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Rapid diagnostic tools for children with Ebola virus disease (EVD) are needed to expedite isolation and treatment. To evaluate a predictive diagnostic tool, we examined retrospective data (2014–2015) from the International Medical Corps Ebola Treatment Centers in West Africa. We incorporated statistically derived candidate predictors into a 7-point Pediatric Ebola Risk Score. Evidence of bleeding or having known or no known Ebola contacts was positively associated with an EVD diagnosis, whereas abdominal pain was negatively associated. Model discrimination using area under the curve (AUC) was 0.87, which outperforms the World Health Organization criteria (AUC 0.56). External validation, performed by using data from International Medical Corps Ebola Treatment Centers in the Democratic Republic of the Congo during 2018–2019, showed an AUC of 0.70. External validation showed that discrimination achieved by using World Health Organization criteria was similar; however, the Pediatric Ebola Risk Score is simpler to use.

Background Ebola Virus Disease (EVD) causes high case fatality rates (CFRs) in young children, yet there are limited data focusing on predicting mortality in pediatric patients. Here we present machine learning-derived prognostic models to predict clinical outcomes in children infected with Ebola virus. Methods Using retrospective data from the Ebola Data Platform, we investigated children with EVD from the West African EVD outbreak in 2014–2016. Elastic net regularization was used to create a prognostic model for EVD mortality. In addition to external validation with data from the 2018–2020 EVD epidemic in the Democratic Republic of the Congo (DRC), we updated the model using selected serum biomarkers. Findings Pediatric EVD mortality was significantly associated with younger age, lower PCR cycle threshold (Ct) values, unexplained bleeding, respiratory distress, bone/muscle pain, anorexia, dysphagia, and diarrhea. These variables were combined to develop the newly described EVD Prognosis in Children (EPiC) predictive model. The area under the receiver operating characteristic curve (AUC) for EPiC was 0.77 (95% CI: 0.74–0.81) in the West Africa derivation dataset and 0.76 (95% CI: 0.64–0.88) in the DRC validation dataset. Updating the model with peak aspartate aminotransferase (AST) or creatinine kinase (CK) measured within the first 48 hours after admission increased the AUC to 0.90 (0.77–1.00) and 0.87 (0.74–1.00), respectively. Conclusion The novel EPiC prognostic model that incorporates clinical information and commonly used biochemical tests, such as AST and CK, can be used to predict mortality in children with EVD. Author summary Although case fatality rates remain high, there are limited data on predicting mortality in children with Ebola Virus Disease (EVD). Furthermore, challenges in predicting EVD outcomes using clinical and laboratory data highlight the need for the development and validation of pediatric predictive models. The novel EVD Prognosis in Children (EPiC) model uses clinical and biochemical information, such as AST and CK, to predict mortality in infected children. While few prognostic models or scoring systems have been developed to predict clinical outcomes of EVD, the majority of them were limited in geographical and temporal scope having been derived using data from one location. As such, the EPiC model is the first externally validated model for the prognosis of pediatric EVD using diverse datasets from geographically and temporally separate outbreaks. This model can be easily applied by bedside clinicians to assess pediatric patients at risk for death and help to allocate resources accordingly.

Abstract Background Antimicrobial resistance (AMR) is a global public health threat and is increasingly prevalent among enteric pathogens in low- and middle-income countries (LMICs). However, the burden of multidrug-resistant organisms (MDROs) in older children, adults, and elderly patients with acute diarrhea in LMICs is poorly understood. This study’s aim was to characterize the prevalence of MDR enteric pathogens isolated from patients with acute diarrhea in Dhaka, Bangladesh, and assess a wide range of risk factors associated with MDR. Methods This study was a secondary analysis of data collected from children over 5 years, adults, and elderly patients with acute diarrhea at the International Centre for Diarrhoeal Disease Research, Bangladesh Dhaka Hospital between March 2019 and March 2020. Clinical, historical, socio-environmental information, and a stool sample for culture and antimicrobial susceptibility testing were collected from each patient. Univariate statistics and multiple logistic regression were used to assess the prevalence of MDR among enteric pathogens and the association between independent variables and presence of MRDOs among culture-positive patients. Results A total of 1198 patients had pathogens isolated by stool culture with antimicrobial susceptibility results. Among culture-positive patients, the prevalence of MDR was 54.3%. The prevalence of MDR was highest in Aeromonas spp. (81.5%), followed by Campylobacter spp. (72.1%), Vibrio cholerae (28.1%), Shigella spp. (26.2%), and Salmonella spp. (5.2%). Factors associated with having MDRO in multiple logistic regression included longer transport time to hospital (>90 min), greater stool frequency, prior antibiotic use prior to hospital presentation, and non-flush toilet use. However, pseudo-R2 was low 0.086, indicating that other unmeasured variables need to be considered to build a more robust predictive model of MDR. Conclusions MDR enteric pathogens were common in this study population with clinical, historical, and socio-environmental risk factors associated with MDROs. These findings may help guide clinical decision-making regarding antibiotic use and selection in patients at greatest risk of complications due to MDROs. Further prospective research is urgently needed to determine what additional factors place patients at greatest risk of MDRO, and the best strategies to mitigate the spread of MDR in enteric pathogens.

Objectives: Few studies have evaluated determinants of multidrug-resistant (MDR) Vibrio cholerae O1 in older children and adults. This study aimed to characterize the prevalence of MDR V. cholerae O1 and associated risk factors among patients over five years of age in Bangladesh. Methods: Stool culture and antimicrobial susceptibility testing were performed as a part of a larger study at Dhaka Hospital in Bangladesh from March 2019–March 2020. Univariate statistics and multiple logistic regression were used to assess the association between a range of variables and MDR V. cholerae O1. Results: MDR was found in 175 of 623 (28.1%) V. cholerae O1 isolates. High levels of resistance were found to erythromycin (99.2%), trimethoprim-sulfamethoxazole (99.7%), and ampicillin (88.9%), while susceptibility was high to tetracyclines (99.7%), azithromycin (99.2%), ciprofloxacin (99.8%), and cephalosporins (98.6%). MDR was associated with prior antibiotic use, longer transport time to hospital, higher income, non-flush toilet use, greater stool frequency, lower blood pressure, lower mid-upper arm circumference, and lower percent dehydration. Conclusions: MDR V. cholerae O1 was common among patients over five in an urban hospital in Bangladesh. Significant factors associated with MDR may be actionable in identifying patients with a high likelihood of MDR.

Novel stimuli elicit behaviors that are collectively known as specific exploration. These behaviors allow the animal to become more familiar with the novel objects within its environment. Specific exploration is frequently suppressed by defensive reactions to predator cues. Herein, we examine if this suppression occurs in Drosophila melanogaster by measuring the response of these flies to wild harvested predators. The flies used in our experiments have been cultured and had not lived under predator threat for multiple decades. In a circular arena with centrally-caged predators, wild type Drosophila actively avoided the pantropical jumping spider, Plexippus paykulli, and the Texas unicorn mantis, Phyllovates chlorophaena, indicating an innate defensive reaction to these predators. Interestingly, wild type Drosophila males also avoided a centrally-caged mock spider, and the avoidance of the mock spider became exaggerated when it was made to move within the cage. Visually impaired Drosophila failed to detect and avoid the Plexippus paykulli and the moving mock spider, while the broadly anosmic orco2 mutants were fully capable of detecting and avoiding Plexippus paykulli, indicating that these flies principally relied upon vison to perceive the predator stimuli. During early exploration of the arena, exploratory activity increased in the presence of Plexippus paykulli and the moving mock spider. The elevated activity induced by Plexippus paykulli disappeared after the fly had finished exploring, suggesting the flies were capable of habituating the predator cues. Taken together, these results indicate that despite being isolated from predators for decades Drosophila will visually detect these predators, retain innate defensive behaviors, respond by increasing exploratory activity in the arena rather than suppressing activity, and may habituate to normal predator cues.

Objectives: Eravacycline, a new tetracycline derivative, exhibits broad-spectrum antimicrobial susceptibility. This study aimed to comprehensively investigate in vitro activities of eravacycline, tigecycline, and ertapenem against various Gram-positive, Gram-negative, and anaerobic bacteria. Methods: Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. The following bacterial species were collected: vancomycin-sensitive (VS) Enterococci species, vancomycin-resistant Enterococci species (VRE), Staphylococcus aureus, Streptococcus anginosus, Bacteroides species, Clostridioides difficile, Clostridium innocuum, Clostridium perfringens, Parabacteroides distasonis, and Stenotrophomonas maltophilia. Results: We found that eravacycline exhibited superior in vitro activity compared to tigecycline and ertapenem. Notably, it exhibited the lowest MIC90 for several bacterial species, including VS E. faecalis (0.12 µg/mL), VS E. faecium (0.12 µg/mL), and others. Besides, VRE was susceptible to eravacycline (MIC90:0.12 µg/mL) and tigecycline (MIC90:0.12 µg/mL), but was all resistant to ertapenem (MIC90 > 64 µg/mL). S. aureus was also susceptible to eravacycline (MIC90:0.5 µg/mL) as well as tigecycline (MIC90:1.0 µg/mL). Furthermore, S. anginosus showed higher susceptibility to eravacycline (MIC90:2.0 µg/mL) and tigecycline (MIC90:4.0 µg/mL), but lower to ertapenem (MIC90:32.0 µg/mL). Eravacycline and tigecycline also demonstrated good susceptibility to anaerobes, including Bacteroides species (susceptibility rate: 100%), P. distasonis (100%), C. difficile (94.1‒100%), C. innocuum (94.1‒96.1%), and C. perfringens (88.9‒96.3%). For S. maltophilia, both tigecycline and eravacycline showed an MIC90 of 2 µg/mL. A moderate-to-strong correlation (rho = 0.608–0.804, P < 0.001) was noted between the MIC values of eravacycline and tigecycline against various bacterial species. Conclusions: Our study highlights the potential of eravacycline as an effective treatment option for multidrug-resistant bacterial infections.

Rapid diagnostic tools for children with Ebola virus disease (EVD) are needed to expedite isolation and treatment. To evaluate a predictive diagnostic tool, we examined retrospective data (2014-2015) from the International Medical Corps Ebola Treatment Centers in West Africa. We incorporated statistically derived candidate predictors into a 7-point Pediatric Ebola Risk Score. Evidence of bleeding or having known or no known Ebola contacts was positively associated with an EVD diagnosis, whereas abdominal pain was negatively associated. Model discrimination using area under the curve (AUC) was 0.87, which outperforms the World Health Organization criteria (AUC 0.56). External validation, performed by using data from International Medical Corps Ebola Treatment Centers in the Democratic Republic of the Congo during 2018-2019, showed an AUC of 0.70. External validation showed that discrimination achieved by using World Health Organization criteria was similar; however, the Pediatric Ebola Risk Score is simpler to use. [ABSTRACT FROM AUTHOR]

In severe or complex cases of peripheral nerve injuries, autologous nerve grafts are the gold standard yielding promising results, but limited availability and donor site morbidity are some of its disadvantages. Although biological or synthetic substitutes are commonly used, clinical outcomes are inconsistent. Biomimetic alternatives derived from allogenic or xenogenic sources offer an attractive off-the-shelf supply, and the key to successful peripheral nerve regeneration focuses on an effective decellularization process. In addition to chemical and enzymatic decellularization protocols, physical processes might offer identical efficiency. In this comprehensive minireview, we summarize recent advances in the physical methods for decellularized nerve xenograft, focusing on the effects of cellular debris clearance and stability of the native architecture of a xenograft. Furthermore, we compare and summarize the advantages and disadvantages, indicating the future challenges and opportunities in developing multidisciplinary processes for decellularized nerve xenograft.

Background: Epithelial-mesenchymal transition (EMT) of airway lung epithelial cells is considered a major driver of fibrosis and airway remodeling. Arsenic exposure is well known to cause the malignant transformation of cells, including those in the lung. Accumulating studies have shown that arsenic exposure is associated with chronic pulmonary diseases. However, clinical treatment for arsenic-induced pulmonary damage has not been well investigated.Materials and Methods: The therapeutic effects of montelukast and its combination with fluticasone on sodium arsenite-induced EMT changes in normal human bronchial cells were investigated. The cell migration ability was evaluated by Transwell and wound healing assays. EMT marker expression was determined by immunoblotting. Furthermore, the role of reactive oxygen species (ROS) generation in arsenic-induced EMT and the effect of montelukast on this process were determined by ROS inhibitor treatment and ROS measurement, respectively.Results: Montelukast was effective at reducing arsenic-induced cell migration and mesenchymal protein (fibronectin, MMP-2, N-cadherin, β-catenin, and SMAD2/3) expression. Arsenic-induced ROS production was attenuated by pretreatment with montelukast. Treatment with the ROS inhibitor N-acetyl cysteine reduced arsenic-induced NF-kB phosphorylation and the mesenchymal protein expression, indicating that ROS production is critical for arsenic-induced EMT. In addition, combined treatment with montelukast and fluticasone reversed the inhibitory effects of montelukast on cell migration. The expression of fibronectin, MMP-2 induced by arsenic was further enhanced by the combination treatment compared with montelukast treatment only.Conclusion: This study demonstrated that montelukast is effective at reducing arsenic-induced EMT in human bronchial epithelial cells. Through the inhibition of arsenic-induced ROS generation and NF-kB activation, which is critical for arsenic-induced EMT, montelukast inhibited arsenic-induced cell migration and the expression of extracellular matrix proteins and several EMT-regulating transcription factors. The combination of fluticasone with montelukast reversed the inhibitory effect of montelukast on arsenic-induced EMT. This study provides therapeutic strategies and mechanisms for arsenic-induced pulmonary epithelial damage.

BACKGROUND/OBJECTIVE:Osteoarthritis typically develops after surgery for traumatic fractures of the acetabulum and may result in total hip arthroplasty (THA). We conducted a population-based retrospective study to investigate the incidence of THA after treatment of acetabular, pelvic, and combined acetabular and pelvic fractures with open reduction-internal fixation surgery compared with that in the control group. DESIGN:A retrospective population-based cohort study. SETTING:Data were gathered from the Taiwan National Health Insurance Research Database. PARTICIPANTS:We enrolled 3041 patients with acetabular fractures, 5618 with pelvic fractures, and 733 with combined pelvic and acetabular fractures between January 1, 1997, and December 31, 2013, totaling 9392 individuals. The control group comprised 664,349 individuals. Study participants were followed up for the occurrence of THA until death or the end of the study period. RESULTS:The THA rates after surgical intervention were 17.82%, 7.28%, and 18.01% in patients with acetabular, pelvic, and combined acetabular and pelvic fractures, respectively. Moreover, they were significantly higher for the acetabular fracture, pelvic fracture, and combined-fracture groups (adjusted hazard ratios [aHRs] = 58.42, 21.68, and 62.04, respectively) than for the control group (p < 0.0001) and significantly higher for the acetabular fracture and combined-fracture groups than for the pelvic fracture group (aHRs = 2.59 and 2.68, respectively; p < 0.0001). CONCLUSION:The incidence rates of THA after surgical intervention in the pelvic fracture, acetabular fracture, and combined-fracture groups were significantly higher than that of the control group.

The geometric tolerance of notching machines used in the fabrication of components for induction motor stators and rotators is less than 50 µm. The blunt edges of worn molds can cause the edge of the sheet metal to form a burr, which can seriously impede assembly and reduce the efficiency of the resulting motor. The overuse of molds without sufficient maintenance leads to wasted sheet material, whereas excessive maintenance shortens the life of the punch/die plate. Diagnosing the mechanical performance of die molds requires extensive experience and fine-grained sensor data. In this study, we embedded polyvinylidene fluoride (PVDF) films within the mechanical mold of a notching machine to obtain direct measurements of the reaction forces imposed by the punch. We also developed an automated diagnosis program based on a support vector machine (SVM) to characterize the performance of the mechanical mold. The proposed cyber-physical system (CPS) facilitated the real-time monitoring of machinery for preventative maintenance as well as the implementation of early warning alarms. The cloud server used to gather mold-related data also generated data logs for managers. The hyperplane of the CPS-PVDF was calibrated using a variety of parameters pertaining to the edge characteristics of punches. Stereo-microscopy analysis of the punched workpiece verified that the accuracy of the fault classification was 97.6%.

BACKGROUND: Children with COVID-19 usually present with mild symptoms. We characterize visits with respect to symptoms and testing in the outpatient setting. METHODS: A retrospective chart review of sick visits in a pediatric academic primary care clinic April-August 2020. We included possible COVID-19 cases, or "persons under investigation" (PUIs), recording symptoms, positive contacts, and COVID-19 testing. Descriptive statistics and Chi-square or Fisher's exact tests for comparisons were used. RESULTS: 32% (476/1,474) of sick visits were PUIs; 20% were telehealth. Symptoms most commonly reported were fever, congestion/rhinorrhea and cough. 76% of PUIs were tested for COVID-19. Only presence of COVID-19 contacts and loss of taste/smell were significantly associated with positive tests (p<0.001). CONCLUSION: Nearly a third of sick visits in an academic pediatric practice were seen for possible COVID-19 symptoms and most were tested. The majority with and without COVID-19 had fever, congestion and/or cough. Our findings suggest low thresholds for testing in children. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the frequency, severity of presentation and initial presentations of new onset diabetes mellitus (DM) in youth in Rhode Island during the early phase of the COVID-19 pandemic compared to the same time frame in 2018 and 2019. METHODS: A retrospective cohort study of youth treated for new onset DM at Hasbro Children’s Hospital between March 1 and May 15, 2020, compared to those diagnosed in the same period in 2018 and 2019. RESULTS: Fewer youth were diagnosed with new onset DM in Spring 2020 and the percentage of youth with DKA at time of DM diagnosis was higher in Spring 2020 compared to prior years (p=0.048). Age, gender, and DKA complications did not differ by year. CONCLUSION: Nearly 50% fewer youth were diagnosed with DM at the start of the COVID-19 pandemic compared to years prior, and those diagnosed with new onset DM in Spring 2020 were more likely to present with DKA. Delays in both initial health care evaluation and the recognition of DM symptoms may have contributed to the decline in overall DM diagnoses and the more severe presentations. Identification of DM symptoms is essential, especially during future surges of COVID-19 or other events that impact the healthcare system, to reduce the risk of DM complications including DKA. [ABSTRACT FROM AUTHOR]