UNASSIGNED: Hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS) are multisystem conditions marked by dysfunctional connective tissue. This feasibility study evaluated a 9-week integrative medicine program in this population.
UNASSIGNED: Using a single-arm study design, adults with HSD or EDS were given recommendations for an anti-inflammatory Mediterranean diet and self-management with additional behavioral and psychosocial support. Preliminary data on feasibility based on recruitment and retention, adherence to the diet, mobile app tracking, changes to perceived well-being via health outcomes, and satisfaction with care were obtained.
UNASSIGNED: Thirteen participants were enrolled within a 4-month timeframe. Eight participants completed the study. Three participants met dietary tracking requirement in at least 4 of 8 intervention weeks and met the macronutrient requirements in at least half of the weeks tracked. No decreases in VAS pain scores after 5 and 9 weeks were noted; however, 62.5% (n = 5) of participants had decreased pain at 9 weeks, compared to baseline. There were significant improvements (p<.05) in six of twelve measurements of satisfaction with care at the end of the intervention.
UNASSIGNED: This study provides a foundation for future research on patient experience and introduces a novel treatment paradigm focused on nutrition and self-management.
Trial Registration: National Institutes of Health clinicaltrials.gov; identifier: NCT04734041.
UNASSIGNED: Lifestyle and dietary interventions are relatively safe and well tolerated in the hypermobility spectrum disorder (HSD) and Ehlers-Danlos disorder (EDS) population.Participants in our 9-week integrative medicine program actively engaged in self-management of their condition and showed promising adherence to dietary and tracking requirements.Effective treatment of the intricacies and dynamics of these highly variable and clinically heterogeneous disorders may require a network of healthcare providers, integrative healthcare, as well as behavioral and psychosocial support.Dietary tracking through mobile apps might help promote self-efficacy and adherence to dietary changes.Symptom tracking might be an effective way for patients to track changes to their health and could provide valuable information for health professionals engaged in managing the disorders.

Due to its unclear etiology, there is no specific medicine to cure the recurrent and incurable inflammatory bowel disease (IBD). Unhealthy dietary habits unconsciously contributed to the progression of IBD, for example a High-Salt-Diet (HSD) is the most neglected and frequently adopted habit. However, the molecular mechanism of how HSD aggravates the progression of IBD has yet to remain uncovered. Herein, we focus on the hypothesis that necroptosis pathway may be involved in the process of IBD exacerbated by HSD. To this end, different gene expression (DEGs) profiles of human epithelia under hypertonic culture conditions were applied to screen candidate pathways. What\'s more, gene expression manipulation, immune microenvironment detection, RIPK3/MLKL gene knockout (KO), and wild-type (WT) mice were carried out to research the promotion of IBD progression under treatments of high salt intake. Based on our present results, gene expression profiles in human normal colon epithelia cell NCM460 were significantly changed under salt- or sucrose-induced hypertonic culture conditions. RIPK3 was significantly up-regulated under both conditions. Furthermore, mice colon epithelia cell CT26 growth was inhibited in a time- and dose-dependent manner by extra NaCl incubation. Autophagy, and Necroptosis pathways were activated and enhanced by LPS pretreatment. HSD significantly exacerbated DSS-induced IBD symptoms in vivo in a dose-dependent manner. Moreover, RIPK3-/- and MLKL-/- mice presented severe IBD symptoms in vivo. Overall, the results demonstrated that HSD aggravated the IBD progression via necroptosis activation, providing novel strategies and promising targets for the clinical treatment of IBD.

Sleep is negatively affected by environmental noise. In the present study, we investigated self-reported high sleep disturbances (being \"highly sleep disturbed\"-HSD) from road traffic (primary and secondary road networks), rail (train and tram) and air traffic noise in the LIFE-Adult cohort study in Leipzig, Germany. For this, we used exposure data from 2012 and outcome data of Wave 2 (collected during 2018-2021). HSD was determined and defined according to internationally standardized norms. The highest risk for transportation noise-related HSD was found for aircraft noise: the odds ratio (OR) was 19.66, 95% CI 11.47-33.71 per 10 dB increase in Lnight. For road and rail traffic, similar risk estimates were observed (road: OR = 2.86, 95% CI 1.92-4.28; rail: OR = 2.67, 95% CI 2.03-3.50 per 10 dB Lnight increase). Further, we compared our exposure-risk curves with the curves of the WHO environmental noise guidelines for the European region. The proportion of individuals with HSD for a given noise level was lower for rail traffic but higher for aircraft noise in the LIFE study than in the WHO curves. For road traffic, curves are not directly comparable because we also included the secondary road network. The results of our study add to the body of evidence for increased health risks by traffic noise. Moreover, the results indicate that aircraft noise is particularly harmful to health. We recommend reconsidering threshold values for nightly aircraft exposure.

Hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS) are frequently underdiagnosed, contributing to patient dissatisfaction in the healthcare system. This study evaluated the health service utilization, care, and subjective experiences of living with chronic illness among adults with HSD and EDS in the United States and Canada.
This was an anonymous, web-based, cross-sectional healthcare survey. The survey obtained basic demographic information, the Patient Assessment of Chronic Illness Care (PACIC+), as well as responses to questions on the use of healthcare and integrative medicine.
A total of 353 surveys were received. The most common complementary therapies used were physical therapy (82%), massage (68%), yoga (58%), chiropractic (48%), and meditation (43%). Mean (SD) summary PACIC and PACIC 5 As scores were 2.16 (0.77) and 2.25 (0.83), respectively. Across all PACIC domains, mean scores of individuals whose typical doctor visit was 30 min or at least an hour were significantly higher than those of individuals who indicated typical visits of 15 min (all p < 0.0001 by one-way ANOVA). There was widespread agreement on the importance of patient-provider relationship and trust, physicians\' understanding of the individual\'s complete medical history, and prioritization of physical and emotional safety (>95% agree or strongly agree to each).
Individuals with HSD or EDS report low satisfaction with chronic illness care and commonly seek out complementary and self-administered therapies, likely in an attempt to manage symptoms. Respondents reported a desire for greater time and attention from physicians. Results from this study could educate the healthcare community to improve support mechanisms for HSD and EDS populations.IMPLICATIONS FOR REHABILITATIONPatients with hypermobility spectrum disorders (HSD) or Ehlers-Danlos syndromes (EDS) express a desire for patient-centered care and peer support from other individuals with HSD or EDS.Individuals with HSD or EDS have typically seen multiple doctors for their condition and their satisfaction with chronic care, as measured by the Patient Assessment of Chronic Illness Care (PACIC+), is low.The use of various complementary and integrative health treatments, as well as specialized diets, is common in this population, and might be beneficial for symptom management.Healthcare delivery for HSD and EDS may require a multidisciplinary healthcare team, as complementary and self-care modalities are typically used in addition to physical therapy, pain medication, and other conventional care.

High-salt diet (HSD) is associated with dysregulated metabolism and metabolic disorders. Although previous studies have indicated its effect on metabolic tissues, the involving molecular mechanisms are not quite understood. In the present study, we provided a comprehensive transcriptome analysis on multiple metabolic tissues of HSD-fed mouse model by RNA sequencing. We observed that several genes associated with de novo lipogenesis and cholesterol biosynthesis were significantly downregulated in white adipose tissue and liver tissue of HSD mice group, such as Fasn, Scd1, Acaca, and Thrsp. Furthermore, combined with secretome datasets, our results further demonstrated that HSD could alter expression levels of organokines in metabolic tissues, for example, Tsk and Manf, in liver tissue and, thus, possibly mediate cross-talk between different metabolic tissues. Our study provided new insight about molecular signatures of HSD on multiple metabolic tissues.

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant (AD) genetic trait characterized by elevated basal serum tryptase ≥8 ng/mL, caused by increased α-tryptase-encoding TPSAB1 copy number. HαT affects 5% to 7% of Western populations and has been associated with joint hypermobility. Hypermobility disorders are likewise frequently AD, but genetic etiologies are often elusive. Genotyping of individuals with hypermobility spectrum disorder (n = 132), hypermobile Ehlers-Danlos syndrome (n = 78), or axial skeletal abnormalities with hypermobility (n = 56) was performed. Clinical features of individuals with and without HαT were compared. When analyzing our combined cohorts, dysphagia (p = 0.007) and retained primary dentition (p = 0.0003) were significantly associated with HαT, while positive associations with anaphylaxis (p = 0.07) and pruritus (P = 0.5) did not reach significance likely due to limited sample size. Overall, HαT prevalence is not increased in individuals with hypermobility disorders, rather linked to a unique endotype, demonstrating how HαT may modify clinical presentations of complex patients.

Irritable bowel syndrome (IBS) is common, but its cause remains unknown. IBS patients present with gastrointestinal (GI) symptoms such as abdominal pain with altered bowel habits; however, some patients also have non-GI symptoms including muscle and joint pains. It is thus plausible that within large IBS cohorts, subgroups exist with distinct clinical phenotypes. Yet, these subgroups have not been clearly identified or characterized. Due to lack of segmentation, treatment-focused symptomatic management is similar for all with IBS and follows indiscriminate algorithms regardless of possible differing clinical phenotype. This universal approach to IBS management may account for the reported lack of efficacy of treatment. One emerging subgroup receiving increasing attention is that with overlap IBS and the underlying heritable connective tissue disorder, hypermobile Ehlers-Danlos syndrome (hEDS). Current evidence suggests that up to 62% of patients with hEDS suffer from IBS. However, despite recognition of the presence of IBS in hEDS, this overlap IBS/hEDS group has not been characterized and these patients are managed in a similar way to those with IBS alone. Future studies are required to characterize and deep phenotype in this overlap IBS/hEDS group.

Aside from their intended actions, fungicides can drive pest insect outbreaks due to virtually continuous use and pest evolution. Small brown planthopper (SBPH), Laodelphax striatellus, outbreaks occurred recently in many provinces in China, with devastating rice losses. Because exposure to the fungicide jinggangmycin (JGM) increased reproduction of the brown plant hopper, Nilaparvata lugens, via its influence on fatty acid synthase, we posed the hypothesis that JGM and carbendazim (CBM) influence SBPH reproduction via their influence on enzymes involved in other aspects of lipid metabolism. Exposure to the fungicide CBM stimulated SBPH reproduction (egg-laying up by 78%) and to another fungicide, JGM, led to decreased egg-laying (down by 47.3%). These inverse effects are mediated by down-regulated expression of l-3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) in JGM-treated females and up-regulated expression of hydroxysteroid dehydrogenase-like protein 2-like (HSD) in CBM-treated females. RNAi knockdown of, separately, LCHAD and HSD led to reduced egg-laying (down by 52% for dsLCHAD and by 73% for dsHSD). dsLCHAD, dsHSD, and JGM treatments also led to severely reduced ovarian development in experimental SBPH, with shorted and thinned valvula and lack of egg cells in ovaries. Valvula of CBM-treated females enlarged, with banana-shaped eggs in ovaries. These data strongly support our hypothesis.

There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs, and other researchers in understanding and interpreting chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically stained tissues for estrogen, progesterone, and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically induced mammary gland anomalies that may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylstilbestrol, or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated, and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies.

Concern has increased regarding the adverse effects of di-(2-ethylhexyl)-phthalate (DEHP) on reproduction. However, limited information is available on the effects of DEHP in marine organisms. The aim of the present study was to examine whether long-term exposure to DEHP and its active metabolite mono-(2-ethylhexyl)-phthalate (MEHP) disrupts endocrine function in marine medaka (Oryzias melastigma). Marine medaka larvae were exposed to either DEHP (0.1 and 0.5mg/L) or MEHP (0.1 and 0.5mg/L) for 6 months, and the effects on reproduction, sex steroid hormones, liver vitellogenin (VTG), gonad histology and the expression of genes involved in the hypothalamic-pituitary-gonad (HPG) axis were investigated. Exposure to DEHP, but not MEHP, from hatching to adulthood accelerated the start of spawning and decreased the egg production of exposed females. Moreover, exposure to both DEHP and MEHP resulted in a reduction in the fertilization rate of oocytes spawned by untreated females paired with treated males. A significant increase in plasma 17β-estradiol (E2) along with a significant decrease in testosterone (T)/E2 ratios was observed in males, which was accompanied by the upregulation of ldlr, star, cyp17a1, 17βhsd, and cyp19a transcription in the testis. Increased concentrations of T and E2 were observed in females, which was consistent with the upregulation of ldlr. The expression of brain gnrhr2, fshβ, cyp19b and steroid hormone receptor genes also corresponded well with hormonal and reproductive changes. The liver VTG level was significantly increased after DEHP and MEHP exposure in males. DEHP induced histological changes in the testes and ovaries: the testes displayed a reduced number of spermatozoa, and the ovaries displayed an increased number of atretic follicles. In addition, the tissue concentrations of MEHP, MEHHP and MEOHP in DEHP-exposed groups were much higher than those in MEHP-exposed groups, and there were no dose- or sex-specific effects. Thus, DEHP exerts more obvious toxic effects compared with MEHP. There were some commonalities in the toxic effects and molecular mechanisms of DEHP and MEHP, suggesting that some of the toxic effects of DEHP may be induced by both DEHP itself and DEHP metabolites (including MEHP). Taken together, these results indicate that exposure to DEHP and MEHP from hatching to adulthood causes endocrine disruption with sex-specific effects in marine medaka, with males being more sensitive than females.