Abnormal expression of oxylipins and related synthesizing/signaling pathways in inflammatory bowel diseases.

We investigated selected oxylipins and related synthesizing/signaling pathways in 28 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and 39 controls. Plasma and mucosal PUFA/oxylipin profiles were analyzed by LC-MS/MS. mRNA expression of 5, 12 and 15-lipooxygenases, FPR2/ALXR, FFAR4/GPR120, annexin A1, and interleukin-10 were analyzed by qRT-PCR. Oxylipin profile and related metabolic pathways were altered in both CD and UC patients. The patterns were characterized by increased prostaglandins, leukotrienes, and lipoxins and overexpression of 5-lipoxygenase, FPR2/ALXR, annexin A1, and interleukin-10 genes, but decreased n-3 PUFAs and 18-hydroxyeisapentaenoic acid. The gene of 15-lipoxygenase was under-expressed mainly in UC patients. CD and UC are associated with unbalanced n-6 ​​and n-3 derivatives and pro-inflammatory and anti-inflammatory/pro-resolving mediators favoring the former compounds. The findings suggest that oxylipins engage in the pathophysiology of the diseases. Targeting oxylipin's metabolic pathways would be a promising therapy for inflammatory bowel diseases.

Predictors of Aneurysm Obliteration in Patients Treated with the WEB Device: Results of a Multicenter Retrospective Study.

BACKGROUND AND PURPOSE: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment. MATERIALS AND METHODS: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up. RESULTS: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis was observed in 485/537 (90.3%) of nonoccluded aneurysms. At the final follow-up, complete occlusion was achieved in 497/763 (65.1%) patients, and retreatment was required for 56/763 (7.3%) patients. On multivariable analysis, history of smoking, maximal aneurysm diameter, and the presence of an aneurysm wall branch were negative predictors of complete occlusion (OR, 0.5, 0.8, and 0.4, respectively). Maximal aneurysm diameter, the presence of an aneurysm wall branch, posterior circulation location, and male sex increase the chances of retreatment (OR, 1.2, 3.8, 3.0, and 2.3 respectively). Intraprocedural occlusion resulted in a 3-fold increase in the long-term occlusion rate and a 5-fold decrease in the retreatment rate (P < .001), offering a specificity of 87% and a positive predictive value of 85% for long-term occlusion. CONCLUSIONS: Intraprocedural occlusion can be used to predict the chance of long-term aneurysm occlusion and the need for retreatment after embolization with a WEB device. Smoking, aneurysm size, and the presence of an aneurysm wall branch are associated with decreased chances of successful treatment.

Assessment and design of filters and masks against COVID-19 via modeling and simulations.

This study aimed to evaluate and design masks against viruses, especially SARS-CoV-2 associated with COVID-19. A continuum filtration model was developed where the rate of particle deposition and "sticking" on the filter fibers is a critical term in the mass transfer, together with permeation velocity, filter porosity, tortuosity, and Brownian diffusion. CFD simulations of the airflow during respiration lead to the recommendation that the filter permeability should be above 4 × 10-11 m2 to direct the airflow for effectiveness against virus particles; otherwise, low filter permeabilities cause the unfiltered air to flow preferentially through the leak gaps between the mask and the headform. Different mask filters with microstructural and geometry data from the literature are assessed via filtration simulations for breathability and filtration efficiency. The results demonstrate that a surgical mask of 25% porosity, pore size of 150 µm and permeability of 4.4 × 10-11 m2 can achieve 100% minimum efficiency while demonstrating high breathability, complying with the criteria of FFP3, N95, and surgical Class II and IIR masks. Selected cotton and synthetic cloths as well as electrospun fiber layers are predicted to comply with FFP2, N95, and surgical mask Class II and IIR standards.

Bacterial Quality and Molecular Detection of Food Poisoning Virulence Genes Isolated from Nasser Lake Fish, Aswan, Egypt.

The microbial analysis of fish is critical for ensuring overall health. Uncooked fish can serve as a conduit for transmitting several types of microbes; the current investigation sought to assess the bacterial levels in various kinds of fish from Nasser Lake, Aswan, Egypt, considered the chief source of potable water in Egypt. Two hundred and fifty fish samples, including 50 of each Oreochromis niloticus, Sander lucioperca, Lates niloticus, Clarias gariepinus, and Mormyrus kannume, from Nasser Lake, Aswan, Egypt, were collected to detect the bacterial load, isolation, and identification of Aeromonas hydrophila, Pseudomonas aeruginosa, and Vibrio parahaemolyticus and their virulence genes. The findings revealed that Oreochromis niloticus and Clarias gariepinus exhibited higher bacterial loads than other fish species. Incidences of bacterial contamination among examined fishes were 28.8%, 20.4%, and 16% for Aeromonas hydrophila, Pseudomonas aeruginosa, and Vibrio parahaemolyticus, respectively. Additionally, PCR analysis detected the presence of aerA (60%) and Act (40%) genes in A. hydrophila, rpoB (70%) and LasB (30%) genes in P. aeruginosa, and ToxR (70%) and tdh (50%) genes in V. parahaemolyticus. The study suggested that the bacterial contamination levels in Oreochromis niloticus and Clarias gariepinus could be notably more significant than in other species that could potentially be harmful to the consumers, especially considering the identification of particular bacteria known to cause foodborne illnesses. Further recommendations emphasized that regular monitoring and assessments are required to preserve their quality.

Predictive factors for critical care dependency after posterior spinal fusion for adolescent idiopathic scoliosis.

Aims: Historically, patients undergoing surgery for adolescent idiopathic scoliosis (AIS) have been nursed postoperatively in a critical care (CC) setting because of the challenges posed by prone positioning, extensive exposures, prolonged operating times, significant blood loss, major intraoperative fluid shifts, cardiopulmonary complications, and difficulty in postoperative pain management. The primary aim of this paper was to determine whether a scoring system, which uses Cobb angle, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and number of levels to be fused, is a valid method of predicting the need for postoperative critical care in AIS patients who are to undergo scoliosis correction with posterior spinal fusion (PSF). Methods: We retrospectively reviewed all AIS patients who had undergone PSF between January 2018 and January 2020 in a specialist tertiary spinal referral centre. All patients were assessed preoperatively in an anaesthetic clinic. Postoperative care was defined as ward-based (WB) or critical care (CC), based on the preoperative FEV1, FVC, major curve Cobb angle, and the planned number of instrumented levels. Results: Overall, 105 patients were enrolled. Their mean age was 15.5 years (11 to 25) with a mean weight of 55 kg (35 to 103). The mean Cobb angle was 68° (38° to 122°). Of these, 38 patients were preoperatively scored to receive postoperative CC. However, only 19% of the cohort (20/105) actually needed CC-level support. Based on these figures, and an average paediatric intensive care unit stay of one day before stepdown to ward-based care, the potential cost-saving on the first postoperative night for this cohort was over £20,000. There was no statistically significant difference between the Total Pathway Score (TPS), the numerical representation of the four factors being assessed, and the actual level of care received (p = 0.052) or the American Society of Anesthesiologists grade (p = 0.187). Binary logistic regression analysis of the TPS variables showed that the preoperative Cobb angle was the only variable which significantly predicted the need for critical care. Conclusion: Most patients undergoing posterior fusion surgery for AIS do not need critical care. Of the readily available preoperative measures, the Cobb angle is the only predictor of the need for higher levels of care, and has a threshold value of 74.5°.

Pneumonectomy for non-small cell lung cancer. A National Cancer Database analysis of geographic and temporal trends, outcomes, and associated factors.

BACKGROUND: The circumstances under which pneumonectomy should be performed are controversial. This study aims to investigate national trends in pneumonectomy use to determine which patients, in what geographic areas, and under what clinical circumstances pneumonectomy is performed in the United States. METHODS: We queried the National Cancer Database and included all patients undergoing anatomic surgical resection for non-small cell lung cancer (2015-2020). The association between demographic and clinical factors and the use of pneumonectomy were investigated. RESULTS: Who: A total of 128,421 patients were identified, of whom 738 (0.6%) underwent pneumonectomy. Those patients were younger (median 65 vs 68 years, P < .001), more often male (59.9% vs 44.9%, P < .001), more likely to be below median income level (44.2% vs 38.6%, P = .002), and more likely to have lower education indicators (53% vs 48.6%, P = .02) than those who underwent other anatomic resections. Notably, there was a decreasing trend in pneumonectomy use during the study period (0.9% down to 0.4%, P < .001). Where: Patients undergoing pneumonectomy were less likely to live in metropolitan areas (77.9% vs 81.7%, P = .008) and to live closer (<12 miles) to their treating facility (45% vs 49%, P = .02). Regional geographic differences also were identified (P < .001). Why: Patients who underwent pneumonectomy were more likely to have received neoadjuvant therapy (20.6% vs 5.3%, P < .001), to be clinically N (+) (39.3% vs 12.3%, P < .001), and to have more advanced tumors (cT3-4: 46.3% vs 11.3%, P < .001). CONCLUSION: Although primarily driven by advanced oncologic features, socioeconomic and geographic factors also were associated independently with the use of pneumonectomy. Standardizing pneumonectomy indications nationwide is crucial to prevent widening outcome gaps for patients with lung cancer.

The Effects of Medium-Chain Triglyceride Oil and Butter on Lipid Profiles.

Background and objective Butter coffee drinks, mainly a form of a saturated fat diet, are widely accepted as a "healthy energy-boosting drink", especially in the young and healthy military population. The objective of our study was to determine the effects of medium-chain triglyceride (MCT) oil and butter on lipid profile, especially apolipoprotein B (ApoB), low-density lipoprotein (LDL)-cholesterol (LDL-C), high-density lipoprotein (HDL)-cholesterol (HDL-C), and other risk factors for coronary heart disease, such as BMI, BP, fasting blood glucose, HbA1c, and high-sensitivity C-reactive protein (hs-CRP) levels in healthy adults. Materials and methods We conducted a prospective study of 60 subjects who were randomized to one of the two following regimens: (1) coffee or (2) coffee with butter plus MCT oil combination. The primary outcome was the effect on ApoB. Secondary outcomes were as follows: non-HDL-C, LDL-C, triglycerides, BP, waist circumference, fasting blood glucose, and HbA1c. These parameters were evaluated at the baseline and after 12 weeks. The Mann-Whitney U test was utilized for analysis of the results. Results While 60 subjects were recruited for the study, only 41 completed it, meeting the minimum required sample size (17 per group) necessary to achieve the desired effect size: 21 males (nine in the control group and 12 in the experimental group) and 20 females (10 in each group). Anthropometric measures were similar between the two groups at baseline, and so were age and BMI (average age: 33.00 ± 5.84 years among controls and 30.86 ± 6.14 years in the experimental group; BMI: 27.35 ± 4.63 kg/m2 vs. 25.74 ± 2.70 kg/m2). The pulse rate was 69.35 ± 10.98 in the control vs. 70.68 ± 10.32 bpm in the experimental group. The waist size was also similar in both groups. Baseline lab findings were as follows: ApoB: 89.85 ± 17.52 (control), 81.60 ± 12.84 mg/dL (experimental); hs-CRP: 0.18 ± 0.27 (control), 0.17 ± 0.27 mg/L (experimental); LDL-C 113.65 ±23.71 (control), 106.50 ± 18.99 mg/dL (experimental); HDL-C 57.35 ± 14.63 (control), 62.41 ± 16.15 mg/dL (experimental); and triglycerides: 76.00 ± 31.30 (control), 56.77 ± 14.77 mg/dL (experimental), and these values were similar. The values after 12 weeks of intervention were as follows: BMI: 27.37 ± 5.24 (control), 26.36 ± 3.55 (experimental); pulse rate: 78.88 ± 14.00 (control), 74.20 ± 11.90 bpm (experimental); ApoB 87.1 ± 17.38 (control), 85.7 ±20.59 mg/dL (experimental); hs-CRP 0.26 ± 0.22 (control), 0.15 ± 0.14 mg/L (experimental); LDL-C 111.59 ± 20.35 (control), 114.10 ± 26.99 mg/dL (experimental); HDL-C 57.71 ± 12.93 (control), 64.85 ± 13.32 mg/dL (experimental); and triglycerides: 74.71 ± 25.39 (control), 60.80 ± 15.77 mg/dL (experimental). Conclusion At a significance level of 5%, there was no difference between the two groups, either at the baseline or at 12 weeks of intervention. Based on our findings, adding MCT oil and butter to coffee may be safe. However, further studies with larger sample sizes and longer duration are needed to validate our findings.

Plasmon resonances of GZO core-Ag shell nanospheres, nanorods, and nanodisks for biosensing and biomedical applications in near-infrared biological windows I and II.

There is currently a great deal of interest in realizing localized surface plasmon resonances (LSPRs) in two distinct windows in the near-infrared (NIR) spectrum for in vivo biosensing and medical applications, the biological window (BW) I and II (BW I, 700-900 nm; BW II, 1000-1700 nm). This study aims to demonstrate that LSPRs of Ga-doped ZnO (GZO) core-silver (Ag) shell structures exhibit promising features for biological applications in the NIR BW I and II. Here, we study three different shapes for nanoshells: the core-shell nanosphere, nanorod, and nanodisk. In the calculation of the optical response of these nanoshells, an effective medium approach is first used to reduce the dielectric function of a nanoshell to that of an equivalent homogenous NP with an effective dielectric function. Then, the LSPR spectra of nanoshells are calculated using the modified long-wavelength approximation (MLWA), which corrects the polarizability of the equivalent NP as obtained by Gans theory. Through numerical investigations, we examine the impacts of the core and shell sizes of the proposed nanoshells as well as the medium refractive index on the position and line width of the plasmon resonance peaks. It is shown that the plasmon resonances of the three proposed nanoshells exhibit astonishing resonance tunability in the NIR region by varying their geometrical parameters. Specifically, the improved spectrum characteristics and tunability of its plasmon resonances make the GZO-Ag nanosphere a more viable platform for NIR applications than the spherical metal colloid. Furthermore, we demonstrate that the sensitivity and figure of merit (FOM) of the plasmon resonances may be significantly increased by using GZO-Ag nanorods and nanodisks in place of GZO-Ag nanospheres. It is found that the optical properties of the transverse plasmon resonance of the GZO-Ag nanodisk are superior to all plasmon resonances produced by the GZO-Ag nanorods and GZO-Ag nanospheres in terms of sensitivity and FOM. The FOM of the transverse plasmon mode of the GZO-Ag nanodisk is almost two orders of magnitude higher than that of the longitudinal and transverse plasmon modes of the GZO-Ag nanorod in BW I and BW II. And it is 1.5 and 2 times higher than the plasmon resonance FOM of GZO-Ag nanospheres in BW I and BW II, respectively.

Ondansetron or beta-sitosterol antagonizes inflammatory responses in liver, kidney, lung and heart tissues of irradiated arthritic rats model.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder mainly affecting joints, yet the systemic inflammation can influence other organs and tissues. The objective of this study was to unravel the ameliorative capability of Ondansetron (O) or ß-sitosterol (BS) against inflammatory reactions and oxidative stress that complicates Extra-articular manifestations (EAM) in liver, kidney, lung, and heart of arthritic and arthritic irradiated rats. METHODS: This was accomplished by exposing adjuvant-induced arthritis (AIA) rats to successive weekly fractions of total body γ-irradiation (2 Gray (Gy)/fraction once per week for four weeks, up to a total dose of 8 Gy). Arthritic and/or arthritic irradiated rats were either treated with BS (40 mg/kg b.wt. /day, orally) or O (2 mg/kg) was given ip) or were kept untreated as model groups. RESULTS: Body weight changes, paw circumference, oxidative stress indices, inflammatory response biomarkers, expression of Janus kinase-2 (JAK-2), Signal transducer and activator of transcription 3 (STAT3), high mobility group box1 (HMGB1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), as well as pro- and anti-inflammatory mediators in the target organs, besides histopathological examination of ankle joints and extra-articular tissues. Treatment of arthritic and/or arthritic irradiated rats with BS or O powerfully alleviated changes in body weight gain, paw swelling, oxidative stress, inflammatory reactions, and histopathological degenerative alterations in articular and non-articular tissues. CONCLUSION: The obtained data imply that BS or O improved the articular and EAM by regulating oxidative and inflammatory indices in arthritic and arthritic irradiated rats.

Evaluation of Solubility, Dissolution Rate, and Oral Bioavailability of ß-Cyclodextrin and Hydroxypropyl ß-Cyclodextrin as Inclusion Complexes of the Tyrosine Kinase Inhibitor, Alectinib.

This study aims to improve the solubility and dissolution rate of alectinib (ALB), a tyrosine kinase inhibitor commonly used for treating non-small-cell carcinoma (NSCLC). Given ALB's low solubility and bioavailability, complexation with ß-cyclodextrin (ßCD) and hydroxy propyl ß-cyclodextrin (HPßCD) was evaluated. Some of the different preparation methods used with varying ALB-to-CD ratios led to the formation of complexes that were characterized using Fourier-Transform Infrared (FTIR) techniques and Differential Scanning Calorimetry (DSC) to prove complex formation. The encapsulation efficiency was also determined. The simulations were carried out for ALB's interactions with ßCD and HPßCD. This study identified the most soluble complex (ALB-HPßCD; 1:2 ratio) and evaluated its dissolution. The bioavailability of the ALB-HPßCD complex was evaluated in Wistar rats relative to free ALB. Pharmacokinetic profiles revealed increased Cmax (240 ± 26.95 ng/mL to 474 ± 50.07 ng/mL) and AUC0-48 (5946.75 ± 265 ng.h/mL to 10520 ± 310 ng.h/mL) with no change in the elimination rate constant. In conclusion, the complexation of ALB-HPßCD manages to increase in vitro solubility, the dissolution rate, and oral bioavailability, providing a favorable approach to improving ALB administration.

Anesthesia Techniques for Vitreoretinal Surgery in the United States: A Report from the Multicenter Perioperative Outcomes Group Research Consortium.

PURPOSE: To explore the patterns of anesthesia use and their determinants during vitreoretinal (VR) surgeries in academic and community hospitals across the US, using data from the Multicenter Perioperative Outcomes Group (MPOG). DESIGN: A retrospective, multicenter, cohort study. METHODS: We queried the MPOG database of 107,066 patients undergoing VR surgeries. Patients (≥18 years) undergoing VR surgery with monitored anesthesia care (MAC) or general anesthesia (GA) from January 1, 2015 to December 31, 2021 were included. Patient-level, case-based, and institutional-level covariates were collected. We performed multivariable mixed-effects models to determine predictors of anesthesia type use. The primary outcome was the type of anesthesia (MAC or GA) used during VR surgeries. As a secondary outcome, MAC cases were further classified based on the additional use of sedation into MAC with or without sedation. RESULTS: We found that 67.45% of VR surgery cases received MAC, and 73.63% of institutions administered MAC to more than half of cases. Random effect modeling revealed that 47.76% of the variation in MAC use was attributed to institutions. A trend toward increased use of MAC with increasing age was observed. Patients diagnosed with chronic pulmonary disease, liver disease, or a history of drug abuse were less likely to receive MAC. Conversely, we found that patients with reported alcohol abuse disorder, diabetes with complications, and those with American Society of Anesthesiologists (ASA) physical status of 4 (vs. 1, 2, or 3) were more likely to use MAC. Compared to non-complex VR surgeries, there was a notably decreased likelihood of MAC use in complex PPV (P = .004), PPV + scleral buckle (SB) for retinal detachment (P < .0001), and primary SB surgery (P < .0001). CONCLUSIONS: Approximately 2/3 of VR anesthesia is under MAC, but GA is still preferred for SBs, complex vitrectomy, and younger patients. We show that large interinstitutional variation for using MAC in practice exists.

Prevalence and viral suppression of hepatitis B virus infection among people living with HIV on antiretroviral therapy in Sierra Leone.

OBJECTIVE: Sub-Saharan Africa is one of the regions with the highest burdens of HIV and hepatitis B virus (HBV), but data on the impact of antiretroviral therapy (ART) on HBV DNA suppression is limited. In this study, we aimed to determine the prevalence and associated factors of a positive hepatitis B surface antigen (HBsAg) among people living with HIV, and assess the suppression of ART on HBV replication in people living with HIV in Sierra Leone. METHODS: A cross-sectional study was designed to recruit people living with HIV aged 18 years or older in ten public hospitals in Sierra Leone between August 2022 and January 2023. Statistical analyses were performed using R software. Logistic regression analysis was used to assess factors independently associated with positive HBsAg and HBV DNA suppression. RESULTS: Of the 3106 people living with HIV recruited in this study, 2311 (74.4%) were women. The median age was 36 years, 166 (5.3%) had serological evidence of HBV vaccination. The overall prevalence of HBsAg positivity was 12.0% (95% CI: 10.9% to 13.2%). Male sex (adjusted OR (aOR) 2.11, 95% CI: 1.67 to 2.68; p<0.001) and being separated (aOR 1.83, 95% CI: 1.06 to 3.16, p=0.031; reference group: being married) were independent predictors of HBsAg seropositivity. Among 331 people living with HIV and HBV receiving ART, 242 (73.1%) achieved HBV DNA suppression (below 20 IU/mL). HBV suppression rate was higher in HIV-virally suppressed patients than those with unsuppressed HIV viral load (p<0.001). In addition, the male sex was more likely to have unsuppressed HBV DNA (aOR 1.17, 95% CI: 1.17 to 3.21; p=0.010). CONCLUSIONS: We reported a high prevalence of HBsAg seropositivity and low HBV immunisation coverage in people living with HIV in Sierra Leone. In addition, we observed that ART can efficiently result in a viral suppression rate of HBV infection. Therefore, achieving the global target of eliminating HBV infection by 2030 requires accelerated access to care for people living with HIV and HBV, including HBV testing, antiviral treatment and hepatitis B vaccination.

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Fenamates and ibuprofen as foundational components in the synthesis of innovative, targeted COX-2 anti-inflammatory drugs, undergoing thorough biopharmacological assessments and in-silico computational studies.

Cyclooxygenase-2 plays a vital role in inflammation by catalyzing arachidonic acid conversion toward prostaglandins, making it a prime therapeutic objective. Selective COX-2 inhibitors represent significant progress in anti-inflammatory therapy, offering improved efficacy and fewer side effects. This study describes the synthesis of novel anti-inflammatory compounds from established pharmaceutically marketed agents like fenamates III-V and ibuprofen VI. Through rigorous in vitro testing, compounds 7b-c, and 12a-b demonstrated substantial in vitro selective inhibition, with IC50 values of 0.07 to 0.09 µM, indicating potent pharmacological activity. In vivo assessment, particularly focusing on compound 7c, revealed significant anti-inflammatory effects. Markedly, it demonstrated the highest inhibition of paw thickness (58.62 %) at the 5-hr mark compared to the carrageenan group, indicating its potency in mitigating inflammation. Furthermore, it exhibited a rapid onset of action, with a 54.88 % inhibition observed at the 1-hr mark. Subsequent comprehensive evaluations encompassing analgesic efficacy, histological characteristics, and toxicological properties indicated that compound 7c did not induce gastric ulcers, in contrast to the ulcerogenic tendency associated with mefenamic acid. Moreover, compound 7c underwent additional investigations through in silico methodologies such as molecular modelling, field alignment, and density functional theory. These analyses underscored the therapeutic potential and safety profile of this novel compound, warranting further exploration and development in the realm of pharmaceutical research.

Novel risk index integrating practical operation limits enhances probabilistic contingency ranking for large-scale photovoltaic plant planning.

This research addresses the pressing need for heightened grid security amid increasing uncertainties in photovoltaic PV generation. The research problem lies in the limitations of conventional contingency analysis metrics, failing to adequately consider both contingency occurrences and uncertainties inherent in PV generation. In response, a comprehensive algorithm is proposed that introduces a novel severity function framework, enhancing traditional contingency ranking metrics. This approach incorporates grid remedial actions and refines line and bus voltage classification by considering available correction time, aiming to offer a more robust security assessment. Motivated by the imperative to address uncertainty in PV generation, the proposed work builds on established analysis tools. A probabilistic load flow algorithm manages PV generation uncertainties, utilizing historical data for contingency incidence uncertainty. Additionally, a probabilistic model for PV plants integrates historical solar data, deriving hourly probability density functions to meet grid code requirements, including reactive power considerations. The justification for this work lies in the algorithm's demonstrated efficacy, validated on the IEEE 14-bus network. Results highlight its ability to identify risks associated with line overloading and bus voltage breaches. Comparative evaluations underscore proper coupling buses for security, favoring distributed capacity to mitigate line overloading risks. The study's key results emphasize voltage risk amplification with reactive power omission, stressing the significance of compensation strategies. This research addresses a critical problem, presenting a comprehensive algorithmic solution to enhance grid security amidst uncertainties in PV integration. Findings offer valuable insights for strategically interaction between large scale PV plants and electrical grid, contributing to an improved grid security paradigm in a dynamic and uncertain energy model.

Factor XI as a new target for prevention of thromboembolism in cardiovascular disease: a meta-analysis of randomized controlled trials.

Anticoagulant therapy is a mainstay in the management of patients with cardiovascular disease. The use of conventional anticoagulants carries potential side effects, mainly bleeding. Drugs targeting Factor XI (FXI) have been investigated in randomized controlled trials as a new option with more favorable outcomes. A comprehensive literature search was conducted to identify relevant studies comparing FXI inhibitors to placebo or standard therapy. The primary outcomes were incidence of all bleeding events, major bleeding, and thromboembolism. Secondary outcomes included incidence of all adverse events (AE), serious AE, and all-cause mortality. A total of 11 studies involving 10,536 patients were included. FXI inhibitors were associated with a trend toward reduction of bleeding events and incidence of thromboembolism compared to the control group (placebo/standard therapy). There was no statistically significant difference between both groups in terms of adverse events and all-cause mortality. When compared to enoxaparin, FXI inhibitors significantly reduced the risk of bleeding events (RR = 0.42, 95% CI: 0.23-0.76, P = 0.004) and thromboembolism (RR = 0.59, 95% CI: 0.44-0.77, P = 0.001). On the other hand, when compared to DOACs, FXI inhibitors were associated with a significant reduction in bleeding events but not thromboembolism. Whereas, compared to placebo, FXI inhibitors did not increase the risk of bleeding events, adverse events, or all-cause mortality (P > 0.05). FXI inhibitors could be a safer and more potent option for prevention of thromboembolism than conventional therapy.

Year-Long Stability of Nucleic Acid Bases in Concentrated Sulfuric Acid: Implications for the Persistence of Organic Chemistry in Venus' Clouds.

We show that the nucleic acid bases adenine, cytosine, guanine, thymine, and uracil, as well as 2,6-diaminopurine, and the "core" nucleic acid bases purine and pyrimidine, are stable for more than one year in concentrated sulfuric acid at room temperature and at acid concentrations relevant for Venus clouds (81% w/w to 98% w/w acid, the rest water). This work builds on our initial stability studies and is the first ever to test the reactivity and structural integrity of organic molecules subjected to extended incubation in concentrated sulfuric acid. The one-year-long stability of nucleic acid bases supports the notion that the Venus cloud environment-composed of concentrated sulfuric acid-may be able to support complex organic chemicals for extended periods of time.

Th2 Cells Are Associated with Tumor Recurrence Following Radiation.

The curative treatment of multiple solid tumors, including head and neck squamous cell carcinoma (HNSCC), utilizes radiation. The outcomes for HPV/p16-negative HNSCC are significantly worse than HPV/p16-positive tumors, with increased radiation resistance leading to worse locoregional recurrence (LRR) and ultimately death. This study analyzed the relationship between immune function and outcomes following radiation in HPV/p16-negative tumors to identify mechanisms of radiation resistance and prognostic immune biomarkers. A discovery cohort of 94 patients with HNSCC treated uniformly with surgery and adjuvant radiation and a validation cohort of 97 similarly treated patients were utilized. Tumor immune infiltrates were derived from RNAseq gene expression. The immune cell types significantly associated with outcomes in the discovery cohort were examined in the independent validation cohort. A positive association between high Th2 infiltration and LRR was identified in the discovery cohort and validated in the validation cohort. Tumor mutations in CREBBP/EP300 and CASP8 were significantly associated with Th2 infiltration. A pathway analysis of genes correlated with Th2 cells revealed the potential repression of the antitumor immune response and the activation of BRCA1-associated DNA damage repair in multiple cohorts. The Th2 infiltrates were enriched in the HPV/p16-negative HNSCC tumors and associated with LRR and mutations in CASP8, CREBBP/EP300, and pathways previously shown to impact the response to radiation.

Epidemiology of Cardiac Myxoma in the Kingdom of Bahrain.

BACKGROUND: Cardiac myxomas (CM) are the most prevalent type of primary cardiac tumour. The majority of primary cardiac tumours, including CM, are found to be benign. In the context of this study, the objective was to investigate and analyse the experience of CM over a period of 10 years, specifically in Bahrain. By examining this particular subset of cardiac tumours, valuable insights can be gained regarding their prevalence, clinical presentation, diagnostic methods, treatment approaches, and outcomes in the Bahraini population. METHODS: We retrospectively evaluated the medical records of 20 patients who presented with CM at the Mohammed bin Khalifa bin Salman Al Khalifa Specialist Cardiac Centre in the Kingdom of Bahrain from January 2010 to January 2021. All patients had transthoracic echocardiography to establish a preoperative diagnosis. All of the patients underwent an operation using the median sternotomy, and a histopathology examination confirmed the final diagnosis. RESULTS: The mean age at the time of presentation was 57 (± 18.1) years, ranging from 17 to 80 years, and 55% (12 patients) were female. Dyspnea (n=8, 40%) and peripheral embolism (n=4, 20%), which include cerebrovascular accidents and acute monocular vision loss, were the most frequently observed symptoms. The largest diameter of the myxoma was 5.1 cm (±1.7). The left atrium was the predominant location for myxoma formation (n=16, 80%), with the majority of the myxomas attached to the atrial septum. CONCLUSION: CM poses a significant risk of cardiac and systemic complications. Early detection and timely gross-complete resection result in excellent early and long-term outcomes.