Study of KIR expression and HLA ligands in CD56+ lymphocytes of drug resistant tuberculosis patients

Analysis of receptor-ligand interactions in the context of diseases necessitates to understand how HLA-KIR genotypes function in diseases. Although CD56+ lymphocytes are derived from multiple lineages, they share a functional association with immunosurviellance and antimicrobial responses. The present study aimed to determine whether KIR phenotype in CD56 lymphocytes and corresponding HLA-class 1 ligands are associated with multidrug resistance tuberculosis (MDR-TB). We compared the frequencies of HLA-C and HLA-BW4 genes, the expression of KIRs 2DL1/2DS1, 2DL2/2DL3, 3DL1, and 2DS4 and the combinations of HLA/KIR in 32 Nifamycin and Isoniazid-resistant TB with those in 68 drug non resistant (NR) sputum smear positive pulmonary TB patients. PCR-SSP and flow cytometry were performed for HLA and KIRs typing, respectively. We showed no significant differences between inhibitory or activating KIRs as well as HLA ligands in MDR TB patients compared with NR-TB . The combinations of inhibitory KIR-HLA ligands in MDR-TB were much more prevalent, but not statistically significant than in NR patients (p=0.07). The frequency of MDR patients with all HLA-C and HLA-BW4 ligands was higher than NR-TB (p<0.009). Conversely, the percentage of MDR patients having only one kind of HLA gene was significantly lower than NR-TB (p<0.01). We conclude that the expression of inhibitory KIRs with corresponding HLA ligands genes, and/or co-existence of three HLA class 1 ligands for inhibitory KIRs may be associated with drug resistance in pulmonary tuberculosis.     

Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression

Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chronically self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted metabolic mapping, where DREADD indicates designer receptors exclusively activated by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect–related physiological and behavioral changes. Altogether, our translational study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability.     

Effectiveness of Therapeutic Exercise on Forward Head Posture: A Systematic Review and Meta-analysis

Objective

The purpose of this systematic review and meta-analysis was to summarize the results related to the effects of corrective exercises on postural variables in individuals with forward head posture (FHP).

Treatment of multiple drug-resistant tuberculosis (MDR-TB) in Iran.

SETTING: Masih Daneshvari Hospital, Tehran, Iran, 2000-2002. OBJECTIVE: To evaluate the effectiveness of multiple drug-resistant tuberculosis (MDR-TB) treatment for the first time in Iran. DESIGN: All cases of MDR-TB with complete follow-up data were recruited and results of their treatments were evaluated. RESULTS: MDR-TB treatment was initiated with 5.23 drugs, on average. Isoniazid, amikacin, and ofloxacin were present in the drug regimen of all patients. Average duration of the treatment was 18.5 months (range, 7-36). Over 76% of the patients responded to the treatment (negative smear and culture). Cure and probable cure were documented in seven (41.2%) and four (23.5%) of the patients, respectively. No failure in the treatment occurred when cycloserine was present in the treatment regimen. CONCLUSION: A majority of the MDR-TB patients in Iran can be cured with the use of appropriate treatment regimens. An even greater success could be achieved by providing more second-line drugs.     

Transient telomere dysfunction induces chromosomal instability and promotes carcinogenesis

Telomere shortening limits the proliferative capacity of a cell, but perhaps surprisingly, shortening is also known to be associated with increased rates of tumor initiation. A current hypothesis suggests that telomere dysfunction increases tumor initiation by induction of chromosomal instability, but that initiated tumors need to reactivate telomerase for genome stabilization and tumor progression. This concept has not been tested in vivo, since appropriate mouse models were lacking. Here, we analyzed hepatocarcinogenesis in a mouse model of inducible telomere dysfunction on a telomerase-proficient background, in telomerase knockout mice with chronic telomere dysfunction (G3 mTerc-/-), and in WT mice with functional telomeres and telomerase. Transient or chronic telomere dysfunction enhanced the rates of chromosomal aberrations during hepatocarcinogenesis, but only telomerase-proficient mice exhibited significantly increased rates of macroscopic tumor formation in response to telomere dysfunction. In contrast, telomere dysfunction resulted in pronounced accumulation of DNA damage, cell-cycle arrest, and apoptosis in telomerase-deficient liver tumors. Together, these data provide in vivo evidence that transient telomere dysfunction during early or late stages of tumorigenesis promotes chromosomal instability and carcinogenesis in telomerase-proficient mice.     

Frequency and distribution of asymptomatic brain lesions in patients with β-thalassemia intermedia

We aimed to determine the frequency of asymptomatic brain lesions in a group of patients with β-thalassemia intermedia (β-TI) and to evaluate correlation of asymptomatic brain lesions with splenectomy, thrombocytosis, blood transfusions, and clinical parameters. Ninety five neurologically intact patients with β-TI were randomly enrolled in this cross-sectional study. Diffusion-weighted imaging brain MRI was performed in every patient to detect cerebral white matter lesions (WML). We found an overall frequency of 15 (15.8?%) for WMLs, 14 (23.7?%) in splenectomized, and 1 (2.8?%) in nonsplenectomized patients. The presence of WML was significantly associated with splenectomy (P?=?0.008) and thrombocytosis (P?=?0.009). However, after adjustment for splenectomy, thrombocytosis was not significantly associated with the presence of WML (P?>?0.05). The number of patients with regular blood transfusions and normal MRI was not significantly higher compared to those with abnormal findings (52.5?% vs. 26.7?%; P?=?0.092). In untransfused patients, hydroxyurea (HU) administration was associated with a lower incidence of WML (P?<?0.001). Although in univariate analysis either splenectomy or thrombocytosis showed significant correlation with the presence of single or multiple WMLs, thrombocytosis by itself did not significantly contribute in developing asymptomatic brain lesions. The lack of significant correlation between lesions and regular blood transfusions could be related to the treatment with HU in untransfused patients, which increased fetal hemoglobin levels and improved the morphology and the pathological indices of the red blood cells. Larger prospective studies are suggested for the accurate evaluation of the correlation of these factors with developing asymptomatic brain lesions.     

Social Epidemiology of Diabetes and Associated Conditions

Research focusing on the social determinants of diabetes has focused on individual-level factors such as health behaviors, socioeconomic status, and depression. Fewer studies that incorporate a broader consideration of the multiple contexts or organizational levels (eg, family, health care setting, neighborhood) within which individuals are embedded exist in the mainstream diabetes literature. Such an approach would enhance our understanding of this complex disease, and thus, future avenues of research should consider the following: (1) a life-course approach, which examines the influence of early life exposures on the development of diabetes; (2) aiming to understand the biological mechanisms of social determinants of diabetes; and (3) implementing interventions on multiple levels. Integrating this multilevel and life-course approach will require transdisciplinary science that brings together highly specialized expertise from multiple disciplines. Broadening the study of social determinants is a necessary step toward improving the prevention and treatment of type 2 diabetes.     

Brown adipose tissue and alzheimer’s disease

Metabolic Brain Disease - Alzheimer’s disease (AD), the most common type of senile dementia, is a chronic neurodegenerative disease characterized by cognitive dysfunction and behavioral...     

Fatal disseminated infection due to Sarocladium kiliense in a diabetic patient with COVID‐19

Sarocladium kiliense is a soil saprophytic mold with worldwide distribution, which can infect humans and other mammals, sporadically. The clinical manifestations include mycetoma, onychomycosis, keratomycosis, pneumonia, and arthritis. Here, we present a disseminated infection due to S. kiliense in a diabetic patient infected to coronavirus disease 2019 (COVID‐19) from Isfahan, Iran.     

Management of internal root resorption in the maxillary central incisor with fractured root using Biodentine

Biodentine is desirable to successfully manage internal root resorption, and the MTA apical plug backfilled with thermoplasticized gutta‐percha is suggested for the tooth with external apical root resorption.