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The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-topregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal antiinflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns. [ABSTRACT FROM AUTHOR]

Non-traumatic orthopedic conditions are pathological conditions involving musculoskeletal system that includes muscles, tendons, bone and joints and associated with frequent medical and surgical care and high treatment costs. There is paucity of information on the pattern of non-traumatic orthopedic conditions in low and middle income countries. The purpose of this study was to determine the epidemiology of non-traumatic orthopedic conditions among inpatients at the Kenyatta National Hospital in Kenya. This was a cross-sectional study with a sample of 175 charts reviewed. Approximately, 70.3% of the inpatients were aged between 25 to 64 years of age with the mean age of 39.97 years (STD 18.78). Ever married tended to be older 53.5 (95% CI: 46.8–60.2) years than other marital statuses. Approximately, 60.6% were males, 38.9% had comorbidities and 49.1% were casuals or unemployed. All inpatients were Kenyans with Nairobi County comprising 52.6% of all inpatients. Approximately, 77.7% were self-referrals. The commonest non-trauma orthopaedic conditions were infection and non-union (35.4%) and spinal degenerative diseases (20.60%) and the least was limb deformities (1.70%). Compared to females, males were 3.703 (p<0.001) times more likely to have infection and non-union. Patients with primary, secondary and tertiary education were 88.2% (p<0.001), 75.6% (p<0.001) and 68.1% (p = 0.016) less likely to have infection and non-union compared to those with no or preschool education. Widows were 8.500 (p = 0.028) times more likely to have spinal degenerative disease than married. Males were 70.8% (p = 0.031) less likely to have osteoarthritis than females. Inpatients with secondary education were 5.250 (p = 0.040) times more likely to have osteoarthritis than those with no or preschool education. In conclusion, majority of inpatients were young and middle aged adults. Infection and non-union and spinal degenerative diseases were the most common non-trauma orthopedic conditions. While males and those with low education were more likely to have infection and non-union, married were more likely to have spinal degenerative disease. Osteoarthritis was more likely among female admissions. [ABSTRACT FROM AUTHOR]

Background: The Mayo Score [MS], endoscopic Mayo Score [eMS] and the Ulcerative Colitis Index of Severity [UCEIS] are employed in the assessment of ulcerative colitis [UC] severity. This study compared the aforementioned indices in terms of predictory value for response to remission induction treatment with anti-TNF and anti-integrin biologics. Methods: A total of 38 patients were retrospectively evaluated in the study, 23 male and 15 female, aged 18–74 years old who had undergone a total of 53 biological therapy courses with either infliximab [IFX] or vedolizumab [VDZ] at the Department of Gastroenterology of the Medical University of Łódź. The clinical and endoscopic activity of UC was assessed at the outset of biological therapy and the 14th week remission induction assessment juncture. Results: The study analyzed 19 IFX and 34 VDZ treatment courses. The response rate of patients receiving IFX reached 73.67% and the response rate was 58.82% for VDZ. The mean MS, eMS and UCEIS improved among all patient groups: 8.316 ± 1.974 to 4.158 ± 2.218 (p < 0.05), 2.632 ± 0.597 to 1.790 ± 0.713 (p < 0.05) and 4.790 ± 1.745 to 3.000 ± 1.453 (p < 0.05) for IFX, 7.088 ± 2.234 to 3.618 ± 2.412 (p < 0.05), 2.706 ± 0.524 to 1.677 ± 1.065 (p < 0.05) and 4.235 ± 1.350 to 2.735 ± 1.880 (p < 0.05) for VDZ. Conclusions: The outcome assessment in induction treatment of UC includes clinical data and endoscopic evaluation. Severity of inflammatory lesion activity according to the eMS and UCEIS indices correlates with the overall disease presentation as evaluated with MS. The UCEIS provides an overall better predictor for biological induction treatment when compared with the eMS in both patient groups, particularly in those receiving VDZ. It provides a promising alternative to the eMS and can be employed for both initial disease severity assessment as well as for treatment response monitoring. [ABSTRACT FROM AUTHOR]

The imbalance of gut microbiota is an important factor leading to inflammatory bowel disease (IBD). Diffusible signal factor (DSF) is a novel quorum-sensing signal that regulates bacterial growth, metabolism, pathogenicity, and host immune response. This study aimed to explore the therapeutic effect and underlying mechanisms of DSF in a zebrafish colitis model induced by sodium dextran sulfate (DSS). The results showed that intake of DSF can significantly improve intestinal symptoms in the zebrafish colitis model, including ameliorating the shortening of the intestine, reducing the increase in the goblet cell number, and restoring intestinal pathological damage. DSF inhibited the upregulation of inflammation-related genes and promoted the expression of claudin1 and occludin1 to protect the tightness of intestinal tissue. The gut microbiome analysis demonstrated that DSF treatment helped the gut microbiota of the zebrafish colitis model recover to normal at the phylum and genus levels, especially in terms of pathogenic bacteria; DSF treatment downregulated the relative abundance of Aeromonas hydrophila and Staphylococcus aureus, and it was confirmed in microbiological experiments that DSF could effectively inhibit the colonization and infection of these two pathogens in the intestine. This study suggests that DSF can alleviate colitis by inhibiting the proliferation of intestinal pathogens and inflammatory responses in the intestine. Therefore, DSF has the potential to become a dietary supplement that assists in the antibiotic and nutritional treatment of IBD. [ABSTRACT FROM AUTHOR]

Objectives: The objective was to assess the serum levels of secretory leukocyte protease inhibitor (SLPI) and elafin in individuals diagnosed with axial spondyloarthritis (AxSpA) and analyze their diagnostic significance and correlation with disease activity. Patients and methods: The case-controlled, cross-sectional study was conducted between August 2021 and April 2023. Sixty patients diagnosed with AxSpA (n=60) were classified according to imaging results as nonradiographic AxSpA (nr-AxSpA [n=30]; 15 males, 15 females; median age: 30 years; range, 27.6 to 34.1 years) and radiographic AxSpA (r-AxSpA [n=30]; 19 males, 11 females; median age: 33 years; range, 30.6 to 38.1 years), forming two patient groups (the nr-axSpA and r-axSpA groups). A total of 30 age- and sex-matched healthy controls (16 females, 14 males; median age: 33 years; range, 29.2 to 37.1 years) were included. Demographic data, laboratory, and clinical characteristics of the participants were recorded. Results: There was no significant difference between SLPI and elafin serum levels in the disease groups. SLPI and elafin levels in AxSpA and nr-AxSpA groups were significantly higher compared to the control group (p<0.05). Based on receiver operating characteristic analysis, the diagnostic values of both parameters were found to be significant in the Ax-SpA and nr-AxSpA groups (p<0.05). There was no significant correlation between serum levels of SLPI and elafin and disease activity parameters. Significant positive correlations were found between SLPI and elafin in both the nr-AxSpA (p<0.05, r=0.870) and r-AxSpA (p<0.05, r=0.725) groups. Conclusion: The levels of SLPI and elafin were found to be significantly elevated in patients with AxSpA, particularly in those with nr-AxSpA, compared to the control group. Therefore, SLPI and elafin can be used as therapeutic biomarkers for the diagnosis of AxSpA and nr-AxSpA. However, no relationship was found with disease activity. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis is a chronic rheumatic disease that poses challenges in its diagnosis, evaluation, and management. The heterogeneity in the manifestations and the absence of definitive diagnosis biomarkers often complicates the process of accurate diagnosis. Furthermore, the involvement of multiple disease domains poses difficulties in assessing disease activity and defining the concept of remission. Despite therapeutic advancements, a subset of patients remains refractory to treatment, leading to the emergence of the concept of "difficult-to-treat" patients and the necessity for novel therapeutic approaches (e.g., drugs with novel mechanisms of action; combinations of treatments). This review addresses key unmet needs in psoriatic arthritis, in terms of diagnosis, classification, evaluation, comorbidities and treatment. [ABSTRACT FROM AUTHOR]

As an important immune stimulator and modulator, IFNγ is crucial for gut homeostasis and its dysregulation links to diverse colon pathologies, such as colitis and colorectal cancer (CRC). Here, we demonstrated that the epigenetic regulator, CBX3 (also known as HP1γ) antagonizes IFNγ signaling in the colon epithelium by transcriptionally repressing two critical IFNγ-responsive genes: STAT1 and CD274 (encoding Programmed death-ligand 1, PD-L1). Accordingly, CBX3 deletion resulted in chronic mouse colon inflammation, accompanied by upregulated STAT1 and CD274 expressions. Chromatin immunoprecipitation indicated that CBX3 tethers to STAT1 and CD274 promoters to inhibit their expression. Reversely, IFNγ significantly reduces CBX3 binding to these promoters and primes gene expression. This antagonist effect between CBX3 and IFNγ on STAT1/PD-L1 expression was also observed in CRC. Strikingly, CBX3 deletion heightened CRC cells sensitivity to IFNγ, which ultimately enhanced their chemosensitivity under IFNγ stimulation in vitro with CRC cells and in vivo with a syngeneic mouse tumor model. Overall, this work reveals that by negatively tuning IFNγ-stimulated immune genes' transcription, CBX3 participates in modulating colon inflammatory response and CRC chemo-resistance. Synopsis: The epigenetic regulator CBX3 (also known as HP1γ) antagonized IFNγ/STAT1/PD-L1 axis and thereby decreased IFNγ-stimulated immune genes transcription, which ultimately modulated colon inflammatory response and CRC chemo-resistance. CBX3 deletion resulted in chronic mouse colon inflammation, accompanied by upregulated STAT1 and PD-L1 levels in the colon epithelium. CBX3 deletion heightened CRC cells' sensitivity to IFNγ stimulation and increased STAT1/PD-L1 expression. CBX3 antagonized IFNγ signaling by tethering to the promotors of Stat1 and Cd274, and transcriptionally repressing their expression. IFNγ stimulation reduced CBX3 binding and primed gene expression. Re-sensitizing CRC cells to IFNγ by deletion CBX3 enhanced their chemosensitivity under IFNγ stimulation in vitro as well as in vivo. The epigenetic regulator CBX3 (also known as HP1γ) antagonized IFNγ/STAT1/PD-L1 axis and thereby decreased IFNγ-stimulated immune genes transcription, which ultimately modulated colon inflammatory response and CRC chemo-resistance. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic underscores the significance of vaccine hesitancy in shaping vaccination outcomes. Understanding the factors underpinning COVID-19 vaccination hesitancy is crucial for tailoring effective vaccination strategies. This cross-sectional study, conducted in three communities across the United States and Lebanon, employed surveys to assess respondents' knowledge, attitudes, and perceptions regarding COVID-19 infection and vaccination. Among the 7196 participants, comprising 6775 from the US and 422 from Lebanon, vaccine hesitancy rates were comparable at 12.2% and 12.8%, respectively. Notably, a substantial proportion of respondents harbored misconceptions, such as attributing the potential to alter DNA (86.4%) or track individuals (92.8%) to COVID-19 vaccines and believing in the virus's artificial origins (81%). US participants had more misconceptions about the COVID-19 vaccine, such as altering DNA or causing infertility. Lebanese participants were more likely to question the origins of the virus and the speed of vaccine development. Additionally, US respondents were less worried about infection, while Lebanese respondents were more indecisive but less likely to outright reject the vaccine. Primary determinants of hesitancy included perceptions that the vaccine poses a greater risk than the infection itself (aOR = 8.7 and 9.4, respectively) and negative recommendations from healthcare providers (aOR = 6.5 and 5.4, respectively). Conversely, positive endorsements from healthcare providers were associated with reduced hesitancy (aOR = 0.02 and 0.4, respectively). Targeting healthcare providers to dispel misinformation and elucidate COVID-19 vaccine risks holds promise for enhancing vaccination uptake. [ABSTRACT FROM AUTHOR]

Background: The early diagnosis and treatment of rheumatoid arthritis (RA) are essential to prevent joint damage and enhance patient outcomes. Diagnosing RA in its early stages is challenging due to the nonspecific and variable clinical signs and symptoms. Our study aimed to identify the most predictive features of hand ultrasound (US) for RA development and assess the performance of machine learning models in diagnosing preclinical RA. Methods: We conducted a prospective cohort study with 326 adults who had experienced hand joint pain for less than 12 months and no clinical arthritis. We assessed the participants clinically and via hand US at baseline and followed them for 24 months. Clinical progression to RA was defined according to the ACR/EULAR criteria. Regression modeling and machine learning approaches were used to analyze the predictive US features. Results: Of the 326 participants (45.10 ± 11.37 years/83% female), 123 (37.7%) developed clinical RA during follow-up. At baseline, 84.6% of the progressors had US synovitis, whereas 16.3% of the non-progressors did (p < 0.0001). Only 5.7% of the progressors had positive PD. Multivariate analysis revealed that the radiocarpal synovial thickness (OR = 39.8), PIP/MCP synovitis (OR = 68 and 39), and wrist effusion (OR = 12.56) on US significantly increased the odds of developing RA. ML confirmed these US features, along with the RF and anti-CCP levels, as the most important predictors of RA. Conclusions: Hand US can identify preclinical synovitis and determine the RA risk. The radiocarpal synovial thickness, PIP/MCP synovitis, wrist effusion, and RF and anti-CCP levels are associated with RA development. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing has paved the way in pharmaceutical applications. This innovative methodology presents novel and inventive remedies for patients and the pharmaceutical sector. Moreover, the benefits of this approach encompass the mitigation of adverse effects, customization of formulations for patients with rare medical conditions, and enhancement of therapeutic effectiveness. The objective of our review was to offer a comprehensive survey of the advancements observed in the drug delivery systems that were produced. A thorough inspection has assessed the diverse dosage forms developed using the three-dimensional printing technique (3DP), especially in the last five years. The pharmaceutical industry places significant emphasis on the benefits of developing dosage forms with intricate designs and geometries, incorporating multiple active ingredients, and tailored release profiles due to their versatility and related advantages. Drug delivery systems can be classified into different modalities, tablets, capsules, suppositories, transdermal delivery systems, microneedles, vaginal delivery systems, and nanoscale dosage forms. The utilization of our classification system facilitates researchers' task of evaluating publications and effectively pinpointing further opportunities for research exploration. [ABSTRACT FROM AUTHOR]

So Shiho Tang (SSHT) is a traditional herbal medicine commonly used in Asian countries. This study evaluated the anti-inflammatory effect of SSHT and the associated mechanism using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and murine dextran sodium sulfate (DSS)-induced ulcerative colitis models. Pre-treatment of RAW 264.7 macrophages with SSHT significantly reduced LPS-induced inflammation by decreasing nitrite production and regulating the mitogen-activated protein kinase pathway. Meanwhile, in mice, DSS-induced colitis symptoms, including colon shortening and body weight loss, were attenuated by SSHT. Moreover, representative compounds of SSHT, including glycyrrhizic acid, ginsenoside Rb1, baicalin, saikosaponin A, and saikosaponin B2, were quantified, and their effects on nitrite production were measured. A potential anti-inflammatory effect was detected in LPS-induced RAW 264.7 cells. Our findings suggest that SSHT is a promising anti-inflammatory agent. Its representative components, including saikosaponin B2, ginsenoside Rb1, and baicalin, may represent the key active compounds responsible for eliciting the anti-inflammatory effects and can, therefore, serve as quality control markers in SSHT preparations. [ABSTRACT FROM AUTHOR]

(1) Background: Although the association between psoriasis and atopic dermatitis (AD) is reported in the literature, scarce data are known about the efficacy of biologic therapy (including TNF and IL-17 inhibitors) in patients with psoriatic arthritis (PsA) and concomitant AD. (2) Objective: We aimed to explore AD in patients with PsA undergoing biologics for their active disease, focusing on prevalence and clinical and potential therapeutic implications. (3) Material and methods: We performed a retrospective analysis of 64 patients with PsA receiving various biological agents, followed-up in an academic outpatient rheumatology department up to 10 years. (4) Results: Atopic diseases were reported in about one third of cases, with a higher incidence of AD (10 cases; 52.6%) vs. atopic rhinitis (6 cases; 31.6%) and allergic asthma (3 cases; 15.8%). Three morphological patterns of AD were recognized including chronic prurigo (3 cases), a chronic lichen simplex (1 case), and eczemas (6 cases). All PsA with concomitant AD displayed a late onset of skin atopy (in their adult life) and demonstrated a specific profile (younger), from urban settings, equally distributed among genders, and requiring switching to a higher number of biologics to achieve disease control. (5) Conclusion: PsA and AD may coexist, requiring special attention when selecting the optimal biologic agent. [ABSTRACT FROM AUTHOR]

Background: Vaccine hesitancy is a complex challenge that demands a comprehensive approach, one that not only acknowledges legitimate concerns within communities but also actively confronts misinformation. In this context, this study aimed to investigate the prevalence of belief in conspiracy theories about COVID-19 vaccines among Brazilians, seeking to understand the factors associated with this behavior. Method: Utilizing a national online survey conducted between May and August 2020, with a sample of 4247 participants, we conducted multivariate analysis to identify the independent determinants of this adherence, calculating adjusted prevalence ratios (APRs) and their 95% confidence intervals. Results: It was revealed that 27.7% of participants believed in at least one conspiracy theory. Factors associated with a higher level of adherence included agreement with at least one piece of COVID-19 misinformation on social media (APR: 3.65; 95% CI: 3.07–4.34), lack of difficulty accessing leisure activities during the pandemic (APR: 3.11; 95% CI: 1.85–5.24), age 50 years or older (APR: 1.70; 95% CI: 1.49–1.94), absence of difficulty accessing protective measures (APR: 1.47; 95% CI: 1.26–1.72), use of face masks (APR: 1.62; 95% CI: 1.33–1.97), non-use of at least one traditional media source for information (APR: 1.47; 95% CI: 1.26–1.72), female gender (APR: 1.41; 95% CI: 1.25–1.60), and age between 30 and 49 years (APR: 1.35; 95% CI: 1.19–1.52). Conclusions: Our findings highlight that it is crucial to recognize that vaccine hesitancy is not merely an isolated phenomenon but often rooted in a complex interplay of social, cultural, psychological, and political factors. There is a need for multifaceted strategies to combat vaccine hesitancy, effectively address conspiracy theories, and consider the various factors associated with their prevalence. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a chronic inflammatory disease caused by abnormal immune responses in the intestinal mucosa and gut microorganisms. Unlike other mugworts, Artemisia argyi H. (A. argyi H.) enhances antioxidant, anti-inflammatory, and anticancer effects, but the improvement effects against gut inflammation have not yet been reported. Therefore, this study aimed to confirm the alleviation of the inflammatory state in the gut by A. argyi H. fermented with Lactobacillus plantarum (FAA), using lipopolysaccharide (LPS)-induced RAW 264.7 cells and dextran sulfate sodium (DSS)-induced colitis models. In vitro, FAA (10, 50, 100, and 200 μg/mL) was pretreated into RAW 264.7 cells, followed with LPS (100 ng/mL), which induced the cell damage. Meanwhile, in vivo, FAA (100, 200 mg/kg/day) was orally administered into 6-week-old C57BL/6N mice for 3 weeks. During the last week of FAA administration, 2.5% DSS was used to induce colitis. The results showed that FAA reduced the production of nitric oxide (p < 0.0001), tumor necrosis factor (TNF)-α, interleukin (IL)-6 (p < 0.0001), and IL-1β (p < 0.0001) in the LPS-induced RAW 264.7 cells. Moreover, in the DSS-induced colitis model, FAA alleviated clinical symptoms (p < 0.001), inhibited the inflammatory state by reducing the production of TNF-α (p < 0.0001) and interferon-γ in intestinal immune cells (p < 0.0001), and strengthened the intestinal barrier by increasing the number of goblet cells (p < 0.0001). Furthermore, the anti-inflammatory effects were confirmed by the alleviation of histological damage (p < 0.001) and down-regulation of the expression of inflammatory proteins (TLR4, p < 0.0001; MyD88, p < 0.0001; Cox-2, p < 0.0001). These results suggest the potential of FAA as a dietary ingredient for preventing inflammation in the gut. [ABSTRACT FROM AUTHOR]

To evaluate the vaccination status and clinical practice of patients with rheumatic diseases (RD) during the COVID-19 pandemic in China and to explore the impact of vaccination on infection severity in patients with RD. A cross-sectional survey was conducted among RD patients in outpatient and inpatient settings of the Rheumatology and Immunology Department in our hospital. Participants' characteristics, vaccination status, COVID-19 infection status, and medication for acute COVID-19 were collected. A total of 749 valid surveys were included in the study. A total of 271 (36.2%) patients were not vaccinated, and 478 (63.8%) patients received at least one dose of COVID-19 vaccine. 83.3% of patients were vaccinated with inactivated vaccines. Several patients with RD experienced the disease flare (57, 11.9%) and some adverse reactions (31, 6.5%) after COVID-19 vaccination. The COVID-19 infection rate was 84.1% in our study, which was not reduced by vaccination. However, vaccinated patients with RD showed decreased frequencies of pneumonia and hospitalization, compared with those of unvaccinated patients. Independent factors associated with hospitalization were COVID-19 vaccination (OR = 0.422, 95% CI 0.227–0.783), advanced age (OR = 1.070, 95% CI 1.046–1.095), ILD (OR = 1.245, 95% CI 1.082–1.432), and glucocorticoid (OR = 4.977, 95% CI 2.326–10.647). Adverse reactions to vaccines and disease flare are not common in RD patients. Although COVID-19 vaccination could not reduce the risk of COVID-19 infection in RD patients, it may effectively decrease the frequencies of pneumonia and hospitalization after infection. It is recommended that patients with RD should receive COVID-19 vaccination if there are no contraindications because the benefits outweigh the risks. [ABSTRACT FROM AUTHOR]

Objectives: The Swedish Inflammatory Bowel Disease Registry (SWIBREG) includes approximately 84% of all patients with inflammatory bowel disease (IBD) treated with immunomodulators, biologics or surgery in Sweden. Data on health-related quality of life (HRQoL) have been collected using EQ-5D-5L in the registry since 2012. Nevertheless, there are few studies assessing the validity of EQ-5D-5L in this patient population. Thus, the aim of this study was to assess the construct validity of EQ-5D-5L amongst patients with IBD (ulcerative colitis and Crohn's disease). Methods: Individual-level data on EQ-5D-5L and other disease-specific measures were extracted from SWIBREG. Known-groups validity was assessed by analysing whether the EQ-5D-5L captured expected differences between patient groups with different activity levels of the disease. Convergent validity was assessed by analysing whether the reported problems in the dimensions of EQ-5D-5L, EQ VAS, and the EQ-5D-5L index value correlated, as hypothesized, with the four dimensions in the Short Health Scale, a symptom index question, and the Physician Global Assessment (PGA) score. Results: In total, 9769 patients with IBD were included in the study. Patients with active IBD reported more health problems in the EQ-5D-5L descriptive system than patients being in remission. The effect sizes for the differences in reported problems between patients with active and inactive disease were at least small (≥0.1) or medium (≥0.3) in all dimensions except self-care. Differences in the mean EQ-5D-5L index and EQ-VAS score between patients with active and inactive disease were statistically significant (p < 0.001) and larger than pre-defined cut-offs for minimally important differences (>0.08 for the index and >11.0 for EQ-VAS). The analysis of convergent validity showed that EQ-5D-5L results correlated as expected with the disease-specific measures in 16 of the 21 analyses. In total, 22 (79%) of the 28 hypotheses were supported. Conclusion: The findings support the construct validity of EQ-5D-5L amongst patients with IBD and contribute to the scarce literature on the validity of the five-level version of EQ-5D in this patient population. These findings have important implications for the choice of HRQoL measure in routine health care registries like SWIBREG as well as for future clinical or health economic studies considering using EQ-5D-5L as a measure of HRQoL. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is a fat-soluble vitamin that prevents cardiovascular diseases and diabetes mellitus (DM). The present research aimed to study the impact of 25-hydroxyvitamin D (25(OH)D) level on the health status of patients with type 2 DM (T2DM) hospitalized in the "Pius Brînzeu" Emergency Clinical County University Hospital in Timisoara, Romania. Methods: The study retrospectively included 160 patients with T2DM who were clinically and biologically evaluated during hospitalization. Results: 13.1% of patients had optimal, 23.1% insufficient, and 63.8% deficient 25(OH)D values. Patients with 25(OH)D deficiency presented poorer glycemic control and were older, with higher weight, but had altered renal function, anemia, and lower iron values. Also, patients with associated neoplasia, diabetic neuropathy, cardiovascular disease (CVD), dementia, and grade 3 arterial hypertension (HTN) had lower values of 25(OH)D. An age > 55 years (sensitivity 69.9, specificity 82.5, AUROC 0.786, p < 0.001) and an HbA1c > 7.7% (sensitivity 89.3, specificity 92.9, AUROC 0.938, p < 0.001) predict 25(OH)D deficiency in T2DM patients. Conclusions: Vitamin D influences almost every system and organ in the body, so it should be a routine test for all patients with DM to correct the deficiency and prevent other diseases and complications. [ABSTRACT FROM AUTHOR]

Fluoridation (Fl) is effective in preventing caries; however, it is unclear to what extent its use is counteracted by misinformation on the internet. This study aimed to evaluate the information provided on professional websites of German dental practices regarding fluoridation. A systematic search was performed by two independent examiners, utilizing three search engines, from 10 September 2021 to 11 December 2021. Modified, validated questionnaires (LIDA, DISCERN) were used to evaluate technical and functional aspects, generic quality, and risk of bias. Demographic information and statements about Fl were also collected. The intra- and inter-rater reliability assessments were excellent. Of the 81 websites analyzed, 64 (79%) mentioned Fl, and 31 (38%) indicated it as a primary focus. Most websites met at least 50% of the LIDA (90%) and DISCERN criteria (99%), indicating that the general quality was good. Thirty (37%) of the websites explained the impact of Fl, and forty-five (56%) indicated an opinion (for/against) on Fl. The practice location and the clinical focus were not associated with the overall quality of websites. Only a minority of websites explained the effects of Fl. Taken together, this study highlights that there is a distinct lack of good-quality information on FL. [ABSTRACT FROM AUTHOR]

We aimed to (1) identify existing triage approaches for referral of patients with suspected inflammatory arthritis (IA) from primary care physicians (PCP) to rheumatologists, (2) describe their characteristics and methodologies for clinical use, and (3) report their level of validation for use in a publicly funded healthcare system. The comprehensive search strategy of multiple databases up to October 2023 identified relevant literature and focussed on approaches applied at the PCP-Rheumatologist referral stage. Primary, quantitative studies, reported in English were included. Triage approaches were grouped into patient conditions as defined by the authors of the reports, including IA, its subtypes and combinations. 13952 records were identified, 425 full text reviewed and 55 reports of 53 unique studies were included. Heterogeneity in disease nomenclature and study sample pretest probability was found. The number of published studies rapidly increased after 2012. Studies were mostly from Europe and North America, in IA and Axial Spondyloarthritis (AxSpa). We found tools ranging the continuum of development with those best performing, indicated by the area under the receiver operating curve (AUC) >0.8), requiring only patient-reported questions. There were AUCs for some tools reported from multiple studies, these were in the outstanding to excellent range for the Early IA Questionnaire (EIAQ) (0.88 to 0.92), acceptable for the Case Finding AxSpa (CaFaSpa) (0.70 to 0.75), and poor to outstanding for the Psoriasis Epidemiology Screening Tool (PEST) (0.61 to 0.91). Given the clinical urgency to improve rheumatology referrals and considering the good., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rheumatology faces a critical shortage of health-care professionals, exacerbated by an ageing patient population and escalating costs, resulting in widening gaps in care. Exponential advances in digital health technologies (DHTs) in the past 5 years offer new opportunities to address these challenges and could contribute to overall improved health care. However, keeping pace with innovations and integrating them into clinical practice can be challenging. This Review explores the transformative potential of DHTs for rheumatology in reshaping the entire patient pathway and redefining the roles of patients and providers, and discusses the potential barriers to DHT integration. Key technologies, such as large language models, clinical decision-support systems, digital therapeutics, electronic patient-reported outcomes, digital biomarkers, robots, self-sampling devices and artificial intelligence-based scribes, can be implemented along the patient pathway. A digital-first hybrid stepped-care patient pathway could combine in-person and remote care, enabling personalized and continuous monitoring through a digital safety net. The potential benefits and risks of transforming the traditional patient-provider relationship into a digital health triad with technology are discussed. Collaborative efforts are needed to navigate the evolving digital health landscape and harness the potential of DHTs to improve rheumatology care., (© 2024. Springer Nature Limited.)

Introduction: Recruitment for idiopathic inflammatory myopathies (IIM) research is a challenge due to the rarity of the disease and the scarcity of specialized myositis centers. Online recruitment may be a feasible alternative to reach rare disease patients. We evaluated various online recruitment methods in a large longitudinal IIM cohort., Methods: The "Myositis Patient Centered Tele-Research" (My Pacer) is a prospective 6-month observational study of IIM, recruited online and through traditional clinic visits. We utilized diverse recruitment methods, such as physician referrals, social media, websites, direct emails, and partnerships with patient-support organizations. Participants self-enrolled and completed pre-screening, e-consenting, and release of medical information via the study-specific app or website. We compared the effectiveness of various recruitment and enrollment methods and the characteristics of the population recruited., Results: A total of 841 participants completed the pre-screening; 408 completed e-consent and registration. From those, 353 (86.5%) were remotely recruited. Email (201; 49.26%) and social media (77; 18.87%) were important recruitment tools. Patient-support organizations were responsible for disseminating the study to 312 (75.46%) participants. The study app was used by 232 (65.72%) individuals for enrollment, with app users being slightly younger than website users (p = 0.001). Participants were mostly female 317 (77.76%), mean age of 54.84 years, White 328 (80.42%), Black 49 (12%), Asian 13 (3.26%), and non-Hispanic 378 (92.65%). Our study reached all U.S. regions and 45 (90%) U.S. states., Conclusions: Social media and partnerships with patient-support organizations lead to a high rate of recruitment, with a wide reach, and a reasonably diverse population., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Dermatomyositis (DM) is a rare inflammatory disease with diverse cutaneous and systemic manifestations, often associated with myositis-specific antibodies. Managing patients with refractory DM, or individuals presenting pecific complications, like calcinosis or rapidly progressive interstitial lung disease, presents unique challenges. This review explores current and promising treatment options for DM, drawing from clinical studies, case series, and case reports that consider the underlying disease pathophysiology. Recent advancements have improved our understanding and management of DM. The discovery of distinct DM autoantibodies and their correlation with specific clinical phenotypes has transformed patient categorization and enhanced our knowledge of the pathogenesis of the disease. Intravenous immunoglobulin, a well-established treatment in dermatomyositis, has regained prominence and a large randomized clinical trial has reaffirmed its efficacy, confirming it as an effective therapeutic option in this group of patients. Identification of the type I interferon pathway as a key pathogenic mechanism in DM has opened up new avenues for more effective treatment strategies. Blocking the JAK/STAT pathway offers potential for improved management of refractory patients and prevention of highly morbid complications. These recent advancements have significantly impacted the management and care of dermatomyositis patients, enabling tailored approaches, targeted interventions, and improved outcomes for individuals affected by this complex condition. [ABSTRACT FROM AUTHOR]

Hydroxy-α-sanshool (HAS), hydroxy-β-sanshool (HBS), hydroxy-γ-sanshool (HRS), and γ-sanshool (RS) are the key components from the Zanthoxylum genus, processing a range of pharmacological activities. The present study investigated the protective capacities of four sanshools on a dextran sulfate sodium (DSS)-induced model of ulcerative colitis (UC). The results showed that sanshool administration alleviated the colitis symptoms by reducing body weight loss and disease activity index (DAI) score, increasing the colon length, and improving colonic injury and the change in immune organ weight. Furthermore, sanshools enhanced the antioxidant enzyme activities, and RS exhibited the lowest effect on the improvement in total antioxidative capacity (T-AOC) and antioxidant abilities compared to the other three sanshools. The p65 nuclear factor κB (p65 NFκB) signaling pathway was inhibited to prevent hyperactivation and decreased the production of inflammatory factors. The gut barrier function in DSS-induced mice was restored by increasing goblet cell number and levels of tight junction proteins (zonula occludens-1, occludin, and claudin-1), and the levels of protein in HAS and HRS groups were higher than that in the HBS group, significantly. The analysis of gut microbiota suggested that sanshool administration significantly boosted the abundance of Lachnospiraceae, Muribaculaceae, Oscillospiraceae, and Alistipes and reduced the level of Buchnera in colitis mice. Collectively, the sanshool treatment could ameliorate colitis by resisting colon injury and regulating intestinal barrier dysfunction and gut microbiota dysbiosis; meanwhile, HRS and HAS have better improvement effects. [ABSTRACT FROM AUTHOR]

Chronic inflammatory and rheumatic diseases (CIRDs) contribute significantly to the global burden of diseases, causing pain and functional impairment in patients. Associated comorbidities lead to additional healthcare costs, lower quality of life and higher mortality rates, and might limit anti-rheumatic treatment options. This narrative review article provides an overview of the prevalence of CIRDs and current recommendations for screening and managing comorbidities in patients with CIRDs, including cardiovascular disease (CVD), malignancies, infections, gastrointestinal diseases, osteoporosis and depression. In addition, it highlights the impact of these comorbidities on the selection of disease-modifying anti-rheumatic drugs. Moreover, the review emphasizes the importance of screening for CVD risk factors and implementing lifestyle changes, exercise, and smoking cessation. Specific screening approaches for malignancies for the CIRD population are discussed, as well as vaccination recommendations, osteoporosis screening and management, and the importance of depression detection. The review identifies unmet needs for updated recommendations and personalised interventions for managing comorbidities in CIRDs beyond rheumatoid arthritis and CVD, considering the diverse therapeutic options and their effects on these comorbidities. A multidisciplinary approach is necessary to effectively address and manage these comorbidities in CIRD patients and tailor therapy to each patient profile. [ABSTRACT FROM AUTHOR]

Disorders in the inflammatory process underlie the pathogenesis of numerous diseases. The utilization of natural products as anti-inflammatory agents is a well-established approach in both traditional medicine and scientific research, with studies consistently demonstrating their efficacy in managing inflammatory conditions. Pequi oil, derived from Caryocar brasiliense, is a rich source of bioactive compounds including fatty acids and carotenoids, which exhibit immunomodulatory potential. This systematic review aims to comprehensively summarize the scientific evidence regarding the anti-inflammatory activity of pequi oil. Extensive literature searches were conducted across prominent databases (Scopus, BVS, CINAHL, Cochrane, LILACS, Embase, MEDLINE, ProQuest, PubMed, FSTA, ScienceDirect, and Web of Science). Studies evaluating the immunomodulatory activity of crude pequi oil using in vitro, in vivo models, or clinical trials were included. Out of the 438 articles identified, 10 met the stringent inclusion criteria. These studies collectively elucidate the potential of pequi oil to modulate gene expression, regulate circulating levels of pro- and anti-inflammatory mediators, and mitigate oxidative stress, immune cell migration, and cardinal signs of inflammation. Moreover, negligible to no toxicity of pequi oil was observed across the diverse evaluated models. Notably, variations in the chemical profile of the oil were noted, depending on the extraction methodology and geographical origin. This systematic review strongly supports the utility of pequi oil in controlling the inflammatory process. However, further comparative studies involving oils obtained via different methods and sourced from various regions are warranted to reinforce our understanding of its effectiveness and safety. [ABSTRACT FROM AUTHOR]

Axial Spondyloarthritis (axSpA) is a chronic, inflammatory, immune-mediated rheumatic disease that comprises two subsets, non-radiographic and radiographic axSpA, and belongs to a heterogeneous group of spondyloarthritides (SpA). Over the years, the concept of SpA has evolved significantly, as reflected in the existing classification criteria. Considerable progress has been made in understanding the genetic and immunological basis of axSpA, in studying the processes of chronic inflammation and pathological new bone formation, which are pathognomonic for the disease. As a result, new medication therapies were developed, which bring more effective ways for disease control. This review presents a brief overview of the literature related to these aspects of disease after summarising the available information on the topic that we considered relevant. Specifically, it delves into recent research illuminating the primary pathological processes of enthesitis and associated osteitis in the context of inflammation in axSpA. The exploration extends to discussion of inflammatory pathways, with a particular focus on Th1/Th17-mediated immunity and molecular signaling pathways of syndesmophyte formation. Additionally, the review sheds light on the pivotal role of cytokine dysregulation, highlighting the significance of the IL-23/17 axis and TNF-α in this intricate network of immune responses which is decisive for therapeutic approaches in the disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The safety profile of COVID-19 vaccination is well documented, but hesitancy among people with immune-mediated inflammatory diseases, often immunocompromised, remains high, partially due to a scarcity of data on safety over a longer term. We herein aimed to assess delayed adverse events (DAEs) occurring >7 days after COVID-19 vaccination in systemic lupus erythematosus (SLE) versus other rheumatic autoimmune diseases (rAIDs), non-rheumatic AIDs (nrAIDs), and healthy controls (HCs). Methods: Self-reported data were captured within the COVID-19 Vaccination in Autoimmune Diseases (COVAD)-2 online survey, which comprised >150 centres and responses from 106 countries, between February and June 2022. Logistic regression analysis adjusting for important confounders (age, sex, ethnicity) was used to compare groups. Results: Of 7203 eligible individuals, 882 (12.2%) patients had SLE, 3161 (43.9%) patients had rAIDs, 426 (5.9%) patients had nrAIDs, and 2734 (38.0%) were HCs. SLE patients had a median age of 39 years (IQR: 31–50); 93.7% were women. SLE patients reported, more frequently, major DAEs (OR: 1.6; 95% CI: 1.2–2.0; p = 0.001) and hospitalisation (OR: 2.2; 95% CI: 1.4–3.4; p < 0.001) compared to HCs, severe rashes (OR: 2.4; 95% CI: 1.3–4.2; p = 0.004) compared to people with rAIDS, and hospitalisation (OR: 2.3; 95% CI: 1.1–4.9; p = 0.029) as well as several minor DAEs compared to people with nrAIDs. Differences were observed between vaccines in terms of frequency of major DAEs and hospitalisations, with the latter seen more frequently in patients receiving the Moderna vaccine. People with SLE with no autoimmune multimorbidity less frequently reported overall minor DAEs compared to SLE patients with comorbid nrAIDs (OR: 0.5; 95% CI: 0.3–1.0; p = 0.036). Conclusion: Hospitalisations post-vaccination were more frequent in SLE patients than in HCs. Monitoring of SLE patients following COVID-19 vaccination can help in identifying DAEs early, informing patients about expected DAEs, and supporting patients, especially those with autoimmune multimorbidity. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the spine and sacroiliac joints. This review discusses recent advances across multiple scientific fields that promise to transform axSpA management. Traditionally, axSpA was considered an immune-mediated disease driven by human leukocyte antigen B27 (HLA-B27), interleukin (IL)-23/IL-17 signaling, biomechanics, and dysbiosis. Diagnosis relies on clinical features, laboratory tests, and imaging, particularly magnetic resonance imaging (MRI) nowadays. Management includes exercise, lifestyle changes, non-steroidal anti-inflammatory drugs and if this is not sufficient to achieve disease control also biological and targeted-synthetic disease modifying anti-rheumatic drugs. Beyond long-recognized genetic risks like HLA-B27, high-throughput sequencing has revealed intricate gene-environment interactions influencing dysbiosis, immune dysfunction, and aberrant bone remodeling. Elucidating these mechanisms promises screening approaches to enable early intervention. Advanced imaging is revolutionizing the assessment of axSpA's hallmark: sacroiliac bone-marrow edema indicating inflammation. Novel magnetic resonance imaging (MRI) techniques sensitively quantify disease activity, while machine learning automates complex analysis to improve diagnostic accuracy and monitoring. Hybrid imaging like synthetic MRI/computed tomography (CT) visualizes structural damage with new clarity. Meanwhile, microbiome analysis has uncovered gut ecosystem alterations that may initiate joint inflammation through HLA-B27 misfolding or immune subversion. Correcting dysbiosis represents an enticing treatment target. Moving forward, emerging techniques must augment patient care. Incorporating patient perspectives will be key to ensure innovations like genetics, microbiome, and imaging biomarkers translate into improved mobility, reduced pain, and increased quality of life. By integrating cutting-edge, multidisciplinary science with patients' lived experience, researchers can unlock the full potential of new technologies to deliver transformative outcomes. The future is bright for precision diagnosis, tightly controlled treatment, and even prevention of axSpA. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is very common worldwide, particularly in Middle-Eastern countries. Recent Lebanese studies demonstrated an improvement in vitamin D status over time. However, the comparison between the years before and during the COVID-19 outbreak has never been analyzed in the Middle-East area. This study aimed to determine the prevalence and the predictors of 25-hydroxyvitamin D (25(OH)D) levels during the last 7 years. Methods: Serum 25(OH)D levels from a large laboratory database were retrospectively collected from Hôtel-Dieu de France Hospital between January 2016 and June 2022 (N = 66,127). Data related to age, gender, season and year of sampling were also retrieved. Results: Mean age of the population was 50.6 ± 19 years, 62.7% were women, 5.3% were children and adolescents, 67.6% adults and 27% elderly. Mean serum 25(OH)D level was 25.7 ± 11.9 ng/mL. The overall population with vitamin D sufficiency (>30 ng/mL) was 31.9%. The increase in mean serum 25(OH)D observed between 2016 and 2022 was 6.36 ng/mL (p < 0.0001). The prevalence of 25(OH)D deficiency (<30 ng/mL) decreased from 76.2% in 2016 to 56.5% in 2022 (p < 0.0001) with a significant difference between the period before and during the COVID-19 outbreak (72.3% vs.42.5%, p < 0.0001). In a multivariate logistic regression, older age, female sex, summer season, years of the COVID-19 outbreak and outpatient samples were protective factors against the risk of hypovitaminosis D (p < 0.0001 for all variables). Conclusion: Our study showed a continuous positive change in vitamin D status time, most notably after the COVID-19 outbreak. Further studies are needed to assess the clinical impact of the pandemic on vitamin D status in our population. [ABSTRACT FROM AUTHOR]

Purpose of Review: Even though the burden of disease attributable to air pollution is high in the Eastern Mediterranean Region (EMR), the number of studies linking environmental exposures to negative health outcomes remains scarce and limited in scope. This review aims to assess the literature on exposure to air pollutants and perinatal health in the EMR and to explain the potential of epigenetics in exploring the processes behind adverse birth outcomes., Recent Findings: In the last three decades, hundreds of studies and publications tackled the health effects of air pollution on birth outcomes and early life development, but only a small number of these studies was conducted in the EMR. The existing literature is concentrated in specific geographic locations and is focused on a limited number of exposures and outcomes. Main limitations include inconsistent and poorly funded air quality monitoring, inappropriate study designs, imprecise and/or unreliable assessments of exposures, and outcomes. Even though the studies establish associations between air pollutants and adverse birth outcomes, the mechanisms through which these processes take place are yet to be fully understood. A likely candidate to explain these processes is epigenetics; however, epigenetics research on the impact of air pollution in EMR is still in its infancy. This review highlights the need for future research examining perinatal health and air pollutants, especially the epigenetic processes that underlie the adverse birth outcomes, to better understand them and to develop effective recommendations and intervention strategies., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Disturbed bile acid homeostasis associated with a rise of primary and a decline of secondary bile acids is a consistent finding in inflammatory bowel diseases (IBDs). Whether fecal bile acids may emerge as biomarkers for IBD diagnosis and disease severity is less clear. Our study aimed to identify associations of 18 fecal bile acid species with IBD entity and disease activity. Methods: Stool samples of 62 IBD patients and 17 controls were collected. Eighteen fecal bile acid species were quantified by LC–MS/MS using stable isotope dilution. Lipid levels normalized to a dry weight of the fecal homogenates and ratios of single bile acid species to total bile acid levels were used for calculations. Results: IBD patients exhibited altered primary and secondary bile acid ratios in stool, with notable distinctions between ulcerative colitis (UC) compared to Crohn's disease (CD) and healthy controls. Fecal calprotectin was negatively correlated with glycolithocholic acid (GLCA) and hyodeoxycholic acid (HDCA) in UC. These bile acids were reduced in stool of UC patients with fecal calprotectin levels > 500 µg/g compared to UC patients with low calprotectin levels. Moreover, negative associations of six secondary bile acids with C-reactive protein (CRP) existed in UC. In CD patients, fecal bile acids did not correlate with CRP or fecal calprotectin. Diarrhoea is common in IBD, and UC patients with diarrhoea had reduced deoxycholic acid (DCA), glycine conjugated DCA (GDCA) and lithocholic acid in stool in contrast to patients with normal stool consistency. Fecal bile acid levels were not associated with diarrhoea in CD patients. UC patients treated with mesalazine had increased levels of fecal GDCA whereas no such changes were observed in CD patients. Bile acid levels of CD and UC patients treated with biologicals or corticosteroids did not change. Relative levels of GHDCA (specificity: 79%, sensitivity: 67%) and glycochenodeoxycholic acid (specificity: 74%, sensitivity: 63%) were the most specific to distinguish UC from CD. Conclusion: Disrupted fecal bile acid homeostasis is associated with disease severity and disease symptoms in UC but not in CD, potentially aiding in distinguishing IBD subtypes and classifying the pathophysiology of diarrhoea in UC. [ABSTRACT FROM AUTHOR]

The aim of this study was to conduct a screening of potential therapeutic compounds found in the Atractylodes macrocephala rhizoma essential oil (AO) and explore its mechanism of action in the treatment of ulcerative colitis (UC). An inflammation cell model was employed in conjunction with phospho-antibody array technology to explore potential therapeutic compounds of AO and their anti-inflammatory and antioxidant effects. Furthermore, we assessed their efficacy and mechanisms of action in treating dextran sulfate sodium (DSS)-induced colitis in mice. Via the screening process, we identified atractylone (ATR) as the primary active compound in AO. It has been demonstrated that ATR can both decrease the levels of tumor necrosis factor (TNF)-α and reactive oxygen species (ROS) and increase the expression of adhesion proteins such as claudin, ZO-1, and occludin in vitro. Moreover, ATR has been shown to improve UC symptoms in vivo. Via a non-targeted metabolomics analysis of colon tissue, we identified 57 distinct metabolites that responded to ATR treatment. Subsequent analysis of the metabolic pathways revealed that the action of ATR was primarily focused on the amino acid metabolism pathway. In summary, ATR may alleviate the symptoms of UC by regulating multiple signaling pathways. Additionally, ATR has a comprehensive function in anti-inflammation, antioxidative stress, and intestinal injury reduction. [ABSTRACT FROM AUTHOR]

Introduction: Managing nutritional deficiencies is an essential component in the treatment of severe obesity. Vitamin D deficiency is often reported in investigations in severely obese cohorts. However, no prior study has summarized findings on this topic. Consequently, the aim of this systematic review and meta-analysis was to investigate the 25-hydroxyvitamin D [25(OH)D] status in individuals with severe obesity in different regions worldwide. We also evaluated levels of calcium, parathyroid hormone (PTH), and magnesium as secondary outcome measures. Methods: We searched Medline, PubMed, Scopus, the Cochrane Library, and EMBASE for relevant observational studies published in English from 2009 to October 2021. The heterogeneity index among the studies was determined using the Cochran (Q) and I2 tests. Based on the heterogeneity results, the random-effect model was applied to estimate the prevalence of vitamin D deficiency. Results: We identified 109 eligible observational studies. Overall, 59.44% of patients had vitamin D deficiency [25(OH)D <20 ng/mL], whereas 26.95% had vitamin D insufficiency [25(OH)D 20–30 ng/mL]. Moreover, the mean 25(OH)D level was 18.65 ng/mL in 96 studies. The pooled mean estimate of the serum calcium, PTH, and magnesium was 9.26 mg/dL (95% confidence interval [CI]: 9.19–9.32, I2 = 99.7%, p < 0.001), 59.24 pg/mL (95% CI: 54.98, 63.51, I2 = 99.7%, p < 0.001), and 0.91 mg/dL (95% CI: 0.84, 0.98, I2 = 100.0%, p < 0.001), respectively. The results of the subgroup analysis indicated that the mean estimates of 25(OH)D were highest in North America (21.71 ng/mL [19.69, 23.74], [I2 = 97.2%, p < 0.001]) and lowest in Southeast Asia (14.93 ng/mL [14.54, 15.33], [I2 = 0.0%, p = 0.778]). Conclusion: The results obtained showed a significant prevalence of vitamin D deficiency among severely obese individuals in various geographical regions, whereas the highest and lowest mean estimates were reported for North America and Southeast Asia, respectively. [ABSTRACT FROM AUTHOR]