Enfermedades musculoesqueléticas y su asociación con el sobrepeso y obesidad en adultos mayores, un estudio transversal / Musculoskeletal diseases and their association with overweight and obesity in older adults, a cross-sectional study

Objetivo: determinar la prevalencia y la asociación de enfermedades musculoesqueléticas con el sobrepeso y obesidad, y las diferencias respecto a edad y sexo. Métodos: el presente estudio es de tipo transversal, descriptivo y analítico, el universo está compuesto por pacientes adultos mayores a 60 años con diagnóstico de enfermedades musculoesqueléticas que acuden a consulta en el periodo de enero a diciembre, del año 2019, en el centro de salud "Villa Oruro", en Tiquipaya, Cochabamba, Bolivia, con un muestreo no probabilístico por conveniencia, la muestra del estudio fue 353 pacientes. Resultados: se evaluó a 353 pacientes mayores a 60 años, 156 hombres y 197 mujeres, con una edad promedio de 71,51 ± 8,45 con índice de masa corporal promedio de 26,68 ± 1,77. Se realizó el análisis estadístico de asociación de variables categóricas, en base a rangos del índice de masa corporal (sobrepeso y obesidad) con las enfermedades musculoesqueléticas. Conclusiones: dentro de la evaluación del sobrepeso y obesidad, y su relación con patologías musculoesqueléticas, la gonartrosis es la más relacionada con la presencia de sobrepeso y obesidad, por lo que se recomienda establecer métodos de educación en la población con hábitos alimenticios y estilos de vida saludables para disminuir la prevalencia de enfermedades musculoesqueléticas asociadas a sobrepeso y obesidad.

Objectives: the aim of this study is to determine the prevalence and association of musculoskeletal diseases with overweight and obesity, and the differences with respect to age and sex. Methods: this type of study is cross-sectional, descriptive and analytical, the universe is composed of adult patients over 60 years of age with a diagnosis of musculoskeletal diseases who come for consultation in the period from January to December, year 2019, of the health center "Villa Oruro", Tiquipaya, Cochabamba, Bolivia, with a non-probabilistic sampling by convenience, the study sample was 353 patients. Results: we evaluated 353 patients over 60 years of age, 156 men and 197 women, with an average age of 71.51 ± 8.45 with an average body mass index of 26.68 ±1.77. Statistical analysis of association of categorical variables, based on body mass index ranges (overweight and obesity) with musculoskeletal diseases, was performed. Conclusions: within the evaluation of overweight and obesity, and their relationship with musculoskeletal pathologies, gonarthrosis is the most related to the presence of overweight and obesity, it is recommended and establish education in the population with healthy eating habits and lifestyles to reduce the prevalence of musculoskeletal diseases associated with overweight and obesity.

Reciprocal regulation of amino acid import and epigenetic state through Lat1 and EZH2.

Lat1 (SLC7A5) is an amino acid transporter often required for tumor cell import of essential amino acids (AA) including Methionine (Met). Met is the obligate precursor of S-adenosylmethionine (SAM), the methyl donor utilized by all methyltransferases including the polycomb repressor complex (PRC2)-specific EZH2. Cell populations sorted for surface Lat1 exhibit activated EZH2, enrichment for Met-cycle intermediates, and aggressive tumor growth in mice. In agreement, EZH2 and Lat1 expression are co-regulated in models of cancer cell differentiation and co-expression is observed at the invasive front of human lung tumors. EZH2 knockdown or small-molecule inhibition leads to de-repression of RXRα resulting in reduced Lat1 expression. Our results describe a Lat1-EZH2 positive feedback loop illustrated by AA depletion or Lat1 knockdown resulting in SAM reduction and concomitant reduction in EZH2 activity. shRNA-mediated knockdown of Lat1 results in tumor growth inhibition and points to Lat1 as a potential therapeutic target.

24-Gy low-voltage x-ray irradiation with ranibizumab therapy for neovascular AMD: 6-month safety and functional outcomes.

BACKGROUND AND OBJECTIVE: To describe the 6-month safety and preliminary efficacy outcomes of the use of 24-Gy radiation with intravitreal ranibizumab for patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: A single treatment of a non-invasive, externally delivered low-voltage x-ray irradiation at a dose of 24 Gy was administered in one session through three locations in the inferior pars plana in a consecutive series of patients with neo-vascular AMD (treatment naïve and previously treated). Optical coherence tomography (OCT) and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity examinations were performed at 1 week, 1 month, and monthly thereafter with quarterly fluorescein angiography. RESULTS: Nineteen patients completed 6 months of follow-up. There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean baseline ETDRS score was 38.3 ± 19.5 letters. At 6 months, the corresponding ETDRS score was 44.7 ± 16.8 letters. At 6 months, the mean change in visual acuity was 6.4 ± 9.8 ETDRS letters. Patients received an average of 0.4 additional ranibizumab injections following the initial two mandated injections. CONCLUSION: A single treatment of external 24-Gy low-voltage x-ray therapy in conjunction with ranibizumab demonstrated an overall improvement in visual acuity in patients with neovascular AMD at 6 months, with no radiation-related adverse effects.

16-Gy low-voltage x-ray irradiation followed by as-needed ranibizumab therapy for AMD: 6-month outcomes of a "radiation-first" strategy.

BACKGROUND AND OBJECTIVE: To describe the effect of a "radiation-first" combination treatment strategy for neovascular age-related macular degeneration (AMD) with ranibizumab rescue therapy. PATIENTS AND METHODS: Non-invasive, externally delivered low-voltage x-ray irradiation at a dose of 16 Gy was given in a single session through three locations in the inferior pars plana in a consecutive series of patients with neovascular AMD. Ranibizumab was administered according to prospectively determined criteria. RESULTS: Thirteen patients completed a 6-month follow-up. All patients lost 15 or fewer ETDRS letters, 7 gained 0 or more ETDRS letters, and 0 gained more than 15 ETDRS letters. Patients received a total of 15 ranibizumab injections following x-ray irradiation at baseline. Two patients received no ranibizumab injections, seven patients received 1 injection, and four patients received 2 injections. CONCLUSION: Low-voltage x-ray treatment followed by ranibizumab rescue demonstrates an independent visual acuity stabilizing effect for patients with wet AMD.

16-Gy low-voltage x-ray irradiation with ranibizumab therapy for AMD: 6-month safety and functional outcomes.

BACKGROUND AND OBJECTIVE: To describe the 6-month safety and preliminary efficacy outcomes of the use of 16-Gy radiation with intravitreal ranibizumab for patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: A single treatment of a non-invasive, externally delivered low-voltage 16-Gy x-ray irradiation was administered in one session through three locations in the inferior pars plana. Optical coherence tomography (OCT) and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) examinations were performed at 1 week, 1 month, and monthly thereafter, with quarterly fluorescein angiography (FA). After the two initial ranibizumab injections, subsequent injections were administered according to the following criteria: VA decline of 10 ETDRS letters compared with baseline, increase of 100-µm central foveal thickness on OCT compared with baseline, the development of new submacular hemorrhage, and the development of a new area of classic choroidal neovascularization on FA. RESULTS: Twenty-six patients completed a 6-month follow-up. There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean baseline ETDRS score was 46.6 letters (range: 5 to 80; standard deviation [SD]: 21.5). At 6 months, the corresponding ETDRS score was 55.6 letters (range: 25 to 80; SD: 18.9) and the mean change in VA was 9.5 ETDRS letters (SD: 10.3). On responder analysis, 96% lost 15 or fewer ETDRS letters, 81% gained 0 or more ETDRS letters, and 50% gained 15 or more ETDRS letters. Patients received a total of 13 ranibizumab injections following two initial injections. At 6 months, patients received an average of 0.5 additional injections following the initial two mandated injections. CONCLUSION: A single treatment of externally applied, non-invasive 16-Gy low-voltage x-ray therapy in conjunction with ranibizumab demonstrated an overall improvement of VA in patients with neovascular AMD at 6 months with no radiation-related adverse effects.

Síndrome de hiperinmunoglobulinemia E: Reporte de dos casos / Hyperimmunoglobulin E syndrome: report of two cases

Introducción. El síndrome de hiperinmunoglobulinemia E es una inmunodeficiencia sistémica poco frecuente, caracterizada por dermatitis eccematosa, abscesos fríos recurrentes, infecciones pulmonares con formación de neumatoceles, facies tosca, niveles elevados de inmunoglobulina E (IgE) en suero y eosinofilia. Casos clínicos. Caso 1. Femenino de 11 años de edad con antecedentes de neumonía recurrente, gastroenteritis de repetición, dermatitis eccematosa de predominio en pliegues, y abscesos fríos; en estudios de laboratorio destacó el hallazgo de 16 070 eosinófilos e IgE de 4 864 Ul. Manejada con gammaglobulina se observó buena respuesta clínica. Caso 2. Femenino de 12 años de edad con historia de otitis recurrente y conjuntivitis supurativa, presentaba eccema crónico generalizado e impetiginizado. En estudios de laboratorio se reportó IgE de 3 000 UI; fue manejada con dapsona, trimetropim/sulfametoxazol y metotrexate. Conclusión. Los 2 casos aquí informados presentaron piel eccematosa, infecciones recurrentes e incremento de los niveles de IgE, compatibles con síndrome de hiperinmunoglobulinemia E en la forma autosómica recesiva.

Background. Hyperimmunoglobulin E syndrome is a rare systemic immunodeficiency characterized by eczematous dermatitis, recurrent cold abscesses, lung infections with pneumatoceles, coarse facial appearance, high IgE levels and eosinophilia. Case reports. Case 1: We report the case of an 11-year-old female with a history of recurrent lung infections, recurrent gastroenteritis, eczematous dermatitis affecting the skin folds and cold abscesses. Laboratory studies showed elevated eosinophils (16 070) and IgE 4864 IU. The patient received treatment with g-globulin, showing adequate clinic response to treatment. Case 2: We present the case of a 12-year-old female with a history of recurrent otitis and suppurative conjunctivitis, showing widespread and chronic infected eczema. Laboratory studies showed elevated IgE (3 000 IU). She was treated with dapsone, trimethoprim/sulfamethoxazole and methotrexate. Conclusions. We presented two patients with eczematous skin, recurrent infections and increased IgE levels, which are compatible with hyperimmunoglobulin E autosomal recessive syndrome.

Synthesis, SAR study and biological evaluation of novel pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as anti-proliferative agents.

Checkpoint deficiency of malignant cells can be exploited in cancer drug discovery. Compounds that selectively kill checkpoint-deficient cells versus checkpoint-proficient cells can be utilized to preferentially target tumor cells, while sparing normal cells. The protein p21(Wafl/Cipl/Sdi1) (hereafter referred to as p21) inhibits progression of the cell cycle by inhibiting the activity of G1 kinases (cyclin D/cdk4 and cyclin E-cdk2) and the G2 kinase (cyclin B/cdkl) in response to DNA damage or abnormal DNA content. The expression of p21 is often low in human cancer cells due to frequent loss of the upstream activator, p53, and is associated with poor prognosis in some cancer patients. Using an isogenic pair of cell lines, HCT116 (p21+/+) and 80S14 (p21-/-), we have disclosed previously a novel series of pyrazolo[1,5-a]pyrimidines that preferentially kill the p21-deficient cells. We will present the synthesis, biological activities and SAR study of a series of pyrazolo[1,5-a]pyrimidines with an optimized phenyl amide moiety at the C-7 position. The mechanism of action of these compounds will also be discussed.

Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel antiproliferative agents: exploration of core and headpiece structure-activity relationships.

A novel series of antiproliferative agents containing pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides, selective for p21-deficient cells, were identified by high-throughput screening. Exploration of the SAR relationships in the headpiece, core, and tailpiece is described. Strict steric, positional, and electronic requirements were observed, with a clear preference for both core nitrogens, a thienoyl headpiece, and meta substituted tailpiece.

[Giant gravidarum granuloma of the scalp]. / Granuloma gravidarum gigante en piel cabelluda.

Lobular capillary hemangioma (pyogenic granuloma) has been reported more frequently in the skin (88%) than in the mucous membranes (12%). Granuloma gravidarum is a pyogenic granuloma that develops during pregnancy, often in the oral mucosa. Estrogens apparently increase the inflammatory response of mucous membranes. In this article, we describe the first case of a granuloma gravidarum of the scalp.

Granuloma gravidarum gigante en piel cabelluda / Giant gravidarum granuloma of the scalp

El hemangioma capilar lobular (granuloma piógeno) ha sido informado con más frecuencia en piel (88%) que en mucosas (12%). El granuloma gravidarum es un granuloma piógeno que se presenta frecuentemente durante el embarazo a nivel de mucosa oral. Ha sido asociado con la acción de los estrógenos y una respuesta inflamatoria exagerada de las mucosas. En este artículo informamos el primer caso de granuloma gravidarum en piel cabelluda.

Lobular capillary hemangioma (pyogenic granuloma) has been reported more frequently in the skin (88%) than in the mucous membranes (12%). Granuloma gravidarum is a pyogenic granuloma that develops during pregnancy, often in the oral mucosa. Estrogens apparently increase the inflammatory response of mucous membranes. In this article, we describe the first case of a granuloma gravidarum of the scalp.

Validation of cyclin D1/CDK4 as an anticancer drug target in MCF-7 breast cancer cells: Effect of regulated overexpression of cyclin D1 and siRNA-mediated inhibition of endogenous cyclin D1 and CDK4 expression.

We have examined the role of cyclin D1 and cyclin-dependent kinase-4 (CDK4) in the cell cycle progression and proliferation of MCF-7 breast cancer cells. Forced expression of cyclin D1 using a tetracycline-regulated expression system, and suppression of endogenous cyclin D1 and CDK4 using small interfering RNA (siRNA) were used to validate this protein complex as a drug target in cancer drug discovery. Overexpression of cyclin D1 increased both phosphorylation of the retinoblastoma gene product (RB) and passage through the G1-S phase transition, resulting in increased proliferation of cells. When cyclin D1 expression was shut off, growth rates fell below those seen in control cell lines transfected with the vector, indicating an increased dependence on this protein for proliferation. Inhibition of endogenous cyclin D1 or CDK4 expression by RNA interference resulted in hypophosphorylation of RB and accumulation of cells in G1. These results support the prevailing view that pharmacological inhibition of cyclin D1/CDK4 complexes is a useful strategy to inhibit the growth of tumors. Furthermore, since MCF-7 cells appear to be dependent on this pathway for their continued proliferation, it is a suitable cell line to test novel cyclin D1/CDK4 inhibitors.

Histoplasmosis y síndrome hemofagocítico en pacientes pediátricos con infección por el virus de inmunodeficiencia humana / Histoplasmosis and hemophagocytic syndrome in patient pediatric with infection for the virus of human immunodeficiency

En áreas endémicas, la histoplasmosis en adultos con infección por el virus de inmunodeficiencia humana, ocurre entre 2 por ciento y 5 por ciento. Los pacientes pediátricos con virus de inmunodeficiencia humana deben ser considerados en riesgo de adquirir histoplasmosis en dichas áreas. Con inmunosupresión severa, en el 95 por ciento de los casos la histoplasmosis es diseminada y puede acompañarse de síndrome hemofagocítico. Objetivo del presente trabajo es evaluar la frecuencia de síndrome hemofagocítico en pacientes pediátricos con infección virus de inmunodeficiencia humana. Se realizó un estudio clínico, retrospectivo y descriptivo. Se revisaron historias clínicas obtenidas del Servicio de Historias Médicas del Hospital de Niños J.M de Los Ríos, de pacientes con diagnóstico de infeccion virus de inmunodeficiencia humana hasta julio 2003, que presentaron histoplasmosis y aquellos que presentaron síndrome hemofagocítico. Se revisaron 237 historias de pacientes con infección virus de inmunodeficiencia humana, de los cuales 4 (1,6 por ciento) presentaron diagnóstico de histoplasmosis; 3 de ellos (75 por ciento) con histoplasmosis diseminada. Uno de estos pacientes presentó síndrome hemofagocítico, el cual fue el único con dicho diagnóstico en la serie revisada (0,42 por ciento). Ningún paciente recibió tratamiento antirretroviral de alta eficacia previo al diagnóstico de histoplasmosis. El paciente con síndrome hemofagocítico e histoplasmosis diseminada recibió profilaxis secundaria asociada al tratamiento antirretroviral de alta eficacia, con sobrevida hasta el momento mayor de 1 año. La frecuencia de histoplasmosis en pacientes pediátricos con virus de inmunodeficiencia humana fue menor que lo descrito en adultos de áreas endémicas, siendo la forma diseminada la más frecuente. El síndrome hemofagocítico en pacientes pediátricos con infección virus de inmunodeficiencia humana tuvo baja incidencia.

Parallel synthesis and biological evaluation of 5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-one cytotoxic agents selective for p21-deficient cells.

A novel series of inhibitors of cancer cell proliferation, selective against p21 cell cycle checkpoint-disrupted cells vs. cells with intact p21 checkpoint, were identified by high-throughput screening. Optimization of both ends of the lead molecule to improve potency, using parallel synthesis and iterative design, is described. The 2-(1,4-dibenzodioxane)-substituted derivative 14 was identified as a highly selective and potent agent displaying an IC50 of 91 nM in the p21-deficient cell line.

Inhibition of tumor cell proliferation by thieno[2,3-d]pyrimidin-4(1H)-one-based analogs.

On the basis of a screening lead from an assay using a pair of p21 isogenic cell lines (p21-proficient cells and p21-deficient cells) to identify chemoselective agents, a series of novel thieno[2,3-d]pyrimidin-4(1H)-one-based analogs was prepared. Some analogs inhibited the growth of human colon tumor cells.

Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel anti-proliferative agents: parallel synthesis for lead optimization of amide region.

A novel series of p21 chemoselective agents containing a pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides were identified by high throughput screening. Optimization of the amide region by parallel synthesis and the iterative design toward understanding structure-activity relationship to improve potency are described. The isopropyl carbamate derivative 34 was identified as a highly chemoselective agent displaying a potency of 51 nM in the p21 deficient cell line.

Bioactive isomalabaricane triterpenes from the marine sponge Rhabdastrella globostellata.

Two new isomalabaricane triterpenes, stellettin H (1) and stellettin I (2), have been isolated from the marine sponge Rhabdastrella globostellata, collected from the Philippines. Stellettins A-D (3-6), (-)-stellettin E (7), and rhabdastrellic acid-A (8) were also isolated and characterized. Stellettin B (4) and (-)-stellettin E (7) showed selective cytotoxicity toward p21(WAF1/Cip1)-deficient human colon tumor (HCT-116) cells with IC(50) values of 0.043 and 0.039 microM, respectively.

Efecto ansiolítico y amnésico del midazolam comparado con el diazepam en la medicación preanestésica / Ansiolytic and amnesia effect of midazolam versus diazepam in preanesthetic medication

Las benzodiacepinas con el diazepam y el midazolam son psicofármacos capaces de modificar de manera diversa los fenómenos intelectuales, sean éstos normales o patológicos. El objetivo del presente trabajo, fue analizar el grado anasiolítico y amnésico del midazolam y el diazepam en la medicación preanestésica. Se estudiaron 40 pacientes divididos en dos grupos de 20 cada uno, todos del sexo masculino, para cirugía electiva ortopédica, con técnica anestésica regional. Al grupo I se le administró midazolam, al grupo II se le aplicó diazepam; a ambos se les realizó el test IDARE y la prueba Guestáltica Visuomotora de Bender en la sala preanestésica y posteriormente a la llegada de los pacientes a recuperación. Los cambios encontrados no fueron significativos en la amnesia y en la ansiolísis, aunque la respuesta a la percepción visuo-espacial y coordinación motriz fue mejor para el grupo de midazolam. Las benzodiacepinas dentro de los tranquilizantes menores son los compuestos más modernos y de mayor uso terapéutico, son sintéticas, ejercen las mismas acciones cualitativas, tienen el mismo mecanismo de acción, aunque existen diferencias cuantitativas en su espectro farmacodinámico