Novel Insights into the Antimicrobial and Antibiofilm Activity of Pyrroloquinoline Quinone (PQQ); In Vitro, In Silico, and Shotgun Proteomic Studies.

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.

Current status of resident simulation training curricula: pearls and pitfalls.

BACKGROUND: Residency programs are required to incorporate simulation into their training program. Ideally, simulation provides a safe environment for a trainee to be exposed to both common and challenging clinical scenarios. The purpose of this review is to detail the current state of the most commonly used laparoscopic, endoscopic, and robotic surgery simulation programs in general surgery residency education, including resources required for successful implementation and benchmarks for evaluation. MATERIALS AND METHODS: Members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Resident and Fellow Task Force (RAFT) Committee performed a literature review using PubMed and training websites. Information regarding the components of the most commonly used laparoscopic, endoscopic, and/or robotic simulation curriculum, including both formal and informal benchmarks for evaluating training competence, were collected. RESULTS: Laparoscopic simulation revolves around the Fundamentals of Laparoscopic Surgery (FLS). Proficiency-based as well as virtual simulation have been utilized for FLS training curricula. Challenges include less direct translation to the technical complexities that can arise in laparoscopic surgery. Endoscopic simulation focuses on the Fundamentals of Endoscopic Surgery. There are virtual reality simulation platforms that can be used for skills assessment and training. Challenges include simulator types and access, as well as structured mentoring and feedback. Robotic simulation training curricula have not been standardized. Simulation includes one primary technology, which can be prohibitive based on cost and requirements for onboarding. CONCLUSIONS: While surgical simulation seems to be a fundamental and integrated part of surgical training, it requires a significant number of resources, which can be daunting for residency training programs. Regardless of the barriers outlined, the need for surgical simulation in laparoscopy, endoscopy, and robotics at surgical education training programs is clear.

Metabolites profiling, in-vitro and molecular docking studies of five legume seeds for Alzheimer's disease.

Even though legumes are valuable medicinal plants with edible seeds that are extensively consumed worldwide, there is little information available on the metabolic variations between different dietary beans and their influence as potential anti-cholinesterase agents. High-resolution liquid chromatography coupled with mass spectrometry in positive and negative ionization modes combined with multivariate analysis were used to explore differences in the metabolic profiles of five commonly edible seeds, fava bean, black-eyed pea, kidney bean, red lentil, and chickpea. A total of 139 metabolites from various classes were identified including saponins, alkaloids, phenolic acids, iridoids, and terpenes. Chickpea showed the highest antioxidant and anti-cholinesterase effects, followed by kidney beans. Supervised and unsupervised chemometric analysis determined that species could be distinguished by their different discriminatory metabolites. The major metabolic pathways in legumes were also studied. Glycerophospholipid metabolism was the most significantly enriched KEGG pathway. Pearson's correlation analysis pinpointed 18 metabolites that were positively correlated with the anti-cholinesterase activity. Molecular docking of the biomarkers to the active sites of acetyl- and butyryl-cholinesterase enzymes revealed promising binding scores, validating the correlation results. The present study will add to the metabolomic analysis of legumes and their nutritional value and advocate their inclusion in anti-Alzheimer's formulations.

Simplification of Mobility Tests and Data Processing to Increase Applicability of Wearable Sensors as Diagnostic Tools for Parkinson's Disease.

Quantitative mobility analysis using wearable sensors, while promising as a diagnostic tool for Parkinson's disease (PD), is not commonly applied in clinical settings. Major obstacles include uncertainty regarding the best protocol for instrumented mobility testing and subsequent data processing, as well as the added workload and complexity of this multi-step process. To simplify sensor-based mobility testing in diagnosing PD, we analyzed data from 262 PD participants and 50 controls performing several motor tasks wearing a sensor on their lower back containing a triaxial accelerometer and a triaxial gyroscope. Using ensembles of heterogeneous machine learning models incorporating a range of classifiers trained on a set of sensor features, we show that our models effectively differentiate between participants with PD and controls, both for mixed-stage PD (92.6% accuracy) and a group selected for mild PD only (89.4% accuracy). Omitting algorithmic segmentation of complex mobility tasks decreased the diagnostic accuracy of our models, as did the inclusion of kinesiological features. Feature importance analysis revealed that Timed Up and Go (TUG) tasks to contribute the highest-yield predictive features, with only minor decreases in accuracy for models based on cognitive TUG as a single mobility task. Our machine learning approach facilitates major simplification of instrumented mobility testing without compromising predictive performance.

Sociodemographic factors leading to preventable emergency department visits after bariatric surgery: a single-institution analysis.

BACKGROUND: An important quality benchmark after bariatric surgery is 30-day emergency department (ED) visits. OBJECTIVES: We aimed to identify risk factors for ED visits not requiring readmission and thus deemed preventable. SETTING: University Hospital. METHODS: Patients who underwent a minimally invasive sleeve gastrectomy between 2017 and 2022 at a single institution were identified. Among these patients, those who presented to the ED within 30 days after surgery were matched 3:1 to controls. Sociodemographic and clinical variables were collected from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database and the electronic medical record. Univariate conditional logistic regression analysis was performed to determine predictive factors of ED visits. RESULTS: Overall, 648 patients underwent sleeve gastrectomy, of which 53 (8.2%) presented to the ED within 30 days postoperatively without requiring readmission. Patients who presented to the ED were more likely to be unemployed (42% versus 24%, P = .04) and have government insurance (68% versus 41%, P = .001). Significant risk factors included lower versus upper socioeconomic bracket (odds ratio [OR] 3.6, P = .042), primary care physician (PCP) outside the health system versus within (OR 2.15, P = .032), greater number of PCP visits within the past year (OR 1.27, P < .001), and greater number of postoperative clinic phone calls (OR 2.04, P < .001). The number of ED visits within 1 year before surgery was a significant risk factor, with an OR of 1.44 for each visit (P < .001). CONCLUSIONS: Modifiable and unmodifiable risk factors contribute to ED visits after bariatric surgery. Identifying these risk factors can aid in the development of quality improvement initiatives.

Identifying the optimal STOP-Bang screening score for obstructive sleep apnea among bariatric surgery patients.

BACKGROUND: Undiagnosed obstructive sleep apnea (OSA) increases the risk of perioperative complications in bariatric patients. Validated screening methods exist, but are not specific to patients with severe obesity. OBJECTIVES: Determine the ideal OSA screening tool for bariatric surgery patients balancing accuracy and cost-effectiveness. SETTING: University Hospital. METHODS: Bariatric surgery patients from January 2018 to September 2023 were identified from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. For patients with a STOP-Bang score of ≥4 referred for polysomnogram additional variables were collected from the electronic medical record. The Berlin Score was retrospectively calculated. RESULTS: Out of 484 patients who underwent bariatric surgery, 167 (34.5%) had a STOP-Bang score ≥4. The receiver operating characteristic (ROC) curve for STOP-Bang scores ≥4 had an area under the curve (AUC) of 78.5% for predicting OSA and 83.7% for OSA requiring treatment (Apnea Hypopnea Index [AHI] ≥ 15), compared to Berlin Scores' AUC of 80.7% and 88.6%, respectively. A STOP-Bang score of 4 had a sensitivity of 55.6% and specificity of 36.8%, while a score of 5 had 29.3% and 66.2%, respectively. A Berlin Score of 3 had a sensitivity of 47.5% and specificity of 69.1%, with 30 patients (44.1%) starting OSA treatment. Thirty-five patients (21%) experienced a delay in insurance submission, averaging 41.5 days, related to OSA workup. CONCLUSION: The Berlin questionnaire outperforms STOP-Bang in predicting OSA requiring treatment. Raising the polysomnography referral score from STOP-Bang ≥4 to ≥5 or utilizing a Berlin Score of ≥3, may alleviate resource burden, reduce costs, and expedite medical optimization for bariatric surgery.

Enhancing groundwater quality assessment in coastal area: A hybrid modeling approach.

Monitoring of groundwater (GW) resources in coastal areas is vital for human needs, agriculture, ecosystems, securing water supply, biodiversity, and environmental sustainability. Although the utilization of water quality index (WQI) models has proven effective in monitoring GW resources, it has faced substantial criticism due to its inconsistent outcomes, prompting the need for more reliable assessment methods. Therefore, this study addressed this concern by employing the data-driven root mean squared (RMS) models to evaluate groundwater quality (GWQ) in the coastal Bhola district near the Bay of Bengal, Bangladesh. To enhance the reliability of the RMS-WQI model, the research incorporated the extreme gradient boosting (XGBoost) machine learning (ML) algorithm. For the assessment of GWQ, the study utilized eleven crucial indicators, including turbidity (TURB), electric conductivity (EC), pH, total dissolved solids (TDS), nitrate (NO3 -), ammonium (NH4 +), sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), and iron (Fe). In terms of the GW indicators, concentration of K, Ca and Mg exceeded the guideline limit in the collected GW samples. The computed RMS-WQI scores ranged from 54.3 to 72.1, with an average of 65.2, categorizing all sampling sites' GWQ as "fair." In terms of model reliability, XGBoost demonstrated exceptional sensitivity (R2 = 0.97) in predicting GWQ accurately. Furthermore, the RMS-WQI model exhibited minimal uncertainty (<1 %) in predicting WQI scores. These findings implied the efficacy of the RMS-WQI model in accurately assessing GWQ in coastal areas, that would ultimately assist regional environmental managers and strategic planners for effective monitoring and sustainable management of coastal GW resources.

Hyperhidrosis and Neurofibromatosis Type 1: A Case Report.

In this report, we present the case of a 20-year-old male with childhood-onset hyperhidrosis affecting his fingers and palm flexor surfaces. Dermatological examination revealed café-au-lait macules, palm and sole involvement, and axillary freckling. A starch-iodine test confirmed localized sweating. Neuroimaging identified neurofibromatosis type 1 (NF1) with subcutaneous nodules and dural ectasia in the thoracic spine. The patient was diagnosed with hyperhidrosis and NF1 based on diagnostic criteria, and he responded well to 20% aluminum chloride for treatment of hyperhidrosis. This case represents a unique occurrence of hyperhidrosis with NF1 in Saudi Arabia. Comprehensive evaluation, including systemic assessment, radiology, and starch-iodine testing, aids in diagnosis and understanding of the underlying mechanisms of this disorder, which remains unexplained.

Genetic diversity and antifungal susceptibilities of environmental Cryptococcus neoformans and Cryptococcus gattii species complexes.

Cryptococcosis is an opportunistic systemic mycosis caused by Cryptococcus neoformans and C. gattii species complexes and is of increasing global importance. Maintaining continued surveillance of the antifungal susceptibility of environmental C. neoformans and C. gattii isolates is desirable for better managing cryptococcosis by identifying resistant isolates and revealing the emergence of intrinsically resistant species. Relevant research data from Egypt are scarce. Thus, this study aimed to report the genetic diversity of C. neoformans and C. gattii species complexes originating from different environmental sources in Egypt, antifungal susceptibility profiles, antifungal combinations, and correlations of susceptibility with genotypes. A total of 400 environmental samples were collected, 220 from birds and 180 from trees. Cryptococcus spp. were found in 58 (14.5%) of the samples, 44 (75.9%) of the isolates were recovered from birds and 14 (24.1%) from trees. These isolates were genotyped using M13 polymerase chain reaction-fingerprinting and URA5 gene restriction fragment length polymorphism analysis. Of the 31 C. neoformans isolates, 24 (77.4%), 6 (19.4%) and one (4.4%) belonged to VNI, VNII, and VNIII genotypes, respectively. The 27 C. gattii isolates belonged to VGI (70.4%), VGII (18.5%), and VGIII (11.1%) genotypes. Non-wild type C. neoformans and C. gattii isolates that may have acquired resistance to azoles, amphotericin B (AMB), and terbinafine (TRB) were observed. C. gattii VGIII was less susceptible to fluconazole (FCZ) and itraconazole (ITZ) than VGI and VGII. C. neoformans isolates showed higher minimum inhibitory concentrations (MICs) to FCZ, ITZ, and voriconazole (VRZ) than those of C. gattii VGI and VGII. Significant (P < 0.001) correlations were found between the MICs of VRZ and ITZ (r = 0.64) in both C. neoformans and C. gattii isolates, FCZ and TRB in C. neoformans isolates, and FCZ and TRB (r = 0.52) in C. gattii isolates.There is no significant differences in the MICs of TRB in combination with FCZ (P = 0.064) or in combination with AMB (P = 0.543) and that of TRB alone against C. gattii genotypes. By calculating the fractional inhibitory concentration (FIC) index, the combination of FCZ + AMB was synergistic against all tested genotypes. These findings expand our knowledge of ecological niches, genetic diversity, and resistance traits of C. neoformans and C. gattii genotypes in Egypt. Further investigations into how they are related to clinical isolates in the region are warranted.

Thermo-activated in situ rectal gel preparation for Ibuprofen using eutectic mixture.

This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.

Objective sonographic measurements of renal pelvic diameter and renal parenchymal thickness can identify renal hypofunction and poor drainage in patients with antenatally detected unilateral ureteropelvic junction obstruction.

INTRODUCTION: Hydronephrosis grading systems risk stratify patients with potential ureteropelvic junction obstruction, but only some criteria are measured objectively. Most notably, there is no consensus definition of renal parenchymal thinning. OBJECTIVES: The objective of this study was to assess the association between sonographic measures of renal length, renal pelvic diameter, and renal parenchymal thickness and the outcomes of a)renal hypofunction(differential renal function{DRF} <40%) and b)high-risk renal drainage(T1/2 > 40 min). STUDY DESIGN: An institutional database of patients who had diuretic renograms(DR) for unilateral hydronephrosis was reviewed. Only infants with Society for Fetal Urology(SFU) grades 3/4 hydronephrosis without hydroureter on postnatal sonogram and had a DR within 120 days were included. The following measurement variables were analyzed: anterior posterior renal pelvic diameter(APRPD), renal length(RL), renal parenchymal thickness(PT), minimal renal parenchymal thickness(MPT = shortest distance from mid-pole calyx to parenchymal edge), and renal pyramidal thickness(PyrT). RL, PT, MPT, PyrT measurements were expressed as ratios (hydronephrotic kidney/contralateral kidney). Multivariate logistic regression was performed for each outcome by comparing three separate renal measurement models. Model 1: RLR, APRPD, MPTR; Model 2: RLR, APRPD, PTR, Model 3: RLR, APRPD, PyrTR. Individual performance of variables from the best performing model were assessed via ROC curve analysis. RESULTS: 196 patients were included (107 with SFU grade 3, 89 with SFU grade 4) hydronephrosis. Median patient age was 29[IQR 16,47.2] days. 10% had hypofunction, and 20% had T1/2 > 40 min 90% with hypofunction and 87% with high-risk drainage had SFU4 hydronephrosis. Model 1 exhibited the best performance, but on multivariate analysis, only APRPD and MPTR were independently associated with both outcomes. No other measure of parenchymal thickness reached statistical significance. The odds of hypofunction and high-risk drainage increase 10% per 1 mm increase in APRPD(aOR 1.1 [CI 1.03-1.2], p = 0.005; aOR 1.1 [CI 1.03-1.2], p = 0.003). For every 0.1unit increase in MPTR the odds of hypofunction decrease by 40%(aOR 0.6 [CI 0.4-0.9], p = 0.019); and the odds of high-risk drainage decrease by 30%(aOR 0.7 [CI 0.5-0.9], p = 0.011). Optimal statistical cut-points of APRPD >16 mm and/or MPTR <0.36 identified patients at risk for obstructive parameters on DR. DISCUSSION AND CONCLUSION: Of the sonographic hydronephrosis measurement variables analyzed, only APRPD and MPTR were independently associated with objective definitions of obstruction based on renal function and drainage categories. Patients who maintain APRPD <16 mm and/or MPTR >0.36 can potentially be monitored with renal sonograms as there is >90% chance that they will not have DRF<40% or T1/2 > 40 min.

Glymphatic pathway: An emerging perspective in the pathophysiology of neurodegenerative diseases.

The central nervous system (CNS) is widely recognized as the only organ system without lymphatic capillaries to promote the removal of interstitial metabolic by-products. Thus, the newly identified glymphatic system which provides a pseudolymphatic activity in the nervous system has been focus of latest research in neurosciences. Also, findings reported that, sleep stimulates the elimination actions of glymphatic system and is linked to normal brain homeostatis. The CNS is cleared of potentially hazardous compounds via the glymphatic system, particularly during sleep. Any age-related alterations in brain functioning and pathophysiology of various neurodegenerative illnesses indicates the disturbance of the brain's glymphatic system. In this context, ß-amyloid as well as tau leaves the CNS through the glymphatic system, it's functioning and CSF discharge markedly altered in elderly brains as per many findings. Thus, glymphatic failure may have a potential mechanism which may be therapeutically targetable in several neurodegenerative and age-associated cognitive diseases. Therefore, there is an urge to focus for more research into the connection among glymphatic system and several potential brain related diseases. Here, in our current review paper, we reviewed current research on the glymphatic system's involvement in a number of prevalent neurodegenerative and neuropsychiatric diseases and, we also discussed several therapeutic approaches, diet and life style modifications which might be used to acquire a more thorough performance and purpose of the glymphatic system to decipher novel prospects for clinical applicability for the management of these diseases.

Epinephrine vs. phenylephrine infusion for prophylaxis against maternal hypotension after spinal anesthesia for cesarean delivery: a randomized controlled trial.

BACKGROUND: The hemodynamic effects of relatively low-dose epinephrine and phenylephrine infusions during cesarean delivery under spinal anesthesia were compared. METHODS: This randomized controlled trial included full-term pregnant women who underwent elective cesarean delivery. After spinal anesthesia, participants received either epinephrine (0.03 mcg/kg/min) or phenylephrine (0.4 mcg/kg/min) infusion that continued until 5 min after delivery. The primary outcome was a composite outcome of the occurrence of any of hypotension, hypertension, bradycardia, and/or tachycardia. Neonatal outcomes, including umbilical artery blood gas and Apgar scores, were assessed. RESULTS: In total, 98 patients in each group were analyzed, and the number of patients with the composite outcome was comparable between the epinephrine and phenylephrine groups (30/98 [31%] vs. 31/98 [32%], respectively; P = 0.877). However, the incidence of hypotension was likely lower in the epinephrine group than in the phenylephrine group (P = 0.066), and the number of hypotensive episodes per patient was lower in the epinephrine group than in the phenylephrine group. On the other hand, the incidence of tachycardia was higher in the epinephrine group than that in the phenylephrine group. The incidence of hypertension was comparable between the two groups and none of the participants developed bradycardia. Neonatal outcomes were comparable between the two groups. CONCLUSIONS: Epinephrine and phenylephrine infusion produced comparable maternal hemodynamics and neonatal outcomes. Epinephrine was associated with a higher incidence of maternal tachycardia and likely lower incidence of maternal hypotension than phenylephrine. IRB number: MD-245-2022. CLINICAL TRIAL REGISTRATION: This study was registered on May 31, 2023 at clinicaltrials.gov registry, NCT05881915, URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05881915term=NCT05881915&draw=2&rank=1.

PI3K inhibitor "alpelisib" alleviates methotrexate induced liver injury in mice and potentiates its cytotoxic effect against MDA-MB-231 triple negative breast cancer cell line.

Hepatotoxicity is the main off-target effect of methotrexate (MTX) limiting its effective clinical use. Besides, MDA-MB231 breast cancer cells show chemoresistance, partly via PI3K/AKT pathway. Therefore, we investigated the ameliorative potentials of the PI3K inhibitor, alpelisib (ALP) on MTX-induced hepatotoxicity (in vivo) and the restraining potentials of ALP on MDA-MB231 chemoresistance to MTX (in vitro). Twenty-eight male BALB/c mice were divided into 4 groups. In treatment groups, mice were administered ALP (2.5 and 5 mg/kg) for 5 days and MTX (20 mg/kg) from day 2 till day 5. The results showed that ALP restored hepatic architecture, reduced immune cell infiltration (F4/80, Ly6G and MPO) and repressed the rise in liver enzymes (AST and ALT) induced by MTX. Additionally, ALP rectified the MTX-induced disruption of cellular oxidant status by boosting antioxidant defense systems (HO-1 and GSH) and repressing lipid peroxidation (MDA and 4-HNE). Finally, ALP curbed MTX-induced hepatocyte apoptosis (NF-κB and BAX) and shifted the cytokine milieu away from inflammation (IL-17, IL-22, IL-6 and IL- 10). The results of the in vitro experiments revealed that ALP alone and in combination with MTX, synergistically, reduced cancer cell viability (MTT assay), migration (wound healing assay) and their capacity to establish colonies (colony formation assay) as compared to MTX alone. RT-PCR revealed the antiproliferative (Bcl-2) and proapoptotic (BAX) potentials of ALP and ALP/MTX combination especially after 24 h. In conclusion, targeting PI3K/AKT pathway is a promising strategy in triple negative breast cancer patients by ameliorating hepatotoxicity and restraining chemoresistance to chemotherapy.

LC/MS-Based Metabolomics Reveals Chemical Variations of Two Broccoli Varieties in Relation to Their Anticholinesterase Activity: In vitro and In silico Studies.

Broccoli is commonly consumed as food and as medicine. However, comprehensive metabolic profiling of two broccoli varieties, Romanesco broccoli (RB) and purple broccoli (PB), in relation to their anticholinergic activity has not been fully disclosed. A total of 110 compounds were tentatively identified using UPLC-Q-TOF-MS metabolomics. Distinctively different metabolomic profiles of the two varieties were revealed by principal component analysis (PCA). Furthermore, by volcano diagram analysis, it was found that PB had a significantly higher content of phenolic acids, flavonoids, and glucosinolates, indicating the different beneficial health potentials of PB that demonstrated higher antioxidant and anticholinergic activities. Moreover, Pearson's correlation analysis revealed 18 metabolites, mainly phenolic and sulfur compounds, as the main bioactive. The binding affinity of these biomarkers to the active sites of acetyl- and butyryl-cholinesterase enzymes was further validated using molecular docking studies. Results emphasize the broccoli significance as a functional food and nutraceutical source and highlight its beneficial effects against Alzheimer's disease.

Exploring the path to polio eradication: insights from consecutive seroprevalence surveys among Pakistani children.

Introduction: After trivalent oral poliovirus vaccine (tOPV) cessation, Pakistan has maintained immunity to type 2 poliovirus by administering inactivated polio vaccine (IPV) in routine immunization, alongside monovalent OPV type 2 (mOPV2) and IPV in supplementary immunization activities (SIAs). This study assesses the change in poliovirus type 2 immunity after tOPV withdrawal and due to SIAs with mOPV2 and IPV among children aged 6-11 months. Methods: Three cross-sectional sequential serological surveys were conducted in 12 polio high-risk areas of Pakistan. 25 clusters from each geographical stratum were selected utilizing probability proportional to size. Results: Seroprevalence of type 2 poliovirus was 49%, with significant variation observed among surveyed areas; <30% in Pishin, >80% in Killa Abdullah, Mardan & Swabi, and Rawalpindi. SIAs with IPV improved immunity from 38 to 57% in Karachi and 60 to 88% in Khyber. SIAs with IPV following mOPV2 improved immunity from 62 to 65% in Killa Abdullah, and combined mOPV2 and IPV SIAs in Pishin improved immunity from 28 to 89%. Results also reflected that immunity rates for serotypes 1 and 3 were consistently above 90% during all three phases and across all geographical areas. Conclusion: The study findings highlight the importance of implementing effective vaccination strategies to prevent the re-emergence of poliovirus. Moreover, the results provide crucial information for policymakers working toward achieving global polio eradication.