Mother-to-Child Transmission of Chagas Disease in El Salvador

To estimate the incidence (any mother to child) and rate (from seropositive mother to child) of mother-to-child transmission of Trypanosoma cruzi, a serological census was conducted, targeting pregnant women and infants born to seropositive mothers, in four municipalities of El Salvador. Of 943 pregnant women, 36 (3.8%) were seropositive for T. cruzi. Of 36, 32 proceeded to serological tests of their infants when they became 6–8 months of age. Six infants seropositive at the age of 6–8 months further proceeded to second-stage serological test at the age of 9–16 months. As the result, one infant was congenitally infected. Thus, serological tests at the age of 6–8 months produced five false positives. To ensure earlier effective medication only for true positives, identification of seropositive infants at the age of 9–16 months is crucial. Incidence and rate of mother-to-child transmission were 0.14 (per 100 person-years) and 4.0%, respectively. Estimated number of children infected through mother-to-child transmission in El Salvador (170 per year) was much higher than that of human immunodeficiency virus (HIV; seven per year). It is recommended that serological testing for T. cruzi be integrated into those for HIV and syphilis as part of antenatal care package.     

IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes

Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.     

Comparison of eight diagnostic algorithms for liver fibrosis in hepatitis C: new algorithms are more precise and entirely noninvasive

The sequential algorithm for fibrosis evaluation (SAFE) and the Bordeaux algorithm (BA), which cross-check FibroTest with the aspartate aminotransferase-to-platelet ratio index (APRI) or FibroScan, are very accurate but provide only a binary diagnosis of significant fibrosis (SAFE or BA for Metavir F ≥ 2) or cirrhosis (SAFE or BA for F4). Therefore, in clinical practice, physicians have to apply the algorithm for F ≥ 2, and then, when needed, the algorithm for F4 ("successive algorithms"). We aimed to evaluate successive SAFE, successive BA, and a new, noninvasive, detailed classification of fibrosis. The study included 1785 patients with chronic hepatitis C, liver biopsy, blood fibrosis tests, and FibroScan (the latter in 729 patients). The most accurate synchronous combination of FibroScan with a blood test (FibroMeter) provided a new detailed (six classes) classification (FM+FS). Successive SAFE had a significantly (P < 10(-3) ) lower diagnostic accuracy (87.3%) than individual SAFE for F ≥ 2 (94.6%) or SAFE for F4 (89.5%), and required significantly more biopsies (70.8% versus 64.0% or 6.4%, respectively, P < 10(-3) ). Similarly, successive BA had significantly (P ≤ 10(-3) ) lower diagnostic accuracy (84.7%) than individual BA for F ≥ 2 (88.3%) or BA for F4 (94.2%), and required significantly more biopsies (49.8% versus 34.6% or 24.6%, respectively, P < 10(-3) ). The diagnostic accuracy of the FM+FS classification (86.7%) was not significantly different from those of successive SAFE or BA. However, this new classification required no biopsy. CONCLUSION: SAFE and BA for significant fibrosis or cirrhosis are very accurate. However, their successive use induces a significant decrease in diagnostic accuracy and a significant increase in required liver biopsy. A new fibrosis classification that synchronously combines two fibrosis tests was as accurate as successive SAFE or BA, while providing an entirely noninvasive (0% liver biopsy) and more precise (six versus two or three fibrosis classes) fibrosis diagnosis.     

Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin.     

Evaluation of Primary Stability of Self‐Tapping and Non‐Self‐Tapping Dental Implants. A 12‐Week Clinical Study

Purpose: The aim of this study was to investigate the relationship between surgical techniques and implant macro‐design (self‐tapping/non‐self‐tapping) for the optimization of implant stability in the low‐density bone present in the posterior maxilla using resonance frequency analysis (RFA). Materials and Methods: A total of 102 implants were studied. Fifty‐six self‐tapping BlueSkyBredent® (Bredent GmbH&Co.Kg®, Senden, Germany) and 56 non‐self‐tapping Standard Plus Straumann® (Institut Straumann AG®, Waldenburg, Switzerland) were placed in the posterior segment of the maxilla. Implants of both types were placed in sites prepared with either lateral bone‐condensing or with bone‐drilling techniques. Implant stability measurements were performed using RFA immediately after implant placement and weekly during a 12‐week follow‐up period. Results: Both types of implants placed after bone condensing achieved significantly higher stability immediately after surgery, as well as during the entire 12‐week observation period compared with those placed following bone drilling. After bone condensation, there were no significant differences in primary stability or in implant stability after the first week between both implant types. From 2 to 12 postoperative weeks, significantly higher stability was shown by self‐tapping implants. After bone drilling, self‐tapping implants achieved significantly higher stability than non‐self‐tapping implants during the entire follow‐up period. Conclusions: The outcomes of the present study indicate that bone drilling is not an effective technique for improving implant stability and, following this technique, the use of self‐tapping implants is highly recommended. Implant stability optimization in the soft bone can be achieved by lateral bone‐condensing technique, regardless of implant macro‐design.     

Slow Resorption of Anorganic Bovine Bone by Osteoclasts in Maxillary Sinus Augmentation

Purpose: Different biomaterials have been suggested for guided bone regeneration (GBR). These might show the ideal properties to let a new bone formation in the grafted area. Among these ideal features, it is essential their controlled resorption in order to be replaced for new vital bone. Bovine bone has been used widely as a good biomaterial for GBR, however there is still an interesting controversy about its resorbable capacity. In this sense, the objective of this study was to examine the behavior of anorganic bovine bone (ABB) in long‐term maxillary sinus graft healing and study its relationship with morphological and morphometrical variables. Materials and Methods: Seventeen maxillary sinus augmentation procedures were performed in patients. Bone cores were obtained from implant receptor sites at 6 months, 3 years, and 7 years of implant placement for histological, morphometric, and immunohistochemical (tartrate resistant acid phosphatase [TRAP]/cathepsin K/CD68) studies. Results: The percentages of bone, ABB particles, connective tissue, osteocytes, and osteoblasts in maxillary sinus grafts were similar at 6 months, 3 years, and 7 years. A progressive and significant decrease was detected in osteoclasts (p = .05, Kruskal‐Wallis test), TRAP and cathepsin K expression (p = .014 and p = .021, respectively), and osteoid lines (p = .038). Conclusion: According to these data, a decrease in osteoclasts over time may, partially, explain the ABB persistence observed in core biopsies. Further studies with more cases and different graft maturation times are required to elucidate the resorption rates and cell events underlying these phenomena.