The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis.

BACKGROUND: Staphylococcus aureus is the most common cause of life-threatening endovascular infections, including infective endocarditis (IE). These infections, especially when caused by methicillin-resistant strains (MRSA), feature limited therapeutic options and high morbidity and mortality rates. METHODS: Herein, we investigated the role of the purine biosynthesis repressor, PurR, in virulence factor expression and vancomycin (VAN) treatment outcomes in experimental IE due to MRSA. RESULTS: The PurR-mediated repression of purine biosynthesis was confirmed by enhanced purF expression and production of an intermediate purine metabolite in purR mutant strain. In addition, enhanced expression of the transcriptional regulators, sigB and sarA, and their key downstream virulence genes (eg, fnbA, and hla) was demonstrated in the purR mutant in vitro and within infected cardiac vegetations. Furthermore, purR deficiency enhanced fnbA/fnbB transcription, translating to increased fibronectin adhesion versus the wild type and purR-complemented strains. Notably, the purR mutant was refractory to significant reduction in target tissues MRSA burden following VAN treatment in the IE model. CONCLUSIONS: These findings suggest that the purine biosynthetic pathway intersects the coordination of virulence factor expression and in vivo persistence during VAN treatment, and may represent an avenue for novel antimicrobial development targeting MRSA.

Deletion of RFX6 impairs iPSC-derived islet organoid development and survival, with no impact on PDX1+/NKX6.1+ progenitors.

AIMS/HYPOTHESIS: Homozygous mutations in RFX6 lead to neonatal diabetes accompanied by a hypoplastic pancreas, whereas heterozygous mutations cause MODY. Recent studies have also shown RFX6 variants to be linked with type 2 diabetes. Despite RFX6's known function in islet development, its specific role in diabetes pathogenesis remains unclear. Here, we aimed to understand the mechanisms underlying the impairment of pancreatic islet development and subsequent hypoplasia due to loss-of-function mutations in RFX6. METHODS: We examined regulatory factor X6 (RFX6) expression during human embryonic stem cell (hESC) differentiation into pancreatic islets and re-analysed a single-cell RNA-seq dataset to identify RFX6-specific cell populations during islet development. Furthermore, induced pluripotent stem cell (iPSC) lines lacking RFX6 were generated using CRISPR/Cas9. Various approaches were then employed to explore the consequences of RFX6 loss across different developmental stages. Subsequently, we evaluated transcriptional changes resulting from RFX6 loss through RNA-seq of pancreatic progenitors (PPs) and endocrine progenitors (EPs). RESULTS: RFX6 expression was detected in PDX1+ cells in the hESC-derived posterior foregut (PF). However, in the PPs, RFX6 did not co-localise with pancreatic and duodenal homeobox 1 (PDX1) or NK homeobox 1 (NKX6.1) but instead co-localised with neurogenin 3, NK2 homeobox 2 and islet hormones in the EPs and islets. Single-cell analysis revealed high RFX6 expression levels in endocrine clusters across various hESC-derived pancreatic differentiation stages. Upon differentiating iPSCs lacking RFX6 into pancreatic islets, a significant decrease in PDX1 expression at the PF stage was observed, although this did not affect PPs co-expressing PDX1 and NKX6.1. RNA-seq analysis showed the downregulation of essential genes involved in pancreatic endocrine differentiation, insulin secretion and ion transport due to RFX6 deficiency. Furthermore, RFX6 deficiency resulted in the formation of smaller islet organoids due to increased cellular apoptosis, linked to reduced catalase expression, implying a protective role for RFX6. Overexpression of RFX6 reversed defective phenotypes in RFX6-knockout PPs, EPs and islets. CONCLUSIONS/INTERPRETATION: These findings suggest that pancreatic hypoplasia and reduced islet cell formation associated with RFX6 mutations are not due to alterations in PDX1+/NKX6.1+ PPs but instead result from cellular apoptosis and downregulation of pancreatic endocrine genes. DATA AVAILABILITY: RNA-seq datasets have been deposited in the Zenodo repository with accession link (DOI: https://doi.org/10.5281/zenodo.10656891 ).

Sensitizing methicillin-resistant Staphylococcus aureus (MRSA) to cefuroxime: the synergic effect of bicarbonate and the wall teichoic acid inhibitor ticlopidine.

Methicillin-resistant Staphylococcus aureus (MRSA) strains are a major challenge for clinicians due, in part, to their resistance to most ß-lactams, the first-line treatment for methicillin-susceptible S. aureus. A phenotype termed "NaHCO3-responsiveness" has been identified, wherein many clinical MRSA isolates are rendered susceptible to standard-of-care ß-lactams in the presence of physiologically relevant concentrations of NaHCO3, in vitro and ex vivo; moreover, such "NaHCO3-responsive" isolates can be effectively cleared by ß-lactams from target tissues in experimental infective endocarditis (IE). One mechanistic impact of NaHCO3 exposure on NaHCO3-responsive MRSA is to repress WTA synthesis. This NaHCO3 effect mimics the phenotype of tarO-deficient MRSA, including sensitization to the PBP2-targeting ß-lactam, cefuroxime (CFX). Herein, we further investigated the impacts of NaHCO3 exposure on CFX susceptibility in the presence and absence of a WTA synthesis inhibitor, ticlopidine (TCP), in a collection of clinical MRSA isolates from skin and soft tissue infections (SSTI) and bloodstream infections (BSI). NaHCO3 and/or TCP enhanced susceptibility to CFX in vitro, by both minimum inhibitor concentration (MIC) and time-kill assays, as well as in an ex vivo simulated endocarditis vegetations (SEV) model, in NaHCO3-responsive MRSA. Furthermore, in experimental IE (presumably in the presence of endogenous NaHCO3), pre-exposure to TCP prior to infection sensitized the NaHCO3-responsive MRSA strain (but not the non-responsive strain) to enhanced clearances by CFX in target tissues. These data support the notion that NaHCO3 is acting similarly to WTA synthesis inhibitors, and that such inhibitors have potential translational applications in the treatment of certain MRSA strains in conjunction with specific ß-lactam agents.

Association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Egyptian children and adolescents.

BACKGROUND: Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. METHODS: This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. RESULTS: The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. CONCLUSIONS: The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. IMPACT: Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.

"Molecular Characterization of Extended Spectrum Beta-Lactamase Resistance in Pediatric Shigella Isolates in Egypt".

Shigellosis is a major cause of morbidity and mortality among children, especially in developing countries. The increased extended-spectrum beta-lactamase (ESBL) resistance in Shigella poses a challenge for effective treatment. To examine the antibiotic resistance and ESBL profile of Shigella isolates from children with acute diarrhea. Shigella was isolated from stool cultures from pediatric patients suffering from acute diarrhea. The isolates were identified by bacteriological tests, serotyping, and multiplex polymerase chain reaction (PCR). The antimicrobial resistance was examined by disc diffusion. Phenotypic tests and PCR examined the ESBLs and CTX-M, SHV, and TEM genes. A total of 100 Shigella (10% prevalence rate) were isolated. The S. sonnei and S. dysenteries were the most prevalent species (33% and 31%, respectively), followed by S. flexneri (27%), and only 9% were S. boydii. The isolates had complete resistance (100%) to ampicillin. There was lower resistance to ciprofloxacin (24%), and no resistance to imipenem. By phenotypic tests, 54% of isolates had ESBL. By PCR, bla-CTX-M gene was the most prevalent (50%), followed by bla-TEM (48.1%). Only one isolate (1.9%) had the bla-SHV gene. The alarmingly high rates of antibiotic resistance and ESBL resistance among Shigella spp highlight the urgent need to restrict the unguided use of these drugs. Continuous monitoring of local and global antibiotic resistance patterns is required to prevent the spread of resistance.

The Use of a Unilateral Curved Spreader Graft in the Management of Crooked Nose Deformity.

AIM OF WORK: The aim of this study is to present a new technique of using spreader grafts in the correction of crooked nose deformity with C-shaped deviation of the middle third of the nose. PATIENTS AND METHODS: This is a prospective case series study conducted on 18 patients with crooked nose deformity with C-shaped deviation of the middle third of the nose. All of the patients were managed by open septorhinoplasty. During surgery, a curved spreader graft was harvested from the nasal septum and placed on the convex side of the C-shaped deviation of the dorsal part of the nasal septum. Objective measurements of the angles of external nasal deviation (END) and the internal nasal valve (INV) angles were performed before and 6 months after the surgery. Subjective assessment of aesthetic satisfaction by the visual analog scale and nasal function by the nasal obstruction symptom evaluation scale was also performed before and 6 months after surgery. RESULTS: Eighteen patients were enrolled in the study and completed the minimum follow-up period of 6 months. The mean follow-up period was 17.3 months. Objectively, there was highly significant ( P < 0.00001) improvement of the END angle and INV angle. Subjectively, there was also highly significant ( P < 0.00001) improvement of both the nasal obstruction symptom evaluation score and the visual analog scale score for aesthetic satisfaction. CONCLUSIONS: The insertion of a curved unilateral spreader graft over the convexity of the deviated nasal dorsum can correct the END, improve the collapsed INV on both sides, and consequently achieve satisfactory aesthetic and functional outcomes.

Mortality and Morbidity in Adults With Rheumatic Heart Disease.

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

Outcomes of Implant Exchange and Latissimus Dorsi Flap Replacement After Breast Implant Complications.

BACKGROUND: Immediate action is required to address some complications of implant-based reconstruction after mastectomy to prevent reconstruction failure. Implant exchange may be simple but poses the risk of further complications while autologous flap reconstruction seems more complex but may pose less subsequent risk. Which of these is preferable remains unclear. METHODS: We reviewed thirty-two female breast cancer patients who had serious complications with their breast implants after post-mastectomy reconstruction. Latissimus dorsi flap (LDF) patients underwent explantation and immediate reconstruction with an LDF, while implant exchange (IE) patients underwent immediate implant removal and exchange with an expander followed by delayed reconstruction with silicon or immediately with a smaller size silicone implant. RESULTS: LDF patients underwent a single operation with an average duration of care of 31 days compared to an average 1.8 procedures (p= 0.005) with an average duration of care of 129.9 days (p < 0.001) among IE patients. Seven IE (50%) had serious complications that required subsequent revision while no LDF patients required additional procedures. Patient overall satisfaction and esthetics results were also superior in the LDF group at six months. CONCLUSION: In patients who want to reconstructively rescue and salvage their severely infected or exposed breast implant, the LDF offers an entirely autologous solution. LDF reconstruction in this setting allows patients to avoid an extended duration of care, reduces their risk of complications, and preserves the reconstructive process. LEVEL OF EVIDENCE III: The journal asks authors to assign a level of evidence to each article. For a complete description of Evidence-Based Medicine ratings, see the Table of Contents or the online Instructions for Authors at www.springer.com/00266 .

Genetic programming expressions for effluent quality prediction: Towards AI-driven monitoring and management of wastewater treatment plants.

Continuous effluent quality prediction in wastewater treatment processes is crucial to proactively reduce the risks to the environment and human health. However, wastewater treatment is an extremely complex process controlled by several uncertain, interdependent, and sometimes poorly characterized physico-chemical-biological process parameters. In addition, there are substantial spatiotemporal variations, uncertainties, and high non-linear interactions among the water quality parameters and process variables involved in the treatment process. Such complexities hinder efficient monitoring, operation, and management of wastewater treatment plants under normal and abnormal conditions. Typical mathematical and statistical tools most often fail to capture such complex interrelationships, and therefore data-driven techniques offer an attractive solution to effectively quantify the performance of wastewater treatment plants. Although several previous studies focused on applying regression-based data-driven models (e.g., artificial neural network) to predict some wastewater treatment effluent parameters, most of these studies employed a limited number of input variables to predict only one or two parameters characterizing the effluent quality (e.g., chemical oxygen demand (COD) and/or suspended solids (SS)). Harnessing the power of Artificial Intelligence (AI), the current study proposes multi-gene genetic programming (MGGP)-based models, using a dataset obtained from an operational wastewater treatment plant, deploying membrane aerated biofilm reactor, to predict the filtrated COD, ammonia (NH4), and SS concentrations along with the carbon-to-nitrogen ratio (C/N) within the effluent. Input features included a set of process variables characterizing the influent quality (e.g., filtered COD, NH4, and SS concentrations), water physics and chemistry parameters (e.g., temperature and pH), and operation conditions (e.g., applied air pressure). The developed MGGP-based models accurately reproduced the observations of the four output variables with correlation coefficient values that ranged between 0.98 and 0.99 during training and between 0.96 and 0.99 during testing, reflecting the power of the developed models in predicting the quality of the effluent from the treatment system. Interpretability analyses were subsequently deployed to confirm the intuitive understanding of input-output interrelations and to identify the governing parameters of the treatment process. The developed MGGP-based models can facilitate the AI-driven monitoring and management of wastewater treatment plants through devising optimal rapid operation and control schemes and assisting the plants' operators in maintaining proper performance of the plants under various normal and disruptive operational conditions.

Clinical and Radiographic Outcomes of Autogenous Inlay Graft vs Autogenous Onlay Graft for Anterior Maxillary Horizontal Ridge Augmentation: A Randomized Control Clinical Study.

AIM: This study aimed to compare the efficacy of autogenous onlay and inlay grafts for anterior maxillary horizontal ridge augmentation. MATERIALS AND METHODS: This randomized clinical trial was performed on 14 patients with a deficient partially edentulous anterior maxillary ridge (3-5 mm in width). Patients were randomized and grouped into two equal groups: Group A was treated with symphyseal autogenous bone block, which was placed and fixed buccally as an onlay graft, and group B: was treated with symphyseal autogenous bone block, which was interpositioned and fixed in space created between buccal and lingual cortex as inlay graft. Patients were evaluated clinically and radiographically to evaluate the increase of bone width at [Baseline, immediate postoperative (T0)] and six months post-graft (T6). RESULTS: A total of 14 patients (8 males and 6 females) with age range from 20 to 43 years old with a mean of 42.1 years were involved in our study. Radiographically, there was a significant statistical difference in comparing between two groups for the creation of a horizontal alveolar bone at T0. In the inlay group, the mean preoperative bone width was 3.9 ± 0.3 mm at T0 and 5.7 ± 0.5 mm at T6. While in the onlay group, the mean preoperative bone width was 3.7 ± 0.7 mm at T0 while at T6 the mean bone width was 6.1 ± 0.8 mm. This was statistically significant. CONCLUSION: Inlay block graft appears to be a successful treatment option for horizontal ridge augmentation in the maxillary arch. CLINICAL SIGNIFICANCE: both techniques are viable techniques for augmentation of atrophic alveolar ridge with uneventful healing. How to cite this article: Elsayed AO, Abdel-Rahman FH, Ahmed WMAS, et al. Clinical and Radiographic Outcomes of Autogenous Inlay Graft vs Autogenous Onlay Graft for Anterior Maxillary Horizontal Ridge Augmentation: A Randomized Control Clinical Study. J Contemp Dent Pract 2024;25(2):107-113.

Combinations of Daptomycin plus Ceftriaxone, but Not Ascending Daptomycin Dose-Regimens, Are Effective in Experimental Endocarditis Caused by Streptococcus mitis-oralis Strains: Target Tissue Clearances and Prevention of Emergence of Daptomycin-Resistance.

The Streptococcus mitis-oralis subgroup of the viridans group streptococci (VGS) are the most common cause of infective endocarditis (IE) in many parts of the world. These organisms are frequently resistant in vitro to standard ß-lactams (e.g., penicillin; ceftriaxone [CRO]), and have the notable capacity for rapidly developing high-level and durable daptomycin resistance (DAP-R) during exposures in vitro, ex vivo, and in vivo. In this study, we used 2 prototypic DAP-susceptible (DAP-S) S. mitis-oralis strains (351; and SF100), which both evolved stable, high-level DAP-R in vitro within 1 to 3 days of DAP passage (5 to 20 µg/mL DAP). Of note, the combination of DAP + CRO prevented this rapid emergence of DAP-R in both strains during in vitro passage. The experimental rabbit IE model was then employed to quantify both the clearance of these strains from multiple target tissues, as well as the emergence of DAP-R in vivo under the following treatment conditions: (i) ascending DAP-alone dose-strategies encompassing human standard-dose and high-dose-regimens; and (ii) combinations of DAP + CRO on these same metrics. Ascending DAP-alone dose-regimens (4 to 18 mg/kg/d) were relatively ineffective at either reducing target organ bioburdens or preventing emergence of DAP-R in vivo. In contrast, the combination of DAP (4 or 8 mg/kg/d) + CRO was effective at clearing both strains from multiple target tissues (often with sterilization of bio-burdens in such organs), as well as preventing the emergence of DAP-R. In patients with serious S. mitis-oralis infections such as IE, especially caused by strains exhibiting intrinsic ß-lactam resistance, initial therapy with combinations of DAP + CRO may be warranted.

Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells.

BACKGROUND: Our recent studies have demonstrated the crucial involvement of FOXA2 in the development of human pancreas. Reduction of FOXA2 expression during the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic islets has been found to reduce α-and ß-cell masses. However, the extent to which such changes are linked to alterations in the expression profile of long non-coding RNAs (lncRNAs) remains unraveled. METHODS: Here, we employed our recently established FOXA2-deficient iPSCs (FOXA2-/- iPSCs) to investigate changes in lncRNA profiles and their correlation with dysregulated mRNAs during the pancreatic progenitor (PP) and pancreatic islet stages. Furthermore, we constructed co-expression networks linking significantly downregulated lncRNAs with differentially expressed pancreatic mRNAs. RESULTS: Our results showed that 442 lncRNAs were downregulated, and 114 lncRNAs were upregulated in PPs lacking FOXA2 compared to controls. Similarly, 177 lncRNAs were downregulated, and 59 lncRNAs were upregulated in islet cells lacking FOXA2 compared to controls. At both stages, we observed a strong correlation between lncRNAs and several crucial pancreatic genes and TFs during pancreatic differentiation. Correlation analysis revealed 12 DE-lncRNAs that strongly correlated with key downregulated pancreatic genes in both PPs and islet cell stages. Selected DE-lncRNAs were validated using RT-qPCR. CONCLUSIONS: Our data indicate that the observed defects in pancreatic islet development due to the FOXA2 loss is associated with significant alterations in the expression profile of lncRNAs. Therefore, our findings provide novel insights into the role of lncRNA and mRNA networks in regulating pancreatic islet development, which warrants further investigations. Video Abstract.

Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Application of classification machine learning algorithms for characterizing nutrient transport in a clay plain agricultural watershed.

Excess nutrients in surface water and groundwater can lead to water quality deterioration in available water resources. Thus, the classification of nutrient concentrations in water resources has gained significant attention during recent decades. Machine learning (ML) algorithms are considered an efficient tool to describe nutrient loss from agricultural land to surface water and groundwater. Previous studies have applied regression and classification ML algorithms to predict nutrient concentrations in surface water and/or groundwater, or to categorize an output variable using a limited number of input variables. However, there have been no studies that examined the application of different ML classification algorithms in agricultural settings to classify various output variables using a wide range of input variables. In this study, twenty-four ML classification algorithms were implemented on a dataset from three locations within the Upper Parkhill watershed, an agricultural watershed in southern Ontario, Canada. Nutrient concentrations in surface water were classified using geochemical and physical water parameters of surface water and groundwater (e.g., pH), climate and field conditions as the input variables. The performance of these algorithms was evaluated using four evaluation metrics (e.g., classification accuracy) to identify the optimal algorithm for classifying the output variables. Ensemble bagged trees was found to be the optimal ML algorithm for classifying nitrate concentration in surface water (accuracy of 90.9%), while the weighted KNN was the most appropriate algorithm for categorizing the total phosphorus concentration (accuracy of 87%). The ensemble subspace discriminant algorithm gave the highest overall classification accuracy for the concentration of soluble reactive phosphorus and total dissolved phosphorus in surface water with an accuracy of 79.2% and 77.9%, respectively. This study exemplifies that ML algorithms can be used to signify exceedance of recommended concentrations of nutrients in surface waters in agricultural watersheds. Results are useful for decision makers to develop nutrient management strategies.

Parental health-seeking behavior on self-medication, antibiotic use, and antimicrobial resistance in children.

Aim and Objectives: The study sought to identify parental trends in children's self-medication, health-seeking behavior, knowledge of self-medication, antibiotic use, and antimicrobial resistance in Asir, Saudi Arabia. Methods: A web-based cross-sectional study was carried out by a survey questionnaire. Snow Ball sampling technique was used to select the Eight hundred and sixteen parents with children in the Asir region by WhatsApp and email, and 650 participants who met the inclusion criteria consented to participate in the study. Results: There were 1809 episodes of childhood illnesses reported during the study period. The mean scores are on knowledge at 8.11 ±â€¯2.43, favorable attitude at 17.60 ±â€¯1.17, and practice was 7.72 ±â€¯1.72, and a significant correlation was found between knowledge, attitude, and practice (KAP) at p = 0.01. Out of 624, the majority of parents showed strong knowledge and proficiency in antibiotics. However, the attitude scores of over 50% towards the usage of antibiotics were subpar. Around 54% of parents were self-medicating their children and 43% were unaware that skipping doses contributes to anti-microbial resistance (AMR). The facilitators for self-medication were male gender (aOR: 2.13; 95% CI: 1.26-3.98, p < 0.05), having more children (aOR: 2.78; 95% CI: 1.27-4.12 p < 0.01), professional qualification (aOR:3.07; 95% CI 1.57- 4.68; p < 0.01), residing in urban area (aOR: 3.17; 95% CI: 2.13-5.61, p < 0.05), working in health care (aOR: 5.99; 95% CI: 1.78-18.2, p < 0.01) and high income (aOR: 3.57; 95% CI: 2.08-6.34, p < 0.05). Conclusions: The findings indicated that the majority of parents had unfavorable views and improper practices of antibiotic usage. Strategic education programs to the targeted population, especially to the parents about side effects of antibiotics, dangerous consequences of self-medication, and crucial AMR concerns must be addressed immediately.

A new promising approach to urodynamic stress urinary incontinence care can help menopausal women.

Introduction: The goal of this study is to evaluate the effectiveness of single-incision mini-sling in the surgical treatment of postmenopausal urodynamic stress urinary incontinence (SUI) compared to the standard trans-obturator mid-urethral sling. Material and methods: This prospective study was carried out in two tertiary centres; Al-Azhar University Maternity & Urology Hospitals. A total of 120 postmenopausal women with urodynamic SUI were randomized to undergo either single-incision mini-sling (n = 60) or standard trans-obturator mid-urethral sling procedure (n = 60) from May 2019 until Oct 2021. Main outcome measures: efficacy was evaluated utilizing objective cure rate (cough stress test) and subjective cure rate (Sandvik incontinence severity index and International Consultations on Incontinence Questionnaire - Short Form), intraoperative and postoperative complications, and postoperative pain (using a visual analogue scale). Results: The single-incision mini-sling (SIMS) and transobturator tape (TOT) groups had no statistically significant difference in subjective and objective cure rates (p > 0.05). Compared with the transvaginal tape O group, patients in the SIMS group had significantly less postoperative pain, shorter operative duration, and less intraoperative blood loss (all p-values < 0.05). No significant difference in perioperative complications was observed between both groups. Conclusions: Single-incision mini-sling was superior to TOT in postmenopausal as SIMS is of similar effectiveness, more safe and minimally invasive with earlier ambulance.

Model study on real-time aeration based on nitrite for effective operation of single-stage anammox.

Anaerobic ammonia oxidation (Anammox) is an innovative technology for cost-efficient nitrogen removal without intensive aeration. However, effective control of the competition between nitrite oxidizing bacteria (XNOB) and Anammox bacteria (XANA) for nitrite is a key challenge for broad applications of single-stage Anammox processes in real wastewater treatment. Therefore, a real-time aeration scheme was proposed to determine dissolved oxygen (DO) based on nitrite concentration for effective control of XNOB growth while maintaining the XANA activity in a single-stage Anammox process. In this study, a non-steady state mathematical model was developed and calibrated using previously reported lab-scale Anammox results to investigate the efficiency of the proposed real-time aeration scheme in enhancing the Anammox process. Based on the calibrated model simulation results, DO of about 0.10 mg-O2/L was found to be ideal for maintaining effective nitrite creation by ammonia oxidizing bacteria (XAOB) while slowing down the growth of XNOB. If DO is too low (e.g., 0.01 mg-O2/L or lower), the overall rate of the ammonia removal is limited due to slow growth of XAOB. On the other hand, high DO (e.g., 1.0 mg-O2/L or higher) inhibits the growth of XANA, resulting in dominancy of XAOB and XNOB. According to the simulation results, nitrite concentration was found to be a rate-limiting parameter on effective nitrogen removal in single-stage Anammox processes. We also found that nitrite concentration can be used as a real-time switch for aeration in a single-stage Anammox process. A schematic aeration method based on real-time nitrite concentration was proposed and examined to control the competition between XANA and XNOB. In the model simulation, the XANA activity was successfully maintained because the schematic aeration prevented an outgrowth of XNOB, allowing energy-efficient nitrogen removal using single-stage Anammox processes.

Influence of hierarchy on risk communication during robot-assisted surgery: a preliminary study.

INTRODUCTION: A hierarchical structure is where all individuals are organized according to importance and are subordinate to a single person. In the operating room (OR), this structure may negatively impact the quality of communication and jeopardize patient safety. We examined how the surgical team's hierarchical relationships affect the frequency and timing of risk communication, and their influence on situational awareness (SA) in the OR. METHODS: Overhead cameras and lapel microphones were used to record the OR environment. Recordings and transcriptions of 10 robot-assisted prostatectomies were examined for risk utterances among team members. Utterances were classified by sender-recipient exchange, timing (determined by phrasing to be proactive or reactive to an error/negative event), and the Oxford Non-Technical Skills (NOTECHS) SA score. Surgeon's and trainee surgeon's utterances were classified by their on-console status. Chi-square tests were used to determine associations between dependent factors, and ANOVAs were used to evaluate the effect of hierarchy and timing on NOTECHS score. RESULTS: Of 4,583 examined utterances, 329 (7%) were risk-related. There was no significant difference in utterance frequency based on hierarchical status of sender and recipient (p = 0.16). Utterances made by the surgeon or trainee surgeon had higher NOTECHS scores when off versus on the console (scores: 1.8 vs 2.4, p < 0.01). These utterances were more reactive on the console (32%) and proactive off the console (28%). Proactive utterances had higher NOTECHS scores than reactive utterances (scores: 2.5 vs 1.8, p < 0.01). CONCLUSION: The surgical hierarchy significantly impacted the frequency of risk communication within the OR. Timing and on-console status further influenced the efficacy of risk communication.

Characterization of regulatory T cells in SARS-CoV-2 infected hemodialysis patients: relation to clinical and radiological severity.

BACKGROUND: Disordered Treg counts and function have been observed in patients with SARS-Cov-2 and are thought to contribute to disease severity. In hemodialysis patients, scarce data are available on the Treg response to SARS-CoV-2 or its relation to the clinical presentation. METHODS: A cross-sectional study included one hundred patients divided into three groups, thirty SARS-CoV-2-infected hemodialysis patients (COV-HD), and thirty confirmed SARSCoV-2 infected patients (COV), and forty non-infected hemodialysis patients (HD). Flow cytometric analysis of CD4, CD25, FoxP3, and CD39+ Tregs was done for all patients and tested for correlation to in-hospital mortality, clinical, radiological severity indices. RESULTS: COV-HD and COV patients had significantly lower Treg cell count than HD patients (Median value of 0.016 cell/ µl vs 0.28 cell/ µl, respectively- P: 0.001). COV-HD patients had higher CD39+ Tregs (median value of 0.006 cell/ µl vs 0.002 cell/ µl, respectively- P: 0.04). COV-HD patients had significantly lower hospital stay (median value of 3 vs 13 days, P:0.001), ICU admission rates (26.5% vs 46.7%, P:0.005) and in-hospital mortality (20.7% versus 43.3%, P:0.003) than COV patients. Treg and CD39 expressing Treg counts were not correlated to severity indices in both groups. A high neutrophil to lymphocyte ratio is strongly correlated to disease severity in COV-HD patients. CONCLUSIONS: This study provides evidence of T-cell, particularly T-regulatory cell decline in SARS-CoV-2 and suggests that hemodialysis per se does not distinctively impact the T-cell response. COV-HD patients exhibited a higher CD39+ Treg count and a better clinical profile, however, larger studies are needed to extrapolate on these findings.

Ileal conduit versus neobladder: A propensity score-matched analysis of the effect on renal function.

OBJECTIVES: To analyze the long-term effects of continent (neobladder) compared with incontinent (ileal conduit) urinary diversion. METHODS: We carried out a retrospective review of our departmental database. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Neobladder and ileal conduit patients were matched in a 1:2 ratio and a propensity score-matched analysis was carried out. Data were summarized using descriptive analysis. Trend plots were generated using baseline and follow-up creatinine values to compare estimated glomerular filtration rate at 3 months, then annually for 5 years. Variables associated with estimated glomerular filtration rate were assessed using multivariate linear analysis. RESULTS: Our cohort consisted of 137 patients (neobladder n = 50 and ileal conduit n = 87) with a median follow-up time of 3 years (interquartile range 1-7 years). The ileal conduit group had shorter operative times (352 vs 444 min, P < 0.01), intracorporeal diversions were more common (66% vs 44%, P = 0.01), had prior abdominal surgery (66% vs 38%, P < 0.01) and had radiation (9% vs 0%, P = 0.03). The neobladder group more commonly had recurrent urinary tract infections (22% vs 3%, P < 0.01) and a steeper decrease in estimated glomerular filtration rate in the first year. On multivariate linear analysis, age/year (-0.59), body mass index per kg/m2 (-0.52), preoperative estimated glomerular filtration rate per unit (0.51), recurrent urinary tract infections (-14.03) and time versus day 90 (year 1, -7.52; year 2, -9.06; year 3, -10.78) were significantly associated with estimated glomerular filtration rate. CONCLUSION: Ileal conduits and neobladders showed a similar effect on the estimated glomerular filtration rate up to 5 years after robot-assisted radical cystectomy. Recurrent urinary tract infections were associated with a worse estimated glomerular filtration rate.