Population structure and admixture in Cerro Largo, Uruguay, based on blood markers and mitochondrial DNA polymorphisms.

Recent studies of the Uruguayan population revealed different amounts of Amerindian and African genetic contributions. Our previous analysis of Afro-Uruguayans from the capital city of the Department of Cerro Largo showed a high proportion of African genes, and the effects of directional mating involving Amerindian women. In this paper, we extended the analysis to a sample of more than 100 individuals representing a random sample of the population of the whole Department. Based on 18 autosomal markers and one X-linked marker, we estimated 82% European, 8% Amerindian, and 10% African contributions to their ancestry, while from seven mitochondrial DNA site-specific polymorphic markers and sequences of hypervariable segment I, we determined 49% European, 30% Amerindian, and 21% African maternal contributions. Directional matings between Amerindian women and European men were detected, but differences involving Africans were not significant. Data about the specific origins of maternal lineages were also provided, and placed in a historical context.     

The V599E BRAF mutation is uncommon in biliary tract cancers.

Activating point mutations of the BRAF oncogene have been identified in several solid tumors, most commonly in cutaneous melanomas and papillary carcinomas of the thyroid. A specific point mutation--V599E--accounts for the overwhelming majority of these mutational events. We explored the frequency of the V599E BRAF mutation in biliary tract cancers. In all, 62 archival biliary tract cancers, including 15 gallbladder cancers, 15 extrahepatic, and 10 intrahepatic cholangiocarcinomas from the United States, and 22 gallbladder carcinomas from Chile were analyzed for the V599E mutation of the BRAF gene using three distinct methods: direct sequencing, a primer extension method (Mutector assay), and the highly sensitive quantitative Gap Ligase Chain Reaction. The common V599E mutation was not identified in any of the 62 biliary cancer samples using these three methods of detection. The V599E somatic mutation of the BRAF gene is absent in biliary tract cancers, at least in the two geographic populations (United States and Chile) examined. Activation of the RAS/RAF/MAP kinase pathway in biliary tract cancers is likely to be secondary to oncogenic RAS mutations, or due to mutations of the BRAF gene at nucleotide positions not explored in the current study.     

Zidovudine and the natural history of the acquired immunodeficiency syndrome

BACKGROUND AND METHODS: We sought to describe the trends in survival from 1983 to 1989 among persons with the acquired immunodeficiency syndrome (AIDS) and to examine the relative effects on the natural history of AIDS of zidovudine use and demographic and clinical characteristics. This longitudinal, observational, population-based study used data from the Maryland Human Immunodeficiency Virus Information System, a data base that links information from the Maryland AIDS Registry with data on public and private health care claims, vital statistics, and hospital, long-term care, and ambulatory care records. RESULTS: The median survival after diagnosis among persons with AIDS (n = 1028) was 140 days longer for those given their diagnoses between 1987 and 1989 than for those given their diagnoses between 1983 and 1985 (450 vs 310 days). Among the 714 persons in whom AIDS was diagnosed after April 1987 (when zidovudine became available), two-year survival was greater among men than women (P less than 0.03), among persons less than 45 years old than among older persons (P less than 0.001), among non-Hispanic whites than among minorities (P less than 0.001), and among persons whose category of human immunodeficiency virus transmission was homosexual contact than among those with heterosexual, transfusion-related, or less common modes of transmission (P less than 0.02). In all the analyses the groups with the longer survival were more likely to have received zidovudine. The median survival among those who received zidovudine was 770 days, as compared with 190 days among those who never received the drug (P less than 0.001). By proportional-hazards analysis, zidovudine therapy was the factor most strongly associated with improved survival. CONCLUSIONS: For Maryland residents with AIDS there has been an improvement in survival since 1987. Zidovudine therapy and perhaps other aspects of care associated with it have contributed substantially to the improved survival.     

Predictors of Caregiver Participation in an Engagement Strategy to Increase Initiation into a Family-Based Preventive Intervention

Previous studies have shown that engagement strategies can help increase enrollment and initiation of families in evidence-based preventive programs under natural service delivery settings. However, little is known about factors that predict completion of these engagement strategies. This study aimed to examine predictors (i.e., perceived need, perceived barriers, and sociocultural context) of caregiver participation in an evidence-based engagement call strategy. This call was expected to increase initiation into a school-based, family-focused prevention program. In addition, this study examined engagement call completion as a predictor of program initiation among already enrolled families. Participants included ethnically diverse families recruited from three Title I schools (n = 413) who were randomized to receive the prevention program. Results showed that interparental conflict—an indicator of perceived need—was associated with an increased likelihood of completing the engagement call. Furthermore, caregivers from low-socioeconomic status (SES), foreign-born, Spanish-speaking, Hispanic families were more likely to complete the call relative to those from low- and mid-SES, US born, English-speaking, ethnically diverse families. Importantly, engagement call completion was associated with an increased likelihood of program initiation. These findings provide limited support that families with higher perceived needs are more likely to participate in an evidence-based engagement call strategy. Results suggested that the call strategy provides a promising way to reduce attrition from family prevention programs, which is commonly observed between enrollment and initiation. Project Number: R01 DA035855; Date of Registration: 06/15/2014.

     

Changes in retinoblastoma gene expression during cervical cancer progression

The role of tumour suppressor genes in the development of human cancers has been studied extensively. In viral carcinogenesis, the inactivation of suppressor proteins such as retinoblastoma (pRb) and p53, and cellular oncogenes overexpression, such as c-myc, has been the subject of a number of investigations. In uterine-cervix carcinomas, where high-risk human papillomavirus (HPV) plays an important role, pRb and p53 are inactivated by E7 and E6 viral oncoproteins, respectively. However, little is known about the in situ expression of some of these proteins in pre-malignant and malignant cervical tissues. On the other hand, it has also been demonstrated that c-myc is involved in cervical carcinogenesis, and that pRb participates in the control of c-myc gene expression. By using immunostaining techniques, we investigated pRb immunodetection pattern in normal tissues, squamous intraepithelial lesions (SILs) and invasive carcinomas from the uterine cervix. Our data show low pRb detection in both normal cervical tissue and invasive lesions, but a higher expression in SILs. C-Myc protein was observed in most of the cellular nuclei of the invasive lesions, while in SILs was low. These findings indicate a heterogeneous pRb immunostaining during the different stages of cervical carcinogenesis, and suggest that this staining pattern could be a common feature implicated in the pathogenesis of uterine-cervix carcinoma.     

Neutrophils as drivers of vascular injury in sickle cell disease

While neutrophils are the main effectors of protective innate immune responses, they are also key players in inflammatory pathologies. Sickle cell disease (SCD) is a genetic blood disorder in which red blood cells (RBCs) are constantly destroyed in the circulation which generates a highly inflammatory environment that culminates in vascular occlusions. Vaso-occlusion is the hallmark of SCD and a predictor of disease severity. Neutrophils initiate and propagate SCD-related vaso-occlusion through adhesive interactions with the activated and dysfunctional endothelium, sickle RBCs, and platelets, leading to acute and chronic complications that progress to irreversible organ damage and ultimately death. The use of SCD humanized mouse models, in combination with in vivo imaging techniques, has emerged as a fundamental tool to understand the dynamics of neutrophils under complex inflammatory contexts and their contribution to vascular injury in SCD. In this review, we discuss the various mechanisms by which circulating neutrophils sense and respond to the wide range of stimuli present in the blood of SCD patients and mice. We argue that the central role of neutrophils in SCD can be rationalized to develop targets for the management of clinical complications in SCD patients.     

Metallothionein (MT)-III: generation of polyclonal antibodies, comparison with MT-I+II in the freeze lesioned rat brain and in a bioassay with astrocytes, and analysis of Alzheimer's disease brains

Metallothionein-III is a low molecular weight, heavy-metal binding protein expressed mainly in the central nervous system. First identified as a growth inhibitory factor (GIF) of rat cortical neurons in vitro, it has subsequently been shown to be a member of the metallothionein (MT) gene family and renamed as MT-III. In this study we have raised polyclonal antibodies in rabbits against recombinant rat MT-III (rMT-III). The sera obtained reacted specifically against recombinant zinc-and cadmium-saturated rMT-III, and did not cross-react with native rat MT-I and MT-II purified from the liver of zinc injected rats. The specificity of the antibody was also demonstrated in immunocytochemical studies by the elimination of the immunostaining by preincubation of the antibody with brain (but not liver) extracts, and by the results obtained in MT-III null mice. The antibody was used to characterize the putative differences between the rat brain MT isoforms, namely MT-I+II and MT-III, in the freeze lesion model of brain damage, and for developing an ELISA for MT-III suitable for brain samples. In the normal rat brain, MT-III was mostly present primarily in astrocytes. However, lectin staining indicated that MT-III immunoreactivity was also present in microglia, monocytes and/or macrophages in the leptomeninges and lying adjacent to major vessels. In freeze lesioned rats, both MT-I+II and MT-III immunoreactivities increased in the ipsilateral cortex. The pattern of MT-III immunoreactivity significantly differed from that of MT-I+II, since the latter was evident in both the vicinity of the lesioned tissue and deeper cortical layers, whereas that of the former was located only in the deeper cortical layers. This suggests different roles for these MT isoforms, and indeed in a new bioassay measuring astrocyte migration in vitro, rMT-III promoted migration to a higher extent than MT-I+II. Thus, MT-III could not only affect neuronal sprouting as previously suggested, but also astrocyte function. Finally, MT-III protein levels of patients with Alzheimer's disease (AD) were, if anything, increased when compared with similarly aged control brains, which was in agreement with the significantly increased MT-III mRNA levels of AD brains.     

Results of surgical treatment of hepatic hydatidosis: Current therapeutic modifications

Hepatic hydatidosis is an endemic disease that affects vast segments of the populations of various countries in the Mediterranean region, South America, the Pacific, and temperate zone nations that possess large numbers of sheep. Four hundred and ten patients bearing 561 hydatid cysts were treated at 2 major hospitals in Madrid, Spain in the period 1974–1989. In order to establish the modifications in diagnostic and therapeutic management introduced as a result of modernization of our clinical facilities and improved technological standards, they were divided into 2 groups: group A corresponded to the period 1974–1984, and group B, corresponded to the period 1985–1989. Since no effective parasiticide agent is available, hepatic hydatidosis must be treated surgically. Today's better knowledge and advancements in liver surgery have made it possible to extirpate the cyst completely with little risk and improved results; hepatic resection should only be considered in exceptional cases; aspiration, drainage procedures, or partial resections of the cyst yield inferior results. We have had no relapse of the hydatid disease in the liver or in any other abdominal site.

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Resumen La hidatidosis hepática es una enfermedad endémica que afecta a vastos segmentas de las poblaciones de diversos países de la región mediterránea, Sur América, el Pacífico, y las naciones de las zonas templadas que mantienen grandes rebanos de ovejas. Cuatrocientos diez pacientes con 561 quistes hidatídicos fueron tratados en 2 grandes hospitales de Madrid, España en el período 1974–1989. Con el propósito de establecer las modificaciones en el manejo diagnóstico y terapéutico ocurridas como resultado de la modernización de nuestras facilidades clínicas y de superiores estándares tecnológicos, dividimos la población total de estos pacientes en 2 grandes grupos: grupo A, correspondiente al período 1974–1984, y grupo B, correspondiente al período 1985–1989. Puesto que no existe un agente parasitocida efectivo, la hidatidosis hepática debe ser tratada quirúrgicamente. El mejor conocimiento actual y el avance en la cirugía hepática han hecho posible la extirpatión completa del quiste con bajo riesgo y mejores resultados; la resection hepática debe ser considerada sólo en casos excepcionales; la aspiración, los procedimientos de drenaje o las resecciones parciales del quiste se asocian con malos resultados. En nuestra experiencia no hemos tenido recurrencia de la enfermedad ni en el hígado ni en otros órganos.

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Résumé Le kyste hydatique du foie est une maladie endémique qui touche une partie importante de la population dans différents pays de la région méditerranéenne, en Amérique du Sud, dans le Pacifique, et dans les pays de la zone tempérée qui ont beaucoup de moutons. Quatre cent dix patients porteurs de 561 kystes hydatiques ont été traités dans les deux plus grands hôpitaux de Madrid en Espagne de 1974 à 1989. Pour mesurer les progrès dans le diagnostic et le traitement dus à la modernisation de notre équipement médical et à une meilleure technologie, les patients ont été divisés en 2 groupes chronologiques: groupe A de 1974 à 1984 et groupe B de 1985 à 1989. Comme il n'y a pas actuellement de médicament efficace contre ce parasite, on doit traiter par la chirurgie le kyste hydatique. Aujourd'hui, les connaissances plus étendues et les progrès dans la chirurgie du foie permettent d'enlever complètement le kyste avec peu de risques et avec de meilleurs résultats; la résection du foie ne doit être envisagée que dans de rares cas. Les procédés d'aspiration ou de drainage ou les résections partielles du kyste donne des résultats moins bons. Nous n'avons pas eu de récidive du kyste hydatique, ni au foie ni dans une autre localisation péritonéale.

     

Gigantic diverticulum of the colon. A complication of diverticulosis?]

We present a patient affected of diverticular disease of the colon, with diverticulosis and two giant diverticula of the sigma, both located at the mesenteric edge. We would like to stress the low incidence of reports about this entity in the medical literature, its uncommon location and the fact of a double lesion coinciding in a single patient. We discuss the most important nosocomial aspects and the different diagnoses. Finally, we support the idea of distinguishing three different entities that in the medical literature are usually unified as a single "giant diverticulum of the colon". We reaffirm ourselves on the importance of an early diagnosis and a correct indication for surgery.