Rapid, antibiotic incubation-free determination of tuberculosis drug resistance using machine learning and Raman spectroscopy.

Tuberculosis (TB) is the world's deadliest infectious disease, with over 1.5 million deaths and 10 million new cases reported anually. The causative organism Mycobacterium tuberculosis (Mtb) can take nearly 40 d to culture, a required step to determine the pathogen's antibiotic susceptibility. Both rapid identification and rapid antibiotic susceptibility testing of Mtb are essential for effective patient treatment and combating antimicrobial resistance. Here, we demonstrate a rapid, culture-free, and antibiotic incubation-free drug susceptibility test for TB using Raman spectroscopy and machine learning. We collect few-to-single-cell Raman spectra from over 25,000 cells of the Mtb complex strain Bacillus Calmette-Guérin (BCG) resistant to one of the four mainstay anti-TB drugs, isoniazid, rifampicin, moxifloxacin, and amikacin, as well as a pan-susceptible wildtype strain. By training a neural network on this data, we classify the antibiotic resistance profile of each strain, both on dried samples and on patient sputum samples. On dried samples, we achieve >98% resistant versus susceptible classification accuracy across all five BCG strains. In patient sputum samples, we achieve ~79% average classification accuracy. We develop a feature recognition algorithm in order to verify that our machine learning model is using biologically relevant spectral features to assess the resistance profiles of our mycobacterial strains. Finally, we demonstrate how this approach can be deployed in resource-limited settings by developing a low-cost, portable Raman microscope that costs <$5,000. We show how this instrument and our machine learning model enable combined microscopy and spectroscopy for accurate few-to-single-cell drug susceptibility testing of BCG.

Fundamentals and Translational Applications of Stem Cells and Biomaterials in Dental, Oral and Craniofacial Regenerative Medicine.

Regenerative dental medicine continuously expands to improve treatments for prevalent clinical problems in dental and oral medicine. Stem cell based translational opportunities include regenerative therapies for tooth restoration, root canal therapy, and inflammatory processes (e.g., periodontitis). The potential of regenerative approaches relies on the biological properties of dental stem cells. These and other multipotent somatic mesenchymal stem cell (MSC) types can in principle be applied as either autologous or allogeneic sources in dental procedures. Dental stem cells have distinct developmental origins and biological markers that determine their translational utility. Dental regenerative medicine is supported by mechanistic knowledge of the molecular pathways that regulate dental stem cell growth and differentiation. Cell fate determination and lineage progression of dental stem cells is regulated by multiple cell signaling pathways (e.g., WNTs, BMPs) and epigenetic mechanisms, including DNA modifications, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs). This review also considers a broad range of novel approaches in which stem cells are applied in combination with biopolymers, ceramics, and composite materials, as well as small molecules (agonistic or anti-agonistic ligands) and natural compounds. Materials that mimic the microenvironment of the stem cell niche are also presented. Promising concepts in bone and dental tissue engineering continue to drive innovation in dental and non-dental restorative procedures.

Basic Fuchsin Dye as the First Fluorophore for Optical Sensing of Morpholine in Fruits Crust and Urine Samples.

In this work, basic fuchsin (BF) dyestuff was presented as the first optical sensor used for the spectrofluorimetric assessment of morpholine (MOR) where BF exhibits morpholine-sensing behavior. The developed fluorimetric avenue is sensitive, facile, selective, and validated for assaying the sensitizing influence of MOR on the BF fluorescence in an aprotic dioxane solvent. Parameters like solvents, BF concentration, order, and time of addition that influence the fluorescence intensity of the probing system were addressed. Optimizing the analytical methodology revealed a linear fluorescence sensitization within the addition of MOR in the two concentration ranges of 5 × 10-9 to 1.0 × 10-7 mol L-1 and 2.0 × 10-7 to 3 × 10-6 mol L-1. The limit of detection (LOD) and limit of quantification (LOQ) were estimated to be 2.0 × 10-9 mol L-1 (0.17 ng mL-1) and 6.66 × 10-9 mol L-1 (0.567 ng mL-1), respectively. High levels of accuracy and precision are achieved when assaying spiked MOR either in pure solutions or samples of fruit peel extract and human urine. Moreover, the green character and practicality/applicability of the method were evaluated by AGREE and BAGI metric tools. These merit outcomes provide insights into the development of fluorescent sensors for MOR detection using fluorescent dyes and meet the Food and Drug Administration's requirements for morpholine detection in real-life applications.

Antibiotic-resistant bacteria contaminating leafy vegetables in Saudi Arabia's eastern region.

BACKGROUND: Food-associated antibiotic-resistant bacteria can cause infections that may critically impact human health. The objectives of this study were to determine the microbial contamination level of green leafy vegetables and their antibiotic resistance pattern. METHODS: Sixty-three samples of leafy vegetables were collected from Dammam Central Fruit and Vegetables Market from January to June 2023. The vegetables included lettuce (Lactuca sativa), parsley (Petroselinum crispum), and watercress (Nasturtium officinale). Samples were tested by standard microbiological techniques for identification and antibiotic susceptibility testing. RESULT: Eight types of bacteria belonging to six different genera were detected. Enterobacteriaceae family was represented by four genera: Klebsiella, Proteus, Morganella, and Enterobacter. The other two genera were Pseudomonas and Aeromonas. Enterobacter cloacae was the most abundant organism, followed by Pseudomonas putida and Aeromonas sobria. On the other hand, Morganella morganii, Aeromonas hydrophila, and Proteus mirabilis were the least abundant. The three vegetable types had different levels of bacterial contamination. All isolated organisms were sensitive to penicillin, cephalosporin, aminoglycoside, and fluoroquinolone. However, Klebsiella oxytoca, M. morganii, and K. pneumonia showed resistance to ampicillin. A. hydrophila, Morganella morganii, and E. cloacae showed resistance to amoxicillin. M. morganii and E. cloacae were found to be resistant to cefalotin. Moreover, A. hydrophila, M. morganii, and E. cloacae were resistant to cefoxitin. Again, A. hydrophila was found to be resistant to imipenem. Only M. morganii was resistant to Ciprofloxacin. Two isolates, P. mirabilis and M. morganii were resistant to tigecycline. Another two, M. morganii and P. mirabilis were resistant to Nitrofurantoin. Only M. morganii was found to be resistant to trimethoprim. CONCLUSION: This study aligns with the broad consensus in the literature about the significance of bacterial contamination in vegetables and the public health implications. The unique focus on antibiotic resistance patterns adds an essential dimension to the existing body of knowledge.

Magnetic resonance imaging of pilonidal sinus disease: interobserver agreement and practical MRI reporting tips.

OBJECTIVE: To evaluate the interobserver agreement for the features of natal cleft pilonidal sinus disease (PSD) on magnetic resonance imaging (MRI) and propose a standardized checklist for reporting PSD on MRI. MATERIALS AND METHODS: Forty MRI studies of 39 discrete patients with PSD were retrospectively evaluated by five independent radiologists using a standardized checklist. Fleiss' Kappa (k) coefficients of agreement were used to test the agreement between categorical variables. The MRI features of the natal cleft sepsis associated with PSD were classified into four main categories: morphology, branching and extensions, external skin openings, and the relationship of the PSD to the coccyx. A survey was created and disseminated online among general surgeons who treat patients with PSD to assess the relevance of the MRI features proposed in the standardized checklist. RESULTS: The overall agreement regarding the identification of morphology of the natal cleft sepsis was moderate (k = 0.59). Lateral and caudal extensions interobserver agreement was substantial (k = 0.64 and 0.71, respectively). However, the overall agreement regarding the individual parts of anal sphincter involved was moderate (k = 0.47). Substantial interobserver agreement was found in assessing the proximity of the PSD to the coccyx (k = 0.62). CONCLUSION: Preoperative MRI can delineate the extensions and branching of PSD with substantial agreement. MRI is superior in describing the deep extensions of PSD with better reliability than assessing the number and locations of the external openings. Expert consensus agreement is needed to establish the MRI features necessary for optimal reporting of PSD. CLINICAL RELEVANCE STATEMENT: MRI can offer valuable information about the extent of sepsis associated with pilonidal sinus disease, particularly in cases with involvement of critical anatomical structures such as the coccyx and anal triangle. MRI can potentially contribute to more accurate patient stratification and surgical planning. KEY POINTS: • The interobserver agreement for assessing PSD's lateral and caudal extension on MRI is substantial. • MRI can describe deep extensions and branching of PSD with superior reliability than assessing the number and site of external openings. • Reporting the relationship between natal cleft sepsis in PSD and the anal region may influence the surgical approach and postoperative healing.

Impact of residual coronary lesions on outcomes of myocardial infarction patients with multi-vessel disease.

BACKGROUND: The residual burden of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) drew a growing interest. The residual SYNTAX Score (rSS) was a strong prognostic factor of adverse events and all-cause mortality in patients who underwent PCI. In addition, the SYNTAX Revascularization Index (SRI), a derivative of rSS, was used to figure out the treated proportion of CAD and could be used as a prognostic utility in PCI for patients with multi-vessel disease (MVD). PURPOSE: We aimed at the assessment of the use of rSS and the SRI as predictors of in-hospital outcomes and up to two-year cumulative follow-up outcomes in patients with MVD who had PCI for the treatment of ST-Elevation Myocardial Infarction (STEMI) or Non-STEMI (NSTEMI). METHODS: We recruited 149 patients who had either STEMI or NSTEMI while having MVD and received treatment with PCI. We divided them into tertiles based on their rSS and SRI values. We calculated baseline SYNTAX Score (bSS) and rSS using the latest version of the calculator on the internet, and we used both scores to calculate SRI. The study end-points were In-hospital composite Major Adverse Cardiovascular Events (MACE) and its components, in-hospital death, and follow-up cumulative MACE up to 2 years. RESULTS: Neither rSS nor SRI were significant predictors of in-hospital adverse events, while female sex, hypertension, and left ventricular ejection fraction were independent predictors of in-hospital MACE. At the two-year follow-up, Kaplan-Meyer analysis showed a significantly increased incidence of MACE within the third rSS tertile (rSS > 12) compared to other tertiles (log rank p = 0.03). At the same time, there was no significant difference between the three SRI tertiles. Unlike SRI, rSS was a significant predictor of cumulative MACE on univariate Cox regression (HR = 1.037, p < 0.001). On multivariate Cox regression, rSS was a significant independent predictor of two-year cumulative MACE (HR = 1.038, p = 0.0025) along with female sex, hypertension, and left ventricular ejection fraction. We also noted that all patients with complete revascularization survived well throughout the entire follow-up period. CONCLUSIONS: Neither rSS nor SRI could be good predictors of in-hospital MACE, while the rSS was a good predictor of MACE at two-year follow-up. Patients with rSS values > 12 had a significantly higher incidence of cumulative MACE after 2 years. The best prognosis was achieved with complete revascularization.

Effect of residual myocardial ischemia on recovery of left ventricular function after primary percutaneous coronary intervention.

BACKGROUND: It is unknown whether the existence of severe bystander damage will affect left ventricular (LV) healing following primary percutaneous coronary intervention (PPCI). The aim of the present analysis was to follow LV recovery using 2D speckle tracking echocardiography (2-D STE) in cases with single versus multiple vessel disease with acute myocardial infarction (AMI) who underwent PPCI and to assess major adverse cardiovascular events (MACEs) within 3 months. PATIENTS AND METHODS: This work was conducted at Assiut University Heart Hospital. Of 1026 screened subjects with AMI needing PPCI and assessed for eligibility, only 89 cases fulfilled the inclusion criteria. They were classified into Group A: single vessel and Group B: multiple vessel (≥ 2 vessels) disease. Their data were obtained on admittance and after 90 days. RESULTS: In group A compared to group B, there was a statistically preferable value at baseline in the global longitudinal strain- Apical 2 chamber (GLS-A2C) (-12.05 ± 3.57 vs. -10.38 ± 3.92, P = 0.039). At follow-up, the improvement was in all 2-D STE variables, including GLS-long axis (GLS-LAX) (-13.09 ± 3.84 vs.-10.75 ± 3.96, P = 0.006), GLS- apical 4 chamber (GLS-A4C) (-13.23 ± 3.51 vs.-10.62 ± 4.08, P = 0.002), GLS-A2C (-13.85 ± 3.41 vs-10.93 ± 3.97, P < 0.001) and GLS- average (GLS-AVG, P = 0.001). There was a considerable negative correlation between the recovery of LV performance and the existence of multi-vessel lesions (P = 0.009). There was no variance between the groups regarding MACEs. CONCLUSIONS: Patients with single vessel lesions who underwent PPCI to the culprit lesion had better recovery of LV function than those with multi-vessel (≥ 2 vessels) lesions who underwent PPCI to the culprit lesion only. The presence of multivessel involvement was an independent risk factor for deterioration in GLS. TRIAL REGISTRATION: Registered in clinical trial, clinicalTrial.gov ID NCT04103008 (25/09/2019). IRB registration: 17,100,834 (05/11/2019).

Side-specific factors for intraoperative hemodynamic instability in laparoscopic adrenalectomy for pheochromocytoma: a comparative study.

BACKGROUND: Adrenalectomy for pheochromocytoma (PHEO) is challenging because of the high risk of intraoperative hemodynamic instability (HDI). This study aimed to compare the incidence and risk factors of intraoperative HDI between laparoscopic left adrenalectomy (LLA) and laparoscopic right adrenalectomy (LRA). METHODS: We retrospectively analyzed two hundred and seventy-one patients aged > 18 years with unilateral benign PHEO of any size who underwent transperitoneal laparoscopic adrenalectomy at our hospitals between September 2016 and September 2023. Patients were divided into LRA (N = 122) and LLA (N = 149) groups. Univariate and multivariate logistic regression analyses were used to predict intraoperative HDI. In multivariate analysis for the prediction of HDI, right-sided PHEO, PHEO size, preoperative comorbidities, and preoperative systolic blood pressure were included. RESULTS: Intraoperative HDI was significantly higher in the LRA group than in the LLA (27% vs. 9.4%, p < 0.001). In the multivariate regression analysis, right-sided tumours showed a higher risk of intraoperative HDI (odds ratio [OR] 5.625, 95% confidence interval [CI], 1.147-27.577, p = 0.033). The tumor size (OR 11.019, 95% CI 3.996-30.38, p < 0.001), presence of preoperative comorbidities [diabetes mellitus, hypertension, and coronary heart disease] (OR 7.918, 95% CI 1.323-47.412, p = 0.023), and preoperative systolic blood pressure (OR 1.265, 95% CI 1.07-1.495, p = 0.006) were associated with a higher risk of HDI in both LRA and LLA, with no superiority of one side over the other. CONCLUSION: LRA was associated with a significantly higher intraoperative HDI than LLA. Right-sided PHEO was a risk factor for intraoperative HDI.

Enhancing functional buffalo yogurt: Improving physicochemical properties, biological activities, and shelf life using marjoram and geranium essential oils.

The use of essential oils (EO) has attracted interest in the food industry because of their wide range of beneficial properties. In this study, a new functional yogurt was developed using 2 EO, marjoram and geranium, at 3 different concentrations (0.2%, 0.4%, and 0.6% vol/vol). The physicochemical properties, including syneresis, viscosity, pH, and chemical composition; bioactivities, including antioxidant activity, anticancer and antibacterial effects, total phenolic content (TPC), and total flavonoid content (TFC); and sensory characteristics of the developed yogurt were evaluated. The findings indicated that the yogurts fortified with 0.6% marjoram or geranium exhibited higher viscosity and lower syneresis compared with other treatments. The yogurt supplemented with 0.6% marjoram displayed significant antibacterial activity against Listeria monocytogenes, Staphylococcus aureus, Salmonella typhimurium, and Escherichia coli. In addition, the yogurt enriched with geranium and marjoram oils at a concentration of 0.6% had notably significant (P < 0.05) higher TFC levels compared with the control sample and other concentrations. In the same context, in terms of TPC, yogurt supplemented with 0.6% marjoram displayed significantly (P < 0.05) elevated levels in comparison to the other samples tested. Yogurt enriched with marjoram oil exhibited noteworthy antioxidant activity, followed by geranium oil, compared with the control samples. The yogurt supplemented with 0.6% marjoram demonstrated strong radical scavenging activity, and the yogurt fortified with 0.6% geranium showed higher anticancer activity against HepG2 human liver carcinoma cells and oxidative stress enzyme activities. Among the various concentrations of EO tested, the yogurts fortified with 0.6% marjoram or geranium EO exhibited the most favorable outcomes, followed by 0.4% marjoram or geranium. To summarize, geranium and marjoram EO can be used as a potential nutritious ingredient and as a natural preservative for milk and related products.

Sex comparison of oxidative stress, mitochondrial dysfunction, and apoptosis triggers induced by single-dose Abamectin in albino rats.

Abamectin (AB) is widely used in agriculture and has been employed as an insecticide, nematicide, and livestock pest control agent. However, it may also pose a serious threat to mammals. The primary purpose of this research was to compare the sex variations between male and female rats during exposure and to assess the risk of toxicity of abamectin, which are still largely unknown. The twenty albino rats were divided randomly into four groups (n = 5): 1) the male control group; 2) the male treatment group treated with AB (1 mg/kg B.W.); 3) the female control group; and 4) the female treatment group treated with AB (1 mg/kg B.W.). AB administration caused a drop in body weight in females more than males with showing oxidative stress in both sexes of animals, as characterized by an increase in MDA content and a decrease in glutathione (GSH) content and superoxide dismutase (SOD) activity. Reported sex-specific effects suggested that females are more susceptible from males in brain tissues for alteration of antioxidant markers while females' liver and kidney tissues showed more level of lipid peroxidation than males. In addition, mitochondrial dysfunction was associated with a significant decrease in NADH dehydrogenase (Complex I) and a significant decrease in mitochondrial ATPase, which led to apoptosis and histopathological alterations in the targeted tissues, indicating that females are higher sensitive than males to these biological events. In brief, the results of this study led to female rats are generally more sensitive than male rats to neurobehavioral and hepatic complications associated with abamectin treatment. Further evaluation should be performed to determine the adverse outcome pathways involved and to determine the effects of sex on improving the risk assessment of abamectin in both sexes.

Transcatheter recanalisation for absent intra-pericardial pulmonary arteries.

Unilateral absence of intra-pericardial pulmonary artery is a rare congenital malformation. If untreated, it can lead to morbidity and mortality in adulthood. Early intervention and restoration of physiologic pulmonary blood flow is necessary. Transcatheter stenting as initial intervention has been rarely reported. We present transcatheter recanalisation and stenting of the obliterated ductus in two newborns with unilateral absence of intra-pericardial pulmonary artery with cross-sectional imaging, procedural details, angiography, and follow up to surgical repair. We believe that such procedure promotes ipsilateral pulmonary vasculature growth to facilitate unifocalization surgery at a later age.

Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock after valve replacement.

BACKGROUND: Limited data evaluated the outcomes of extracorporeal membrane oxygenation (ECMO) in patients with prosthetic valves. This study aimed to compare the outcomes of ECMO support for postcardiotomy cardiogenic shock in patients with mechanical versus bioprosthetic valves. METHODS: This retrospective study included patients with ECMO support for postcardiotomy cardiogenic shock after valve replacement. Patients were grouped into bioprosthetic (n = 49) and mechanical valve (n = 22) groups. RESULTS: There were no differences in ECMO duration, inotropic support, intra-aortic balloon pump (IABP), stroke, duration of ICU, and hospital stay between groups. Postoperative thrombosis occurred in 2 patients with bioprosthetic valves (5.41%) and 2 with mechanical valves (14.29%), p = .30. All patients with thrombosis had central ECMO cannulation, concomitant IABP, and inotropic support during ECMO. All thrombi were related to the mitral valve. Three patients with thrombi had hospital mortality.Survival at 6, 12, and 36 months for bioprosthetic valve patients was 30.88%, 28.55%, and 25.34% and for mechanical valves was 36.36% for all time intervals (Log-rank p = .93). One patient had bioprosthetic aortic valve endocarditis after 1 year. Three patients with bioprosthetic valves had structural valve degeneration after 1, 2, and 5 years. CONCLUSIONS: Outcomes of ECMO in patients with prosthetic valves are comparable between bioprosthetic and mechanical valves. Thrombosis might occur in both valve types and was associated with high mortality. ECMO could affect the long-term durability of the bioprosthetic valves.

Combining Acoustic Bioprinting with AI-Assisted Raman Spectroscopy for High-Throughput Identification of Bacteria in Blood.

Identifying pathogens in complex samples such as blood, urine, and wastewater is critical to detect infection and inform optimal treatment. Surface-enhanced Raman spectroscopy (SERS) and machine learning (ML) can distinguish among multiple pathogen species, but processing complex fluid samples to sensitively and specifically detect pathogens remains an outstanding challenge. Here, we develop an acoustic bioprinter to digitize samples into millions of droplets, each containing just a few cells, which are identified with SERS and ML. We demonstrate rapid printing of 2 pL droplets from solutions containing S. epidermidis, E. coli, and blood; when they are mixed with gold nanorods (GNRs), SERS enhancements of up to 1500× are achieved.We then train a ML model and achieve ≥99% classification accuracy from cellularly pure samples and ≥87% accuracy from cellularly mixed samples. We also obtain ≥90% accuracy from droplets with pathogen:blood cell ratios <1. Our combined bioprinting and SERS platform could accelerate rapid, sensitive pathogen detection in clinical, environmental, and industrial settings.

Influence of matrix metalloproteinase 9 variant rs17576 on ischemic stroke risk and severity in acute coronary syndrome.

BACKGROUND: Ischemic injury is a common mechanism in both ischemic stroke (IS) and acute coronary syndrome (ACS). Matrix metalloproteinase 9 (MMP-9), an endopeptidase that degrades extracellular matrix, is important in the pathogenesis of IS. The purpose of this study is to evaluate the association between the SNP rs17576 in MMP-9 gene with (1) the risk and severity of acute ischemic stroke in Saudi Arab individuals with recent acute coronary syndrome, and (2) the risk of acute coronary syndrome in Saudi Arab individuals without ischemic stroke. METHODS: A case control study of 200 IS patients, 520 ACS patients (without IS), and 500 aged-matched healthy controls were genotyped to detect the MMP-9 polymorphism rs17156. RESULTS: Our study demonstrated a non-significant difference in the genotype and allele frequencies of the MMP9 rs17576 polymorphism between the patients with IS and patients with ACS without IS (P = 0.31 for the GA genotype, 0.25 for the AA genotype and P = 0.20 for the A allele). AA genotype was found to be statistically significant between IS and control groups; [OR=1.84, 95 % CI (1.08-3.14), p =0.015]. A allele showed a significant difference between the two groups [OR=1.28, 95 % CI (1.00-1.64), p =0.028]. By comparing ACS without IS and controls, AA genotype was significant [OR=1.46, 95 % CI (1.01-2.12), p =0.029]. Stratification by NIHSS score revealed higher mortality and early neurologic deterioration in IS patients with NIHSS score ≥ 16 (p < 0.001, 0.044 respectively). CONCLUSION: We deduced the lack of association either with allele or genotype frequencies (p>0.05) between the IS cases and the cases of ACS without IS. In contrast there was a significant association of mutant genotype AA between either the IS group or ACS (without IS) group, and the control group. In addition, different rs17576 genotypes were not associated with raised mortality or a tendency to develop early neurologic deterioration.

Neuroprotective effect of Withania somnifera leaves extract nanoemulsion against penconazole-induced neurotoxicity in albino rats via modulating TGF-ß1/Smad2 signaling pathway.

Penconazole (PEN) is a systemic triazole fungicide used to control various fungal diseases on grapes, stone fruits, cucurbits, and strawberries. Still, it leaves residues on treated crops after collection with many hazardous effects on population including neurotoxicity. Withania somnifera leaves extract (WSLE) is known for its memory and brain function enhancing ability. To evoke such action efficiently, WSLE bioactive metabolites are needed to cross the blood-brain barrier, that could limit the availability of such compounds to be localized within the brain. Therefore, in the present study, the association between PEN exposure and neurotoxicity was evaluated, and formulated WSLE nanoemulsion was investigated for improving the permeability of the plant extract across the blood-brain barrier. The rats were divided into five groups (n = 6). The control group was administered distilled water, group II was treated with W. somnifera leaves extract nanoemulsion (WSLE NE), group III received PEN, group IV received PEN and WSLE, and group V received PEN and WSLE NE. All rats were gavaged daily for 6 weeks. Characterization of compounds in WSLE using LC-MS/MS analysis was estimated. Neurobehavioral disorders were evaluated in all groups. Oxidative stress biomarkers, antioxidant enzyme activities, and inflammatory cytokines were measured in brain tissue. Furthermore, the gene expression patterns of GFAP, APP, vimentin, TGF-ß1, Smad2 and Bax were measured. Histopathological changes and immunohistochemical expression in the peripheral sciatic nerve and cerebral cortex were evaluated. A total of 91 compounds of different chemo-types were detected and identified in WSLE in both ionization modes. Our data showed behavioral impairment in the PEN-treated group, with significant elevation of oxidative stress biomarkers, proinflammatory cytokines, neuronal damage, and apoptosis. In contrast, the PEN-treated group with WSLE NE showed marked improvement in behavioral performance and histopathological alteration with a significant increase in antioxidant enzyme activity and anti-inflammatory cytokines compared to the group administered WSLE alone. The PEN-treated group with WSLE NE in turn significantly downregulated the expression levels of GFAP, APP, vimentin, TGF-ß1, Smad2 and Bax in brain tissue. In conclusion, WSLE NE markedly enhanced the permeability of plant extract constituents through the blood brain barrier to boost its neuroprotective effect against PEN-induced neurotoxicity.

Expression of miR-34a, RASSF1A and E-cadherin in relation to PRB in endometrioid carcinoma and its precursor.

The current study aims to evaluate the levels of miR-34a, RASSF1A, and E-cadherin in relation to the levels of isoform B of progesterone receptor (PRB) in endometrioid carcinoma (EC) and atypical hyperplasia (AEH) and their association with clinicopathological parameters. 105 cases (35 EC, 35 AEH, and 35 control) were involved in this study. Cases of AEH received treatment, and other samples were obtained after 6 months to assess the response. E-cadherin and PRB were assessed by immunohistochemistry (IHC), RASSFA methylation by MSP-PCR, and its serum level by ELISA and miR-34a via quantitative PCR. The expressions of miR-34a, RASSF1A, E-cadherin, and PRB differ among the studied groups; all were higher in normal compared with AEH and EC, with a statistically significant difference. The higher PRB expression and decreased miR-34a and RASSF1A expression were associated with resistance to hormonal therapy in AEH. High PRB in EC is associated with lower RASSFA1, E-cadherin, and miR-34a. Decreased expressions of RASSF1A, miR-34a, and E-cadherin had a significant connection to advanced stages. Expression of PRB and miR-34a and serum levels of RASSF1A predict response to treatment in cases of AEH. High PRB and low E-cadherin expression are associated with progressive disease in EC.

Comparison of Patient Demographics and Risk of Surgical Site Infections Following Open Reduction and Internal Fixation of Trimalleolar Ankle Fractures: A Nationwide Analysis of a Private Payor.

Surgical site infections (SSIs) are a notable complication following open reduction and internal fixation (ORIF) for ankle fractures. The purpose of this study was to (1) compare baseline demographics of patients who did and did not develop SSIs within 90 days following ORIF for trimalleolar ankle fractures and (2) identify risk factors associated with SSIs in this setting. A retrospective analysis from 2010 to 2020 was completed using a national administrative database. The study group consisted of patients who underwent ORIF for trimalleolar ankle fractures and developed SSIs within 90 days postoperatively. Patients without SSIs served as the comparison cohort. Baseline demographics of the two cohorts were compared utilizing Pearson's Chi-Square Analyses. A multivariate binomial logistic regression model determined the association of various comorbidities on developing SSIs in this setting. Out of a total sample of 22,118 patients, 1000 individuals (4.52%) developed SSIs. The study revealed that the SSI cohort exhibited a greater burden of comorbidities, as evidenced by significant differences in various individual comorbidities and average Elixhauser-Comorbidity Indices scores. The most strongly associated risk factors for the development of SSIs following ORIF for trimalleolar ankle fractures were peripheral vascular disease (OR: 1.53, p < .0001), diabetes mellitus (OR: 1.26, p = .0010), iron deficiency anemia (OR: 1.24, p = .0010), male sex (OR: 1.22, p = .0010), and tobacco use (OR: 1.15, p = .0010). This study identified several patient risk factors that were associated with developing SSIs after ORIF for trimalleolar ankle fractures, recognizing potential patient-directed interventions that may reduce the rate of SSIs in this setting.

Primary arthrodesis for diabetic ankle fractures using a modified retrograde femoral intramedullary locking nail combined with lateral plating, surgical technique, and early results of a pilot study.

PURPOSE: We aimed to report the early results of performing acute ankle arthrodesis using a modified retrograde femoral intramedullary locking IMN concomitant with plating at the same setting for managing diabetic patients' acute ankle fractures. METHODS: We prospectively included patients who presented acutely with ankle fractures, where hemoglobin A1C (HbA1C) on admission was > 7%, and the Adelaide Fracture in the Diabetic Ankle (AFDA) algorithm score was 5 or above. All patients were treated by acute ankle arthrodesis using a modified retrograde femoral IMN combined with lateral plating. Functional assessment was reported according to a modified American Orthopaedic Foot and Ankle Society ankle hindfoot scale (AOFAS), and complications were documented. RESULTS: Six patients had an average age of 55.7 years (37-65). The average HbA1C on admission was 7.9 (7.3-9), and the average AFDA score was 7.3 (6-8). The average operative time was 79.2 min (70-90). All patients, except for one, achieved union at the arthrodesis site after an average of 10.3 weeks (8-14). After an average last follow-up of 9 months (6-12), the average modified AOFAS was 73.2 (82 to 62); four patients had an excellent score and one good. Complications developed in two, one deep infection after 2 weeks treated by metal removal and Ilizarov, and the other patient developed a stress fracture at the tibial end of the nail, which was treated by open reduction and internal fixation using a plate and screws. CONCLUSION: Using a modified femoral IMN combined with lateral plating is a promising technique to achieve ankle arthrodesis in diabetic patients with acute ankle fractures with acceptable outcomes; however, further studies with larger numbers are needed. LEVEL OF EVIDENCE: IV.

Comparison of patient demographics and patient-specific risk factors for readmissions following open reduction and internal fixation for acetabular fractures.

PURPOSE: Acetabular fractures are highly complex injuries often resulting from high-energy trauma. The gold standard treatment for these injuries has become open reduction internal fixation (ORIF). The purpose of this study is to further this understanding and investigate how (1) patient demographics and (2) patient-specific risk factors affect 90-day readmission rates. METHODS: A retrospective, nationwide query of private insurance database from January 1st, 2010 to October 31st, 2020 was performed using ICD-9, ICD-10, and CPT codes. Patients who underwent acetabular ORIF and were readmitted within 90 days following index procedure were included, patients who were not readmitted served as controls. Patients were divided by demographics and specific risk factors associated with readmission. RESULTS: The query yielded a total of 3942 patients. Age and sex were found to be non-significant contributing risk factors to 90-day readmissions. Data also showed that statistically significant comorbidities included arrhythmia, cerebrovascular disease, coagulopathy, fluid and electrolyte abnormalities, and pathologic weight loss. CONCLUSION: This study illustrated how several patient-specific risk factors may contribute to increased 90-day readmission risk following acetabular ORIF. A heightened awareness of these comorbidities in patients requiring acetabular ORIF is required to improve patient outcomes and minimize rates of readmission. Further investigation is needed to improve patient outcomes, and increase awareness of potential post-operative complications in these higher-risk patient populations.

Outcomes of Left Main Revascularization in Patients with Anemia: Gulf Left Main Registry.

INTRODUCTION: The aim of this study was to evaluate the effects of baseline anemia and anemia following revascularization on outcomes in patients with unprotected left main coronary artery (ULMCA) disease. METHODS: This was a retrospective, multicenter, observational study conducted between January 2015 and December 2019. The data on patients with ULMCA who underwent revascularization through percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) were stratified by the hemoglobin level at baseline into anemic and non-anemic groups to compare in-hospital events. The pre-discharge hemoglobin following revascularization was categorized into very low (<80 g/L for men and women), low (≥80 and ≤119 g/L for women and ≤129 g/L for men), and normal (≥130 g/L for men and ≥120 g/L for women) to assess impact on follow-up outcomes. RESULTS: A total of 2,138 patients were included, 796 (37.2%) of whom had anemia at baseline. A total of 319 developed anemia after revascularization and moved from being non-anemic at baseline to anemic at discharge. There was no difference in hospital major adverse cardiac and cerebrovascular event (MACCE) and mortality between CABG and PCI in anemic patients. At a median follow-up time of 20 months (interquartile range [IQR]: 27), patients with pre-discharge anemia who underwent PCI had a higher incidence of congestive heart failure (CHF) (p < 0.0001), and those who underwent CABG had significantly higher follow-up mortality (HR: 9.85 (95% CI: 2.53-38.43), p = 0.001). CONCLUSION: In this Gulf LM study, baseline anemia had no impact upon in-hospital MACCE and total mortality following revascularization (PCI or CABG). However, pre-discharge anemia is associated with worse outcomes after ULMCA disease revascularization, with significantly higher all-cause mortality in patients who had CABG, and a higher incidence of CHF in PCI patients, at a median follow-up time of 20 months (IQR: 27).