The role of gut microbiota in autoimmune disease progression and therapy: a comprehensive synthesis

Autoimmune diseases arise from the immune system’s dysregulated attack on the body’s own tissues, influenced by a complex interplay of genetics, environment, and the microbiome. This comprehensive review and meta-analysis examines the dynamic relationship between gut microbiota and autoimmune diseases, highlighting their role in disease onset, progression, and potential therapeutic interventions. Emerging evidence underscores the bidirectional interactions between microbiota and immune pathways, particularly through mechanisms like mucosal immune modulation and regulatory T-cell activity. Microbiota dysbiosis, characterized by altered diversity and function, is consistently associated with autoimmune conditions such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. The review identifies critical microbiota-driven factors, including antigenic mimicry and inflammatory signaling pathways that disrupt immune tolerance and exacerbate autoimmunity. Meta-analysis findings reveal a consistent reduction in microbial diversity across autoimmune diseases, emphasizing the role of specific taxa and their metabolites in influencing disease severity and immune responses. Therapeutic strategies, such as probiotics, prebiotics, and microbiome-targeted interventions, offer promising avenues to restore microbiome balance and mitigate autoimmune inflammation. Despite significant advances, challenges in methodology, limited longitudinal studies, and heterogeneity in results highlight the need for standardized research protocols and larger, well-controlled clinical trials. Future studies should prioritize personalized approaches to microbiome modulation, integrating dietary, genetic, and environmental factors to improve disease management and prevention. This work consolidates current knowledge, providing a framework for future research and clinical applications in the field of microbiome-autoimmune interactions

Optical studies of three dimensional confinement in photonic and electronic systems.

In the first part of this thesis the optical properties of three dimensional opal photonic crystals are investigated. The samples were grown by sedimentation of silica spheres into a face centred cubic structure. Structural studies show that self-assembled opal photonic crystals are polycrystalline materials consisting of misoriented domains of size 50 μm to 100 μm. The angle dependent transmission technique is used to characterise the stop band of the samples. Due to the weak refractive index contrast in opal photonic crystals, only stop bands along the [111] direction are observed. The experimental transmission spectra are compared with theoretical transmission spectra calculated according to a three dimensional model based on the transfer matrix method. The experimental stop band is found to be six times broader than the calculated one, and also the experimental Bragg attenuation length is found to be five to seven times larger than the calculated one. Angle resolved diffraction and scattering techniques are used to investigate the origin of the discrepancies between experiment and theory. Analysis of the diffraction spectra indicate that the samples consist of misoriented domains of thickness 10 μm with a Gaussian distribution of 10° FWHM around the [111] direction. The scattering spectra show a strong resonant enhancement at the centre or edges (depending on the refractive index contrast) of the stop band. This observation is attributed to the multiple incoherent backward/forward reflections between the sample domains. By analysing the balance of photon flux originating from a slab of opal the shape of the experimental transmission stop band is fully explained. To investigate the effect of an incomplete photonic structure on the emission properties of light sources located inside the photonic crystal, the samples were infiltrated with solutions of laser dyes having fluorescence bands which overlap with the photonic gap of the host crystal. The optical fluorescence spectra reveal a stop band region with a centre varying with angle according to Bragg’s law. It is found that the fluorescence stop band is much shallower and narrower than that observed in transmission spectra. The gap narrowing in the fluorescence spectra is attributed to the scattering events inside the opal taking into account the spectral dependence of the Bragg attenuation length. High refractive index contrast opal photonic crystals are achieved by infiltration with chalcogenide glasses (AS2S3 and AsSe) by precipitation from solution. Optical imaging of the samples after infiltration shows that chalcogenide glasses tend to aggregate into submillimeter areas inside opals. Spatially resolved reflectivity spectroscopy is used to characterise the infiltrated areas. Large shifts (up to 80 nm) in the position of the stop band has been achieved from the infiltrated samples in comparison to the samples before infiltration. In the second part of this thesis, mid-infrared (2.5 μm -25 μm) intersubband transitions in the conduction band of uncoupled and vertically coupled and also in the valence band of self-assembled In(Ga)As/GaAs quantum dots are investigated using direct absorption measurements and photocurrent spectroscopy. The investigated dots show three dimensional electronic confinement. Intersubband transitions are investigated as a function of the polarisation angle of the incident radiation, external electric field and temperature. The experimental results indicate that intersubband transitions in the conduction band of the uncoupled dots are allowed for radiation polarised in the growth direction, similar to that found for quantum wells. By strongly coupling quantum dots in the growth direction (10 Å GaAs barrier between the dots) we have achieved a reversal of the intersubband selection rule for optical transitions between conduction band states, compared with that observed for uncoupled dots. We find that for strongly coupled dots the dominant absorption occurs for light polarised perpendicular to the growth direction (s-polarised), consistent with eight-band strain dependent k.p calculations. This contrasting behaviour results from the very different composition of the basis wave functions in the conduction band states for coupled and uncoupled dots due to differences in the conduction-valence band mixing. This effect enhances the oscillator strength of transitions between the ground and excited states in the conduction band for coupled dots. The results from p-type samples show that intersubband transitions in the valence band of self-assembled quantum dots are strongly polarised perpendicular to the growth direction (s polarised). The results are attributed to the anisotropy of the hole subbands and also to the strong band mixing between the valence subbands. The results suggest the suitability of strongly coupled self-assembled quantum dots and p-type quantum dots for high efficiency normal incidence infrared photo detectors

Twice-daily insulin glargine for patients with uncontrolled type 2 diabetes mellitus.

Insulin glargine is recombinant human insulin analog that is commonly used in patients with type 2 diabetes as well as those with type 1 diabetes. Pharmacokinetic and pharmacodynamics studies of insulin glargine had shown that it has an onset of action that ranged from 1.2 to 1.8 h while its duration of action is 18 to 26 h. Because of its long duration of action insulin glargine is usually prescribed once daily. However, several reports have shown that the administration of insulin glargine once daily is not enough to achieve adequate glucose control in some patients requiring a twice daily dosing. The first report on using insulin glargine twice daily was published shortly after its availability. It described a patient with type 1 diabetes who had consistently elevated bedtime glucose values on once daily insulin glargine administered in the evening. There was significant improvement in glucose values after changing the frequency of insulin glargine to twice daily as a split dose every 12 h. Albright and colleagues found that twice daily glargine therapy was required in patients with type 1 diabetes who developed morning hypoglycemia and/or afternoon hyperglycemia while on once daily therapy; the twice daily regimen was associated with a significant reduction in HbA1c levels compared to patients who were on once daily therapy

OP0098 SUICIDAL BEHAVIOUR IN FIBROMYALGIA PATIENTS: META-ANALYSIS AND SYSTEMATIC REVIEW OF THE LITERATURE

n/

Folate and B12 Levels Correlate with Histological Severity in NASH Patients

Background: The correlation between abnormal vitamin serum levels and chronic liver disease has been previously described in literature. However, the association between the severity of folate serum levels (B9), vitamin B12 and nonalcoholic steatohepatitis (NASH) has not been widely evaluated. Therefore, the aim of this study was to investigate the existence of such a correlation in a cohort of NASH patients. Methods: All patients aged 18 years and older who were diagnosed with biopsy-proven NASH at the EMMS hospital in Nazareth during the years 2015–2017 were enrolled in this study. Data regarding demographic, clinical and laboratory parameters was collected. Patients with other liver diseases were excluded. Results: Eighty-three NASH patients were enrolled during the study period. The mean age was 41 ± 11 years and the majority of patients were male. Mean values of folate and B12 were 9.85 ± 10.90 ng/mL and 387.53 ± 205.50 pg/mL, respectively. Half of the patients were presented with a grade 1 steatosis (43.4%), a grade 2 fibrosis (50.6%) and a grade 3 activity score (55.4%). The fibrosis grade was significantly correlated with low folate levels on multivariate analysis (p-value < 0.01). Similarly, low B12 levels were significantly associated with a higher fibrosis grade and NASH activity (p-value < 0.001 and p-value < 0.05 respectively). Conclusion: Our study demonstrated a statistically significant correlation between low levels of folate and vitamin B12 with the histological severity of NASH. These findings could have diagnostic and therapeutic implications for patient management and follow-up

Comparison between Efficacy of Human Milk Fortification Using Human Milk Fortifier versus Preterm Formula: A Retrospective Single-institutional Experience

Objectives: This study sought to evaluate the relative efficacy of expressed breast milk (EBM) fortified using human milk fortifier (HMF) compared to commercial preterm formula (PF) on preterm and very low birth weight (VLBW) infants in a major tertiary healthcare center in Oman. Methods: This retrospective cohort study included two cohorts of preterm (< 32 weeks gestation) or VLBW infants (birth weight < 1500 g) treated in the neonatal intensive care unit (NICU). Cohort one included infants who were given PF-fortified EBM between January and December 2016, and cohort two were given newly-introduced HMF-fortified EBM between November 2018 and December 2019. Analysis was performed to compare the cohorts with respect to baseline characteristics, primary outcomes, and secondary outcomes. Results: A total of 103 neonates were included (cohort 1: n = 55, cohort 2: n = 48). There were no significant differences in the growth of the weekly length, the growth of the head circumference, or discharge growth parameters. Compared to PF, HMF was associated with significantly better weight gain velocity (g/kg/day) during the first week (p =0.009) and second week (p =0.050) after starting fortification, lower need for other adjunctive forms of fortification (p =0.035), and lower rates of necrotizing enterocolitis in premature infants or VLBW (p =0.018). Conclusions: This is likely to be the first study to analyze the relative efficacy of HMF and PF in the Middle East. The results of this study will be helpful in guiding standards of nutritional care in NICUs in Oman

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Ramadan Fasting Exerts Immunomodulatory Effects: Insights from a Systematic Review

Ramadan is the ninth month of the Islamic lunar calendar and is observed by Muslims as a month of fasting. All Muslim adults are expected to fast; nevertheless certain subgroups, including sick, frail subjects, and pregnant women, among others, are exempted. Ramadan fasting has been shown to impact on body systems in different manners. The influence of Ramadan fasting on immune system regulation remains elusive; however, immune system changes, such as the modulation of body response to various infectious, stressful, and other harmful events, are of great interest during fasting. In this paper, we performed an extensive systematic literature review of different scholarly databases (ISI/Web of Science, Scopus, PubMed,/MEDLINE, Google Scholar, Directory of Open Access Journals, EbscoHOST, Scirus, Science Direct, the Cochrane Library, and ProQuest), using the following key words: “fasting,” “Ramadan,” “Islam,” and “immunity.” Conclusions drawn from these findings included: (1) Ramadan fasting has been shown to only mildly influence the immune system and the alterations induced are transient, returning to basal pre-Ramadan status shortly afterward. (2) Ramadan fasting during the second trimester of pregnancy was shown to be safe and did not result in negative fetal outcomes, or maternal oxidative status alterations. (3) In cardiac patients, Ramadan fasting can have beneficial effects including lipid profile improvement and alleviation of oxidative stress. (4) In asthmatic patients as well as in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and autoimmune disorders, fasting was safe. (5) In psychiatric patients, such as those suffering from schizophrenia, fasting could increase immunologic markers. (6) Fasting Muslim athletes who maintain intensive training schedule during Ramadan showed fluctuations of immunologic markers

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030