Multi-informant evaluation of Cognitive Disengagement Syndrome (formerly Slow Cognitive Tempo). Children's self-reported measures in relation to parents / Evaluación multi-informante del Síndrome de Desconexión Cognitiva (anteriormente Tempo Cognitivo Lento). Medidas autoinformadas de los niños con relación a padres

El objetivo fue examinar, desde una aproximación multi-informante, las medidas del Síndrome de Desconexión Cognitiva (SDC) de padres/madres e hijos/as y su relación con síntomas internalizantes y externalizantes. 279 niños/as (9-13 años), y sus padres/madres completaron las evaluaciones sobre SDC, la inatención del trastorno por déficit de atención e hiperactividad (TDAH) y otras medidas internalizadas y externalizadas. Los ítems de las tres medidas de SDC convergieron razonablemente bien en el factor SDC. Se aportaron pruebas discriminantes de la validez de las relaciones entre las puntuaciones de las pruebas y las medidas de los tres constructos diferentes (SDC, soledad y preferencia por la soledad). La asociación más estrecha estuvo entre la evaluación parental de las medidas de SDC con ansiedad y depresión, y entre inatención con hiperactividad/impulsividad y trastorno negativista desafiante. Se observó capacidad predictiva de la medida de SDC sobre la soledad y preferencia por estar solo autoinformadas. Se encontró una posible asociación entre la medida del SDC evaluado por padres/madres y sexo y edad de los niños. En conclusión, los datos apoyan la inclusión de medidas autoinformadas en la evaluación del SDC. Las medidas del SDC en niños se vinculan con medidas internalizantes y, la inatención con las externalizantes.(AU)

Motivation to learn: an international multilevel study on student autonomy and teacher emphasis on content usefulness / Motivación para aprender: un estudio internacional multinivel sobre la autonomía de los estudiantes y el énfasis de los docentes en la utilidad del contenido

En la educación superior, pocos estudios relacionan factores contextuales en la clase, como el énfasis del profesor en la utilidad del contenido y las características motivacionales de los estudiantes. El objetivo fue probar un modelo multinivel sobre la relación entre el énfasis del docente en la utilidad del contenido durante la clase, la autonomía de los estudiantes y, a su vez, la motivación para aprender. Participaron 3033 estudiantes universitarios matriculados de 1º a 4º grado de Ciencias de la Actividad Física y del Deporte, de universidades de España (N = 602), Portugal (N = 469), México (N = 1177), Chile (N = 372), y Brasil (N = 413). Se realizó un modelo de ecuaciones estructurales multinivel, en el que los participantes respondieron preguntas sobre el énfasis del profesor en la utilidad del contenido de la clase, la autonomía y la motivación para aprender. Se hipotetizó que el énfasis del profesor en la utilidad del contenido predecía la autonomía del estudiante que, por su vez, predecía la motivación para aprender. Los resultados, a nivel grupal e individual, indican que el énfasis del docente en la utilidad del contenido predijo la autonomía del estudiante, y la autonomía predijo la motivación para aprender.(AU)

Teacher autonomy support is related to improved student learn-ing. In higher education, few studies relate classroom contextual factors, such as teacher emphasis on content usefulness, and students' motivational characteristics. The aim was to test a multilevel model about the relation between the extent of teachers’ emphasis on the usefulness of class con-tent with student autonomy, and, in turn, on motivation to learn. The par-ticipants were 3033 university students enrolled from 1st to 4th grade of Sciences of the Physical Activity and Sport, from universities in Spain (N = 602), Portugal (N = 469), Mexico (N = 1177), Chile (N = 372), and Brazil (N = 413). A multilevel structural equation model was performed, in which participants answered questions about the teacher's emphasis on the use-fulness of class content, basic psychological need for autonomy, and moti-vation to learn. At the group and individual levels, the hypothesis is that the teacher's emphasis on the usefulness of class content predict the stu-dent autonomy, in turn, student autonomy predicts student motivation to learn. Results found at the group level and at the individual level the strength of teacher emphasis on class content predicted student autonomy; student autonomy predicted student motivation to learn.(AU)

Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

Encuesta nacional para pediatras de Argentina: vacunación en la práctica diaria, percepción de conocimientos y barreras / National survey for pediatricians in Argentina: Vaccination in daily practice, perception of knowledge and barriers

Introducción. El descenso de las coberturas de vacunación fue muy significativo en la última década. Los pediatras son una pieza fundamental para recuperar coberturas y aumentar la confianza en la vacunación. Objetivos. Describir la percepción de los pediatras acerca del conocimiento y prácticas sobre vacunas, e identificar barreras en el acceso. Métodos. Estudio analítico observacional, mediante encuesta en línea. Se incluyeron variables del perfil del profesional, capacitación y barreras en inmunizaciones. Resultados. Participaron 1696 pediatras (tasa de respuesta: 10,7 %), media de 50,4 años. El 78,7 % fueron mujeres. El 78,2 % contaba con ≥10 años de ejercicio profesional. El 78,4 % realizaba atención ambulatoria y el 56,0 % en el subsector privado. El 72,5 % realizó una capacitación en los últimos 2 años. Se manifestaron "capacitados" para transmitir a sus pacientes los beneficios de las vacunas: 97,2 %; objetivos de campañas: 87,7 %; contraindicaciones: 82,4 %; efectos adversos: 78,9 %; recupero de esquemas: 71,2 %; notificación de ESAVI: 59,5 %. La proporción fue estadísticamente superior, en todos los aspectos, en pediatras con ≥10 años de ejercicio y en aquellos con capacitación reciente (p ≤ 0,01). Barreras identificadas en el acceso a la vacunación: falsas contraindicaciones (62,3 %); falta temporaria de vacunas (46,4 %); motivos culturales (41,4 %); horario restringido del vacunatorio (40,6 %). Conclusiones. La percepción del grado de capacitación fue variable según el aspecto de la vacunación. Aquellos con mayor tiempo de ejercicio profesional y con actualización reciente se manifestaron con mayor grado de capacidad. Se identificaron múltiples barreras frecuentes asociadas al acceso en la vacunación.

Introduction. The decline in vaccination coverage has been very significant in the past decade. Pediatriciansplay a key role in catching-up coverage and increasing confidence in vaccination. Objectives. To describe pediatricians' perceptions of vaccine knowledge and practices and to identify barriers to access. Methods. Observational, analytical study using an online survey. Variables related to professional profile, training and barriers to vaccination were included. Results. A total of 1696 pediatricians participated (response rate: 10.7%). Their mean age was 50.4 years; 78.7% were women; 78.2% had ≥ 10 years of experience; 78.4% provided outpatient care and 56.0%, in the private subsector; and 72.5% received training in the past 2 years. Respondents described themselves as "trained" in convey the following aspects to their patients: benefits of vaccines: 97.2%; campaign objectives: 87.7%; contraindications: 82.4%; adverse effects: 78.9%; catchup vaccination: 71.2%; reporting of events supposedly attributable to vaccination or immunization: 59.5%. The proportion was statistically higher in all aspects, among pediatricians with ≥ 10 years of experience and those who received training recently (p ≤ 0.01). The barriers identified in access to vaccination were false contraindications (62.3%), temporary vaccine shortage (46.4%), cultural reasons (41.4%), and restricted vaccination center hours (40.6%). Conclusions. The perception of the level of training varied depending on the vaccination-related aspect. Pediatricians with more years of professional experience and those who received recent updates perceivedthemselves as more trained. Multiple barriers associated with access to vaccination were identified.

Early feeding practices and eating behaviour in preschool children: The CORALS cohort.

This study aimed to investigate if the duration of breastfeeding and the method at initiation of complementary feeding affect eating behaviour in children aged 3-6 years. This is a cross-sectional analysis from the Childhood Obesity Risk Assessment Longitudinal Study project, an ongoing longitudinal cohort study that aims to identify childhood obesity risk factors in Spanish children. A total of 1215 children aged 3-6 years were included. Breastfeeding duration and the method of initiation of complementary feeding [baby-led weaning (BLW), traditional/spoon or mixed method] were evaluated. Eating behaviour at 3-6 years was assessed with the Child Eating Behaviour Questionnaire. Generalized linear models were fitted to assess the association between the aforementioned exposures and eating behaviour. Children breastfed for ≥4 months were less likely to be fussy eaters at 3-6 years compared to those breastfed for <1 month (OR: 0.86 95% CI: 0.76-0.98; p = 0.031). Compared to those children using the traditional/spoon-feeding method, those initiating complementary feeding through BLW or through a mixed approach were more likely to have higher scores on the enjoyment of food (EF) (OR, 95% CI: 1.33, 1.13-1.57; p = 0.001 and 1.17, 1.05-1.30; p = 0.002, respectively) and lower scores on food fussiness (FF) at 3-6 years (0.76, 0.62-0.91; p = 0.004 and 0.87, 0.78-0.98; p = 0.033, respectively). Breastfeeding for ≥4 months and initiation of complementary feeding with the BLW and a mixed approach were associated with greater EF and lower FF, which should endure practice.

Common and uncommon mouse models of growth hormone deficiency.

Mouse models of growth hormone deficiency (GHD) have provided important tools for uncovering the various actions of GH. Nearly 100 years of research using these mouse lines has greatly enhanced our knowledge of the GH/IGF-1 axis. Some of the shared phenotypes of the five "common" mouse models of GHD include reduced body size, delayed sexual maturation, decreased fertility, reduced muscle mass, increased adiposity, and enhanced insulin sensitivity. Since these common mouse lines outlive their normal-sized littermates - and have protection from age-associated disease - they have become important fixtures in the aging field. On the other hand, the twelve "uncommon" mouse models of GHD described herein have tremendously divergent health outcomes ranging from beneficial aging phenotypes (similar to those described for the common models) to extremely detrimental features (such as improper development of the CNS, numerous sensory organ defects, and embryonic lethality). Moreover, advancements in next generation sequencing technologies have led to the identification of an expanding array of genes that are recognized as causative agents to numerous rare syndromes with concomitant GHD. Accordingly, this review provides researchers with a comprehensive up-to-date collection of the common and uncommon mouse models of GHD that have been used to study various aspects of physiology and metabolism associated with multiple forms of GHD. For each mouse line presented, the closest comparable human syndromes are discussed providing important parallels to the clinic.

Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention and intervention.

Identifying risk protein targets and their therapeutic drugs is crucial for effective cancer prevention. Here, we conduct integrative and fine-mapping analyses of large genome-wide association studies data for breast, colorectal, lung, ovarian, pancreatic, and prostate cancers, and characterize 710 lead variants independently associated with cancer risk. Through mapping protein quantitative trait loci (pQTL) for these variants using plasma proteomics data from over 75,000 participants, we identify 365 proteins associated with cancer risk. Subsequent colocalization analysis identifies 101 proteins, including 74 not reported in previous studies. We further characterize 36 potential druggable proteins for cancers or other disease indications. Analyzing >3.5 million electronic health records, we uncover five drugs (Haloperidol, Trazodone, Tranexamic Acid, Haloperidol, and Captopril) associated with increased cancer risk and two drugs (Caffeine and Acetazolamide) linked to reduced colorectal cancer risk. This study offers novel insights into therapeutic drugs targeting risk proteins for cancer prevention and intervention.

BirthSeq, a new method to isolate and analyze dated cells in different vertebrates.

Embryonic development is a complex and dynamic process that unfolds over time and involves the production and diversification of increasing numbers of cells. The impact of developmental time on the formation of the central nervous system is well-documented, with evidence showing that time plays a critical role in establishing the identity of neuronal subtypes. However, the study of how time translates into genetic instructions driving cell fate is limited by the scarcity of suitable experimental tools. We introduce BirthSeq, a new method for isolating and analyzing cells based on their birth date. This innovative technique allows for in vivo labeling of cells, isolation via FACS, and analysis using high-throughput techniques. We tuned up BirthSeq in developmental organs across three vertebrate species (mouse, chick, and gecko), and fully made use of it for single-cell RNA sequencing and novel spatially resolved transcriptomic approaches in mouse and chick, respectively. Overall, BirthSeq provides a versatile tool for studying virtually any tissue in different vertebrate organism, helping to fill the necessity in developmental biology research by targeting cells and their temporal cues.

Rodent Inferior Vena Cava Venoplasty Balloon Model.

Balloon venoplasty is a commonly used clinical technique to treat deep vein stenosis and occlusion as a consequence of trauma, congenital anatomic abnormalities, acute deep vein thrombosis (DVT), or stenting. Chronic deep venous obstruction is histopathologically characterized by thrombosis, fibrosis, or both. Currently, no direct treatment is available to target these pathological processes. Therefore, a reliable in vivo animal model to test novel interventions is necessary. The rodent survival inferior vena cava (IVC) venoplasty balloon model (VBM) allows the study of balloon venoplasty in non-thrombotic and post-thrombotic conditions across multiple time points. The local and systemic effect of coated and uncoated venoplasty balloons can be quantified via tissue, thrombus, and blood assays such as real-time polymerase chain reaction (RT-PCR), western blot, enzyme-linked immunosorbent assay (ELISA), zymography, vein wall and thrombus cellular analysis, whole blood and plasma assays, and histological analysis. The VBM is reproducible, replicates surgical human interventions, can identify local vein wall-thrombi protein changes, and allows multiple analyses from the same sample, decreasing the number of animals required per group.

Efficacy and safety of sagittal synostosis surgery in older (> 12 months) patients: a systematic review and meta-analysis.

PURPOSE: Sagittal synostosis is the most common isolated craniosynostosis. Surgical treatment of this synostosis has been extensively described in the global literature, with promising outcomes when it is performed in the first 12 months of life. However, in some cases, patients older than 12 months arrive at the craniofacial center with this synostosis. A comprehensive study on efficacy and perioperative outcomes has yet to be fully explored in this population. This systematic review and meta-analysis aimed to assess the available evidence of surgical outcomes for the treatment of sagittal synostosis among older patients to analyze the efficacy and safety of synostosis surgery in this unique population. METHODS: PubMed, Embase, and Scopus were searched for studies published from inception to March 2024 reporting surgical outcomes of synostosis surgery in older patients (> 12 months) with isolated sagittal synostosis. The main outcome was the reoperation rate, with secondary endpoints including transfusion rates, aesthetic outcomes, and surgical complications. RESULTS: Nine studies were included in the final analysis. The pooled proportion of the reoperation rate was 1%. The rate of excellent aesthetic results was 95%. The need for transfusion associated with the procedures was 86%, and finally, surgical complications attained a pooled ratio of 2%, indicating minimal morbidity associated with the surgical repair. CONCLUSION: Sagittal synostosis surgery is a safe and effective procedure to perform in older patients; this meta-analysis suggests that open surgery confers a significant rate of excellent aesthetic results with a low reoperation rate and minimal complications associated with the intervention. Future research with direct comparisons among different techniques will validate the findings of this study, which will all contribute to the rigor of synostosis management.

Development and characterization of a novel variant of long-acting bovine follicle-stimulating hormone (brscFSH).

Assisted reproduction is a key aspect of modern animal breeding, providing valuable assistance in improving breeding programs. In this field, the administration of exogenous hormones, such as follicle-stimulating hormone (FSH), plays a crucial role in the induction of multiple ovulations. However, commercial FSH used in veterinary practice has been derived primarily from pituitary glands, obtained mostly from pigs for nearly four decades. Although these hormones have contributed significantly to the advancement of assisted reproductive techniques, they have certain limitations that warrant further improvements. These limitations include contamination with luteinizing hormone (LH), the potential risk of pathogen contamination, the potential to trigger an immune response in non-pig species, and the short half-life in circulation, requiring the implementation of complex 8-dose superovulation schedules. Our research team has developed and characterized a new variant of bovine follicle-stimulating hormone (bscrFSH) to address these limitations. The new hormone is produced recombinantly in CHO cell cultures, with a specific productivity of about 30 pg/cell/day. The bscrFSH can be purified to a high purity of 97 % using a single step of immobilized metal affinity chromatography (IMAC). N-glycan analysis of bscrFSH showed that approximately 74 % of the glycans corresponded to charged structures, including mono-, di-, tri-, and tetra-sialylated glycans. Superovulation trials conducted in cattle revealed that bscrFSH, administered at a total dose of about 0.5 µg per kg of body weight, using a decrescent schedule of 4 doses with 24-h intervals, resulted in an average yield of 8-12 transferable embryos per animal. Further research is required; however, the preliminary findings indicate that bscrFSH, currently packaged under the provisional brand name of Cebitropin B, holds potential as a commercial product for assisted reproduction in ruminants.

Psychometric properties of the Pictorial Pain Interference Questionnaire for Assessing Functional Interference in Chronic Low Back Pain.

OBJECTIVE: To analyze the psychometric properties of the Pictorial Pain Interference Questionnaire (PPIQ) for evaluating functional interference in the population with chronic low back pain (CLBP). DESIGN: Cross-sectional study. SETTING: Hospital Puerta del Mar (Cádiz). PARTICIPANTS: Subjects with CLBP. INTERVENTIONS: Not Applicable. MAIN OUTCOME MEASURES: Functional interference was assessed using PPIQ. The following data were also collected: sociodemographic data; pain intensity (Numeric Pain Rating Scale [NPRS]); physical functioning (30-s arm curl [30ACT], 30-s chair stand [30CST], and timed up-and-go [TUG] tests), fitness (International Physical Activity Questionnaire [IPAQ]); quality of life (SF-12v1); sleep quality (12-MOS Sleep); anxiety and depression (Hospital Anxiety and Depression Scale [HADS]); and social support (Duke-UNK Functional Social Support Questionnaire [DUKE-UNC-DSSI]). Internal consistency was analyzed using Cronbach's alpha, structural validity using exploratory factor analysis (EFA), and discriminant and convergent validity using bivariate analysis. RESULTS: Ninety-nine subjects with CLBP were included (mean age: 54.37(SD:12.44); women, 67.7%). The EFA extracted two factors: "Physical function and "Social and sleep", which explained 57.75% of the variance. Excellent internal consistency was observed for the overall PPIQ score (Cronbach's α=0.866). Convergent validity was observed between the PPIQ and other functional measures (rho: 0.52 and -0.47 for the TUG and 30CST, respectively; p<0.001) and with the following variables: physical and mental component summaries (PCS and MCS) of the SF12v1 (rho: -0. 55 and -0.52, respectively (p<0.001); anxiety and depression of the HADS (rho: 0.47 and 0.59 respectively (p<0.001); NPRS (rho: 0.45; p<0.001); and index 9 of the 12-MOS Sleep (r: 0.49; p<0.001). CONCLUSIONS: The PPIQ is a valid instrument with good psychometric properties for measuring functional interference in people with CLBP. This questionnaire appears to be a feasible alternative when language or communication barriers exist in CLBP population.

The lack of synapsin alters presynaptic plasticity at hippocampal mossy fibers in male mice.

Synapsins are highly abundant presynaptic proteins that play a crucial role in neurotransmission and plasticity via the clustering of synaptic vesicles. The synapsin III isoform is usually downregulated after development, but in hippocampal mossy fiber boutons it persists in adulthood. Mossy fiber boutons express presynaptic forms of short- and long-term plasticity, which are thought to underlie different forms of learning. Previous research on synapsins at this synapse focused on synapsin isoforms I and II. Thus, a complete picture regarding the role of synapsins in mossy fiber plasticity is still missing. Here, we investigated presynaptic plasticity at hippocampal mossy fiber boutons by combining electrophysiological field recordings and transmission electron microscopy in a mouse model lacking all synapsin isoforms. We found decreased short-term plasticity - i.e. decreased facilitation and post-tetanic potentiation - but increased long-term potentiation in male synapsin triple knockout mice. At the ultrastructural level, we observed more dispersed vesicles and a higher density of active zones in mossy fiber boutons from knockout animals. Our results indicate that all synapsin isoforms are required for fine regulation of short- and long-term presynaptic plasticity at the mossy fiber synapse.Significance statement Synapsins cluster vesicles at presynaptic terminals and shape presynaptic plasticity at giant hippocampal mossy fiber boutons. Deletion of all synapsin isoforms results in decreased short- but increased long-term plasticity.

Komi type 2 pancreaticobiliary maljunction: Minimal access surgical treatment (with video).

Pancreaticobiliary maljunction (PBM) is associated with the development of neoplasms of bile ducts. Cholecystectomy with diversion of the biliary-pancreatic flow is considered the treatment of choice. To describe the surgical treatment employed for a patient with Komi's type 2 PBM and its long-term results. Laparoscopic common bile duct exploration, intraoperative cholangioscopy, and Roux-en-Y hepatico-jejunostomy were performed. Postoperative evolution was satisfactory. The patient was discharge 72 hours after the surgery. There was no associated morbidity. At 62-month follow-up, clinical examination, laboratory tests, and imaging studies confirmed an adequate patency of bilio-enteric anastomosis. The surgical approach employed was effective and safe, with satisfactory long-term results.

Strain-Phonon Cooperation as a Necessary Ingredient to Understand the Jahn-Teller Effect in Solids.

Spatial degeneracy is the cause of the complex electronic, geometrical, and magnetic structures found in a number of materials whose more representative example is KCuF3. In the literature the properties of this lattice are usually explained through the Kugel--Khomskii model, based on superexchange interactions. Here we provide rigorous theoretical and computational arguments against this view proving that structural and magnetic properties essentially arise from electron-vibration (vibronic) interactions. Moreover, based on the work of Öpik and Pryce, we show that the coupling between lattice (homogeneous strain) and motif (phonons) distortions is essential to understand the main stable configurations of the lattice. Using this information, we predict a new low-energy phase in KCuF3 that could strongly alter its properties and provide guidance on how to stabilize it through strain engineering.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

Genome and RNA sequencing were essential to reveal cryptic intronic variants associated to defective ATP6AP1 mRNA processing.

The diagnosis of Mendelian disorders has notably advanced with integration of whole exome and genome sequencing (WES and WGS) in clinical practice. However, challenges in variant interpretation and uncovered variants by WES still leave a substantial percentage of patients undiagnosed. In this context, integrating RNA sequencing (RNA-seq) improves diagnostic workflows, particularly for WES inconclusive cases. Additionally, functional studies are often necessary to elucidate the impact of prioritized variants on gene expression and protein function. Our study focused on three unrelated male patients (P1-P3) with ATP6AP1-CDG (congenital disorder of glycosylation), presenting with intellectual disability and varying degrees of hepatopathy, glycosylation defects, and an initially inconclusive diagnosis through WES. Subsequent RNA-seq was pivotal in identifying the underlying genetic causes in P1 and P2, detecting ATP6AP1 underexpression and aberrant splicing. Molecular studies in fibroblasts confirmed these findings and identified the rare intronic variants c.289-233C > T and c.289-289G > A in P1 and P2, respectively. Trio-WGS also revealed the variant c.289-289G > A in P3, which was a de novo change in both patients. Functional assays expressing the mutant alleles in HAP1 cells demonstrated the pathogenic impact of these variants by reproducing the splicing alterations observed in patients. Our study underscores the role of RNA-seq and WGS in enhancing diagnostic rates for genetic diseases such as CDG, providing new insights into ATP6AP1-CDG molecular bases by identifying the first two deep intronic variants in this X-linked gene. Additionally, our study highlights the need to integrate RNA-seq and WGS, followed by functional validation, in routine diagnostics for a comprehensive evaluation of patients with an unidentified molecular etiology.

Improved stability and specificity of baits for oral administration of substances to wild boar.

Oral vaccination is one of the most effective interventions for disease control in wildlife. As a result of the recent global reemergence of African swine fever and ongoing classical swine fever and animal tuberculosis, oral vaccination of Eurasian wild boar (Sus scrofa) receives increased interest. Several baits for wild boar and feral pigs have been described, but developing more stable and personalized formulations is important. This paper proposes a new bait formulation primarily composed of corn flour, piglet feed, sugar, and honey as a binder to obtain improved elasticity. The bait consists of a matrix with no protective coats, has a hemispherical shape (ø 3.4 ×1.6 cm), and displays an anise aroma and blue color. The color and aroma did not affect bait choice by wild boar, while bait coloring contributed to avoid consumption by non-target species (corvids). Baits with the new formulation were significantly more resistant to humidity and high temperatures than previous versions. Simulations suggest that baits with the new formulation are elastic enough to resist impacts from a maximum altitude of 750 m. Thus, the new bait prototype solves several problems of previous bait formulations while keeping a format that can be selectively consumed by piglets and adult wild boar.