Severe hypoleptinaemia associated with insulin resistance in patients with common variable immunodeficiency

Objective Common variable immunodeficiency (CVI) is a primary immunodeficiency syndrome characterized by impaired production of antibodies and recurrent infections. Delay in diagnosis leads to metabolic wastage and low body weight. Leptin, a hormone produced by white adipose tissue, modulates insulin action by signal transduction cross‐talk and by direct action on pancreatic beta‐cells. We hypothesized that patients with CVI might present a defective regulation of leptin production and insulin resistance. Patients Thirteen CVI patients (39 ± 11 years) under gammaglobulin replacement were evaluated in parallel with 13 gender‐, age‐, body weight‐ and body mass index (BMI)‐matched healthy voluntaries, and with data from two large population series, the Bruneck and the Hoorn Studies. Measurements Serum leptin and insulin levels, homeostasis model assessment – insulin resistance (HOMA‐IR), body composition, haematological, biochemical and immunoglobulin measurements were obtained. Data were analysed by a one‐way analysis of variance (anova ) and by Pearson's rank analysis. The institutional ethics committee approved the study, and informed consent was obtained from patients and controls. Results No differences were found between CVI and the control group when comparing gender distribution, age, body weight, BMI, waist/hip ratio, relative body fat and fasting glucose levels. Leptin levels were lower (P < 0·05) in CVI patients than in controls and lower than fasting leptin levels detected in a large population study. CVI patients’ serum leptin levels did not correlate with BMI (r = 0·074, P = 0·8) and their high HOMA‐IR indicated insulin resistance. Conclusions CVI patients are relatively hypoleptinaemic and insulin resistant, and their serum leptin levels are not correlated to their BMI.     

Evaluation of the effects of catheter sampling for the study of platelet behavior in the pulmonary and coronary circulation

To study the effects of sampling through cardiac catheters on indices of platelet function, we measured the levels of platelet factor 4 (PF₄), beta thromboglobulin (BTG), and platelet aggregate ratio (PAR) in 10 patients with atrioventricular accessory pathway (AVNAP), six patients with primary pulmonary hypertension (PPH), and six patients with critical narrowing of the left anterior descending artery (LAD). In AVNAP and LAD patients samples were drawn simultaneously from a peripheral vein, coronary sinus, and brachial artery; in AVNAP patients samples were also obtained from the axillary vein before the coronary sinus was entered. In PPH patients samples were drawn from pulmonary artery, aorta, and a peripheral vein; in these patients the effects of an intravenous infusion of prostacyclin (PGl₂) (2 to 8 ng/kg/min) on PF₄, BTG, and PAR were also studied at all sampling sites. In all patients arterial, coronary sinus, pulmonary arterial, and axillary venous levels of PF₄, BTG, and PAR significantly exceeded those measured in the peripheral vein. PGl₂ infusion resulted in a significant decrease of PF₄ at all sampling sites, while no consistent BTG changes were observed and PAR levels did not decrease in the peripheral vein. Although a considerable interpatient variability in PF₄ levels was observed, a significant (r = 0.91) correlation was found in patients with AVNAP between simultaneous coronary sinus and arterial PF₄ levels. The value of PF₄ coronary sinus-arterial difference in LAD patients was consistently higher than that calculated in AVNAP patients (54.5 ± 28.9 vs 4.2 ± 3.8 ng/ml). In conclusion: (1) a considerable and variable degree of platelet activation occurs with catheter sampling, preventing the measurement of absolute levels of platelet metabolites; (2) among the indices examined PF₄ appears the most sensitive for detecting changes in platelet activity; and (3) the measurement of coronary sinus-arterial PF₄ differences may provide information on directional changes in transcardiac platelet behavior.     

Onabotulinumtoxin type A improves lower urinary tract symptoms and quality of life in patients with human T cell lymphotropic virus type 1 associated overactive bladder

Aim

To evaluate the efficacy of the onabotulinum toxin type A in the treatment of HTLV-1 associated overactive bladder and its impact on quality of life (QoL).

Novel Rhizobium lineages isolated from root nodules of the common bean (Phaseolus vulgaris L.) in Andean and Mesoamerican areas

The taxonomic affiliations of nineteen root-nodule bacteria isolated from the common bean (Phaseolus vulgaris L.) in Mexico, Ecuador and Brazil were investigated by analyses of 16S rRNA and of four protein-coding housekeeping genes. One strain from Mexico could be assigned to Rhizobium etli and two from Brazil to Rhizobium leucaenae, whereas another from Mexico corresponded to a recently described bean-nodulating species-level lineage related to R. etli and Rhizobium phaseoli. Ten strains isolated in Ecuador and Mexico corresponded to three novel Rhizobium lineages that fall into the R. phaseoli/R. etli/Rhizobium leguminosarum clade. One of those lineages, with representatives isolated mostly from Ecuador, seems to be dominant in beans from that Andean region. Only one of the Mexican strains clustered within the Rhizobium tropici clade, but as an independent lineage. Interestingly, four strains were affiliated with species within the Rhizobium radiobacter clade. The existence of yet non-described native Rhizobium lineages in both the Andean and Mesoamerican areas is discussed in relation to common-bean diversity and environmental conditions.     

Variation in genes implicated in B‐cell development and antibody production affects susceptibility to pemphigus

Pemphigus foliaceus (PF) is an autoimmune blistering skin disease characterized by the presence of pathogenic autoantibodies against desmoglein 1, a component of intercellular desmosome junctions. PF occurs sporadically across the globe and is endemic in some Brazilian regions. Because PF is a B‐cell‐mediated disease, we aimed to study the impact of variants within genes encoding molecules involved in the different steps of B‐cell development and antibody production on the susceptibility of endemic PF. We analysed 3,336 single nucleotide polymorphisms (SNPs) from 167 candidate genes genotyped with Illumina microarray in a cohort of 227 PF patients and 193 controls. After quality control and exclusion of non‐informative and redundant SNPs, 607 variants in 149 genes remained in the logistic regression analysis, in which sex and ancestry were included as covariates. Our results revealed 10 SNPs within or nearby 11 genes that were associated with susceptibility to endemic PF (OR >1.56; p < 0.005): rs6657275*G (TGFB2); rs1818545*A (RAG1/RAG2/IFTAP);rs10781530*A (PAXX), rs10870140*G and rs10781522*A (TRAF2); rs535068*A (TNFRSF1B); rs324011*A (STAT6);rs6432018*C (YWHAQ); rs17149161*C (YWHAG); and rs2070729*C (IRF1). Interestingly, these SNPs have been previously associated with differential gene expression, mostly in peripheral blood, in publicly available databases. For the first time, we show that polymorphisms in genes involved in B‐cell development and antibody production confer differential susceptibility to endemic PF, and therefore are candidates for possible functional studies to understand immunoglobulin gene rearrangement and its impact on diseases.     

Characterizing patient-oncologist communication in genomic tumor testing: The 21-gene recurrence score as an exemplar

ObjectiveWomen with early-stage, ER + breast cancer are recommend to receive genomic profiling tests, such as the 21-gene Recurrence Score (RS) test, to guide treatment decisions. We examined test- and treatment-related information discussed and the associations between RS categories and aspects of communication during patient-oncologist clinical encounters.MethodsAs part of a larger trial, clinical encounters (N = 46) were audiorecorded and coded for 1) RS- and treatment-related information, 2) shared decision making, 3) patient active participation, and 4) oncologist patient-centered communication. We examined differences by RS category using mixed models, adjusting for nesting within oncologist.ResultsPatients with a high RS were more likely to receive a chemotherapy recommendation (p < .01), hear about the risks/side effects of chemotherapy (p < .01), and offer their preferences (p = .02) than those with intermediate or low RS. Elements of shared decision making increased with RS. Oncologist patient-centered communication (M = 4.09/5, SD = .25) and patient active participation (M = 3.5/4, SD = 1.0) were high across RS.ConclusionFindings suggest that disease severity, rather than clinical uncertainty, impact treatment recommendations and shared decision making.Practice implicationsOncologists adjust test- and treatment-related information and shared decision making by disease severity. This information provides a framework to inform decision making in complex cancer and genomics settings.     

Accuracy of CAD-CAM systems for removable partial denture framework fabrication: A systematic review

Statement of problemRemovable partial dentures (RPDs) are traditionally made by casting, a complex, error-prone, and time-consuming process. Computer-aided design and computer-aided manufacturing (CAD-CAM) RPD systems may simplify the clinical steps and minimize errors; however, the accuracy of CAD-CAM RPD systems is unclear.PurposeThe purpose of this systematic review was to determine whether CAD-CAM systems are accurate for the manufacturing of RPD frameworks.Material and methodsA literature search was conducted through Medline-PubMed, Scopus, Lilacs, Web of Science, and Cochrane Library databases using specific keywords for articles published up to November 2019. Three reviewers obtained data and compared the results. All studies evaluated the framework accuracy or fit of prostheses fabricated with conventional and digital techniques.ResultsA total of 7 articles, 2 clinical studies, and 5 in vitro studies that complied with the inclusion criteria were evaluated. One in vitro study compared indirect (extraoral) and direct (intraoral) scanning for partially edentulous ridges and shows that digital scans were better than conventional impressions in terms of trueness. In the other studies included, although the frameworks analyzed had clinically acceptable discrepancies (<311 μm), the material influenced the fit. Polyetheretherketone (PEEK) showed better fit than traditional metal cast RPDs. Co-Cr alloy RPDs produced by rapid prototyping exhibited the highest discrepancies when produced by sintering laser melting.ConclusionsThe results show that the digital technique for RPD frameworks is accurate. In the studies included, the analyzed frameworks had clinically acceptable gaps, but the results were heterogeneous among studies because the articles used different measurement methods with small sample sizes. Few studies discussed the long-term clinical performance. The digital technique for RPD frameworks was accurate because the misfits and mismatches found in in vitro and clinical studies were within the acceptable clinical limit for RPDs.     

Minimal tooth preparation for posterior monolithic ceramic crowns: Effect on the mechanical behavior,reliability and translucency

ObjectiveDespite the increased use of monolithic crowns, their performance has yet to be determined when the minimal tooth preparation (MTP) principle is considered. The goal of this study was to evaluate the effect of MTP on the mechanical behavior, reliability and translucency of posterior monolithic ceramic crowns.MethodsDentin analogues were machined using two preparation designs (0.5 or 1 mm reduction) to receive first molar crowns in order to evaluate the monolithic crown performance. Next, 126 crowns were divided (21/g) according to the material (High translucent zirconia – YZHT, Zirconia reinforced lithium silicate – ZLS and Hybrid ceramic – HC) and thickness (0.5 or 1 mm). Tensile stress concentration was calculated using the finite element method. The crowns were adhesivelly cemented and step stress fatigued to calculate reliability for missions at 600 and 1000 N. Translucency was analyzed in 10 discs of each material and thickness.ResultsHigher stress concentration was found in thinner crowns and those with higher elastic modulus. YZHT crowns were suspended when fatigue reached 1500 N load, thus 1-parameter Weibull was used to analyze the data. Reliability was only affected by thickness at 1000 N. ZLS.5 showed lower survival than HC.5, which was similar to the groups that presented 100% survival. YZHT showed the highest strength and data scattering. ZLS1 (22.3 ± 1.4) presented higher translucency than HC1 (19.2 ± 0.6) and YZHT1 (12.0 ± 2.9), whereas ZLS.5 and HC.5 were similar to each other (26.5 ± 2.3, 26.7 ± 2.2) and superior to YZHT.5 (12.7 ± 1.2).SignificanceHC.5 combined high reliability and translucency with low stress concentration, yielding better crown performance and tooth preservation.