Diagnostic Accuracy of the Triglyceride-Glucose Index (TyG), TyG Body Mass Index, and TyG Waist Circumference Index for Liver Steatosis Detection.

BACKGROUND: The triglyceride-glucose index (TyG) and a combination of body mass index (BMI) and waist circumference (WC) have been proposed as predictive scores for liver steatosis (LS). The aim of this study was to determine the diagnostic accuracy of these indices compared with controlled attenuation parameters (CAPs) and other predictive scores of LS. METHODS: A retrospective analysis of patients who attended a check-up unit in 2021 was performed. LS was determined by CAP. Anthropometric and biochemical parameters for calculating TyG, TyG-BMI, TyG-WC, fatty liver index, and hepatic steatosis index were obtained. ROC curve was used to establish the best cut-off point of each TyG index for LS detection. The accuracy was determined for all patients, as well as for overweight and diabetic patients. RESULTS: Medical records of 855 patients with a median age of 48 [IQR, 44-54] years and a BMI of 25.7 [IQR 23.4-28.1] kg/m2 were included. According to CAP, LS prevalence was 31.8% (n = 272). TyG-BMI and TyG-WC show better AUCs compared with CAP (0.82, 0.81), FLI (0.96, both), and HSI (0.93, 0.85). For diabetic patients, TyG-WC shows an AUC of 0.70. Meanwhile, TyG-BMI shows better accuracy (0.75) compared with CAP. CONCLUSIONS: TyG-BMI and TyG-WC showed a superior predictive accuracy for detecting LS compared with the TyG index.

Low quality of maternal and child nutritional care at the primary care in Mexico: an urgent call to action for policymakers and stakeholders.

BACKGROUND: Maternal and child malnutrition represents a public health problem in Mexico Primary care (PC) is responsible for introducing women and children under five to the health system, detecting diseases on time, and providing medical services, including pharmacological treatment if necessary. Providing these services with quality is essential to improve maternal and child health. This study evaluated the quality of nutritional care during preconception, pregnancy, postpartum, infancy, and preschool age at the PC health units across six Mexican states between 2020 and 2021. METHODS: We conducted a cross-sectional study with a mixed approach in units of the Secretary of Health to assess the quality of nutritional care during preconception, pregnancy, postpartum, childhood, and preschool age. The level of quality was calculated by the percentage of compliance with 16 indicators that integrated a Quality Index of Maternal and Child Nutritional Care (ICANMI, by its Spanish acronym). Compliance by indicator, by life stage, and overall was categorized using the following cut-off points: poor quality (≤ 70%), insufficient quality (71-89%), and good quality (≥ 90%). The perceptions of the barriers and facilitators that affect maternal and child nutrition were evaluated through semi-structured interviews with health professionals (HP) and users. All qualitative instruments were developed with a gender and intercultural perspective. RESULTS: Considering the whole sample studied, maternal and child nutritional care quality during the five life stages evaluated was bad (compliance: ≤12%), reflected in the ICANMI, which had a compliance of 8.3%. Principal barriers identified to providing high-quality nutritional care were the lack of knowledge and training of health professionals, shortages of equipment, medicine, personnel, and materials, the disappearance of the social cash transfer program Prospera, the absence of local indigenous language translators to support communication between doctor and patient, and the persistence of machismo and other practices of control over women. CONCLUSIONS: These findings underscore the need for initiatives to improve the quality of nutritional care in PC facilities across Chihuahua, State of Mexico, Veracruz, Oaxaca, Chiapas, and Yucatan. It is necessary for government and health authorities, along with various stakeholders, to collaboratively devise, implement, and assess intercultural and gender-oriented policies and programs geared towards ensuring the health infrastructure and enhancing the training of health professionals to diagnose and treat the prevalence and occurrence of diverse forms of malnutrition in both maternal and child populations.

RESUMEN: ANTECEDENTES: La mala nutrición materno-infantil (MMI) representa un problema de salud pública en México. El primer nivel tiene la respondabilidad de introducir a mujeres y niños menores de 5 años al sistema de salud, detectar oportunamente las enfermedades y brindar servicios médicos incluido el farmacológico de ser necesario. Prestar estos servicios con calidad resulta elemental para mejorar la salud de la población materno-infantil. El objetivo de este estudio fue evaluar la calidad de la atención nutricional durante las etapas de preconcepción, embarazo, posparto, infancia y edad preescolar en centros de salud de seis estados de México entre 2020 y 2021. MéTODOS: Se realizó un estudio transversal con metodología mixta en 95 centros de salud la Secretaría de Salud de México para evaluar la calidad de la atención nutricional durante la preconcepción, el embarazo, el posparto, la infancia y la etapa preescolar. El nivel de calidad se calculó mediante el porcentaje de cumplimiento de 16 indicadores que a su vez integraron un Índice de Calidad de la Atención Nutricional Materno Infantil (ICANMI). El cumplimiento por indicador, etapa de vida y global fue categorizado utilizando los siguientes puntos de corte: mala calidad (≤ 70%), calidad insuficiente (71-89%) y buena calidad (≥ 90%). La percepción sobre las barreras y facilitadores que afectan la atención nutricional materno-infantil fueron identificadas a través de entrevistas semiestructuradas y grupos focales realizadas a profesionales de salud, usuarias y usuarios. Todos los instrumentos cualitativos fueron desarrollados con un enfoque de género e interculturalidad. RESULTADOS: La calidad de la atención nutricional materno infantil durante las cinco etapas de la vida evaluadas fue mala (cumplimiento: ≤12%), mientras que el ICANMI tuvo un cumplimiento de 8.3%. Las principales barreras identificadas para brindar una atención nutricional de alta calidad fueron la falta de conocimiento y capacitación de los profesionales de la salud, la escasez de equipos, medicamentos, personal y materiales, la desaparición del programa social de transferencias monetarias Prospera, la ausencia de una lengua indígena local, entre otros. Así como la persistencia de prácticas como el machismo y otras de control sobre las mujeres. CONCLUSIONES: Estos hallazgos subrayan la necesidad inmediata de implementar iniciativas que mejoren el estándar de atención nutricional en los centros de salud en Chihuahua, Estado de México, Veracruz, Oaxaca, Chiapas y Yucatán. Es necesario que el gobierno y las autoridades sanitarias, junto con diversas partes interesadas, diseñen, implementen y evalúen en colaboración políticas y programas orientados a mejorar la calidad de la atención nutricional, con perspectiva de género e interculturalidad. Este esfuerzo tiene como objetivo mitigar la prevalencia y aparición de diversas formas de desnutrición tanto en la población materna como infantil.

Prebiotics and Probiotics: Therapeutic Tools for Nonalcoholic Fatty Liver Disease.

Alterations in the gut-liver axis and changes in the gut microbiome are among the risk factors for the pathogenesis of non-alcoholic fatty liver disease (NAFLD). These patients show increased bacterial overgrowth in the small intestine and impaired intestinal permeability. Therefore, therapeutic options such as probiotics or prebiotics have been investigated to modulate intestinal microbiota composition to improve NAFLD. Most in vivo and in vitro probiotic studies have focused on reducing hepatic fat accumulation. The beneficial effects of probiotics on NAFLD have been demonstrated in animal models, and the most widely used microorganisms are those of the Lactobacillus and Bifidobacterium genera. In animal models, probiotics help restore the intestinal microbiota and improve the integrity of the intestinal barrier. This narrative review summarizes published evidence and the likely benefits of probiotics and prebiotics as a therapeutic option for patients with NAFLD.

The Interlink Between Metabolic-Associated Fatty Liver Disease and Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) affects around 10% of women in the reproductive age group and is characterized by ovulatory dysfunction, hyperandrogenism, and/or polycystic ovarian morphology. PCOS is highly associated with metabolic-associated fatty liver disease (MAFLD) as both diseases share common risk factors. At the time of diagnosis of PCOS, screening for MAFLD is necessary because most patients with MAFLD are asymptomatic. The importance of early detection of MAFLD in patients with PCOS is that a timely intervention in patients with steatosis or steatohepatitis can reduce the probability of liver disease progression.

Excavating sponges from the Pacific of Central America, descriptions and a faunistic record.

Excavating sponges are one of the main groups of bioeroders in coral reefs. Their diversity has been thoroughly studied in some regions: in the Caribbean, the Mediterranean, and the Indo-Pacific, including the Mexican Pacific. However, there is a lack of information from the Pacific of Central America, with only a few records from Panama and Costa Rica. This study provides additional distributional records and taxonomic descriptions of species collected between 2011 and 2016 at nine localities along the Pacific coast of El Salvador, Nicaragua, Costa Rica and Panama. A total of fourteen species of excavating sponges from three orders, three families, and five genera are considered valid in this area. Nine are new records for Central America, six are new records for El Salvador, three are new records for Nicaragua and eleven are new records for Costa Rica. The species collected from Panama were already recorded before. The species here described are Cliona amplicavata, Cliona californiana, Cliona euryphylle, Cliona microstrongylata, Cliona aff. mucronata, Cliona pocillopora, Cliona tropicalis, Cliona vermifera, Cliothosa tylostrongylata, Pione cf. carpenteri, Pione mazatlanensis, Thoosa calpulli, Thoosa mismalolli and Siphonodictyon crypticum. We also reviewed the literature related to excavating sponges from Central America, and the taxonomic status of respective species was updated. We provide a faunistic record of 14 excavating sponge species for Central America. Our data are expected to be useful for management and conservation purposes.

Minimal (Limited) Pseudohyperplastic Prostatic Adenocarcinoma in Needle Prostatic Biopsy.

BACKGROUND: Study of minimum adenocarcinoma has been done almost exclusively on conventional acinar adenocarcinoma. Pseudohyperplastic adenocarcinoma can be confused with benign lesions because of its well-differentiated appearance and has not been studied when the biopsy shows few malignant glands (limited carcinoma). METHODS: We reviewed 94 pseudohyperplastic adenocarcinomas diagnosed in prostatic biopsies for a period of 12 years and selected those measuring less than 1 mm or involving less than 5% of the biopsied tissue. We also reviewed 200 consecutive consultations. RESULTS: Four (4.2%) of the 94 cases were limited pseudohyperplastic adenocarcinomas, and 3 were from consultations. Three of them were mistaken for hyperplastic nodules, prostatic adenosis, or prostatic intraepithelial neoplasm. The number of glands varied between 6 and 50 (average 23). Three nodular histological patterns were identified-nodular, adenosis-like, and pseudohyperplastic carcinoma resembling prostatic intraepithelial neoplasia. The diagnosis of adenocarcinoma was not related to the number of neoplastic glands. Histological criteria that were useful included: crowded medium to large glands, papillary infoldings, branching glands, straight luminal borders, hyperchromatic nuclei, nucleomegaly, and apparent nucleoli. Areas of transition to conventional acinar adenocarcinoma were useful in recognizing four of these neoplasms, but were barely apparent in 2 of them. Hyperchromatic nuclei were found in all cases, whereas apparent nucleoli and nucleomegaly were only present in 4. CONCLUSIONS: The architectural and cytological criteria for limited acinar adenocarcinoma are only partially useful in interpreting minimum pseudohyperplastic adenocarcinomas. Knowledge of the criteria for malignancy in both neoplasms is important in order to avoid underdiagnosis of malignancy.

Development of indole/indazole-aminopyrimidines as inhibitors of c-Jun N-terminal kinase (JNK): optimization for JNK potency and physicochemical properties.

A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for JNK1 and 20 nM for JNK2, with greater than 40-fold selectivity against other kinases with good physicochemical and pharmacokinetic properties.

Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase.

The development of a new series of p38α inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38α, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.

Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxypropoxy)phenyl]methanone (RO3201195), an orally bioavailable and highly selective inhibitor of p38 MAP kinase.

A novel class of highly selective inhibitors of p38 MAP kinase was discovered from high throughput screening. The synthesis and optimization of a series of 5-amino-N-phenyl-1H-pyrazol-4-yl-3-phenylmethanones is described. An X-ray crystal structure of this series bound in the ATP binding pocket of unphosphorylated p38alpha established the presence of a unique hydrogen bond between the exocyclic amine of the inhibitor and threonine 106 which likely contributes to the selectivity for p38. The crystallographic information was used to optimize the potency and physicochemical properties of the series. The incorporation of the 2,3-dihydroxypropoxy moiety on the pyrazole scaffold resulted in a compound with excellent drug-like properties including high oral bioavailability. These efforts identified 63 (RO3201195) as an orally bioavailable and highly selective inhibitor of p38 which was selected for advancement into Phase I clinical trials.

Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase.

Inhibition of the biosynthesis of proinflammatory cytokines such as tumor necrosis factor and interleukin-1 via p38 has been an approach toward the development of a disease modifying agent for the treatment of chronic inflammation and autoimmune diseases. The development of a new core structure of p38 inhibitors, 3-(4-fluorophenyl)-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine, is described. X-ray crystallographic data of the lead bound to the active site of p38 was used to guide the optimization of the series. Specific focus was placed on modulating the physical properties of the core while maintaining potent inhibition of p38. These efforts identified 42c as a potent inhibitor of p38, which also possessed the required physical properties worthy of advanced studies.