Bartlettdreyer6985
Treatment-resistant schizophrenia may be related to structural brain alterations. However, the mechanisms underlying these changes remain unclear. The present study had two main aims (1) to explore differences in cortical thickness between patients with treatment-resistant schizophrenia non-responsive to clozapine (ultra-treatment-resistant schizophrenia, UTRS), patients with treatment-resistant schizophrenia responsive to clozapine (Cloz-Resp), patients responsive to first-line non-clozapine antipsychotics (FL-Resp), and healthy controls (HCs); and (2) to test our hypothesis of structural compromise as a manifestation of neurotoxic effects from elevated glutamate (Glu) (i.e. glutamate-mediated excitotoxicity) by examining the relationships between glutamatergic neurometabolite levels (Glu and glutamate + glutamine (Glx)) in the dorsal anterior cingulate cortex (dACC) and cortical thickness. T1-weighted images and 1H-MRS data were obtained from UTRS (n = 24), Cloz-Resp (n = 25), FL-Resp (n = 19), and HCs (n = 26). Vertex-wise analyses showed that patients with UTRS had widespread cortical thinning in the bilateral frontal, temporal, parietal, and occipital gyri compared to HCs and FL-Resp patients. In the patient group, negative associations were found between dACC Glx levels and cortical thickness in the right dorsolateral prefrontal cortex after correcting for multiple comparisons and controlling for age, sex, antipsychotic dose, and illness severity. In conclusion, glutamate-mediated excitotoxicity may be one of the mechanisms underlying structural compromise seen in treatment-resistant schizophrenia. Future studies should longitudinally examine the associations between glutamatergic neurometabolite levels and cortical thickness in the context of treatment and illness progression. PURPOSE To investigate the experiences of adults living with chronic myeloid leukaemia and treated with tyrosine kinase inhibitors, with particular reference to factors influencing adherence. METHODS A thematic synthesis of all published qualitative studies examining adults with chronic myeloid leukaemia, receiving tyrosine kinase inhibitors. Eligible publications were identified by searching five electronic databases using defined criteria. The synthesis involved complete coding of extracted data and inductive theme development. RESULTS Nine studies were included and three overarching themes defined. Overarching themes were 1) Disease impacts whole life; 2) Disease management strategies; and 3) Valued aspects of care. Side-effects often required physical and psychological adaptation. Patients developed individual decision-making processes to promote adherence and manage side effects. Unintentional non-adherence occurred due to forgetfulness and system failures. Intentional omission also occurred, which together with side effects, was unlikely to be reported to healthcare professionals (HCPs). HCP reassurance about missed doses could reinforce non-adherence. Information needs varied over time and between individuals. Knowledge among patients about treatment was often lacking and could lead to misunderstandings. Patients valued psychological support from HCPs and suggested an individualised approach, facilitating discussion of symptoms, adherence and their perspectives about living with chronic myeloid leukaemia, would improve care. CONCLUSIONS Patients with chronic myeloid leukaemia experienced significant side-effects from treatment and changes to their psychological and physical well-being. They developed their own strategies to manage their disease and treatment. This should be recognised in interventions to improve education, support and the delivery of care that is compassionate and adequately resourced. Crown All rights reserved.OBJECTIVES It is established that resistance to rifampicin (RIF) in 90% of the RIF resistantM. tuberculosis strains is attributable to point mutations in the rpoB gene while 50-95% of M. tuberculosis resistance to isoniazid (INH) is caused by mutations in katG gene. However, the patterns and frequencies of mutations vary with geographical differences. In Zambia, the genetic resistance of M. tuberculosis to RIF and INH were unreported before this study. METHODS Using sequencing, we analyzed rpoB, katG and inhA genes for 99 multidrug-resistant (MDR) and 49 pan-susceptible M. tuberculosis isolates stored at a tuberculosis reference laboratory from 2013 to 2016 and compared with published profiles from other African countries. RESULTS Ninety six percent (95/99) of the MDR-TB isolates carried mutations in bothrpoB and katG genes. No mutations were detected among the pan-susceptible isolates. rpoB gene codon 531 and katG gene codon 315 at 55.6 % (55/99) and 94.9 % (94/99) were the most altered among the RIF and INH resistant isolates, respectively. Distinctly, katG mutations were predominantly high among Zambian isolates (96%) compared to other countries in the region. CONCLUSION The drug resistant associated mutations to RIF and INH circulating in Zambia are similar to what have been reported globally, therefore our data validates the applicability of molecular diagnostic tools in Zambia. However,katG mutations were predominantly high among M. tuberculosis isolates in this study compared to other regional countries and might disassociate cross-boundary transmission of MDR-TB from other African nations. OBJECTIVES Biofilm -forming capacity of Staphylococcus aureus (S. aureus) as a commensal opportunistic bacterial species induce a growth in antibiotic resistance in chronic diseases. Since expression of biofilm- related genes and antibiotic resistance function are interdependent, the present study was an attempt to inquire biofilm formation and its relationship with antibiotic resistance in clinical isolates. METHODS 208 S. aureus clinical isolates from four major provinces of Iran were investigated in terms of presence of adhesion genes (icaA, icaD, icaB, icaC, fnbpA, fnbpB, clfA, clfB, cna, sasC, sasG and bap) using PCR. In addition, microtiter plate (Mtp) assay was performed to examine quantitative biofilm formation of the isolates and their antibiotic resistance patterns against 16 antibiotics determined upon CLSI criteria. selleck RESULTS The results revealed high prevalence rate (almost 100%) of icaADBC and MSCRAMMs genes in the isolates. Moreover, bap gene was not detected in any of the tested clinical isolates.