Trimethylamine N-oxide and kidney diseases: what do we know? / N-óxido de trimetilamina e doenças renais: o que sabemos?

Abstract In the human gut, there is a metabolically active microbiome whose metabolic products reach various organs and are used in the physiological activities of the body. When dysbiosis of intestinal microbial homeostasis occurs, pathogenic metabolites may increase and one of them is trimethyl amine-N-oxide (TMAO). TMAO is thought to have a role in the pathogenesis of insulin resistance, diabetes, hyperlipidemia, atherosclerotic heart diseases, and cerebrovascular events. TMAO level is also associated with renal inflammation, fibrosis, acute kidney injury, diabetic kidney disease, and chronic kidney disease. In this review, the effect of TMAO on various kidney diseases is discussed.

Resumo No intestino humano, existe um microbioma metabolicamente ativo cujos produtos metabólicos alcançam diversos órgãos e são utilizados nas atividades fisiológicas do corpo. Quando ocorre disbiose da homeostase microbiana intestinal, os metabólitos patogênicos podem aumentar, e um deles é o N-óxido de trimetilamina (TMAO). Acredita-se que o TMAO tenha um papel na patogênese da resistência à insulina, diabetes, hiperlipidemia, doenças cardíacas ateroscleróticas e eventos cerebrovasculares. O nível de TMAO também está associado à inflamação renal, fibrose, lesão renal aguda, doença renal diabética e doença renal crônica. Nesta revisão, discute-se o efeito do TMAO em diversas doenças renais.

Using guinea pig as a model for evaluation of equine influenza vaccine

Equine influenza is a highly contagious viral disease, specially among 1-5 years old naive horses. Vaccination is considered the best way to control the disease spread and outbreaks. Although foals are the main animal used for evaluation of equine influenza vaccines, guinea pigs were chosen as an alternative model in the present work, as they have a negligible antibody titer against equine influenza virus and are cheaper and easier to handle than foals. Five equine influenza vaccine batches were evaluated in two animal models, foals and guinea pigs, by injection of two doses/animal with 4 weeks apart using 2 mL/animal/dose and evaluation of immune responses by hemagglutination inhibition test and enzyme-linked immunosorbent assay. On the 7th week post vaccination, equine influenza antibodies titers reached maximum values of 9-10.2 and 8.7-10 hemagglutination inhibition units for foals and guinea pigs, respectively; sample/negative ratios were 0.126-0.464 and 0.128-0.445 for both animals, respectively. The use of guinea pigs as an animal model for the evaluation of equine influenza vaccines could be recommended instead of foals.

La gripe equina es una enfermedad viral muy contagiosa, especialmente entre los caballos jóvenes de 1 a 5 años de edad. La vacunación se considera la mejor forma de controlar la propagación y los brotes de la enfermedad. Aunque los potros son el principal animal utilizado para la evaluación de vacunas contra la gripe equina, en el presente trabajo se eligieron cobayos como modelo alternativo, ya que tienen un título insignificante de anticuerpos contra el virus de la gripe equina y son más baratos y fáciles de manejar que los potros. Se evaluaron cinco lotes de vacunas contra la gripe equina en dos modelos animales, potros y cobayos, mediante la inyección de dos dosis/animal con 4 semanas de intervalo utilizando 2 mL/animal/dosis y la evaluación de las respuestas inmunitarias mediante la prueba de inhibición de la hemaglutinación y el ensayo inmunoenzimático. En la 7ª semana posvacunación, los títulos de anticuerpos contra la gripe equina alcanzaron valores máximos de 9-10,2 y 8,7-10 unidades de inhibición de la hemaglutinación para potros y cobayos, respectivamente; las relaciones muestras/negativos fueron de 0,126-0,464 y 0,128-0,445 para ambos animales, respectivamente. Podría recomendarse el uso de cobayos como modelo animal para la evaluación de vacunas contra la gripe equina, en lugar de potros.

Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review

ABSTRACT Objective To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. Methods This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. Results The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. Conclusion This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

The role of trimethylamine-N-oxide level in the diagnosis of diabetic retinopathy and the differential diagnosis of diabetic and nondiabetic retinopathy / Papel do nível de N-óxido de trimetilamina no diagnóstico da retinopatia diabética e no diagnóstico diferencial da retinopatia diabética e não-diabética

ABSTRACT Purpose: Trimethylamine N-oxide serum levels have been associated with type 2 diabetes mellitus and its complications. The current study aimed to find out if plasma trimethylamine N-oxide level may be a novel marker in the diagnosis of diabetic retinopathy and if it can be used in the differential diagnosis of diabetic and nondiabetic retinopathy. Methods: The study included 30 patients with diabetic retinopathy, 30 patients with nondiabetic retinopathy, 30 patients with type 2 diabetes mellitus without retinopathy, and 30 healthy control participants. Biochemical parameters, serum IL-6, TNF-α, and trimethylamine N-oxide levels were measured in all participants. Results: Trimethylamine N-oxide level was significantly higher in diabetic retinopathy than in the other groups (p<0.001). There was no significant difference in trimethylamine N-oxide levels between nondiabetic retinopathy and control or type 2 diabetes mellitus Groups. There was a significant positive correlation between trimethylamine N-oxide level and elevated FPG, BMI, HOMA-IR score, BUN, IL-6, and TNF-α levels. Conclusion: The current study showed that the trimethylamine N-oxide level is elevated in diabetic retinopathy. These findings suggest that serum trimethylamine N-oxide level might be a novel marker for diabetic retinopathy, and it might be used in the differential diagnosis of diabetic and nondiabetic retinopathy.

RESUMO Objetivo: Os níveis séricos de N-óxido de trimetilamina têm sido associados ao diabetes mellitus tipo 2 e suas complicações. O presente estudo tem como objetivo responder a duas questões, entre elas: O nível plasmático de N-óxido de trimetilamina poderia ser um novo marcador no diagnóstico de retinopatia diabética? e Ele poderia ser utilizado no diagnóstico diferencial de retinopatia diabética e não diabética? Métodos: Trinta pacientes com retinopatia diabética, 30 pacientes com retinopatia não diabética, 30 pacientes com diabetes mellitus tipo 2 sem retinopatia e 30 participantes saudáveis do grupo controle foram incluídos no estudo. Parâmetros bioquímicos, níveis séricos de IL-6, de TNF-α e de N-óxido de trimetilamina foram medidos em todos os participantes. Resultados: O nível de N-óxido de trimetilamina foi significativamente maior na retinopatia diabética do que nos outros grupos (p<0,001). Não houve diferença significativa no nível de N-óxido de trimetilamina entre o grupo de retinopatia não diabética, do grupo controle ou do grupo de diabetes mellitus tipo 2. Houve uma correlação positiva significativa entre o nível de N-óxido de trimetilamina e os níveis elevados de FPG, IMC, HOMA-IR, BUN, IL-6 e TNF-α. Conclusão: O estudo atual mostrou que o nível de N-óxido de trimetilamina encontra-se elevado na retinopatia diabética. Esses achados sugerem que o nível sérico de N-óxido de trimetilamina pode ser um novo marcador na retinopatia diabética, podendo ser usado no diagnóstico diferencial de retinopatia diabética e não diabética.

Research progress on m5C methylation and its prospects in tumor immunotherapy / 口腔疾病防治

@#Epigenetic modification plays an important role in the biological regulatory process of eukaryotic cells. Tumor immunotherapy is an important means and clinical strategy for the treatment of some cancers. 5-Methylcytosine (m5C) is an important component of the epigenetic regulatory network discovered after m6A and has become a new topic for life science research in recent years. The m5C methylation of RNA can affect the fate of the modified RNA molecules and play an important role in various biological processes, including RNA stability, protein synthesis and transcriptional regulation. Recent studies have shown that m5C writers, erasers and readers are related to a variety of cellular biological processes and systemic diseases, including the occurrence, metastasis and tumor immune microenvironment. m5C methylation can widely affect gene expression and the biological process of tumorigenesis and development at multiple levels, but its specific mechanism and potential interaction with other epigenetic modifications in tumor immunotherapy are still unclear, and its regulatory mechanism, risk assessment and role in targeted therapy for malignant tumors need to be further studied. This article will review the dynamic regulatory network of m5C, the biological role of m5C modification in solid tumors and potential targets in tumor immunotherapy.

Effects of paternal pre-conceptional n-3 polyunsaturated fatty acids on telomere length in the offspring / 公共卫生与预防医学

Objective To investigate the effects of paternal pre-conceptional n-3 polyunsaturated fatty acids (n-3 PUFAs) on telomere length (TL) in the offspring. Methods Three to four-week old male C57 BL/6J mice (Father) were randomly divided into three groups and fed either an n-3 PUFA-deficient (n-3 D) (n-6:n-3 PUFA ratio = 47.2:1) diet, a diet with normal n-3 PUFA content (n-3 N) (n-6:n-3 PUFA ratio = 4.3:1), or a diet with high n-3 PUFA content (n-3 H) (n-6:n-3 ratio = 1.5:1), for 12 weeks. Then, the offspring were generated by mating the father mice with 12-week-old virgin female C57 BL/6J mice. The TL, mRNA expression of telomere transcriptase and binding proteins, as well as DNA methylation in the TERT promoter region were determined in adult offspring mice. Results Compared to n-3 N diet, paternal feeding with n-3 D diet during preconception decreased offspring TL in the peripheral blood cells, liver, adipose tissue and brain, accompanied by upregulated hepatic mRNA expression of TIN2 in the female, and downregulated hepatic expression of TERC, and binding proteins TRF2 and POT1a in the male. Meanwhile, paternal n-3 D diet shortened testis TL in offspring instead of themselves, with altered mRNA expression of TERT and binding proteins TRF1, TRF2 and POT1a. Paternal n-3 H diet showed no differences in effects on offspring TL and expressions of TERC and binding proteins with n-3 N diet, but normalized the alterations in associated parameters resulted from paternal n-3 D diet. In addition, although paternal n-3 D or n-3 H diet did not affect testis TL in themselves compared to n-3 N diet, fathers fed n-3 H diet had longer testis TL and higher expression of TRF1, TRF2, POT1a and RAP1 than those fed n-3 D diet. Finally, the DNA methylation fraction in the TERT promoter in offspring testes and male offspring liver was no difference between paternal n-3 D and n-3 N diet groups. CpG sites with altered methylation were less (1 site) between paternal n-3 H and n-3 N diet groups than those (5 sites) between paternal n-3 H and n-3 D diet groups in male offspring liver and testes. Conclusion Maintaining paternal optimal n-3 PUFA status in pre-conception increases offspring TL, probably mediated by inheritance from increased TL in father and regulation on expressions of telomere transcriptase and binding proteins in the offspring, which may be helpful for promoting offspring development and disease prevention in adulthood.

Prevention and treatment of lipoic acid-niacin on blue-light-induced retinal damage in rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the preventive effect and optimal drug dose of lipoic acid-niacin(N2L)against blue light-induced retinal damage in SD rats, and to explore its possible protective mechanism.METHODS: A total of 36 specific pathogen free-grade male SD rats of 150-200 g were selected and randomly divided into normal control group, blue light injury group, N2L low-dose group(1.0 mg/kg), N2L medium-dose group(2.5 mg/kg), N2L high-dose group(5.0 mg/kg), and physiological saline group, with 6 rats in each group. The normal control group was reared in a 12 h dark and light cycle, and the rest of the groups received 9 h of daily light exposure, 3 h of blue light irradiation with a wavelength of 455 nm and an intensity of 3000±50 lx, and 12 h of darkness to establish the injury model, and were exposed to light exposure for 14 d. For 14 consecutive durations, a 1 mL dose of the corresponding drug was injected intraperitoneally. The rats were reared for another 5 d with a regular 12 h light-dark cycle and were examined by electroretinography. Specimens were prepared by over anesthesia, HE staining, and the thickness of the outer nuclear layer was observed under a optical microscope; superoxide dismutases(SOD)activity was detected by CheKineTM SOD Activity Assay Kit; and the retinal Caspase-3, quinone oxidoreductase 1(NQO1), glutathione S transferase(GST), Bcl-2, and Bax protein expression in rat retina were detected by Western blot.RESULTS: The amplitude of b-wave in dark-vision ERG 3.0 and 10.0(cd·s)/m2 stimulated light, b-wave in bright-vision ERG 3.0(cd·s)/m2 stimulated light, and the amplitude of the 2nd wave peak of oscillatory potential were significantly lower in blue light injury group than that in the normal control group(all P&#x0026;#x003C;0.01), while the amplitude was significantly higher in the N2L medium-dose group than in the blue light injury group(all P&#x0026;#x003C;0.05), and was not statistically different from that of the normal control group; the thickness of the retina in the blue light injury group was decreased in the ONL compared with that of the normal control group(P&#x0026;#x003C;0.001), while in the N2L medium dose group, it was thicker than that of the blue light injury group(P&#x0026;#x003C;0.001), and there was no statistically significant difference from the normal control group; SOD activity was significantly higher in the N2L medium-dose group than in the remaining 5 groups(P&#x0026;#x003C;0.05); the expression of Caspase-3, Bax, and NQO1 in the blue light injury group was higher than that of the normal control group(all P&#x0026;#x003C;0.01), and expression of Bax and Caspase-3 was significantly lower in the N2L medium-dose group compared with the blue light injury group(all P&#x0026;#x003C;0.001), whereas GST, NQO1 and Bcl-2 were significantly increased(all P&#x0026;#x003C;0.01).CONCLUSION:A concentration of 2.5 mg/kg N2L can effectively antagonize the damaging effect of blue light on the retina of SD rats, and it is expected to be a preventive and curative drug for it.

Identification and Analysis of NnOMT and NnNMT Gene Families in Nelumbo nucifera / 中国实验方剂学杂志

ObjectiveThe biosynthetic pathways of benzylisoquinoline alkaloids（BIAs） in Nelumbo nucifera are of great theoretical and economic value. In this paper， N. nucifera O-methyltransferase（NnOMT） and N. nucifera N-methyltransferase（NnNMT） gene families were identified and analyzed by bioinformatics in order to facilitate the biosynthetic pathway of BIAs in N. nucifera. MethodBased on the whole genome of N. nucifera， UniPort and National Center for Biotechnology Information（NCBI） databases were used to identify the NnOMT and NnNMT gene families of N. nucifera， and analyze their physicochemical properties and subcellular localization， then TBtools， MEME， MEGA 11.0， FigTree 1.4.4 and other tools were used to analyze the phylogeny， sequence characteristics， gene structure， functional annotation and cis-acting elements of NnOMT and NnNMT genes identified in the previous stage. ResultA total of 61 NnOMT and NnNMT genes were identified in this paper， the number of amino acids encoded by these genes ranged from 168 aa to 580 aa， the isoelectric point ranged from 4.76 to 9.16， and the relative molecular weight ranged from 18 699.52 Da to 64 934.53 Da， most of which showed acidic and mostly hydrophilic proteins. There were 10 conserved motifs， Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis enriched a total of 12 pathways， including metabolism， biosynthesis of phenylpropane and isoquinoline alkaloids， etc. And Visualization of Gene Ontology（GO） enrichment results showed that 61 NnOMT and NnNMT genes were annotated to 32 items， which included 16 molecular functions［such as reduced nicotinamide adenine dinucleotide（NADH） activity and exopeptidase activity］ and 16 biological processes（such as metabolic process of carbon tetrachloride， anaerobic carbon tetrachloride metabolic process and responses to exogenous biological stimuli）. There were a variety of cis-acting elements in the promoter regions of NnOMT and NnNMT genes， mainly promoter and enhancer regions element， light responsive element and methyl jasmonate responsive element. ConclusionIn this study， a comprehensive bioinformatics analysis of 61 NnOMT and NnNMT genes is carried out based on the genome data of N. nucifera， which lays a foundation for research on the gene structure and function of NnOMT and NnNMT gene families， and provides a reference for biosynthetic pathway elucidation of BIAs in N. nucifera.

Lesiones cutáneas asociadas con el uso de respiradores N95 en profesionales de la salud de Brasil durante 2020 / Skin lesions associated with the use of N95 respirators among health professionals in Brazil in 2020 / Lesões de pele associadas ao uso de respiradores N95 entre profissionais de saúde no Brasil em 2020

Objetivo: investigar la prevalencia de lesiones cutáneas y factores asociados con el uso de respiradores N95 en profesionales de la salud de Brasil. Método: estudio transversal realizado con 11.368 profesionales de la salud en el que se empleó un método de muestreo dirigido por encuestados adaptado para entornos en línea. Se ejecutaron análisis univariados y multivariados para investigar la asociación entre la variable "lesiones cutáneas por utilizar respiradores N95" y sexo, categoría profesional, lugar de trabajo, capacitación, diagnóstico de COVID-19 y disponibilidad de suficiente provisión de Equipo de Protección Personal de buena calidad. Resultados: la prevalencia de lesiones cutáneas fue del 61,8%. Las mujeres fueron 1,203 veces (IC 95%: 1,154-1,255) más propensas a desarrollar lesiones que los hombres. La probabilidad de lesiones cutáneas en psicólogos (RP=0,805; IC 95%: 0,678-0,956) y dentistas (RP=0,884; IC 95%: 0,788-0,992) fue menor en comparación con la encontrada en los profesionales de Enfermería. Los profesionales con diagnóstico positivo de COVID-19 y que trabajan en la Unidad de Cuidados Intensivos son más propensos a sufrir lesiones cutáneas (RP=1,074; IC 95%: 1,042-1,107); (RP=1,203; IC 95%: 1,168-1,241), respectivamente, Conclusión: la prevalencia de lesiones cutáneas causadas por utilizar respiradores N95 fue del 61,8% y estuvo asociada al sexo femenino, a la categoría profesional, al lugar de trabajo, a la capacitación, a diagnóstico de COVID-19 y a la disponibilidad de suficiente provisión de Equipo de Protección Personal de buena calidad.

Objective: to investigate the prevalence of skin lesions and factors associated with the use of N95 respirators among health professionals in Brazil. Method: cross-sectional study conducted with 11,368 health professionals using a respondent-driven sampling method adapted for online environments. Univariate and multivariate analyses were performed to investigate the association between the "skin lesions with the use of N95 respirators" variable and gender, professional category, workplace, training, COVID-19 diagnosis, and availability of sufficient and high-quality Personal Protective Equipment. Results: the prevalence of skin lesions was 61.8%. Women were 1.203 times (95% CI: 1.154-1.255) more likely to develop a lesion than men. The chances of skin lesions in psychologists (PR=0.805; 95% CI: 0.678-0.956) and dentists (PR=0.884; 95% CI: 0.788-0.992), were lower when compared to Nursing professionals. Professionals with a positive COVID-19 diagnosis and working in the Intensive Care Unit have an increased chance of presenting skin lesions (PR=1.074; 95% CI: 1.042-1.107); (PR=1.203; 95% CI: 1.168-1.241), respectively. Conclusion: the prevalence of skin lesions caused by the use of N95 respirators was 61.8% and was associated with female gender, professional category, workplace, training, COVID-19 diagnosis, and availability of sufficient and highquality Personal Protective Equipment.

Objetivo: investigar a prevalência de lesões de pele e fatores associados ao uso de respiradores N95 entre profissionais de saúde no Brasil. Método: estudo transversal realizado com 11.368 profissionais de saúde por meio de um método de amostragem dirigido por respondentes adaptado para ambientes online. Análises univariadas e multivariadas foram realizadas para investigar a associação entre a variável "lesão de pele com uso de respirador N95" e sexo, categoria profissional, local de trabalho, treinamento, diagnóstico de COVID-19 e disponibilidade suficiente de equipamentos de proteção individual de qualidade. Resultados: a prevalência de lesões cutâneas foi de 61,8%. As mulheres foram 1,203 vezes (IC 95%: 1.154-1.255) mais propensas a desenvolver uma lesão do que os homens. As chances de lesão de pele em psicólogos (RP=0,805; IC 95%: 0,678-0,956) e dentistas (RP=0,884; IC 95%: 0,788-0,992) foram menores quando comparados aos profissionais de Enfermagem. Profissionais com diagnóstico positivo para COVID-19 e que trabalham em Unidade de Cuidados Intensivos têm maior chance de apresentar lesões de pele (RP=1,074; IC 95%: 1,042-1,107); (RP=1,203; IC 95%: 1,168- 1,241), respectivamente. Conclusão: a prevalência de lesões de pele causadas pelo uso do respirador N95 foi de 61,8% e esteve associada ao sexo feminino, categoria profissional, local de trabalho, treinamento, diagnóstico de COVID-19 e disponibilidade suficiente de equipamentos de proteção individual de qualidade.

Encefalitis autoinmune posherpética. Caso clínico pediátrico / Autoimmune post-herpes simplex encephalitis. A pediatric clinical case report

La encefalitis por virus herpes simple (VHS) es una causa frecuente de encefalitis grave y potencialmente fatal. La encefalitis autoinmune posherpética (EAPH) afecta a un porcentaje de los pacientes que han presentado encefalitis herpética (EH) y se caracteriza por la aparición de nuevos síntomas neurológico/psiquiátricos, y/o por el empeoramiento de los déficits adquiridos durante la infección viral dentro de un lapso temporal predecible. Se produce por un mecanismo no relacionado con el VHS, sino por fenómenos autoinmunes, y es susceptible de tratamiento con inmunomoduladores. Se presenta el caso de un varón de 5 años de edad con EAPH que requirió tratamiento inmunomodulador, de primera y segunda línea, con buena evolución y remisión de los síntomas.

Herpes simplex virus (HSV) encephalitis is a common cause of severe and potentially fatal encephalitis. Autoimmune post-herpes simplex encephalitis (AIPHSE) affects a percentage of patients who developed herpes simplex encephalitis (HSE) and is characterized by the onset of new neurological/psychiatric symptoms and/or worsening of deficits acquired during the herpes infection within a predictable time frame. It is caused by a mechanism not related to HSV, but by autoimmune conditions, and is susceptible to treatment with immunomodulators. Here we describe the case of a 5-year-old boy with AIPHSE who required first- and second-line immunomodulatory treatment, with an adequate course and remission of symptoms.

High-grade tumor budding is a risk factor for survival in patients with laryngeal squamous cell carcinoma

Abstract Objective: With the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. Methods: 268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. Results: Tumor budding was divided into low-grade tumor budding (0-6/0.785mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1 -6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. Conclusions: Smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. Level of Evidence: Level 4.

Manifestaciones dermatológicas en una lactante con síndrome de kwashiorkor Claves para el diagnóstico y tratamiento oportuno / Dermatological Manifestations in an Infant with Kwashiorkor Syndrome: Keys for Diagnosis and Timely Treatment

Resumen El síndrome de kwashiorkor se caracteriza por malnutrición proteica y edema generalizado; algunos de los factores de riesgo que se asocian a su aparición son: vivir en pobreza, el destete reciente, las infecciones y las dietas basadas en maíz y arroz. Este síndrome puede generar manifestaciones cutáneas como piel delgada y seca, hiperpigmentación, áreas confluentes de descamación, cabello seco, hipopigmentado y desprendible, así como una dermatitis erosiva con predominio en pliegues cutáneos. El diagnóstico se basa principalmente en una evaluación nutricional integral, exploración física y estudios de laboratorio, y el éxito del tratamiento se basa en la rehabilitación nutricional temprana. Caso clínico: lactante del sexo femenino de 8 meses de edad, que acudió al Instituto Nacional de Pediatría (INP), por presentar una dermatosis generalizada de tipo descamativa de 1 mes de evolución, que fue tratada con ketoconazol tópico. Al interrogatorio la madre refiere alimentación exclusiva con atole de maíz por un diagnóstico de "alergia a la leche" y falta de recursos económicos para comprar la fórmula hidrolizada. La paciente presentaba una dermatosis diseminada que afectaba todos los segmentos corporales, caracterizada por placas hiperpigmentadas, bien definidas, de forma irregular, con descamación en láminas gruesas en región perioral y extremidades, así como áreas erosionadas, pálidas y edema generalizado en extremidades. Se realizaron exámenes de laboratorio que mostraron que la paciente tenía anemia (Hb 11.2 g/dL) e hipoalbuminemia (3.3 g/dL) que, en conjunto con las manifestaciones clínicas, integraron el diagnóstico de síndrome de Kwashiorkor. Se informaron los hallazgos clínicos y de laboratorio al servicio de Gastroenterología y Nutrición, quienes realizaron una valoración nutricional integral y decidieron iniciar tratamiento nutricional; por parte del servicio de Dermatología, se indicó el uso de emolientes y cuidados generales de la piel. Veinte días después la dermatosis y el edema habían remitido.

Abstract Kwashiorkor syndrome is characterized by protein malnutrition and edema, risk factors are recent weaning, infections, and diets based on corn and rice. This malnutrition can lead to skin manifestations such as thin, dry skin, hyperpigmentation, confluent areas of scaling, dry, hypopigmented, and detachable hair, as well as erosive dermatitis, predominantly in skin folds. The diagnosis is based on a nutritional evaluation exam, physical examination and laboratory finding, the treatment is based on early nutritional rehabilitation. Clinical case: 8-month-old female infant who attended the Instituto Nacional de Pediatría, presenting a scaling dermatosis of 1 month's evolution that was treated with topical ketoconazole. The mother reported exclusive feeding with corn gruel due to the diagnosis of "lactose allergy" and commented not enough resources to buy hydrolyzed formula. The patient presented a disseminated dermatosis to all body segments, characterized by well-defined, irregularly shaped, hyperpigmented plaques with scaling in thick sheets in the perioral region and extremities, as well as areas of eroded skin and paleness and edema of extremities. Laboratory tests were taken, where anemia (Hb 11.2 g/dl) and hipoalbuminemia (3.3 g/dl) were documented, the diagnosis of kwashiorkor syndrome was integrated. The clinical and laboratory findings were reported to the Gastroenterology and Nutrition service, who performed a nutritional assessment, and began nutritional treatment, emollients and general skin care were documented; twenty days later, the dermatosis and edema had subsided.

Secuelas cognitivas en encefalitis inmunomediadas: cohorte de pacientes en Argentina / Cognitive sequelae in immunomediated encephalitis: cohort of patients in Argentina

Resumen Introducción: Las encefalitis inmunomediadas son un desorden neurológico de origen autoinmune. Actual mente es escasa la descripción de las secuelas cognitivas crónicas. El objetivo del presente trabajo fue caracterizar la secuela cognitiva de diferentes tipos de encefalitis inmunomediadas en una cohorte de un centro único de Argentina. Métodos: Estudio prospectivo, observacional, trans versal, de pacientes en seguimiento en un hospital de la Ciudad de Buenos Aires, con diagnóstico de encefalitis inmunomediada probable y definitiva. Se evaluaron variables epidemiológicas, clínicas, paraclínicas y tra tamiento. Se determinó la secuela cognitiva a través de una evaluación neurocognitiva realizada a partir del año de la presentación clínica. Resultados: Fueron incluidos 15 pacientes, todos con resultado disminuido en al menos un test. La memoria fue el dominio más afectado. Aquellos que se encon traban bajo tratamiento inmunosupresor al momento de evaluarse presentaron menores resultados en el aprendizaje seriado (media -2.94; desvío estándar 1.54) versus los que se encontraban sin tratamiento (media -1.18; desvío estándar 1.40; p = 0.05) y en la prueba de reconocimiento (media -10.34; desvío estándar 8.02) ver sus sin tratamiento (media -1.39; desvío estándar 2.21; p = 0.003). Los pacientes con estatus epiléptico tuvieron resultados deficitarios en la prueba de reconocimiento (media -7.2; desvío estándar 7.91) en comparación a los que no lo tenían (media -1.47; desvío estándar 2.34; p = 0.05). Conclusión: Nuestros resultados demuestran que, a pesar del curso monofásico de la enfermedad, todos los pacientes presentan daño cognitivo persistente más allá del año del inicio del cuadro. Estudios prospectivos de mayor envergadura serían necesarios para confirmar nuestros hallazgos.

Abstract Introduction: Autoimmune encephalitis represents a group of immune-mediated neurological disorders. At present, the description of the chronic cognitive sequela is scarce. The objective of this study was to characterize the cognitive after effects of different types of autoimmune encephalitis in a cohort from a single center in Argentina. Methods: Prospective, observational, cross-sectional study of patients under follow-up at a hospital in Buenos Aires city, with a diagnosis of probable and definitive immune-mediated encephalitis. Epidemiological, clini cal, paraclinical and treatment related variables were evaluated. Cognitive sequela was determined through a neurocognitive evaluation performed at least a year after the clinical presentation. Results: Fifteen patients were included. All had di minished results in at least one test. Memory was the most affected domain. Patients who were under im munosuppressive treatment at the time of evaluation presented lower results in serial learning (mean -2.94; standard deviation 1.54) versus those who weren't under treatment (mean -1.18; standard deviation 1.40; p = 0.05). The same pattern was observed on the recognition test of treatment group (mean -10.34; standard deviation 8.02) versus treatment-free group (mean -1.39; standard deviation 2.21; p =0.003). Patients with status epilepticus had poorer results in the recognition test (mean -7.2; standard deviation 7.91) compared to those without it (mean -1.47; standard deviation 2.34; p = 0.05). Conclusion: Our results show that, despite the mo nophasic course of this disease, all patients had persis tent cognitive damage beyond the year of onset. Larger prospective studies are required to confirm our findings.

Relationship of E-cadherin, Beta-catenin, N-cadherin, ZEB1 and ?SMA as Epithelial Mesenchymal Transition markers with prognostic factors in early and advanced stage laryngeal squamous cell carcinomas

Aims: To investigate the relationship between E-cadherin, beta-catenin, N-cadherin, ZEB1, and ?SMA as epithelial-mesenchymal transformation markers with tumor stage, lymph node metastasis (LNM), and overall survival (OS) in laryngeal squamous cell carcinomas (LSCC). Materials and Methods: A total of 100 cases diagnosed with LSCC were included in the study. Data about the lymphovascular invasion (LVI), perineural invasion (PNI), necrosis, and LNM were recorded by evaluating hematoxylin-eosin–stained slides. Markers of E-cadherin, beta-catenin, N-cadherin, ZEB1, and ?SMA were applied to the sections prepared from paraffin blocks of tumor samples. Results: Ninety-five male and five female patients were included in the study, and 38 of them exited. A significant relationship was observed between OS with advanced tumor stage, presence of LNM and PNI. A significant relationship was found between increased tumor Zeb1 expression and advanced tumor stage. In univariate and multivariate analyses, a significant negative relationship with OS, and increased Zeb1 expression in tumor and tumor stroma was seen. Any relationship was not observed between E-cadherin, beta-catenin, N-cadherin, and ?SMA and OS. Conclusion: Among the EMT markers, we evaluated in our study, it was seen that Zeb1, which is an EMT transcription factor, is associated with tumor stage, LNM, and OS. Remarkably, Zeb1 expression observed in tumor stroma was also significant for OS. Any similar data reported for LSCCs have not been encountered in the literature, and it was thought that it would be appropriate to support our findings with further studies to be performed on this subject.

Possible therapeutics for Pseudomyxoma peritonei: a rare, lethal, and the least investigated disease

Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics - such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers. (AU)

The Resurgence of Hallucinogen Drugs in Clinical Research

ABSTRACT Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT2A) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT2A receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.

Síntesis de tioureas con isoniacida y niacida estructural: test frente a bacterias Gram + y Gram -

Se sintetizaron los compuestos N-(2-ni-cotinoilhidrazina-1-carbonotioil)benzamida (H3L1) y su isómero N-(2-isonicoti-noilhidrazina-1-carbonotioil)benzamida (H3L2) tipo N, S, O dadores, por reacción del isotiocianato de benzoilo con la hidracida nicotínica y la isoniacida, respectivamente. Los compuestos H3L1 y H3L2 fueron caracterizados por 1H-RM-N,13C-RMN, FT-IR y análisis elemental. Se realizó el análisis computacional utilizando las funciones de Fukui para determinar las razones por las cuales no se formaron los 1,2,4-triazoles. Se hicieron pruebas preliminares de los compuestos sintetizados frente a Staphylococcus aureus (Gram+) y Escherichia coli (Gram-). Se demostró importante actividad frente a las bacterias mencionadas.

The compounds N-(2-nicotinoylhydra-zine-1-carbonothioyl)benzamide (H3L1) and its isomer N-(2-isonicotinoylhydra-zine-1-carbonothioyl)benzamide (H3L2) type N, S, O donors, by reaction of benzoyl isothiocyanate with nicotinic hydrazide and isoniazid respectively were synthesized. The H3L1 and H3L2 compounds were characterized by 1H-NMR, 13C-NMR, FT-IR and elemental analysis. Computational analysis using the Fukui functions were performed to determine the reasons why the 1,2,4-triazoles were not formed. Preliminary tests of the synthesized compounds were carried out against Staphylo-coccus aureus (Gram+) and Escherichia coli (Gram-), having demonstrated significant activity against such bacteria.

Os compostos N-(2-nicotinoilhidrazina-1-carbonotioil)benzamida (H3L1) e seu isòmero N-(2-isonicotinoilhidrazina-1-carbonotioil)benzamida foram sintetizados. (H3L2) doadores tipo N, S, O, por reação de isotiocianato de benzoíla com hidrazida nicotínica e isoniazida, respectivamente. Os compostos H3L1 e H3L2 foram caracterizados por 1H-NMR, 13C-NMR, FT-IR e análise elementar. A análise computacional usando as funções de Fukui foi realizada para determinar as razões pelas quais os 1,2,4-triazóis não foram formados. Testes preliminares dos compostos sintetizados foram realizados contra Staphylococcus aureus (Gram+) e Escherichia coli (Gram-), tendo demonstrado atividade significativa contra as referidas bactérias.

Chemical and sensory assessment of extra virgin olive oil blends with omega-3 polyunsaturated fatty acids from plant origin

Extra virgin olive oil (EVOO) is known for its health benefits, although it provides a minimum amount of n-3 polyunsaturated fatty acids (n-3 PUFA), which play an important role in the human organism. In this study, EVOO was blended with vegetable oils which are rich sources of n-3 PUFA alpha-linolenic acid (ALA) and/or stearidonic acid (SDA) (chia, walnut, linseed and viper's bugloss seed oils). Fatty acid profiles, induction time, and organoleptic characteristics of the resulting blends were assessed. The n-3 PUFA enrichment in the blends was proportional to the degree of blending. Sensory analysis carried out by a trained panel showed that it is possible to enrich EVOO with up to 20% chia, linseed and viper's bugloss seed oil without altering the original organoleptic characteristics of EVOO. However, the induction time of the blends was significantly reduced compared with EVOO even after adding n-3 PUFA in small proportions, meaning that shelf-life time of these blends is much lower than that of EVOO, which should be considered when preparing these products for commercial purposes.

El aceite de oliva extra virgen (AOEV) es ampliamente conocido por sus beneficios para la salud, aunque apenas aporta ácidos grasos poliinsaturados n-3 (AGPI n-3), los cuales juegan un papel importante en el organismo humano. En este estudio se elaboraron mezclas de AOEV con aceites vegetales ricos en ácido alfa-linolénico (ALA) y/o estearidónico (SDA) (chia, nuez, linaza y viborera). Se evaluaron los perfiles de ácidos grasos, tiempos de inducción y características organolépticas de las mezclas resultantes. El enriquecimiento en AGPI n-3 fue proporcional al grado de mezcla. El análisis sensorial llevado a cabo por un panel entrenado mostró que es posible enriquecer AOEV con hasta un 20% de aceite de chia, linaza o viborera sin alterar las características organolépticas originales del AOEV. Sin embargo, los tiempos de inducción de las mezclas fueron significativamente menores que el del AOEV, incluso tras añadir AGPI n-3 en pequeñas proporciones, lo que significa que el tiempo de vida media de las mezclas es mucho menor que el del AOEV. Este hecho debería tenerse en cuenta al preparar las mezclas con propósitos comerciales.

Regulación del calcio por SERC-A antes de la enfermedad de Alzheimer y durante la misma / Calcium regulation by SERC-A before and during Alzheimer disease

Hay muchos factores implicados en la incidencia de la enfermedad de Alzheimer que, en combinación, terminan por impedir o dificultar las funciones neuronales normales. Actualmente, poco se conoce sobre la regulación del calcio, antes de la enfermedad y durante la misma. La inestabilidad interna de los niveles de calcio se asocia a un mayor riesgo vascular, condición prevalente en un gran número de individuos ya comprometidos por la enfermedad de Alzheimer. Esta revisión proporciona una reevaluación de los mecanismos moleculares de la ATPasa dependiente de Ca2+ del retículo sarcoendoplásmico (SERC-A) en la enfermedad y analiza los aspectos más destacados de la función de los canales de calcio dependientes de voltaje; de esta manera, se podrán abrir nuevas alternativas de tratamiento. Estos mecanismos de regulación son clínicamente relevantes, ya que se ha implicado la función irregular de SERC-A en diversas alteraciones de la función cerebral.

There are many factors involved in the incidence of Alzheimer's disease that, in combination, impede or hinder normal neuronal functions. Little is currently known about calcium regulation before and during the disease. Internal instability of calcium levels is associated with increased vascular risk, a prevalent condition in a high number of individuals already compromised by Alzheimer's disease. This review provides a reevaluation of the molecular mechanism of the sarcoendoplasmic reticulum calcium ATPase (SERC-A) in the disease and discusses salient aspects of voltage-gated calcium channel function; in these way new alternatives could be open for its treatment. These regulation mechanisms are clinically relevant since the irregular functions of SERC+A has been implicated in pathologies of brain function.

Hypofractionated (2.75 Gy per fraction) versus Conventionally Fractionated Primary Radiotherapy for T2N0M0 Carcinoma of the Glottis

Abstract Introduction Radiotherapy provides excellent outcome in early stage glottic cancer; however, the optimal radiotherapy dose fractionation remains unknown. Objective To investigate the outcome of patients with T2N0M0 treated with either hypofractionated (HypoFxn) or conventionally fractionated radical (ConFxn) radiotherapy. Methods According to our institutional protocol, patients with T2N0M0 glottic cancer can be treated either with ConfFxn or HypoFxn radiotherapy, as per clinician's and patient's choice, following shared decision making discussing the advantages and disadvantages of both modalities. A total of 77 patients with T2N0M0 squamous cell carcinoma of glottis treated with either HypoFxn 55Gy in 20 fractions (n = 19) or ConFxn 63 to 65Gy in 30 fractions (n = 58) were included. Results With median follow-up of 3.4 years, there was no significant difference in disease-free survival (median: HypoFxn = 65.2 months, and ConFxn = 75.3 months; p = 0.874), local recurrence free survival rates (median: HypoFxn = 78.8 months vs. ConFxn = 81.2 months; p = 0.274), and overall survival (median: HypoFxn = 65.9 months vs. ConFxn = 67.7 months; p = 0.532). Elective neck irradiation was given to 43 patients, all in the ConFxn group, and this was associated with poorer local control (p = 0.027). The use of radiotherapy modality, three-dimensional conformal radiotherapy (3DRT) versus intensity modulated radiotherapy (IMRT), was not a prognostic factor (p = 0.36). In the HypoFxn group, grade III acute dysphagia requiring nasogastric tube was 16%, compared with 25% in the ConFxn group (p = 0.446). Conclusion HypoFxn radiotherapy provides a comparable treatment outcome with acceptable toxicity. The addition of prophylactic irradiation of the neck lymph nodes has no impact on regional control.