Perioperative Dyselectrolytemia in Patients Undergoing Transurethral Resection of the Prostate Using 0.9% Normal Saline Irrigation.

BACKGROUND: The choice of irrigation fluid used in transurethral resection of the prostate (TURP) has a significant impact on serum electrolyte levels. Among the many available options, 0.9% normal saline (NS) is considered to be more physiological. MATERIAL AND METHODS: This observational study was conducted on 60 adult males aged 50-70 years, classified as American Society of Anesthesiologists grade 1 and 2, undergoing TURP with 0.9% NS irrigation under spinal anesthesia achieved with a mixture of 0.5% heavy bupivacaine. The patients' hematocrit and serum electrolyte levels were obtained after six hours and compared with preoperative values. RESULTS: Hematocrit reduced from 40.32 ± 6.27 to 31.07 ± 5.40 (p < 0.001). Both serum sodium and potassium decreased from 136.77 ± 3.27 to 128.31 ± 5.91 and from 4.02 ± 0.26 to 3.81 ± 0.36, respectively (p < 0.001). However, serum chloride showed only a minimal increase from 101.58 ± 2.88 to 102.25 ± 1.66 (p < 0.12). CONCLUSION: Although the changes in serum sodium and potassium were statistically significant, they did not have any physiological consequences in our study. However, this emphasizes the importance of vigilant electrolyte monitoring to identify and mitigate the risk of electrolyte disturbances during TURP surgeries.

Molecular expression, purification and structural characterization of recombinant L-Glutaminase from Streptomyces roseolus.

The present research reports the anti-cancer potential of recombinant L-Glutaminase from Streptomyces roseolus. L-Glutaminase gene was synthesized by codon-optimization, cloned and successfully expressed in E. coli BL21 (DE3). Affinity purified recombinant L-Glutaminase revealed a molecular mass of 32 kDa. Purified recombinant L-Glutaminase revealed stability at pH 7.0-8.0 with optimum activity at 70 °C further indicating its thermostable nature based on thermodynamic characterization. Recombinant L-Glutaminase exhibited profound stability in the presence of several biochemical parameters and demonstrated its metalloenzyme nature and was also found to be highly specific towards favorable substrate (l-Glutamine) based on kinetics. It demonstrated antioxidant property and pronounced cytotoxic effect against breast cancer (MCF-7 cell lines) in a dose dependent behavior with IC50 of 40.68 µg/mL. Matrix-assisted laser desorption ionization-time of flight-mass spectroscopy (MALDI-TOF-MS) analysis of desired mass peaks ascertained the recombinant L-Glutaminase identity. N-terminal amino acid sequence characterization through Edman degradation revealed highest resemblance for L-glutaminase within the Streptomyces sp. family. The purified protein was characterized structurally and functionally by employing spectroscopic methods like Raman, circular dichroism and nuclear magnetic resonance. The thermostability was assessed by thermogravimetric analysis. The outcomes of the study, suggests the promising application of recombinant L-Glutaminase as targeted therapeutic candidate for breast cancer.

Association of Ground Glass Opacities with Systemic Inflammation and Progression of Emphysema.

RATIONAL: Ground glass opacities (GGO) in the absence of interstitial lung disease are understudied. OBJECTIVE: To assess the association of GGO with white blood cells (WBCs) and progression of quantified chest CT emphysema. METHODS: We analyzed data of participants in the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). Chest radiologists and pulmonologists labeled regions of the lung as GGO and adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGO (%GGOAMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGOAMFM with WBC, changes in %emphysema, and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Among 2,714 participants, 1,680 had COPD and 1,034 had normal spirometry. Among COPD participants, based on the multivariable analysis, current smoking and chronic productive cough was associated with higher %GGOAMFM. Higher %GGOAMFM was cross-sectionally associated with higher WBCs and neutrophils levels. Higher %GGOAMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at one-year follow visit by 11.7% (Relative increase; 95%CI 7.5-16.1%;P<0.001). We found no association between %GGOAMFM and one-year FEV1 decline but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up time of 1,544 days (Interquartile Interval=1,118-2,059). Among normal spirometry participants, we found similar results except that %GGOAMFM was associated with progression to COPD at one-year follow-up. CONCLUSIONS: Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.

Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation.

BACKGROUND: Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation, has shown efficacy and safety in a phase 3 trial involving patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation and an elevated risk of exacerbation. Whether the findings would be confirmed in a second phase 3 trial was unclear. METHODS: In a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of 300 cells per microliter or higher to receive subcutaneous dupilumab (300 mg) or placebo every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Key secondary end points, analyzed in a hierarchical manner to adjust for multiplicity, included the changes from baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) at weeks 12 and 52 and in the St. George's Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better quality of life) total score at week 52. RESULTS: A total of 935 patients underwent randomization: 470 were assigned to the dupilumab group and 465 to the placebo group. As prespecified, the primary analysis was performed after a positive interim analysis and included all available data for the 935 participants, 721 of whom were included in the analysis at week 52. The annualized rate of moderate or severe exacerbations was 0.86 (95% confidence interval [CI], 0.70 to 1.06) with dupilumab and 1.30 (95% CI, 1.05 to 1.60) with placebo; the rate ratio as compared with placebo was 0.66 (95% CI, 0.54 to 0.82; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 with dupilumab (least-squares mean change, 139 ml [95% CI, 105 to 173]) as compared with placebo (least-squares mean change, 57 ml [95% CI, 23 to 91]), with a significant least-squares mean difference at week 12 of 82 ml (P<0.001) and at week 52 of 62 ml (P = 0.02). No significant between-group difference was observed in the change in SGRQ scores from baseline to 52 weeks. The incidence of adverse events was similar in the two groups and consistent with the established profile of dupilumab. CONCLUSIONS: In patients with COPD and type 2 inflammation as indicated by elevated blood eosinophil counts, dupilumab was associated with fewer exacerbations and better lung function than placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; NOTUS ClinicalTrials.gov number, NCT04456673.).

ß-Blocker Use and Clinical Outcomes in Patients With COPD Following Acute Myocardial Infarction.

Importance: While ß-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI). Objective: To investigate whether ß-blocker prescription at hospital discharge is associated with increased risk of mortality or adverse cardiopulmonary outcomes in patients with COPD and AMI. Design, Setting, and Participants: This prospective, longitudinal cohort study with 6 months of follow-up enrolled patients aged 35 years or older with COPD who underwent cardiac catheterization for AMI at 18 BLOCK-COPD network hospitals in the US from June 2020 through May 2022. Exposure: Prescription for any ß-blocker at hospital discharge. Main Outcomes and Measures: The primary outcome was time to the composite outcome of death or all-cause hospitalization or revascularization. Secondary outcomes included death, hospitalization, or revascularization for CVD events, death or hospitalization for COPD or respiratory events, and treatment for COPD exacerbations. Results: Among 3531 patients who underwent cardiac catheterization for AMI, prevalence of COPD was 17.1% (95% CI, 15.8%-18.4%). Of 579 total patients with COPD and AMI, 502 (86.7%) were prescribed a ß-blocker at discharge. Among the 562 patients with COPD included in the final analysis, median age was 70.0 years (range, 38.0-94.0 years) and 329 (58.5%) were male; 553 of the 579 patients (95.5%) had follow-up information. Among those discharged with ß-blockers, there was no increased risk of the primary end point of all-cause mortality, revascularization, or hospitalization (hazard ratio [HR], 1.01; 95% CI, 0.66-1.54; P = .96) or of cardiovascular events (HR, 1.11; 95% CI, 0.65-1.92; P = .69), COPD-related or respiratory events (HR, 0.75; 95% CI, 0.34-1.66; P = .48), or treatment for COPD exacerbations (rate ratio, 1.01; 95% CI, 0.53-1.91; P = .98). Conclusions and Relevance: In this cohort study, ß-blocker prescription at hospital discharge was not associated with increased risk of adverse outcomes in patients with COPD and AMI. These findings support use of ß-blockers in patients with COPD and recent AMI.

Counterpoint: In-Home Pulmonary Rehabilitation Is an Attractive Alternative.

Center-based pulmonary rehabilitation is positioned as the accepted standard for pulmonary rehabilitation. There, however, are several barriers to its utilization, and usage rates remain as low as 4%, despite decades of trying to improve access. The question then arises as to who is really benefiting from center-based pulmonary rehabilitation as this therapy is barely available to eligible patients. Alternative modes of delivery of pulmonary rehabilitation have been tested. Meta-analyses indicate that these alternate modes are associated with clinical improvements comparable with center-based pulmonary rehabilitation in several outcomes that are important for patients, including the 6-min walk distance, dyspnea, and quality of life. These modes are also associated with better adherence to the intervention than center-based pulmonary rehabilitation. Telehealth pulmonary rehabilitation and home-based pulmonary rehabilitation, therefore, are attractive alternatives to center-based pulmonary rehabilitation and will exponentially increase pulmonary rehabilitation capacity.

Hypocholesterolemic potential of Bacillus amyloliquefaciens KAVK1 modulates lipid accumulation on 3T3-L1 adipose cells and high fat diet-induced obese rat model.

The significance of microorganisms occurring in foods is predominantly targeted due to their application for identifying a novel range of the bacterial spectrum. Diverse microbial species are capable of exhibiting potential pharmacological activities like antimicrobial and anticancer. Microbial strains capable of reducing obesity-related syndromes have also been reported. In the present study, the hypocholesterolemic efficacy of Bacillus amyloliquefaciens isolated from dairy products was scrutinised by in vitro (3T3-L1 adipose cells) and in vivo (high-fat diet-induced obese Wistar albino rats) methods. Potential cholesterol-lowering isolates were screened using a plate assay method and optimised by physical parameters. Molecular identification of the topmost five cholesterol-lowering isolates was acquired by amplification of the 16 S rRNA gene region. Bacillus amyloliquefaciens strain KAVK1, followed by strains KAVK2, KAVK3, KAVK4, and KAVK5 were molecularly determined. Further, cholesterol-lowering strains degraded the spectral patterns determined by the side chain of a cholesterol molecule. The anti-lipase activity was demonstrated using the porcine pancreatic lipase inhibitory method and compared with the reference compound Atorvastatin. Lyophilised strain KAVK1 revealed maximum pancreatic lipase inhibition. Strain KAVK1 attenuated lipid accumulation in 3T3-L1 adipose cell line predicted by Oil Red O staining method. Significant reduction of body weight and change in lipid profile was recognised after the supplement of KAVK1 to obese rats. Histopathological changes in organs were predominantly marked. The result of this study implies that the cholesterol-lowering B. amyloliquefaciens KAVK1 strain was used to treat hypercholesterolemia.

Update on Cancer Predisposition Syndromes and Surveillance Guidelines for Childhood Brain Tumors.

Tumors of the central nervous system (CNS) comprise the second most common group of neoplasms in childhood. The incidence of germline predisposition among children with brain tumors continues to grow as our knowledge on disease etiology increases. Some children with brain tumors may present with nonmalignant phenotypic features of specific syndromes (e.g., nevoid basal cell carcinoma syndrome, neurofibromatosis type 1 and type 2, DICER1 syndrome, and constitutional mismatch-repair deficiency), while others may present with a strong family history of cancer (e.g., Li-Fraumeni syndrome) or with a rare tumor commonly found in the context of germline predisposition (e.g., rhabdoid tumor predisposition syndrome). Approximately 50% of patients with a brain tumor may be the first in a family identified to have a predisposition. The past decade has witnessed a rapid expansion in our molecular understanding of CNS tumors. A significant proportion of CNS tumors are now well characterized and known to harbor specific genetic changes that can be found in the germline. Additional novel predisposition syndromes are also being described. Identification of these germline syndromes in individual patients has not only enabled cascade testing of family members and early tumor surveillance but also increasingly affected cancer management in those patients. Therefore, the AACR Cancer Predisposition Working Group chose to highlight these advances in CNS tumor predisposition and summarize and/or generate surveillance recommendations for established and more recently emerging pediatric brain tumor predisposition syndromes.

The Effect of Water Stress on Bioactive Compounds in Australian-Grown Black Sesame.

Sesame is an emerging crop of interest in Australia and has attracted widespread interest due to the health-benefitting properties of its bioactive compounds, including fatty acids, lignans, and polyphenols. This study aimed to investigate the impact of drought stress on these bioactive compounds, using eleven cultivars of black sesame seeds grown in Australia. Specific varieties responded positively to water deficit (WD) conditions, showing increased levels of TPC, FRAP, CUPRAC, and lignans. Varieties 1, 4, 7, and 12 showed significantly increased FRAP values ranging from 158.02 ± 10.43 to 195.22 ± 9.63 mg TE/100 g DW in the WD treatment compared to the well-watered (WW) treatment, whereas varieties 7, 10, 12, 13, and 18 demonstrated the highest CUPRAC values of all varieties (2584.86 ± 99.68-2969.56 ± 159.72 mg TE/100 g) across both WW and WD conditions, with no significant variations between irrigation regimes. Moreover, lignan contents (sesamin and sesamolin) were higher in varieties 1, 2, 5, and 8 grown in WD conditions. Compared to the optimal unsaturated to saturated fatty acid ratio (Σ UFA/Σ SFA ratio) of 0.45, all sesame genotypes showed superior ratios (ranging between 1.86 and 2.34). Moreover, the ω-6/ω-3 PUFA ratio varied from 33.7-65.5, with lower ratios in varieties 2, 4, 5, 8, and 18 under WD conditions. The high levels of phenolic compounds and healthy fats suggest the potential of black sesame to be incorporated into diets as a functional food. Furthermore, the enhanced phytochemistry of these cultivars in WD conditions is promising for widespread adoption. However, larger trial studies to confirm these findings across different geographic locations and seasons are warranted.

Comparison of adverse effects following immunisation degree after the administration COVID-19 vaccine of different platforms.

INTRODUCTION: Vaccination is an effective way to overcome the spread of Coronavirus Disease 19 (COVID-19). However, it can give rise to adverse event following immunisation (AEFI). AEFI is an important aspect that is assessed in vaccine safety standards. It is assumed that different vaccine platforms can give rise to different degrees of AEFI severity, but so far there have been no studies that discuss the differences in the degree of AEFI on each type of COVID- 19 vaccine platform. AIM: Evaluate the differences in the degree of AEFI on each type of COVID-19 vaccine platform. MATERIALS AND METHODS: The research used a quantitative analytical observational design with a cross sectional approach. Data collection from participants was carried out by filling out questionnaires. The collected data was tabulated and statistical analysis was carried out. RESULTS: A total of 217 respondents who received three doses of vaccine participated in the study. Of the 651 vaccine doses studied, the results showed that there were significant differences in the degree of AEFI between the three types of vaccine platforms. The degree of AEFI was significantly different (p < 0.05) between each type of vaccine platform, with the degree of AEFI starting from the lowest, namely inactivated vaccine, then viral vector vaccine and the highest was nucleic acid vaccine. CONCLUSION: The degree of AEFI differs significantly between each COVID-19 vaccine platform. The degree of AEFI, from the mildest to the most severe, was inactivated vaccine, viral vector vaccine and nucleic acid vaccine. No serious AEFI was reported.

Deep volcanic residual U-Net for nodal metastasis (Nmet) identification from lung cancer.

Lymph node metastasis detections are more clinically significant task associated with the presence and reappearance of lung cancer. The development of the computer-assisted diagnostic approach has greatly supported the diagnosis of human disorders in the field of medicine including lung cancer. Lung cancer treatment is possible if it is detected at the initial stage. Radiologists have great difficulty identifying and categorizing lung cancers in the initial phase. So, several methods were used to predict the lung cancer but does not provide accurate solutions with increased error rate. To overcome these issues, a Deep Volcanic Residual U-Net (DVR U-Net) for nodal metastasis is proposed in this manuscript which identifies the LC accurately in the early stage. Initially, the input images are taken from two datasets. After that, these input data are pre-processed using Anisotropic Diffusion Filter with a Fuzzy based Contrast-Limited Adaptive Histogram Equalization (ADFFCLAHE) method. Then the pre-processed images are given to the DVR U-Net to segment and extract the volume of interest for estimating the nodal stage of each volume of interest. Finally, DVR U-Net effectively detects and classifies the N + (nodal metastasis) or N- (non-nodal metastasis). The introduced method attains 99.9% higher accuracy as compared with the existing methods. Also, the statistical analysis of the Shapiro-Wilk test, Friedman test and Wilcoxon Signed-Rank test are executed to prove the statistical effectiveness of the implemented method.

The Role of Microglia in Sex- and Region-Specific Blood-Brain Barrier Integrity During Nicotine Withdrawal.

Background: Smoking is the largest preventable cause of death and disease in the United States, with <5% of quit attempts being successful. Microglia activation and proinflammatory neuroimmune signaling in reward neurocircuitry are implicated in nicotine withdrawal symptomology. Microglia are integral regulators of blood-brain barrier (BBB) functionality as well; however, whether the effects of nicotine withdrawal on microglia function impact BBB integrity is unknown. Methods: Mice were treated with chronic nicotine (12 mg/kg/day) and subjected to 48 hours nicotine withdrawal. Regional BBB permeability, together with messenger RNA and protein expression of tight junction proteins, were assessed. PLX5622 chow was used to deplete microglia to evaluate the role of microglia in regulating BBB integrity and nicotine withdrawal symptomology. Results: Female mice had higher baseline BBB permeability in the prefrontal cortex and hippocampus than males. Nicotine withdrawal further exacerbated the BBB permeability selectively in the prefrontal cortex of females. These effects were concurrent with prefrontal cortex alterations in a subset of tight junction proteins with increased proinflammatory responses following nicotine withdrawal in females. Depletion of microglia via PLX5622 treatment prevented all these molecular effects and attenuated withdrawal-induced anxiety-like behavior in female mice. Conclusions: These results are the first to show sex differences in regional BBB permeability during nicotine withdrawal. This represents a possible link to both the reduced smoking cessation success seen in women and women's increased risk for smoking-related neurovascular disorders. Furthermore, these findings open an avenue for sex-specific therapeutics that target microglia and BBB dysfunction during nicotine withdrawal in women.