Beneficial Mitochondrial Biogenesis in Gastrocnemius Muscle Promoted by High-Intensity Interval Training in Elderly Female Rats.

OBJECTIVE: Exercise can attenuate mitochondrial dysfunction caused by aging. Our study aimed to compare 12 weeks of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the expression of mitochondria proteins [e.g., AMP-activated protein kinase (AMPK), Estrogen-related receptor alpha (ERRα), p38 mitogen-activated protein kinase (P38MAPK), and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α)] in gastrocnemius muscle of old female rats. MATERIALS AND METHODS: In this experimental study, thirty six old female Wistar rats (18-month-old and 270-310 g) were divided into three groups: i. HIIT, ii. MICT, and iii. Control group (C). The HIIT protocol was performed for 12 weeks with 16-28 minutes (2 minutes training with 85-90% VO2max in high intensity and 2 minutes training with 45-75% VO2max low intensity). The MICT was performed for 30-60 minutes with the intensity of 65-70% VO2max. The gastrocnemius muscle expression of AMPK, ERRα, P38MAPK, and PGC1α proteins were determined by Western blotting. RESULTS: The expression of AMPK (P=0.004), P38MAPK (P=0.003), PGC-1α (P=0.028), and ERRα (P=0.006) in HIIT was higher than C group. AMPK (P=0.03), P38MAPK (P=0.032), PGC-1α (P=0.015), and ERRα (P=0.028) in MICT was higher than the C group. Also expression of AMPK (P=0.008), P38MAPK (P=0.009), PGC-1α (P=0.020) and ERRα (P=0.014) in MICT was higher than MICT group. CONCLUSION: It seems that exercise training has beneficial effects on mitochondrial biogenesis, but the HIIT training method is more effective than MICT in improving mitochondrial function in aging.

Preinvasive Colorectal Lesions of African Americans Display an Immunosuppressive Signature Compared to Caucasian Americans.

BACKGROUND: African Americans (AAs) have higher colorectal cancer (CRC) incidence and mortality rate than Caucasian Americans (CAs). Recent studies suggest that immune responses within CRCs contribute to the disparities. If racially distinct immune signatures are present in the early phases of carcinogenesis, they could be used to develop interventions to prevent or slow disease. METHODS: We selected a convenience sample of 95 patients (48 CAs, 47 AAs) with preinvasive colorectal adenomas from the surgical pathology laboratory at the Medical University of South Carolina. Using immunofluorescent-conjugated antibodies on tissue slides from the lesions, we quantified specific immune cell populations: mast cells (CD117+), Th17 cells (CD4+RORC+), and NK cell ligand (MICA/B) and inflammatory cytokines, including IL-6, IL-17A, and IFN-γ. We compared the mean density counts (MDCs) and density rate ratios (RR) and 95% CI of immune markers between AAs to CAs using negative binomial regression analysis. We adjusted our models for age, sex, clinicopathologic characteristics (histology, location, dysplasia), and batch. RESULTS: We observed no racial differences in age or sex at the baseline endoscopic exam. AAs compared to CAs had a higher prevalence of proximal adenomas (66% vs. 40%) and a lower prevalence of rectal adenomas (11% vs. 23%) (p =0.04) but no other differences in pathologic characteristics. In age, sex, and batch adjusted models, AAs vs. CAs had lower RRs for cells labeled with IFNγ (RR 0.50 (95% CI 0.32-0.81); p=0.004) and NK cell ligand (RR 0.67 (0.43-1.04); p=0.07). In models adjusted for age, sex, and clinicopathologic variables, AAs had reduced RRs relative to CAs for CD4 (p=0.02), NK cell ligands (p=0.01), Th17 (p=0.005), mast cells (p=0.04) and IFN-γ (p< 0.0001). CONCLUSIONS: Overall, the lower RRs in AAs vs. CAs suggests reduced effector response capacity and an immunosuppressive ('cold') tumor environment. Our results also highlight the importance of colonic location of adenoma in influencing these differences; the reduced immune responses in AAs relative to CAs may indicate impaired immune surveillance in early carcinogenesis. Future studies are needed to understand the role of risk factors (such as obesity) in influencing differences in immune responses by race.

Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia.

BACKGROUND: We examined the safety and efficacy of a treatment protocol containing Favipiravir for the treatment of SARS-CoV-2. METHODS: We did a multicenter randomized open-labeled clinical trial on moderate to severe cases infections of SARS-CoV-2. Patients with typical ground glass appearance on chest computerized tomography scan (CT scan) and oxygen saturation (SpO2) of less than 93% were enrolled. They were randomly allocated into Favipiravir (1.6 gr loading, 1.8 gr daily) and Lopinavir/Ritonavir (800/200 mg daily) treatment regimens in addition to standard care. In-hospital mortality, ICU admission, intubation, time to clinical recovery, changes in daily SpO2 after 5 min discontinuation of supplemental oxygen, and length of hospital stay were quantified and compared in the two groups. RESULTS: 380 patients were randomly allocated into Favipiravir (193) and Lopinavir/Ritonavir (187) groups in 13 centers. The number of deaths, intubations, and ICU admissions were not significantly different (26, 27, 31 and 21, 17, 25 respectively). Mean hospital stay was also not different (7.9 days [SD = 6] in the Favipiravir and 8.1 [SD = 6.5] days in Lopinavir/Ritonavir groups) (p = 0.61). Time to clinical recovery in the Favipiravir group was similar to Lopinavir/Ritonavir group (HR = 0.94, 95% CI 0.75 - 1.17) and likewise the changes in the daily SpO2 after discontinuation of supplemental oxygen (p = 0.46) CONCLUSION: Adding Favipiravir to the treatment protocol did not reduce the number of ICU admissions or intubations or In-hospital mortality compared to Lopinavir/Ritonavir regimen. It also did not shorten time to clinical recovery and length of hospital stay.

Pre-operative laparoscopic staging of gastric cancer in patients who are candidates for neo-adjuvant chemotherapy: A Cross Sectional Study.

Objective The aim of this study is to evaluate the laparoscopic method in gastric cancer staging before surgery in patients undergoing Neo-adjuvant chemotherapy. Methods This was a cross-sectional study on patients with T3-T4 and node positive non-metastatic gastric adenocarcinoma who was candidates for neo-adjuvant chemotherapy. The patients were excluded from the study when they were not in the condition to continue the study. All eligible patients underwent metastases work up by abdominal, pelvic and chest CT scans and then received neo-adjuvant chemotherapy. Pre-operative laparoscopy was performed before definitive surgery. The collected data was analyzed using SPSS software. The statistical significance, sensitivity, specificity and predictive values were calculated from this data. Results In this study, out of 50 patients, 26 (52%) were male. The mean age of the patients was 62.44 ± 12.136 years. Most tumors were located in one-third distal of stomach (21 patients, 42%). The accuracy of the laparoscopic method, to determine the degree of involvement of the lymph nodes, revealed that the method had a sensitivity of 84%, a specificity of 47.62%, a positive likelihood ratio (PLR) of 1.6, a negative likelihood ratio (NLR) of 0.33%, a positive predictive value of 65.62% and a negative predictive value of 71.43%. The accuracy of the laparoscopic method, regarding determining the presence or absence of metastasis, revealed that the method had a sensitivity, specificity, positive predictive value, and a negative predictive value of 100%. Conclusion Based on the evidence of this study, and other studies in this field, it seems that the use of a step-by-step combination methods in gastric cancer staging would be logical. Alone, no singular method would be sufficient in providing the physician with sufficient information to successfully stage the tumor and thus determine the appropriate treatment. Therefore, the combination of methods should be used which, in view of the economic constraints of health systems, would be recommended for high-risk patients for metastasis (N+/ T3-T4), diagnostic pre-operative laparoscopy.

Multi-center study finds postoperative residual non-enhancing component of glioblastoma as a new determinant of patient outcome.

INTRODUCTION: The aim of the present study is to assess whether postoperative residual non-enhancing volume (PRNV) is correlated and predictive of overall survival (OS) in glioblastoma (GBM) patients. METHODS: We retrospectively analyzed a total 134 GBM patients obtained from The University of Texas MD Anderson Cancer Center (training cohort, n = 97) and The Cancer Genome Atlas (validation cohort, n = 37). All patients had undergone postoperative magnetic resonance imaging immediately after surgery. We evaluated the survival outcomes with regard to PRNV. The role of possible prognostic factors that may affect survival after resection, including age, sex, preoperative Karnofsky performance status, postoperative nodular enhancement, surgically induced enhancement, and postoperative necrosis, was investigated using univariate and multivariate Cox proportional hazards regression analyses. Additionally, a recursive partitioning analysis (RPA) was used to identify prognostic groups. RESULTS: Our analyses revealed that a high PRNV (HR 1.051; p-corrected = 0.046) and old age (HR 1.031; p-corrected = 0.006) were independent predictors of overall survival. This trend was also observed in the validation cohort (higher PRNV: HR 1.127, p-corrected = 0.002; older age: HR 1.034, p-corrected = 0.022). RPA analysis identified two prognostic risk groups: low-risk group (PRNV < 70.2 cm3; n = 55) and high-risk group (PRNV ≥ 70.2 cm3; n = 42). GBM patients with low PRNV had a significant survival benefit (5.6 months; p = 0.0037). CONCLUSION: Our results demonstrate that high PRNV is associated with poor OS. Such results could be of great importance in a clinical setting, particularly in the postoperative management and monitoring of therapy.

Radiomic Texture Analysis Mapping Predicts Areas of True Functional MRI Activity.

Individual analysis of functional Magnetic Resonance Imaging (fMRI) scans requires user-adjustment of the statistical threshold in order to maximize true functional activity and eliminate false positives. In this study, we propose a novel technique that uses radiomic texture analysis (TA) features associated with heterogeneity to predict areas of true functional activity. Scans of 15 right-handed healthy volunteers were analyzed using SPM8. The resulting functional maps were thresholded to optimize visualization of language areas, resulting in 116 regions of interests (ROIs). A board-certified neuroradiologist classified different ROIs into Expected (E) and Non-Expected (NE) based on their anatomical locations. TA was performed using the mean Echo-Planner Imaging (EPI) volume, and 20 rotation-invariant texture features were obtained for each ROI. Using forward stepwise logistic regression, we built a predictive model that discriminated between E and NE areas of functional activity, with a cross-validation AUC and success rate of 79.84% and 80.19% respectively (specificity/sensitivity of 78.34%/82.61%). This study found that radiomic TA of fMRI scans may allow for determination of areas of true functional activity, and thus eliminate clinician bias.

Multicenter imaging outcomes study of The Cancer Genome Atlas glioblastoma patient cohort: imaging predictors of overall and progression-free survival.

BACKGROUND: Despite an aggressive therapeutic approach, the prognosis for most patients with glioblastoma (GBM) remains poor. The aim of this study was to determine the significance of preoperative MRI variables, both quantitative and qualitative, with regard to overall and progression-free survival in GBM. METHODS: We retrospectively identified 94 untreated GBM patients from the Cancer Imaging Archive who had pretreatment MRI and corresponding patient outcomes and clinical information in The Cancer Genome Atlas. Qualitative imaging assessments were based on the Visually Accessible Rembrandt Images feature-set criteria. Volumetric parameters were obtained of the specific tumor components: contrast enhancement, necrosis, and edema/invasion. Cox regression was used to assess prognostic and survival significance of each image. RESULTS: Univariable Cox regression analysis demonstrated 10 imaging features and 2 clinical variables to be significantly associated with overall survival. Multivariable Cox regression analysis showed that tumor-enhancing volume (P = .03) and eloquent brain involvement (P < .001) were independent prognostic indicators of overall survival. In the multivariable Cox analysis of the volumetric features, the edema/invasion volume of more than 85 000 mm(3) and the proportion of enhancing tumor were significantly correlated with higher mortality (Ps = .004 and .003, respectively). CONCLUSIONS: Preoperative MRI parameters have a significant prognostic role in predicting survival in patients with GBM, thus making them useful for patient stratification and endpoint biomarkers in clinical trials.

Intrathecal injection of magnesium sulfate: shivering prevention during cesarean section: a randomized, double-blinded, controlled study.

BACKGROUND: Regional anesthesia is known to significantly impair thermoregulation and predispose patients to hypothermia. We hypothesized that the addition of an intrathecal injection of magnesium sulfate (MgSO4) to bupivacaine would improve perioperative shivering in female patients undergoing elective caesarean section. METHODS: In a block-randomized, double-blinded, controlled trial 72 patients scheduled for elective caesarean section with spinal anesthesia were separated into two groups. In the treatment group, 2 ml of 0.5% bupivacaine plus 25 mg MgSO4 (0.5 ml) were injected intrathecally, and in the control group 2 ml of 0.5% bupivacaine plus 0.5 ml normal saline were injected intrathecally. Core temperature was measured before and after drug injection at predetermined intervals. Sedation was graded using the Ramsay sedation scale. RESULTS: No significant intergroup differences in appearance of shivering were seen immediately or at 5, 30, 40, 50, 60, and 90 min after block administration. However, at 10, 15, and 20 min post block, there was a significant difference in shivering. The group administered MgSO4 showed lower shivering grades compared with the control group. Core temperature was significantly reduced in the MgSO4 group compared to the normal saline group 30 min after blocking. CONCLUSIONS: Intrathecal injection of MgSO4 improved perioperative shivering in female patients undergoing elective caesarean section.

Helicobacter pylori genotypes can predict gastric tissue histopathology: a longitudinal study of Iranian patients.

INTRODUCTION: Several factors have been suggested to account for differences in the virulence of Helicobacter pylori infections in various populations. Evidence suggests the existence of different strains of H. pylori with different degrees of virulence. The present study aimed to investigate the gastric histopathology in Iranian patients infected with H. pylori and to investigate the relationship between the severity of gastritis and four different bacterial virulence-associated genotypes. METHODS AND MATERIALS: All of the patients with positive results from a pathological examination, a rapid urease test, and PCR analysis for H. pylori infection were consecutively included into the study. The classification and grading of gastritis were performed according to the Sydney System. Esophagitis was classified endoscopically according to the Savary-Miller grading system. The primers used in this study targeted 16S rRNa (521 bp), Urease A (411 bp), Cag A (400 bp), and 26 kDa (303 bp). RESULTS: Twenty-eight patients were included in the study. The presence of Cag A showed a significant relationship with higher gastritis grades (3.0±0.7 vs. 2.3±0.9, p=0.024) and higher scores for H. pylori infection (3.0±0.7 vs. 2.3±0.7, p=0.027). The patients infected with 26 kDa-positive H. pylori had significantly higher infection scores (3.5±0.6 vs. 2.5±0.6, p=0.020). CONCLUSION: This study showed that CagA-positive H. pylori infection is associated with more severe gastritis and with increased bacterial density and inflammation in the biopsy specimens. The 303-bp positive genotype was also significantly associated with higher grades of esophagitis. Additional in-depth trials will be helpful in extending our findings.