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Purpose: Lung auscultation has long been a standard of care for the diagnosis of respiratory diseases. Recent advances in electronic auscultation and signal processing have yet to find clinical acceptance; however, computerized lung sound analysis may be ideal for pediatric populations in settings, where skilled healthcare providers are commonly unavailable. We described features of normal lung sounds in young children using a novel signal processing approach to lay a foundation for identifying pathologic respiratory sounds. Methods: 186 healthy children with normal pulmonary exams and without respiratory complaints were enrolled at a tertiary care hospital in Lima, Peru. Lung sounds were recorded at eight thoracic sites using a digital stethoscope. 151 (81 %) of the recordings were eligible for further analysis. Heavy-crying segments were automatically rejected and features extracted from spectral and temporal signal representations contributed to profiling of lung sounds. Results: Mean age, height, and weight among study participants were 2.2 years (SD 1.4), 84.7 cm (SD 13.2), and 12.0 kg (SD 3.6), respectively; and, 47 % were boys. We identified ten distinct spectral and spectro-temporal signal parameters and most demonstrated linear relationships with age, height, and weight, while no differences with genders were noted. Older children had a faster decaying spectrum than younger ones. Features like spectral peak width, lower-frequency Mel-frequency cepstral coefficients, and spectro-temporal modulations also showed variations with recording site. Conclusions: Lung sound extracted features varied significantly with child characteristics and lung site. A comparison with adult studies revealed differences in the extracted features for children. While sound-reduction techniques will improve analysis, we offer a novel, reproducible tool for sound analysis in real-world environments. [ABSTRACT FROM AUTHOR]

Background and Objectives: Neurosurgical management of idiopathic intracranial hypertension (IIH) can be challenging given high rates of revision associated with cerebrospinal fluid shunting. In this study, we present a technical report and early outcomes for lumbocaval shunt (LCS) placement in difficult-to-manage cases., Methods: A literature search was performed for previous reports of LCS or lumboatrial shunt. Electronic medical records of patients who underwent placement of LCS for the treatment of IIH at a single institution were reviewed. Based on early experience and outcomes, our modified technique for LCS is described., Results: Six patients (4 females, median age 36 years [IQR 31-43]) underwent placement of LCS between October 2023 and April 2024. LCS was completed in all cases without intraoperative complications. The median operative time was 88.5 minutes [IQR 79.5-158.8]. One patient developed low-pressure headaches that resolved after the addition of a shunt-assist device. Five of 6 patients reported improved headache at the last follow-up visit, with 4 of 5 patients reporting that their high-pressure headaches completely resolved (median time to the last follow-up of one month [IQR 1-2 months]). During the study period, one shunt revision was performed because of migration of the lumbar shunt into a suprafascial pocket. This led to modification of the surgical technique, specifically the inclusion of anchoring dips., Conclusion: LCS may represent an alternative shunting technique in difficult-to-manage patients with IIH. Further assessment of long-term outcomes is needed., Competing Interests: The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article., (© The Author(s) 2024. Published by Wolters Kluwer Health, Inc. on behalf of Congress of Neurological Surgeons.)

Background: Cardiogenic shock (CS) mortality remains near 40%. In addition to inadequate cardiac output, patients with severe CS may exhibit vasodilation. We aimed to examine the prevalence and consequences of vasodilation in CS., Methods: We analyzed all patients hospitalized at a CS referral center who were diagnosed with CS stages B to E and did not have concurrent sepsis or recent cardiac surgery. Vasodilation was defined by lower systemic vascular resistance (SVR), higher norepinephrine equivalent dose, or a blunted SVR response to pressors. Threshold SVR values were determined by their relation to 14-day mortality in spline models. The primary outcome was death within 14 days of CS onset in multivariable-adjusted Cox models., Results: This study included 713 patients with a mean age of 60 years and 27% females; 14-day mortality was 28%, and 38% were vasodilated. The median SVR was 1308 dynes•s•cm -5 (interquartile range, 870-1652), median norepinephrine equivalent was 0.11 µg/kg per minute (interquartile range, 0-0.2), and 28% had a blunted pressor response. Each 100-dynes•s•cm -5 decrease in SVR below 800 was associated with 20% higher mortality (adjusted hazard ratio, 1.23; P =0.004). Each 0.1-µg/kg per minute increase in norepinephrine equivalent dose was associated with 15% higher mortality (adjusted hazard ratio, 1.12; P <0.001). A blunted pressor response was associated with a nearly 2-fold mortality increase (adjusted hazard ratio, 1.74; P =0.003)., Conclusions: Pathophysiologic vasodilation is prevalent in CS and independently associated with an increased risk of death. CS vasodilation can be identified by SVR <800 dynes•s•cm -5 , high doses of pressors, or a blunted SVR response to pressors. Additional studies exploring mechanisms and treatments for CS vasodilation are needed., Competing Interests: Dr Drakos served as a consultant to Abbott. The other authors report no conflicts.

Objective: The influence of socioeconomic factors on racial disparities among patients with sporadic meningiomas is well established, yet other potential causative factors warrant further exploration. The authors of this study aimed to determine whether there is significant variation in the genomic profile of meningiomas among patients of different races and ethnicities and its correlation with clinical outcomes., Methods: The demographic, genomic, and clinical data of patients aged 18 years and older who had undergone surgery for sporadic meningioma between September 2008 and November 2021 were analyzed. Statistical analyses were performed to detect differences across all racial/ethnic groups, as were direct comparisons between Black and non-Black groups plus Hispanic and non-Hispanic groups., Results: This study included 460 patients with intracranial meningioma. Hispanic patients were significantly younger at surgery (53.9 vs 60.2 years, p = 0.0006) and more likely to show symptoms. Black patients had a higher incidence of anterior skull base tumors (OR 3.2, 95% CI 1.7-6.3, p = 0.0008) and somatic hedgehog mutations (OR 5.3, 95% CI 1.6-16.6, p = 0.003). Hispanics were less likely to exhibit the aggressive genomic characteristic of chromosome 1p deletion (OR 0.28, 95% CI 0.07-1.2, p = 0.06) and displayed higher rates of TRAF7 somatic driver mutations (OR 2.96 95% CI 1.1-7.8, p = 0.036). Black patients had higher rates of recurrence (OR 2.6, 95% CI 1.3-5.2, p = 0.009) and shorter progression-free survival (PFS; HR 2.9, 95% CI 1.6-5.4, p = 0.002) despite extents of resection (EORs) similar to those of non-Black patients (p = 0.745). No significant differences in overall survival were observed among groups., Conclusions: Despite similar EORs, Black patients had worse clinical outcomes following meningioma resection, characterized by a higher prevalence of somatic hedgehog mutations, increased recurrence rates, and shorter PFS. Meanwhile, Hispanic patients had less aggressive meningiomas, a predisposition for TRAF7 mutations, and no difference in PFS. These findings could inform the care and treatment strategies for meningiomas, and they establish the foundation for future studies focusing on the genomic origins of these observed differences.

We implemented 2 interventions to improve utilization and contamination at our institution: kits to improve appropriate sample collection and an electronic order alert displaying appropriate indications of fungal blood cultures. An electronic order alert when ordering fungal blood cultures was associated with decreased utilization without decrease in positivity rate.

Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008-December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51-91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90-4.19) and in counties with >5 floodings per year versus no flooding (rate ratio 1.38, 95% CI 1.26-1.52). Higher risk for NTM infection was associated with older age, rurality, and more flooding. Clinicians and public health professionals should be aware of increased risk for NTM infections, especially in similar environments.

Purpose: Social determinants of health broadly affect healthcare access and outcomes. Studies report that minorities and low socioeconomic status (SES) patients undergoing intracranial meningioma resection demonstrate worse outcomes and higher mortality rates. This systematic review and meta-analysis summarizes the available research reporting racial and SES disparities in intracranial meningioma resection outcomes., Methods: A systematic review was conducted using PRISMA guidelines and included peer-reviewed, English-language articles from the United States between 2000 and 2022 that reported racial and SES disparities in meningioma outcomes. Outcomes included overall survival (OS), extent of resection (EOR), hospitalization costs, length of stay (LOS), 30-day readmission, recurrence, and receipt of surgery and adjuvant radiotherapy. A quantitative meta-analysis was performed only on survival outcomes by race. All other variables were summarized as a systematic review., Results: 633 articles were identified; 19 studies met inclusion criteria. Black or low SES patients were more likely to have increased hospitalization costs, rates of 30-day readmission, LOS, recurrence and less likely to undergo surgery, gross total resection, and adjuvant radiotherapy for their tumors. Six studies were used for the quantitative meta-analysis of race and OS. Compared to White patients, Black patients had significantly worse survival outcomes, and Asian patients had significantly better survival outcomes., Conclusion: Disparities in outcomes exist for patients who undergo surgery for meningioma, such that Black and low SES patients have worse outcomes. The literature is quite sparse and contains confounding relationships not often accounted for appropriately. Further studies are needed to help understand these disparities to improve outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities-however, they can also be found in the posterior fossa. The authors investigated whether NF2 mutant meningiomas differ in clinical and genomic features based on their location relative to the tentorium., Methods: Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic NF2 mutant meningiomas were reviewed and analyzed., Results: A total of 191 NF2 mutant meningiomas were included (165 supratentorial, 26 infratentorial). Supratentorial NF2 mutant meningiomas were significantly associated with edema (64.0% vs 28.0%, p < 0.001); higher grade-i.e., WHO grade II or III (41.8% vs 3.9%, p < 0.001); elevated Ki-67 (55.0% vs 13.6%, p < 0.001); and larger volume (mean 45.5 cm3 vs 14.9 cm3, p < 0.001). Furthermore, supratentorial tumors were more likely to harbor the higher-risk feature of chromosome 1p deletion (p = 0.038) and had a larger fraction of the genome altered with loss of heterozygosity (p < 0.001). Infratentorial meningiomas were more likely to undergo subtotal resection than supratentorial tumors (37.5% vs 15.8%, p = 0.021); however, there was no significant difference in overall (p = 0.2) or progression-free (p = 0.4) survival., Conclusions: Supratentorial NF2 mutant meningiomas are associated with more aggressive clinical and genomic features as compared with their infratentorial counterparts. Although infratentorial tumors have higher rates of subtotal resection, there is no associated difference in survival or recurrence. These findings help to better inform surgical decision-making in the management of NF2 mutant meningiomas based on location, and may guide postoperative management of these tumors.

Four patients with pulmonary valve (PV) disease and patent foramen ovale (PFO) presented with dyspnea on exertion. Work-up revealed hypoxemia secondary to right-to-left intracardiac shunt. We demonstrate that correction of the primary culprit right heart overload lesion via PV replacement enabled safe PFO repair and resolution of hypoxemia., Competing Interests: C. Huie Lin, MD, PhD, is a data monitoring committee member of ACI Clinical, speaker for Abiomed, proctor for Abbott, and course director for Gore Medical. All other authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Background: Online resources and social media have become increasingly ubiquitous in medical education. Little is known about the need for educational resources aimed at infectious disease (ID) fellows., Methods: We conducted an educational needs assessment through a survey that aimed to describe ID fellows' current use of online and social media tools, assess the value of online learning, and identify the educational content preferred by ID fellows. We subsequently convened focus groups with ID fellows to explore how digital tools contribute to fellow learning., Results: A total of 110 ID fellows responded to the survey. Over half were second-year fellows (61, 55%). Although many respondents were satisfied with the educational resources provided by their fellowship program (70, 64%), the majority were interested in an online collaborative educational resource (97, 88%). Twitter was the most popular social media platform for education and the most valued online resource for learning. Focus groups identified several themes regarding social medial learning: broadened community, low barrier to learning, technology-enhanced learning, and limitations of current tools. Overall, the focus groups suggest that fellows value social media and online learning., Conclusions: ID fellows are currently using online and social media resources, which they view as valuable educational tools. Fellowship programs should consider these resources as complementary to traditional teaching and as a means to augment ID fellow education., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Epileptic seizures are a common and potentially devastating complication of metastatic brain tumors. Although tumor-related seizures have been described in previous case series, most studies have focused on primary brain tumors and have not differentiated between different types of cerebral metastases. The authors analyzed a large surgical cohort of patients with brain metastases to examine risk factors associated with preoperative and postoperative seizures and to better understand the seizure risk factors of metastatic brain tumors., Methods: Patients who underwent resection of a brain metastasis at the University of California, San Francisco (UCSF), were retrospectively reviewed. Patients included in the study were ≥ 18 years of age, required resection of a brain metastasis, and were treated at UCSF. Primary cancers included melanoma, non-small cell lung adenocarcinoma, breast adenocarcinoma, colorectal adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, renal cell carcinoma, urothelial carcinoma, ovarian carcinoma, cervical squamous cell carcinoma, and endometrial adenocarcinoma. Patients were evaluated for primary cancer type and seizure occurrence, as well as need for use of antiepileptic drugs preoperatively, at time of discharge, and at 6 months postoperatively. Additionally, Engel classification scores were assigned to those patients who initially presented with seizures preoperatively. Univariate and multivariate regression analyses were used to assess the association of tumor type with preoperative seizures., Results: Data were retrospectively analyzed for 348 consecutive patients who underwent surgical treatment of brain metastases between 1998 and 2019. The cohort had a mean age of 60 years at the time of surgery and was 59% female. The mean and median follow-up durations after the date of surgery for the cohort were 22 months and 10.8 months, respectively. In univariate analysis, frontal lobe location (p = 0.05), melanoma (p = 0.02), KRAS mutation in lung carcinoma (p = 0.04), intratumoral hemorrhage (p = 0.04), and prior radiotherapy (p = 0.04) were associated with seizure presentation. Postoperative checkpoint inhibitor use (p = 0.002), prior radiotherapy (p = 0.05), older age (p = 0.002), distant CNS progression (p = 0.004), and parietal lobe tumor location (p = 0.002) were associated with seizures at 6 months postoperatively. The final multivariate model confirmed the independent effects of tumor location in the frontal lobe and presence of intratumoral hemorrhage as predictors of preoperative seizures, and checkpoint inhibitor use and parietal lobe location were identified as significant predictors of seizures at 6 months postoperatively., Conclusions: Within this surgical cohort of patients with brain metastases, seizures were seen in almost a quarter of patients preoperatively. Frontal lobe metastases and hemorrhagic tumors were associated with higher risk of preoperative seizures, whereas checkpoint inhibitor use and parietal lobe tumors appeared to be associated with seizures at 6 months postoperatively. Future research should focus on the effect of metastatic lesion-targeting therapeutic interventions on seizure control in these patients.

Persistent Staphylococcus aureus bacteremia (SAB) has been associated with increased mortality. Enhanced microbial detection with new blood culture technology may improve detection of S. aureus in patients with SAB. We performed a 24-month retrospective study of hospitalized adults with SAB and an infectious diseases consult comparing two time periods pre- (January to December 2018) and postimplementation (January to December 2019) in which the VersaTREK and BacT/Alert Virtuo blood culture systems were used, respectively. Measurements included SAB duration, time to positivity, source of bacteremia, antimicrobial therapy, and mortality. A total of 416 episodes of SAB occurred during the study period: 176 (42%) pre- and 240 (58%) postimplementation. Patients in both periods had similar clinical characteristics; however, patients in the postimplementation period were more likely to have intermediate (3 to 6 days; 23% versus 40%; P  < 0.001) and prolonged SAB duration (>7 days; 4% versus 14%; P  < 0.001). Combination antistaphylococcal therapy was more frequent postimplementation (6.3% pre- versus 15.8% postimplementation; P  = 0.003), and the median time to source control was shorter (4 versus 2 days; P  = 0.02). Median time to positivity for the index blood culture was shorter postimplementation (17.8 h pre- versus 13.3 h postimplementation; P  < 0.001). There was no difference in 90-day all-cause readmissions (51% versus 44%; P  = 0.11) or mortality (32% versus 32%; P  = 0.95). An increased frequency of prolonged SAB with increased use of combination antistaphylococcal therapy was noted with implementation of a new blood culture system, likely secondary to the blood culture media; however, no differences on adverse outcomes were noted.

Many neuromuscular diseases, such as myasthenia gravis (MG), are associated with dysfunction of the neuromuscular junction (NMJ), which is difficult to characterize in animal models due to physiological differences between animals and humans. Tissue engineering offers opportunities to provide in vitro models of functional human NMJs that can be used to diagnose and investigate NMJ pathologies and test potential therapeutics. By incorporating optogenetic proteins into induced pluripotent stem cells (iPSCs), we generated neurons that can be stimulated with specific wavelengths of light. If the NMJ is healthy and functional, a neurochemical signal from the motoneuron results in muscle contraction. Through the integration of optogenetics and microfabrication with tissue engineering, we established an unbiased and automated methodology for characterizing NMJ function using video analysis. A standardized protocol was developed for NMJ formation, optical stimulation with simultaneous video recording, and video analysis of tissue contractility. Stimulation of optogenetic motoneurons by light to induce skeletal muscle contractions recapitulates human NMJ physiology and allows for repeated functional measurements of NMJ over time and in response to various inputs. We demonstrate this platform's ability to show functional improvements in neuromuscular connectivity over time and characterize the damaging effects of patient MG antibodies or neurotoxins on NMJ function.

Background: Although overall survival (OS) has improved in patients with brain metastases (BMs), control of recurrent BMs remains a therapeutic challenge. Salvage surgery may achieve acceptable control rates in the setting of progression after previous stereotactic radiosurgery (SRS), yet it remains a question how additional adjuvant therapies may affect outcomes and how patient selection for salvage surgery may be optimized., Methods: Patients receiving salvage surgery for BM progression after previous SRS were retrospectively reviewed from a single center. Outcomes of interest included local tumor progression, leptomeningeal dissemination, and OS. Cox proportional hazard models and nominal logistic regression were applied to determine factors associated with outcomes of interest., Results: A total of 43 patients with 50 BMs were included. After salvage surgery, local progression was observed for 17 BMs (34%), leptomeningeal dissemination was observed in 17 patients (39.5%), and censored median OS was 17.9 months. On multivariate analysis, use of brachytherapy was associated with improved local control (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04-0.6; P = 0.008). For patients treated with SRS ≥4.5 months before salvage surgery, both brachytherapy (HR, 0.07; 95% CI, 0.01-0.39; P = 0.002) and postoperative adjuvant SRS (HR, 0.14; 95% CI, 0.02-1.00; P = 0.05) were associated with improved local control compared with no adjuvant radiation therapy. Presence of extracranial malignancy (HR, 6.70; 95% CI, 2.58-17.42; P < 0.0001) was associated with shorter survival. Graded prognostic assessment underestimated survival in 79.1% of patients, with a mean difference of 18.9 months between graded prognostic assessment-estimated and actual OS., Conclusions: In properly selected patients, salvage surgery may be an appropriate therapy for BM progression after previous SRS. Adjuvant brachytherapy and repeat SRS can offer significant benefit for local control with salvage resection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study aims to describe the short-term therapeutic results of patients treated with operative arthroscopy and medical infiltration with platelet-rich fibrin in upper and lower articular space. The study design is descriptive observational with retrospective case series of patients with Wilkes II and III. These patients were managed with operative arthroscopy viscosupplementation with platelet-rich fibrin (PRF) and were followed up for up to 8 months to evaluate their response to treatment. 17 patients were included in the study. In the pre-surgical assessment (T1) mean VAS was 7.1 and MID was 22.2 mm. Eight months later (T4) a relevant improvement in both mentioned variables MID 38.2 ± 4.1 and VAS 1.1 ± 0.2 was observed. Regarding the reduction of pain, a significant improvement in symptoms were found, this being 84.6% ± 3.5% and in mandibular mobility satisfactory results were also obtained, improving in 41.7% ± 20.9%. Within the limitations of the study temporomandibular joint arthroscopy and medical infiltration platelet-rich fibrin viscosupplementation is a procedure of limited invasiveness that shows promising results., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Engineered cardiac tissues derived from human induced pluripotent stem cells (iPSCs) are increasingly used for drug discovery, pharmacology and in models of development and disease. While there are numerous platforms to engineer cardiac tissues, they often require expensive and nonconventional equipment and utilize complex video-processing algorithms. As a result, only specialized academic laboratories have been able to harness this technology. In addition, methodologies and tissue features have been challenging to reproduce between different groups and models. Here, we describe a facile technology (milliPillar) that covers the entire pipeline required for studies of engineered cardiac tissues. We include methodologies for (i) platform fabrication, (ii) cardiac tissue generation, (iii) electrical stimulation, (iv) automated real-time data acquisition, and (v) advanced video analyses. We validate these methodologies and demonstrate the versatility of the platform by showcasing the fabrication of tissues in different hydrogel materials and using cardiomyocytes derived from different iPSC lines in combination with different types of stromal cells. We also validate the long-term culture of tissues within the platform and provide protocols for automated analysis of force generation and calcium flux using both brightfield and fluorescence imaging. Lastly, we demonstrate the compatibility of the milliPillar platform with electromechanical stimulation to enhance cardiac tissue function. We expect that this resource will provide a valuable and user-friendly tool for the generation and real-time assessment of engineered human cardiac tissues for basic and translational studies.

The bioMérieux BacT/Alert Virtuo blood culture system used in combination with resin-containing media may enhance the growth of microorganisms. Our objective was to assess the impact of transitioning to the Virtuo system in comparison to the VersaTREK blood culture system at a tertiary care medical center. We retrospectively reviewed all blood cultures performed at a 1,250-bed academic medical center between January and December 2018 (VersaTREK) and January and December 2019 (Virtuo). Blood culture positivity rates and contamination rates were compared before and after Virtuo implementation. Of 101,438 blood cultures performed during the study period, 48,839 (48.1%) were processed preimplementation and 52,599 (51.9%) postimplementation. The blood culture positivity rate increased from 8.1% preimplementation to 11.7% postimplementation ( P  < 0.001). Staphylococcus aureus was the most frequently isolated species in both time periods and had a higher recovery rate postimplementation (1.5% of all blood cultures obtained preimplementation versus 3.4% postimplementation; P  < 0.001). A higher recovery rate in the postimplementation period was also noted for coagulase-negative staphylococci (1.9% preimplementation versus 2.7% postimplementation; P  < 0.001), as well as modest but statistically significant changes for Escherichia coli (0.8% versus 1.0%; P  < 0.001), Klebsiella pneumoniae (0.4% versus 0.5%; P  = 0.005), and Candida albicans. (0.1% versus 0.2%; P  = 0.038). The inpatient blood culture contamination rate was higher postimplementation (1.5% preimplementation versus 1.9% postimplementation; P  < 0.001). The Virtuo blood culture system was associated with a higher observed proportion of positive blood cultures than the VersaTREK system. Future studies are needed to assess whether an increased rate of positive blood cultures is associated with changes in clinical outcomes.

Functional human tissues engineered from patient-specific induced pluripotent stem cells (hiPSCs) hold great promise for investigating the progression, mechanisms, and treatment of musculoskeletal diseases in a controlled and systematic manner. For example, bioengineered models of innervated human skeletal muscle could be used to identify novel therapeutic targets and treatments for patients with complex central and peripheral nervous system disorders. There is a need to develop standardized and objective quantitative methods for engineering and using these complex tissues, in order increase their robustness, reproducibility, and predictiveness across users. Here we describe a standardized method for engineering an isogenic, patient specific human neuromuscular junction (NMJ) that allows for automated quantification of NMJ function to diagnose disease using a small sample of blood serum and evaluate new therapeutic modalities. By combining tissue engineering, optogenetics, microfabrication, optoelectronics and video processing, we created a novel platform for the precise investigation of the development and degeneration of human NMJ. We demonstrate the utility of this platform for the detection and diagnosis of myasthenia gravis, an antibody-mediated autoimmune disease that disrupts the NMJ function., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Community-acquired pneumonia remains the leading cause of death in children worldwide, and current diagnostic guidelines in resource-poor settings are neither sensitive nor specific. We sought to determine the ability to correctly diagnose radiographically confirmed clinical pneumonia when diagnostics tools were added to clinical signs and symptoms in a cohort of children with acute respiratory illnesses in Peru., Methods: Children < 5 years of age with an acute respiratory illness presenting to a tertiary hospital in Lima, Peru, were enrolled. The ability to predict radiographically confirmed clinical pneumonia was assessed using logistic regression under four additive scenarios: clinical signs and symptoms only, addition of lung auscultation, addition of oxyhemoglobin saturation (Spo 2 ), and addition of lung ultrasound., Results: Of 832 children (mean age, 21.3 months; 59% boys), 453 (54.6%) had clinical pneumonia and 221 (26.6%) were radiographically confirmed. Children with radiographically confirmed clinical pneumonia had lower average Spo 2 than those without (95.9% vs 96.6%, respectively; P < .01). The ability to correctly identify radiographically confirmed clinical pneumonia using clinical signs and symptoms was limited (area under the curve [AUC] = 0.62; 95% CI, 0.58-0.67) with a sensitivity of 66% (95% CI, 59%-73%) and specificity of 53% (95% CI, 49%-57%). The addition of lung auscultation improved classification (AUC = 0.73; 95% CI, 0.69-0.77) with a sensitivity of 75% (95% CI, 69%-81%) and specificity of 53% (95% CI, 49%-57%) for the presence of crackles. In contrast, the addition of Spo 2 did not improve classification (AUC = 0.73; 95% CI, 0.69-0.77) with a sensitivity of 40% (95% CI, 33%-47%) and specificity of 72% (95% CI, 68%-75%) for an Spo 2  ≤ 92%. Adding consolidation on lung ultrasound was associated with the largest improvement in classification (AUC = 0.85; 95% CI, 0.82-0.89) with a sensitivity of 55% (95% CI, 48%-63%) and specificity of 95% (95% CI, 93%-97%)., Conclusions: The addition of lung ultrasound and auscultation to clinical signs and symptoms improved the ability to correctly classify radiographically confirmed clinical pneumonia. Implementation of auscultation- and ultrasound-based diagnostic tools can be considered to improve diagnostic yield of pneumonia in resource-poor settings., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Mast cells (MCs) play pivotal roles in many inflammatory conditions including infections, anaphylaxis, and asthma. MCs store immunoregulatory compounds in their large cytoplasmic granules and, upon stimulation, secrete them via regulated exocytosis. Exocytosis in many cells requires the participation of Munc18 proteins (also known as syntaxin-binding proteins), and we found that mature MCs express all three mammalian isoforms: Munc18-1, -2, and -3. To study their functions in MC effector responses and test the role of MC degranulation in anaphylaxis, we used conditional knockout (cKO) mice in which each Munc18 protein was deleted exclusively in MCs. Using recordings of plasma membrane capacitance for high-resolution analysis of exocytosis in individual MCs, we observed an almost complete absence of exocytosis in Munc18-2-deficient MCs but intact exocytosis in MCs lacking Munc18-1 or Munc18-3. Stereological analysis of EM images of stimulated MCs revealed that the deletion of Munc18-2 also abolishes the homotypic membrane fusion required for compound exocytosis. We confirmed the severe defect in regulated exocytosis in the absence of Munc18-2 by measuring the secretion of mediators stored in MC granules. Munc18-2 cKO mice had normal morphology, development, and distribution of their MCs, indicating that Munc18-2 is not essential for the migration, retention, and maturation of MC-committed progenitors. Despite that, we found that Munc18-2 cKO mice were significantly protected from anaphylaxis. In conclusion, MC-regulated exocytosis is required for the anaphylactic response, and Munc18-2 is the sole Munc18 isoform that mediates membrane fusion during MC degranulation., (© 2018 Gutierrez et al.)

Background: Pneumonia is a leading cause of morbidity and mortality in children worldwide; however, its diagnosis can be challenging, especially in settings where skilled clinicians or standard imaging are unavailable. We sought to determine the diagnostic accuracy of lung ultrasound when compared to radiographically-confirmed clinical pediatric pneumonia., Methods: Between January 2012 and September 2013, we consecutively enrolled children aged 2-59 months with primary respiratory complaints at the outpatient clinics, emergency department, and inpatient wards of the Instituto Nacional de Salud del Niño in Lima, Peru. All participants underwent clinical evaluation by a pediatrician and lung ultrasonography by one of three general practitioners. We also consecutively enrolled children without respiratory symptoms. Children with respiratory symptoms had a chest radiograph. We obtained ancillary laboratory testing in a subset., Results: Final clinical diagnoses included 453 children with pneumonia, 133 with asthma, 103 with bronchiolitis, and 143 with upper respiratory infections. In total, CXR confirmed the diagnosis in 191 (42%) of 453 children with clinical pneumonia. A consolidation on lung ultrasound, which is our primary endpoint for pneumonia, had a sensitivity of 88.5%, specificity of 100%, and an area under-the-curve of 0.94 (95% CI 0.92-0.97) when compared to radiographically-confirmed clinical pneumonia. When any abnormality on lung ultrasound was compared to radiographically-confirmed clinical pneumonia the sensitivity increased to 92.2% and the specificity decreased to 95.2%, with an area under-the-curve of 0.94 (95% CI 0.91-0.96)., Conclusions: Lung ultrasound had high diagnostic accuracy for the diagnosis of radiographically-confirmed pneumonia. Added benefits of lung ultrasound include rapid testing and high inter-rater agreement. Lung ultrasound may serve as an alternative tool for the diagnosis of pediatric pneumonia., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The World Health Organization (WHO) case management algorithm for acute lower respiratory infections has moderate sensitivity and poor specificity for the diagnosis of pneumonia. We sought to determine the feasibility of using point-of-care ultrasound in resource-limited settings to identify pneumonia by general health practitioners and to determine agreement between the WHO algorithm and lung consolidations identified by point-of-care ultrasound., Methods: An expert radiologist taught two general practitioners how to perform point-of-care ultrasound over a seven-day period. We then conducted a prospective study of children aged 2 months to 3 years in Peru and Nepal with and without respiratory symptoms, which were evaluated by point-of-care ultrasound to identify lung consolidation., Results: We enrolled 378 children: 127 were controls without respiratory symptoms, 82 had respiratory symptoms without clinical pneumonia, and 169 had clinical pneumonia by WHO criteria. Point-of-care ultrasound was performed in the community (n = 180), in outpatient offices (n = 95), in hospital wards (n = 19), and in Emergency Departments (n = 84). Average time to perform point-of-care ultrasound was 6.4 ± 2.2 min. Inter-observer agreement for point-of-care ultrasound interpretation between general practitioners was high (κ = 0.79, 95 % CI 0.73-0.81). The diagnosis of pneumonia using the WHO algorithm yielded a sensitivity of 69.6 % (95 % CI 55.7-80.8 %), specificity of 59.6 % (95 % CI 54.0-65.0 %), and positive and negative likelihood ratios of 1.73 (95 % CI 1.39-2.15) and 0.51 (95 % CI 0.30-0.76) when lung consolidation on point-of-care ultrasound was used as the reference., Conclusions: The WHO algorithm disagreed with point-of-care ultrasound findings in more than one-third of children and had an overall low performance when compared with point-of-care ultrasound to identify lung consolidation. A paired approach with point-of-care ultrasound may improve case management in resource-limited settings.

Aeroelastic effects are relatively common in the design of modern civil constructions such as office blocks, airport terminal buildings, and factories. Typical flexible structures exposed to the action of wind are shading devices, normally slats or louvers. A typical cross-section for such elements is a Z-shaped profile, made out of a central web and two-side wings. Galloping instabilities are often determined in practice using the Glauert-Den Hartog criterion. This criterion relies on accurate predictions of the dependence of the aerodynamic force coefficients with the angle of attack. The results of a parametric analysis based on a numerical analysis and performed on different Z-shaped louvers to determine translational galloping instability regions are presented in this paper. These numerical analysis results have been validated with a parametric analysis of Z-shaped profiles based on static wind tunnel tests. In order to perform this validation, the DLR TAU Code, which is a standard code within the European aeronautical industry, has been used. This study highlights the focus on the numerical prediction of the effect of galloping, which is shown in a visible way, through stability maps. Comparisons between numerical and experimental data are presented with respect to various meshes and turbulence models.