Human cytomegalovirus glycoprotein B genotypes in Brazilian mothers and their congenitally infected infants

A case-control study design was used in order to compare the distribution of human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes in 48 mothers of 49 congenitally infected infants with that observed in 144 mothers of 146 uninfected infants to study genetic variation of HCMV strains and maternal-fetal transmission. Congenital infection with HCMV was characterized by DNA detection and virus isolation from two urine or saliva samples collected prior to the third week of life. Genotyping of HCMV was carried out by a polymerase chain reaction-restriction fragment length polymorphism analysis of the variable region of the gB gene, testing for four genotypes. Genotype frequency was similar among the 28 non-transmitting mothers who were shedding virus (gB1: 25%; gB2: 28.6%; gB3: 42.8%; gB4: 0%), the 37 transmitting mothers (gB1: 21.6%; gB2: 46%; gB3: 27%; gB4: 0%), and the 49 infected infants (gB1: 39%; gB2: 37%; gB3: 24%; gB4: 0%). The same genotype was detected at different body sites (urine, saliva, and blood) of each infected newborn and in the respective mother (breast milk, urine, and saliva). Co-infection with multiple genotypes was observed in the immediate postpartum period in two mothers of infected infants (5.4%) and one non-transmitting mother (3.6%). The gB genotype was not correlated with intrauterine HCMV transmission. The genotype distribution found reflects the overall frequency of wild strains circulating in this geographic region. A single genotype is responsible for congenital HCMV infection. Co-infection with more than one strain, as characterized by gB genotype, was infrequent in women who were presumably immunocompetent.     

Direct Susceptibility Testing of Mycobacterium tuberculosis for Pyrazinamide by Use of the Bactec MGIT 960 System

Pyrazinamide (PZA) is a key antituberculosis drug, yet no rapid susceptibility test is commercially available. PZA drug susceptibility testing (DST) was performed directly on sputum samples from 327 patients and compared with the indirect method by using the Bactec MGIT 960 system in the context of patient screening for participation in a drug trial. Compared to standard indirect PZA DST, direct DST was successful in only 59% of cases, but results obtained were highly accurate and available faster. Agreement between the direct and indirect methods varied from 90 to 100% in each laboratory. The median times for obtaining PZA results from the time when the specimen was collected ranged from 11 to 16 days for the direct test and 18 to 95 days for the indirect test across laboratories. The direct method is accurate and reproducible across laboratories. It can be expected to accelerate results in >50% of cases, but it cannot replace indirect DST for PZA. Phenotypic methods remain the gold standard for DST in drug trials. If future studies can optimize the method to decrease the number of uninterpretable results, direct MGIT DST could be the new phenotypic DST standard for clinical trials, providing more rapid detection of resistance to new drugs in experimental regimens.     

CD4 T cells in tumor immunity

T cell immunity is the key to protective immune responses against tumors. Traditionally, this function has been ascribed to CD8 T lymphocytes with cytotoxic activity, which are restricted by MHC class I molecules. In recent years the realization that CD4 T cells can also play a relevant role in protective anti-tumor responses has received growing attention. Here we will discuss the role of MHC class II-restricted T cells in response to, and in the regulation of, tumor antigens. Emphasis will be placed on four areas: (1) the role of CD4 T cell immunity in tumor protection in animal models and putative mode of action, (2) tumor antigens recognized by human CD4 T cells, (3) the cooperation between two CD4 T cells of different specificity as a new way to jump start the response against sub-immunogenic determinants of tumor antigens in a tolerant environment, and (4) the negative impact of regulatory CD4 T cells on anti-tumor T cell responses. By drawing attention to these four areas, it is our intention to provide the reader with a comprehensive view of issues of contemporary importance for this field, in the expectation that the information will help a better design of therapeutic cancer vaccines.     

Reference values for the fetal lateral ventricle atrium measurement in the second and third trimesters of pregnancy in a Brazilian population

Objective: To establish reference values for the fetal atrium lateral ventricle measurements in the second and third trimesters of pregnancy in a Brazilian population.

Methods: A retrospective cross-sectional study was performed with low-risk pregnant women who underwent ultrasound examination at 16–41 weeks of gestation. The atrium of lateral ventricle measurement was performed in the transventricular plane at the end of choroid plexus. We assessed reference curves (percentiles 5th, 50th and 95th) for the atrium of lateral ventricle measurement with gestational age (GA), using the best-fit polynomial equation, and determination coefficient (R²) and modeling the variability.

Results: The fetal atrium of lateral ventricle measurements was assessed in 519 singleton pregnancies. However, seven fetuses were excluded because of central nervous system malformations, and therefore data from 512 pregnancies were included in the analysis. The mean?±?standard deviation (range) of the fetal atrium lateral ventricle measurement (mm) was 5.1?±?1.4 (1.6–9.7). A best-fit curve was a first-degree polynomial regression: atrium lateral ventricle?=?6.455???0.049?×?GA (R²?=?0.05).

Conclusion: Reference values for the fetal atrium lateral ventricle measurements in the second and third trimesters of pregnancy in a Brazilian population were established.     

Activity of tea tree oil and nerolidol alone or in combination against Pediculus capitis (head lice) and its eggs

Acanthamoeba castellanii causes amoebic keratitis which is a painful sight-threatening disease of the eyes. Its eradication is difficult because the amoebas encyst making it highly resistant to anti-amoebic drugs, but several medicinal plants have proven to be more effective than the usual therapy. This study aimed to evaluate the in vitro amoebicidal activity of ethanol extracts of Arachis hypogaea L. (peanut), Curcuma longa L. (turmeric), and Pancratium maritimum L. (sea daffodil) on A. castellanii cysts. Acanthamoeba were isolated from keratitic patients, cultivated on 1.5% non-nutrient agar, and then incubated with different concentrations of plant extracts which were further evaluated for their cysticidal activity. The results showed that all extracts had significant inhibitory effect on the multiplication of Acanthamoeba cysts as compared to the drug control (chlorhexidine) and non-treated control, and the inhibition was time and dose dependent. The ethanol extract of A. hypogaea had a remarkable cysticidal effect with minimal inhibitory concentration (MIC) of 100 mg/ml in all incubation periods, while the concentrations of 10 and 1 mg/ml were able to completely inhibit growth after 48 and 72 h, respectively. The concentrations 0.1 and 0.01 mg/ml failed to completely inhibit the cyst growth, but showed growth reduction by 64.4–82.6% in all incubation periods. C. longa had a MIC of 1 g and 100 mg/ml after 48 and 72 h, respectively, while the concentrations 10, 1, and 0.1 mg/ml caused growth reduction by 60–90.3% in all incubation periods. P. maritimum had a MIC of 200 mg/ml after 72 h, while the 20-, 2-, 0.2-, and 0.02-mg/ml concentrations showed growth reduction by 34–94.3% in all incubation periods. All extracts seemed to be more effective than chlorhexidine which caused only growth reduction by 55.3–80.2% in all incubation periods and failed to completely inhibit the cyst growth. In conclusion, ethanol extracts of A. hypogaea, C. longa, and P. maritimum could be considered a new natural agent against the Acanthamoeba cyst.     

The neuronal nitric oxide synthase (nNOS) gene contributes to the regulation of tyrosine hydroxylase (TH) by cocaine

Recently, we demonstrated that intact nitric oxide (NO) signaling is essential for the development of cocaine behavioral sensitization in adulthood [M.A. Balda, K.L. Anderson, Y. Itzhak, Differential role of the nNOS gene in the development of behavioral sensitization to cocaine in adolescent and adult B6;129S mice, Psychopharmacology (Berl) 200 (2008) 509–519]. Given the requirement of dopamine (DA) transmission in cocaine-induced behavioral sensitization and the interactions between NO and DA systems, the present study investigated the role of the neuronal nitric oxide synthase (nNOS) gene and the effect of cocaine on the expression of tyrosine hydroxylase (TH)-immunoreactive (-ir) neurons. Adult (postnatal day 80) wild type (WT) and nNOS knockout (KO) mice received saline or a sensitizing regimen of cocaine (20 mg/kg) for 5 days. After 24 h, TH immunoreactivity was assessed in the ventral tegmental area (VTA) and the dorsal striatum (dST) using stereology and Western blotting, respectively. We report that (a) nNOS KO mice express lower levels of TH-ir neurons in the VTA compared to WT counterparts, (b) cocaine administration to WT mice significantly increased striatal TH expression, and (c) the same cocaine administration to nNOS KO mice significantly decreased striatal TH expression. Thus, the nitrergic system may contribute to cocaine-induced behavioral sensitization by regulating dopaminergic neurotransmission.     

Optimized light therapy for non-seasonal major depressive disorder: effects of timing and season

BackgroundLight Therapy (LT) when combined with standard antidepressant treatment for unipolar depression hastens recovery. We studied the influence of LT timing on the antidepressant efficacy of LT and the influence of the season of treatment and recurrence on the response to treatment.MethodsWe studied 70 inpatients affected by Unipolar Depression, treated for three weeks with combined LT and venlafaxine. Two-third of the patients received LT following a predictive algorithm based on MEQ scores; the others received LT at 11:00 a.m. Severity of depression was rated on the Hamilton Depression Rating Scale (HDRS). A subgroup of patients wore activity monitors.ResultsHDRS scores significantly decreased during treatment (Friedman's ANOVA: χ2 = 186.82, p < 0.00001). LT administered in the early morning showed a better relative efficacy than late morning (F = 4.576; p = 0.012) with the clinical improvement correlating with an advance in rest–activity rhythm acrophase (r = ? 0.336; p = 0.017). Season of hospitalization interacted with LT timing and time in influencing response to treatment (F = 3.101; p = 0.049) and season of episode recurrence significantly interacted with LT timing, season of hospitalization and time (F = 5.925; p = 0.0035).LimitationsThe major limitation of the study is the small sample size when considering simultaneously LT schedules, season of treatment and recurrence. Moreover, even if none of the patients fulfilled DSM-IV criteria for seasonal pattern of recurrence, they were not administered any questionnaire about seasonality.ConclusionsWe confirmed the usefulness of LT as a non-pharmacological antidepressant therapy for non-seasonal depression. Season and timing of administration and timing of the rest–activity cycle affected response to treatment.     

Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD

Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degeneration (FTLD) by haploinsufficiency mechanism, although their effects on brain tissue dysfunction and damage still remain to be clarified. In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the DMN. Our findings suggest that compensatory mechanisms of brain plasticity are present in GRN-related FTLD, but with different patterns at a preclinical and symptomatic disease stage.     

Corrosion fatigue of biomedical metallic alloys: mechanisms and mitigation

Cyclic stresses are often related to the premature mechanical failure of metallic biomaterials. The complex interaction between fatigue and corrosion in the physiological environment has been subject of many investigations. In this context, microstructure, heat treatments, plastic deformation, surface finishing and coatings have decisive influence on the mechanisms of fatigue crack nucleation and growth. Furthermore, wear is frequently present and contributes to the process. However, despite all the effort at elucidating the mechanisms that govern corrosion fatigue of biomedical alloys, failures continue to occur. This work reviews the literature on corrosion-fatigue-related phenomena of Ti alloys, surgical stainless steels, Co-Cr-Mo and Mg alloys. The aim was to discuss the correlation between structural and surface aspects of these materials and the onset of fatigue in the highly saline environment of the human body. By understanding such correlation, mitigation of corrosion fatigue failure may be achieved in a reliable scientific-based manner. Different mitigation methods are also reviewed and discussed throughout the text. It is intended that the information condensed in this article should be a valuable tool in the development of increasingly successful designs against the corrosion fatigue of metallic implants.