Sex-specific and polygenic effects underlying resting heart rate and associated risk of cardiovascular disease.

AIMS: Resting heart rate (RHR) is associated with cardiovascular disease (CVD) and mortality. This study aimed to identify genetic loci associated with RHR, develop a genome-wide polygenic risk score (PRS) for RHR, and assess associations between the RHR PRS and CVD outcomes, to better understand the biological mechanisms linking RHR to disease. Sex-specific analyses were conducted to potentially elucidate different pathways between the sexes. METHODS: We performed a genome-wide meta-analysis of RHR (n=550,467) using two independent study populations, The Trøndelag Health Study (HUNT) and the UK Biobank (UKB), comprising 69,155 and 481,312 participants, respectively. We also developed a genome-wide PRS for RHR using UKB and tested for association between the PRS and 13 disease outcomes in HUNT. RESULTS: We identified 403, 253, and 167 independent single nucleotide polymorphisms (SNPs) significantly associated with RHR in the total population, women, and men, respectively. The sex-specified analyses indicated differences in the genetic contribution to RHR and revealed loci significantly associated with RHR in only one of the sexes. The SNPs were mapped to genes enriched in heart tissue and cardiac conduction pathways, as well as disease-pathways, including dilated cardiomyopathy. The PRS for RHR was associated with increased risk of hypertension and dilated cardiomyopathy, and decreased risk of atrial fibrillation. CONCLUSION: Our findings provide insight into the pleiotropic effects of the RHR variants, contributing towards an improved understanding of mechanisms linking RHR and disease. In addition, the sex-specific results might contribute to a more refined understanding of RHR as a risk factor for the different diseases.

We conducted a genome-wide meta-analysis on resting heart rate (RHR), created a polygenic risk score for RHR and examined the associations to cardiovascular disease outcomes. Sex-specific analyses indicated differences in the genetic contribution to RHR between men and women.High genetically predicted RHR was associated with increased risk of dilated cardiomyopathy and hypertension, and decreased risk of atrial fibrillation.

Exploring shared genetics between maximal oxygen uptake and disease: the HUNT study.

Low cardiorespiratory fitness, measured as maximal oxygen uptake (V̇o2max), is associated with all-cause mortality and disease-specific morbidity and mortality and is estimated to have a large genetic component (∼60%). However, the underlying mechanisms explaining the associations are not known, and no association study has assessed shared genetics between directly measured V̇o2max and disease. We believe that identifying the mechanisms explaining how low V̇o2max is related to increased disease risk can contribute to prevention and therapy. We used a phenome-wide association study approach to test for shared genetics. A total of 64,479 participants from the Trøndelag Health Study (HUNT) were included. Genetic variants previously linked to V̇o2max were tested for association with diseases related to the cardiovascular system, diabetes, dementia, mental disorders, and cancer as well as clinical measurements and biomarkers from HUNT. In the total population, three single-nucleotide polymorphisms (SNPs) in and near the follicle-stimulating hormone receptor gene (FSHR) were found to be associated (false discovery rate < 0.05) with serum creatinine levels and one intronic SNP in the Rap-associating DIL domain gene (RADIL) with diabetes type 1 with neurological manifestations. In males, four intronic SNPs in the PBX/knotted homeobox 2 gene (PKNOX2) were found to be associated with endocarditis. None of the association tests in the female population reached overall statistical significance; the associations with the lowest P values included other cardiac conduction disorders, subdural hemorrhage, and myocarditis. The results might suggest shared genetics between V̇o2max and disease. However, further effort should be put into investigating the potential shared genetics between inborn V̇o2max and disease in larger cohorts to increase statistical power.NEW & NOTEWORTHY To our knowledge, this is the first genetic association study exploring how genes linked to cardiorespiratory fitness (CRF) relate to disease risk. By investigating shared genetics, we found indications that genetic variants linked to directly measured CRF also affect the level of blood creatinine, risk of diabetes, and endocarditis. Less certain findings showed that genetic variants of high CRF might cause lower body mass index, healthier HDL cholesterol, and lower resting heart rate.

Genome-Wide Association Study Identifies New Genetic Determinants of Cardiorespiratory Fitness: The Trøndelag Health Study.

PURPOSE: Low cardiorespiratory fitness (CRF) is a major risk factor for cardiovascular disease (CVD) and a stronger predictor of CVD morbidity and mortality than established risk factors. The genetic component of CRF, quantified as peak oxygen uptake (V̇O 2peak ), is estimated to be ~60%. Unfortunately, current studies on genetic markers for CRF have been limited by small sample sizes and using estimated CRF. To overcome these limitations, we performed a large-scale systematic screening for genetic variants associated with V̇O 2peak . METHODS: A genome-wide association study was performed with BOLT-LMM including directly measured V̇O 2peak from 4525 participants in the HUNT3 Fitness study and 14 million single-nucleotide polymorphisms (SNP). For validation, similar analyses were performed in the United Kingdom Biobank (UKB), where CRF was assessed through a submaximal bicycle test, including ~60,000 participants and ~60 million SNP. Functional mapping and annotation of the genome-wide association study results was conducted using FUMA. RESULTS: In HUNT, two genome-wide significant SNP associated with V̇O 2peak were identified in the total population, two in males, and 35 in females. Two SNP in the female population showed nominally significant association in the UKB. One of the replicated SNP is located in PIK3R5 , shown to be of importance for cardiac function and CVD. Bioinformatic analyses of the total and male population revealed candidate SNP in PPP3CA , previously associated with CRF. CONCLUSIONS: We identified 38 novel SNP associated with V̇O 2peak in HUNT. Two SNP were nominally replicated in UKB. Several interesting genes emerged from the functional analyses, among them one previously reported to be associated with CVD and another with CRF.

Impacts of violence on the mental health of Afro-descendant survivors in Colombia.

The Colombian armed conflict has disproportionately affected minorities, especially afro-Colombian communities. However, there is a lack of evidence about mental health of victims. This study aims to describe the prevalence of mental illness and its associated factors in Afro-descendant violence survivors in Buenaventura and Quibdó, Colombia. A cross-sectional study was carried out using data from a previous trial which aimed to reduce mental health symptoms (ClinicalTrials.gov: NCT01856673). Data of 710 adults identified through a snowball sampling technique was analysed. Diagnoses of depression, anxiety, post-traumatic stress disorder (PTSD), and dysfunction were established using adapted versions of the Hopkins Symptoms Checklist and the Harvard Trauma Questionnaire, plus variables identified in a qualitative study. Multivariate regressions were used to identify associated factors with these diagnoses. The prevalence of depression, anxiety and PTSD in both cities was 26.62% (95% confidence interval [95%CI]: 20.30;23.89), 36.53% (95%CI: 30.63;42.36), and 39.15% (95%CI: 33.36;44.83), respectively. Being married and having registered with the government as victim of the conflict were found to be protective factors for depression and PTSD, respectively. Psychological trauma, unemployment, and traumatic experiences, amongst others, were found as risk factors. The Colombian armed conflict, plus disparities and social exclusion, may be associated with mental health morbidity.

Manejo de la ventilación durante la fibrobroncoscopia con máscara laríngea / Management of ventilation during bronchofiberscopy with laryngeal mask

Introducción: la fibrobroncoscopia es el método de exploración y de inspección directa de la laringe y el árbol traqueobronquial con un tubo largo, delgado y flexible de fibra de vidrio como medio óptico llamado fibrobroncoscopio. Objetivo: describir el comportamiento de la ventilación durante la fibrobroncoscopia. Método: se estudiaron 30 pacientes anunciados para broncoscopia en el Hospital Comandante Manuel Fajardo Rivero ventilados con Fastrach. Se estudiaron variables de ventilación (presión inspiratoria de la vía aérea así como volúmenes corrientes). Resultados: durante los momentos (comparación inicial-final) no hubo diferencias significativas entre las medias de los volúmenes tidales. Al analizar las presiones de la vía aérea de los pacientes se observó que no hubo diferencia en las mediciones de las presiones en los diferentes momentos y que se mantuvieron dentro de la normalidad. Conclusiones: la máscara laríngea Fastrach permitió que el control de la ventilación se produjera de manera continua durante los intentos de introducción del fibroscopio; se garantizaron volúmenes adecuados de ventilación, con niveles de presión en la vía aérea(AU)

Daño hepático: relación con el daño múltiple de órganos en 1 143 fallecidos con sepsis / Liver damage: relationship to multiple damage of organs failure in 1143 died by sepsis

Las alteraciones de la regulación inmunitaria en el hígado y el aparato digestivo predisponen al daño múltiple de órganos y dificultan su resolución. La aparición clínica de la disfunción hepática puede ser tardía con respecto al inicio de la sepsis, empeorar la evolución clínica del enfermo y favorecer la aparición del daño múltiple de órganos. Se analizaron 1 143 autopsias de fallecidos con sepsis. Se utilizó el Sistema Automatizado de Registro y Control de Anatomía Patológica y se enfatizó en el diagnóstico histológico del hígado, en el que las alteraciones estructurales más evidentes fueron la hepatitis reactiva, la esteatosis hepática y la colestasis hepática, siempre relacionadas con la sepsis. Se revisó la relación de estos patrones estructurales del hígado del paciente con sepsis grave y daño múltiple de órganos. Todos los que desarrollaron daño múltiple de órganos presentaron hepatitis reactiva, el 39.62 por ciento de los pacientes con esteatosis hepática y el 33.33 por ciento de los pacientes con colestasis hepática desarrollaron daño múltiple de órganos(AU)

Estudio anatomopatológico del hígado en 200 fallecidos con sepsis grave y grave de alto riesgo / Pathologic examination of the liver in 200 deaths and severe with severe sepsis at high risk

Introducción: La sepsis es una respuesta sistémica del huésped a la infección que puede conducir a sepsis grave y choque séptico. El hígado es un órgano diana del daño por la sepsis. Objetivo: determinar las características anatomopatológicas del hígado en los fallecidos con sepsis grave y grave de alto riesgo y relacionarlas con la localización del sitio de la infección y la presencia de íctero. Método: estudio retrospectivo, observacional, descriptivo en 200 fallecidos por sepsis. Se determinaron los patrones histológicos del hígado y se relacionaron con la localización del sitio de la infección y el íctero y se aplicó la prueba Chi uadrado. Resultados: la infiltración por mononucleares se apreció en un 79 porciento, seguida de un 78.5 por ciento por la necrosis aislada, la dilatación sinusoidal en un 74 por ciento y con un 72.5 por ciento la hiperplasia de las células de Kupffer. El íctero se asoció con esteatosis macrovesicular (p<0.01) y con migración de neutrófilos a sinusoides (p<0.05) y la sepsis abdominal con la apoptosis del hepatocito y con la esteatosis microvesicular y macrovesicular. Discusión: la sepsis afecta directamente a las estructuras y las funciones del hígado. La sepsis intraabdominal se asoció con la apoptosis, mientras que el íctero se asoció con la esteatosis macrovesicular y con la migración de neutrófilos a sinusoides(AU)

Nueva escala de severidad del daño hepático por sepsis / New injury severity scale liver sepsis

La sepsis tiene elevada mortalidad, el hígado se afecta tempranamente, los Especialistas en Medicina Intensiva y Emergencia utilizan herramientas para predecir la evolución de los pacientes. Objetivo: diseñar una escala para unificar criterios en el diagnóstico de la severidad del daño hepático por sepsis. Material y método: estudio retrospectivo, observacional, descriptivo a 200 fallecidos por sepsis; se determinaron patrones histológicos del hígado y variables epidemiológicas y clínicas y se diseñó una escala para evaluar la severidad del daño hepático en la sepsis, la que fue validada internamente. Resultados: el daño hepático se clasificó como severo y no severo, el severo resultó tres veces mayor en enfermos de color de piel no blanca y 17 veces mayor en pacientes con APACHE II (riesgo de mortalidad) mayor que 76 por ciento e infección abdominal; el modelo identificó mejor el daño hepático severo con exactitud de 89.5 por ciento, sensibilidad de 97.6 por ciento y especificidad de 52.8 por ciento y el área bajo la curva de receiver operating characteristics fue de 0.78, con una significación asociada al estadígrafo calculado menor que 0.01 y predijo mejor que el azar, con intervalo de confianza de 0.71 a 0.85. Conclusiones: el modelo tuvo alta sensibilidad, identificó mejor el daño hepático severo y predijo mejor que el azar (AU)

Adenocarcinoma in the ileostomy of a patient with long-standing ulcerative colitis: a case report and review of the literature.

Primary adenocarcinoma in a permanent ileostomy carries a poor prognosis from other gastrointestinal malignancies. Surveillance and identification of patient at risk for ileostomy malignancies is a challenging problem. There are not reliable biological markers. The clinical evaluation, suspicion of the disease, common presenting symptoms including difficulty fitting the stomal appliance, bowel obstruction, and a friable mass should be considered as part of the evaluation and screening in a long standing terminal ileostomy. Biopsy of newly developed lesions in the periostomal area is recommended for diagnosis and treatment. This is a case of a primary adenocarcinoma in an ileostomy forty years after total colectomy for ulcerative colitis.

The mediating roles of cancer-related rumination in the relationship between dispositional hope and psychological outcomes among childhood cancer survivors.

OBJECTIVE: This study aimed to examine the effects of dispositional hope on psychopathology as well as self-perceived positive change in childhood cancer survivors through the potential mediation of cancer-related ruminations. METHODS: A cross-sectional design was used, and a group of childhood cancer survivors (N = 89; mean age = 23.2 years; age range = 17.2-31.3 years) were studied. Dispositional hope level was measured by the Hope Scale; positive and negative cancer-related ruminations were assessed by the Chinese Cancer-related Rumination Scale; depression symptoms were measured by Beck Depression Inventory; and anxiety symptoms were measured by Beck Anxiety Inventory. Positive adjustment outcome of posttraumatic growth (PTG) was assessed by the Chinese Post-traumatic Growth Inventory. Multiple regressions were used to analyze the relationship between dispositional hope and the outcome variables of PTG, anxiety and depression and the potential mediators of positive and negative cancer-related rumination. RESULTS: Dispositional hope was positively related to PTG, and the correlation was specifically mediated by positive cancer-related rumination. Dispositional hope also correlated with lower levels of depression and anxiety, specifically mediated by negative cancer-related rumination. CONCLUSION: The present finding supported hope as a significant positive factor for childhood cancer survivors, which was associated with PTG and better psychological adjustment. The findings may inform development of therapeutic intervention programs aimed at increasing childhood cancer patients' hope levels, which may be correlated with more positive cancer-related thoughts and better adjustment. The present study, which examined survivors diagnosed at young age, may enrich existing studies on the effect of onset age and adjustment outcomes.

Epidemiology, identification, treatment and return to play of musculoskeletal-based ice hockey injuries.

UNLABELLED: Ice hockey is a high contact sport where players are inherently at an increased risk for traumatic and time-loss injury. With its increasing popularity and high incidence of injury, further research is necessary to understand the risks and injuries associated with the sport and to develop performance-based outcome measures to guide return to play. This review, tailored to the practicing sports medicine team physician, focuses on the stepwise identification, treatment, time loss, return to play and subsequent risk of injury for the most common areas of injury: the head, shoulder, hip and knee. Injuries were categorised into upper and lower extremity with an emphasis on glenohumeral and acromioclavicular joint injuries, femoroacetabular impingement, medial collateral ligament tears, and high ankle sprains. With return to play a primary goal for these high-level athletes, recovery in ice hockey becomes a complex issue with efficient protocols tailored to the requirements of the sport vital to the athlete and clinician alike. By reviewing the treatments and sport-specific care, athletes can be better managed with the ultimate goal of returning to their preinjury level of play. LEVEL OF EVIDENCE: Level IV.

Máscara laríngea Fastrach en la fibrobroncoscopia diagnóstica / Fastrach Laryngeal mask in diagnostic fibrobronchoscopy

Introducción: la hipoxia y la dificultad para el establecimiento de la vía aéreason dos problemas que se enfrentan durante la realización de lafibrobroncoscopia. En la actualidad muchos centros hospitalarios en el mundo realizan la broncoscopia a través de la máscara laríngea. Objetivos: describir el uso de la máscara laríngea Fastrach para la realización de la fibrobroncoscopia. Métodos: se estudiaron 30 pacientes anunciados para broncoscopia en elHospital Militar Comandante Manuel Fajardo Rivero que fueron ventilados con Fastrach y se estudiaron las variables hemodinámicas, de oxigenación y de ventilación, los tiempos específicos relacionados con la máscara laríngea y el procedimiento y las complicaciones asociadas. Resultados: aunque los valores de las variables hemodinámicas reflejarondiferencias muy significativas en los diferentes momentos, fueron normales;similar comportamiento tuvo la ventilación. Se informaron los tiempos específicos de la maniobra, de remoción del dispositivo y del procedimiento (12.14±4.55segundos, 335.88±89.91 segundos y 1500±600 segundos, respectivamente). En todos los pacientes el procedimiento se realizó con éxito y con pocas complicaciones asociadas. Conclusiones: estabilidad hemodinámica, pocas complicaciones asociadas, inserción y remoción exitosas y la máscara laríngea Fastrach ofreció adecuadascondiciones de ventilación y oxigenación durante la fibrobroncoscopia diagnóstica(AU)

Evaluation of circular DNA substrates for whole genome amplification prior to forensic analysis.

Forensic biological evidence often contains low quantities of DNA or substantially degraded DNA which makes samples refractory to genotype analysis. One approach that shows promise to overcome the limited quantity of DNA is whole genome amplification (WGA). One WGA technique, termed rolling circle amplification (RCA), involves the amplification of circular DNA fragments and this study evaluates a single-stranded (ss) DNA ligase enzyme for generating circular DNA templates for RCA WGA. Fast, efficient ligation of several sizes of ssDNA templates was achieved. The enzyme also ligated double-stranded (ds) DNA templates, a novel activity not previously reported. Adapter sequences containing optimal terminal nucleotide ends for increased ligation efficiency were designed and ligation of adapters to template DNA was optimized. Increased amplification of DNA templates was observed following WGA; however, no amplification advantage for ssDNA ligase treatment of templates was evident compared to linear templates. A multi-step process to utilize ssDNA ligase prior to WGA was developed and short tandem repeat (STR) analysis of simulated low template (LT) and fragmented DNA was evaluated. The process resulted in the loss of template DNA and failed STR analysis whereas input of linear genomic DNA template directly into WGA prior to STR analysis improved STR genotyping results compared to non-WGA treated samples. Inclusion of an extreme thermostable single-stranded DNA binding protein (SSB) during WGA also increased DNA yields. While STR artifacts such as peak imbalance, drop-in, and dropout persisted, WGA shows potential for successful genetic profiling of LT and fragmented DNA samples. Further research and development is warranted prior to use of WGA in forensic casework.

Isolates of Verticillium dahliae Pathogenic to Crucifers Are of at Least Three Distinct Molecular Types.

ABSTRACT Diverse isolates of the soilborne wilt fungi Verticillium dahliae and V. albo-atrum were studied to understand the nature and origins of those infecting cruciferous hosts. All isolates from cruciferous crops produced microsclerotia, and the majority produced long conidia with a high nuclear DNA content; these isolates were divided into two groups by amplified fragment length polymorphism (AFLP) analysis. One group could be subdivided by other criteria such as rRNA sequences and mitochondrial DNA restriction fragment length polymorphism (RFLP) analysis. Two crucifer isolates were short spored and had a low nuclear DNA content. The results are consistent with the crucifer isolates being interspecific hybrids. The long-spored isolates are best regarded as amphihaploids (or allodiploids) with the AFLP groups probably each representing separate interspecific hybridization events. The short-spored crucifer isolates appear to be derived from interspecific hybrids and are here called 'secondary haploids'. Molecular evidence suggests that one parent in the crosses was similar to V. dahliae. The other parent of the amphihaploids seems to have been more similar to V. albo-atrum than to V. dahliae, but was distinct from all isolates of either species so far studied. The implications for the taxonomy of crucifer isolates are discussed and the use of the name V. longisporum, proposed elsewhere for just some of these isolates, is discouraged.

Keratinolytic activity of five human isolates of the dermatophytes.

The keratinolytic activity of five species of the dermatophytes which include Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum audouinii and M. gypseum isolated from school children were tested using human hair as the substrate. M. gypseum was found to possess the highest keratinolytic activity with a net value of released protein being 78.8 ug/ml after five weeks of incubation. Also the net value of released protein for T. tonsurans, T. rubrum, T. mentagrophytes and M. audouinii were 55.5 ug/ml, 52.5 ug/ml, 43.8 ug/ml and 26.3 ug/\ml respectively. Only T. mentagrophytes and M. gypseum were able to cause structural damage in form of perforations on the hair shaft. Also during the degradation of the hair, the pH of the basal medium for each dermatophyte increased. The increase in pH was highest in the medium with M. gypseum but lowest in that of M. audouinii.