Craniocervical instability in patients with Ehlers-Danlos syndromes: outcomes analysis following occipito-cervical fusion.

Craniocervical instability (CCI) is increasingly recognized in hereditary disorders of connective tissue and in some patients following suboccipital decompression for Chiari malformation (CMI) or low-lying cerebellar tonsils (LLCT). CCI is characterized by severe headache and neck pain, cervical medullary syndrome, lower cranial nerve deficits, myelopathy, and radiological metrics, for which occipital cervical fusion (OCF) has been advocated. We conducted a retrospective analysis of patients with CCI and Ehlers-Danlos syndrome (EDS) to determine whether the surgical outcomes supported the criteria by which patients were selected for OCF. Fifty-three consecutive subjects diagnosed with EDS, who presented with severe head and neck pain, lower cranial nerve deficits, cervical medullary syndrome, myelopathy, and radiologic findings of CCI, underwent open reduction, stabilization, and OCF. Thirty-two of these patients underwent suboccipital decompression for obstruction of cerebral spinal fluid flow. Questionnaire data and clinical findings were abstracted by a research nurse. Follow-up questionnaires were administered at 5-28 months (mean 15.1). The study group demonstrated significant improvement in headache and neck pain (p < 0.001), decreased use of pain medication (p < 0.0001), and improved Karnofsky Performance Status score (p < 0.001). Statistically significant improvement was also demonstrated for nausea, syncope (p < 0.001), speech difficulties, concentration, vertigo, dizziness, numbness, arm weakness, and fatigue (p = 0.001). The mental fatigue score and orthostatic grading score were improved (p < 0.01). There was no difference in pain improvement between patients with CMI/LLCT and those without. This outcomes analysis of patients with disabling CCI in the setting of EDS demonstrated significant benefits of OCF. The results support the reasonableness of the selection criteria for OCF. We advocate for a multi-center, prospective clinical trial of OCF in this population.

Outcomes of orthopaedic surgery in Ehlers-Danlos syndromes: a scoping review.

BACKGROUND: Patients with Ehlers-Danlos syndromes (EDS) often experience high rates of joint subluxations and dislocations, and associated pain that may require surgical interventions. Orthopaedic surgical management is challenging in this population, and patients will often undergo multiple unsuccessful surgeries. Outcomes data specific to patients with EDS are sparse in the orthopaedic surgery literature. We conducted a scoping review to evaluate the evidence and outcomes for orthopaedic surgery specifically for the EDS population. METHODS: PubMed MEDLINE, Embase, The Cochrane Library, Cochrane Controlled Register of Trials (CENTRAL), CINHL, and Scopus from their inception to February 28, 2024 for all studies that reported outcomes for orthopaedic surgery in patients with EDS. Two reviewers independently determined study eligibility, rated study quality, and extracted data. Methodology followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The studies in this scoping review include Level III (retrospective cohort and case control) and Level IV (case series) evidence. RESULTS: The literature search yielded a total of 71 citations published between 1990 and 2023. All were primary studies. 38 were single case studies, 14 were case series, and 19 were retrospective cohort studies. No randomized clinical studies or systematic reviews were identified. Overall, the reported findings for the various anatomical sites and procedures indicated that surgery outcomes were inconsistent. Our review highlights the need for future research to determine whether currently established surgical approaches for various orthopaedic conditions offer long-term clinical benefit in patients with EDS. This is clearly a challenging diagnosis, and more rigorous clinical studies are required to identify optimal treatment approaches. CONCLUSIONS: Our review found little evidence-based research to guide optimal surgical treatment in EDS. Established surgical techniques that have been shown to be successful in the wider orthopaedic population should be studied to determine their efficacy in the EDS population.

Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-ß monoclonal antibodies in dominantly inherited Alzheimer's disease.

PURPOSE: Pittsburgh Compound-B (11C-PiB) and 18F-florbetapir are amyloid-ß (Aß) positron emission tomography (PET) radiotracers that have been used as endpoints in Alzheimer's disease (AD) clinical trials to evaluate the efficacy of anti-Aß monoclonal antibodies. However, comparing drug effects between and within trials may become complicated if different Aß radiotracers were used. To study the consequences of using different Aß radiotracers to measure Aß clearance, we performed a head-to-head comparison of 11C-PiB and 18F-florbetapir in a Phase 2/3 clinical trial of anti-Aß monoclonal antibodies. METHODS: Sixty-six mutation-positive participants enrolled in the gantenerumab and placebo arms of the first Dominantly Inherited Alzheimer Network Trials Unit clinical trial (DIAN-TU-001) underwent both 11C-PiB and 18F-florbetapir PET imaging at baseline and during at least one follow-up visit. For each PET scan, regional standardized uptake value ratios (SUVRs), regional Centiloids, a global cortical SUVR, and a global cortical Centiloid value were calculated. Longitudinal changes in SUVRs and Centiloids were estimated using linear mixed models. Differences in longitudinal change between PET radiotracers and between drug arms were estimated using paired and Welch two sample t-tests, respectively. Simulated clinical trials were conducted to evaluate the consequences of some research sites using 11C-PiB while other sites use 18F-florbetapir for Aß PET imaging. RESULTS: In the placebo arm, the absolute rate of longitudinal change measured by global cortical 11C-PiB SUVRs did not differ from that of global cortical 18F-florbetapir SUVRs. In the gantenerumab arm, global cortical 11C-PiB SUVRs decreased more rapidly than global cortical 18F-florbetapir SUVRs. Drug effects were statistically significant across both Aß radiotracers. In contrast, the rates of longitudinal change measured in global cortical Centiloids did not differ between Aß radiotracers in either the placebo or gantenerumab arms, and drug effects remained statistically significant. Regional analyses largely recapitulated these global cortical analyses. Across simulated clinical trials, type I error was higher in trials where both Aß radiotracers were used versus trials where only one Aß radiotracer was used. Power was lower in trials where 18F-florbetapir was primarily used versus trials where 11C-PiB was primarily used. CONCLUSION: Gantenerumab treatment induces longitudinal changes in Aß PET, and the absolute rates of these longitudinal changes differ significantly between Aß radiotracers. These differences were not seen in the placebo arm, suggesting that Aß-clearing treatments may pose unique challenges when attempting to compare longitudinal results across different Aß radiotracers. Our results suggest converting Aß PET SUVR measurements to Centiloids (both globally and regionally) can harmonize these differences without losing sensitivity to drug effects. Nonetheless, until consensus is achieved on how to harmonize drug effects across radiotracers, and since using multiple radiotracers in the same trial may increase type I error, multisite studies should consider potential variability due to different radiotracers when interpreting Aß PET biomarker data and, if feasible, use a single radiotracer for the best results. TRIAL REGISTRATION: ClinicalTrials.gov NCT01760005. Registered 31 December 2012. Retrospectively registered.

Longitudinal analysis of symptoms in the Ehlers-Danlos syndromes.

Our study extends a cross-sectional dataset on the Ehlers-Danlos syndromes (EDS) assembled by the National Institute on Aging (NIA), under a protocol entitled Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue. We were successful in contacting 171 of the original 252 participants with EDS. Our study cohort included 91 participants who completed at least one of the following surveys: Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory (MFI-20), and Short Form (SF-36) Health Survey, at both baseline and follow-up. Follow-up surveys occurred a median of 11.6 years after the baseline survey. We used mixed effects linear regression models to examine the change in scores for multiple indices reported by participants. There were small mean changes reflected in our estimates for the EDS population as a whole. There was wide heterogeneity between reported individual experiences, with some participants markedly improved and some dramatically worse. Men had a greater increase in mean pain severity over time than women. This is the first study to report a decade of longitudinal data in EDS.

Colliding and interacting microbiomes and microbial communities - consequences for human health.

Living 'things' coexist with microorganisms, known as the microbiota/microbiome that provides essential physiological functions to its host. Despite this reliance, the microbiome is malleable and can be altered by several factors including birth-mode, age, antibiotics, nutrition, and disease. In this minireview, we consider how other microbiomes and microbial communities impact the host microbiome and the host through the concept of microbiome collisions (initial exposures) and interactions. Interactions include changes in host microbiome composition and functionality and/or host responses. Understanding the impact of other microbiomes and microbial communities on the microbiome and host are important considering the decline in human microbiota diversity in the developed world - paralleled by the surge of non-communicable, inflammatory-based diseases. Thus, surrounding ourselves with rich and diverse beneficial microbiomes and microbial communities to collide and interact with should help to diminish the loss in microbial diversity and protect from certain diseases. In the same vein, our microbiomes not only influence our health but potentially the health of those close to us. We also consider strategies for enhanced host microbiome collisions and interactions through the surrounding environment that ensure increased microbiome diversity and functionality contributing to enhanced symbiotic return to the host in terms of health benefit.

Heritable disorders of connective tissue: Description of a data repository and initial cohort characterization.

We describe a data repository on heritable disorders of connective tissue (HDCT) assembled by the National Institutes of Health's National Institute on Aging (NIA) Intramural Research Program between 2001 and 2013. Participants included affected persons with a wide range of heritable connective tissue phenotypes, and unaffected family members. Elements include comprehensive history and physical examination, standardized laboratory data, physiologic measures and imaging, standardized patient-reported outcome measures, and an extensive linked biorepository. The NIA made a commitment to make the repository available to extramural investigators and deposited samples at Coriell Tissue Repository (N = 126) and GenTAC registry (N = 132). The clinical dataset was transferred to Penn State University College of Medicine Clinical and Translational Science Institute in 2016, and data elements inventoried. The consented cohort of 1,009 participants averaged 39 ± 18 years (mean ± SD, range 2-95) at consent; gender distribution is 71% F and 83% self-report Caucasian ethnicity. Diagnostic categories include Ehlers-Danlos syndrome (classical N = 50, hypermobile N = 99, vascular N = 101, rare types and unclassified N = 178), Marfan syndrome (N = 33), Stickler syndrome (N = 60), fibromuscular dysplasia (N = 135), Other HDCT (N = 72). Unaffected family members (N = 218) contributed DNA for the molecular archive only. We aim to develop further discrete data from unstructured elements, analyze multisymptom HDCT manifestations, encourage data use by other researchers and thereby better understand the complexity of these high-morbidity conditions and their multifaceted effects on affected persons.

Improving Biomedical Engineering Education Through Continuity in Adaptive, Experiential, and Interdisciplinary Learning Environments.

This study reports our experience of developing a series of biomedical engineering (BME) courses having active and experiential learning components in an interdisciplinary learning environment. In the first course, BME465: biomechanics, students were immersed in a simulation laboratory setting involving mannequins that are currently used for teaching in the School of Nursing. Each team identified possible technological challenges directly related to the biomechanics of the mannequin and presented an improvement overcoming the challenge. This approach of exposing engineering students to a problem in a clinical learning environment enhanced the adaptive and experiential learning capabilities of the course. In the following semester, through BME448: medical devices, engineering students were partnered with nursing students and exposed to simulation scenarios and real-world clinical settings. They were required to identify three unmet needs in the real-world clinical settings and propose a viable engineering solution. This approach helped BME students to understand and employ real-world applications of engineering principles in problem solving while being exposed to an interdisciplinary collaborative environment. A final step was for engineering students to execute their proposed solution from either BME465 or BME448 courses by undertaking it as their capstone senior design project (ENGR401-402). Overall, the inclusion of clinical immersions in interdisciplinary teams in a series of courses not only allowed the integration of active and experiential learning in continuity but also offered engineers more practice of their profession, adaptive expertise, and an understanding of roles and expertise of other professionals involved in enhancement of healthcare and patient safety.

Intercountry Consensus Building: Lessons From Developing a Chronic-Conditions Self-Management Support Framework.

Self-management support initiatives that aim to improve the self-care of chronic conditions are considered a key part of a health promotion strategy for addressing the impacts of long-term illness. Given the growth of these activities and still evolving evidence base, thoughtful intercountry collaborations with subject matter experts can be an effective way to expedite building self-management support capacity, promoting the advancement of evidence, and developing effective policies and programs. The challenge is to find an effective consensus building process that promotes linkages between researchers and health promotion decisions makers across vast geographical boundaries and limited resources. This paper describes the international, multistage, face-to-face, and online process that was used for developing an international framework for self-management support by researchers, educators, health care providers, policy makers, program managers/directors, program planners, consultants, patient group representatives, and consumers in 16 countries. We reflect on key lessons from this international initiative and discuss how this type of process may be useful for other health promotion groups trying to exchange knowledge and build consensus on how to move a field of research, policy, and/or practice forward, and advance the evidence-base of practice and the relevance of research.

Other misconduct evidence in appeals against conviction in child sexual abuse trials.

Child sexual abuse (CSA) trials may feature evidence relating to behaviours beyond the charges laid. This 'other misconduct' evidence can add context to the offending and may relate to more than one complaint or victim, indicating a pattern of thinking and behaviour, or that multiple incidents are unlikely to be coincidental. Directions to the jury regarding such evidence are complex and error prone, giving grounds for appeal. This study investigates successful appeals against conviction based on other misconduct evidence by analysing child and adult sexual assault cases listed in the Supreme Court of Appeal (Victoria) between 2004 and 2014. The appeals were equally successful in child and adult cases and equally likely to result in retrial. Specific errors in directions were identified and explanations are presented. Jury directions continue to be a source of error in sexual assault trials and can result in further attrition from the criminal justice system.

Contribution of the novel sulfur-producing adjunct Lactobacillus nodensis to flavor development in Gouda cheese.

We assessed the efficacy of Lactobacillus nodensis CSK964 as an adjunct culture in Gouda cheese under various industrial conditions. We set up 4 different systems: a direct vat inoculum with and without adjunct using the calf rennet Kalase, and an undefined bulk starter culture with and without adjunct using the microbial rennet Milase (both rennets from CSK Food Enrichment, Ede, the Netherlands). During ripening, we subjected the cheeses to the following analyses: viability of starter and adjunct cells, composition, proteolysis, and flavor development by detection of sulfur compounds and descriptive sensory analysis. In general, the presence of Lb. nodensis increased secondary proteolysis and influenced cheese flavor, particularly in relation to volatile sulfur compounds; hydrogen sulfide and methanethiol were present in higher abundances in cheeses containing Lb. nodensis. The primary starter also influenced the range of volatile sulfur compounds produced. Methanethiol and dimethyl disulfide were more abundant in the nisin-producing direct vat inoculum cheese with adjunct; hydrogen sulfide was more prevalent when bulk starter culture was used with Lb. nodensis. Sensory analysis revealed that the direct vat inoculum cheese with adjunct scored significantly better in terms of smell and taste than the direct vat inoculum cheese without adjunct and lacked the dominant sulfur flavors of the bulk starter cheese with adjunct. Subsequent analysis using lead acetate paper and modified motility broth as indicators of hydrogen sulfide production confirmed that Lb. nodensis produced hydrogen sulfide in broth and in the cheese matrix. This study suggests that the inclusion of Lb. nodensis as an adjunct culture can significantly alter the flavor profile of the final cheese. However, the selection of a suitable primary starter is imperative to ensure a desirable product.

Toward consensus on self-management support: the international chronic condition self-management support framework.

Self-management support (SMS) initiatives have been hampered by insufficient attention to underserved and disadvantaged populations, a lack of integration between health, personal and social domains, over emphasis on individual responsibility and insufficient attention to ethical issues. This paper describes a SMS framework that provides guidance in developing comprehensive and coordinated approaches to SMS that may address these gaps and provides direction for decision makers in developing and implementing SMS initiatives in key areas at local levels. The framework was developed by researchers, policy-makers, practitioners and consumers from 5 English-speaking countries and reviewed by 203 individuals in 16 countries using an e-survey process. While developments in SMS will inevitably reflect local and regional contexts and needs, the strategic framework provides an emerging consensus on how we need to move SMS conceptualization, planning and development forward. The framework provides definitions of self-management (SM) and SMS, a collective vision, eight guiding principles and seven strategic directions. The framework combines important and relevant SM issues into a strategic document that provides potential value to the SMS field by helping decision-makers plan SMS initiatives that reflect local and regional needs and by catalyzing and expanding our thinking about the SMS field in relation to system thinking; shared responsibility; health equity and ethical issues. The framework was developed with the understanding that our knowledge and experience of SMS is continually evolving and that it should be modified and adapted as more evidence is available, and approaches in SMS advance.

The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model.

INTRODUCTION: The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial is an adaptive platform trial testing multiple drugs to slow or prevent the progression of Alzheimer's disease in autosomal dominant Alzheimer's disease (ADAD) families. With completion of enrollment of the first two drug arms, the DIAN-TU now plans to add new drugs to the platform, designated as the Next Generation (NexGen) prevention trial. METHODS: In collaboration with ADAD families, philanthropic organizations, academic leaders, the DIAN-TU Pharma Consortium, the National Institutes of Health, and regulatory colleagues, the DIAN-TU developed innovative clinical study designs for the DIAN-TU NexGen prevention trial. RESULTS: Our expanded trial toolbox consists of a disease progression model for ADAD, primary end point DIAN-TU cognitive performance composite, biomarker development, self-administered cognitive assessments, adaptive dose adjustments, and blinded data collection through the last participant completion. CONCLUSION: These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD.

Characteristics of Successful and Unsuccessful Appeals Against Conviction for Child Sexual Abuse.

The current study investigated (a) the effect of legislative reforms and amendments to judges' directions to juries in the success of appeals against conviction for child sexual abuse and (b) the role of delay between the offence(s) and the trial in these appeals. Appeals listed in the Victorian Court of Appeal in Australia between 2004 and 2014 were identified. Data were extracted for a number of variables including the appeal's success and the delay between the first offence and the trial. Of the 238 appeals identified, 118 (49.6%) were successful. Legislative reform showed the only significant difference between successful and unsuccessful appeals: There were more successful appeals than expected following legislative changes in 2006. Delay was raised as a ground for appeal in 11 of the 118 successful cases. Delay was associated with the ages of the victims and offenders, sex of the victims, and the victim-offender relationship. Overall, the results do not appear consistent with the goal of the reforms, which was to avoid appeals and retrials that may have occurred as a result of judicial error. Future research should determine whether the trend towards higher success of appeals is continuing, particularly in light of further legislative changes.

Teaching and Learning Medication Calculations: A Grounded Theory of Conceptual Understanding.

OBJECTIVE: The purpose of this study was to identify the process of nursing students' attainment of conceptual understanding when learning medication dosage calculations. DESIGN: This study utilized a grounded theory research design with a blended theoretical framework of constructivism and symbolic interaction. RESULTS: A process of conceptual understanding began with the teaching and learning experiences in the classroom and progressed to students' reengagement with the course content outside of the classroom. Confusion was the core category of the process. Students who were able to work through the confusion and solve problems were able to attain conceptual understanding and progress to more complex problem solving. CONCLUSIONS: Nurse educators need to identify teaching and learning strategies that promote conceptual understanding. Helping students to get beyond memorization and move to understanding of medication calculations can help students' critical thinking and problem solving ability and lead to conceptual understanding.

Using Concept Mapping to Develop a Strategy for Self-Management Support for Underserved Populations Living With Chronic Conditions, British Columbia, August 2013-June 2014.

INTRODUCTION: Self-management support (SMS) is an essential component of public health approaches to chronic conditions. Given increasing concerns about health equity, the needs of diverse populations must be considered. This study examined potential solutions for addressing the gaps in self-management support initiatives for underserved populations. METHODS: Stakeholders representing government, nongovernment organizations, Aboriginal communities, health authorities, medical practices, and research institutions generated, sorted, and rated ideas on what could be done to improve self-management support for underserved populations. Concept mapping was used to facilitate the collection and organization of the data and to generate conceptual maps. RESULTS: Participants generated 92 ideas that were sorted into 11 clusters (foster partnerships, promote integrated community care, enhance health care provider training, shift government policy, support community development, increase community education, enable client engagement, incorporate client support systems, recognize client capacity, tailor self-management support programs, and develop client skills, training, and tools) and grouped into system, community, and individual levels within a partnership framework. CONCLUSION: The strategy can stimulate public health dialogue and be a roadmap for developing SMS initiatives. It has the potential to address SMS and chronic condition inequities in underserved populations in several ways: 1) by targeting populations that have greater inequities, 2) by advocating for shifts in government policies that create and perpetuate inequities, 3) by promoting partnerships that may increase the number of SMS initiatives for underserved groups, and 4) by promoting training and engagement that increase the relevance, uptake, and overall effectiveness of SMS.

Estimates of the excess cost burden of Ehlers-Danlos syndromes: a United States MarketScan® claims database analysis.

Introduction: Patients with Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD) have significant health challenges that are well-documented, however their impact in terms of cost is not known. Our research objective was to examine the cost burden of EDS and HSD in the United States. We focused this analysis on those with commercial insurance plans. Methods: We queried the MarketScan® database for year 2021 for claims that contained an ICD-10 diagnosis code for EDS or hypermobility. Excess costs for patients in the EDS and HSD cohorts were determined by matching each patient to one patient in the database that did not have a claim for EDS or HSD and comparing total costs for the calendar year. We determined whether patients had claims for selected comorbid conditions likely to impact costs during the calendar year. Results: Sample sizes were 5,113 for adult (age ≥ 18) patients with EDS, 4,880 for adult patients with HSD, 1,059 for child (age 5-17) patients with EDS, and 2,427 for child patients with HSD. The mean excess costs were $21,100 for adult EDS patients, $11,600 for adult HSD patients, $17,000 for child EDS patients, and $11,000 for child HSD patients. EDS and HSD cohorts, both adults and children, with any of the comorbidities had greater healthcare costs. The largest difference was found in the EDS cohort with gastrointestinal comorbid conditions, with more than double the costs for adults. Discussion: We found that patients in the MarketScan database, adults and children, who had EDS or HSD had substantially higher associated excess healthcare costs than patients without EDS or HSD when considering age, sex, geographic location, and comorbidities. These disproportionate healthcare costs in this population have health policy and economic implications, including the need for rapid diagnosis, access to treatment, and accelerated research to advance treatments.

Vertical distributions of megafauna on inactive vent sulfide features correspond to their feeding modes.

The discovery of inactive hydrothermal vent sulfide features near 9°50'N on the East Pacific Rise provides an opportunity to investigate the distribution and feeding ecology of communities inhabiting this type of habitat. We quantify megafaunal distributions on two features, Lucky's Mound and Sentry Spire, to determine how taxonomic composition and feeding traits vary with vertical elevation. Fifty-one morphotypes, categorized by feeding mode, were identified from three levels of the features (spire, apron, and base) and the surrounding flat oceanic rise. About half of the morphotypes (26 of 51) were only observed at the sulfide features. Passive suspension feeders were more abundant on the spires, where horizontal particulate flux is expected to be elevated, than the base or rise. Deposit feeders tended to be more abundant on the base and rise, where deposition is expected to be enhanced, but were unexpectedly abundant higher up on Sentry Spire. Community differences between the two sulfide features suggest that other processes, such as feature-specific chemoautotrophic production, may also influence distributions.

Larvae from afar colonize deep-sea hydrothermal vents after a catastrophic eruption.

The planktonic larval stage is a critical component of life history in marine benthic species because it confers the ability to disperse, potentially connecting remote populations and leading to colonization of new sites. Larval-mediated connectivity is particularly intriguing in deep-sea hydrothermal vent communities, where the habitat is patchy, transient, and often separated by tens or hundreds of kilometers. A recent catastrophic eruption at vents near 9 degrees 50'N on the East Pacific Rise created a natural clearance experiment and provided an opportunity to study larval supply in the absence of local source populations. Previous field observations have suggested that established vent populations may retain larvae and be largely self-sustaining. If this hypothesis is correct, the removal of local populations should result in a dramatic change in the flux, and possibly species composition, of settling larvae. Fortuitously, monitoring of larval supply and colonization at the site had been established before the eruption and resumed shortly afterward. We detected a striking change in species composition of larvae and colonists after the eruption, most notably the appearance of the gastropod Ctenopelta porifera, an immigrant from possibly more than 300 km away, and the disappearance of a suite of species that formerly had been prominent. This switch demonstrates that larval supply can change markedly after removal of local source populations, enabling recolonization via immigrants from distant sites with different species composition. Population connectivity at this site appears to be temporally variable, depending not only on stochasticity in larval supply, but also on the presence of resident populations.

Efficacy of Bifidobacterium longum alone or in multi-strain probiotic formulations during early life and beyond.

The significance of Bifidobacterium to human health can be appreciated from its early colonization of the neonatal gut, where Bifidobacterium longum represents the most abundant species. While its relative abundance declines with age, it is further reduced in several diseases. Research into the beneficial properties of B. longum has unveiled a range of mechanisms, including the production of bioactive molecules, such as short-chain fatty acids, polysaccharides, and serine protease inhibitors. From its intestinal niche, B. longum can have far-reaching effects in the body influencing immune responses in the lungs and even skin, as well as influencing brain activity. In this review, we present the biological and clinical impacts of this species on a range of human conditions beginning in neonatal life and beyond. The available scientific evidence reveals a strong rationale for continued research and further clinical trials that investigate the ability of B. longum to treat or prevent a range of diseases across the human lifespan.

A qualitative study of pain and related symptoms experienced by people with Ehlers-Danlos syndromes.

Introduction: Individuals with Ehlers-Danlos syndromes (EDS) often have complex and multi-faceted symptoms across the lifespan. Pain and the related symptoms of fatigue and sleep disorders are common. The objective of this qualitative study was to understand how participants manage their pain and related symptoms. Methods: The design was a qualitative thematic content analysis. Twenty-eight interviews were conducted to collect data from individuals who were participants in a prior quantitative longitudinal study. A semi-structured interview guide was designed to focus on and understand the trajectory of pain, sleep, fatigue, and general function. The interview continued with questions about coping mechanisms and obstacles to maintaining a sense of well-being. Results: Symptoms reported by participants were widespread and often interwoven. Pain was universal and often resulted in fatigue and disordered sleep which impacted physical function. Most participants reported that their symptoms worsened over time. Participants reported a wide range of effective interventions and most reported developing self-care strategies to adapt to their disabilities/limitations. Solutions included complementary interventions discovered when conventional medicine was unsuccessful. Very few relied on a "system" of health care and instead developed their own strategies to adapt to their disabilities/limitations. Discussion: EDS symptoms are often debilitating, and their progression is unknown. For most participants, symptoms worsened over the time. Even though participants in our study, by experience, were self-reliant, the importance of knowledgeable medical providers to help guide self-care should be emphasized.