TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation.

It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans.

Innovative pathological network-based multitarget approaches for Alzheimer's disease treatment.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and is a major health threat globally. Its prevalence is forecasted to exponentially increase during the next 30 years due to the global aging population. Currently, approved drugs are merely symptomatic, being ineffective in delaying or blocking the relentless disease advance. Intensive AD research describes this disease as a highly complex multifactorial disease. Disclosure of novel pathological pathways and their interconnections has had a major impact on medicinal chemistry drug development for AD over the last two decades. The complex network of pathological events involved in the onset of the disease has prompted the development of multitarget drugs. These chemical entities combine pharmacological activities toward two or more drug targets of interest. These multitarget-directed ligands are proposed to modify different nodes in the pathological network aiming to delay or even stop disease progression. Here, we review the multitarget drug development strategy for AD during the last decade.

The Melatonin Derivative ITH13001 Prevents Hypertension and Cardiovascular Alterations in Angiotensin II-Infused Mice.

Inflammatory mechanisms and oxidative stress seem to contribute to the pathogenesis of hypertension. ITH13001 is a melatonin-phenyl-acrylate hybrid that moderately induces the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) and has a potent oxidant scavenging effect compared with other derivatives of its family. Here we investigated the effect of ITH13001 on hypertension and the associated cardiovascular alterations. Angiotensin II (AngII)-infused mice were treated with ITH13001 (1 mg/kg per day, i.p.) for 2 weeks. The ITH13001 treatment prevented: 1) the development of hypertension, cardiac hypertrophy, and increased collagen and B-type natriuretic peptide (Bnp) expression in the heart; 2) the reduction of elasticity, incremental distensibility, fenestrae area, intraluminal diameter, and endothelial cell number in mesenteric resistance arteries (MRA); 3) the endothelial dysfunction in aorta and MRA; 4) the plasma and cardiovascular oxidative stress and the reduced aortic nitric oxide (NO) bioavailability; 5) the increased cardiac levels of the cytokines interleukin (IL)-1ß, IL-6, and C-C motif chemokine ligand 2 (Ccl2), the T cell marker cluster of differentiation 3 (Cd3), the inflammasome NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), the proinflammatory enzymes inducible nitric oxide synthase (iNOS) and COX-2, the toll-like receptor 4 (TLR4) adapter protein myeloid differentiation primary response 88 (MyD88), and the nuclear factor kappa B (NF-κB) subunit p65; 6) the greater aortic expression of the cytokines tumor necrosis factor alpha (Tnf-α), Ccl2 and IL-6, Cd3, iNOS, MyD88, and NLRP3. Although ITH13001 increased nuclear Nrf2 levels and heme oxygenase 1 (HO-1) expression in vascular smooth muscle cells, both cardiac and vascular Nrf2, Ho-1, and NADPH quinone dehydrogenase 1 (Nqo1) levels remained unmodified irrespective of AngII infusion. Summarizing, ITH13001 improved hypertension-associated cardiovascular alterations independently of Nrf2 pathway activation, likely due to its direct antioxidant and anti-inflammatory properties. Therefore, ITH13001 could be a useful therapeutic strategy in patients with resistant hypertension. SIGNIFICANCE STATEMENT: Despite the existing therapeutic arsenal, only half of the patients treated for hypertension have adequately controlled blood pressure; therefore, the search for new compounds to control this pathology and the associated damage to end-target organs (cerebral, cardiac, vascular, renal) is of particular interest. The present study demonstrates that a new melatonin derivative, ITH13001, prevents hypertension development and the associated cardiovascular alterations due to its antioxidant and anti-inflammatory properties, making this compound a potential candidate for treatment of resistant hypertensive patients.

Socialización de experiencias y logros en la salud pública y la Colaboración Médica Cubana desde las redes sociales. Venezuela 2021-2022

Introducción: Las redes sociales son formas de interacción social, que fomentan un intercambio dinámico entre personas, grupos e instituciones en contextos disímiles. Objetivo: Socializar la experiencia y los logros de la salud pública y la Colaboración Médica Cubana desde las redes sociales en Venezuela desde enero de 2021 hasta octubre de 2022. Métodos: Se realiza una investigación de tipo observacional descriptiva en el periodo comprendido desde enero de 2021 hasta octubre de 2022 y aplicado en la Misión Médica Cubana en Venezuela con una población de 14 213 profesionales de la salud dividida en 24 estados. Resultados: En el año 2021 se realizaron 21 tuitazos con un millón 876 898 tuits. Para el año 2022 Facebook se comportó con 32 489 seguidores, Twiter con 16 832, Instagram Cubacooperave, 3 905, Yotube.com/c/cubacooperave 2 830, Tiktok 890 y Telegram 371 suscriptores. Se realizaron 26 actividades nacionales, 11 Tuitazos y 15 Jornadas en las Redes, 144 en TV, 200 en Radio y 100 en la Prensa escrita. Conclusiones: El reto es utilizar la posibilidad que ofrece la tecnología para ampliar los horizontes del uso de las redes sociales, realizar acciones de alfabetización informacional dirigidas a los gestores y usuarios de las mismas en pos de una divulgación adecuada del trabajo en la Misión Médica Cubana en Venezuela.

Introduction: Social networks are forms of social interaction that foster a dynamic exchange among people, groups, and institutions in dissimilar contexts. Objective: To socialize the experience and achievements of public health and the Cuban Medical Collaboration in social networks in Venezuela from January 2021 to October 2022. Method: An observational descriptive research was conducted from January 2021 to October 2022 and applied to the Cuban Medical Mission in Venezuela in a population of 14 213 health professionals divided into 24 states. Results: In the year 2021, there was a total of 21 tweets with 1 876 898 tweets published. In 2022, the Facebook network had 32 489 followers; Twitter, 16 832; Instragram Cubacooperave, 3 905; the Yotube.com/c/Cubacooperave channel, 2 830; Tik Tok, 890; and Telegram had 371 subscribers. A total of 26 national activities such as 11 Tuits, 15 Network Events; 144 TV, 200 Radio, and 100 written Press activities were performed. Conclusions: The challenge is to use the possibility offered by technology to broaden the horizons of the use of social networks, as well as to establish information literacy actions directed towards the managers and users of these networks for the sake of an adequate dissemination of the work carried out by the Cuban Medical Mission in Venezuela.

[Remitting seronegative symetrical synovitis with pitting edema. One case report]. / Sinovitis simétrica seronegativa remitente con edema y fóvea. Presentación de un caso.

Background: RS3PE (remitting seronegative symmetrical synovitis with edema and pitting) is a rare entity of unknown etiology that has been related to genetic predisposition due to the presence of HLA-A2 in 50% of cases and less frequently HLA-B7. Its pathogenesis is unknown, but it has been related to growth factors, and some mediators (TNF, IL-6). It is common in elderly people and the course of this illness presents with acute symmetrical polyarthritis, accompanied by edema in hands and feet. The diagnosis requires a high index of suspicion and to differentiate it from other entities such as rheumatoid arthritis, complex regional pain syndrome, rheumatic polymyalgia, in addition to ruling out malignant neoplasms, since there are many reports of its association with both solid and hematological neoplasms, being of bad prognosis when there is association. When there is no association with cancer, it responds well to the use of low doses of steroids and its prognosis is usually favorable. Clinical case: 80-year-old woman with an acute onset with polyarthralgia, functional limitation associated with pitting edema in hands and feet. After approaching the patient and ruling out associated neoplasms, it was diagnosed RS3PE. It was managed with prednisone, observing a good response, with remission of the manifestations at 6 weeks and subsequent suspension of the steroid. Conclusions: RS3PE is a rare entity, and a high index of suspicion is required for the diagnosis. A complete approach is important to rule out cancer in patients affected with this syndrome. Prednisone continues to be the best therapeutic option.

Introducción: la RS3PE (sinovitis simétrica seronegativa remitente con edema y fóvea) es una entidad rara de etiología desconocida que se ha relacionado con predisposición genética por la presencia de HLA-A2 en el 50% de los casos y con menor frecuencia HLA-B7. Se desconoce su patogenia, pero se ha relacionado con factores de crecimiento y algunos mediadores (TNF, IL-6). Se presenta en personas de edad avanzada, cursa con poliartritis aguda simétrica, acompañada de edema en manos y pies. El diagnóstico requiere de un alto índice de sospecha y diferenciarlo de otras entidades como artritis reumatoide, síndrome de dolor regional complejo, polimialgia reumática, además de descartar neoplasias malignas, ya que existen muchos reportes de su asociación con neoplasias tanto sólidas como hematológicas y es de mal pronóstico cuando existe asociación. Cuando no existe asociación con cáncer tiene buena respuesta al uso de dosis bajas de esteroides y su pronóstico suele ser favorable. Caso clínico: mujer de 80 años con un cuadro de inicio agudo con poliartralgias, limitación funcional asociada a edema de manos y pies con fóvea. Después del abordaje y de descartar neoplasias asociadas, se diagnosticó RS3PE. Se manejó con prednisona y hubo buena respuesta, con remisión de las manifestaciones a las 6 semanas y suspensión posterior del esteroide. Conclusiones: la RS3PE es una entidad rara y para diagnosticarla se requiere un alto índice de sospecha. Es importante el abordaje completo para descartar cáncer en los pacientes afectados con este síndrome. La prednisona continúa siendo la mejor opción terapéutica.

KEAP1-NRF2 protein-protein interaction inhibitors: Design, pharmacological properties and therapeutic potential.

The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is considered the master regulator of the phase II antioxidant response. It controls a plethora of cytoprotective genes related to oxidative stress, inflammation, and protein homeostasis, among other processes. Activation of these pathways has been described in numerous pathologies including cancer, cardiovascular, respiratory, renal, digestive, metabolic, autoimmune, and neurodegenerative diseases. Considering the increasing interest of discovering novel NRF2 activators due to its clinical application, initial efforts were devoted to the development of electrophilic drugs able to induce NRF2 nuclear accumulation by targeting its natural repressor protein Kelch-like ECH-associated protein 1 (KEAP1) through covalent modifications on cysteine residues. However, off-target effects of these drugs prompted the development of an innovative strategy, the search of KEAP1-NRF2 protein-protein interaction (PPI) inhibitors. These innovative activators are proposed to target NRF2 in a more selective way, leading to potentially improved drugs with the application for a variety of diseases that are currently under investigation. In this review, we summarize known KEAP1-NRF2 PPI inhibitors to date and the bases of their design highlighting the most important features of their respective interactions. We also discuss the preclinical pharmacological properties described for the most promising compounds.

Sistema de actividades para desarrollar la competencia intercultural en la Facultad de Ciencias Médicas "Enrique Cabrera", La Habana

Introducción: La lengua influye en el modo de pensar, vivir y relacionarse de cada uno de sus hablantes debido a su papel en el reflejo de las prácticas de cada colectivo humano y la transmisión de conocimientos. Esto significa que la comunicación y el aprendizaje de inglés como lengua extranjera incluyen los elementos de la cultura reflejados en esta lengua. Objetivo: Realizar un sistema de actividades para desarrollar la competencia intercultural en estudiantes de Medicina de la Facultad de Ciencias Médicas "Enrique Cabrera", La Habana, Cuba. Método: Se propone un sistema de actividades mediante un temario de prueba, estudio documental, recopilación e información durante toda la etapa del proceso investigativo. Fueron empleados varios métodos de investigación, en los métodos empíricos, la observación la encuesta y la entrevista. En los métodos teóricos el análisis histórico-lógico, el enfoque sistémico y la modelación, así como los procedimientos lógicos del pensamiento y los métodos matemáticos-estadísticos. Resultados: El aprendizaje del inglés como lengua internacional y de los saberes interculturales correspondientes es especialmente válido en la asignatura de inglés, basado en un sistema de actividades, para la formación de los futuros galenos, quienes deben aprender a comunicarse en esa lengua, lo que implica dominar los contenidos interculturales que permiten una interacción eficiente con personas, autoridades, organizaciones y obras de los países donde realizan sus funciones. Conclusiones: El aprendizaje del inglés como lengua internacional y de los saberes interculturales correspondientes, a través de un sistema de actividades, resulta primordial en la formación de estudiantes de Medicina de la Facultad de Ciencias Médicas "Enrique Cabrera".

Introduction: Language influences the way of thinking, living and the relationships of speakers because its role for reflecting the realities of each human group and the transmission of knowledge. This means that the communication and learning of English as foreign language includes elements present in the language culture. Objective: To design a system of activities to build the intercultural competence in medical students of the Facultad de Ciencias Médicas Enrique Cabrera, La Habana, Cuba. Method: A system of activities is proposed supported by test agenda, documentary study, collection and information gathered through whole research process. Several research methods were used in the study, for instance, the empirical methods (comprising the observational, survey, and interview methods), the theoretical methods (historical-logical analysis, the systemic approach and modeling), also were used the logical thinking procedures and mathematical-statistical methods. Results: Learning English as international language and the corresponding intercultural knowledge has a great value in the English subject. This learning process was supported by the application of a system of activities for training of future doctors, who must learn to communicate in this language, which implies mastering the intercultural contents that allow them to interact efficiently with people, authorities, organizations and works in the countries where they perform their functions. Conclusions: Learning English as international language and the corresponding intercultural knowledge, using a system of activities, is essential for training of medical students at the Facultad de Ciencias Médicas Enrique Cabrera.

Introdução: A língua influencia a forma de pensar, viver e se relacionar de cada um de seus falantes devido ao seu papel de refletir as práticas de cada grupo humano e a transmissão de conhecimentos. Isso significa que a comunicação e o aprendizado do inglês como língua estrangeira incluem os elementos da cultura refletidos nesse idioma. Objetivo: Realizar um sistema de atividades para desenvolver a competência intercultural em estudantes de Medicina da Facultad de Ciencias Médicas "Enrique Cabrera", Havana, Cuba. Método: Propõe-se um sistema de atividades por meio de agenda de teste, estudo documental, compilação e informação durante toda a etapa do processo investigativo. Foram utilizados vários métodos de investigação, nos métodos empíricos, a observação, o inquérito e a entrevista. Nos métodos teóricos, a análise histórico-lógica, a abordagem sistémica e a modelação, bem como os procedimentos de pensamento lógico e os métodos matemático-estatísticos. Resultados: Aprender inglês como língua internacional e o correspondente conhecimento intercultural é especialmente válido na disciplina de inglês, baseada em um sistema de atividades, para a formação de futuros médicos, que devem aprender a se comunicar nessa língua, o que implica o domínio intercultural conteúdo que permite uma interação eficiente com pessoas, autoridades, organizações e obras nos países onde desempenham suas funções. Conclusões: A aprendizagem do inglês como língua internacional e o conhecimento intercultural correspondente, através de um sistema de atividades, é essencial na formação dos estudantes de medicina da Faculdade de Medicina "Enrique Cabrera Cossío".

Enantioselective Synthesis and Pharmacological Evaluation of Aza-CGP37157-Lipoic Acid Hybrids for the Treatment of Alzheimer's Disease.

Hybrids based on an aza-analogue of CGP37157, a mitochondrial Na+/Ca2+ exchanger antagonist, and lipoic acid were obtained in order to combine in a single molecule the antioxidant and NRF2 induction properties of lipoic acid and the neuroprotective activity of CGP37157. The four possible enantiomers of the hybrid structure were synthesized by using as the key step a fully diastereoselective reduction induced by Ellman's chiral auxiliary. After computational druggability studies that predicted good ADME profiles and blood-brain permeation for all compounds, the DPPH assay showed moderate oxidant scavenger capacity. Following a cytotoxicity evaluation that proved the compounds to be non-neurotoxic at the concentrations tested, they were assayed for NRF2 induction capacity and for anti-inflammatory properties and measured by their ability to inhibit nitrite production in the lipopolysaccharide-stimulated BV2 microglial cell model. Moreover, the compounds were studied for their neuroprotective effect in a model of oxidative stress achieved by treatment of SH-SY5Y neuroblastoma cells with the rotenone-oligomycin combination and also in a model of hyperphosphorylation induced by treatment with okadaic acid. The stereocenter configuration showed a critical influence in NRF2 induction properties, and also in the neuroprotection against oxidative stress experiment, leading to the identification of the compound with S and R configuration as an interesting hit with a good neuroprotective profile against oxidative stress and hyperphosphorylation, together with a relevant anti-neuroinflammatory activity. This interesting multitarget profile will be further characterized in future work.

Free nipple graft: current indications and applications of a centenary breast surgery technique ­ an integrative review

Introduction: Free nipple graft is a mammaplasty technique first described about 100 years ago. Its indication, restricted to reduction mammoplasty earlier, has been expanding into areas in mastology intervention, such as transgender and oncological surgery. Aim: The aim of this study was to evaluate the efficacy and outcomes of the technique. Methods: Electronic literature search was conducted, using PubMed and LILACS databases. The search strategy consisted of the keywords, MeSH terms, and free text words and variants for the free nipple graft and its application in reduction and mammaplasty, transgender, and oncoplastic surgery. Results: A total of 397 articles were found and, after inclusion and exclusion criteria, 15 were selected. Their outcomes have been shown, despite lack of standardized scores, as well as clinical trials to postulate better scientific evidence on its use and indications, that the technique, analyzed in over 1290 patients, achieved high safety rates and reproducibility. Conclusion: Aesthetics and patients satisfaction were found positive, as recommended by the authors in different studies discussed in this article.

Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation.

The use of cyclodextrins as drug nano-carrier systems for drug delivery is gaining importance in the pharmaceutical industry due to the interesting pharmacokinetic properties of the resulting inclusion complexes. In the present work, complexes of the anti-cancer alkaloids camptothecin and luotonin A have been prepared with ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin. These cyclodextrin complexes were characterized by nuclear magnetic resonance spectroscopy (NMR). The variations in the 1H-NMR and 13C-NMR chemical shifts allowed to establish the inclusion modes of the compounds into the cyclodextrin cavities, which were supported by docking and molecular dynamics studies. The efficiency of the complexation was quantified by UV-Vis spectrophotometry and spectrofluorimetry, which showed that the protonation equilibria of camptothecin and luotonin A were drastically hampered upon formation of the inclusion complexes. The stabilization of camptothecin towards hydrolysis inside the cyclodextrin cavity was verified by the quantitation of the active lactone form by reverse phase liquid chromatography fluorimetric detection, both in basic conditions and in the presence of serum albumin. The antitumor activity of luotonin A and camptothecin complexes were studied in several cancer cell lines (breast, lung, hepatic carcinoma, ovarian carcinoma and human neuroblastoma) and an enhanced activity was found compared to the free alkaloids, particularly in the case of hydroxypropyl-ß-cyclodextrin derivatives. This result shows that the cyclodextrin inclusion strategy has much potential towards reaching the goal of employing luotonin A or its analogues as stable analogues of camptothecin.

Inflammatory Biomarkers in the Pathogenesis of Respiratory Dysfunction in People Living with HIV

BACKGROUND: Although the association between HIV infection and airways obstruction is well known, its etiopathogenesis is not clear. OBJECTIVES: Our aim was to analyze the association between biomarkers of systemic inflammation and bacterial translocation and pulmonary function tests in HIV infected patients and compare it between smokers and non-smokers. METHODS: Cross-sectional, observational study. Inclusion criteria: people living with HIV with undetectable plasma viral load. Exclusion criteria: other comorbidities associated with systemic inflammation. Outcome variables: spirometry and diffusing capacity for carbon monoxide; explanatory variables: inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha), bacterial translocation (soluble CD14 [sCD14] and bacterial 16S rDNA), and variables related to HIV infection. Associations were tested using the Pearson/Spearman correlation tests, the student t test, and multivariable linear regression. RESULTS: We included 71 patients (54.9% smokers). We did not observe significant differences in pulmonary function tests according to biomarkers of inflammation or bacterial translocation. In non-smokers (n=32), sCD14 was negatively correlated with forced expiratory volume in 1 second (R = -0.35, P = 0.048) and forced vital capacity (R= -0.40, P=0.023). Age, time since HIV diagnosis and CD4+ nadir were associated with alterations in PFTs. In smokers, the only association observed was between the pack-years and pulmonary obstruction. CONCLUSION: In non-smokers HIV patients, lung dysfunction can be, at least partially, related to bacterial translocation (sCD14), CD4+ nadir and time since HIV diagnosis.

Osteosíntesis mínima invasiva percutánea con placa en fractura de tibia distal / Percutaneous Minimally Invasive Plate Osteosynthesis in Distal Tibial Fracture

Introducción: Las fracturas diafisarias de la tibia tienen una alta incidencia por año, incluidas las del tercio distal. Son las más frecuentes de los huesos largos y se observan sobre todo en adultos jóvenes. Se producen, generalmente, por traumatismos de alta energía como accidentes del tránsito y caídas de alturas. Objetivo: Presentar los resultados del tratamiento realizado a un paciente con fractura extrarticular del tercio distal de la tibia, mediante una técnica de osteosíntesis percutánea mínimamente invasiva. Presentación del caso: Paciente de 45 años, masculino, de piel blanca que sufrió accidente del tránsito, y fue atendido en el servicio de Ortopedia y Traumatología del Hospital General Docente Dr. Antonio Luaces Iraola, con trauma en pierna izquierda. Presentó dolor, inflamación e imposibilidad para caminar. A la exploración física se constató dolor, deformidad, crepitación, movilidad anormal, aumento de volumen e impotencia funcional absoluta. Se realizó radiografía, se corroboró diagnóstico y se decidió tratamiento quirúrgico con técnica mínima invasiva percutánea. Se siguieron los principios de la osteosíntesis biológica y se utilizó placa de segunda generación del sistema AO. Conclusiones: El tiempo quirúrgico fue de 45 minutos, la estadía hospitalaria fue de 48 horas. Se comenzó apoyo parcial a las ocho semanas, y total a las 15 semanas. Se logró la consolidación total de la fractura a las 16 semanas de operado, evaluado de excelente a través de la American Orthopaedic Foot and Ankle Society (AOFAS) score(AU)

Introduction: Diaphyseal fractures of the tibia have high incidence per year, including those of the distal third. They are the most common of the long bones and are seen mostly in young adults. They are generally caused by high-energy trauma such as traffic accidents and falls from heights. Objective: To present the results of the treatment on a patient with extra-articular fracture of the distal third of the tibia, using minimally invasive percutaneous osteosynthesis technique. Case report: A white 45-year-old male patient was injured in a traffic accident, and he was treated in the Orthopedics and Traumatology service at Dr. Antonio Luaces Iraola General Teaching Hospital, because of a trauma to his left leg. He had pain, swelling and inability to walk. Physical examination revealed pain, deformity, crepitus, abnormal mobility, increased volume, and absolute functional impotence. X-rays were performed. The diagnosis was confirmed, and surgical treatment was decided with a minimally invasive percutaneous technique. The principles of biological osteosynthesis were followed and a second generation plate of AO system was used. Conclusions: The surgical time was 45 minutes. The hospital stay was 48 hours. Partial support of the leg was started at eight weeks, and full support at 15 weeks. Full fracture healing was achieved 16 weeks after surgery, the procedure was evaluated as excellent according to the American Orthopedic Foot and Ankle Society (AOFAS) score(AU)

Eficacia diagnóstica del ultrasonido de alta resolución en pacientes con rupturas del manguito rotador / Diagnostic Efficacy of High-Resolution Ultrasound in Patients with Rotator Cuff Ruptures

RESUMEN Introducción: Diferentes estudios relacionan el diagnóstico del ultrasonido de alta resolución con el diagnóstico artroscópico del manguito rotador, ambos métodos son favorables y muestran una alta sensibilidad y especificidad al compararlos. Objetivo: Establecer la eficacia diagnóstica entre los hallazgos ecográficos de alta resolución y el diagnóstico artroscópico de rupturas parciales y completas del manguito rotador. Métodos: Se realizó un estudio analítico transversal con el objetivo de evaluar la eficacia diagnóstica del ultrasonido de alta resolución en pacientes del Hospital Provincial General Docente Dr. Antonio Luaces Iraola, de Ciego de Ávila, con diagnóstico clínico de rupturas parciales y completas del manguito rotador, de enero del 2016 a enero del 2019. El universo estuvo constituido por 62 pacientes con diagnóstico clínico de ruptura del manguito rotador que presentaban indicaciones quirúrgicas, a los que se les indicó un estudio imagenológico con ultrasonido de alta resolución y, con posterioridad, se les realizó la intervención quirúrgica por artroscopia, que fue tomada como criterio de verdad. Resultados: Predominó el sexo masculino, con una edad media menor que los del sexo femenino. Los hallazgos diagnósticos por ambos métodos mostraron concordancia en más de dos tercios de los pacientes que presentaron rupturas parciales y completas del espesor del manguito rotador. La ultrasonografía según el método empleado resultó un medio diagnóstico eficaz para las rupturas parciales y completas del espesor del manguito rotador. Conclusiones: El ultrasonido de alta resolución presentó una adecuada correlación en el diagnóstico de lesiones parciales o completas del manguito rotador, confirmada por artroscopia y es considerado un medio diagnóstico eficaz(AU)

ABSTRACT Introduction: Different studies relate the diagnosis of high-resolution ultrasound with the arthroscopic diagnosis of the rotator cuff. Both methods are favorable and show high sensitivity and specificity when they are compared. Objective: To establish diagnostic efficacy between the findings of high-resolution ultrasound and the arthroscopic diagnosis of partial and complete ruptures of the rotator cuff. Methods: A cross-sectional analytical study was carried out, aimed at evaluating the diagnostic efficacy of high-resolution ultrasound in patients of Dr. Antonio Luaces Iraola Provincial General Teaching Hospital, in Ciego de Ávila, with a clinical diagnosis of partial and complete ruptures of the rotator cuff, from January 2016 to January 2019. The universe consisted of 62 patients with a clinical diagnosis of rotator cuff rupture who presented surgical indications, and who were also indicated for an imaging study with high-resolution ultrasound and, subsequently, performed arthroscopic surgery, taken as a criterion of truth. Results: The male sex predominated, with an average age lower than those corresponding to female sex. The diagnostic findings by both methods showed agreement in more than two thirds of the patients who presented partial and complete ruptures of the rotator cuff's thickness. Ultrasonography, according to the method used, was an effective diagnostic tool for partial and complete ruptures of the rotator cuff's thickness. Conclusions: High-resolution ultrasound showed an adequate correlation in the diagnosis of partial or complete ruptures of rotator cuff, as confirmed by arthroscopy. It is considered an effective diagnostic means(AU)

Guía práctica para la confección del expediente de Especialista de Segundo grado / Practical Guide for Preparing the File for Second Degree Specialist

El especialista de Segundo grado es un profesional de las ciencias de la salud que demuestra un dominio de excelencia en su especialidad con alto nivel de conocimientos y competencia profesional lo que debe quedar demostrado ante un tribunal de especialización de segundo grado. En este sentido, por Acuerdo del Consejo de Estado de fecha 29 de junio de 2009 se emite la resolución 132, que aprobó el Reglamento para la obtención del Segundo grado en las ciencias de la salud, y que dispone en cuatro capítulos los siguientes aspectos: los requisitos y formalidades para la obtención del título, la tramitación de las solicitudes, la constitución y funcionamiento de los tribunales y las reclamaciones ante el viceministro para la Docencia y la Investigación en el caso de desacuerdo del aspirante con el dictamen del tribunal evaluado....

New Nrf2-Inducer Compound ITH12674 Slows the Progression of Retinitis Pigmentosa in the Mouse Model rd10.

BACKGROUND/AIMS: It is well established that oxidative stress and inflammation are common pathogenic features of retinal degenerative diseases. ITH12674 is a novel compound that induces the transcription factor Nrf2; in so doing, the molecule exhibits anti-inflammatory, and antioxidant properties, and affords neuroprotection in rat cortical neurons subjected to oxidative stress. We here tested the hypothesis that ITH12674 could slow the retinal degeneration that causes blindness in rd10 mice, a model of retinitis pigmentosa. METHODS: Animals were intraperitoneally treated with 1 or 10 mg/Kg ITH12674 or placebo from P16 to P30. At P30, retinal functionality and visual acuity were analyzed by electroretinography and optomotor test. By immunohistochemistry we quantified the photoreceptor rows and analyzed their morphology and connectivity. Oxidative stress and inflammatory state was studied by Western blot, and microglia reactivity was monitored by flow cytometry. The blood-brain barrier permeation of ITH12674 was evaluated using a PAMPA-BBB assay. RESULTS: In rd10 mice treated with 10 mg/Kg of the compound, the following changes were observed (with respect to placebo): (i) a decrease of vision loss with higher scotopic a- and b-waves; (ii) increased visual acuity; (iii) preservation of cone photoreceptors morphology, as well as their synaptic connectivity; (iv) reduced expression of TNF-α and NF-κB; (v) increased expression of p38 MAPK and Atg12-Atg5 complex; and (vi) decreased CD11c, MHC class II and CD169 positive cell populations. CONCLUSION: These data support the view that a Nrf2 inducer compound may arise as a new therapeutic strategy to combat retinal neurodegeneration. At present, we are chemically optimising compound ITH12674 with the focus on improving its neuroprotective potential in retinal neurodegenerative diseases.

Tuning melatonin receptor subtype selectivity in oxadiazolone-based analogues: Discovery of QR2 ligands and NRF2 activators with neurogenic properties.

New multi-target indole and naphthalene derivatives containing the oxadiazolone scaffold as a bioisostere of the melatonin acetamido group have been developed. The novel compounds were characterized at melatonin receptors MT1R and MT2R, quinone reductase 2 (QR2), lipoxygenase-5 (LOX-5), and monoamine oxidases (MAO-A and MAO-B), and also as radical scavengers. We found that selectivity within the oxadiazolone series can be modulated by modifying the side chain functionality and co-planarity with the indole or naphthalene ring. In phenotypic assays, several oxadiazolone-based derivatives induced signalling mediated by the transcription factor NRF2 and promoted the maturation of neural stem-cells into a neuronal phenotype. Activation of NRF2 could be due to the binding of indole derivatives to KEAP1, as deduced from surface plasmon resonance (SPR) experiments. Molecular modelling studies using the crystal structures of QR2 and the KEAP1 Kelch-domain, as well as the recently described X-ray free-electron laser (XFEL) structures of chimeric MT1R and MT2R, provided a rationale for the experimental data and afforded valuable insights for future drug design endeavours.

Melatonin-sulforaphane hybrid ITH12674 attenuates glial response in vivo by blocking LPS binding to MD2 and receptor oligomerization.

Neuroinflammation is increasingly associated to the onset and progression of neurodegenerative diseases. Furthermore, several lines of evidence have demonstrated the capacity of aberrant protein aggregates to activate the immune response, accelerating the advance of the disease. Compound ITH12674 is a melatonin-sulforaphane hybrid designed to exert a dual drug-prodrug mechanism of action that combines potent NRF2 induction and free radical scavenger activity. ITH12674 also showed neuroprotective properties in oxidative stress related models, that were dependant on its NRF2 inducing properties. Given the high impact of neuroinflammation in the pathogenesis of neurodegeneration, we foresaw to study the anti-inflammatory properties of ITH12674. ITH12674 reduced inflammatory markers in glial cell cultures and hippocampal tissue after LPS administration. The anti-inflammatory effect was related to inhibition of TLR4 receptors due to a direct interaction with the TLR4/MD2 complex at the hydrophobic cavity of MD2. ITH12674 is endowed with anti-inflammatory properties, that are complementary to the NRF2 inducing activity and neuroprotective properties. Thus, ITH12674 could be of potential interest for the treatment of diseases with chronic neuroinflammation.

Patients' view of the differences in topical creams for radiation dermatitis prevention. A pilot study of cosmetic properties.

AIM: To investigate the feasibility of including patients' reports on the cosmetic properties of topical formulations for acute radiation dermatitis (ARD). BACKGROUND: No topical agent tested for acute radiation dermatitis (ARD) has proven to be better than any other, all achieving similar objective outcomes. No clear guidelines have therefore been established in clinics. Because the vehicle for such creams has shown to be an important factor in patient adherence to treatments in other dermatological diseases, patients' opinions are evaluated. MATERIAL AND METHODS: Seventy breast cancer patients referred for postoperative radiotherapy after conservative surgery were enrolled. Patients were assigned to use one of the 7 topical agents that are most-commonly used in the prevention of ARD. Patients' reports were assessed using continuous visual analogue scales (VAS), objective signs and symptoms produced by ARD, and were rated using the RTOG and RISRAS scales. RESULTS: The creams tested differed in their cosmetic properties significantly (p = 0.044). The performance of the agent, their absorption and any residue left over were also significantly different (p = 0.022, 0.014 and 0.02, respectively). CONCLUSIONS: Topical agents for preventive ARD are reported by patients to show different cosmetic properties. Cosmetic properties are important when choosing topical agents for ARD prevention. Recommending those with better cosmetic profiles would improve patient adherence to treatments.

Neurocognitive Impairment in Well-Controlled HIV-Infected Patients: A Cross-Sectional Study.

The reported prevalence of HIV-associated neurocognitive disorders in HIV people depends on the population studied and the methodology used. We analyze the prevalence of neurocognitive impairment (NCI) and associated factors in patients on successful antiretroviral therapy (ART), without comorbidities. Cross-sectional observational study in HIV subjects, ≥18 years old, on stable ART, and HIV viral load of <50 copies/mL. Patients with medical or psychiatric comorbidities and substance abuse were excluded. NCI was diagnosed using Frascati criteria, examining seven neurocognitive domains (NDs). We analyzed the association between NCI and HIV-related clinical variables, carotid intima-media thickness, bacterial translocation, and plasma inflammatory biomarkers [soluble CD14, interleukin-6 (IL-6), and tumor necrosis factor-α]. The prevalence of NCI was calculated with a 95% confidence interval (CI). We fitted a logistic regression model to assess the strength of the associations. Eighty-four patients were included with an observed NCI prevalence of 29.8% (95% CI: 21.0-40.2): 19% had asymptomatic NCI, 8.3% had mild neurocognitive disorder, and 2.4% had HIV-associated dementia. Delayed recall was the most commonly affected ND (27.4%). People diagnosed at least 10 years ago (odds ratio [OR]: 6.5, 95% CI: 1.6-21.7) and those with IL-6 levels above 1.8 pg/mL (OR: 6.0, 95% CI: 1.1-31.3) showed higher odds of NCI in adjusted analyses. Participants with carotid plaques had lower scores for delayed recall: -0.9 ± 1.1 versus -0.2 ± 1.1 (p = .04). Prevalence of NCI is high in otherwise healthy adults with HIV-infection. In this population, more than 10 years since HIV diagnosis and high IL-6 levels are associated with NCI. Delayed recall ND is worse in patients with subclinical atherosclerosis.