Retraction: A Giant Porencephaly: A Rare Etiology of Pediatric Seizures.

[This retracts the article DOI: 10.7759/cureus.19623.].

Therapeutic effects of genistein in experimentally induced ulcerative colitis in rats via affecting mitochondrial biogenesis.

Ulcerative colitis (UC) is an inflammatory bowel disease that affects the mucosa of the colon, resulting in severe inflammation and ulcers. Genistein is a polyphenolic isoflavone present in several vegetables, such as soybeans and fava beans. Therefore, we conducted the following study to determine the therapeutic effects of genistein on UC in rats by influencing antioxidant activity and mitochondrial biogenesis and the subsequent effects on the apoptotic pathway. UC was induced in rats by single intracolonic administration of 2 ml of 4% acetic acid. Then, UC rats were treated with 25-mg/kg genistein. Colon samples were obtained to assess the gene and protein expression of nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), peroxisome proliferator-activated receptor-gamma coactivator (PGC-1), mitochondrial transcription factor A (TFAM), B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), caspase-3, caspase-8, and caspase-9. In addition, colon sections were stained with hematoxylin/eosin to investigate the cell structure. The microimages of UC rats revealed inflammatory cell infiltration, hemorrhage, and the destruction of intestinal glands, and these effects were improved by treatment with genistein. Finally, treatment with genistein significantly increased the expression of PGC-1, TFAM, Nrf2, HO-1, and BCL2 and reduced the expression of BAX, caspase-3, caspase-8, and caspase-9. In conclusion, genistein exerted therapeutic effects against UC in rats. This therapeutic activity involved enhancing antioxidant activity and increasing mitochondrial biogenesis, which reduced cell apoptosis.

Exploring the Chemical Constituents, Antioxidant, Xanthine Oxidase and COX Inhibitory Activity of Commiphora gileadensis Commonly Grown Wild in Saudi Arabia.

The use of the synthetic drugs has increased in the last few decades; however, these drugs exhibit various side effects. Scientists are therefore seeking alternatives from natural sources. Commiphora gileadensis has long been used to treat various disorders. It is commonly known as bisham or balm of Makkah. This plant contains various phytochemicals, including polyphenols and flavonoids, with biological potential. We found that steam-distilled essential oil of C. gileadensis exhibited higher antioxidant activity (IC50, 22.2 µg/mL) than ascorbic acid (IC50, 1.25 µg/mL). The major constituents (>2%) in the essential oil were ß-myrcene, nonane, verticiol, ß-phellandrene, ß-cadinene, terpinen-4-ol, ß-eudesmol, α-pinene, cis-ß-copaene and verticillol, which might be responsible for the antioxidant and antimicrobial activity against Gram-positive bacteria. The extract of C. gileadensis exhibited inhibitory activity against cyclooxygenase (IC50, 450.1 µg/mL), xanthine oxidase (251.2 µg/mL) and protein denaturation (110.5 µg/mL) compared to standard treatments, making it a viable treatment from a natural plant source. LC-MS analysis revealed the presence of phenolic compounds such as caffeic acid phenyl ester, hesperetin, hesperidin, chrysin and transient amounts of catechin, gallic acid, rutin and caffeic acid. The chemical constituents of this plant can be explored further to investigate its wide variety of therapeutic potential.

The Evolving Trends in Infective Endocarditis and Determinants of Mortality: a 10-year Experience From a Tertiary Care Epicenter.

The epidemiology of infective endocarditis (IE) continues to evolve in areas affected by the opioid epidemic. Understanding the demographics of the disease allows us to better tailor therapy towards this at-risk population. This was an observational study of adults (age ≥ 18) admitted to the University of Kentucky hospital with IE between January 2009 and December 2018. 1,255 patients were included in the final analysis. The mean age was 42 years, 45% were female and injection drug use was seen in 66% of patients. On multivariable analysis, higher Charlson comorbidity indices, left sided, and multivalve involvement were associated with increased mortality, whereas surgical intervention demonstrated a trend towards lower mortality. Our results highlight the alarming increase in injection drug use related IE and the high mortality rates despite therapeutic advances. Patients with left sided IE, multivalve involvement and a higher Charlson comorbidity index had decreased survival.

Periodontitis is associated with an increased hazard of mortality in a longitudinal cohort study over 50 years.

AIM: To evaluate the association between periodontal disease and all-cause mortality in a longitudinal cohort study over 50 years. MATERIALS AND METHODS: Participants (N = 1156) in the Veterans Affairs Dental Longitudinal Study, aged 25-85 years at enrollment in 1968, received comprehensive medical and oral exams approximately every 3 years through 2007. Periodontal status was defined using person-level, mean whole-mouth radiographic alveolar bone loss (ABL) scores using a five-point Schei ruler, each unit representing 20% increments of ABL. Time-varying Cox regression models estimated hazard ratios (HRs) for the association between continuous and categorical ABL and mortality, adjusting for covariates. RESULTS: Each one-unit increase in mean ABL score was associated with a 14% increase in the hazard of mortality (adjusted HR = 1.14, 95% confidence interval [CI] 1.02, 1.27). When assessed categorically, HRs for average scores of 2 to <3 and 3 to ≤5 showed increasing associations with hazard of mortality, relative to 0 to <1 (adjusted HR = 1.17, 95% CI 0.94, 1.46; and HR = 1.65, 95% CI 0.94, 2.85, respectively). By contrast, we observed null associations for average scores of 1 to <2 relative to 0 to <1 (adjusted HR = 1.00, 95% CI 0.86, 1.17). CONCLUSIONS: Time-varying periodontal status assessed using radiographic ABL was positively associated with all-cause mortality even after confounder adjustment.

Causal and Associational Language in Observational Health Research: A Systematic Evaluation.

We estimated the degree to which language used in the high-profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched for and screened 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, 3 reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as none (no causal implication) in 13.8%, weak in 34.2%, moderate in 33.2%, and strong in 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers' ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.

Exploring periodontitis misclassification mechanisms under partial-mouth protocols.

AIM: To investigate the sources of periodontitis misclassification under partial-mouth protocols (PMPs) and to explore possible approaches to enhancing protocol validity. MATERIALS AND METHODS: Using data from 10,680 adults with 244,999 teeth from the National Health and Nutrition Examination Survey, we compared tooth-, site-, and quadrant-specific periodontal parameters and case identification under full-mouth protocols and PMPs. Separately, we utilized population measures of tooth-specific periodontal severity to generate PMPs with tooth selection based on the population ranking of clinical severity and assessed the sensitivity of case identification. RESULTS: Symmetry of clinical severity was generally confirmed, with the exception of lingual inter-proximal sites, which yielded greater sensitivity in identifying periodontitis compared to buccal sites due to more severe pocketing and attachment loss on average. Misclassification of severe periodontitis occurred more frequently under commonly implemented PMPs compared to ranking-based selection of teeth, which yielded sensitivity estimates of 70.1%-79.4% with the selection of 8 teeth and reached 90% with the selection of only 14 teeth. CONCLUSIONS: Clinical symmetry and sources of periodontitis misclassification were confirmed. The proposed selection of teeth based on population rankings of clinical severity yielded optimal sensitivity estimates for the detection of severe periodontitis and may present a favourable alternative to current options.

Edentulism is associated with increased risk of all-cause mortality in adult men.

BACKGROUND: Prior reports of positive associations between edentulism and all-cause mortality have been limited by onetime assessments of edentulism and inadequate control of known confounding variables. The authors aimed to assess the association between edentulism and mortality using a longitudinal clinical oral health cohort. METHODS: The authors used data from the Department of Veterans Affairs Dental Longitudinal Study, an ongoing, closed-panel cohort study from 1968 through 2019 (N = 1,229). Dentition status was evaluated through triennial clinical examinations. Mortality was assessed via the National Death Registry. The authors used Cox regression models to estimate the association between edentulism and all-cause mortality after covariate adjustment. Furthermore, the authors calculated propensity scores and assessed hazard ratios (HRs) in a trimmed, matched, and inverse probability weighted sample. RESULTS: Participants who were edentulous (N = 112) had 1.24 (95% CI, 1.00 to 1.55) times the hazard of all-cause mortality compared with those who were nonedentulous, after adjustment with time-varying covariates. Use of propensity scores in the model resulted in slightly elevated HRs compared with the standard Cox model, regardless of propensity score method; adjusted HRs were 1.35 (95% CI, 1.01 to 1.80) after matching, 1.26 (95% CI, 1.00 to 1.59) after trimming, and 1.29 (95% CI, 1.18 to 1.42) after inverse probability weighting. CONCLUSIONS: Edentulism was associated with an increased risk of all-cause mortality in a cohort that captured incident edentulism. This association was consistent after multiple methods to account for confounding. PRACTICAL IMPLICATIONS: The findings of this study suggest that edentulism is associated with an increase in risk of mortality, after accounting for salient confounding variables using multiple approaches. Efforts to improve equitable access to tooth-preserving treatments are critical.

Ruta graveolens, Peganum harmala, and Citrullus colocynthis methanolic extracts have in vitro protoscolocidal effects and act against bacteria isolated from echinococcal hydatid cyst fluid.

Echinococcosis is a common and endemic disease that affects both humans and animals. In this study, the in vitro activities of methanolic extracts of Ruta graveolens, Peganum harmala aerial parts, and Citrullus colocynthis seeds against protoscolosis and isolated bacterial strains from hydatid cysts were assessed using disc diffusion methods and Minimum Inhibitory Concentration (MIC). The chemical composition of three methanolic extracts was studied using LC-MS. After 3 h of exposure to 40 mg/mL R. graveolens extract, a tenfold protoscolocidal effect was seen when compared to the convintional medication (ABZ) for the same duration (P < 0.05). The bacteria listed below were isolated from hydatid cyst fluid collected from a variety of sick locations, including the lung and liver. Micrococcus spp., E. coli, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter amnigenus, Pseudomonas aeruginosa, Staphylococcus xylosus, and Achromobacter xylosoxidans are among the bacteria that have been identified. The most effective extract was R. graveolens, followed by P. harmala and C. colocynthis, according to the results of antibacterial activity using the disc diffusion method. R. graveolens extract had the lowest MIC values (less than 2 mg/mL) against all microorganisms tested. This shows that the R. graveolens extract has additional properties, such as the ability to be both scolocidal and bactericidal. Because these bacteria are among the most prevalent pathogenic bacteria that increase the risk of secondary infection during hydatid cysts, the results of inhibitory zones and MICs of the R. graveolens methanol extract are considered highly promising.

Interoperator reliability of an on-site machine learning-based prototype to estimate CT angiography-derived fractional flow reserve.

BACKGROUND: Advances in CT and machine learning have enabled on-site non-invasive assessment of fractional flow reserve (FFRCT). PURPOSE: To assess the interoperator and intraoperator variability of coronary CT angiography-derived FFRCT using a machine learning-based postprocessing prototype. MATERIALS AND METHODS: We included 60 symptomatic patients who underwent coronary CT angiography. FFRCT was calculated by two independent operators after training using a machine learning-based on-site prototype. FFRCT was measured 1 cm distal to the coronary plaque or in the middle of the segments if no coronary lesions were present. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate interoperator variability effect in FFRCT estimates. Sensitivity analysis was done by cardiac risk factors, degree of stenosis and image quality. RESULTS: A total of 535 coronary segments in 60 patients were assessed. The overall ICC was 0.986 per patient (95% CI 0.977 to 0.992) and 0.972 per segment (95% CI 0.967 to 0.977). The absolute mean difference in FFRCT estimates was 0.012 per patient (95% CI for limits of agreement: -0.035 to 0.039) and 0.02 per segment (95% CI for limits of agreement: -0.077 to 0.080). Tight limits of agreement were seen on Bland-Altman analysis. Distal segments had greater variability compared with proximal/mid segments (absolute mean difference 0.011 vs 0.025, p<0.001). Results were similar on sensitivity analysis. CONCLUSION: A high degree of interoperator and intraoperator reproducibility can be achieved by on-site machine learning-based FFRCT assessment. Future research is required to evaluate the physiological relevance and prognostic value of FFRCT.

National Diagnostic Reference Levels for Nuclear Medicine in Kuwait.

The diagnostic reference level (DRL) is a patient-exposure optimization tool used to evaluate and provide guidance for radiation doses in medical imaging. In the past few decades, there has been a global increase in the number of diagnostic imaging procedures, including nuclear medicine procedures, and consequently in patient radiation exposure. This increase has encouraged international and national health-care organizations to take action and keep up with such changes to meet the expectation of increasing use of ionizing radiation in medicine. Methods: DRLs in Kuwait were established by investigating the administered activity of radiopharmaceuticals and CT radiation doses in hybrid imaging systems. The DRLs were determined on the basis of the 75th percentile of radiopharmaceutical administered activity distribution as recommended by the International Commission on Radiological Protection. Results: The DRLs determined in Kuwait agree well with other published DRLs in Europe, Japan, Korea, Australia, and the United States. Conclusion: This study presents the establishment process and the results of the first national DRLs for nuclear medicine procedures in Kuwait as a way to optimize radiation exposure.

Diagnosis of cardiac sarcoidosis: a primer for non-imagers.

Sarcoidosis is a multisystem granulomatous disorder that can potentially involve any organ. Cardiac involvement in sarcoidosis has been reported in up to 25% of patients based on autopsy and imaging studies. The gold standard for diagnosing cardiac sarcoidosis is endomyocardial biopsy demonstrating non-caseating granulomas; however, this technique lacks sensitivity due to the patchy nature of myocardial involvement. This, along with the non-specific clinical presentation, renders the diagnosis of cardiac sarcoidosis extremely challenging. Difficulties in obtaining histopathologic diagnosis and the advances in imaging modalities have led to a paradigm shift toward non-invasive imaging in the diagnosis of cardiac sarcoidosis. Advances in cardiac imaging modalities have also allowed unprecedented insights into the prevalence and natural history of cardiac sarcoidosis. This review discusses the role of non-invasive imaging for diagnosis, risk stratification, and monitoring the response to therapies in cardiac sarcoidosis. Echocardiography remains the first-line modality due to widespread availability and affordability. Cardiac magnetic resonance imaging (CMR) can be used to study cardiac structure, function, and most importantly tissue characterization to detect inflammation and fibrosis. Fluoro-deoxy glucose positron emission tomography (FDG PET) is the gold standard for non-invasive detection of cardiac inflammation, and it offers the unique ability to assess response to therapeutic interventions. Hybrid imaging is a promising technique that allows us to combine the unique strengths of CMR and FDG PET. Understanding the advantages and disadvantages of each of these imaging modalities is crucial in order to tailor the diagnostic algorithm and utilize the most appropriate modality for each patient.

Enhancement of the dissolution and in-vitro activity of a new antineoplastic agent.

The cell-surface molecule CD44 plays a major role in the regulation of cancer stem cells. The CD44 inhibitor compound N'-(1-dimethylaminomethyl-2-oxoindolin-3-ylidene)-2-(benzyloxy)benzohydrazide (OYB), anticancer agent is practically insoluble in water. Hence, the solid dispersion (SD) technique was used for enhancing the dissolution of OYB. The SD of OYB was achieved using OYB:poloxamer 188 (1:7) via the fusion method. The anticancer activities of the free-OYB solution and the SD formulation (OYB-SD) were investigated in-vitro. The dissolution rate of OYB-SD (1:7) increased by 2-fold compared with the untreated drug (51.52-100% at pH 1.2 and 8.25-19.15% at pH 7 buffer). In addition, OYB-SD afforded 3-folds cytotoxic effect, against LoVo cells, compared to the untreated compound (IC50 4.72 ± 0.57 and 13.97 ± 0.90 µg/ml, respectively) and against HepG2 (∼3-fold) (4.98 ± 0.368 and 13.85 ± 1.82 µg/ml, respectively) and MCF-7 (1.4-fold) cells (15.20 ± 0.20 and 21.12 ± 0.51 µg/ml, respectively), and enhanced the apoptotic potential in LoVo cells compared with free-OYB. The improved cytotoxic activity of the drug might be attributable to the enhanced dissolution of OYB.