Occupational Therapy in Psychiatric Short-Term Hospitalization Units: Scoping Review.

Given the context, the overarching aim is to identify scientific publications on occupational therapy in Psychiatric-Short-Term-Hospitalization-Units. Specific objectives include: (a) Analyzing the historical development of this research area; (b) Synthesizing existing evidence on the nature of documentary sources on occupational therapy in in Psychiatric-Short-Term-Hospitalization-Units; (c) Detailing the volume of scientific literature on occupational therapy in these units; (e) Evaluating available evidence on occupational therapy interventions to improve functionality, quality of life, and recovery in individuals admitted to in Psychiatric-Short-Term-Hospitalization-Units. A scoping review method was employed to conduct a historical mapping of research on in Psychiatric-Short-Term-Hospitalization-Units. The review proceeded in five stages following PRISMA guidelines. After applying selection criteria, the search identified 446 references. Findings are presented under three headings: (a) Historical trends in the scientific literature on occupational therapy and in Psychiatric-Short-Term-Hospitalization-Units; (b) Nature and volume of articles included in the occupational therapy synthesis in Psychiatric Short-Term Hospitalization Units; (c) Data extraction on methodological variables in the research of occupational therapy articles in in Psychiatric-Short-Term-Hospitalization-Units; and (d) Data extraction on research outcome variables of occupational therapy articles in Psychiatric Short-Term Hospitalization Units. The growth of occupational therapy in in Psychiatric-Short-Term-Hospitalization-Units is emphasized, with an increase in qualitative studies. Occupational therapy is underscored as an integral part of care, supporting the diversity and effectiveness of interventions. Common diagnoses include schizophrenia and depressive disorders. Group interventions and the spiritual dimension positively influence the quality of care and meaningful routines for recovery in in Psychiatric-Short-Term-Hospitalization-Units.

Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.

Type 2 diabetes in latin America: recommendations on the flash glucose monitoring system.

OBJECTIVE: To establish recommendations through the consensus of a Latin American experts panel on the use of the flash glucose monitoring system (fCGM) in people living with type 2 diabetes mellitus (T2DM) regarding the benefits and challenges of using the fCGM. METHODS: An executive committee of experts was created, comprised by a panel of fifteen physicians, including endocrinologists and internal medicine physicians, with expertise in management of adult patients with T2DM. The experts were from various countries: Colombia, Chile, Peru, Mexico, Argentina, and Brazil. The modified Delphi method was used, considering a consensus level of at least 80% of the participants. A seventeen-item instrument was developed to establish recommendations on the use of fCGM in patients with T2DM in Latin American. RESULTS: The number of glucose scans recommended per day with the fCGM for patients managed with oral antidiabetic drugs or basal insulin was a median of 6 scans per day, and for those managed with multiple insulin doses, a median of 10 scans per day was recommended. Additionally, a holistic and individualized management approach was recommended, taking into account new treatment directions and identifying patients who would benefit from the use of the fCGM. CONCLUSION: Continuous use of the fCGM is recommended for people living with T2DM, regardless of their type of treatment. These metrics must be evaluated individually for each patient profile.

Food insecurity and sociodemographic factors in Latin America during the COVID-19 pandemic.

Objective: To understand the association of food insecurity with sociodemographic factors in a sample population in Latin America during the COVID-19 pandemic. Methods: This was a multicenter cross-sectional study conducted in 10 countries in Latin America using an online survey through various digital platforms from October 14, 2020 to February 15, 2021. Statistical analysis of data was performed by applying descriptive statistics, chi-square test, and logistic regression analysis. Results: Of a total of 6 357 surveys, 58.2% of respondents experienced food security, 29.3% were slightly food insecure, 9.2% were moderately food insecure, and 3.3% were severely food insecure. Concerning the association food insecurity and sociodemographic variables, there is a significant association in the variables studied, including area of residence, education level, occupation, number of persons in the household, household with children younger than 10 years of age, and socioeconomic level. Conclusions: These findings indicate that sociodemographic factors associated with food insecurity during the COVID-19 pandemic in Latin America were rural residence; complete and incomplete basic and secondary schooling; occupation (homemaker, unemployed, and self-employed); low, medium-low, and medium socioeconomic level; household with more than four persons; and household with children younger than 10 years of age.

Combining anaerobic digestion slurry and different biochars to develop a biochar-based slow-release NPK fertilizer.

In this research, we developed a biochar-based fertilizer using biogas slurry and biochar derived from lignocellulosic agro-residues. Biogas slurry was obtained through the anaerobic digestion of the organic fraction of municipal solid waste (fresh vegetable biomass and/or prepared food), while biochars were derived from residues from quinoa, maize, rice, and sugarcane. The biochar-based fertilizers were prepared using an impregnation process, where the biogas slurry was mixed with each of the raw biochars. Subsequently, we characterized the N, P and K concentrations of the obtained biochar-based fertilizers. Additionally, we analyzed their surface properties using SEM/EDS and FTIR and conducted a slow-release test on these biochar-based fertilizers to assess their capability to gradually release nutrients. Lastly, a bioassay using cucumber plants was conducted to determine the N, P, and K bioavailability. Our findings revealed a significant correlation (r > 0.67) between the atomic O/C ratio, H/C ratio, cation exchange capacity, surface area, and the base cations concentration with N, P, and/or K adsorption on biochar. These properties, in turn, were linked to the capability of the biochar-based fertilizer to release nutrients in a controlled manner. The biochar-based fertilizer derived from corn residues showed <15 % release of N, P and K at 24 h. Utilization of these biochar-based fertilizers had a positive impact on the mineral nutrition of cucumber plants, resulting in an average increase of 61 % in N, 32 % in P, and 19 % in K concentrations. Our results underscore the potential of biochar-based fertilizers in controlled nutrient release and enhanced plant nutrition. Integration of biochar and biogas slurry offers a promising and sustainable approach for NPK recovery and fertilizer production in agriculture. This study presents an innovative and sustainable approach combining the use of biochar for NPK recovery from biogas slurry and its use as a biochar-based fertilizer in agriculture.

Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Tyrosine kinase 2 modulates splenic B cells through type I IFN and TLR7 signaling.

Tyrosine kinase 2 (TYK2) is involved in type I interferon (IFN-I) signaling through IFN receptor 1 (IFNAR1). This signaling pathway is crucial in the early antiviral response and remains incompletely understood on B cells. Therefore, to understand the role of TYK2 in B cells, we studied these cells under homeostatic conditions and following in vitro activation using Tyk2-deficient (Tyk2-/-) mice. Splenic B cell subpopulations were altered in Tyk2-/- compared to wild type (WT) mice. Marginal zone (MZ) cells were decreased and aged B cells (ABC) were increased, whereas follicular (FO) cells remained unchanged. Likewise, there was an imbalance in transitional B cells in juvenile Tyk2-/- mice. RNA sequencing analysis of adult MZ and FO cells isolated from Tyk2-/- and WT mice in homeostasis revealed altered expression of IFN-I and Toll-like receptor 7 (TLR7) signaling pathway genes. Flow cytometry assays corroborated a lower expression of TLR7 in MZ B cells from Tyk2-/- mice. Splenic B cell cultures showed reduced proliferation and differentiation responses after activation with TLR7 ligands in Tyk2-/- compared to WT mice, with a similar response to lipopolysaccharide (LPS) or anti-CD40 + IL-4. IgM, IgG, IL-10 and IL-6 secretion was also decreased in Tyk2-/- B cell cultures. This reduced response of the TLR7 pathway in Tyk2-/- mice was partially restored by IFNα addition. In conclusion, there is a crosstalk between TYK2 and TLR7 mediated by an IFN-I feedback loop, which contributes to the establishment of MZ B cells and to B cell proliferation and differentiation.

Food insecurity and sociodemographic factors in Latin America during the COVID-19 pandemic / Inseguridad alimentaria y factores sociodemográficos en América Latina durante la pandemia de COVID-19 / Insegurança alimentar e fatores sociodemográficos na América Latina durante a pandemia de COVID-19

[ABSTRACT]. Objective. To understand the association of food insecurity with sociodemographic factors in a sample popu- lation in Latin America during the COVID-19 pandemic. Methods. This was a multicenter cross-sectional study conducted in 10 countries in Latin America using an online survey through various digital platforms from October 14, 2020 to February 15, 2021. Statistical analysis of data was performed by applying descriptive statistics, chi-square test, and logistic regression analysis. Results. Of a total of 6 357 surveys, 58.2% of respondents experienced food security, 29.3% were slightly food insecure, 9.2% were moderately food insecure, and 3.3% were severely food insecure. Concerning the association food insecurity and sociodemographic variables, there is a significant association in the variables studied, including area of residence, education level, occupation, number of persons in the household, house- hold with children younger than 10 years of age, and socioeconomic level. Conclusions. These findings indicate that sociodemographic factors associated with food insecurity during the COVID-19 pandemic in Latin America were rural residence; complete and incomplete basic and secondary schooling; occupation (homemaker, unemployed, and self-employed); low, medium-low, and medium socioeco- nomic level; household with more than four persons; and household with children younger than 10 years of age.

[RESUMEN]. Objetivo. Determinar la asociación de la inseguridad alimentaria con factores sociodemográficos en una muestra de población de América Latina durante la pandemia de COVID-19. Métodos. Se llevó a cabo un estudio transversal multicéntrico en diez países de América Latina mediante una encuesta en línea a través de diversas plataformas digitales, entre el 14 de octubre del 2020 y el 15 de febrero del 2021. Se realizó un análisis estadístico de los datos usando procedimientos de estadística descriptiva, la prueba ji al cuadrado y un análisis de regresión logística. Resultados. En un total de 6 357 encuestas, el 58,2% de las personas encuestadas gozaba de seguridad ali- mentaria, el 29,3% tenía una inseguridad alimentaria leve, el 9,2% una inseguridad alimentaria moderada y el 3,3% una inseguridad alimentaria grave. Por lo que respecta a la asociación entre la inseguridad alimentaria y las variables sociodemográficas, hay una asociación significativa para algunas de las variables estudiadas, como la zona de residencia, el nivel de estudios, la actividad laboral, el número de personas en el hogar, el hogar con menores de 10 años y el nivel socioeconómico. Conclusiones. Estos resultados indican que los factores sociodemográficos asociados a la inseguridad alimentaria durante la pandemia de COVID-19 en América Latina fueron la residencia en zonas rurales; la edu- cación primaria y secundaria completa o no; la actividad laboral (trabajo doméstico, personas desempleadas y trabajadores autónomos); el nivel socioeconómico bajo, medio bajo, y medio; el hogar con más de cuatro personas; y el hogar con menores de 10 años.

[RESUMO]. Objetivo. Compreender a relação entre insegurança alimentar e fatores sociodemográficos em uma amostra populacional da América Latina durante a pandemia de COVID-19. Métodos. Estudo transversal multicêntrico realizado em 10 países da América Latina por meio de uma pesquisa on-line conduzida em diferentes plataformas digitais de 14 de outubro de 2020 a 15 de fevereiro de 2021. A análise estatística dos dados foi realizada por meio da aplicação de estatísticas descritivas, teste qui-quadrado e análise de regressão logística. Resultados. De um total de 6 357 questionários, 58,2% dos entrevistados afirmaram ter segurança alimentar, 29,3% indicaram um nível de insegurança alimentar leve, 9,2% tinham insegurança alimentar moderada e 3,3%, insegurança alimentar grave. No que diz respeito à relação entre insegurança alimentar e variáveis sociodemográficas, há uma relação significativa com as variáveis estudadas, incluindo área de residência, nível de escolaridade, ocupação, número de pessoas no domicílio, domicílio com crianças com menos de 10 anos de idade e nível socioeconômico. Conclusões. Os achados apontam que os fatores sociodemográficos associados à insegurança alimentar durante a pandemia de COVID-19 na América Latina foram residência em zona rural; ensino fundamental e médio completo e incompleto; ocupação (do lar, desempregado(a) e autônomo(a)); nível socioeconômico baixo, médio-baixo e médio; domicílio com mais de quatro pessoas; e domicílio com crianças menores de 10 anos de idade.

Exploring Pelvic Symptom Dynamics in Relation to the Menstrual Cycle: Implications for Clinical Assessment and Management.

BACKGROUND: Pelvic floor dysfunctions (PFDs) encompass an array of conditions with discrepant classification systems, hampering accurate prevalence estimation. Despite potentially affecting up to 25% of women during their lifetime, many remain undiagnosed, underestimating the true extent. OBJECTIVES: This cross-sectional study aimed to examine the impacts of the menstrual cycle on PFDs and dysfunctions. Secondary objectives included investigating differences between athletic and nonathletic women. METHODS: An online questionnaire examined the effects of the menstrual cycle (MC) on 477 women's pelvic symptoms (aged 16-63 years), stratified by athletic status. This ad hoc instrument built upon a validated screening tool for female athletes. RESULTS: Most participants reported symptom fluctuations across menstrual phases, with many modifying or reducing exercise participation. A concerning number experienced daily undiagnosed pelvic floor symptoms, emphasizing needs for comprehensive medical evaluation. CONCLUSIONS: Exacerbated pelvic symptoms showed complex relationships with menstruation, highlighting the importance of considering the MC in customized clinical management approaches. Symptoms demonstrated differential links to menstruation, indicating needs for individualized evaluation and tailored treatment plans based on symptom profiles and hormonal interactions. Educating professionals and patients remains essential to enhancing awareness, detection, and therapeutic outcomes. Further controlled longitudinal research should elucidate intricate relationships between menstrual cycles and pelvic symptom variability.

A smartphone-integrated aptasensor for pesticide detection using gold-decorated microparticles.

The increasing incidence of environmental concerns related to excessive use of pesticides, such as imidacloprid and carbendazim, poses risks to pollinators, water bodies, and human health, prompting regulatory scrutiny and bans in developed countries. In this study, we propose a portable smartphone-based biosensor for rapid and label-free colorimetric detection by using the gold-decorated polystyrene microparticles (Ps-AuNP) functionalized with specific aptamers to imidacloprid and carbendazim on a microfluidic paper-based analytical device (µ-PAD). Four aptamers were selected for the detection of these pesticides and their sensitivity and selectivity performance was evaluated. The sensitivity results show a detection limit for imidacloprid of 3.12 ppm and 1.56 ppm for carbendazim. The aptamers also exhibited high selectivity performance against other pesticides, such as thiamethoxam, fenamiphos, isoproturon, and atrazine. However, the platform presented cross-selectivity when detecting imidacloprid, carbendazim, and linuron, which is discussed herein. Overall, we present a promising platform for simple, on-site, and rapid colorimetric screening of specific pesticides, while highlighting the challenges of aptasensors in achieving selectivity amidst diverse molecular structures.

STIM2 variants regulate Orai1/TRPC1/TRPC4-mediated store-operated Ca2+ entry and mitochondrial Ca2+ homeostasis in cardiomyocytes.

The stromal interaction molecules (STIMs) are the sarcoplasmic reticulum (SR) Ca2+ sensors that trigger store-operated Ca2+ entry (SOCE) in a variety of cell types. While STIM1 isoform has been the focus of the research in cardiac pathophysiology, the function of the homolog STIM2 remains unknown. Using Ca2+ imaging and patch-clamp techniques, we showed that knockdown (KD) of STIM2 by siRNAs increased SOCE and the ISOC current in neonatal rat ventricular cardiomyocytes (NRVMs). Within this cardiomyocyte model, we identified the transcript expression of Stim2.1 and Stim2.2 splice variants, with predominance for Stim2.2. Using conventional and super-resolution confocal microscopy (STED), we found that exogenous STIM2.1 and STIM2.2 formed pre-clusters with a reticular organization at rest. Following SR Ca2+ store depletion, some STIM2.1 and STIM2.2 clusters were translocated to SR-plasma membrane (PM) junctions and co-localized with Orai1. The overexpression strategy revealed that STIM2.1 suppressed Orai1-mediated SOCE and the ISOC current while STIM2.2 enhanced SOCE. STIM2.2-enhanced SOCE was also dependent on TRPC1 and TRPC4. Even if STIM2 KD or splice variants overexpression did not affect cytosolic Ca2+ cycling, we observed, using Rhod-2/AM Ca2+ imaging, that Orai1 inhibition or STIM2.1 overexpression abolished the mitochondrial Ca2+ (mCa2+) uptake, as opposed to STIM2 KD. We also found that STIM2 was present in the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) by interacting with the inositol trisphosphate receptors (IP3Rs), voltage-dependent anion channel (VDAC), mitochondrial Ca2+ uniporter (MCU), and mitofusin-2 (MNF2). Our results suggested that, in NRVMs, STIM2.1 constitutes the predominant functional variant that negatively regulates Orai1-generated SOCE. It participates in the control of mCa2+ uptake capacity possibly via the STIM2-IP3Rs-VDAC-MCU and MNF2 complex.

Artificial intelligence, applications and challenges in simulation-based education

The rapid advancement of Artificial Intelligence (AI) has taken the world by "surprise" due to the lack of regulation over this technological innovation which, while promising application opportunities in different fields of knowledge, including education, simultaneously generates concern, rejection and even fear. In the field of Health Sciences Education, clinical simulation has transformed educational practice; however, its formal insertion is still heterogeneous, and we are now facing a new technological revolution where AI has the potential to transform the way we conceive its application.

El rápido avance de la inteligencia artificial (IA) ha tomado al mundo por "sorpresa" debido a la falta de regulación sobre esta innovación tecnológica, que si bien promete oportunidades de aplicación en diferentes campos del conocimiento, incluido el educativo, también genera preocupación e incluso miedo y rechazo. En el campo de la Educación en Ciencias de la Salud la Simulación Clínica ha transformado la práctica educativa; sin embargo, aún es heterogénea su inserción formal, y ahora nos enfrentamos a una nueva revolución tecnológica, en la que las IA tienen el potencial de transformar la manera en que concebimos su aplicación.

Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver.

The metabolic functions of the liver are spatially organized in a phenomenon called zonation, linked to the differential exposure of portal and central hepatocytes to nutrient-rich blood. The mTORC1 signaling pathway controls cellular metabolism in response to nutrients and insulin fluctuations. Here we show that simultaneous genetic activation of nutrient and hormone signaling to mTORC1 in hepatocytes results in impaired establishment of postnatal metabolic and zonal identity of hepatocytes. Mutant hepatocytes fail to upregulate postnatally the expression of Frizzled receptors 1 and 8, and show reduced Wnt/ß-catenin activation. This defect, alongside diminished paracrine Wnt2 ligand expression by endothelial cells, underlies impaired postnatal maturation. Impaired zonation is recapitulated in a model of constant supply of nutrients by parenteral nutrition to piglets. Our work shows the role of hepatocyte sensing of fluctuations in nutrients and hormones for triggering a latent metabolic zonation program.

Dependency on host vitamin B12 has shaped Mycobacterium tuberculosis Complex evolution.

Human and animal tuberculosis is caused by the Mycobacterium tuberculosis Complex (MTBC), which has evolved a genomic decay of cobalamin (vitamin B12) biosynthetic genes. Accordingly, and in sharp contrast to environmental, opportunistic and ancestor mycobacteria; we demonstrate that M. tuberculosis (Mtb), M. africanum, and animal-adapted lineages, lack endogenous production of cobalamin, yet they retain the capacity for exogenous uptake. A B12 anemic model in immunocompromised and immunocompetent mice, demonstrates improved survival, and lower bacteria in organs, in B12 anemic animals infected with Mtb relative to non-anemic controls. Conversely, no differences were observed between mice groups infected with M. canettii, an ancestor mycobacterium which retains cobalamin biosynthesis. Interrogation of the B12 transcriptome in three MTBC strains defined L-methionine synthesis by metE and metH genes as a key phenotype. Expression of metE is repressed by a cobalamin riboswitch, while MetH requires the cobalamin cofactor. Thus, deletion of metE predominantly attenuates Mtb in anemic mice; although inactivation of metH exclusively causes attenuation in non-anemic controls. Here, we show how sub-physiological levels of B12 in the host antagonizes Mtb virulence, and describe a yet unknown mechanism of host-pathogen cross-talk with implications for B12 anemic populations.

Long or complicated mpox in patients with uncontrolled HIV infection.

To date, former research about the impact of HIV infection on mpox poor outcomes is still limited and controversial. Therefore, the aim of this study was to assess the impact of HIV on the clinical course of mpox, in a large population of patients from Spain. Nationwide case-series study. Patients from 18 Spanish hospitals, with PCR-confirmed mpox from April 27, 2022 to June 30, 2023 were included in this study. The main outcome was the development of long or complicated (LC) mpox, defined as: (i) duration of the clinical course ≥ 28 days, or; (ii) disseminated disease, or: (iii) emergence of severe complications. One thousand eight hundred twenty-three individuals were included. Seven hundred eighty-six (43%) were people living with HIV (PLWH), of whom 11 (1%) had a CD4 cell count < 200 cells/mm3 and 33 (3%) <350 cells/mm3 . HIV viral load ≥ 1000 cp/mL was found in 27 (3%) PLWH, none of them were on effective ART. Fifteen (60%) PLWH with HIV-RNA ≥ 1000 cp/mL showed LC versus 182 (29%) PLWH with plasma HIV-RNA load < 1000 copies/mL and 192 (24%) individuals without HIV infection (p < 0.001). In multivariate analysis, adjusted by age, sex, CD4 cell counts and HIV viral load at the time of mpox, only plasma HIV-RNA ≥ 1000 cp/mL was associated with a greater risk of developing LC mpox [adjusted OR = 4.06 (95% confidence interval 1.57-10.51), p = 0.004]. PLWH with uncontrolled HIV infection, due to lack of ART, are at a greater risk of developing LC mpox. Efforts should be made to ensure HIV testing is carried out in patients with mpox and to start ART without delay in those tested positive.

Illuminating a Solvent-Dependent Hierarchy for Aromatic CH/π Complexes with Dynamic Covalent Glyco-Balances.

CH/π interactions are prevalent among aromatic complexes and represent invaluable tools for stabilizing well-defined molecular architectures. Their energy contributions are exceptionally sensitive to various structural and environmental factors, resulting in a context-dependent nature that has led to conflicting findings in the scientific literature. Consequently, a universally accepted hierarchy for aromatic CH/π interactions has remained elusive. Herein, we present a comprehensive experimental investigation of aromatic CH/π complexes, employing a novel approach that involves isotopically labeled glyco-balances generated in situ. This innovative strategy not only allows us to uncover thermodynamic insights but also delves into the often less-accessible domain of kinetic information. Our analyses have yielded more than 180 new free energy values while considering key factors such as solvent properties, the interaction geometry, and the presence and nature of accompanying counterions. Remarkably, the obtained results challenge conventional wisdom regarding the stability order of common aromatic complexes. While it was believed that cationic CH/π interactions held the highest strength, followed by polarized CH/π, nonpolarized CH/π, and finally anionic CH/π interactions, our study reveals that this hierarchy can be subverted depending on the environment. Indeed, the performance of polarized CH/π interactions can match or even outcompete that of cationic CH/π interactions making them a more reliable stabilization strategy across the entire spectrum of solvent polarity. Overall, our results provide valuable guidelines for the selection of optimal interacting partners in every chemical environment, allowing the design of tailored aromatic complexes with applications in supramolecular chemistry, organocatalysis, and/or material sciences.

De Novo Access to BODIPY C-Glycosides as Linker-Free Nonsymmetrical BODIPY-Carbohydrate Conjugates.

Recent years have witnessed an increasing interest in the synthesis and study of BODIPY-glycoconjugates. Most of the described synthetic methods toward these derivatives involve postfunctional modifications of the BODIPY core followed by the covalent attachment of the fluorophore and the carbohydrate through a "connector". Conversely, few de novo synthetic approaches to linker-free carbohydrate-BODIPY hybrids have been described. We have developed a reliable modular, de novo, synthetic strategy to linker-free BODIPY-sugar derivatives using the condensation of pyrrole C-glycosides with a pyrrole-carbaldehyde derivative mediated by POCl3. This methodology allows labeling of carbohydrate biomolecules with fluorescent-enough BODIPYs within the biological window, stable in aqueous media, and able to display singlet oxygen generation.

L-serine treatment in patients with GRIN-related encephalopathy: a phase 2A, non-randomized study.

GRIN-related disorders are rare developmental encephalopathies with variable manifestations and limited therapeutic options. Here, we present the first non-randomized, open-label, single-arm trial (NCT04646447) designed to evaluate the tolerability and efficacy of L-serine in children with GRIN genetic variants leading to loss-of-function. In this phase 2A trial, patients aged 2-18 years with GRIN loss-of-function pathogenic variants received L-serine for 52 weeks. Primary end points included safety and efficacy by measuring changes in the Vineland Adaptive Behavior Scales, Bayley Scales, age-appropriate Wechsler Scales, Gross Motor Function-88, Sleep Disturbance Scale for Children, Pediatric Quality of Life Inventory, Child Behavior Checklist and the Caregiver-Teacher Report Form following 12 months of treatment. Secondary outcomes included seizure frequency and intensity reduction and EEG improvement. Assessments were performed 3 months and 1 day before starting treatment and 1, 3, 6 and 12 months after beginning the supplement. Twenty-four participants were enrolled (13 males/11 females, mean age 9.8 years, SD 4.8), 23 of whom completed the study. Patients had GRIN2B, GRIN1 and GRIN2A variants (12, 6 and 5 cases, respectively). Their clinical phenotypes showed 91% had intellectual disability (61% severe), 83% had behavioural problems, 78% had movement disorders and 58% had epilepsy. Based on the Vineland Adaptive Behavior Composite standard scores, nine children were classified as mildly impaired (cut-off score > 55), whereas 14 were assigned to the clinically severe group. An improvement was detected in the Daily Living Skills domain (P = 0035) from the Vineland Scales within the mild group. Expressive (P = 0.005), Personal (P = 0.003), Community (P = 0.009), Interpersonal (P = 0.005) and Fine Motor (P = 0.031) subdomains improved for the whole cohort, although improvement was mostly found in the mild group. The Growth Scale Values in the Cognitive subdomain of the Bayley-III Scale showed a significant improvement in the severe group (P = 0.016), with a mean increase of 21.6 points. L-serine treatment was associated with significant improvement in the median Gross Motor Function-88 total score (P = 0.002) and the mean Pediatric Quality of Life total score (P = 0.00068), regardless of severity. L-serine normalized the EEG pattern in five children and the frequency of seizures in one clinically affected child. One patient discontinued treatment due to irritability and insomnia. The trial provides evidence that L-serine is a safe treatment for children with GRIN loss-of-function variants, having the potential to improve adaptive behaviour, motor function and quality of life, with a better response to the treatment in mild phenotypes.

Atypical Hemolytic Uremic Syndrome: A Nationwide Colombian Pediatric Series.

Objectives. Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease with genetic predisposition and represents up to 10% of pediatric hemolytic uremic syndrome (HUS) cases. Few studies have evaluated aHUS in Latin American population. We studied a Colombian pediatric cohort to delineate disease presentation and outcomes. Methods. A multicenter cohort of 27 Colombian children with aHUS were included. Patients were grouped by age at onset. Clinical features were compared using analysis of variance (ANOVA) and Fisher exact tests. Renal biopsy was performed on 6 patients who were suspected of having other renal diseases before aHUS diagnosis. Results. Most patients were male (70%). The onset of aHUS occurred frequently before age 4 years (60%) and followed gastroenteritis as the main triggering event (52%). Age groups showed comparable clinical presentation, disease severity, treatment, and outcomes. Pulmonary involvement (67%) was the main extrarenal manifestation, particularly in the 1 to 7 age group (P = .01). Renal biopsies were as follows: 3 had membranoproliferative glomerulonephritis (MPGN) type I, one MPGN type III, one C3-glomerulonephritis, and one rapidly progressive GN. Genetic screening was available in 6 patients and identified 2xCFHR5, 2xMCP, 1xADAMTS13/THBD, and 1xDGKE mutations. A total of 15 relapses were seen, of which 8 (72%) occurred in the 1 to 7 age group. The renal outcome was not significantly different regardless of age group. Conclusion. In our cohort, we observed a relatively high frequency of extrarenal involvement at first presentation represented by pulmonary manifestations. The renal prognosis at initial presentation was worse than in previous reports.