Physical Therapist Interventions Versus or Combined with Surgical Treatment in Nontraumatic Degenerative Meniscal Pathology: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: This study aimed to synthesize the evidence from randomized clinical trials (RCTs) in people with nontraumatic degenerative meniscal pathology, comparing physical therapist interventions versus or combined with arthroscopic partial meniscectomy (APM). METHODS: Seven electronic databases were searched. Methodological quality was evaluated using the Physiotherapy Evidence Database scale. Data synthesis was performed with random-effects network meta-analysis, and results were summarized using the standardized mean differences. RESULTS: From 2103 studies, 10 RCTs comprising 1411 individuals were included. Ninety percent of the selected RCTs were classified as good quality according to the Physiotherapy Evidence Database scale. All interventions (physical therapist interventions, APM, and APM plus physical therapist interventions) showed reduced pain and physical impairments at 3 months follow-up. However, when a physical therapist intervention was included, greater reductions in pain at rest (APM versus physical therapist interventions: 0.73 [95% CI = 0.20 to 1.26]; APM versus APM plus physical therapist interventions: 0.59 [95% CI = 0.15 to 1.03]) and greater increases in the strength of knee extensor muscles (APM versus physical therapist interventions: 0.44 [95% CI = 0.07 to 0.80]; APM versus APM plus physical therapist interventions: 0.73 [95% CI = 0.29 to 1.16]) were observed at 3 months. In contrast, no differences were found between treatments beyond 3 months. CONCLUSIONS: Physical therapist interventions based on exercise programs demonstrate superior short-term outcomes in pain reduction and knee extensor strength compared to surgical treatment. IMPACT: For nontraumatic degenerative meniscal pathology, conservative treatment utilizing a physical therapist intervention approach should be prioritized as the first choice over surgical treatment. It offers comparable or superior short-term pain reduction and strength improvements, with a lower risk of side effects. In cases where surgery is deemed necessary, including postsurgical physical therapist interventions are highly recommended to enhance muscle strength and alleviate pain.

Community Perceptions of Arsenic Contaminated Drinking Water and Preferences for Risk Communication in California's San Joaquin Valley.

Due to chronic exposure to elevated levels of arsenic in drinking water, thousands of Californians have increased risk for internal cancers and other adverse health effects. The mortality risk of cancer is 1 in 400 people exposed to above 10 µg/L of arsenic in their drinking water. The purpose of this community assessment was to understand the perceptions and awareness of the residents and public water representatives in rural, unincorporated farming communities of color in San Joaquin Valley, California. In our research, we asked 27 community informants about their (1) available water sources, (2) knowledge about the health impacts of arsenic, and (3) preferences for risk communication and education regarding the health impacts of arsenic-contaminated drinking water. Through our qualitative coding and analysis, we found that most community informants indicated that there was limited community awareness about the health effects of drinking water with elevated arsenic levels. Preferences for risk communication included using in-language, culturally relevant, and health literate health promotion strategies and teaching these topics through the local K-8 schools' science curriculum with a language brokerage approach to transfer student knowledge to family members. Key recommendations include implementing these communication preferences to increase community-wide knowledge about safe drinking water.

[Benefits of early social transition in transgender minors. Family perspectives: qualitative study.] / Beneficios de la transición social temprana en menores transgénero. Perspectivas de familias: estudio cualitativo.

OBJECTIVE: The term trans brings together all transgender identities. The early social transition towards the affirmed gender has benefits in the child's development. For families, transit is a period of great uncertainty, requiring support aimed at families of trans minors. The aim of this paper was to explore the needs and experiencies of parents and close-relatives who supported the social transition of their children. METHODS: We worked with focus groups of functional families of transgender minors who had begun the transition (n=14), with a medium-high educational level and who belonged to urban areas of Tenerife. Through a semi-structured interview, they commented on their experiences in the process of supporting the social transition of their children. The data was recorded in a video recording and processed through content analysis and categorization. RESULTS: Early social transition had positive and immediate benefits on child development as well as in the reduction of anxiety. There was a general improvement in mood, self-esteem, and social and family relationships. The accompaniment of specialists and associations helped in the different social situations and favoured resilience. CONCLUSIONS: Early social transition is positive in the personal and socio-family sphere of the minor. To improve their resilience, families demand accompaniment in this process, as well as meeting other trans people who serve as transpositive references. In addition, they point out the need for specific training in health professionals.

OBJETIVO: El término trans aglutina a todas las identidades transgénero. La transición social temprana hacia el género sentido tiene beneficios en el desarrollo del menor. Para las familias, el tránsito es un periodo de grandes incertidumbres, siendo necesario el acompañamiento dirigido a las familias de menores trans. El objetivo del artículo fue explorar, desde una perspectiva paterna y familiar, las necesidades y experiencias sobre el tránsito de menores trans que sirvieran de referente a otros padres/madres que apoyan el tránsito social de sus hijos e hijas. METODOS: Se trabajó con grupos focales de familias funcionales de menores transgénero que habían iniciado la transición (n=14), de nivel educativo medio-alto y que pertenecían a zonas urbanas de Tenerife. Mediante entrevista semiestructurada, comentaron sus experiencias en el proceso de dar soporte al tránsito social de sus hijos e hijas. Los datos fueron registrados en una videograbación y se procesaron mediante análisis de contenido y categorización. RESULTADOS: La transición social temprana tuvo beneficios positivos e inmediatos en el desarrollo del menor, además de en la disminución de la ansiedad. Hubo una mejora general en el humor, la autoestima y las relaciones tanto sociales como familiares. El acompañamiento de especialistas y asociaciones ayudó en las distintas situaciones sociales y favoreció la resiliencia. CONCLUSIONES: El tránsito social temprano es positivo en la esfera personal y sociofamiliar del menor. Para mejorar su resiliencia, las familias demandan acompañamiento en este proceso, así como conocer otras personas trans que les sirvan como referentes transpositivos. Además, señalan la necesidad de formación específica en los profesionales sanitarios.

Beneficios de la transición social temprana en menores transgénero. Perspectivas de familias: estudio cualitativo / Benefits of early social transition in transgender minors. Family perspectives: qualitative study

FUNDAMENTOS: El término trans aglutina a todas las identidades transgénero. La transición social temprana hacia el género sentido tiene beneficios en el desarrollo del menor. Para las familias, el tránsito es un periodo de grandes incertidumbres, siendo necesario el acompañamiento dirigido a las familias de menores trans. El objetivo del artículo fue explorar, desde una perspectiva paterna y familiar, las necesidades y experiencias sobre el tránsito de menores trans que sirvieran de referente a otros padres/madres que apoyan el tránsito social de sus hijos e hijas.MÉTODOS: Se trabajó con grupos focales de familias funcionales de menores transgénero que habían iniciado la transición (n=14), de nivel educativo medio-alto y que pertenecían a zonas urbanas de Tenerife. Mediante entrevista semiestructurada, comentaron sus experiencias en el proceso de dar soporte al tránsito social de sus hijos e hijas. Los datos fueron registrados en una videograbación y se procesaron mediante análisis de contenido y categorización. RESULTADOS: La transición social temprana tuvo beneficios positivos e inmediatos en el desarrollo del menor, además de en la disminución de la ansiedad. Hubo una mejora general en el humor, la autoestima y las relaciones tanto sociales como familiares. El acompañamiento de especialistas y asociaciones ayudó en las distintas situaciones sociales y favoreció la resiliencia. CONCLUSIONES: El tránsito social temprano es positivo en la esfera personal y sociofamiliar del menor. Para mejorar su resiliencia, las familias demandan acompañamiento en este proceso, así como conocer otras personas trans que les sirvan como referentes transpositivos. Además, señalan la necesidad de formación específica en los profesionales sanitarios.(AU)

BACKGROUND: The term trans brings together all transgender identities. The early social transition towards the affirmed gender has benefits in the child’s development. For families, transit is a period of great uncertainty, requiring support aimed at families of trans minors. The aim of this paper was to explore the needs and experiencies of parents and close-relatives who supported the social transition of their children. METHODS: We worked with focus groups of functional families of transgender minors who had begun the transition (n=14), with a medium-high educational level and who belonged to urban areas of Tenerife. Through a semi-structured interview, they commented on their experiences in the process of supporting the social transition of their children. The data was recorded in a video recording and processed through content analysis and categorization. RESULTS: Early social transition had positive and immediate benefits on child development as well as in the reduction of anxiety. There was a general improvement in mood, self-esteem, and social and family relationships. The accompaniment of specialists and associations helped in the different social situations and favoured resilience.CONCLUSIONS: Early social transition is positive in the personal and socio-family sphere of the minor. To improve their resilience, families demand accompaniment in this process, as well as meeting other trans people who serve as transpositive references. In addition, they point out the need for specific training in health professionals.(AU)

Augmented renal clearance. An unnoticed relevant event.

Augmented renal clearance (ARC) is a phenomenon that can lead to a therapeutic failure of those drugs of renal clearance. The purpose of the study was to ascertain the prevalence of ARC in the critically ill patient, to study the glomerular filtration rate (GFR) throughout the follow-up and analyze the concordance between the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimation formula and measured GFR. Observational, prospective, multicenter study. ARC was defined as a creatinine clearance greater than 130 ml/min/1.73 m2. Eighteen hospitals were recruited. GFR measurements carried out twice weekly during a 2-month follow-up period. A total of 561 patients were included. ARC was found to have a non-negligible prevalence of 30%. More even, up to 10.7% already had ARC at intensive care unit (ICU) admission. No specific pattern of GFR was found during the follow-up. Patients in the ARC group were younger 56.5 (53.5-58.5) versus 66 (63.5-68.5) years than in the non-ARC group, p < 0.001. ICU mortality was lower in the ARC group, 6.9% versus 14.5%, p = 0.003. There was no concordance between the estimation of GFR by the CKD-EPI formula and GFR calculated from the 4-h urine. ARC is found in up to 30% of ICU patients, so renal removal drugs could be under dosed by up to 30%. And ARC is already detected on admission in 10%. It is a dynamic phenomenon without an established pattern that usually occurs in younger patients that can last for several weeks. And the CKD-EPI formula does not work to estimate the real creatinine clearance of these patients.

Síndrome de forestier: caso clínico y revisión de la literatura / Forestier syndrome: clinical case and literature review

Antecedentes: El síndrome de Forestier también conocido como Hiperostosis Esquelética Idiopática Difusa (DISH, por sus siglas en inglés), es una enfermedad de etiología desco-nocida que se caracteriza por osificación del ligamento espinal anterior, siendo las porciones cervicales y torácicas las que se afectan más frecuentemente. Esta enfermedad es más frecuente en hombres y se asocia con diabetes, hipertensión arterial, disli-pidemia y trastornos endocrinos. Descripción del caso clínico:Paciente femenina de 63 años con antecedente de dolor cervical desde hace 32 años, que 6 años después del inicio del cuadro, presentó limitación en la movilidad del cuello; presentando va-rios episodios de disfonía desde hace 10 años; al momento de la consulta la paciente presentó limitación de la movilidad del cue-llo y dolor cervical. La imagen de resonancia magnética reportó: presencia de crecimiento óseo anterior de los cuerpos vertebra-les, este hallazgo está en relación con el síndrome de Forestier. Conclusiones: Por ser una enfermedad poco conocida es sub-diagnosticada y a menudo confundida con otras patologías. Los pacientes son diagnosticados muchos años después de que apa-recieron los primeros síntomas que incluyen dolor, limitación de la movilidad, disfagia y dificultad respiratoria. El tratamiento incluye manejo sintomático, terapia física y manejo quirúrgico...(AU)

Dormant but Active: Chilling Accumulation Modulates the Epigenome and Transcriptome of Prunus avium During Bud Dormancy.

Temperate deciduous fruit tree species like sweet cherry (Prunus avium) require long periods of low temperatures to trigger dormancy release and flowering. In addition to sequence-based genetic diversity, epigenetic variation may contribute to different chilling requirements among varieties. For the low chill variety 'Royal Dawn' and high chill variety 'Kordia', we studied the methylome of floral buds during chilling accumulation using MethylC-seq to identify differentially methylated regions (DMRs) during chilling hours (CH) accumulation, followed by transcriptome analysis to correlate changes in gene expression with DNA methylation. We found that during chilling accumulation, DNA methylation increased from 173 CH in 'Royal Dawn' and 443 CH in 'Kordia' and was mostly associated with the CHH context. In addition, transcriptional changes were observed from 443 CH in 'Kordia' with 1,210 differentially expressed genes, increasing to 4,292 genes at 1,295 CH. While 'Royal Dawn' showed approximately 5,000 genes differentially expressed at 348 CH and 516 CH, showing a reprogramming that was specific for each genotype. From conserved upregulated genes that overlapped with hypomethylated regions and downregulated genes that overlapped with hypermethylated regions in both varieties, we identified genes related to cold-sensing, cold-signaling, oxidation-reduction process, metabolism of phenylpropanoids and lipids, and a MADS-box SVP-like gene. As a complementary analysis, we used conserved and non-conserved DEGs that presented a negative correlation between DNA methylations and mRNA levels across all chilling conditions, obtaining Gene Ontology (GO) categories related to abiotic stress, metabolism, and oxidative stress. Altogether, this data indicates that changes in DNA methylation precedes transcript changes and may occur as an early response to low temperatures to increase the cold tolerance in the endodormancy period, contributing with the first methylome information about the effect of environmental cues over two different genotypes of sweet cherry.

Rehabilitación como intervención terapéutica: análisis bibliométrico de informes de casos clínicos, Revista Médica Hondureña 1995-2019 / Rehabilitation as a therapeutic intervention: bibliometric analysis of case reports, Revista Médica Hondureña 1995-2019

Antecedentes: La Revista Médica Hondureña (RMH) se ha caracterizado durante más de 90 años por ser el principal medio de difusión médico-científico en Honduras. Objetivo: Identificar si el manejo rehabilitador es considerado como opción terapéutica de acuerdo a la discapacidad de los casos clínicos publicados en la RMH en el periodo 1995-2019 y revisar algunas condiciones que generan discapacidad cuando no son atendidas oportunamente. Métodos: Revisión bibliométrica de los artículos de la sección Casos Clínicos, desde el Volumen 63 Número 1 Año 1995 al Volumen 87 Número 2 Año 2019, 98 números en total. En cada artículo se revisó si se había incluido la rehabilitación dentro del manejo terapéutico, y/o si había sido mencionado como parte integral del manejo de los pacientes. Resultados: De 206 artículos revisados, 11 (5.3%) describieron la rehabilitación como parte del manejo recibido; en 8 publicaciones el autor describió en la revisión de literatura que el manejo ideal en tales casos incluye la rehabilitación. De acuerdo a parámetros ya establecidos en Medicina Física y Rehabilitación, los casos informados en 106 (51.4%) artículos se habrían beneficiado de recibir manejo de rehabilitación. Discusión: A través de esta revisión bibliométrica de veinticinco años, se ha podido documentar que en Honduras aún no se reconoce el beneficio de la rehabilitación en las distintas patologías, tanto en el manejo hospitalario como ambulatorio. La Medicina Física y Rehabilitación contribuye a disminuir y/o evitar complicaciones en los pacientes, por lo que exhortamos a médicos generales y de otras especialidades a tomar conciencia de ello...(AU)

Superiority of wall motion score index over left ventricle ejection fraction in predicting cardiovascular events after an acute myocardial infarction.

BACKGROUND:: There are few data on the prognostic significance of the wall motion score index compared with left ventricle ejection fraction after an acute myocardial infarction. Our objective was to compare them after the hyperacute phase. METHODS:: Transthoracic echocardiograms were performed in 352 consecutive patients with myocardial infarction, after the first 48 hours of admission and before hospital discharge (median 56.3 hours (48.2-83.1)). We evaluated the ability of the wall motion score index and left ventricular ejection fraction to predict the combined endpoint (mortality and rehospitalization for heart failure) as a primary objective and the independent events of the combined endpoint as a secondary objective. RESULTS:: In 80.7% of patients, the wall motion score index was high despite having an ejection fraction >40%. No patient had an ejection fraction <55% with a normal index. After a follow-up of 30.5 months (24.2-49.5), both variables were predictors of the composite endpoint and all-cause mortality ( p<0.0001), although only the wall motion score index was a predictor of readmission for heart failure ( p=0.007). By multivariate analysis, a wall motion score index >1.8 proved to be the most powerful predictor of the composite endpoint (hazard ratio: 8.5; 95% confidence interval 3.7-18.8; p<0.0001). The superiority of the wall motion score index over ejection fraction was especially significant in patients with less myocardial damage (non-ST elevation myocardial infarction, or left ventricle ejection fraction >40%). CONCLUSIONS:: Both variables provide important prognostic information after a myocardial infarction. Beyond the hyperacute phase, wall motion score index is a more powerful prognostic predictor, especially in subgroups with less myocardial damage.

Huge recurrent gastric neuroendocrine tumor: a second-line chemotherapeutic dilemma.

Chemotherapy is considered "state of the art" for the treatment of poorly differentiated neuroendocrine neoplasms. Unfortunately, there is no standard effective post-first-line treatment for relapsing high-grade gastroenteropancreatic neuroendocrine neoplasms. We report the case of a patient with a gastric neuroendocrine carcinoma stage IV, with massive gastrointestinal bleeding at diagnosis. After the first line of platin-based chemotherapy a major tumoral response was documented, but the patient relapsed after 4 months. A second line of chemotherapy treatment was given, with the FOLFOX regimen, and the patient has been free of progression for almost 2 years. There is no second-line standard treatment accepted for this type of carcinoma, but 5-fluorouracil combined with oxaliplatin showed interesting antitumor activity.

Aerial pruning mechanism, initial real environment test.

In this research, a pruning mechanism for aerial pruning tasks is tested in a real environment. Since the final goal of the aerial pruning robot will be to prune tree branches close to power lines, some experiments related to wireless communication and pruning performance were conducted. The experiments consisted of testing the communication between two XBee RF modules for monitoring purposes as well as testing the speed control of the circular saw used for pruning tree branches. Results show that both the monitoring and the pruning tasks were successfully done in a real environment.

Expression of dog1 in low-grade fibromyxoid sarcoma: A study of 19 cases and review of the literature.

DOG1 is a highly-sensitive marker often included in the immunohistochemical panel for the diagnosis of gastrointestinal stromal tumors (GISTs). Recent research has shown that DOG1 may also be expressed by low-grade fibromyxoid sarcomas (LGFMSs); this may give rise to diagnostic error when the sarcoma is located in the abdominal cavity. This paper reports on immnohistochemical expression of DOG1 in 19 LGFMSs using two different monoclonal antibodies: K9 (Leica, Novocastra Laboratories, Newcastle upon Tyne, UK) and SP31 (Thermo Scientific, Freemont, USA). All LGFMSs displayed the standard histological pattern of alternating myxoid and fibrous areas, low cellularity and bland spindle-cell morphology. Positive staining for MUC4 was observed in 18/19 cases (94.7%), while there was rearrangement of the FUS gene in 14/19 (73.7%) cases and of the EWR1 gene in 2/19 (10.5%). The sarcoma staining negative for MUC4 displayed FUS gene rearrangement. Whole-section immunohistochemistry revealed positive staining for DOG1 in 8/19 cases (42.1%), though only with clone K9. Cytoplasmic as well as membrane staining was observed in all cases; staining was focal (10-30%) and of varying intensity (1+ to 2+). In conclusion, DOG1 clone K9 exhibited low sensitivity (42.1%) for the diagnosis of LGFMS, although higher than clone SP31. Since the two clones display similar sensitivity and specificity for GIST diagnosis, SP31 would appear to be more specific for this purpose, since no reaction was observed here with LGFMS, a GIST-mimicking lesion.

Second ISCB Latin American Student Council Symposium (LA-SCS) 2016.

This report summarizes the scientific content and activities of the second edition of the Latin American Symposium (LA-SCS), organized by the Student Council (SC) of the International Society for Computational Biology (ISCB), held in conjunction with the Fourth Latin American conference from the International Society for Computational Biology (ISCB-LA 2016) in Buenos Aires, Argentina, on November 19, 2016.

Synthesis of disaccharides using ß-glucosidases from Aspergillus niger, A. awamori and Prunus dulcis.

OBJECTIVE: Glucose conversion into disaccharides was performed with ß-glucosidases from Prunus dulcis (ß-Pd), Aspergillus niger (ß-An) and A. awamori (ß-Aa), in reactions containing initial glucose of 700 and 900 g l-1. RESULTS: The reactions' time courses were followed regarding glucose and product concentrations. In all cases, there was a predominant formation of gentiobiose over cellobiose and also of oligosaccharides with a higher molecular mass. For reactions containing 700 g glucose l-1, the final substrate conversions were 33, 38, and 23.5% for ß-An, ß-Aa, and ß-Pd, respectively. The use of ß-An yielded 103 g gentiobiose l-1 (15.5% yield), which is the highest reported for a fungal ß-glucosidase. The increase in glucose concentration to 900 g l-1 resulted in a significant increase in disaccharide synthesis by ß-Pd, reaching 128 g gentiobiose l-1 (15% yield), while for ß-An and ß-Aa, there was a shift toward the synthesis of higher oligosaccharides. CONCLUSION: ß-Pd and the fungal ß-An and ß-Aa ß-glucosidases present quite dissimilar kinetics and selective properties regarding the synthesis of disaccharides; while ß-Pd showed the highest productivity for gentiobiose synthesis, ß-An presented the highest specificity.

Gastrostomy vs nasogastric tube feeding in patients with head and neck cancer during radiotherapy alone or combined chemoradiotherapy

INTRODUCTION: Patients with head and neck cancer (HNC) submitted to radiotherapy alone or combined chemoradiotherapy present a high prevalence of malnutrition at baseline. Prophylactic use of gastrostomy has been suggested for these patients for delivering enteral nutrition. On the other hand, other authors have failed to demonstrate the effectiveness of this measure over nasogastric tube feeding. MATERIAL AND METHODS: We studied 40 patients with HNC with moderate or severe malnutrition who were offered either prophylactic percutaneous gastrostomy before starting oncologic treatment or close follow-up with nutritional counseling with the placement of a nasogastric tube when necessary. RESULTS: There were no significant changes throughout the study period in weight (p = 0.338), body mass index (BMI) (p = 0.314) or serum proteins (p = 0.729), and these changes showed no differences between the gastrostomy vsnasogastric tube feeding groups. The amount of delivered energy was above the estimated energy needs with both gastrostomy and nasogastric tube feeding, but there were no differences in the total energy provided by enteral nutrition between groups. Patients in the gastrostomy group received enteral nutrition support for a longer period of time (p = 0.007). CONCLUSIONS: Both gastrostomy and nasogastric tube feeding are effective methods of delivering enteral nutrition in patients with HNC submitted to radiotherapy alone or combined chemoradiotherapy, with no differences between them in terms of avoiding further nutritional deterioration.

Gastrostomy vs nasogastric tube feeding in patients with head and neck cancer during radiotherapy alone or combined chemoradiotherapy / Gastrostomía o sonda nasogástrica en pacientes con cáncer de cabeza y cuello durante la radioterapia o tratamiento combinado con quimiorradioterapia

Introduction: Patients with head and neck cancer (HNC) submitted to radiotherapy alone or combined chemoradiotherapy present a high prevalence of malnutrition at baseline. Prophylactic use of gastrostomy has been suggested for these patients for delivering enteral nutrition. On the other hand, other authors have failed to demonstrate the effectiveness of this measure over nasogastric tube feeding. Material and methods: We studied 40 patients with HNC with moderate or severe malnutrition who were offered either prophylactic percutaneous gastrostomy before starting oncologic treatment or close follow-up with nutritional counseling with the placement of a nasogastric tube when necessary. Results: There were no significant changes throughout the study period in weight (p = 0.338), body mass index (BMI) (p = 0.314) or serum proteins (p = 0.729), and these changes showed no differences between the gastrostomy vs nasogastric tube feeding groups. The amount of delivered energy was above the estimated energy needs with both gastrostomy and nasogastric tube feeding, but there were no differences in the total energy provided by enteral nutrition between groups. Patients in the gastrostomy group received enteral nutrition support for a longer period of time (p = 0.007). Conclusions: Both gastrostomy and nasogastric tube feeding are effective methods of delivering enteral nutrition in patients with HNC submitted to radiotherapy alone or combined chemoradiotherapy, with no differences between them in terms of avoiding further nutritional deterioration (AU)

Introducción: los pacientes con cáncer de cabeza y cuello (CCC) que reciben radioterapia o tratamiento combinado con radioterapia y quimioterapia presentan una elevada prevalencia de desnutrición. El uso profiláctico de la gastrostomía se ha sugerido para el soporte nutricional enteral en estos pacientes. Sin embargo, otros autores no han demostrado un beneficio claro de esta medida frente al uso de la sonda nasogástrica. Material y métodos: se realizó el estudio en cuarenta pacientes con CCC con desnutrición moderada o grave, a los cuales se les ofreció la gastrostomía percutánea antes de empezar el tratamiento oncológico o bien seguimiento estrecho mediante consejo nutricional y la colocación de una sonda nasogástrica en el momento necesario. Resultados: no se encontraron cambios significativos en cuanto a peso, (p = 0,338), índice de masa corporal (p = 0,314) o proteínas séricas (p= 0,729) durante el seguimiento, y estos cambios tampoco fueron diferentes entre los pacientes con gastrostomía o con sonda nasogástrica. Las calorías recibidas fueron superiores a los requerimientos estimados en ambos grupos, pero no existieron diferencias entre ellos. Los pacientes con gastrostomía recibieron nutrición enteral durante más tiempo (p = 0,007). Conclusiones: tanto la gastrostomía como la sonda nasogástrica son eficaces para el soporte nutricional enteral en pacientes con CCC que reciben radioterapia o tratamiento combinado con quimioterapia y radioterapia, sin mostrar diferencias en la evolución nutricional entre ambas (AU)

Structure-Driven Pharmacology of Transient Receptor Potential Channel Vanilloid 1.

The transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor that mediates the flux of cations across the membrane in response to several stimuli, including heat, voltage, and ligands. The best known agonist of TRPV1 channels is capsaicin, the pungent component of "hot" chili peppers. In addition, peptides found in the venom of poisonous animals, along with the lipids phosphatidylinositol 4,5-biphosphate, lysophosphatidic acid, and cholesterol, bind to TRPV1 with high affinity to modulate channel gating. Here, we discuss the functional evidence regarding ligand-dependent activation of TRPV1 channels in light of structural data recently obtained by cryoelectron microscopy. This review focuses on the mechanistic insights into ligand binding and allosteric gating of TRPV1 channels and the relevance of accurate polymodal receptor biophysical characterization for drug design in novel pain therapies.

A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo.

The high-grade pulmonary neuroendocrine tumors, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), remain among the most deadly malignancies. Therapies that effectively target and kill tumor-initiating cells (TICs) in these cancers should translate to improved patient survival. Patient-derived xenograft (PDX) tumors serve as excellent models to study tumor biology and characterize TICs. Increased expression of delta-like 3 (DLL3) was discovered in SCLC and LCNEC PDX tumors and confirmed in primary SCLC and LCNEC tumors. DLL3 protein is expressed on the surface of tumor cells but not in normal adult tissues. A DLL3-targeted antibody-drug conjugate (ADC), SC16LD6.5, comprised of a humanized anti-DLL3 monoclonal antibody conjugated to a DNA-damaging pyrrolobenzodiazepine (PBD) dimer toxin, induced durable tumor regression in vivo across multiple PDX models. Serial transplantation experiments executed with limiting dilutions of cells provided functional evidence confirming that the lack of tumor recurrence after SC16LD6.5 exposure resulted from effective targeting of DLL3-expressing TICs. In vivo efficacy correlated with DLL3 expression, and responses were observed in PDX models initiated from patients with both limited and extensive-stage disease and were independent of their sensitivity to standard-of-care chemotherapy regimens. SC16LD6.5 effectively targets and eradicates DLL3-expressing TICs in SCLC and LCNEC PDX tumors and is a promising first-in-class ADC for the treatment of high-grade pulmonary neuroendocrine tumors.

Defining the dermoscopic characteristics of fast-growing cutaneous melanomas.

A high growth rate in melanomas has been associated with a more aggressive phenotype and worse survival. The aim of this study was to define the dermoscopic characteristics associated with this type of cutaneous melanoma. We carried out a retrospective study of 132 cutaneous melanomas, analyzing certain clinical characteristics and the most important dermoscopic variables related to the melanomas. Fast-growing melanomas were considered to be those with a growth rate of more than 0.5 mm per month. Fast-growing melanomas more often lacked an atypical network, were symmetrical, presented ulceration, and were hypopigmented. The dermoscopic vascular pattern often showed atypical irregular vessels and milky-red areas. The association of these two is a specific characteristic. Fast-growing melanomas have a characteristic phenotype and dermoscopy can be useful for their identification.