Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.

Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.

Fortalecimiento muscular de cadera y rodilla en el síndrome doloroso patelofemoral: Revisión sistemática y metaanálisis / Hip and knee muscle strengthening in patellofemoral pain syndrome: Systematic review and meta-analysis / Fortalecimento muscular do quadril e joelho na síndrome da dor patelofemoral: revisão sistemática e meta-análise

El síndrome doloroso patelofemoral (SDPF) es una condición musculoesquelética frecuente que se manifiesta con dolor retro y peripatelar. El fortalecimiento muscular de cadera y rodilla (FCR) ha sido propuesto como un tratamiento apropiado para el SDPF. Es precisa una revisión que compare los resultados del FCR con otras intervenciones utilizando evidencia científica actual. OBJETIVO: evaluar la efectividad del FCR en pacientes con SDPF. MATERIALES Y MÉTODOS: la revisión sistemática (RS) y metaanálisis (MA) siguieron las directrices PRISMA. El cribaje y selección de estudios se realizó mediante el programa Rayyan. Nueve artículos fueron incluidos y evaluados con la escala PEDro y la herramienta Riesgo de Sesgo de Cochrane. El MA se realizó en la aplicación Jamovi. Las variables utilizadas fueron dolor, funcionalidad y fuerza muscular. RESULTADOS: el MA demostró que el FCR fue superior en la disminución del dolor (2.30;1.18, 3.42; 95%IC) (1.76; 0.70, 2.81; 95%IC) y el incremento de la funcionalidad (14.30 ;7.49, 21.11; 95%IC) (8.66 ;3.08, 14.23; 95%IC) comparado con los grupos sin intervención (NI) y los del fortalecimiento de rodilla (FR), respectivamente; mientras que la adición de intervenciones al fortalecimiento de cadera y rodilla (FCR+) demostró mayores beneficios en la funcionalidad (-5.71; -8.32, -3.10; 95%IC) al compararse con el FCR. Así mismo, el análisis cualitativo de la variable fuerza muscular estableció que el FCR obtuvo mejores resultados que los grupos de FR y FCR+ ejercicios de control motor. CONCLUSIONES: el FCR es una intervención efectiva en la reducción del dolor, el incremento de la funcionalidad y fuerza muscular en pacientes con SDPF.

Patellofemoral pain syndrome (PFPS) is a common musculoskeletal condition that manifests with retro- and peripatellar pain. Hip and knee muscle strengthening (HKS) has been proposed as an appropriate treatment for PFPS. A review comparing the results of HKS with other interventions using current scientific evidence is needed. OBJECTIVE: to evaluate the effectiveness of HKS in patients with PFPS. MATERIALS AND METHODS: the systematic review (SR) and meta-analysis (MA) followed PRISMA guidelines. Screening and selection of studies was performed using the Rayyan program. Nine articles were included and evaluated with the PEDro scale and the Cochrane Risk of Bias tool. The MA was performed in the Jamovi application. The variables used were pain, functionality and muscle strength. RESULTS: the MA showed that the HKS was superior in decreasing pain (2.30; 1.18, 3.42; 95%CI) (1.76; 0.70, 2.81; 95%CI) and increasing functionality (14.30; 7.49, 21.11; 95%CI) (8.66; 3.08, 14.23; 95%CI) compared to the no intervention (NI) and knee strengthening (KS) groups, respectively; while the addition of interventions to hip and knee strengthening (HKS+) demonstrated greater benefits in functionality (-5.71; -8.32, -3.10; 95%CI) when compared to HKS. Likewise, qualitative analysis of the muscle strength variable established that the HKS obtained better results than the KS and HKS+ motor control exercises groups. CONCLUSIONS: HKS is an effective intervention in reducing pain, increasing functionality and muscle strength in patients with PFPS.

A síndrome da dor patelofemoral (SDPF) é uma condição musculoesquelética comum que se manifesta com dor retro e peripatelar. O fortalecimento dos músculos do quadril e joelho (FQJ) foi proposto como um tratamento adequado para o SDPF. É necessária uma revisão comparando os resultados da FQJ com outras intervenções utilizando as evidências científicas atuais. OBJETIVO: avaliar a eficácia da FQJ em pacientes com SDPF. MATERIAIS E MÉTODOS: a revisão sistemática (RS) e a meta-análise (MA) seguiram as diretrizes do PRISMA. A triagem e seleção dos estudos foi realizada utilizando o software Rayyan. Nove artigos foram incluídos e avaliados utilizando a escala PEDro e a ferramenta Cochrane Risk of Bias. O MA foi realizado na aplicação Jamovi. As variáveis utilizadas foram dor, funcionalidade e força muscular. RESULTADOS: o MA mostrou que o FQJ foi superior em diminuição da dor (2,30; 1,18, 3,42; 95%CI) (1,76; 0,70, 2,81; 95%CI) e aumento da função (14,30; 7,49, 21,11; 95%CI) (8,66; 3,08, 14.23; 95%CI) em comparação com os grupos sem intervenção (NI) e de fortalecimento do joelho (FJ), respectivamente; enquanto a adição de intervenções de fortalecimento do quadril e joelho (FQJ+) demonstrou maiores benefícios em função (-5,71; -8,32, -3,10; 95%CI) quando comparado com o FQJ. Da mesma forma, a análise qualitativa da variável força muscular estabeleceu que o FQJ teve melhor desempenho do que os grupos FJ e FQJ+ exercícios de controlo do motor. CONCLUSÕES: o FQJ é uma intervenção eficaz na redução da dor, aumentando a funcionalidade e a força muscular em pacientes com SDPF.

Evaluation of the microbiological quality of natural processed products for medicinal use marketed in Quito, Ecuador. / Evaluación de la calidad microbiológica de productos naturales procesados de uso medicinal comercializados en Quito, Ecuador.

OBJECTIVES: To determine the microbiological quality of samples from processed natural products used for medicinal purposes and marketed in Quito, Ecuador. MATERIALS AND METHODS: Aerobic microorganisms, molds and yeasts were counted by conventional standardized techniques, according to the United States Pharmacopoeia (USP), in samples from 83 products. The microorganisms found were identified and their antimicrobial sensitivity was determined using the agar diffusion method. RESULTS: The total aerobic microorganism count exceeded the specified limits in 17.0% of syrups, 27.0% of topical products and 43.0% of oral solids; the molds and yeasts count exceeded the limit in 33.0% of syrups, 7.0% of topical products and 36.0% of oral solids. Products for eye use did not pass the sterility test. The most frequently isolated bacterial genus was Bacillus, followed by Escherichia coli, Klebsiella and Enterobacter. Salmonella and Staphylococcus aureus were not found in any product, but potentially pathogenic microorganisms such as Pseudomonas were isolated in 40.0% of the eye drops. Enterobacter and Escherichia coli showed resistance to multiple compounds and Pseudomonas was not resistant to any antibiotic. CONCLUSIONS: The microbiological quality of the products examined was not adequate. Potentially pathogenic and antibiotic resistant microorganisms were isolated from the samples. These products may not be suitable for distribution and consumption, even though many of them have sanitary registration. Control and regulation by the corresponding authorities is essential.

OBJETIVOS: Determinar la calidad microbiológica de una muestra de productos naturales procesados de uso medicinal de libre comercio en Quito, Ecuador. MATERIALES Y MÉTODOS: 83 productos se sometieron a recuentos de microorganismos aerobios, mohos y levaduras por técnicas convencionales estandarizadas, de acuerdo a la Farmacopea de los Estados Unidos (USP, por sus siglas en inglés). Se identificaron los microorganismos presentes y se determinó su sensibilidad antimicrobiana usando el método de difusión en agar. RESULTADOS: El 17,0% de los jarabes, el 27,0% de los productos tópicos y el 43,0% de los sólidos orales excedieron los límites especificados para el recuento total de microorganismos aerobios, mientras que el 33,0% de los jarabes, el 7,0% de los productos tópicos y el 36,0% de los sólidos orales excedieron el límite para mohos y levaduras. Los productos de uso ocular no pasaron la prueba de esterilidad. El género bacteriano más frecuentemente aislado fue Bacillus, seguido por Escherichia coli, Klebsiella y Enterobacter. Salmonella ni Staphylococcus aureus se encontraron en ningún producto, pero microorganismos potencialmente patógenos como Pseudomonas se aislaron en el 40,0% de los colirios. Enterobacter y Escherichia coli mostraron resistencia a múltiples compuestos y Pseudomonas no fue resistente a ningún antibiótico. CONCLUSIONES: La calidad microbiológica de los productos examinados no fue adecuada. Se aislaron microorganismos potencialmente patógenos y resistentes a antibióticos. Estos productos podrían no ser aptos para su distribución y consumo, aun cuando muchos de ellos cuenten con registro sanitario. El control y regulación por los entes responsables es indispensable.

Evaluación de la calidad microbiológica de productos naturales procesados de uso medicinal comercializados en Quito, Ecuador / Evaluation of the microbiological quality of natural processed products for medicinal use marketed in Quito, Ecuador

RESUMEN Objetivos: Determinar la calidad microbiológica de una muestra de productos naturales procesados de uso medicinal de libre comercio en Quito, Ecuador. Materiales y métodos: 83 productos se sometieron a recuentos de microorganismos aerobios, mohos y levaduras por técnicas convencionales estandarizadas, de acuerdo a la Farmacopea de los Estados Unidos (USP, por sus siglas en inglés). Se identificaron los microorganismos presentes y se determinó su sensibilidad antimicrobiana usando el método de difusión en agar. Resultados: El 17,0% de los jarabes, el 27,0% de los productos tópicos y el 43,0% de los sólidos orales excedieron los límites especificados para el recuento total de microorganismos aerobios, mientras que el 33,0% de los jarabes, el 7,0% de los productos tópicos y el 36,0% de los sólidos orales excedieron el límite para mohos y levaduras. Los productos de uso ocular no pasaron la prueba de esterilidad. El género bacteriano más frecuentemente aislado fue Bacillus, seguido por Escherichia coli, Klebsiella y Enterobacter. Salmonella ni Staphylococcus aureus se encontraron en ningún producto, pero microorganismos potencialmente patógenos como Pseudomonas se aislaron en el 40,0% de los colirios. Enterobacter y Escherichia coli mostraron resistencia a múltiples compuestos y Pseudomonas no fue resistente a ningún antibiótico. Conclusiones: La calidad microbiológica de los productos examinados no fue adecuada. Se aislaron microorganismos potencialmente patógenos y resistentes a antibióticos. Estos productos podrían no ser aptos para su distribución y consumo, aun cuando muchos de ellos cuenten con registro sanitario. El control y regulación por los entes responsables es indispensable.

ABSTRACT Objectives: To determine the microbiological quality of samples from processed natural products used for medicinal purposes and marketed in Quito, Ecuador. Materials and methods: Aerobic microorganisms, molds and yeasts were counted by conventional standardized techniques, according to the United States Pharmacopoeia (USP), in samples from 83 products. The microorganisms found were identified and their antimicrobial sensitivity was determined using the agar diffusion method. Results: The total aerobic microorganism count exceeded the specified limits in 17.0% of syrups, 27.0% of topical products and 43.0% of oral solids; the molds and yeasts count exceeded the limit in 33.0% of syrups, 7.0% of topical products and 36.0% of oral solids. Products for eye use did not pass the sterility test. The most frequently isolated bacterial genus was Bacillus, followed by Escherichia coli, Klebsiella and Enterobacter. Salmonella and Staphylococcus aureus were not found in any product, but potentially pathogenic microorganisms such as Pseudomonas were isolated in 40.0% of the eye drops. Enterobacter and Escherichia coli showed resistance to multiple compounds and Pseudomonas was not resistant to any antibiotic. Conclusions: The microbiological quality of the products examined was not adequate. Potentially pathogenic and antibiotic resistant microorganisms were isolated from the samples. These products may not be suitable for distribution and consumption, even though many of them have sanitary registration. Control and regulation by the corresponding authorities is essential.

The training and fieldwork experiences of community health workers conducting population-based, noninvasive screening for CVD in LMIC.

BACKGROUND: Cardiovascular disease (CVD) is on the rise in low- and middle-income countries and is proving difficult to combat due to the emphasis on improving outcomes in maternal and child health and infectious diseases against a backdrop of severe human resource and infrastructure constraints. Effective task-sharing from physicians or nurses to community health workers (CHW) to conduct population-based screening for persons at risk has the potential to mitigate the impact of CVD on vulnerable populations. CHW in Bangladesh, Guatemala, Mexico, and South Africa were trained to conduct noninvasive population-based screening for persons at high risk for CVD. OBJECTIVES: This study sought to quantitatively assess the performance of CHW during training and to qualitatively capture their training and fieldwork experiences while conducting noninvasive screening for CVD risk in their communities. METHODS: Written tests were used to assess CHW's acquisition of content knowledge during training, and focus group discussions were conducted to capture their training and fieldwork experiences. RESULTS: Training was effective at increasing the CHW's content knowledge of CVD, and this knowledge was largely retained up to 6 months after the completion of fieldwork. Common themes that need to be addressed when designing task-sharing with CHW in chronic diseases are identified, including language, respect, and compensation. The importance of having intimate knowledge of the community receiving services from design to implementation is underscored. CONCLUSIONS: Effective training for screening for CVD in community settings should have a strong didactic core that is supplemented with culture-specific adaptations in the delivery of instruction. The incorporation of expert and intimate knowledge of the communities themselves is critical, from the design to implementation phases of training. Challenges such as role definition, defining career paths, and providing adequate remuneration must be addressed.

Training and supervision of community health workers conducting population-based, noninvasive screening for CVD in LMIC: implications for scaling up.

BACKGROUND: Community health workers (CHW) can screen for cardiovascular disease risk as well as health professionals using a noninvasive screening tool. However, this demonstrated success does not guarantee effective scaling of the intervention to a population level. OBJECTIVES: This study sought to report lessons learned from supervisors' experiences monitoring CHW and perceptions of other stakeholders regarding features for successful scaling of interventions that incorporate task-sharing with CHW. METHODS: We conducted a qualitative analysis of in-depth interviews to explore stakeholder perceptions. Data was collected through interviews of 36 supervisors and administrators at nongovernmental organizations contracted to deliver and manage primary care services using CHW, directors, and staff at the government health care clinics, and officials from the departments of health responsible for the implementation of health policy. RESULTS: CHW are recognized for their value in offsetting severe human resource shortages and for their expert community knowledge. There is a lack of clear definitions for roles, expectations, and career paths for CHW. Formal evaluation and supervisory systems are highly desirable but nonexistent or poorly implemented, creating a critical deficit for effective implementation of programs using task-sharing. There is acknowledgment of environmental challenges (e.g., safety) and systemic challenges (e.g., respect from trained health professionals) that hamper the effectiveness of CHW. The government-community relationships presumed to form the basis of redesigned health care services have to be supported more explicitly and consistently on both sides in order to increase the acceptability of CHW and their effectiveness. CONCLUSIONS: The criteria critical for successful scaling of CHW-led screening are consistent with evidence for scaling-up communicable disease programs. Policy makers have to commit appropriate levels of resources and political will to ensure successful scaling of this intervention.

Implementation of a stroke registry is associated with an improvement in stroke performance measures in a tertiary hospital in Mexico.

BACKGROUND: Stroke registries provide a simple way for improving patient care, and its use has been associated with a better adherence to the published guidelines. Few Latin American countries had established stroke registries. Our study is the first in Mexico to report the effects of implementing a stroke registry. To determine if the implementation of a systematized registry is associated with an improved adherence to the performance measures. METHODS: We compared prospective data (August 2008-November 2010) against historical controls (February 2005-July 2008). Our stroke registry (i-Registro Neurovascular) consists of a standardized clinical form that includes demographic and clinical variables (risk factors, medications, neuroimaging, etiology, acute and outpatient treatments, and neurologic scores [National Institutes of Health Stroke Scale and modified Rankin Scale]). We evaluated 9 performance measures suggested by the American Heart Association and the Joint Commission. RESULTS: We analyzed the data from 574 patients, 260 from the prospective phase and 314 from historical controls. No significant statistical differences in demographic characteristics or stroke risk factors were found. The implementation of the stroke registry was associated with a statistically significant (P < .05) improvement in almost all of the acute performance measures. The composite measure also showed an improvement form 52.6%-68.8% (P < .001). CONCLUSIONS: The implementation of a systematized registry significantly improved our clinical practice. This intervention is a low cost and readily achievable and a viable option for encouraging an increased report of guidelines adherence of other hospitals in Latin America.

Debaryomyces hansenii and Rhodotorula mucilaginosa comprised the yeast core gut microbiota of wild and reared carnivorous salmonids, croaker and yellowtail.

This is the first study using molecular and culture-based methods aimed at investigating the composition of the intestinal yeast microbiota of wild and reared carnivorous salmonids, croaker and yellowtail, to characterize their cores and to evaluate the enzymatic activities of the cultivated yeast. Among 103 samples from salmonids, croaker and yellowtail, yeast were detected in 85.4%, with 43 species identified. The core of reared fish was composed of eight species, in contrast to the wild fish core, which consisted of two species: Debaryomyces hansenii and Rhodotorula mucilaginosa. Despite the smaller diversity of the wild fish core, similar enzymatic profiles were detected for the species from the wild and reared cores. For principal component analysis, samples grouped together independently of host species, domestication status and location. A high proportion of yeast produced aminopeptidases and lipases, which may be explained by the high proportion of protein and lipids in the carnivorous diet. This study reveals the presence of a yeast community in the fish gut that appears to be strongly shaped by a carnivorous diet. Yeast in the gut increases the repertoire of microorganisms interacting with the host intestine, which could influence health and disease.

Effect of flavonoids from Exellodendron coriaceum (Chrysobalanaceae) on glucose-6-phosphatase.

From the n-butanol extract of the aerial parts of Exellodendron coriaceum (Benth.) Prance the flavonoids quercetin-3-O-beta-D-galactopyranoside (1), quercetin-3-O-alpha-L-arabinopyranoside (2), quercetin-3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-rhamnopyranoside (3), and quercetin-3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-galactopyranoside (4) were isolated. Additionally from this extract three flavonoids were isolated and partially characterized as quercetin glycosides. All these compounds were tested for their hypoglycemic activity using the glucose-6-phosphatase microsomal hepatic system. The flavonoids inhibited the activity of the enzyme when intact microsomes were used, the highest percentage of inhibition being 65%. To the best of our knowledge, this is the first report of chemical and biological activity of E. coriaceum.