Molecular evolution and population genetics of glutamate decarboxylase acid resistance pathway in lactic acid bacteria.

Glutamate decarboxylase (GAD) pathway (GDP) is a major acid resistance mechanism enabling microorganisms' survival in low pH environments. We aimed to study the molecular evolution and population genetics of GDP in Lactic Acid Bacteria (LAB) to understand evolutionary processes shaping adaptation to acidic environments comparing species where the GDP genes are organized in an operon structure (Levilactobacillus brevis) versus lack of an operon structure (Lactiplantibacillus plantarum). Within species molecular population genetic analyses of GDP genes in L. brevis and L. plantarum sampled from diverse fermented food and other environments showed abundant synonymous and non-synonymous nucleotide diversity, mostly driven by low frequency changes, distributed throughout the coding regions for all genes in both species. GAD genes showed higher level of replacement polymorphism compared to transporter genes (gadC and YjeM) for both species, and GAD genes that are outside of an operon structure showed even higher level of replacement polymorphism. Population genetic tests suggest negative selection against replacement changes in all genes. Molecular structure and amino acid characteristics analyses showed that in none of the GDP genes replacement changes alter 3D structure or charge distribution supporting negative selection against non-conservative amino acid changes. Phylogenetic and between species divergence analyses suggested adaptive protein evolution on GDP genes comparing phylogenetically distant species, but conservative evolution comparing closely related species. GDP genes within an operon structure showed slower molecular evolution and higher conservation. All GAD and transporter genes showed high codon usage bias in examined LAB species suggesting high expression and utilization of acid resistance genes. Substantial discordances between species, GAD, and transporter gene tree topologies were observed suggesting molecular evolution of GDP genes do not follow speciation events. Distribution of operon structure on the species tree suggested multiple independent gain or loss of operon structure in LABs. In conclusion, GDP genes in LABs exhibit a dynamic molecular evolutionary history shaped by gene loss, gene transfer, negative and positive selection to maintain its active role in acid resistance mechanism, and enable organisms to thrive in acidic environments.

The importance of neopterin in COVID-19: The prognostic value and relation with the disease severity.

Coronavirus Disease 2019 [COVID-19], caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], has rapidly evolved into a global health emergency. Neopterin [NPT], produced by macrophages when stimulated with interferon [IFN-]gamma, is an essential cytokine in the antiviral immune response. NPT has been used as a marker for the early assessment of disease severity in different diseases. The leading cause of NPT production is the pro-inflammatory cytokine IFN-. Macrophage activation has also been revealed to be linked with disease severity in SARS-CoV-2 patients. We demonstrate the importance of NPT in the pathogenesis of SARS-CoV-2 and suggest that targeting NPT in SARS-CoV-2 infection may be critical in the early prediction of disease progression and provision of timely management of infected individuals.

Dosimetric evaluation of left ventricle and left anterior descending artery in left breast radiotherapy.

INTRODUCTION: We evaluated the dosimetric results of the identification of the left ventricle (LV) and left anterior descending artery (LAD) as organs at risk (OARs) in adjuvant radiotherapy (RT) after breast-conserving surgery (BCS). MATERIALS AND METHODS: Twenty-two patients who had previously received RT in our center were evaluated retrospectively. All patients had undergone BCS operation for left breast cancer. LV and LAD were contoured as OARs on the same simulation CTs for these patients whose treatment was previously completed in which LV and LAD were not defined as OARs. Complying with the initial plans, intensity-modulated RT plans with 7-9 fields were made on the computer. Planning target volume (PTV), homogeneity index (HI), conformity index (CI), monitor unit (MU) values, and doses of OARs were compared using the Wilcoxon signed-rank test (p < 0.05). RESULTS: There were no significant differences in PTV 50 (D 50% and D 98%), PTV 60 (D 2% and D 50%), HI, CI, and MU values when treatment plans and control plans were compared (p > 0.05). While it was possible to protect the heart, LAD, and LV better, LAD and LV were not contoured in the treatment plans, and they received higher doses compared to the control plans (p < 0.05). There was no significant difference in the other OARs. CONCLUSION: In conclusion, it is essential to define the lower anatomical regions of the heart as OARs. Otherwise, the doses taken by these regions are ignored and may be maintained less than possible. In our study, it was shown that LV and LAD doses were significantly reduced even in the same center and planning by the same team.

Expectations in patients with total knee arthroplasty.

OBJECTIVE: The primary objective of total knee arthroplasty (TKA) is to decrease pain and restore functional knee joint. Current hypotheses indicate higher knee flexion is required in terms of life style, culture and expectations in Eastern communities. Therefore, society-specific features related to life style and cultural habits are needed. The objective of this study was to investigate the expectations of patients undergoing TKA. METHODS: The study included 131 patients (18 male, 113 female; mean age: 66.2 ± 8.3 years) who underwent cemented TKA due to knee osteoarthritis. All patients were operated by the same surgeon using the same implant and surgical technique. Patients were evaluated using the Hospital for Special Surgery (HSS) knee score, a 15-item clinical knee assessment questionnaire and the HSS knee arthroplasty expectation questionnaire. RESULTS: Mean HSS score for the right knee was 89.2 ± 10.5 and for the left knee was 89.6 ± 9.4. The two most expected outcomes were improvements in pain (99.2%) and gait (96.2%) and the two least expected outcomes were improvements in psychological well-being (22.9%) and communicative skills (35.1%). Expectations were not affected by education and working conditions. CONCLUSION: Patients' most expected outcomes were improvement in pain and restoration of function (gait, climbing stairs and no need of assistive devices), similar to Western and American communities.