Vulnerability and suffering in the work of a community health agent in the family health program

This qualitative research was aimed at investigating the representations and significations that a group of community health agents (CHAs) has concerning the vulnerabilities for suffering in their work to which they are exposed to, as well as the manifestations of this suffering as they perform their actions in the Family Health Program (PSF, in the Portuguese language acronym). The semistructured interview with the group of agents explored the meaning of being a CHA and their perception of their work organization; the analysis was based on the hermeneutics theoretical-methodology referential and on the theories related to labor psychodynamics. The findings show the existence of considerable suffering vulnerability, generated by an idealized ideation of the practice and by the scarce perspective for rearranging the constitutive ingredients of work organization, since these professionals depend on factors that are beyond their grasp, which include the limitations of the assistential model proposed by the PSF.     

Genetic profiling in healthy subjects from the Stanislas cohort based on 24 polymorphisms: effects on biological variables.

BACKGROUND: The association of genetic profiles with biological or clinical assessments is not clearly established especially among apparently healthy subjects. METHODS: A multivariate statistical analysis was performed on 24 polymorphisms related to the main metabolic pathways involved in cardiovascular diseases (CVDs). They were collected among 1551 healthy subjects of the Stanislas cohort to obtain genetic profiles. Association with biological variables was then studied at baseline (t0) and 5 years later (t5). RESULTS: Six genetic clusters were identified with relevant profiles and five polymorphisms from the selectin, apolipoprotein C3 and lipoprotein lipase genes (SELE-98G/T, APOC3-3175C/G, APOC3-482C/T, APOC3-1100C/T, LPL-93T/G) were sufficiently characteristic to associate 99.6% of the subjects with their corresponding cluster. A 5-year follow-up showed that clinical and biological measurements in relation to CVD risk factors already differ with triglyceride (p=0.009 for t0 and p=0.005 for t5) and high-density lipoprotein cholesterol (p=0.014 for t0 and p=0.003 for t5) for these previous genetic clusters. CONCLUSIONS: This study presents the hypothesis that SELE could be protective, whereas APOC3 could be associated with risk. It remains to be seen whether these polymorphisms will be predictive of CVD events among the selected clusters of different metabolic subtypes after a 10-year follow-up.     

Asiatic acid and corosolic acid enhance the susceptibility of Pseudomonas aeruginosa biofilms to tobramycin

Asiatic acid and corosolic acid are two natural products identified as biofilm inhibitors in a biofilm inhibition assay. We evaluated the activities of these two compounds on Pseudomonas aeruginosa biofilms grown in rotating disk reactors (RDRs) in combination with tobramycin and ciprofloxacin. To determine the ruggedness of our systems, the antibiotic susceptibilities of these biofilms were assessed with tobramycin and ciprofloxacin. The biofilm bacteria produced in the RDR were shown to display remarkable tolerance to 10 mug/ml of ciprofloxacin, thus mimicking the tolerance observed in recalcitrant bacterial infections. These studies further demonstrate that a nonmucoid strain of P. aeruginosa can form a biofilm that tolerates ciprofloxacin at clinically relevant concentrations. Neither asiatic acid nor corosolic acid reduced the viable cell density of P. aeruginosa biofilms. However, both compounds increased the susceptibility of biofilm bacteria to subsequent treatment with tobramycin, suggesting asiatic acid and corosolic acid to be compounds that potentiate the activity of antibiotics. A similar statistical interaction was observed between ciprofloxacin and subsequent treatment with tobramycin.     

Haptoglobin phenotype and risk of cervical neoplasia: a case-control study

BACKGROUND: Haptoglobin is an acute-phase glycoprotein that influences host response to infections and tumours. The haptoglobin locus is polymorphic with 2 classes of alleles (Hp(1) and Hp(2)) yielding 3 phenotypes: Hp1-1, Hp2-2, and Hp2-1 with structurally and functionally distinct protein products, suggesting that haptoglobin polymorphism may influence susceptibility to infections and cancers. METHODS: We examined the relation between haptoglobin phenotype and high-grade cervical intraepithelial neoplasia (CIN) in a hospital-based case-control study. Cases (n = 307) were women with biopsy-confirmed CIN-2 or CIN-3. Controls (n = 358) were a random sample of women with normal cytology. The PGMY polymerase chain reaction and reverse line blot methods were used for HPV detection and genotyping. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis. RESULTS: Among controls, phenotype distribution corresponded to allele frequencies of 0.39 for Hp(1) and 0.61 for Hp(2) with no significant deviation from the Hardy-Weinberg equilibrium (p=0.66). With all women included in the analysis, the Hp1-1 phenotype was associated with increased risk of CIN (OR contrasting Hp1-1 vs. Hp2-2 = 1.0; 95% CI: 0.6-1.5). However, in analyses restricted to HPV-positive participants, the Hp1-1 phenotype was associated with 2.7-fold (95% CI: 1.0-7.2) higher risk of CIN. CONCLUSIONS: If confirmed, these findings indicate an increased risk of CIN among women with the Hp1-1 phenotype.     

The influence of glucocorticoid receptor single nucleotide polymorphisms on outcome after haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation (HSCT) remains the only cure for most haematological malignancies, however, the mortality rate remains high. Complications after HSCT include relapse, graft versus host disease (GvHD), graft rejection and infection. Over the last few years several groups, have demonstrated that non‐HLA gene polymorphisms can be predictive of outcome after HSCT. Since the glucocorticoid cortisol is pivotal in the regulation of the immune system, we decided to examine single nucleotide polymorphisms (SNPs; rs6198, rs33388 and rs33389) within the glucocorticoid receptor (GR) and correlate with HSCT outcome. The training set consisted of patients (n = 458) who underwent HSCT for acute leukaemia between 1983 and 2005. In the recipients, the absence of the ACT haplotype and absence of the T allele of rs33388 were associated with decreased OS and the absence of the ACT haplotype, the absence of the T allele of rs33388 and the presence of the ATA haplotype were associated with increased risk of relapse. In addition, the presence of the ACT haplotype in the recipient showed a trend to be associated with increased risk of chronic graft versus host disease (cGvHD). The patients in this cohort received mainly myeloablative conditioning (n = 327). The SNPs in the glucocorticoid receptor were then investigated in a validation set (n = 251) of HSCT patients transplanted for acute leukaemia from 2006. This cohort contained significantly more patients that had received reduced intensity conditioning (RIC). Some of the results could be validated in these patients. However, contrary to the training set, the absence of the haplotype ACT in the donor in this cohort was associated with increased risk of cGvHD. Differences in the conditioning were shown to influence the results. These results are the first to associate GR SNPs with HSCT outcome and demonstrate the inherent problems of replicating SNP association studies in HSCT, due to different pre‐transplant regimens.     

Human hepatic stem cells from fetal and postnatal donors

Human hepatic stem cells (hHpSCs), which are pluripotent precursors of hepatoblasts and thence of hepatocytic and biliary epithelia, are located in ductal plates in fetal livers and in Canals of Hering in adult livers. They can be isolated by immunoselection for epithelial cell adhesion molecule-positive (EpCAM+) cells, and they constitute approximately 0.5-2.5% of liver parenchyma of all donor ages. The self-renewal capacity of hHpSCs is indicated by phenotypic stability after expansion for >150 population doublings in a serum-free, defined medium and with a doubling time of approximately 36 h. Survival and proliferation of hHpSCs require paracrine signaling by hepatic stellate cells and/or angioblasts that coisolate with them. The hHpSCs are approximately 9 microm in diameter, express cytokeratins 8, 18, and 19, CD133/1, telomerase, CD44H, claudin 3, and albumin (weakly). They are negative for alpha-fetoprotein (AFP), intercellular adhesion molecule (ICAM) 1, and for markers of adult liver cells (cytochrome P450s), hemopoietic cells (CD45), and mesenchymal cells (vascular endothelial growth factor receptor and desmin). If transferred to STO feeders, hHpSCs give rise to hepatoblasts, which are recognizable by cordlike colony morphology and up-regulation of AFP, P4503A7, and ICAM1. Transplantation of freshly isolated EpCAM+ cells or of hHpSCs expanded in culture into NOD/SCID mice results in mature liver tissue expressing human-specific proteins. The hHpSCs are candidates for liver cell therapies.     

Intracranial EEG potentials estimated from MEG sources: A new approach to correlate MEG and iEEG data in epilepsy

Detection of epileptic spikes in MagnetoEncephaloGraphy (MEG) requires synchronized neuronal activity over a minimum of 4cm2. We previously validated the Maximum Entropy on the Mean (MEM) as a source localization able to recover the spatial extent of the epileptic spike generators. The purpose of this study was to evaluate quantitatively, using intracranial EEG (iEEG), the spatial extent recovered from MEG sources by estimating iEEG potentials generated by these MEG sources. We evaluated five patients with focal epilepsy who had a pre‐operative MEG acquisition and iEEG with MRI‐compatible electrodes. Individual MEG epileptic spikes were localized along the cortical surface segmented from a pre‐operative MRI, which was co‐registered with the MRI obtained with iEEG electrodes in place for identification of iEEG contacts. An iEEG forward model estimated the influence of every dipolar source of the cortical surface on each iEEG contact. This iEEG forward model was applied to MEG sources to estimate iEEG potentials that would have been generated by these sources. MEG‐estimated iEEG potentials were compared with measured iEEG potentials using four source localization methods: two variants of MEM and two standard methods equivalent to minimum norm and LORETA estimates. Our results demonstrated an excellent MEG/iEEG correspondence in the presumed focus for four out of five patients. In one patient, the deep generator identified in iEEG could not be localized in MEG. MEG‐estimated iEEG potentials is a promising method to evaluate which MEG sources could be retrieved and validated with iEEG data, providing accurate results especially when applied to MEM localizations. Hum Brain Mapp 37:1661–1683, 2016. © 2016 Wiley Periodicals, Inc .     

Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome

Journal of Clinical Immunology - Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the...