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Plantago lanceolata L. (plantain) increases herbage dry matter (DM) production and quality during warm and dry conditions due to its deep roots and drought tolerance and reduces nitrogen losses in grazing systems compared to traditional pastures. However, plantain density usually declines after the third growing season, mainly due to defoliation management. The effects of defoliation frequency and intensity on water-soluble carbohydrate (WSC) reserves and below-ground plant responses need further research to optimize grazing strategies for improved productivity and sustainability of grazing systems. Our study investigated the effects of defoliation frequencies (15, 25, and 35 cm of extended leaf length, ELL) and intensities (5 and 8 cm of residual heights) on morphological traits and WSC concentrations in plantain biomass under controlled environmental conditions. Defoliation frequency significantly influenced morphological and chemical characteristics and biomass distribution more than residual height. Less frequent defoliations promoted above-ground herbage DM production, reproductive stems, and root biomass. Root architecture showed adaptations in response to defoliation frequency, optimizing resource acquisition efficiency. Frequent defoliation reduced high molecular weight WSC concentrations in leaves, affecting regrowth capacity and DM mass. A defoliation frequency of 25 cm ELL (~15 days) balances herbage production and root development, promoting long-term pasture sustainability. [ABSTRACT FROM AUTHOR]

The objective of the present study was to characterize the nutritional composition, fatty acid profile, and IgG concentration of the milk produced by Chilean Corralero horse (CCH) mares from breeding farms located in southern Chile. Forty-five milk samples were collected from three of the biggest breeding farms (coded as A, B and C) specialized in breeding and selection of CCH in Chile (15 mares sampled per farm). Farms differed in days in milk (DIM). A negative association between DIM and ash, milk protein, milk solids, saturated fatty acids (SFA), and gross energy (GE) was found, whereas DIM had a positive association with monounsaturated fatty acids (MUFA). Milk components like fat, lactose, and energy content varied independently of DIM, indicating other influencing factors such as farm-specific management practices. Offspring sex moderately affected GE content, with milk from mares bearing female offspring having higher GE. Macronutrient profiles of the CCH mares' milk were within the reported range for other horse breeds but tended to have lower fat and total solids. Compared to cow and human milk, horse milk is richer in lactose and lower in fat and protein. Immunoglobulin G concentration was only affected by the farm (B > A) which could be linked to dietary factors and pasture composition rather than maternal parity or other known factors. Overall, CCH mare milk has notable nutritional characteristics, with implications for both foal health and potential human consumption, posing less cardiac risk compared to cow's milk as indicated by lower atherogenic and thrombogenic indices. [ABSTRACT FROM AUTHOR]

Traditional pastures in temperate regions face limitations such as reduced growth and nutritional quality during the summer season. Plantain (P. lanceolata L.) offers advantages like increased yield and decreased nitrogen losses from grazing ruminants. Effective grazing management is essential for pasture health, and defoliation frequency and intensity play a pivotal role. This study aimed to evaluate plantain's regrowth, yield, and morpho-physiological and chemical responses under different defoliation frequencies and intensities, with the goal of enhancing its management in pastures. The study was conducted in pots within a controlled-environment growth chamber, examining the impact of three defoliation frequencies (based on extended leaf length: 15, 25 and 35 cm) and two defoliation intensities (5 and 8 cm of residual heights) with four replicates (24 pots as experimental units). The variables of interest were morphological characteristics, dry matter (DM) accumulation, herbage chemical composition, growth rate traits, and photosynthetic parameters. Defoliation frequency affected plantain's growth and nutritional composition. More frequent cuts (15 cm) resulted in lower DM yield per cut and lower stem content, while less frequent cuts (35 cm) produced higher values. Defoliation intensity influenced the proportion of leaves and stems in the total DM, with 5 cm cuts favoring leaves. Nutrient content was also affected by defoliation frequency, with less frequent cuts (35 cm) showing lower crude protein concentration and metabolizable energy content but higher neutral detergent fiber and water-soluble carbohydrate concentration. Plantain's growth rate variables were mainly influenced by defoliation frequency, with less frequent cuts promoting faster leaf appearance and growth of new leaves. The basal fluorescence variables and chlorophyll content were affected by cutting frequency, being highest when cut less frequently (35 cm), while no differences were found in the actual quantum efficiency among different defoliation frequencies and intensities. The fraction of light dedicated to non-photochemical quenching was highest when cut less frequently and more intensively. Overall, defoliation at 25 cm of extended leaf length balanced plantain forage quality and regrowth capacity. [ABSTRACT FROM AUTHOR]

Agricultural soils account for about 60% of the global atmospheric emissions of the potent greenhouse gas nitrous oxide (N2O). One of the main processes producing N2O is denitrification, which occurs under oxygen-limiting conditions when carbon is readily available. On grazed pastures, urine patches create ideal conditions for denitrification, especially in soils with high organic matter content, like Andisols. This lab study looks at the effects of Urine-urea-N load on the Andisol potential to emit N2O. For this, we investigated the effects of three levels of urea-N concentrations in cow urine on emissions of N2O, N2, and CO2 under controlled conditions optimised for denitrification to occur. Results show total N2O emissions increased with increasing urine-N concentration and indicate that denitrification was the main N2O-producing process during the first 2–3 days after urine application, though it was most likely soil native N rather than urine-N being utilised at this stage. An increase in soil nitrate indicates that a second peak of N2O emissions was most likely due to the nitrification of ammonium hydrolysed from the added urine, showing that nitrification and denitrification have the potential to play a big part in N losses and greenhouse gas production from these soils. [ABSTRACT FROM AUTHOR]

Objective: Anaerobic bacteremia represents 0.5-12% of all bacteremias and its mortality is high, ranging from 25-44%. The aim was to know our data to compare them with existing data and demonstrate the importance of actively searching for these microorganisms in blood culture samples., Methods: A retrospective descriptive study in which the medical records of patients with significant episodes of anaerobic bacteremia were reviewed over a period of 8 years (2014-2022)., Results: A total of 59,898 blood cultures were processed, of which 10,451 were positive (17%). An anaerobic microorganism was identified in 209 patients. Anaerobic bacteremia accounted for 2.11% of the total number of positive blood cultures. The mean age was 63.55 years (17-96), 66% of whom were men. The origin was community in 63.64%, of nosocomial origin in 15.31% and associated with health care in 17.70%. The focus of infection was the abdominal (39.23%), followed by the respiratory (13.88%) and skin and soft tissues (13.39%). The most frequent comorbidities were: arterial hypertension (49.76%), dyslipidemia (29.67%), neoplasia (26.32%) and diabetes (26.32%). The main species isolated were the group Bacteroides spp. (44.50%) (n=93) highlighting Bacteroides group fragilis (n=65), followed by Clostridium spp. (20%) (n=42) highlighting Clostridium perfringens (n=30). The clinical evolution was good in 67.46%. The mean length of stay was 27.8 days and was associated with 20% mortality., Conclusions: Bacteremias due to anaerobes represented 2.11% of the total number of true bacteremias, so we consider the active search for these microorganisms to be appropriate., (©The Author 2024. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Ustekinumab is approved for ulcerative colitis (UC)., Aims: To assess the durability of ustekinumab in patients with UC and its short-term effectiveness, durability and tolerability in clinical practice., Methods: Retrospective, multicentre study of patients who had received their first ustekinumab dose at least 16 weeks before inclusion. Patients were followed until treatment discontinuation or last visit. Only patients with active disease at the start of ustekinumab treatment were considered in the effectiveness analysis. Patients who stopped ustekinumab before their last visit were considered not to be in subsequent remission., Results: We included 620 patients; 155 (25%) discontinued ustekinumab during follow-up (median 12 months). Rate of discontinuation was 20% per patient-year of follow-up. Anaemia at baseline (hazard ratio, HR 1.5; 95% confidence interval [CI] 1.1-2.1), steroids at baseline (HR 1.5; 95% CI 1.06-2.08) and more severe clinical activity at baseline (HR 1.5; 95% CI 1.09-2.06) were associated with higher risk of discontinuation. At the end of induction, 226 (40%) patients were in steroid-free clinical remission. Moderate-severe vs mild disease activity at baseline (odds ratio [OR] 0.3; 95% CI 0.2-0.5), male sex (OR 0.5; 95% CI 0.4-0.8), and increased number of previous biologics (OR 0.6; 95% CI 0.6-0.8) were associated with lower likelihood of steroid-free clinical remission at week 16. One hundred and seventy-six patients (28%) had at least one adverse event. We observed no negative impact of ustekinumab on extraintestinal manifestations and/or immune-mediated diseases., Conclusions: Ustekinumab durability in UC was relatively high, and treatment was effective in highly refractory patients. The safety profile was consistent with previous studies., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Suicidal behavior constitutes a multi-cause phenomenon that may also be present in people without a mental disorder. This study aims to analyze suicidal behavior outcomes in a sample of attempters, from a symptom-based approach., Methods: The sample comprised 673 patients (72% female; M  = 40.9 years) who attended a hospital emergency department due to a suicide attempt. A wide range of clinical factors (e.g., psychopathology symptoms, psychiatric diagnoses, impulsivity, acquired capability), was administered within 15 days after the index attempt. Nine psychopathology domains were explored to identify the profile of symptoms, using latent profile analysis. The relationship between the profile membership and suicide outcome (i.e., intensity of suicidal ideation, number of suicide behaviors, and medical injury derived from index attempt) was also studied, using linear and logistic regression., Results: Three psychopathology profiles were identified: high-symptom profile (45.02% of participants), moderate-symptom profile (42.50%), and low-symptom profile (12.48%). High-symptom profile members were more likely to show higher risk of non-suicidal self-injury, acquired capability for suicide, and more severe suicide behavior and ideation. On the other hand, a more severe physical injury was associated with low-symptom profile membership in comparison to membership from the other profiles ( OR  < 0.45, p  < .05)., Conclusions: A symptom-based approach may be useful to monitor patients and determine the risk of attempt repetition in the future and potential medical injury, and to optimize prevention and intervention strategies.

Background: The number of migrants arriving on the shores of the Canary Islands continues to increase. The conditions under which the crossing is made, in small crowded, unsanitary boats (pateras or cayucos), have many and significant health problems., Objective: To describe the demographic, clinical, microbiological characteristics and evolution of a series of patients who recently arrived by patera and required hospitalization., Patients and Methods: This observational, cross-sectional, and retrospective study included all patients newly arrived in Gran Canaria (Spain) by patera or cayuco from 2020 to 2022. Acute patera syndrome (APS) was defined as one or more of the following: dehydration, hypothermia, shock or rhabdomyolysis. Skin and soft tissue or musculoskeletal patera syndrome (SSTMSPS) was defined as conditions characterized by lesions of the skin, subcutaneous tissue, bone, or joint, excluding superficial erosions., Results: During the study period, 193 migrants were admitted, mostly males with a median age of 23 years from West Africa. A total of 36.99% presented with APS with a single diagnostic criterion (most commonly dehydration, 86.9%), 11.56% with SSTMPS and 51.44% with both syndromes. A total of 109 patients presented with SSTMSPS, the most common being lower extremity ulcers. The most frequently isolated microorganisms were gram-negative (i.e. Shewanella algae). The McMahon score effectively predicted the need for renal replacement therapy in cases of rhabdomyolysis. Twenty patients presented with pneumomediastinum, which was benign. SARS-CoV-2 infection was not a problem in any of them. Surgical intervention was required in 22% of cases, including 8 amputations, all of which were minor. No patient died during admission., Conclusion: Patera syndrome has specific characteristics that should be identified promptly to initiate the most effective treatment for optimal outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pisos-Álamo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Natural systems exhibit high spatial variability across multiple scales. Models that can capture ecosystem dynamics across space and time by explicitly incorporating major biological mechanisms are crucial, both for management and for ecological insight. In the case of coral reef systems, much focus has been on modelling variability between reefs, despite substantial variability also existing within reefs. We developed C~scape, a coral metacommunity modelling framework that integrates the demography of corals with population-level responses to physical and environmental spatial layers, to facilitate spatiotemporal predictions of coral dynamics across reefs at fine (100s of metres to kilometres) scales. We used satellite-derived habitat maps to modulate community growth spatially, as a proxy for the many interacting physical and environmental factors-e.g., depth, light, wave exposure, temperature, and substrate type-that drive within-reef variability in coral demography. With a case study from the Great Barrier Reef, we demonstrate the model's capability for producing hindcasts of coral cover dynamics and show that overlooking within-reef variability may lead to misleading conclusions about metacommunity dynamics. C~scape provides a valuable framework for exploring a range of management and restoration scenarios at relevant spatial scales., (© 2024. Crown.)

Background and Aims: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era., Methods: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes., Results: A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC., Conclusions: In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder caused by sarcomeric gene variants and associated with left ventricular hypertrophy and diastolic dysfunction. The role of the microtubule network has recently gained interest with the findings that microtubule detyrosination (dTyr-MT) is markedly elevated in heart failure. Acute reduction of dTyr-MT by inhibition of the detyrosinase (VASH [vasohibin]/SVBP [small VASH-binding protein] complex) or activation of the tyrosinase (TTL [tubulin tyrosine ligase]) markedly improved contractility and reduced stiffness in human failing cardiomyocytes and thus posed a new perspective for HCM treatment. In this study, we tested the impact of chronic tubulin tyrosination in an HCM mouse model ( Mybpc3 knock-in), in human HCM cardiomyocytes, and in SVBP-deficient human engineered heart tissues (EHTs)., Methods: Adeno-associated virus serotype 9-mediated TTL transfer was applied in neonatal wild-type rodents, in 3-week-old knock-in mice, and in HCM human induced pluripotent stem cell-derived cardiomyocytes., Results: We show (1) TTL for 6 weeks dose dependently reduced dTyr-MT and improved contractility without affecting cytosolic calcium transients in wild-type cardiomyocytes; (2) TTL for 12 weeks reduced the abundance of dTyr-MT in the myocardium, improved diastolic filling, compliance, cardiac output, and stroke volume in knock-in mice; (3) TTL for 10 days normalized cell area in HCM human induced pluripotent stem cell-derived cardiomyocytes; (4) TTL overexpression activated transcription of tubulins and other cytoskeleton components but did not significantly impact the proteome in knock-in mice; (5) SVBP-deficient EHTs exhibited reduced dTyr-MT levels, higher force, and faster relaxation than TTL-deficient and wild-type EHTs. RNA sequencing and mass spectrometry analysis revealed distinct enrichment of cardiomyocyte components and pathways in SVBP-deficient versus TTL-deficient EHTs., Conclusions: This study provides the first proof of concept that chronic activation of tubulin tyrosination in HCM mice and in human EHTs improves heart function and holds promise for targeting the nonsarcomeric cytoskeleton in heart disease., Competing Interests: L. Carrier is a member of Scientific Advisory Board of and has shares in the company DiNAQOR AG (https://www.dinaqor.com/). B.L. Prosser is an inventor on a pending US patent application number 15/959181 for “Composition and Methods for Improving Heart Function and Treating Heart Failure.” The other authors report no conflicts.

Objective: Poor glycemic control in the perioperative period has been reported to be associated with early and late major adverse limb events (MALEs). However, these studies were mostly from large databases or lacked long-term outcomes. We examined the long-term effects of high hemoglobin A1c (HbA1c) level on patency, MALE, limb salvage (LS) and survival after lower extremity revascularization procedures in patients with diabetes., Methods: Patients with diabetes who underwent revascularization for Rutherford class 3 to 6 ischemia between May 2002 and December 2018 were identified. Patients with an HbA1c of ≤7% were compared with those with an HbA1c of >7% for patency, MALE, survival, LS, and amputation-free survival., Results: Of 706 patients, 699 had HbA1c data (775 limbs), with 311 (357 limbs) in the HbA1c ≤7% and 388 (418 limbs) in the HbA1c >7% groups. Patients with an HbA1c of >7% were younger (69.9 ± 10.2 years vs 71.7 ± 9.5 years; P = .011), had higher lipid levels, insulin use (70% vs 49%; P < .01), American Society of Anesthesiologists classification of 4, and had a lower prevalence of chronic kidney disease (32% v s41%; P = .023). Patients with an HbA1c of >7% were more likely to present with chronic limb-threatening ischemia (CLTI) (79% vs 72%; P = .019) and undergo infrapopliteal interventions (49% vs 42%; P = .005), with no difference in anatomical complexity (TransAtlantic Inter Society Consensus class C/D, 75% vs 77%; P = .72) or type of revascularization (24% vs 18% open, 66% vs 70% endovascular, 10% vs 12% hybrid; P = .236). Patency and freedom from MALE were significantly lower in patients with an HbA1c of >7% for infrainguinal revascularizations, whereas amputation-free survival and overall survival were similar. In patients with chronic limb-threatening ischemia, LS rates at 5 years were significantly lower in patients undergoing open revascularization (HbA1c > 7%: 64% ± 6% vs HbA1c < 7%:86% ± 5%; P = .020), whereas it was similar after endovascular interventions (HbA1c > 7%:79% ± 4% vs HbA1c < 7%:77% ± 3%; P = .631). Seventy patients with an HbA1c of >7% lost limbs vs 38 patients with an HbA1c of ≤7% (P = .007). In multivariate analysis, HbA1c was associated significantly with primary patency. HbA1c, insulin use, level of intervention, and angiotensin-converting enzyme inhibitor use were associated with MALE., Conclusions: A perioperative HbA1c of >7% is associated with poorer patency rates and increased MALE, especially at the infrainguinal level revascularization in patients with diabetes, with no significant impact on survival. LS is impacted after open, but not after endovascular revascularization., Competing Interests: Disclosures None., (Copyright © 2024. Published by Elsevier Inc.)

Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aβ-40, Aβ-42, and higher incidence of Alzheimer's disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration., (© 2024. The Author(s).)

Importance: Functional movement disorders (FMDs) are frequent and disabling neurological disorders with a substantial socioeconomic impact. Few randomized studies have analyzed the effectiveness of combined physiotherapy and psychotherapy in patients' quality of life., Objective: To assess the efficacy of multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) in FMDs., Design, Setting, and Participants: This was a parallel, rater-blinded, single-center, randomized clinical trial. Recruitment took place from June 2022 to April 2023, and follow-up visits were performed at months 3 and 5, concluding in October 2023. Participants were recruited from a national referral center for movement disorders: the Movement Disorders Unit from the Hospital Universitario Virgen Rocio in Seville, Spain. Patients had to be 18 years or older with a confirmed FMD diagnosis and capable of giving consent to participate. Patients who did not meet eligibility criteria or refused to participate were excluded. Any uncontrolled psychiatric disorder was considered an exclusion criterion., Interventions: Patients were randomly assigned, in a ratio of 1:1 to multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy), or a control intervention (psychological support intervention)., Main Outcomes and Measures: Primary outcomes: between-group differences in changes from baseline to month 3 and month 5 in patients' quality of life (EQ-5D-5L score: EQ Index and EQ visual analog scale [EQ VAS]; and 36-Item Short-Form Survey Physical Component Summary [SF-36 PCS] and SF-36 Mental Component Summary [MCS]). Linear mixed models were applied, controlling by baseline severity and applying Bonferroni correction., Results: Of 70 patients screened with an FMD, 40 were enrolled (mean [SD] age, 43.5 [12.8] years; age range, 18-66 years; 32 female [80%]; mean [SD] age at FMD onset, 38.4 [12.1] years), and 38 completed all the follow-up visits and were included in the analysis for primary outcomes. Multidisciplinary treatment improved SF-36 PCS with a mean between-group difference at 3 months of 4.23 points (95% CI, -0.9 to 9.4 points; P = .11) and a significant mean between-group difference at 5 months of 5.62 points (95% CI, 2.3-8.9 points; P < .001), after multiple-comparisons adjustment. There were no significant differences in other quality-of-life outcomes such as SF-36 MCS (mean between-group difference at 3 and 5 months: 0.72 points; 95% CI, -5.5 to 7.0 points; P = .82 and 0.69 points; 95% CI, 2.3-8.9 points; P = .83, respectively), EQ VAS (9.34 points; 95% CI, -0.6 to 19.3 points; P = .07 and 13.7 points; 95% CI, -1.7 to 29.0 points; P = .09, respectively) and EQ Index (0.001 point; 95% CI, -0.1 to 0.1 point; P = .98 and 0.08 points; 95% CI, 0-0.2 points; P = .13, respectively). At months 3 and 5, 42% and 47% of patients, respectively, in the multidisciplinary group reported improved health using the EQ-5D system, compared with 26% and 16% of patients, respectively, in the control group., Conclusions and Relevance: Results show that multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) effectively improves FMD symptoms and physical aspects of patients' quality of life. Further studies must be performed to evaluate the potential cost-effectiveness of this approach in FMD., Trial Registration: ClinicalTrials.gov Identifier: NCT05634486.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex clinical manifestations that arise between 18 and 36 months of age. Social interaction deficiencies, a restricted range of interests, and repetitive stereotyped behaviors are characteristics which are sometimes difficult to detect early. Several studies show that microRNAs (miRs/miRNAs) are strongly implicated in the development of the disorder and affect the expression of genes related to different neurological pathways involved in ASD. The present systematic review and meta-analysis addresses the current status of miRNA studies in different body fluids and the most frequently dysregulated miRNAs in patients with ASD. We used a combined approach to summarize miRNA fold changes in different studies using the mean values. In addition, we summarized p values for differential miRNA expression using the Fisher method. Our literature search yielded a total of 133 relevant articles, 27 of which were selected for qualitative analysis based on the inclusion and exclusion criteria, and 16 studies evaluating miRNAs whose data were completely reported were ultimately included in the meta-analysis. The most frequently dysregulated miRNAs across the analyzed studies were miR-451a, miR-144-3p, miR-23b, miR-106b, miR150-5p, miR320a, miR92a-2-5p, and miR486-3p. Among the most dysregulated miRNAs in individuals with ASD, miR-451a is the most relevant to clinical practice and is associated with impaired social interaction. Other miRNAs, including miR19a-3p, miR-494, miR-142-3p, miR-3687, and miR-27a-3p, are differentially expressed in various tissues and body fluids of patients with ASD. Therefore, all these miRNAs can be considered candidates for ASD biomarkers. Saliva may be the optimal biological fluid for miRNA measurements, because it is easy to collect from children compared to other biological fluids., (© 2023. The Author(s).)

Background: Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials. Our aim was to describe the characteristics of patients with refractory UP and their disease-related complications, and to identify the need for immunosuppressive therapies., Methods: We identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio-demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy., Results: From a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86-6.69; p < 0.001) required immunosuppressants., Conclusions: Among patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent., (© 2024 John Wiley & Sons Ltd.)

Breast cancer, a prevalent malignancy among women, has various physical and psychological impacts. This comprehensive review offers an in-depth look at multidisciplinary dermo-aesthetic intervention approaches, emphasizing the balance between oncological therapies and the management of these effects. The information presented spans specialties such as aesthetic medicine, plastic surgery, dermatology, physiotherapy, nutrition, odontology, and gynecology. This review, which serves as a clinical guide, aims to establish a safe protocol for non-medical interventions involving oncologists, physicians, and specialists from various areas in patients with breast cancer focused on improving their quality of life. This work offers personalized and integrative care strategies for the eradication of cancer. However, it is still necessary for patients to consult with their oncologist before undergoing any dermo aesthetic treatment. However, it is still necessary for patients to consult with their oncologist before undergoing any dermo aesthetic treatment., (© 2024. The Author(s).)

Introduction: Background: chronic iron-deficiency anaemia in children has a negative impact on neuronal and cognitive development. Despite current knowledge on this subject, in Bolivia iron intake along the psychomotor development stimulation as part of a comprehensive rehabilitation process for children with severe chronic malnutrition is not yet used. Objective: to evaluate the effect of a neurorestorative diet, consisting of iron supplements and other micronutrients, along with psychomotor stimulation in preschool children with chronic malnutrition, iron-deficiency anaemia and severe psychomotor delay. Patients and methods: twenty-four children between 1 and 56 months of age admitted to the integral nutritional recovery centre (INRC), Paediatric Hospital of Cochabamba, Bolivia were included. A strategy of intervention was applied consisting of nutritional replenishment through the administration of elaborated meals prepared from local foods with high heme and non-heme iron concentration, added with vegetables plus the administration of micronutrient´s supplementation and the psychomotor stimulation. Anthropometric indices, psychomotor and biochemical parameters were measured at four times points, during the hospitalisation period. Results: at the beginning, the anthropometric and psychomotor parameters were decreased (between -2 and -3 z score and below 50 % respectively). Combined strategy intervention with iron and other micronutrients together photons produced significant changes between the evaluated time points, both in anthropometric and psychomotor parameters, although these changes were less than expected. Conclusions: the combined strategy used in this study allowed recovery from the anaemia and minimal growth due to the low birth weight or chronic malnutrition. However, the intervention was insufficient to achieve a complete recovery.

Background: The role of beta calcitonin gene-related peptide (beta-CGRP) in gastrointestinal tract is obscure, but experimental models suggest an effect on the homeostasis of the intestinal mucosa. We measured beta-CGRP circulating levels in a large series of subjects with a recent diagnosis of inflammatory bowel disease (IBD), in order to assess the potential role of this neuropeptide in IBD pathogenesis., Methods: Morning serum beta-CGRP levels were measured by ELISA (CUSABIO, China) in 96 patients recently diagnosed of IBD and compared with those belonging from 50 matched healthy controls (HC) and 50 chronic migraine (CM) patients., Results: Beta-CGRP levels were lower in patients with IBD (3.1 ± 1.9 pg/mL; 2.9 [2.4-3.4] pg/mL) as compared to HC (4.7 ± 2.6; 4.9 [4.0-5.8] pg/mL; p < 0.001) and to CM patients (4.6 ± 2.6; 4.7 [3.3-6.2] pg/mL; p < 0.001). Beta-CGRP levels in CM were not significantly different to those of HC (p = 0.92). Regarding IBD diagnostic subtypes, beta-CGRP levels for ulcerative colitis (3.0 ± 1.9pg/mL; 2.5 [2.1-3.4] pg/mL) and Crohn's disease (3.3 ± 2.0 pg/mL; 3.2 [2.4-3.9] pg/mL) were significantly lower to those of HC (p < 0.01 and p < 0.05, respectively) and CM (p < 0.01 and p < 0.05, respectively)., Conclusions: We have found a significant reduction in serum beta-CGRP levels in patients with a recent diagnosis of all kinds of IBD as compared to two control groups without active intestinal disease, HC and CM, which may suggest a role for this neuropeptide in the pathophysiology of IBD. Our data indicate a protective role of beta-CGRP in the homeostasis of the alimentary tract., (© 2024. The Author(s).)

Resilience is the capacity to adapt to stressful life events. As such, this trait is associated with physical and mental functions and conditions. Here, we aimed to identify the genetic factors contributing to shape resilience. We performed variant- and gene-based meta-analyses of genome-wide association studies from six German cohorts (N = 15822) using the 11-item version of the Resilience Scale (RS-11) as outcome measure. Variant- and gene-level results were combined to explore the biological context using network analysis. In addition, we conducted tests of correlation between RS-11 and the polygenic scores (PGSs) for 12 personality and mental health traits in one of these cohorts (PROCAM-2, N = 3879). The variant-based analysis found no signals associated with resilience at the genome-wide level (p < 5 × 10 -8 ), but suggested five genomic loci (p < 1 × 10 -5 ). The gene-based analysis identified three genes (ROBO1, CIB3 and LYPD4) associated with resilience at genome-wide level (p < 2.48 × 10 -6 ) and 32 potential candidates (p < 1 × 10 -4 ). Network analysis revealed enrichment of biological pathways related to neuronal proliferation and differentiation, synaptic organization, immune responses and vascular homeostasis. We also found significant correlations (FDR < 0.05) between RS-11 and the PGSs for neuroticism and general happiness. Overall, our observations suggest low heritability of resilience. Large, international efforts will be required to uncover the genetic factors that contribute to shape trait resilience. Nevertheless, as the largest investigation of the genetics of resilience in general population to date, our study already offers valuable insights into the biology potentially underlying resilience and resilience's relationship with other personality traits and mental health., (© 2024. The Author(s).)

To advance sustainable and resilient agricultural management policies, especially during land use changes, it is imperative to monitor, report, and verify soil organic carbon (SOC) content rigorously to inform its stock. However, conventional methods often entail challenging, time-consuming, and costly direct soil measurements. Integrating data from long-term experiments (LTEs) with freely available remote sensing (RS) techniques presents exciting prospects for assessing SOC temporal and spatial change. The objective of this study was to develop a low-cost, field-based statistical model that could be used as a decision-making aid to understand the temporal and spatial variation of SOC content in temperate farmland under different land use and management. A ten-year dataset from the North Wyke Farm Platform, a 20-field, LTE system established in southwestern England in 2010, was used as a case study in conjunction with an RS dataset. Linear, additive and mixed regression models were compared for predicting SOC content based upon combinations of environmental variables that are freely accessible (termed open) and those that require direct measurement or farmer questionnaires (termed closed). These included an RS-derived Ecosystem Services Provision Index (ESPI), topography (slope, aspect), weather (temperature, precipitation), soil (soil units, total nitrogen [TN], pH), and field management practices. Additive models (specifically Generalised Additive Models (GAMs)) were found to be the most effective at predicting space-time SOC variability. When the combined open and closed factors (excluding TN) were considered, significant predictors of SOC were: management related to ploughing being the most important predictor, soil unit (class), aspect, and temperature (GAM fit with a normalised RMSE = 9.1%, equivalent to 0.4% of SOC content). The relative strength of the best-fitting GAM with open data only, which included ESPI, aspect, and slope (normalised RMSE = 13.0%, equivalent to 0.6% of SOC content), suggested that this more practical and cost-effective model enables sufficiently accurate prediction of SOC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The coexistence of human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD) is uncommon. Data on the impact of HIV on IBD course and its management is scarce., Aim: To describe the IBD phenotype, therapeutic requirements and prevalence of opportunistic infections (OI) in IBD patients with a coexistent HIV infection., Methods: Case-control, retrospective study including all HIV positive patients diagnosed with IBD in the ENEIDA registry. Patients with positive HIV serology (HIV-IBD) were compared to controls (HIV seronegative), matched 1:3 by year of IBD diagnosis, age, gender and type of IBD., Results: A total of 364 patients (91 HIV-IBD and 273 IBD controls) were included. In the whole cohort, 58% had ulcerative colitis (UC), 35% had Crohn's disease (CD) and 7% were IBD unclassified. The HIV-IBD group presented a significantly higher proportion of proctitis in UC and colonic location in CD but fewer extraintestinal manifestations than controls. Regarding treatments, non-biological therapies (37.4% vs. 57.9%; P=0.001) and biologicals (26.4% vs. 42.1%; P=0.007), were used less frequently among patients in the HIV-IBD group. Conversely, HIV-IBD patients developed more OI than controls regardless of non-biological therapies use. In the multivariate analysis, HIV infection (OR 4.765, 95%CI 2.48-9.14; P<0.001) and having ≥1 comorbidity (OR 2.445, 95%CI 1.23-4.85; P=0.010) were risk factors for developing OI, while CD was protective (OR 0.372, 95%CI 0.18-0.78;P=0.009)., Conclusions: HIV infection appears to be associated with a less aggressive phenotype of IBD and a lesser use of non-biological therapies and biologicals but entails a greater risk of developing OI., (Copyright © 2024 by The American College of Gastroenterology.)

Background & Aims: Growing evidence suggests an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to clinically and mechanistically characterize steatotic liver disease (SLD) in a prospective cohort of patients with IMID compared to controls., Methods: Cross-sectional, case-control study including a subset of patients with IMID. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with 'limma-voom'. Gene set-enrichment analysis was performed using the fgsea R package with a preranked "limma t-statistic" gene list., Results: A total of 1,456 patients with IMID and 2,945 controls were included. Advanced SLD (liver stiffness measurement ≥9.7 kPa) (13.46% vs. 3.79%; p < 0.001) and advanced MASLD (12.8% vs . 2.8%; p < 0.001) prevalence were significantly higher among patients with IMID than controls. In multivariate analysis, concomitant IMID was an independent, and the strongest, predictor of advanced SLD (adjusted odds ratio 3.318; 95% CI 2.225-4.947; p <0.001). Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID-MASLD and control-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism., Conclusions: The prevalence of advanced SLD and MASLD is disproportionately elevated in IMID cohorts. Our findings suggest that IMIDs may catalyze a distinct MASLD pathway, divergent from classical metabolic routes, highlighting the need for tailored clinical management strategies., Impact and Implications: The prevalence of steatotic liver disease with advanced fibrosis is increased in patients with immune-mediated inflammatory diseases, independent of classic metabolic risk factors or high-risk alcohol consumption. Transcriptomic analysis revealed a unique gene expression signature associated with cellular activities that are compatible with a liver condition leading to an accelerated and aggressive form of steatotic liver disease. Our findings underscore the importance of heightened screening for advanced liver disease risk across various medical disciplines overseeing patients with immune-mediated inflammatory diseases., (© 2024 The Authors.)

Objective: To analyze the specificity of calcitonin gene-related peptide (CGRP) levels, we measured alpha-CGRP circulating levels in a large series of patients with a recent diagnosis of inflammatory bowel disease (IBD) who were interviewed regarding comorbid headache., Background: Several studies have found an association between migraine and IBD., Methods: In this cross-sectional study performed in an IBD clinic, morning serum alpha-CGRP levels were measured by enzyme-linked immunosorbent assay in 96 patients who were recently diagnosed with IBD and compared to those from 50 similar patients with chronic migraine (CM) and 50 healthy controls (HC)., Results: Alpha-CGRP levels were higher in patients with IBD (median [interquartile range] 56.9 [35.6-73.9] pg/mL) and patients with CM (53.0 [36.7-73.9] pg/mL) compared to HC (37.2 [30.0-51.8] pg/mL; p = 0.003; p = 0.019, respectively). Regarding IBD diagnostic subtypes, alpha-CGRP levels for ulcerative colitis (67.2 ± 49.3 pg/mL; 57.0 [35.6-73.4] pg/mL) and Crohn's disease (54.9 ± 27.5 pg/mL; 57.7 [29.1-76.1] pg/mL) were significantly higher than those of HC (p = 0.013, p = 0.040, respectively). Alpha-CGRP levels were further different in patients with IBD with migraine (70.9 [51.8-88.7] pg/mL) compared to HC (p < 0.001), patients with IBD without headache (57.5 [33.3-73.8] pg/mL; p = 0.049), and patients with IBD with tension-type headache but without migraine (41.7 [28.5-66.9] pg/mL; p = 0.004), though alpha-CGRP levels in patients with IBD without migraine (53.7 [32.9-73.5] pg/mL) remained different over HC (p = 0.028)., Conclusion: Together with CM, circulating alpha-CGRP levels are different in patients with IBD, perhaps reflecting a chronic inflammatory state. IBD is an example of how alpha-CGRP levels are not a totally specific migraine biomarker. However, alpha-CGRP levels were further increased in patients with IBD who have a history of migraine, which reinforces its role as a biomarker in migraine patients, always bearing in mind their comorbidities., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Effective treatment of non-ST-segment elevation acute coronary syndromes (NSTEACS) requires careful assessment of both ischaemic and bleeding risks. We aimed to analyse risk distribution and evaluate antiplatelet prescription behaviours in real-life settings., Methods: Data from 1100 NSTEACS patients in Buenos Aires, Argentina, from the Buenos Aires I Registry, with a 15-month follow-up, were analysed. In-hospital and 6-month GRACE scores, CRUSADE, and Precise DAPT scores were calculated., Results: The mean age was 65.4 ± 11.5 years with a majority being male (77.2%). In-hospital mortality was 2.7%, primarily due to cardiovascular causes (1.8%). Bleeding events occurred in 20.9% of patients, with 4.9% classified as ≥ BARC 3. Predominance of low bleeding (71.3%) and ischaemic (55.8%) risks on admission was observed. At 6 months, the low-risk Precise category (70.9%) and GRACE (44.1%) categories prevailed. Linear correlation analysis showed a moderately positive correlation ( r  = 0.61, p  < .05) between ischaemic-haemorrhagic risks. Regarding the prescription of antiplatelet agents, in the low ischaemic-haemorrhagic risk group, there was a predominance of aspirin + clopidogrel (41.2%) over other high-potency antiplatelet regimens (aspirin + ticagrelor or prasugrel). In the low ischaemic and high haemorrhagic risk group, aspirin and clopidogrel were also predominant (58%)., Conclusions: Our analysis underscores the significant relationship between ischaemic and haemorrhagic risks during NSTEACS hospitalisation. Despite the majority of patients falling into the low-intermediate risk category, the prescription of P2Y12 inhibitors in real-life settings does not consistently align with these risks.

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF., (© 2024. The Author(s).)

Background: Suicide is an international health concern with immeasurable impact from the perspective of human and social suffering. Prior suicide attempts, anxious and depressive symptoms, and relatively lower health-related quality of life (HRQoL) are among the most replicated risk factors for suicide. Our goal was to visualize the distribution of these features and their interconnections with use of a network analysis approach in individuals who recently attempted suicide., Methods: Individuals with a recent suicide attempt were recruited from nine University Hospitals across Spain as part of the SURVIVE cohort study. Anxious and depressive symptoms, and perceived HRQoL were included in the network analysis. Network structures were estimated with the EBICglasso model. Centrality measures and bridge symptoms connecting communities were explored. Subnetworks comparing younger and older individuals, and women and men were analyzed., Results: A total of 1106 individuals with a recent suicide attempt were included. Depressed mood was the symptom with the greatest influence in the overall network, followed by anxiety symptoms such as feeling nervous, worrying, restless, and having difficulties to relax. Perceived general health was associated with increased suicidal ideation in the whole sample. Older people showed a specific connection between perceived general health and depressed mood., Limitations: The cross-sectional design does not allow determination of established causality., Conclusions: Depressed mood was the core network's symptom and, therefore, an important target in the management and prevention of suicide. HRQoL had more influence on the network of older populations, in which it should be a primary focus., Competing Interests: Declaration of competing interest IG has received grants and served as consultant, advisor or CME speaker for the following identities: ADAMED, Angelini, Casen Recordati, Esteve, Ferrer, Gedeon Richter, Janssen Cilag, Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare, Viatris outside the submitted work. She also receives royalties from Oxford University Press, Elsevier, Editorial Médica Panamericana. EV has received grants and served as consultant, advisor, or CME speaker for the following entities: AB-Biotics, AbbVie, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Idorsia, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work. Dr. Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. The rest of authors have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II., Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism., Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II., (© 2024. The Author(s).)

Parkinson's disease (PD) caused by SNCA gene triplication (3X SNCA ) leads to early onset, rapid progression, and often dementia. Understanding the impact of 3X SNCA and its absence is crucial. This study investigates the differentiation of human induced pluripotent stem cell (hiPSC)-derived floor-plate progenitors into dopaminergic neurons. Three different genotypes were evaluated in this study: patient-derived hiPSCs with 3X SNCA , a gene-edited isogenic line with a frame-shift mutation on all SNCA alleles ( SNCA 4KO), and a normal wild-type control. Our aim was to assess how the substantia nigra pars compacta (SNpc) microenvironment, damaged by 6-hydroxydopamine (6-OHDA), influences tyrosine hydroxylase-positive (Th+) neuron differentiation in these genetic variations. This study confirms successful in vitro differentiation into neuronal lineage in all cell lines. However, the SNCA 4KO line showed unusual LIM homeobox transcription factor 1 alpha (Lmx1a) extranuclear distribution. Crucially, both 3X SNCA and SNCA 4KO lines had reduced Th+ neuron expression, despite initial successful neuronal differentiation after two months post-transplantation. This indicates that while the SNpc environment supports early neuronal survival, SNCA gene alterations-either amplification or knock-out-negatively impact Th+ dopaminergic neuron maturation. These findings highlight SNCA 's critical role in PD and underscore the value of hiPSC models in studying neurodegenerative diseases.

Objective: Olfactory dysfunction (OD) represents a frequent complaint in general population and especially in patients with chronic sinonasal diseases. The aim of this study was the cross-cultural adaptation and validation of the Self-reported Mini Olfactory Questionnaire (Self-MOQ) into Italian., Methods: One hundred fifty patients affected by chronic sinonasal diseases and reporting hyposmia were enrolled. Other 150 normosmic subjects without inflammatory or neoplastic sinonasal disorders were used as a control group. The Short-form 36 (SF-36) questionnaire was used for clinical validity., Results: Cronbach's alpha coefficient was 0.825. The test-retest reliability was excellent. The good correlation between the Self-MOQ and the Visual Analogue Scale scores (p < 0.05) demonstrated the construct validity of the questionnaire. The Self-MOQ was able to distinguish between subjects with or without OD (p < 0.05). Higher Self-MOQ score was found in case of nasal obstruction and posterior rhinorrhoea (p < 0.05). Self-MOQ showed significant correlation with SF-36 general health, SF-36 role functioning/physical, and SF-36 pain (p < 0.05)., Conclusions: The Italian version of the Self-MOQ showed good internal consistency, test-retest reliability, construct, and clinical validity., (Copyright © 2024 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)