Absence of brain involvement and factors related to positive serology in a prospective series of 61 cases with pulmonary hydatid disease

A prospective series of 65 patients with surgically confirmed lung cystic hydatid disease was evaluated in terms of their radiologic characteristics, serologic response, and presence of cysts in other organs. Cysts were mostly single and located in lower lung lobes. Liver compromise was found in 34% of the patients. Despite a systematic search, no patient showed brain cysts in this series. Twelve patients had previous hydatid disease: six in the liver and eight in the lung (two had involvement of both organs in the past). Serology using bovine cyst fluid in an immunoblot assay was 85% sensitive. Serologic response was not associated with number or cyst or compromise of other organs but was clearly associated to the presence of at least one complicated cyst. Cyst status in terms of complications should be described to allow appropriate assessment of serologic evaluations.     

Exercise capacity in adult African-Americans referred for exercise stress testing: is fitness affected by race?

STUDY OBJECTIVES: To determine the factors associated with exercise capacity. DESIGN: Retrospective evaluation of large stress-testing database. SETTING: Multispecialty tertiary care center. PATIENTS: A total of 5,069 consecutive patients who were referred for exercise stress testing. MEASUREMENTS: We compared levels of fitness in 641 African-Americans (52% male) with 4,428 whites (73% male), and performed univariate and multivariate analyses to determine the predictors of fitness (including race). RESULTS: Compared with African-American men (mean [+/- SD] age, 60 +/- 11 years), white men (mean age, 63 +/- 11 years) have significantly higher exercise capacity (10.7 +/- 3.5 vs 11.4 +/- 3.4 metabolic equivalents [METs], respectively; p < 0.001). The exercise capacity in African-American and white women was similar (8.5 +/- 2.9 vs 8.7 +/- 3.0 METs, respectively). However, body mass indexes (BMIs) were significantly higher in both African-American men (29.1 +/- 4.3 vs 28.2 +/- 4.3 kg/m(2), respectively; p < 0.001) and women (30.2 +/- 5.7 vs 27.9 +/- 5.5 kg/m(2), respectively; p < 0.0001) compared to their white counterparts, as was the prevalence of obesity (men, 44% vs 33%, respectively; women, 37% vs 27%, respectively; both p < 0.001). Although a model containing age, gender, BMI, and race only accounted for 32% of exercise capacity, all independently (p < 0.0001) predicted higher exercise capacity, as follows: younger age (r(2) = 0.14); male gender (r(2) = 0.12); BMI (r(2) = 0.06); and white race (r(2) = 0.004). CONCLUSIONS: In an adult population of individuals who were referred for exercise stress testing, African-Americans were more obese and had significantly lower exercise capacity than their white counterparts. Emphasis on weight reduction and increasing physical fitness is particularly needed for the prevention of cardiovascular diseases in African-Americans.     

Developmental changes of cardiac repolarization in rabbits: implications for the role of sex hormones

OBJECTIVES: Firstly, to compare gender-dependent differences of cardiac repolarization in both adult and young rabbits. Secondly, to analyze the effect of gonadectomy on these gender differences in cardiac repolarization. METHODS: We evaluated potential gender differences in cardiac repolarization with both microelectrode and ECG recordings. QT(end), JT(end), and T(peak-end) intervals and action potential durations at 30%, 50% and 90% of full repolarization were used to assess ventricular repolarization in adult (normal and gonadectomized) and young rabbits of both sexes. RESULTS: Adult rabbits exhibited clear gender-related differences in repolarization evidenced by significantly longer JT(end) and T(peak-end) intervals and significantly longer APD30, APD50 and APD90 in females. These gender-related differences in repolarization were absent in young rabbits and were abolished by gonadectomy. CONCLUSIONS: Developmental changes of repolarization are present in rabbits. These changes are in agreement with those reported in humans and may further support the role played by sex hormones in the modulation of cardiac repolarization.     

Transcatheter Versus Surgical Aortic Valve Replacement in Young,Low-Risk Patients With Severe Aortic Stenosis

Transcatheter aortic valve replacement (TAVR) is approved for all patient risk profiles and is an option for all patients irrespective of age. However, patients enrolled in the low- and intermediate-risk trials were in their 70s, and those in the high-risk trials were in their 80s. TAVR has never been systematically tested in young (<65 years), low-risk patients. Unanswered questions remain, including the safety and effectiveness of TAVR in patients with bicuspid aortic valves; future coronary access; durability of transcatheter heart valves; technical considerations for surgical transcatheter heart valve explantation; management of concomitant conditions such as aortopathy, mitral valve disease, and coronary artery disease; and the safety and feasibility of future TAVR-in-TAVR. The authors predict that balancing these questions with patients’ clear preference for less invasive treatment will become common. In this paper, the authors consider each of these questions and discuss risks and benefits of theoretical treatment strategies in the lifetime management of young patients with severe aortic stenosis.     

Endogenous selective inhibitors of 11beta-hydroxysteroid dehydrogenase isoforms 1 and 2 of adrenal origin

In earlier studies [Latif, S.A., Sheff, M.F., Ribeiro, C.E., Morris, D.J., 1997. Selective inhibition of sheep kidney 11beta-hydroxysteroid-dehydrogenase isoform 2 activity by 5alpha-reduced (but not 5beta) derivatives of adrenocorticosteroids. Steroids 62, 230-237], only derivatives of steroid hormones possessing the 5alpha-Ring A-reduced configuration selectively inhibited 11beta-HSD2-dehydrogenase, whereas their 5beta-derivatives were inactive. This present study focuses on an expanded group of endogenous 11-oxygenated, 5alpha and 5beta-Ring A-reduced metabolites of adrenocorticosteroids, and progestogen and androgen steroid hormones. These substances were tested for their inhibitory properties against 11beta-HSD2, 11beta-HSD1-dehydrogenase and 11beta-HSD1 reductase. The present studies showed that the following compounds stand out as potent inhibitors. These are 5alpha-DH-corticosterone, 3alpha,5alpha-TH-corticosterone, 11beta-OH-progesterone, 11beta-OH-allopregnanolone, 11beta-OH-testosterone, and 11beta-OH-androstanediol, inhibitors of 11beta-HSD1-dehydrogenase; 3alpha,5alpha-TH-11-dehydro-corticosterone, 11-keto-progesterone, 11-keto-allopregnanolone, and 11-keto-3beta,5alpha-TH-testosterone, inhibitors of 11beta-HSD1 reductase; 3alpha,5alpha-TH-aldosterone, 5alpha-DH-corticosterone, 3alpha,5alpha-TH-corticosterone,11-dehydro-corticosterone, 3alpha,5alpha-TH-11-dehydro-corticosterone, 11beta-OH-progesterone, 11-keto-progesterone, 11beta-OH-allopregnanolone, 11-keto-allopregnanolone, 11beta-OH-testosterone, and 11-keto-testosterone, inhibitors of 11beta-HSD2. All of these substances have the potential to be derived from adrenally synthesized corticosteroids. Substances with similar structures to those described may help in the design of exogenous agents for the management of a variety of disease states involving 11beta-HSD isoenzymes.     

Anticoagulation in the elderly

This review will address the general approach to the management of the typical elderly patient requiring anticoagulation. Most of the data has been derived from studies of patients with non-valvular atrial fibrillation. Data from postmyocardial infarction trials have also been included. A practical clinical approach to anticoagulation in the elderly is described. Emphasis has been placed on maximizing the benefit and reducing the risk of anticoagulation in the rapidly expanding group of elderly patients aged ≥75 who are at the greatest risk of stroke and are likely to benefit the most from antithrombotic therapy.     

Development and characterization of a new chitosan-based scaffold associated with gelatin,microparticulate dentin and genipin for endodontic regeneration

ObjectiveAn ideal scaffold for endodontic regeneration should allow the predictableness of the new tissue organization and limit the negative impact of residual bacteria. Therefore, composition and functionalization of the scaffold play an important role in tissue bioengineering. The objective of this study was to assess the morphological, physicochemical, biological and antimicrobial properties of a new solid chitosan-based scaffold associated with gelatin, microparticulate dentin and genipin.MethodsScaffolds based on chitosan (Ch); chitosan associated with gelatin and genipin (ChGG); and chitosan associated with gelatin, microparticulate dentin and genipin (ChGDG) were prepared by using the freeze-drying method. The morphology of the scaffolds was analyzed by scanning electron microscopy (SEM). The physicochemical properties were assessed for biodegradation, swelling and total released proteins. The biological aspects of the scaffolds were assessed using human cells from the apical papilla (hCAPs). Cell morphology and adhesion to the scaffolds were evaluated by SEM, cytotoxicity and cell proliferation by MTT reduction-assay. Cell differentiation in scaffolds was assessed by using alizarin red assay. The antimicrobial effect of the scaffolds was evaluated by using the bacterial culture method, and bacterial adhesion to the scaffolds was observed by SEM.ResultsAll the scaffolds presented porous structures. The ChCDG had more protein release, adhesion, proliferation and differentiation of hCAPs, and bacteriostatic effect on Enterococcus faecalis than Ch and ChGG (p < 0.05).SignificanceThe chitosan associated with gelatin, microparticulate dentin and genipin has morphological, physicochemical, biological and antibacterial characteristics suitable for their potential use as scaffold in regenerative endodontics.     

Somatic Alterations Contributing to Metastasis of a Castration‐Resistant Prostate Cancer

Metastatic castration‐resistant prostate cancer (mCRPC) is a lethal disease, and molecular markers that differentiate indolent from aggressive subtypes are needed. We sequenced the exomes of five metastatic tumors and healthy kidney tissue from an index case with mCRPC to identify lesions associated with disease progression and metastasis. An Ashkenazi Jewish (AJ) germline founder mutation, del185AG in BRCA1, was observed and AJ ancestry was confirmed. Sixty‐two somatic variants altered proteins in tumors, including cancer‐associated genes, TMPRSS2‐ERG, PBRM1, and TET2. The majority (n = 53) of somatic variants were present in all metastases and only a subset (n = 31) was observed in the primary tumor. Integrating tumor next‐generation sequencing and DNA copy number showed somatic loss of BRCA1 and TMPRSS2‐ERG. We sequenced 19 genes with deleterious mutations in the index case in additional mCRPC samples and detected a frameshift, two somatic missense alterations, tumor loss of heterozygosity, and combinations of germline missense SNPs in TET2. In summary, genetic analysis of metastases from an index case permitted us to infer a chronology for the clonal spread of disease based on sequential accrual of somatic lesions. The role of TET2 in mCRPC deserves additional analysis and may define a subset of metastatic disease.     

EEC‐ and ADULT‐Associated TP63 Mutations Exhibit Functional Heterogeneity Toward P63 Responsive Sequences

TP63 germ‐line mutations are responsible for a group of human ectodermal dysplasia syndromes, underlining the key role of P63 in the development of ectoderm‐derived tissues. Here, we report the identification of two TP63 alleles, G134V (p.Gly173Val) and insR155 (p.Thr193_Tyr194insArg), associated to ADULT and EEC syndromes, respectively. These alleles, along with previously identified G134D (p.Gly173Asp) and R204W (p.Arg243Trp), were functionally characterized in yeast, studied in a mammalian cell line and modeled based on the crystal structure of the P63 DNA‐binding domain. Although the p.Arg243Trp mutant showed both complete loss of transactivation function and ability to interfere over wild‐type P63, the impact of p.Gly173Asp, p.Gly173Val, and p.Thr193_Tyr194insArg varied depending on the response element (RE) tested. Interestingly, p.Gly173Asp and p.Gly173Val mutants were characterized by a severe defect in transactivation along with interfering ability on two DN‐P63α‐specific REs derived from genes closely related to the clinical manifestations of the TP63‐associated syndromes, namely PERP and COL18A1. The modeling of the mutations supported the distinct functional effect of each mutant. The present results highlight the importance of integrating different functional endpoints that take in account the features of P63 proteins' target sequences to examine the impact of TP63 mutations and the associated clinical variability.