Assessing Utility of 24-Hour Ambulatory Blood Pressure Monitoring to Distinguish Pediatric Populations Presenting with Elevated Blood Pressure in Rhode Island.

This retrospective study aimed to assess the value of 24-hour ambulatory blood pressure monitoring (ABPM) in distinguishing primary from secondary hypertension in pediatric patients. Our study was conducted on 293 patients referred to a pediatric nephrology clinic over 11 years. Various ABPM parameters were analyzed, including daytime and nighttime systolic and diastolic blood pressures, heart rate, and blood pressure load. Among the participants, 74% were normotensive (white-coat hypertension), 21.5% had primary hypertension, and 4.4% had secondary hypertension. There were no significant differences in the analyzed variables between primary and secondary hypertension groups. Our findings suggest that ABPM might not reliably differentiate between the two in this cohort. As white-coat hypertension becomes more prevalent, ABPM remains a valuable tool in preventing unnecessary workups in children without sustained hypertension. However, our study did not identify specific endpoints for distinguishing primary from secondary hypertension.

Systematic Review and Meta-analysis of Blood Glucose Response to High-intensity Interval Exercise in Adults With Type 1 Diabetes.

OBJECTIVES: Exercise-induced hyperglycemia is recognized in type 1 diabetes (T1D) clinical guidelines, but its association with high-intensity intermittent exercise (HIIE) in acute studies is inconsistent. In this meta-analysis, we examined the available evidence of blood glucose responses to HIIE in adults with T1D. The secondary, aim was to examine predictors of blood glucose responses to HIIE. We hypothesized that there would be no consistent effect on blood glucose from HIIE, unless examined in the context of participant prandial status. METHODS: We conducted a literature search using key words related to T1D and HIIE. Studies were required to include at least 6 participants with T1D with a mean age >18 years, involve an HIIE intervention, and contain pre- and postexercise measures of blood glucose. Analyses of extracted data were performed using a general inverse variance statistical method with a random effects model and a weighted multiple regression. RESULTS: Nineteen interventions from 15 reports were included in the analysis. A mean overall blood glucose decrease of -1.3 mmol/L (95% confidence interval [CI], -2.3 to -0.2 mmol/L) was found during exercise, albeit with high heterogeneity (I2=84%). When performed after an overnight fast, exercise increased blood glucose by +1.7 mmol/L (95% CI, 0.4 to 3.0 mmol/L), whereas postprandial exercise decreased blood glucose by -2.1 mmol/L (95% CI, -2.8 to -1.4 mmol/L), with a statistically significant difference between groups (p<0.0001). No associations with fitness (p=0.4), sex (p=0.4), age (p=0.9), exercise duration (p=0.9), or interval duration (p=0.2) were found. CONCLUSION: The effect of HIIE on blood glucose is inconsistent, but partially explained by prandial status.

Tiroiditis subaguda posterior a la administración de la vacuna COVID-19. Presentación de tres casos clínicos / Subacute thyroiditis following COVID-19 vaccine administration. Presentation of three clinical cases

La tiroiditis subaguda (TSA) es un trastorno inflamatorio autolimitado de la glándula tiroides. Es más común en mujeres y se caracteriza por dolor cervical, síntomas inflamatorios sistémicos y disfunción tiroidea. La TSA se ha asociado a una infección viral previa, generalmente respiratoria o enteral. Múltiples virus se han relacionado con TSA. Desde mayo de 2020 se reportaron casos de TSA relacionados con la infección por SARS-CoV-2. Describimos 3 casos de SAT después de la vacuna COVID-19. Dos casos fueron inoculados con vacuna SARS-CoV-2 inactivada (CoronaVac) y uno con vacuna de ARNm Pfizer-BioNTech. Los síntomas clínicos comenzaron pocas semanas después de la inoculación. Presentaron dolor cervical anterior, fiebre, astenia y tirotoxicosis transitoria. En todos los casos la evolución fue favorable. Hasta donde sabemos, estos son los primeros casos de SAT posteriores a la vacuna COVID-19 descritos en Chile.

Subacute thyroiditis (SAT) is a self-limited inflammatory disorder of the thyroid gland. The disease is more common in women and is characterized by neck pain, systemic symptoms, and thyroid dysfunction. SAT It has been associated with viral, respiratory or enteral infection. Multiple viruses had been related to SAT. Since May 2020, cases of SAT related to SARS-CoV-2 infection were reported. We describe 3 cases of SAT following COVID-19 vaccine. Two cases were inoculated with inactivated SARS-CoV-2 vaccine (CoronaVac) and one with mRNA vaccine Pfizer­BioNTech. The clinical symptoms began few weeks after inoculation. They presented with neck pain, fever, general malaise and transient thyrotoxicosis. All cases revered spontaneously. To our knowledge, these are the first cases of SAT following COVID-19 vaccine described in Chile.

Double-blind placebo-controlled randomized clinical trial to assess the efficacy of montelukast in mild to moderate respiratory symptoms of patients with long COVID: E-SPERANZA COVID Project study protocol.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to affect the globe. After 18 months of the SARS-CoV-2 emergence, clinicians have clearly defined a subgroup of patients with lasting, disabling symptoms. While big strides have been made in understanding the acute phase of SARS-CoV-2 infection, the pathophysiology of long COVID is still largely unknown, and evidence-based, effective treatments for this condition remain unavailable. OBJECTIVES: To evaluate the efficacy of 10 mg oral montelukast every 24 h versus placebo in improving quality of life associated with mild to moderate respiratory symptoms in patients with long COVID as measured with the COPD Assessment Test (CAT) questionnaire. The secondary objectives will evaluate the effect of montelukast versus placebo on improving exercise capacity, COVID-19 symptoms (asthenia, headache, mental confusion or brain fog, ageusia, and anosmia), oxygen desaturation during exertion, functional status, and mortality. METHODS AND ANALYSIS: Phase III, randomized, double-blind clinical trial. We will include 18- to 80-year-old patients with SARS-CoV-2 infection and mild to moderate respiratory symptoms lasting more than 4 weeks. Participants will be randomly allocated in a 1:1 ratio to the intervention (experimental treatment with 10 mg/day montelukast) or the control group (placebo group), during a 28-day treatment. Follow-up will finish 56 days after the start of treatment. The primary outcome will be health-related quality of life associated with respiratory symptoms according to the COPD Assessment Test 4 weeks after starting the treatment. The following are the secondary outcomes: (a) exercise capacity and oxygen saturation (1-min sit-to-stand test); (b) Post-COVID-19 Functional Status Scale; (c) other symptoms: asthenia, headache, mental confusion (brain fog), ageusia, and anosmia (Likert scale); (d) use of healthcare resources; (e) mortality; (f) sick leave duration in days; and (g) side effects of montelukast. ETHICS AND DISSEMINATION: This study has been approved by the Clinical Research Ethics Committee of the IDIAPJGol (reference number 21/091-C). The trial results will be published in open access, peer-reviewed journals and explained in webinars to increase awareness and understanding about long COVID among primary health professionals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04695704 . Registered on January 5, 2021. EudraCT number 2021-000605-24. Prospectively registered.

Validación del termómetro como factor determinante de la eficacia en la toma de temperatura por infección de COVID-19 / Validation of the thermometer as a determining factor in the effectiveness of temperature measuring in covid-19 infection

FUNDAMENTOS: La pandemia por COVID-19 ha alcanzado más de cinco millones de contagios y trescientos mil fallecidos en el mundo. Todos ellos precisan la evaluación de factores pronósticos; además de la edad avanzada, las comorbilidades o la respuesta inflamatoria, es también evidente la necesidad de evaluar la temperatura corporal para determinar el contagio, la exposición, especialmente en personas con diferentes factores de riesgo, y distintos patrones evolutivos para conocer su influencia sobre los desenlaces clínicos. MÉTODOS: Se realizó un estudio transversal de tomas de temperatura a 42 sujetos voluntarios, para valorar la fiabilidad en términos de concordancia entre dos termómetros utilizados en las tomas de temperatura corporal; se compararon las mediciones de 2 termómetros en las zonas frontal y oído en 2 salas (mayor y menor iluminación). Se compararon los intervalos de confianza y se calculó el coeficiente de Correlación Intraclase (CCI) para obtener las diferencias estadísticas, proporcionando unos límites de concordancia a partir del cálculo del intervalo de confianza para la diferencia de dos mediciones. RESULTADOS: Con un intervalo de confianza del 95 %, una p < 0,5 y en las condiciones medidas, y sobre la muestra de sujetos, observamos que la correlación de las mediciones no tiene diferencia estadística significativa, pero sí en los diferentes ambientes con mayor iluminación. CONCLUSIONES: La media de temperatura corporal (frontal) medida con el termómetro láser es mayor que la temperatura (frontal) medida con el termómetro Testo. Existe diferencia significativa en las mediciones realizadas en las 2 salas, siendo mayores en la sala con menor iluminación. Hay correlación en las mediciones de temperatura del mismo instrumento en la zona frontal y en oído. Los termómetros láser son más efectivos para detectar las variaciones en la temperatura corporal, y más asertivos para identificar uno de los síntomas más asociados a la infección por SARS-CoV-2

BACKGROUND: The COVID-19 pandemic has reached more than five million infections and three hundred thousand deaths worldwide, all of which require the assessment of prognostic factors; in addition to advanced age, comorbidities or the inflammatory response, is also evident the need to assess body temperature to determine contagion, exposure, especially in people with different risk factors, and different evolutionary patterns to know its influence on clinical outcomes. METHODS: A cross-sectional study of temperature measurements was performed on 42 volunteer subjects, to assess the reliability in terms of agreement between two thermometers used in body temperature measurements; the measurements of 2 thermometers in the frontal and ear areas were compared in 2 rooms (higher and lower lighting). Confidence intervals were compared and the Intraclass Correlation Coefficient (ICC) was calculated to obtain the statistical differences, providing limits of agreement from the calculation of the confidence interval for the difference of two measurements. RESULTS: With a 95 % confidence interval, a p <0.5 and under the measured conditions, and on our sample of subjects, we observe that the correlation of the measurements does not have significant statistical difference, but indeed in different environments with greater lighting. CONCLUSIONS: The average body temperature (front) measured with the laser thermometer is greater than the temperature (front) measured with the Testo thermometer. There is a significant difference in the measurements made in the 2 rooms, being greater in the room with less lighting. There is correlation in the temperature measurements of the same instrument in the frontal zone and in the ear. Laser thermometers are more effective in detecting variations in body temperature, and more assertive in identifying one of the symptoms most associated with SARS-CoV-2 infection

Spatial Distribution Patterns of Bacterioplankton in the Oxygen Minimum Zone of the Tropical Mexican Pacific.

Microbial communities within oxygen minimum zones (OMZs) are crucial drivers of marine biogeochemical cycles; however, we still lack an understanding of how these communities are distributed across an OMZ. We explored vertical (from 5 to 500 m depth) and horizontal (coast to open ocean) distribution of bacterioplankton and its relationships with the main oceanographic conditions in three transects of the tropical Mexican Pacific OMZ. The distribution of the microbial diversity and the main clades changed along the transition from oxygen-rich surface water to the OMZ core, demonstrating the sensitivity of key bacterial groups to deoxygenation. The euphotic zone was dominated by Synechococcales, followed by Flavobacteriales, Verrucomicrobiales, Rhodobacterales, SAR86, and Cellvibrionales, whereas the OMZ core was dominated by SAR11, followed by SAR406, SAR324, SAR202, UBA10353 marine group, Thiomicrospirales and Nitrospinales. The marked environmental gradients along the water column also supported a high potential for niche partitioning among OMZ microorganisms. Additionally, in the OMZ core, bacterial assemblages from the same water mass were more similar to each other than those from another water mass. There were also important differences between coastal and open-ocean communities: Flavobacteriales, Verrucomicrobiales, Rhodobacterales, SAR86, and Cellvibrionales were more abundant in coastal areas, while Synechococcales, SAR406, SAR324, SAR202, UBA10353 marine group, and Thiomicrospirales were more abundant in the open ocean. Our results suggest a biogeographic structure of the bacterioplankton in this OMZ region, with limited community mixing across water masses, except in upwelling events, and little dispersion of the community by currents in the euphotic zone.

Feasibility and reliability of a physical fitness tests battery for adults with intellectual disabilities: The SAMU DIS-FIT battery.

BACKGROUND: People with intellectual disability (ID) have lower performances in physical fitness (PF) tests than people without ID, a situation that exists during all the life stages. However, the assessment of the FP of persons with ID often uses instruments that were designed for non-disabled people. AIM: To check the reliability and feasibility of 8 PF tests in adults with mild to moderate ID. METHODS: A cross-sectional study was carried out with a test-retest design in a maximum interval of 2 weeks with 240 adults (160 men and 80 women) with mild to moderate ID in order to assess the feasibility and reliability of the following 8 tests: body mass index (BMI), waist circumference (WC), the timed up & go test (TUG), the deep trunk flexion test (DTF), the hand grip test (HG), the timed stand test (TST), the 30-s sit-up (SUP) test, and the 6-min walk test (6MWT). The complete battery was called the SAMU-Disability Fitness Battery (SAMU-DISFIT). The psychometric properties of the battery, feasibility, reliability, the standard error of the measurement (SEM) and the minimal detectable change (MDC) were calculated. RESULTS: The TUG, DTF, HG, TST, and 6MWT showed an intraclass correlation coefficient (ICC) from fair to high reliability. Only the SUP test in men had an ICC lower than 0.7 and high SEM values. CONCLUSION: The psychometric properties provide robust data on the use of the SAMU-DISFIT battery in people with ID and can be considered a useful tool for assessing PF in adults with mild to moderate ID in future research.

Feasibility and Reliability of a Physical Fitness Test Battery in Individuals with Down Syndrome.

BACKGROUND: Down syndrome (DS) is a genetic disorder that occurs because of an abnormal division between cells that results in an extra copy of chromosome 21. Some studies show that physical exercise in people with DS increases some cognitive capacities, such as memory, and improves the quality of life. AIM: The main aim of this study was to perform an analysis of the reliability and feasibility of the SAMU-Disability Fitness (DISFIT) battery in adults with DS. METHODS: A cross-sectional study with a test-retest design was performed in a maximum interval of 2 weeks in 37 subjects (11 women and 26 men) aged between 21 and 58 years old with DS. Eight field-based fitness tests were proposed to assess the physical fitness (PF) of adults with DS: Body Mass Index (BMI), Waist Circumference (WC), the Timed Up and Go test (TUG), the Deep Trunk Flexibility test (DTF), the Hand Grip test (HG), the Timed Stand Test (TST), the 30-s Sit-Up (SUP) and the 6-Min Walk Test (6MWT). RESULTS: The intra-class correlation coefficient (ICC) in all the tests was good and high (>0.80), except for the 6MWT, whose reliability was fair. CONCLUSION: The SAMU-DISFIT battery is a reliable and feasible physical fitness battery which has been created with the purpose of establishing tests which measure the four basic components of PF (flexibility, cardiorespiratory fitness, musculoskeletal fitness and motor fitness) in adults with DS.

ACVR1 R206H cooperates with H3.1K27M in promoting diffuse intrinsic pontine glioma pathogenesis.

Diffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor, with approximately 25% of DIPGs harboring activating ACVR1 mutations that commonly co-associate with H3.1K27M mutations. Here we show that in vitro expression of ACVR1 R206H with and without H3.1K27M upregulates mesenchymal markers and activates Stat3 signaling. In vivo expression of ACVR1 R206H or G328V with H3.1K27M and p53 deletion induces glioma-like lesions but is not sufficient for full gliomagenesis. However, in combination with PDGFA signaling, ACVR1 R206H and H3.1K27M significantly decrease survival and increase tumor incidence. Treatment of ACVR1 R206H mutant DIPGs with exogenous Noggin or the ACVR1 inhibitor LDN212854 significantly prolongs survival, with human ACVR1 mutant DIPG cell lines also being sensitive to LDN212854 treatment. Together, our results demonstrate that ACVR1 R206H and H3.1K27M promote tumor initiation, accelerate gliomagenesis, promote a mesenchymal profile partly due to Stat3 activation, and identify LDN212854 as a promising compound to treat DIPG.

Endoscopic Balloon Dilation for Treatment of Congenital Antral Web.

Congenital antral webs are a rare but relevant cause of gastric outlet obstruction in infants and children. The condition may lead to feeding refusal, vomiting, and poor growth. Due to the relative rarity of the disease, cases of congenital antral web are frequently misdiagnosed or diagnosed with significant delay as physicians favorably pursue diagnoses of pyloric stenosis and gastric ulcer disease, which are more prevalent. We report a case of an eight-month-old female who presented with persistent non-bilious emesis, feeding difficulties, and failure to thrive and was discovered to have an antral web. The web was successfully treated with endoscopic balloon dilation, which resolved her symptoms. Two years later, the patient remains asymptomatic and is thriving with weight at the 75th percentile for her age.

La anatomía comparada del corazón, una necesidad de práctica de laboratorio en la carrera de medicina / The comparative anatomy of the heart, a need for laboratory practice in the medical career

Introducción: en este curso inició el Plan D para la carrera Medicina, y estando inmersos en la preparación de las nuevas asignaturas rectoras que incluidas anteriormente en Morfofisiología, se propone una práctica de laboratorio con métodos de anatomía comparada. Objetivo: proponer la implementación de una práctica de laboratorio sobre la Anatomía del corazón para el segundo año de medicina, basada en métodos de anatomía comparada. Método: se realizó un estudio cuasiexperimental en la Filial de Ciencias Médicas Manuel Piti Fajardo durante los cursos 2015-16 y 2016-17. Donde se impartió la actividad propuesta al total de estudiantes (104) realizándose la observación de un corazón real de cerdo en comparación con el humano, mostrando aspectos de la anatomía externa e interna, y usando la guía de estudio de la anatomía cardiaca mediante la disección de un corazón porcino. Se aplicaron métodos teóricos: histórico lógico, analítico-sintético, inductivo-deductivo; de los empíricos se aplicó la observación, el análisis de documentos y la técnica del PNI. Resultados: los resultados de la evaluación sistemática fueron comparados con los alcanzados por los 128 estudiantes del curso anterior, encontrándose diferencias significativas entre ellas, se amplió el porcentaje de calificaciones con calidad, se disminuyó ligeramente el porcentaje de calificados de regular y disminuyó el porcentaje de suspensos. Conclusiones: los resultados han sido superiores con la introducción de esta práctica por lo que se propone como parte del programa de la asignatura "Sistemas cardiovascular, respiratorio, digestivo y renal", Plan D, segundo año, Medicina

Introduction: A Lab Practice is proposed to give an answer to methodological problems dealing with a new Curriculum of the Medical Career called Plan D in Medicine Career. It took place in Manuel Piti Fajardo Medical School in San Cristóbal during 2015-2016 and 2016-2017academic courses, is related to a new subject called Cardiovascular, Respiratory, Digestive and Renal systems which were taught before with the name of Morph-physiology. Objective: to offer a suggestion for a lab practice where students have to get familiar to the cardiovascular system using a pig's heart to observe its internal and external characteristics comparing it with a human heart. Methods: it consists of a quasi-experimental study based on a Lab Practice where students have to use a pig's heart to observe its internal and external characteristics comparing it with a human heart. Theoretical methods such us Inductive-Deductive method, Analytic- Synthetic method, Historical - Logical method were used and some empirical methods like observation, documentary analysis and P.N.I. were applied too. The methodology used for carrying out the study is similar to the one used by Biology students in the University of Havana. Results: Systematic evaluation results are presented comparing them, with the ones done before. The initial and final diagnoses are shown. Conclusion: the suggestion is made to work with the plan D curriculum, improving medical students' knowledge, related to a new subjecting Medicine Career called Cardiovascular, Respiratory, Digestive and Renal systems which were taught before with the name of Morph-physiology(AU)

Quantitative risk assessment of WSSV transmission through partial harvesting and transport practices for shrimp aquaculture in Mexico.

This quantitative risk assessment provided an analytical framework to estimate white spot syndrome virus (WSSV) transmission risks in the following different scenarios: (1) partial harvest from rearing ponds and (2) post-harvest transportation, assuming that the introduction of contaminated water with viral particles into shrimp culture ponds is the main source of viral transmission risk. Probabilities of infecting shrimp with waterborne WSSV were obtained by approaching the functional form that best fits (likelihood ratio test) published data on the dose-response relationship for WSSV orally inoculated through water into shrimp. Expert opinion defined the ranges for the following uncertain factors: (1) the concentrations of WSSV in the water spilled from the vehicles transporting the infected shrimp, (2) the total volume of these spills, and (3) the dilution into culture ponds. Multiple scenarios were analysed, starting with a viral load (VL) of 1×102mL-1 in the contaminated water spilled that reached the culture pond, whose probability of infection of an individual shrimp (Pi) was negligible (1.7×10-7). Increasing the VL to 1×104.5mL-1 and 1×107mL-1 yielded results into very low (Pi=5.3×10-5) and high risk (Pi=1.6×10-2) categories, respectively. Furthermore, different pond stocking density (SD) scenarios (20 and 30 post-larvae [PL]/m2) were evaluated, and the probability of infection of at least one out of the total number of shrimp exposed (PN) was derived; for the scenarios with a low VL (1×102mL-1), the PN remained at a negligible risk level (PN, 2.4×10-7 to 1.8×10-6). For most of the scenarios with the moderate VL (1×104.5mL-1), the PN scaled up to a low risk category (PN, 1.1×10-4 to 5.6×10-4), whereas for the scenarios with a high VL (1×107mL-1), the risk levels were high (PN, 2.3×10-2 to 3.5×10-2) or very high (PN, 1.1×10-1 to 1.6×10-1) depending on the volume of contaminated water spilled in the culture pond (VCWSCP, 4 or 20L). In the sensitivity analysis, for a SD of 30 PL/m2, it was shown that starting with a VL of 1×105mL-1 and a VCWSCP of 12L, the PN was moderate (1.05×10-3). This was the threshold for greater risks, given the increase in either the VCWSCP or VL. These findings supported recommendations to prevent WSSV spread through more controlled transportation and partial harvesting practices.

[Clinical features of patients with Basedow Graves disease seen at a university hospital]. / Caracterización de pacientes controlados por enfermedad de Basedow Graves en un hospital universitario.

BACKGROUND: Basedow Graves disease (BGD) is the leading cause of hyperthyroidism. The characteristics of patients seen at a university hospital may differ from those described in the general population. AIM: To describe the clinical features of patients with BGD seen at a university hospital. MATERIAL AND METHODS: Review of medical records of all patients seen at our hospital between 2009 and 2014 with the diagnosis of thyrotoxicosis, hyperthyroidism or BGD. Clinical features, laboratory results and treatments were recorded. RESULTS: We reviewed clinical records of 272 patients; 15 had to be excluded due to incomplete data. BGD was present in 77.9% (n = 212). The mean age of the latter was 42 years (range 10-81) and 76% were women. Ninety six percent were hyperthyroid at diagnosis and thyroid stimulating hormone was below 0.1 mIU/L in all patients. Median free thyroxin and triiodothyronine levels were 3.26 ng/dl and 3.16 ng/ml, respectively. Thyrotropin-receptor antibodies were positive in 98.5% and 85.7% had positive thyroid peroxidase antibodies. Graves orbitopathy (GO) was clinically present in 55% of patients. Of this group, 47% had an active GO, 26% had a moderate to severe disease and 7.8% had sight-threatening GO. As treatment, 26% received radioiodine, 44% anti-thyroid drugs exclusively, 28% underwent thyroidectomy and 2% did not require therapy. CONCLUSIONS: In this group of patients, we observed a greater frequency of severe eye disease and a high rate of surgical management. This finding could be explained by referral to highly qualified surgical and ophthalmological teams.

Histone H3.3K27M Represses p16 to Accelerate Gliomagenesis in a Murine Model of DIPG.

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date, the tumor-driving effects of H3.3K27M remain largely unknown. Here, it is demonstrated that H3.3K27M cooperates with PDGF-B in vivo, enhancing gliomagenesis and reducing survival of p53 wild-type (WT) and knockout murine models of DIPG. H3.3K27M expression drives increased proliferation of tumor-derived murine neurospheres, suggesting that cell-cycle deregulation contributes to increased malignancy in mutant tumors. RNA sequencing on tumor tissue from H3.3K27M-expressing mice indicated global upregulation of PRC2 target genes, and a subset of newly repressed genes enriched in regulators of development and cell proliferation. Strikingly, H3.3K27M induced targeted repression of the p16/ink4a (CDKN2A) locus, a critical regulator of the G0-G1 to S-phase transition. Increased levels of H3K27me3 were observed at the p16 promoter; however, pharmacologic reduction of methylation at this promoter did not rescue p16 expression. Although DNA methylation is also present at this promoter, it is not K27M dependent. Intriguingly, inhibition of DNA methylation restores p16 levels and is cytotoxic against murine tumor cells. Importantly, these data reveal that H3.3K27M-mediated p16 repression is an important mechanism underlying the proliferation of H3.3K27M tumor cells, as in vivo cdkn2a knockout eliminates the survival difference between H3.3K27M and H3.3WT tumor-bearing mice.Implications: This study shows that H3.3K27M mutation and PDGF signaling act in concert to accelerate gliomagenesis in a genetic mouse model and identifies repression of p16 tumor suppressor as a target of H3.3K27M, highlighting the G1-S cell-cycle transition as a promising therapeutic avenue. Mol Cancer Res; 15(9); 1243-54. ©2017 AACR.

Caracterización de pacientes controlados por enfermedad de Basedow Graves en un hospital universitario / Clinical features of patients with Basedow Graves disease seen at a university hospital

Background: Basedow Graves disease (BGD) is the leading cause of hyperthyroidism. The characteristics of patients seen at a university hospital may differ from those described in the general population. Aim: To describe the clinical features of patients with BGD seen at a university hospital. Material and Methods: Review of medical records of all patients seen at our hospital between 2009 and 2014 with the diagnosis of thyrotoxicosis, hyperthyroidism or BGD. Clinical features, laboratory results and treatments were recorded. Results: We reviewed clinical records of 272 patients; 15 had to be excluded due to incomplete data. BGD was present in 77.9% (n = 212). The mean age of the latter was 42 years (range 10-81) and 76% were women. Ninety six percent were hyperthyroid at diagnosis and thyroid stimulating hormone was below 0.1 mIU/L in all patients. Median free thyroxin and triiodothyronine levels were 3.26 ng/dl and 3.16 ng/ml, respectively. Thyrotropin-receptor antibodies were positive in 98.5% and 85.7% had positive thyroid peroxidase antibodies. Graves orbitopathy (GO) was clinically present in 55% of patients. Of this group, 47% had an active GO, 26% had a moderate to severe disease and 7.8% had sight-threatening GO. As treatment, 26% received radioiodine, 44% anti-thyroid drugs exclusively, 28% underwent thyroidectomy and 2% did not require therapy. Conclusions: In this group of patients, we observed a greater frequency of severe eye disease and a high rate of surgical management. This finding could be explained by referral to highly qualified surgical and ophthalmological teams.

Determinación de niveles de vitamina D en pacientes con fibromialgia: estudio de casos y controles / Vitamin D levels in patients with fibromyalgia: case control study

Introduction: fibromyalgia (FM) is characterized by diffuse chronic muscle pain, fatigue and disability, affecting quality of life. In recent years there are many reports that show a high prevalence of vitamin D deficiency in different populations. In patients with FM there are conflicting results about the associations with vitamin D deficiency. Method: Case control study matched controls by age and sex. A clinical interview, measurement of 25-OH vitamin D, calcium, phosphorus and intact PTH was measured. The definitions of the American Society of Endocrinology were used: Insufficient vitamin D levels of 21-29 ng/ml and deficiency when they are less than 20 ng/ml. Results: 39 female patients were included in each group. The average age was 46.33 years (SD 10.6) in patients with FM and 45.92 years (SD 11.9) in controls. VD average levels in women with FM was 26.13 ng/ml (SD 8.3) and the controls of 28.45 ng/ml (SD 8.7) p = 0.082. No group differences were found when using cutoffs of 30 ng/dl (OR 2.75 with p = 0.35 [95 percent CI 0.96 to 8.06]) or 20 ng/dl (OR 0,6 p = 0.38 [95 percent CI 0.15 to 2.18]). No VD patients with levels below 10 ng/dl were presented. Conclusions: We found no differences between groups in VD levels when considering the average levels of VD or using different cutoffs.

Tumor location, but not H3.3K27M, significantly influences the blood-brain-barrier permeability in a genetic mouse model of pediatric high-grade glioma.

Pediatric high-grade gliomas (pHGGs) occur with strikingly different frequencies in infratentorial and supratentorial regions. Although histologically these malignancies appear similar, they represent distinct diseases. Recent genomic studies have identified histone K27M H3.3/H3.1 mutations in the majority of brainstem pHGGs; these mutations are rarely encountered in pHGGs that arise in the cerebral cortex. Previous research in brainstem pHGGs suggests a restricted permeability of the blood-brain-barrier (BBB). In this work, we use dynamic contrast-enhanced (DCE) MRI to evaluate BBB permeability in a genetic mouse model of pHGG as a function of location (cortex vs. brainstem, n = 8 mice/group) and histone mutation (mutant H3.3K27M vs. wild-type H3.3, n = 8 mice/group). The pHGG models are induced either in the brainstem or the cerebral cortex and are driven by PDGF signaling and p53 loss with either H3.3K27M or wild-type H3.3. T2-weighted MRI was used to determine tumor location/extent followed by 4D DCE-MRI for estimating the rate constant (K (trans) ) for tracer exchange across the barrier. BBB permeability was 67 % higher in cortical pHGGs relative to brainstem pHGGs (t test, p = 0.012) but was not significantly affected by the expression of mutant H3.3K27M versus wild-type H3.3 (t-test, p = 0.78). Although mice became symptomatic at approximately the same time, the mean volume of cortical tumors was 3.6 times higher than the mean volume of brainstem tumors. The difference between the mean volume of gliomas with wild-type and mutant H3.3 was insignificant. Mean K (trans) was significantly correlated to glioma volume. These results present a possible explanation for the poor response of brainstem pHGGs to systemic therapy. Our findings illustrate a potential role played by the microenvironment in shaping tumor growth and BBB permeability.

Factores de crecimiento aportados por el lisado plaquetario en el tratamiento tópico de úlceras posflebíticas / Platelet lysate-derived growth factors for topical treatment of postphlebitis ulcers

Introducción: los factores de crecimiento plaquetario son proteínas bioactivas que se sintetizan y almacenan en las plaquetas. Objetivo: evaluar la efectividad de los factores de crecimiento aportados por el lisado plaquetario alogénico en el tratamiento tópico de úlceras posflebíticas Métodos: se realizó un estudio cuasi-experimental con control simultáneo en la consulta de medicina regenerativa, Hospital General Docente "Comandante Pinares", entre enero de 2008 y diciembre de 2012. Se evaluaron 135 pacientes con el diagnóstico de úlceras posflebíticas con inadecuada respuesta al tratamiento convencional y ausencia de otras enfermedades de base que impidieran una respuesta a la terapia regenerativa. Los pacientes se dividieron en dos grupos: 90 recibieron tratamiento con la aplicación local del lisado plaquetario obtenido de las plaquetas alogénicas ABO compatibles y 45 mantuvieron el tratamiento convencional (grupo control). El tiempo de respuesta fue la característica distintiva para medir la eficacia entre ambos tratamientos. Resultados: predominó el sexo femenino y edad de más de 50 años. Los síntomas cardinales del síndrome posflebítico, estuvieron presentes en un mayor número de pacientes del grupo tratado con el lisado plaquetario, sin embargo, a los 30 días, se constató una mejoría de los mismos así como una disminución significativa del área promedio de las úlceras. En el grupo tratado con lisado, 86 pacientes remitieron sus síntomas en menos de seis semanas, frente a solo ocho en el mismo tiempo en el grupo convencional. Conclusiones: el uso de factores de crecimiento aportados por el lisado plaquetario alogénico fue efectivo en el tratamiento tópico de úlceras posflebíticas(AU)

Introduction: platelet-derived growth factors are bio-active proteins that are synthesized and stored in the platelets. Objective: to evaluate the effectiveness of allogenic platelet lysate-derived growth factors in the topical treatment of postphlebitis ulcers. Methods: a quasi-experimental study with simultaneous control was conducted from January 2008 through December 2012 in the regenerative medicine service of "Comandante Pinares" general teaching hospital located in San Cristobal, Artemisa province, Cuba. One hundred and thirty five patients with diagnosis of postphlebitis ulcers, inadequate response to the conventional treatment and absence of other illnesses that could hinder such response to regenerative therapy were evaluated. The patients were divided into two groups: 90 treated with local use of compatible ABO allogenic platelet-derived platelet lysate and 45 kept under the conventional treatment (control group). The reaction time was the distinctive characteristic to measure the effectiveness of both treatments. Results: females and over 50 years-old age predominated. The main symptoms of the posphlebitic syndrome were present in a high number of patients in the group treated with the platelet lysate. Thirty days later, these symptoms significantly improved and the average ulcer area dramatically decreased. There was observed symptoms remission in eighty six patients in less than six weeks in contrast with only eight in the conventional group during this period. Conclusions: the use of allogenic platelet lysate-derived growth factors was effective in the topical treatment of postphlebitis ulcers(AU)