject PCL-M scores before and after program participation, signed rank S (N = 595) = -47,367, p < 0.001. This translates to a moderate effect size, Cohen's d (N = 595) = -0.55, 95% confidence interval = -0.62 to -0.47, and a mean decrease of 7 points on the PCL-M at postintervention, demonstrating response to treatment. There were significant increases in knowledge and self-efficacy and high levels of satisfaction with the program overall, content, materials, and delivery. CONCLUSIONS: The treatment program has served ∼800 servicemembers since inception and has since expanded to five installations. The provision of whole systems care where the approach is holistic, multimodal, and multidisciplinary may be a way forward for the successful treatment of PTSD and other debilitating behavioral health conditions in military contexts and beyond.