Search

Introduction: Pyrazinamide (PZA) susceptibility testing plays a critical role in determining the appropriate treatment regimens for multidrug-resistant tuberculosis. We conducted a systematic revie...

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) represents an urgent threat worldwide. We aimed to investigate the frequency of carbapenem-resistant Klebsiella pneumoniae and Escherichi...

Multiple sclerosis is an autoimmune disease of the central nervous system with symptoms of neurodegenerative diseases. The symptoms vary depending on damage location. Some of the symptoms include cognitive disorders, anxiety and depression, visual impairment, respiratory, speech and swallowing disorders, muscle spasm and fatigue. Due to the lack of a definitive treatment method, various therapeutic approaches are proposed to control the disease. Drugs are classified into attack control drugs, complication control drugs and disease-modifying drugs. Vitamin D is a hormone-like steroidal compound with immune modulatory and anti-inflammatory properties. Vitamin D deficiency is associated with a variety of inflammatory, neurologic and autoimmune diseases. Many studies on patients as well as experimental autoimmune encephalomyelitis studies have shown that the administration of vitamin D reduces inflammation in inflammatory diseases of the central nervous system. As argued, vitamin D level was significantly lower in MS compared to healthy subjects as controls. Also, a higher level of vitamin D is reported in relapsing-remitting MS patients compared to patients with progressive MS. It is observed that higher serum levels of vitamin D can reduce the severity of symptoms, progress, and also delays the relapses. Few studies considered vitamin D to be ineffective in stopping or inhibition the disease. Despite the controversies concerning the role of vitamin D in MS progress, there is a lot of interest in further research in this regard with the hope of reaching a common ground. Therefore, frequent reviews of past and recent studies are essential to achieve the same results.

Conventional culture-based drug susceptibility testing (DST) of Mycobacterium tuberculosis to pyrazinamide (PZA) is time-consuming and difficult to perform. The current systematic review and meta-analysis was aimed to evaluate the diagnostic accuracy of Wayne assay against culture-based DSTs as the reference standard. We searched the MEDLINE/Pubmed, Embase, and Web of Science databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures (i.e., sensitivity and specificity) were pooled with a random-effects model. Statistical analyses were performed with STATA (version 14, Stata Corporation, College Station, TX, USA), RevMan (version 5.3; The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark), and Meta-DiSc (version 1.4, Cochrane Colloquium, Barcelona, Spain). A total of 31 articles comprising data for 2457 isolates of M. tuberculosis were included in the final analysis. The pooled sensitivity and specificity of the Wayne assay against all reference tests (the combination of BACTEC MGIT 960, BACTEC 460, and proportion method) were 86.6% (95% CI: 84.3-88.7) and 96.0% (95% CI: 94.8-97). The positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) estimates were found to be 17.6 (95% CI: 10.5-29.3), 0.11 (95% CI: 0.06-0.20), 164 (95% CI: 83-320) and 97%, respectively. Deek's test result indicated no evidence for publication bias (P > 0.05). Although the current study shows that the Wayne test is sensitive and specific for detecting PZA resistance, it may be used in combination with conventional DSTs to diagnose PZA resistance accurately.

Mutations of mutS and mutL genes have been linked with the emergence of hypermutator (HPM) phenotype in several bacteria. Nevertheless, there is scarce evidence that these mutations occurred in HPM Acinetobacter baumannii, therefore, it remains unknown whether the mutations located in domains mediating the functions of MutS and MutL. To address this information gap, the nucleotide sequences of mutS and mutL were characterized and their mutations were identified. Additionally, we proposed in silico models of mutated proteins and analyzed the secondary and tertiary structures, and the interaction interfaces of MutL and MutS. The HPM A. baumannii and a wild-type strain were subjected to PCR amplification of full length mutS and mutL, cloning, and sequencing. Following several reads of both strands of each gene and sequence assembly, the mutations were identified. Thereafter, the three-dimensional (3-D) structure of A. baumannii ATCC 19606 was developed and utilized as a template for homology modeling of the mutated amino acid sequences using the Phyre2 and I-TASSER, VMD 1.9.3, LigPlus v.1.4.5, PyMOL v.0.99 software. Regardless of silent mutations (n = 43), 11 missense mutations were identified in the MutS domains of HPM strain such as A4T, T272S, D278N in N-terminus, connector, and core domains, respectively. Three mutations -I357T, A408S, N447S- and 16 silent mutations were observed in MutL. Secondary structure prediction of MutS revealed that the amount of alpha helices, beta sheets, and coils in HPM were 35, 29, and 63, respectively, while these values were 36, 28, and 63 for A. baumannii ATCC 19606 as non mutator. In the case of MutL, for both HPM and non-mutator, 20, 21, and 39 of complete protein were alpha helices, beta sheets, and coils, respectively. Superimposition of structures of MutS of HPM on non-mutator revealed that T272, D278, G457, S528, A533, Y715, and E747 are closely matched with S272, D278, A457, P528, V533, C715, and K747, respectively in non-mutator strain. When the structure of MutL model in HPM was superimposed on its counterpart in non-mutator, all but residues S447, S408, and T357 were identical. Many mutations along the mutS and mutL were noted, but most of the mutations were observed in the interaction interfaces of MutS and MutL. Other substitutions were predominantly detected in C-terminus of MutS that may lead to reduced ATP binding and hydrolysis. Three substitution mutations were adjacent to C-terminus of MutL and are raising the suggestion of reduction in MutL dimerization. It seems that a combination of these mutations is implicated in increased mutation frequency and accordingly emergence of HPM strain.