Disease Symptoms Research Articles

P1281 Active perianal fistulising Crohn’s Disease is associated with a higher burden of psychological distress, depression, anxiety, stress and opioid use

Abstract Background Perianal fistulising Crohn’s disease (PFCD) is an aggressive phenotype of Crohn’s disease (CD) which can cause pain, sepsis and faecal incontinence with relevant impairment in quality of life (QOL). We aimed to describe the effect of PFCD on QOL as measured by mental health indicators, opioid use and days out of role (DooR) due to inflammatory bowel disease (IBD) symptoms. Methods Crohn’s Colitis Care (CCCare) is a cloud-based clinical management system which has been used in routine clinical care in Australia and New Zealand since 2018. The CCCare Clinical Registry was interrogated in September 2024. Adults with CD across 25 IBD centres with an outpatient encounter between September 2023 and September 2024 were included. Mental health was assessed using the Kessler Psychological Distress Scale (K10) and the Depression Anxiety and Stress Scale (DASS-21). Results A total of 8317 people were identified with CD, of whom 2.7% (n = 222) had active PFCD, defined as a fistula on the most recent physical examination, imaging or endoscopy. Another 4.6% (n = 379) had previously documented PFCD and 92.8% (n = 7716) never had documented PFCD. The median age of the cohort was 42.0 years (IQR 30.0 – 57.0) with an even gender distribution (50.1% female). Most of the cohort resided in Australia (63.1%, n = 5249) and the remaining 36.9% in New Zealand (n = 3068). People with active PFCD were more likely to be currently using opioid analgesia for their IBD (2.7% vs 0.5% vs 0.2%; p < 0.01) and to have at least one DooR since their last clinical assessment (12.7 vs 6.9 vs 6.0%; p < 0.01) compared to those with previous or never PFCD. People with active or previous PFCD were more likely to actively smoke than those without PFCD ever (14.4 vs 14.2 vs 7.3%; p < 0.01). 303 people had a completed DASS-21 and 141 a K10 within the study period. People with active PFCD had numerically higher median scores across all mental health indices but there was no statistically significant difference. A numerically higher percentage of people with active PFCD were experiencing psychological distress or reported at least mild anxiety, depression or stress compared to those with previous or have never had PFCD (table 1). Conclusion People with active PFCD have higher rates of opioid use, more time out of role, and higher scores in K10 and DASS-21 compared to those with previous PFCD or never had PFCD. This highlights the psychosocial burden on PFCD, and therefore the need to optimise management of PFCD as well as address psychiatric comorbidities. People with active PFCD were more likely to be active smokers, emphasising the importance of addressing smoking cessation in the multidisciplinary management approach.

P1213 The role of stress in dietary choices and disease outcomes in Inflammatory Bowel Disease

Abstract Background The role of nutrition in managing Inflammatory Bowel Disease (IBD) is widely discussed, yet its interplay with stress-related factors influencing eating behaviour and disease management remains complex. Stress-induced eating behaviours, such as increased comfort foods consumption, may exacerbate symptoms and hinder effective disease management, impacting clinical outcomes and quality of life. This study, part of EU-funded MiGut-Health project, assesses the relationship between stress, eating behaviours, and disease management in IBD patients, focusing on comfort food consumption, psychological food involvement, and disease-related factors, including health engagement, stool consistency, and disease activity. Methods In August 2024, a cross-sectional study was conducted applying an online survey to a cohort of 2,276 adult IBD patients across Italy. The survey included validated scales: the Patient Health Engagement Scale (PHE-s), Psychological Food Involvement Scale (PFIS), Perceived Stress Scale (PSS-10), Salzburg Stress Eating Scale, Inflammatory Bowel Disease Symptom Inventory (IBDSI-SF), and Bristol Stool Chart, along with items on Comfort Food Consumption. Data analysis involved descriptive analysis and independent samples t-test. Results Participants reported moderate perceived stress (mean=17.3 ± 7.75), with 35.5% indicating increased comfort food consumption when stressed, primarily chocolate (23.2%), sweet snacks (22.0%), and savoury snacks (21.0%). Individuals with high stress (32.6%) were more likely to consume fast food (mean=0.4 ± 0.66, p < 0.001) and sweetened beverages (mean=0.7 ± 1.21, p < 0.001). They placed greater importance on comfort food groups for managing stress (mean=2.7 ± 1.17 vs 2.5 ± 1.14, p < 0.001). Disease activity was notably higher in the high-stress group (mean=29.2 ± 15.61 vs. 16.8 ± 11.66, p < 0.001), alongside looser stool consistency (mean=4.8 ± 1.59 vs. 4.3 ± 1.45, p < 0.001). High-stress patients also demonstrated lower health engagement (mean=2.1 ± 0.68 vs. 2.6 ± 0.74, p < 0.001) and reduced psychological food involvement (mean=4.1 ± 1.17 vs. 4.4 ± 1.09, p < 0.001). Conclusion Stress significantly shapes eating behaviours and disease management in IBD patients. High stress correlates with increased comfort foods consumption, reduced psychological food involvement, and poorer disease outcomes, including heightened symptoms, looser stool consistency, and diminished health engagement. These findings highlight the complex relationship between stress and disease-related factors, suggesting the need for integrated interventions targeting stress management to improve dietary behaviours and overall disease management in IBD.

P0713 Feasibility of a Physical Activity intervention in Patients with IBD - the PASIBO Study

Abstract Background Recent studies suggest that physical activity (PA) may improve the quality of life and relieve fatigue in patients with inflammatory bowel disease (IBD). However, there is no consensus as to what type of PA intervention should be offered to patients with IBD and barriers related to stigmatization and disease symptoms calls for an individually tailored approach. We developed a PA intervention involving patients, health professionals and other stakeholders in a co-creation process. This study aims to determine the feasibility and acceptability of a tailored PA intervention in adult men and women with IBD, focusing on recruitment, retention and outcome assessments. Methods In a randomized, controlled feasibility study, 30 patients with IBD were recruited from Digestive Disease Center, Bispebjerg Hospital, Copenhagen and randomized to an intervention (n=15) or a control (n=15) group. The 20-week intervention comprised group-based education, four nurse-led motivational interviews and three optional components (individual physiotherapy session, exercise ‘buddy’ and/or exercise videos). Outcome assessments at baseline and after 20 weeks, included accelerometer-measured PA, patient-reported outcomes, cardiometabolic biomarkers and anthropometrics. Interviews with participants informed intervention acceptability. Results A total of 164 participants were screened to enroll 30 patients with IBD. Hereof 47% were women, mean age was 39.7 years (SD 13.7), and 57% had Crohn’s disease, while 43% had ulcerative colitis (table 1). Participants in the intervention group were slightly younger, were more often co-habiting, more frequently employed and had more co-morbidity than participants in the control group (table 1). All participants completed the 20-week outcome assessment, and all 15 intervention participants completed the four motivational sessions, setting personalized goals. The most common goals were increasing active transportation and daily walking. Most participants chose to add videos or a physiotherapy session, while none selected the exercise ‘buddy’ option. Interviews highlighted the importance of the personalized approach and the focus on the full PA spectrum. The chosen outcome measures appeared feasible, and findings pre/post intervention indicated a potential beneficial impact of PA on fatigue and Quality of life in the intervention group (Table 2). Conclusion The study showed that an individually tailored PA intervention focusing on motivation and opportunities to increase PA in daily life is feasible and acceptable. The results are informing a subsequent, adequately powered, multi-centre trial.

A Model for Detecting Xanthomonas campestris Using Machine Learning Techniques Enhanced by Optimization Algorithms

The bacterium Xanthomonas campestris poses a significant threat to global agriculture due to its ability to infect leaves, fruits, and stems under various climatic conditions. Its rapid spread across large crop areas results in economic losses, compromises agricultural productivity, increases management costs, and threatens food security, especially in small-scale agricultural systems. To address this issue, this study developed a model that combines fuzzy logic and neural networks, optimized with intelligent algorithms, to detect symptoms of this foliar disease in 15 essential crop species under different environmental conditions using images. For this purpose, Sugeno-type fuzzy inference systems and adaptive neuro-fuzzy inference systems (ANFIS) were employed, configured with rules and clustering methods designed to address cases where diagnostic uncertainty arises due to the imprecision of different agricultural scenarios. The model achieved an accuracy of 93.81%, demonstrating robustness against variations in lighting, shadows, and capture angles, and proving effective in identifying patterns associated with the disease at early stages, enabling rapid and reliable diagnoses. This advancement represents a significant contribution to the automated detection of plant diseases, providing an accessible tool that enhances agricultural productivity and promotes sustainable practices in crop care.

Blockade of mGluR1 and mGluR5 in the lateral habenula produces the opposite effects in the regulation of depressive-like behaviors in the hemiparkinsonian rats.

Depression is one of the most common non-motor symptoms in Parkinson's disease (PD) and the hyperactivity of the lateral habenula (LHb) may contribute to depression. The present study was performed to investigate the effects and mechanisms of group I metabotropic glutamate receptors (mGluRs) in the LHb on PD-related depressive-like behaviors. Unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) were used to establish the PD rat model. The group I mGluRs agonist and antagonists for mGluR1 and mGluR5 were microinjected into the LHb to observe their effects on PD-related depressive-like behaviors, electrical activities of the LHb, release of monoamines in the medial prefrontal cortex (mPFC) in sham and the lesioned rats. Lesions of the SNc induced depressive-like behaviors and hyperactivity of LHb neurons. Activation of group I mGluRs by 3,5-DHPG induced or enhanced depressive-like behaviors, increased the firing rate of the LHb neurons, and decreased dopamine (DA) and serotonin (5-HT) levels in the mPFC in the two groups of rats. Blockade of mGluR1 by YM298198 also produced similar effects with 3,5-DHPG, however, blockade of mGluR5 by MTEP produced opposite effects. Western blotting data showed that lesions of the SNc in rats down-regulated the expression of mGluR1 and mGluR5 in the LHb. These results suggest that mGluR1 and mGluR5 in the LHb induce opposite effects on depressive-like behaviors, which may attribute to the changed firing rate of LHb neurons by the presynaptic and postsynaptic mechanisms, and the changes in the monoamine levels.

Pallidothalamic Circuit-Selective Manipulation Ameliorates Motor Symptoms in A Rat Model of Parkinsonian.

Deep brain stimulation (DBS) effectively treats motor symptoms of advanced Parkinson's disease (PD), with the globus pallidus interna (GPi) commonly targeted. However, its therapeutic mechanisms remain unclear. We employed optogenetic stimulation in the entopeduncular nucleus (EP), the rat homologue of GPi, in a unilateral 6-OHDA lesioned female Sprague Dawley rat model of PD. We quantified behavioral effects of optogenetic EP DBS on motor symptoms and conducted single-unit recordings in EP and ventral lateral motor thalamus (VL) to examine changes in neural activity. Behavioral tests showed high-frequency optogenetic EP DBS (75, 100, 130Hz) reduced ipsilateral turning and corrected forelimb stepping, while low-frequency (5 and 20Hz) had no effect. EP and VL neurons exhibited mixed response during stimulation, with both increased and decreased firing. Notably, the average firing rate of all recorded neurons in the EP and VL significantly increased at 130 Hz but not at other frequencies. While beta-band oscillatory activity was reduced in most EP neurons across high frequencies (75, 100, 130 Hz), reductions in beta-band oscillations with the VL occurred only at 130 Hz. These findings suggest that the neural firing rates within EP and VL circuits were differentially modulated by EP DBS, they may not fully explain the frequency-dependent behavioral effect. Instead, high-frequency optogenetic EP DBS at 130Hz may ameliorate parkinsonian motor symptoms by reducing abnormal oscillatory activity in the EP-VL circuits. This study underscores the therapeutic potential of circuit-specific modulation in the pallidothalamic pathway using optogenetic EP DBS to alleviate motor deficits in a PD rat model.Significance Statement The contribution of EP local cells to the therapeutic effects of EP DBS in PD has been unclear. Our study addressed this by employing local cell-specific optogenetic stimulation. Directly stimulating EP local neurons using optogenetics effectively reduced parkinsonian symptoms in the 6-OHDA lesioned rat. These findings highlight the importance of precise circuit manipulation through optogenetic techniques within the pallidothalamic pathway, suggesting a promising approach for ameliorating motor deficits in PD.

Effect of management system and pedoclimatic factors on Fusarium and Didymella communities associated with pea (Pisum sativum) roots in Germany

From 2016 to 2019, 128 organic and conventional spring and winter pea fields in Germany were surveyed to determine the effects of cropping history and pedo-climatic conditions on pea root health, the diversity of Fusarium and Didymella communities and their collective effect on pea yield. Roots generally appeared healthy or showed minor disease symptoms despite the frequent occurrence of 4 Didymella and 14 Fusarium species. Soil pH interacted with the occurrence of the Fusarium oxysporum species complex (FOSC) and F. tricinctum that correlated with reduced or increased soil pH values, respectively. While legumes in the cropping history or reduced time between legumes correlated with occurrence of D. pinodella and to a lesser degree with the members of the F. solani species complex (FSSC), the reverse was true at least in organic spring peas for F. redolens. Only in conventional systems increased root infections with F. redolens and the FSSC were linked to root rot incidence whereas yields negatively correlated with the FOSC and positively with F. tricinctum isolation frequencies. Overall, this study shows that pea root rot pathobiome is rather stable and that the damage caused is mostly due to the interaction with environmental conditions.

An S100A8/A9 neutralizing antibody potently ameliorates contact hypersensitivity and atopic dermatitis symptoms.

Contact hypersensitivity (CHS) and atopic dermatitis (AD) are pervasive inflammatory skin diseases with similar symptoms, and the global prevalence of both conditions is steadily rising. Many compounds and biotics have been developed to target molecules critical to the etiology or pathogenesis of CHS and AD. However, such molecules are sometimes ineffective or lose potency over the therapeutic course. Therefore, innovative medicines are still needed for the treatment of intractable cases. We have been focused on S100A8/A9, a heterodimer complex of S100A8 and S100A9 abundant in the extracellular milieu of the inflammatory skin lesion. Although S100A8/A9 is recognized primarily as a diagnostic marker protein, we previously showed that it also plays a crucial role in CHS and AD progression. This insight inspired us to develop its inhibitory antibody, leading to the groundbreaking Ab45. In the present study, we demonstrated that Ab45 effectively prevented disease symptoms in various models, and that its disease-ameliorating activity likely involves the downregulation of several disease-relevant molecules, including Il-23a, Il-36g, S100a8, and S100a9. We also created a humanized version of Ab45, HuAb45, which exhibited similar effectiveness. These antibodies show great promise for the treatment of CHS and AD, and possibly for other inflammatory skin diseases as well.

Molecular Characterization of Yellow Mosaic Disease Causing Begomoviruses in Pigeonpea (Cajanus cajan L.) from Three Agro-ecological Zones of India.

Pigeonpea (Cajanus cajan L.) plants exhibiting symptoms of yellow mosaic disease (YMD) were collected in winter 2023 from multiple agricultural fields of Kanpur, Sehore, and Madhubani, representing three different agro-ecological zones in India. The recorded disease incidence ranged from 3 to 5%, 1 to 4%, and 12 to 20% in these zones, respectively. This study aimed to identify and characterize the causal agent, suspected to be a begomovirus, an emerging plant pathogen of pigeonpea causing YMD. Total DNA was extracted from 28 YMD-affected leaf samples and subjected to rolling circle amplification for PCR-based virus detection. Of all the tested samples, one tested positive for mungbean yellow mosaic virus (MYMV), while the remaining tested positive for mungbean yellow mosaic India virus (MYMIV). Subsequently, PCR-based amplification and sequencing of the full-length DNA-A and DNA-B components were conducted. BLASTn analysis revealed that the assembled sequences of the DNA-A and DNA-B components had the highest nucleotide identity with MYMIV (DNA-A: 97-99%, DNA-B: 95-97%) and MYMV (DNA-A: 99%, DNA-B: 98%). Phylogenetic analysis supported these findings. Additionally, the DNA-A and DNA-B components obtained from each sample were found to be cognate, with over 92% similarity in their common region. Thus, the cognate DNA components constituted the isolates of MYMIV and MYMV identified from pigeonpea. The identified isolates exhibited the typical genome organization of an Old World bipartite begomovirus, with no recombination events detected. This study reports, for the first time, the complete annotated genomes of MYMIV from Sehore and Madhubani, as well as MYMIV and MYMV from Kanpur, infecting pigeonpea.

FIRST DATA ON THE MOLECULAR GENETIC DIVERSITY OF HHV6B AND ITS IMPACT ON THE CLINICAL AND LABORATORY COURSE OF MONONUCLEOSIS-LIKE SYNDROME IN CHILDREN

Human herpes virus 6B (HHV6B) is a ubiquitous causative agent of mononucleosis-like syndrome (MLS) and other diseases. The diversity of HHV6B infection may be due to virus genetic polymorphism. Molecular genetic diversity of circulating HHV6B, as well as its impact on the clinical and laboratory features of HHV6B infection have not been studied. The aim of the work was to study the intraspecific diversity of HHV6B circulating among children in Nizhny Novgorod (Russia) region, and to investigate its effect on MLS clinical and laboratory features. Blood leukocytes and saliva DNA samples from healthy children and children with HHV6B infection were analyzed for HHV6B DNA detection. Original intraspecific HHV6B classification based on detecting signature nucleotide substitutions in the sequence of the U90 gene fragment, was used for virus typing. A relationship between HHV6B genovariant and clinical/laboratory MLS characteristics was studied using multivariate statistical methods. Circulation of four HHV6B genovariants was shown among children in Nizhny Novgorod region: HHV6B/GV2e, HHV6B/GV2b (dominant genovariants), HHV6B/GV1a and HHV6B/GV2a (minor genovariants). Children with MLS infected with HHV6B/GV2e genovariant were more likely to have laboratory signs of cytolysis and increased peripheral blood lymphocyte count. Children with MLS infected with the HHV6B/GV2b genovariant were more likely to have higher mature neutrophil level. An increase of HHV6B viral load in leukocytes was accompanied by aggravated intoxication symptoms. Co-infection with the Epstein-Barr virus (EBV) led to more severe symptoms of acute tonsillitis, hepatosplenomegaly, and lymphadenopathy. Patients with EBV were more likely to have higher ALAT and lymphocyte level along with decreased mature neutrophil count. In children with MLS, EBV coinfection caused smaller HHV6B viral load in blood leukocytes (in children with HHV6B DNA 10 or more copies/105 cells) and lower HHV6B DNA detection frequency in saliva (in children with HHV6B DNA less than 10 copies/105 leukocytes). The results show the influence of genetic HHV6B polymorphism upon the clinical and laboratory features of MLS in children, and also demonstrate that HHV6B/GV2e and EBV cause similar disease symptoms.

Metabolic, hormonal profiles and comorbidities in pituitary Cushing’s syndrome, adrenal Cushing’s syndrome and mild autonomous cortisol secretion: a comparative study

ABSTRACT Purpose Our study aimed to discern disparities in metabolic, hormonal profiles, and comorbidities among patients with pituitary Cushing (PC), adrenal Cushing (AC), and Mild autonomous cortisol secretion (MACS). Methods We conducted a retrospective analysis involving 76 patients diagnosed with PC (n = 26), AC (n = 21), and MACS (n = 29) at our clinic. We compared the groups’ demographic data, clinical characteristics, biochemical profiles, hormonal analyses, and surgical interventions. Results No significant differences were noted in age, height, body mass index, or gender distribution among the groups, although a higher proportion of females was observed across all three groups. However, PC patients exhibited markedly elevated 24-hour urinary cortisol levels compared to AC and MACS patients. Furthermore, alanine aminotransferase, triglycerides, very low-density lipoprotein, insulin, and basal cortisol levels were significantly elevated in PC and AC cases compared to MACS cases. Interestingly, no significant differences were observed in terms of comorbidities among the groups. Conclusion Our findings suggest that urinary cortisol levels were significantly higher in the PC group than in the AC and MACS groups, potentially indicating that high-amplitude adrenocorticotropic hormone stimulation may lead to increased cortisol secretion in PC patients. The increased utilization of imaging methods has facilitated the earlier detection of adrenal incidentalomas, enabling the diagnosis of adrenal Cushing’s cases with milder cortisol elevations. Additionally, the severity of disease symptoms worsens with increasing cortisol levels.Notably, moderate increases in cortisol are associated with heightened comorbidities, underscoring the importance of vigilant management in Cushing’s syndrome patients. Despite a lower degree of hypercortisolism in MACS, there were no differences in comorbidities, suggesting that even mild cortisol secretion abnormalities are sufficient to establish the presence of comorbidities. Even moderate increases in cortisol levels can impact bone metabolism.

Characterizing Parkinson's Disease-Associated Pain in Native Patients with Malayalam Version of the King's Parkinson's Disease Pain Scale.

Pain is an important non-motor symptom in Parkinson's disease (PD) and is often under-recognized. Pain is also a symptom frequently reported by non-PD elderly subjects. The King's Parkinson's Disease Pain Scale (KPPS) is a valid tool to characterize and quantify pain in PD and has been translated into several languages. We translated KPPS to Malayalam for native patients with PD and examined the pain characteristics in consecutive patients. Correlations with comprehensive disease-specific rating scales, including the Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Non-Motor Symptoms Scale (NMSS), were explored. A group of age- and gender-matched subjects without PD were interviewed using KPPS to examine how the pain reported by the non-PD aging population is different from that in PD. In this study, 82% of patients with PD reported at least one type of pain, compared to 31.3% of age- and gender-matched control subjects (P < 0.001). KPPS total scores (18.2 ± 14.0 vs. 1.8 ± 3.2; P < 0.001) and all the individual domain scores were significantly higher in patients. Pain scores correlated with age in control subjects (R = 0.46, P < 0.001), but not in patients; females reported more pain in both groups. Patients' pain scores were higher in the postural instability and gait difficulty subtype and showed significant correlations with MDS-UPDRS and NMSS scores. Pain is a prevalent symptom in PD and differs from the pain reported by a non-PD aging population. The Malayalam version of KPPS is a valid tool to characterize pain in native, Malayalam-speaking patients.

Poliprotect®, a Medical Device Made of Substances, Potently Protects the Human Esophageal Mucosa Challenged by Multiple Agents: Evidence from In Vitro and Ex Vivo Electrophysiological Models.

The integrity of esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD) or GERD-like symptoms is the first mechanism of protection to decrease the sensitivity to gastric reflux and heartburn symptoms. We investigated the protective effects of Poliprotect® (PPRO), a CE-marked medical device, on esophageal epithelial integrity using in vitro and ex vivo models. In vitro, the protective effects of PPRO were tested on Caco-2 cells. PPRO demonstrated safety and protection against oxidative damage induced by hydrogen peroxide. It also preserved epithelial integrity by maintaining transepithelial electrical resistance (TEER) against damage from calcium removal or bile acid exposure (taurodeoxycholic acid, TDCA). Ex vivo, esophageal biopsies from patients subjected to endoscopy were mounted in Ussing chambers and exposed to damaging agents (HCl or HCl + TDCA). Untreated biopsies (control) showed significant loss of epithelial resistance (up to -33%). In contrast, low concentrations of PPRO (50-100 µg/mL) provided strong protection against these damages (p < 0.001), even after 60 min of washing. Histological analysis confirmed the barrier-enhancing effect of PPRO. Overall, PPRO effectively protected the esophageal epithelium from damage in both models, suggesting its potential role in alleviating GERD or GERD-like symptoms by strengthening mucosal barriers and reducing epithelial sensitivity to reflux.

The effects of intermittent fasting on antioxidant and inflammatory markers and liver enzymes in postmenopausal, overweight and obese women with rheumatoid arthritis: a randomized controlled trial

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting postmenopausal women. This study investigated the effects of intermittent fasting (IF) on antioxidant and inflammatory markers and liver enzymes in postmenopausal, overweight and obese women with RA. This 8-week randomized controlled trial included 44 postmenopausal women with RA divided into an intervention group following a 16:8 IF diet and a control group maintaining their usual diet and received recommendations for healthy eating. Inflammatory indices, oxidative stress markers, and liver enzymes were measured at baseline and post intervention. The IF group showed significant decreases in serum malondialdehyde (MDA) levels (P = 0.02) and neutrophil-to-lymphocyte ratio (P = 0.018) and increased catalase levels (P = 0.004) compared to the control group. Liver enzymes aspartate transaminase (AST) and alanine transaminase (ALT) also decreased significantly in the IF group (P = 0.02 and P = 0.03, respectively). No significant differences were observed in the other measured parameters between groups. In conclusion, the 16:8 IF diet demonstrated beneficial effects on some oxidative stress markers, inflammatory indices, and liver enzymes in postmenopausal, overweight, and obese women with RA. These findings suggest that IF may be an effective non-pharmacological intervention for managing RA in this population, potentially addressing both primary disease symptoms and associated metabolic complications. Further research is needed to elucidate the long-term effects and mechanisms of IF in the management of RA.

Position statement of the Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the management of inflammatory bowel disease in Primary Care

Primary Care is the first point of contact for most patients after the onset of symptoms of inflammatory bowel disease (IBD). Establishing an initial diagnostic process based on compatible symptoms and agreed criteria and referral pathways, depending on the degree of suspicion and the patient's situation, can reduce diagnostic delays. Once the patient is referred to the Digestive specialist and the diagnosis of IBD is established, a treatment and follow-up plan is structured. The management of the patient must be shared with the participation of the family practitioners in the diagnosis and treatment of concomitant or intercurrent pathologies, the recognition of flare-ups or complications (of IBD or treatments), education tasks or adherence control. With the purpose of developing a comprehensive guide on the management of IBD aimed at Primary Care doctors, we have developed this positioning document collaboratively between the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU).

Hepatoprotective Potential of Indian Medicinal Plants.

The liver is essential for both the body's removal of waste materials and the metabolism of nutrients, it is critical for sustaining general health. However, a number of factors, including viral infections, immune system malfunctions, cancer, alcohol intake, and drug toxicity, are contributing to the rising prevalence of liver problems. Alternative approaches to liver disease treatment are being investigated due to the potential limitations of conventional medical treatments. In this regard, the possible hepatoprotective effects of medicinal plants containing bioactive chemicals high in antioxidants have drawn attention. This review's objective is to provide an overview of the Indian medicinal plants' therapeutic value. A variety of databases, including PubMed, Web of Science, Scopus, Academic Journals Embase, Google Scholar, and Science Direct, were searched for relevant literature using keywords such as "hepatoprotective," "hepatotoxins," "medicinal plants," and "phytoconstituents". This article focuses on plant-based medicines that guard against oxidative stress and pollutants, highlighting the potential of herbal remedies as alternatives to traditional liver disease treatments. Reviewing the hepatoprotective qualities of a number of medicinal plants, such as Ginkgo biloba, Woodfordia fruticosa, Thymus quinquecostatus, and Terminalia arjuna, offer more details about their effectiveness. Terminalia arjuna: Preclinical research demonstrates a 30-40% decrease in liver enzyme levels and a 50-60% rise in antioxidant indicators; clinical trials reveal a 25-30% decrease in liver enzyme levels. Thymus quinquecostatus: Research on animals shows a 35-45% decrease in liver enzymes, and preliminary clinical findings indicate a 20-30% improvement in liver function. Woodfordia fruticosa: Although clinical evidence is not as strong as preclinical trials, early investigations indicate a 25-35% improvement in liver enzymes and a 50-60% reduction in liver damage indicators. Ginkgo biloba: Shown enhanced liver function and a 40-50% decrease in liver enzymes; clinical trials have also shown improvements in liver enzymes and a 20-30% decrease in fibrosis markers in NAFLD patients. In conclusion, the increased prevalence of liver diseases emphasizes the necessity for nonconventional therapeutic options. Medicinal plants, as opposed to conventional medicines, have promising hepatoprotective effects with fewer adverse effects since they include bioactive substances such as sterols, anthocyanins, terpenoids, saponin glycosides, and polyphenolics. Clinical trials have shown the potential of some plant medications to support liver health. For example, clinical trials have demonstrated the effectiveness of Picrorhiza kurroa in treating liver disorders including viral hepatitis, with a notable decrease in liver enzyme levels. Xanthones found in Garcinia mangostana have been shown in preclinical and clinical trials to have liver-protective qualities, enhancing liver function and lowering oxidative stress indicators. Clinical research has demonstrated that citrus medica helps people with liver problems by reducing inflammation and improving liver function. Anthocyanin-rich Vaccinium myrtillus (Bilberry) has been shown to lower oxidative stress and enhance liver enzyme profiles in fatty liver disease patients. These plant-based medicines can greatly enhance the treatment arsenal for liver ailments by addressing the underlying causes and symptoms of liver diseases. In order to substantiate their role in hepatoprotection, future research should concentrate on verifying these findings through additional clinical trials.

Subthalamic and nigral stimulation for freezing of gait in Parkinson's disease: Randomized pilot trial

Background Freezing of gait (FoG) is a debilitating symptom of Parkinson's disease (PD) with limited response to dopaminergic medication and subthalamic deep brain stimulation (STN-DBS). Substantia nigra pars reticulata (SNr) stimulation could improve FoG. Objective To analyze the effect of combined STN-SNr stimulation at different frequencies on FoG. Methods We performed a double-blind, cross-over, randomized pilot trial involving STN-DBS treated PD patients with FoG. Participants received: high-frequency (HF) STN-DBS (S), combined HF-STN and SNr stimulation (C1), and combined HF-STN and low-frequency (LF) SNr stimulation (C2), for one month each. The primary endpoint was the score change in the New-Freezing-of-Gait-Questionnaire (NFOG-Q). Secondary analyses were performed on motor complications, axial symptoms, daily living activities, psychiatric symptoms, sleep, and patient preference. Results Fifteen patients received at least one combined stimulation. No significant difference in NFOG-Q scores was found between S, C1, and C2; one-third of patients showed a clinically significant improvement (≥8 points) with combined stimulations. Motor complications improved significantly with C1 and C2 (C1-S: 3.6 ± 3.8 vs. 4.9 ± 3.8, p = 0.046; C2-S: 2.7 ± 3.1 vs. 4.9 ± 3.8, p = 0.005). 80% of patients preferred the combined STN-SNr stimulation while blinded. All adverse events were manageable. Conclusions Our study did not prove a statistically significant improvement in NFOG-Q with STN-SNr stimulation; however, one-third of patients experienced a clinically meaningful FoG improvement, and the majority preferred to maintain STN-SNr stimulation. STN-SNr stimulation was both safe and effective in addressing motor complications and improving sleep quality, highlighting the importance of further exploration into the effects of combined STN-SNr stimulation.

Opicapone for Parkinson's disease-related sleep disturbances: The OASIS clinical trial

Background While sleep disturbances are among the most frequent non-motor symptoms of Parkinson's disease (PD), there is a lack of evidence to support its treatment. Objective To evaluate the efficacy of opicapone 50 mg in treating sleep disturbances in patients with PD and end-of-dose motor fluctuations. Methods OASIS was an exploratory, open-label, single-arm clinical trial in PD patients with end-of-dose motor fluctuations and associated sleep disturbances. The primary endpoint was change from baseline to week 6 in Parkinson's Disease Sleep Scale 2 (PDSS-2). Secondary endpoints included functional motor and non-motor assessments (Movement Disorder Society [MDS]-Unified Parkinson's Disease Rating Scale [UPDRS], MDS-Non-motor Scale [NMS], 8-item PD Questionnaire [PDQ-8], 16-item PD Fatigue Scale [PFS-16], ON/OFF home diary), Clinical and Patient Global Impression of Change (CGI-C; PGI-C) and adverse events. Results At week 6, there was a significant reduction of −7.9 points (95%CI −13.6, −2.2; p = 0.0099) in PDSS-2 total score, with a significant mean change of −4.7 in the PDSS-2 domain of disturbed sleep (95%CI: −7.2, −2.3; p = 0.0009). Significant reductions were also observed in PFS-16 (−9.6; p = 0.0211), MDS-NMS total score (−28.9; p = 0.0015), MDS-UPDRS-III (−6.3; p = 0.0253), MDS-UPDRS-IV (−1.2; p = 0.0044) and PDQ-8 (−14.2; p = 0.0051). Absolute OFF-time was reduced (−142.1 min). Most patients (93.3%) and most clinicians (80.0%) reported improvements on PGI-C and CGI-C, respectively. Opicapone was well tolerated. Conclusions Adding opicapone 50 mg to levodopa/DDCI therapy in patients with PD and motor fluctuations and sleep disturbances improved both sleep disturbances and OFF time in these patients.

Access to and Transitions within the Medical Care Process of Persons with Down Syndrome and Dementia: A Qualitative Analysis

Compared to the general population, individuals with Down syndrome carry a much higher genetic risk of developing early onset Alzheimer's dementia. This leads to unique challenges and the need for a targeted patient journey.In a qualitative interview study with medical professionals, patient organisations and formal and informal care persons, we assessed barriers within the medical care process of this patient group as well as current approaches to overcome these problems. The study is one module of a multi-method project founded by the Innovation Fund of the German Joint Commission. The results presented here focus on access to and transitions within the medical care process. 14 guided interviews were conducted by a team of moderators by video conference, recorded and transcribed. The analysis of the results was carried out as a qualitative content analysis based on the methods of Mayring.Given the varying degree of premorbid intellectual disability, difficulties recognizing dementia symptoms were reported leading to delays in initiating the diagnostic process. Limited knowledge of the special disease risk and symptom manifestation in routine medical care as well as the lack of specialized medical institutions were identified as additional hurdles. Insufficient dissemination of information about existing specialised institutions to regular physicians and caregivers was criticized. All stakeholder groups drew attention to limitations in access to occupational and speech therapy because of the inadequate number of specialized therapists. Improvements suggested by the interview partners focussed on topics such as the implementation of guidance of the patient journey to and within the medical care process by one institution, easily accessible information for patients and caregivers as well as optimised training for physicians in routine care.Barriers such as insufficient availability of specialised service providers and information deficits about the specific disease risks and symptoms of the population have also been identified in international literatur; in addition, management and coordination deficits in the fragmented German health care system represent well known additional barriers. Approaches to improve the situation can be seen, on the one hand, in improved information and training offers for caregivers and service providers, and, on the other hand, in the expansion of the range of specialized service providers, in particular the Medical Centres for Adults with Disabilities. Informed by these study results and the results of other project modules, health policy recommendations for the improvement of the patient journey of patients with Down syndrome and dementia will be developed in the last project module.

Rapid screening of acetylcholinesterase inhibitors in Qi-Fu-Yin using magnetic metal-organic frameworks immobilized with acetylcholinesterase.

Current immobilization approaches for ligand fishing often experience challenges such as limited protein loading capacity and difficulties in the recycling process. To overcome these challenges, we synthesized a magnetic metal-organic frameworks (MMOFs) composite, which can be rapidly separated and has a large specific surface area, and employed it to immobilize acetylcholinesterase (AChE). The synthesized MMOFs@AChE composite exhibited a high immobilization yield (129.7mg/g) and excellent relative activity recovery (88.1%). Furthermore, immobilized AChE can improve its resistance to alkaline environments and high temperatures. After being stored at 4°C for a month, the immobilized enzyme maintained 91.4% of its original activity, significantly higher than the free enzyme (77.6%). Furthermore, it preserved more than 80% of its initial activity after five cycles and 68.7% after eight cycles. The composite MMOFs@AChE was then incubated with Qi-Fu-Yin extract to fish for ligands binding to AChE. Notably, Qi-Fu-Yin can alleviate Alzheimer's disease (AD) symptoms by modulating the AChE pathway, while active compounds remain unclear. Sixteen potential AChE inhibitors were identified through UHPLC-Q-Exactive-Orbitrap-MS/MS. The results of ligand fishing were validated through molecular docking studies, molecular dynamics simulation, surface plasmon resonance and AChE inhibitory activity assays. The screened compounds may exert inhibitory effects on AChE by altering the spatial configuration of the catalytic site or by influencing the binding of the substrate to the catalytic site, catalytic anionic site and peripheral anionic site regions. The MMOFs@AChE-based ligand fishing platform offers an efficient, effective, and convenient approach for enzymatic inhibitors discovery from natural products.