Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain).

The singular BRCA1/2 mutational landscape of Asturias is updated 10 years after the first study. We analyzed BRCA1 and BRCA2 pathogenic variants in 1653 index cases. In total, 238 families were identified to carry a pathogenic variant, 163 families in BRCA1 and 75 families in BRCA2. This yielded a prevalence rate of 14.4%. Seven recurrent variants were found accounting for 55% of the cases. Among them, three are widely distributed (BRCA1 c.211A>G, c.470_471del and c.3331_3334del) and four had been reported as novel in Asturias: two in BRCA1 (c.1674del and c.2901_2902dup) and two in BRCA2 (c.2095C>T and c.4040_4035delinsC). A common haplotype was established for all recurrent variants indicating a shared ancestral origin. Three splicing analyses are shown: BRCA1:c.5152+3A>C and BRCA1:c.5333-3T>G that lead to skipping of exon 18, and 22 respectively, and BRCA1:c.5278-1G>T giving rise to two transcripts, one lacking exon 21 (p.Ille1760Glyfs*60) and one lacking the first 8 nucleotides of exon 21 (p.Phe1761Asnfs*14), supporting pathogenicity for these variants.

Evolución y características de los ingresos por COVID-19 pediátricos en un hospital terciario

Introducción. La mayoría de infecciones por SARS-CoV2 en población pediátrica cursan asintomáticas o con síntomas leves, con porcentaje mínimo de casos graves descritos como síndrome inflamatorio multisistémico asociado al SARS-CoV2 (SIM-PEDs). El objetivo fue describir las características clínico-epidemiológicas de aquellos pacientes pediátricos ingresados con diagnóstico confirmado de SARS-CoV2, y las posibles diferencias de la enfermedad considerando dos períodos epidemiológicos. Material y métodos. Estudio retrospectivo observacional de pacientes pediátricos ingresados con diagnóstico de COVID-19, de un hospital terciario. Se recogieron de forma consecutiva, entre marzo de 2020 hasta febrero 2022, analizando datos demográficos, clínicos, pruebas complementarias, tratamiento administrado y evolución. Resultados. Se incluyeron 69 pacientes, clasificándose en 6 grupos según diagnóstico. Los pacientes con neumonía asociaban mayor hipoxemia, mayor edad y eran predominantemente varones (p<0.01), con respecto al grupo de infecciones respiratorias sin condensación. SIM-PEDs fueron pacientes más graves, con afectación analítica marcada y mayor ingreso en UCIP. Durante el 2º periodo se observa una tendencia a la disminución de la infección respiratoria (69% al 47%), menor estancia hospitalaria (de 4 a 3 días), y aumento de los ingresos por otra patología (7,7% al 30,6%). Conclusiones. Los cuadros clínicos de COVID-19 más frecuentes en niños son respiratorios leves-moderados con buena evolución. Hay una tendencia a menor duración de estancia hospitalaria y aumento de ingresos por otra patología en pacientes asintomáticos en el segundo periodo. SIM-PEDs es otra forma de expresión de infección por SARS-COV2 de mayor gravedad, pero habitualmente con buen pronóstico tras diagnóstico precoz y requiriendo frecuentemente ingreso en UCIP. (provisto por Infomedic International)

Introduction. Most SARS-CoV2 infections in pediatric population are asymptomatic or have mild symptoms, with a small percentage of severe cases described as SARS-CoV2-associated multisystem inflammatory syndrome (MIS-C). The objective was to describe the clinical-epidemiological characteristics of those pediatric patients admitted with a SARS-CoV2 confirmed diagnosis, and the possible differences in the disease considering two epidemiological periods. Methods. Observational retrospective study of pediatric patients admitted with a diagnosis of COVID-19, from a tertiary hospital. They were collected consecutively, between March 2020 and February 2022, analyzing demographic and clinical data, complementary tests, administered treatment and evolution. Results. 69 patients were included, classified into 6 groups according to diagnosis. Patients with pneumonia associated greater hypoxemia, older age and were predominantly male (p<0.01), with respect to the group of respiratory infections without condensation. MIS-C were more severe patients, with marked analytic involvement and greater admission to the PICU. During the 2nd period, there was a trend towards a decrease in respiratory infection (69% to 47%), a shorter hospital stays (4 to 3 days), and an increase in admissions for another pathology (7.7% to 30,6%). Discussion. The most frequent clinical manifestations of COVID-19 in children are mild-moderate respiratory symptoms with a good prognosis. There is a trend towards a shorter length of hospital stay and an increase in admissions for another pathology in asymptomatic patients in the second period. MIS-C is another form of expression of SARS-COV2 infection of greater severity, but usually with a good prognosis after early diagnosis and frequently requiring PICU admission. (provided by Infomedic International)

Factores asociados al uso de métodos anticonceptivos en mujeres en edad fértil de 15 a 49 años según encuesta demográfica en Perú / Associated factors within the use of contraceptive methods in women of childbearing age between 15 to 49 years old according to a demographic survey in Peru

Introducción: Los métodos anticonceptivos son importantes herramientas para lograr una planificación familiar deseada. Objetivo: Determinar los factores asociados al uso de métodos anticonceptivos en mujeres en edad fértil de 15 a 49 años según ENDES 2018. Material y métodos: Estudio descriptivo, observacional, analítico y retrospectivo. Se analizó la muestra de la Encuesta Nacional Demográfica de Salud Familiar (ENDES), del año 2018 a mujeres peruanas entre 15 a 49 años que respondieron el módulo de métodos anticonceptivos. Resultados: Mayor prevalencia de usuarias de métodos anticonceptivos en el área urbana (RP=1,046, IC:1,037 ­ 1,054), según estado conyugal se evidencia un mayor uso en casadas o convivientes (RP=1,080 IC:1,071 ­ 1,090), en el nivel educativo se obtiene que mujeres con estudios superiores tiene mayor prevalencia de uso de anticonceptivos (RP= 1,021, IC:1,016 ­ 1,026) y, finalmente, la edad en la 1ª relación sexual menor a los 17 años tiene mayor prevalencia (RP = 1,017 IC:1,016 ­ 1,026). Conclusión: Existe asociación positiva entre residir en área urbana, edad de primera relación sexual menor a 17 años, ser casada o conviviente y tener grado de instrucción superior y el uso de métodos anticonceptivos.

Background: Contraceptive methods are an important tool to achieve the desired family planning.To determine the factors associated Objective:within the use of contraceptive methods in women of childbearing age between 15 to 49 years old according to the ENDES 2018. Material and methods: Descriptive, observational, analytical and retrospective study. The sample, of the National Demographic Survey of Family Health (ENDES) 2018, to Peruvian women between 15 to 49 years old who responded to the contraceptive methods module was analyzed. Results: There is a higher prevalence of women using contraceptive methods in the urban area (PR = 1,046, CI: 1,037 - 1,054), according the marital status there is a high use in married women of contraceptive use (PR = 1,080 CI: 1,071 - 1,090), in the educational level it's obtained that women with higher education have a higher prevalence of contraceptive use (PR = 1,021, CI: 1,016 - 1,026) and, finally, that the age in the first sex relationship before 17 years has a higher prevalence (PR = 1,017 CI: 1,016 - 1,026). Conclusion: There is a positive association between living in an urban area, age of first sexual intercourse less than 17 years, being married and having high educational level in the use of contraceptive methods.

Bilaminar Graft of the Anterior Capsule and Internal Limiting Membrane: A Novel Surgical Technique for the Treatment of Macular Hole and Focal Macular Detachment Associated with High Myopia and Posterior Staphyloma.

This case report describes a novel surgical technique for the treatment of macular hole and focal macular detachment associated with high myopia and posterior staphyloma. A 65-year-old female presented with a stage 3C myopic traction maculopathy and VA of 20/600. OCT examination confirmed a macular hole of 958 µm diameter, posterior staphyloma, and macular detachment. We performed combined phacoemulsification surgery with 23G pars plana vitrectomy; the anterior capsule was preserved and divided into two equal circular laminar flaps. We proceeded with central and peripheral vitrectomy, brilliant blue staining, and partial ILM peeling; capsular sheets were introduced sequentially in the vitreous chamber, the first one was implanted below the hole and attached to pigment epithelium, the second lamina was inserted into the hole, and the remaining portion of ILM was implanted crosswise below the edges of the hole. Macular-hole closure and progressive reapplication of the macular detachment were obtained, with a final VA of 20/80. Treatment of macular holes and focal macular detachment in high myopic eyes is complex, even for experienced surgeons. We propose a new technique with additional mechanisms based on anterior lens capsule and internal limiting membrane tissue properties that showed functional and anatomical improvement and could be considered an alternative treatment.

CHARACTERIZING COVID-19-RELATED RETINAL VASCULAR OCCLUSIONS: A Case Series and Review of the Literature.

PURPOSE: To describe clinical and ophthalmologic features and outcomes of patients with coronavirus disease-19 with retinal vascular occlusions. METHODS: Retrospective multicenter case series and PubMed review of cases reported from March 2020 to September 2021. Outcome measures are as follows: type of occlusion, treatments, best-corrected visual acuity, and central macular thickness on optical coherence tomography. RESULTS: Thirty-nine patients were identified. Fifteen patients with a median age of 39 (30-67) years were included in the multicenter study. Vascular occlusions included central retinal vein occlusion (12 eyes), branch retinal vein occlusion (4 eyes), and central retinal artery occlusion (2 eyes). Three cases were bilateral. Baseline best-corrected visual acuity was 20/45 (no light perception-20/20). Baseline central macular thickness was 348.64 (±83) µm. Nine eyes received anti-vascular endothelial growth factor agents, dexamethasone intravitreal implant, or both. Final best-corrected visual acuity was 20/25 (no light perception-20/20), and central macular thickness was 273.7 ± 68 µm (follow-up of 19.6 ± 6 weeks). Among the 24 cases from the literature review, retinal vein occlusion was the predominant lesion. Clinical characteristics and outcomes were similar to those found in our series. CONCLUSION: Coronavirus disease-19-associated retinal vascular occlusions tend to occur in individuals younger than 60 years. Retinal vein occlusion is the most frequent occlusive event, and outcomes are favorable in most cases.

Integrated health intervention on polypharmacy and inappropriate prescribing in elderly people with multimorbidity: Results at the end of the intervention and at 6 months after the intervention.

BACKGROUND AND OBJECTIVE: To analyse the impact of an integrated health intervention focused on polypharmacy and inappropriate prescribing (IP) in elderly people with multimorbidity. MATERIAL AND METHODS: Patients were referred for assessment and intervention from primary care or hospital to an interdisciplinary team composed of primary and hospital medical staff and nurses. Pharmacological assessment was centred on polypharmacy and IP using the STOPP/START criteria. Changes in polypharmacy and in IP were analysed at the end of the intervention and at 6 months. RESULTS: One hundred consecutive patients (mean (SD) age 81.5(8.0) years, 54(54%) male) were analysed. Mean prescribed medicines at baseline was > 10. There were no significant changes at the end of the intervention and at 6 months. The proportion of patients with two or more STOPP criteria reduced from 37% at the beginning of the intervention to 18% at the end (p< .001), and the proportion of those with START criteria from 13% to 6% (p = .004). These differences persisted at 6 months. The number of STOPP and START criteria before the intervention was associated with a decrease in the STOPP and START criteria at the end of the intervention and at 6 months. A reduction in polypharmacy (p= .041) and in falls (p= .034) was observed at 6 months in those with a decrease in the STOPP criteria at the end of the intervention. CONCLUSIONS: An integrated health intervention centred on polypharmacy and IP in elderly people improves inappropriate prescribing that persists beyond the intervention.

Neumonía atípica vs COVID-19 en tratamiento de linfoma de Hodgkin / Atypical pneumonia vs COVID-19 in treating Hodgkin's lymphoma

Introducción: En tiempos de pandemia por COVID-19 toda sintomatología respiratoria o síndrome febril lleva a descartar dicha infección, pero hay que tener en cuenta, sobre todo en pacientes onco-hematológicos, como diagnóstico diferencial la neumonía atípica por Pneumocystis Jirovecii (PCP). Objetivo: Describir el caso de neumonía atípica vs COVID-19 en un paciente con linfoma de Hodgkin. Caso clínico: Paciente mujer de 30 años con diagnóstico de linfoma de Hodgkin tipo clásico estadio clínico III (ECIII), que inicia tratamiento sistémico con quimioterapia esquema R-ABVD (plan de 6 cursos con partes A y B). Recibe 3 cursos R-ABVD con respuesta completa según tomografía. Al programar 4to curso parte B presenta persistencia febril hasta 39,8°C asociado a diaforesis nocturna, que se agudiza en la última semana, por lo que se decide hospitalizarla. Se realiza tomografía contrastada (TEM c/c) de tórax: opacidades en patrón de vidrio deslustrado intercalados con lesiones fibrosas en ambos pulmones, no adenopatías; deshidrogenasa láctica (DHL): 656 UI/L. Sin clínica respiratoria, ni examen físico respiratorio alterado. A descartar PCP vs neumonía COVID-19. Sin leucocitosis, reacción en cadena de polimerasa (PCR) COVID-19 negativa. Se define como neumonía no asociada a coronavirus, por lo que recibe 12 días de antibiótico con Sulfametoxazol + Trimetoprim. A la evolución clínica: mejoría de malestar general y afebril. Finaliza 6 cursos de R-ABVD, con respuesta completa en reevaluación tomográfica, asintomática y presentando prueba rápida para COVID-19 no reactiva. Conclusiones: En el contexto de pandemia por COVID-19 el diagnóstico diferencial debe ser oportuno(AU)

Introduction: In times of COVID-19 pandemic, all respiratory symptoms or febrile syndrome leads to ruling out said infection, but atypical Pneumocystis Jirovecii pneumonia (PCP) must be taken into account, especially in onco-hematological patients, as differential diagnosis. Objective: To describe the case of atypical pneumonia vs. COVID-19 in a patient with Hodgkin's lymphoma. Clinical case report: The case of a 30-year-old female patient with diagnosis of clinical stage III Hodgkin lymphoma (IBD) is reported. She began systemic treatment with R-ABVD chemotherapy scheme (6-course plan with parts A and B). She received 3 R-ABVD courses with complete response according to tomography. When scheduling 4th course, part B, she had feverish persistence up to 39.8 ° C associated with nocturnal diaphoresis, worsening in the last week, so hospitalization was decided. A contrast tomography (TEM c / c) of the thorax was performed: ground-glass opacities interspersed with fibrous lesions in both lungs, no adenopathy; lactic dehydrogenase (DHL): 656 IU / L. No respiratory symptoms, or altered respiratory physical examination, to rule out PCP vs. COVID-19 pneumonia. No leukocytosis, negative COVID-19 polymerase chain reaction (PCR). It is defined as non-coronavirus associated pneumonia, so she received 2 days of Sulfamethoxazole + Trimethoprim antibiotics. On the clinical course, she exhibited improvement of general malaise and she was afebrile. She completed 6 courses of R-ABVD, with complete response in tomographic re-evaluation, she was asymptomatic and had non-reactive rapid test for COVID-19. Conclusions: In the context of COVID-19 pandemic, the differential diagnosis must be timely(AU)

Doxycycline decreases amyloidogenic light chain-induced autophagy in isolated primary cardiac myocytes.

BACKGROUND: Immunoglobulin light chain (AL) cardiac amyloidosis is characterized by extracellular deposition of amyloid fibrils in the heart and is potentially fatal. Untreated, it manifests clinically as heart failure with a precipitous decline and a median survival of <6 months. AL cardiac amyloidosis is associated with impaired extracellular matrix homeostasis in the heart with increased matrix metalloproteinase (MMP) levels. This commmunication provides novel insights into a potential role for doxycycline, a non-selective MMP inhibitor in AL cardiac amyloidosis. METHODS/RESULTS: Adult rat ventricular myocytes stimulated with AL (obtained from cardiac amyloidosis patients) increased MMP-2 and MMP-9 activities (P < .05); the expression of autophagy marker microtubule associated protein 1 LC-3 isoform II (LC3-II) (P < .01), and the autophagy-related proteins ATG-4B (P < .05) and ATG-5 (P < .05) as compared to untreated cardiomyocytes. Doxycycline abrogated MMP activities (P < .0001) and decreased AL-induced autophagy via ATG-5 (P < .05). CONCLUSIONS: These in vitro studies demonstrated that doxycycline, in addition to inhibiting MMP, also modulated AL-induced autophagy in cardiomyocytes and provide potential insights for future therapeutic targets for AL-induced proteotoxicity. Novel therapies for cardiotoxicity and heart failure in AL cardiac amyloidosis remain an important unmet need.

O-GlcNAcylation Mediates Glucose-Induced Alterations in Endothelial Cell Phenotype in Human Diabetes Mellitus.

Background Posttranslational protein modification with O-linked N-acetylglucosamine (O-GlcNAc) is linked to high glucose levels in type 2 diabetes mellitus (T2DM) and may alter cellular function. We sought to elucidate the involvement of O-GlcNAc modification in endothelial dysfunction in patients with T2DM. Methods and Results Freshly isolated endothelial cells obtained by J-wire biopsy from a forearm vein of patients with T2DM (n=18) was compared with controls (n=10). Endothelial O-GlcNAc levels were 1.8-ford higher in T2DM patients than in nondiabetic controls (P=0.003). Higher endothelial O-GlcNAc levels correlated with serum fasting blood glucose level (r=0.433, P=0.024) and hemoglobin A1c (r=0.418, P=0.042). In endothelial cells from patients with T2DM, normal glucose conditions (24 hours at 5 mmol/L) lowered O-GlcNAc levels and restored insulin-mediated activation of endothelial nitric oxide synthase, whereas high glucose conditions (30 mmol/L) maintained both O-GlcNAc levels and impaired insulin action. Treatment of endothelial cells with Thiamet G, an O-GlcNAcase inhibitor, increased O-GlcNAc levels and blunted the improvement of insulin-mediated endothelial nitric oxide synthase phosphorylation by glucose normalization. Conclusions Taken together, our findings indicate a role for O-GlcNAc modification in the dynamic, glucose-induced impairment of endothelial nitric oxide synthase activation in endothelial cells from patients with T2DM. O-GlcNAc protein modification may be a treatment target for vascular dysfunction in T2DM.

Management of Primary Obstructive Megaureter by Endoscopic High-Pressure Balloon Dilatation. IDEAL Framework Model as a New Tool for Systematic Review.

Introduction: Therapeutic management of primary obstructive megaureter (POM) requiring surgery has been under debate for the last 15 years especially regarding the outcomes of endoscopic techniques compared to most traditional approaches. This review aims to analyze endoscopic High-Pressure Balloon Dilatation (HPBD) using the IDEAL model, a five-stage framework that describes surgical innovations (Idea, Development, Exploration, Assessment, and Long-term Study) and provides recommendations for a rigorous stepwise surgical research pathway. This model has been developed and demonstrated its value in evaluating surgical innovations assessing data quality and providing relevant information for the optimal design and feasibility of research in surgery. Materials and Methods: A systematic review of the published series of endoscopic HPBD in patients with POM was done using the IDEAL model as a tool to assess evidence quality. Reported clinical outcomes are also analyzed and reviewed. Results: The analysis of the results of the systematic assessment of the reported cohort of patients treated with HPBD for POM that the technique up to date is in stage 2a and stage 2b, or development. Evidence quality among the reported cohorts of patients with POM treated with HPBD is adequate, although systematization and standardization should be improved. Clinical outcomes of HPBD in the management of POM consistently show a 87.7% success rate with a negligible operative complication rate once "learning curve" has been surpassed. Symptomatic vesicoureteral reflux (VUR) is the main reason for ureteric reimplantation, but asymptomatic VUR does not seem to influence clinical outcome. Conclusions: The IDEAL framework and recommendations have allowed a systematic analysis of the evidence quality of the reported experience in the management of children with POM with HPBD of the vesicoureteral junction. The available evidence demonstrates that HPBD is an effective treatment for patients with POM, with a long-term success rate of 87.7% with very low morbidity. Future research mandates a standardization of data reporting, "ideally" following IDEAL recommendations, that would be required for any intervention and facilitate comparative analysis.

Comparación del confort de dos protectores bucales en jugadores de fútbol americano / Comparing the comfort of two mouth protectors in football players

Los deportes de contacto aumentan el riesgo de traumatismo causando alteraciones funcionales, estéticas y psicológicas. Los protectores bucales son parte del equipo de seguridad que protegen al deportista de estos accidentes, es importante que brinde confort para lograr el mejor rendimiento físico. Objetivo: Comparar el confort de los jugadores de fútbol americano con el uso de protectores prefabricados y protectores personalizados. Metodología: Se realizó un estudio cuasiexperimental, analítico y prospectivo donde se incluyeron 15 jugadores de futbol americano de la Facultad de Estudios Superiores Acatlán, UNAM, que firmaron consentimiento informado. La autora principal de este proyecto fabricó los protectores bucales superiores con hoja de copolímero de etilvinilacetato (EVA) #35. El protector prefabricado fue de silicón. Los jugadores realizaron dos prácticas de entrenamientos donde hicieron 30 minutos de carrera, 15 de estiramiento, 60 de fuerza y destreza en donde requerían de estar en constante comunicación verbal y 30 de cardiovascular en gimnasio (usaron un protector en cada entrenamiento). Se aplicó un cuestionario ­previamente validado por consenso de expertos­ para evaluar el confort en la respiración, lenguaje, náuseas, adaptación, comodidad e hidratación bucal con cada tipo de protector. La información se analizó en el programa SPSS v19.0; se usaron proporciones para las variables cualitativas y medidas de tendencia central y dispersión para las cuantitativas. Para comparar el confort con el uso de ambos protectores se empleó la prueba χ2, con un nivel de significancia p < 0.05. Resultados: La media de edad fue de 20 ± 2 años. Con el protector personalizado 11 jugadores (0.73) refirieron que respiraron y hablaron mejor, sintieron menos náusea 12 (0.80), mejor adaptación 11 (0.73) y mayor comodidad 12 (0.80) que, con el uso de protector bucal prefabricado, encontrando diferencias estadísticamente significativas (p < 0.05) y ocho (0.53) refirió menos hidratación bucal (p > 0.05). Doce (0.80) de los jugadores mencionaron tener mayor confort con el protector personalizado. Conclusiones: Con la metodología empleada y en la muestra estudiada, el uso de un protector bucal personalizado fabricado con hoja de copolímero de etilvinilacetato (EVA) #35 ofrece una mejor adaptación y comodidad, después de dos prácticas de entrenamiento (AU)

The contact sports, increase the risk of trauma causing functional, aesthetic and psychological alterations, mouth guards are part of the safety equipment that protects the athlete from this kind of accidents, it is also important that the mouth guard had to provides comfort, for achieve a best physical performance. Objective: Make the comparison with the comfort of American football players with the use of prefabricated protectors and customized protectors. Method: A quasi-experimental, analytical and prospective study was carried out, including 15 American football players from the Facultad de Estudios Superiores Acatlán, UNAM, who signed an informed consent. The lead author of this project manufactured the upper mouth guards with ethylvinylacetate (EVA) #35 copolymer foil. The prefabricated protector was made of silicone. The players performed two practice sessions where they did 30 minutes of running, 15 of stretching, 60 of strength and skill where they required being in constant verbal communication and 30 of cardiovascular in a gymnasium (they used a protector in each training). A questionnaire ­previously validated by expert consensus­ was applied to evaluate comfort in breathing, language, nausea, adaptation, comfort and oral hydration with each type of protector. The information was analyzed in the program SPSS v19.0; proportions were used for the qualitative variables and measures of central tendency and dispersion for the quantitative ones. To compare the comfort with the use of both protectors the test χ2 was used, with a level of signifi cance p < 0.05. Results: The mean age was 20 ± 2 years. With the personalized protector, 11 players (0.73) reported that they breathed and spoke better, feeling less nausea 12 (0.80), better adaptation 11 (0.73) and greater comfort 12 (0.80) than with the use of prefabricated mouth guards, fi nding statistically signifi cant diff erences (p < 0.05) and 8 (0.53) reported less oral hydration (p > 0.05). 12 (0.80) of players mentioned having more comfort with the custom protector. Conclusions: The use of a personalized mouth guard off ers better fi t and comfort made with sheet copolymer of ethylvinylacetate, after two training practices (AU)

Genital reconstruction with Integra™ artificial dermis after radical resection in a boy with diffuse lymphangiomatosis. / Reconstrucción genital con dermis artificial Integra® tras resección radical en un niño con linfangiomatosis difusa.

OBJECTIVE: Lymphangiomatosis is a rare disease affecting lymphatic vessels that causes a marked increase of them in the affected area. The final objective of treatment of the genital disease is to preserve sexual function and voiding with a satisfactory aesthetic result with the aim to minimize the emotional impact. METHODS: For the first time in children, we report a case of local reconstruction using artificial dermis after the excision of a genital lymphatic malformation in an eight year old patient. RESULTS: We performed surgical excision of the lymphatic malformation genital component and reconstruction of the scrotal and penile area in two steps, using an autologous graft over artificial dermis. No complications were registered. Both aesthetic and functional results were excellent, and spontaneous erections that were not present before, were also evidenced. No local recurrence was seen at two year follow up. CONCLUSION: The use of artificial dermis for genital surface reconstruction enables radical excision of tissues involved by diffuse lymphangiomatosis in this location. Surgical technique is simple, postoperative care is easy, being ambulatory care feasible. Final result is an elastic, fine skin, very satisfactory aesthetically, and functionally normal, which even keeps local sensitivity. In the long term, this will benefit the sexual field, so damaged in this patients.

Activation of non-canonical WNT signaling in human visceral adipose tissue contributes to local and systemic inflammation.

The accumulation of visceral adiposity is strongly associated with systemic inflammation and increased cardiometabolic risk. WNT5A, a non-canonical WNT ligand, has been shown to promote adipose tissue inflammation and insulin resistance in animal studies. Among other non-canonical pathways, WNT5A activates planar cell polarity (PCP) signaling. The current study investigated the potential contribution of non-canonical WNT5A/PCP signaling to visceral adipose tissue (VAT) inflammation and associated metabolic dysfunction in individuals with obesity. VAT and subcutaneous adipose tissue (SAT) samples obtained from subjects undergoing bariatric surgery were analyzed by qRT-PCR for expression of WNT/PCP genes. In vitro experiments were conducted with preadipocytes isolated from VAT and SAT biopsies. The expression of 23 out of 33 PCP genes was enriched in VAT compared to SAT. Strong positive expression correlations of individual PCP genes were observed in VAT. WNT5A expression in VAT, but not in SAT, correlated with indexes of JNK signaling activity, IL6, waist-to-hip ratio and hsCRP. In vitro, WNT5A promoted the expression of IL6 in human preadipocytes. In conclusion, elevated non-canonical WNT5A signaling in VAT contributes to the exacerbated IL-6 production in this depot and the low-grade systemic inflammation typically associated with visceral adiposity.

Tumor de las células de la granulosa: importancia de la inmunohistoquímica en el diagnóstico

Se presenta un caso de una paciente joven de 30 años quien consultó por trastornos menstruales y dolor abdominal de evolución de 1 año. Se le diagnóstico una tumoración de ovario poco frecuente como son los tumores de las células de la granulosa por medio de marcadores de inmunohistoquímica.

It is presented a case of a young woman who had menstrual problems and abdominal pain since one year ago. It was diagnosed an uncommon ovarian tumor such as tumor of granulosa cells using immunohistochemical markers.

High-pressure balloon assessment of pelviureteric junction prior to laparoscopic "vascular hitch".

AIM: To assess if calibration of the ureteropelvic junction (UPJ) using a high-pressure balloon inflated at the UPJ level in patients with suspected crossing vessels (CV) could differentiate between intrinsic and extrinsic stenosis prior to laparoscopic vascular hitch (VH). MATERIALS AND METHODS: We reviewed patients with UPJO diagnosed at childhood or adolescence without previous evidence of antenatal or infant hydronephrosis (10 patients). By cystoscopy, a high-pressure balloon is sited at the UPJ and the balloon inflated to 8-12 atm under radiological screening. We considered intrinsic PUJO to be presente where a 'waist' was observed at the PUJ on inflation of the balloon and a laparoscopic dismembered pyeloplasty is performed When no 'waist' is observed we considered this to represent extrinsic stenosis and a laparoscopic VH was performed. Patients with absence of intrinsic PUJ stenosis documented with this method are included for the study. RESULTS: Six patients presented pure extrinsic stenosis. The mean age at presentation was 10.8 years. Mean duration of surgery was 99 min and mean hospital stay was 24 hours in all cases. We found no intraoperative or postoperative complications. All children remain symptoms free at a mean follow up of 14 months. Ultrasound and renogram improved in all cases. CONCLUSION: When no 'waist' is observed we considered this to represent extrinsic stenosis and a laparoscopic VH was performed. In these patients, laparoscopic transposition of lower pole crossing vessels ('vascular hitch') may be a safe and reliable surgical technique.

Restoration of autophagy in endothelial cells from patients with diabetes mellitus improves nitric oxide signaling.

BACKGROUND: Endothelial dysfunction contributes to cardiovascular disease in diabetes mellitus. Autophagy is a multistep mechanism for the removal of damaged proteins and organelles from the cell. Under diabetic conditions, inadequate autophagy promotes cellular dysfunction and insulin resistance in non-vascular tissue. We hypothesized that impaired autophagy contributes to endothelial dysfunction in diabetes mellitus. METHODS AND RESULTS: We measured autophagy markers and endothelial nitric oxide synthase (eNOS) activation in freshly isolated endothelial cells from diabetic subjects (n = 45) and non-diabetic controls (n = 41). p62 levels were higher in cells from diabetics (34.2 ± 3.6 vs. 20.0 ± 1.6, P = 0.001), indicating reduced autophagic flux. Bafilomycin inhibited insulin-induced activation of eNOS (64.7 ± 22% to -47.8 ± 8%, P = 0.04) in cells from controls, confirming that intact autophagy is necessary for eNOS signaling. In endothelial cells from diabetics, activation of autophagy with spermidine restored eNOS activation, suggesting that impaired autophagy contributes to endothelial dysfunction (P = 0.01). Indicators of autophagy initiation including the number of LC3-bound puncta and beclin 1 expression were similar in diabetics and controls, whereas an autophagy terminal phase indicator, the lysosomal protein Lamp2a, was higher in diabetics. In endothelial cells under diabetic conditions, the beneficial effect of spermidine on eNOS activation was blocked by autophagy inhibitors bafilomycin or 3-methyladenine. Blocking the terminal stage of autophagy with bafilomycin increased p62 (P = 0.01) in cells from diabetics to a lesser extent than in cells from controls (P = 0.04), suggesting ongoing, but inadequate autophagic clearance. CONCLUSION: Inadequate autophagy contributes to endothelial dysfunction in patients with diabetes and may be a target for therapy of diabetic vascular disease.

High-pressure balloon assessment of pelviureteric junction prior to laparoscopic "vascular hitch"

ABSTRACT Aim To assess if calibration of the ureteropelvic junction (UPJ) using a high-pressure balloon inflated at the UPJ level in patients with suspected crossing vessels (CV) could differentiate between intrinsic and extrinsic stenosis prior to laparoscopic vascular hitch (VH). Materials and Methods We reviewed patients with UPJO diagnosed at childhood or adolescence without previous evidence of antenatal or infant hydronephrosis (10 patients). By cystoscopy, a high-pressure balloon is sited at the UPJ and the balloon inflated to 8-12 atm under radiological screening. We considered intrinsic PUJO to be present where a ‘waist’ was observed at the PUJ on inflation of the balloon and a laparoscopic dismembered pyeloplasty is performed When no ‘waist’ is observed we considered this to represent extrinsic stenosis and a laparoscopic VH was performed. Patients with absence of intrinsic PUJ stenosis documented with this method are included for the study. Results Six patients presented pure extrinsic stenosis. The mean age at presentation was 10.8 years. Mean duration of surgery was 99 min and mean hospital stay was 24 hours in all cases. We found no intraoperative or postoperative complications. All children remain symptoms free at a mean follow up of 14 months. Ultrasound and renogram improved in all cases. Conclusion When no ‘waist’ is observed we considered this to represent extrinsic stenosis and a laparoscopic VH was performed. In these patients, laparoscopic transposition of lower pole crossing vessels (‘vascular hitch’) may be a safe and reliable surgical technique.

Endothelial Dysfunction in Human Diabetes Is Mediated by Wnt5a-JNK Signaling.

OBJECTIVE: Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus. APPROACH AND RESULTS: We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition. CONCLUSIONS: Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus.

Slip-Knot-Loop Suture for Continuous Suturing in Laparoscopy.

AIMS: One of the challenges of laparoscopic surgery is the time required to perform intracorporeal knots. This can result in considerably longer operating times when compared with the open approach. An example of this is pediatric laparoscopic pyeloplasty, where extensive laparoscopic suturing is required. To reduce the time suturing, the authors developed a new knotting technique for laparoscopic suturing. MATERIALS AND METHODS: The authors modified a neurosurgical knot technique to speed up intricate continuous suturing, and a simple slip-knot-loop suture was created. Twenty continuous sutures were performed with five "bites" of tissue each. Ten were performed with a conventional intracorporeal knot to anchor the suture (Group 1), and 10 were performed using the slip-knot-looped suture to anchor (Group 2). This new knotting technique was used to perform five bowel anastomoses on pig intestine and tested for leaks by distending them with saline for 5 minutes. RESULTS: The mean time to perform the suture for Group 1 was 300 seconds, and the mean time for Group 2 was 236 seconds. Unpaired two-tailed Student's t test comparing the means was significant (P < .001). No leaks occurred in any of the five anastomoses. CONCLUSIONS: This new slip-knot-loop technique modified for pyeloplasty was easy to use, was quicker than conventional knot tying, and produced safe knots and leak-free anastomoses. This knot is transferable to any laparoscopic procedure where continuous suturing is to be used.