Needles in haystacks: monitoring the potential escape of bioaerosolised antibacterial resistance genes from wastewater treatment plants with air and phyllosphere sampling.

Wastewater treatment plants are well-known point sources of emissions of antibacterial resistance genes (ARGs) into the environment. Although most work to date has focused on ARG dispersal via effluent, aerial dispersal in bioaerosols is a poorly understood, but likely important vector for ARG dispersal. Recent evidence suggests that ARG profiles of the conifer needle phyllosphere could be used to measure bioaerosol dispersal from anthropogenic sources. Here, we assessed airborne dispersal of ARGs from wastewater treatment plants in Wales, UK and Quebec, Canada, using conifer needles as passive bioaerosol monitors. ARG profiles of wastewater were compared to those of conifer phyllosphere using high-throughput qPCR. ARG richness was significantly lower in conifer phyllosphere samples than wastewater samples, though no differences were observed across the dispersal gradients. Mean copy number of ARGs followed a similar trend. ARG profiles showed limited, but consistent patterns with increasing distance from wastewater treatment plants, but these did not align with those of wastewater samples. For example, proportional abundance of aminoglycosides decreased over the dispersal gradient in Wales, whereas mobile genetic elements showed the inverse relationship. In summary, while distinct ARG profiles exist along dispersal gradients, links to those of wastewater were not apparent.

Original Article--Clinical and Procedural Characteristics of Successful Transcatheter Device Closure of Ostium Secundum Atrial Septal Defect in Symptomatic Children Weighing <15 kg: A Retrospective Study Spanning One Decade From South India.

Objectives: This retrospective study sought to determine the feasibility of transcatheter atrial septal defect device closure in patients less than 15 kg, as well as to assess complication rates and the reasons for unsuccessful device closure. Background: In general, the risks associated with transcatheter atrial septal defect device closure are believed and reported to be relatively low, but the evidence stems from trials involving adults and older children. Current guidelines do not recommend atrial defect closure in device closure in children <15 kg, due to limited data available for feasibility and safety of device closure in this group of patients. Methods: Retrospective review of all patients who underwent elective transcatheter closure of ostium secundum atrial septal defect between September 2013 to February 2022. We excluded all children above 15 kg, as well as those with complex congenital heart defects. Major and minor complications were predefined and indications for referral were evaluated. Results: We identified 81 patients meeting criteria with a median procedural age of 3 years (1 year-8 years), and median weight of 12 kg (4-15 kg). Successful device closure was achieved in 95.1% (77/81) and in 4.9% (4/81), the procedure was aborted. There was 1 major (1.2%) and 1 minor (1.2%) complication, total complication rate (2.4%). 100% of the referrals had right heart enlargement and exertional dyspnoea, 18.5% had recurrent lower respiratory tract infection and 9.9% had failure to thrive. Rate of resolution of residual shunt was 95.1%. at post-procedure day 1 and 98.8% at post-procedure 3 and 6 months respectively. Conclusions: Percutaneous atrial septal defect closure can be done effectively and safely in symptomatic children weighing less than 15 kg in experienced centres. However, deferral for closure until the historically established timeline of around 4-5 years of age should be strongly considered in asymptomatic children.

Investigation of mutation spectrum amongst patients with familial primary cardiomyopathy using targeted NGS in Indian population.

Genetic cardiomyopathies (CM) are disorders that affect morphology and function of cardiac muscle. Significant number of genes have been implicated in causing the phenotype. It is one of the leading genetic causes of death in young. We performed a study to understand the genetic variants in primary cardiomyopathies in an Indian cohort. Study comprised of 22 probands (13 with family history) representing hypertrophic (n = 10), dilated (n = 7), restrictive (n = 2) and arrhythmogenic ventricular(n = 3) cardiomyopathies. Genomic DNA was target captured with a panel of 46 genes and libraries sequenced on Illumina platform. Analysis identified, reported pathogenic as well as novel pathogenic (n = 6) variants in 16 probands. Of the 10 HCM patients, candidate variants were identified in nine of them involving sarcomere genes (62%, MYBPC3, MYH6, MYH7, MYL3, TTN), Z-disc (10%, ACTN2, LDB3, NEXN,), desmosome (10%, DSG2, DSP, PKP2) cytoskeletal (4%, DTNA) and ion channel (10% RYR2). In four DCM patients, variants were identified in genes NEXN, LMNA and TTN. Three arrhythmogenic right ventricular cardiomyopathy (ARVD) patients carried mutations in desmosome genes. Rare TTN variants were identified in multiple patients. Targeted capture and sequencing resulted in identification of candidate variants in about 70% of the samples which will help in management of disease in affected individual as well as in screening and early diagnosis in asymptomatic family members. Amongst the analysed cases, 22% were inconclusive without any significant variant identified. Study illustrates the utility of next-generation multi-gene panel as a cost-effective genetic testing to screen all forms of primary cardiomyopathies.

Brain Frontal-Lobe Misery Perfusion in COVID-19 ICU Survivors: An MRI Pilot Study.

Post-acute COVID-19 syndrome (PCS) is highly prevalent. Critically ill patients requiring intensive care unit (ICU) admission are at a higher risk of developing PCS. The mechanisms underlying PCS are still under investigation and may involve microvascular damage in the brain. Cerebral misery perfusion, characterized by reduced cerebral blood flow (CBF) and elevated oxygen extraction fraction (OEF) in affected brain areas, has been demonstrated in cerebrovascular diseases such as carotid occlusion and stroke. This pilot study aimed to examine whether COVID-19 ICU survivors exhibited regional misery perfusion, indicating cerebral microvascular damage. In total, 7 COVID-19 ICU survivors (4 female, 20-77 years old) and 19 age- and sex-matched healthy controls (12 female, 22-77 years old) were studied. The average interval between ICU admission and the MRI scan was 118.6 ± 30.3 days. The regional OEF was measured using a recently developed technique, accelerated T2-relaxation-under-phase-contrast MRI, while the regional CBF was assessed using pseudo-continuous arterial spin labeling. COVID-19 ICU survivors exhibited elevated OEF (ß = 5.21 ± 2.48%, p = 0.047) and reduced relative CBF (ß = -0.083 ± 0.025, p = 0.003) in the frontal lobe compared to healthy controls. In conclusion, misery perfusion was observed in the frontal lobe of COVID-19 ICU survivors, suggesting microvascular damage in this critical brain area for high-level cognitive functions that are known to manifest deficits in PCS. Physiological biomarkers such as OEF and CBF may provide new tools to improve the understanding and treatment of PCS.

Conductive gradient hydrogels allow spatial control of adult stem cell fate.

Electrical gradients are fundamental to physiological processes including cell migration, tissue formation, organ development, and response to injury and regeneration. Current electrical modulation of cells is primarily studied under a uniform electrical field. Here we demonstrate the fabrication of conductive gradient hydrogels (CGGs) that display mechanical properties and varying local electrical gradients mimicking physiological conditions. The electrically-stimulated CGGs enhanced human mesenchymal stem cell (hMSC) viability and attachment. Cells on CGGs under electrical stimulation showed a high expression of neural progenitor markers such as Nestin, GFAP, and Sox2. More importantly, CGGs showed cell differentiation toward oligodendrocyte lineage (Oligo2) in the center of the scaffold where the electric field was uniform with a greater intensity, while cells preferred neuronal lineage (NeuN) on the edge of the scaffold on a varying electric field at lower magnitude. Our data suggest that CGGs can serve as a useful platform to study the effects of electrical gradients on stem cells and potentially provide insights on developing new neural engineering applications.

Impact of ambient air pollution and socio-environmental factors on the health of children younger than 5 years in India: a population-based analysis.

Background: Ambient air pollution and household environmental factors affect child health, particularly in low-income and middle-income countries. This study aimed to investigate the association between ambient air pollution (PM2·5) levels, socio-environmental factors (including household wealth, housing quality measures, smoking status), and the occurrence of respiratory illness in Indian children. Methods: In this retrospective and observational study, we analysed data from India's National Family Health Survey (NFHS-5, 2019-2021) combined with NASA's Global Annual PM2·5 Grids database. Bivariate and multivariable generalized additive models were employed to examine associations between key social-environmental factors and respiratory illness in children younger than 5 years. Findings: We analysed data from 224,214 children younger than 5 years, representing 165,561 families from 29,757 geographic clusters. Our results showed extremely high annual PM2·5 levels throughout India (median 63·4·g/m3, IQR 41·9-81·6), with higher exposure for rural and impoverished families. In bivariate analyses, PM2·5 was significantly associated with reported respiratory illness (p < 0·001). Using generalized additive models and after accounting for key social and environmental factors, a monotonic increasing and non-linear relationship was observed between PM2·5 and respiratory illness (p < 0·001), with increased likelihood of illness observed even at values near and below India's National Ambient Air Quality Standards of 40 µg/m3. Interpretation: The study highlights the significant association of social-environmental conditions with health outcomes among young children in India. Efforts specifically targeting ambient air pollution and child health during monsoon season could have significant health benefits among this population and help achieve the goal of ending preventable deaths of children younger than 5 years. Funding: National Institutes of Health (NIH T-32-HL139443-3).

Missing the mark? Exploratory analysis of the 10-year-old cutoff as an independent marker of high-risk disease in pediatric B-ALL.

This single-center, retrospective study evaluated age as a risk factor for relapsed/refractory disease and/or death in 153 children with B-cell acute lymphoblastic leukemia. The study sample included children near the 10-year age cutoff for high-risk disease (6.0-13.9 years at diagnosis) and without other high-risk features (high white cell count, unfavorable cytogenetics). Children 10.0-13.9 years treated per high-risk protocols did not have inferior outcomes compared with children aged 6.0-9.9 years initiating treatment per standard-risk protocols. The study indicates that, in the era of cytogenetics, an age threshold of 10 years might not be an independent prognostic marker. Multicenter analyses are needed.

Wirelessly Powered-Electrically Conductive Polymer System for Stem Cell Enhanced Stroke Recovery.

Effective stroke recovery therapeutics remain limited. Stem cell therapies have yielded promising results, but the harsh ischemic environment of the post-stroke brain reduces their therapeutic potential. Previously, we developed a conductive polymer scaffold system that enabled stem cell delivery with simultaneous electrical modulation of the cells and surrounding neural environment. This wired polymer scaffold proved efficacious in optimizing ideal conditions for stem cell mediated motor improvements in a rodent model of stroke. To further enable preclinical studies and enhance translational potential, we identified a method to improve this system by eliminating its dependence upon a tethered power source. We have herein developed a wirelessly powered, electrically conductive polymer system that eases therapeutic application and enables full mobility. As a proof of concept, we demonstrate that the wirelessly powered scaffold is able to stimulate neural stem cells in vitro, as well as in vivo in a rodent model of stroke. This system modulates the stroke microenvironment and increases the production of endogenous stem cells. In summation, this novel, wirelessly powered conductive scaffold can serve as a mobile platform for a wide variety of therapeutics involving electrical stimulation.

Speckle tracking echocardiography-derived left ventricular global longitudinal strain in ex-thalassaemics.

AIMS: Long term survivors of haematopoietic stem cell transplantation (HSCT) for ß-thalassemia major are designated "ex-thalassaemics". Whether ex-thalassaemics continue to harbour residual myocardial dysfunction and thereby stand the risk of heart failure-related morbidity and mortality is unknown. The aim of this study was to assess the prevalence and predictors of subclinical left ventricular (LV) dysfunction in an apparently normal ex-thalassaemic population. METHODS: We conducted a single centre cross-sectional study among 62 ex-thalassaemic patients, who had undergone HSCT for ß-thalassaemia major at our centre. The primary outcome variable was LV systolic dysfunction, as assessed by 1) LV global longitudinal strain (GLS) derived by 2D speckle tracking echocardiography and 2) LV ejection fraction (EF) derived by 2D Simpsons Biplane method. RESULTS: Among the 62 patients included in the study, 7 [11.3%] were found to have LV systolic dysfunction, all of which were subclinical. Of these, 4 [6.5%] had abnormal GLS and LVEF, 2 [3.2%] had abnormal GLS with normal LVEF, and 1 [1.6%] had abnormal LVEF with low normal mean GLS. There were no statistically significant predictors of LV dysfunction in this cohort. CONCLUSION: There was a high prevalence of subclinical myocardial dysfunction in the ex-thalassaemic population reiterating the need for close follow up of these patients. 2D Speckle tracking echocardiography-derived LV global longitudinal strain is an effective tool in detecting subclinical myocardial dysfunction in this cohort.

Diversity in interventional radiology: Survey of medical student interest with focus on women and members of underrepresented in medicine racial and ethnic groups.

PURPOSE: To assess: 1) the percentage of female and underrepresented in medicine (URiM) medical students interested in interventional radiology (IR), and 2) the motivations for and deterrents from IR for female and URiM students. METHODS: The study was IRB exempt. Data from a 19-item survey sent to 5 US medical schools were collected from 10/2018-01/2019 using REDCap and analyzed with SAS GLIMMIX. RESULTS: 16% (56/346) of women and 27% (69/258) of men strongly considered IR. 21% (19/89) of URiM versus 21% (105/508) of non-URiM students, p = .88, seriously considered IR. On a 0-to-4 scale (0 = not a motivator, 4 = strong motivator), women rated "Female mentorship" "2.5" versus males' "0.4", p < .0001, independent of IR interest URiM students uninterested in IR rated "Lack of ethnic diversity in training""2.3" versus "1.2" for IR-interested URiM, p < .01. 18% (9/50) of IR-interested women reported adequate gender-specific mentorship in IR in medical school. Of IR-interested URiM students 5% (1/19) reported adequate ethnicity/race-specific mentorship. CONCLUSION: Fewer female medical students considered IR compared to males. Female mentorship was a significant motivator for women. Similar numbers of URiM and non-URiM students consider IR. Few women and URiM students report adequate gender/ethnicity/race-specific mentorship. For students not interested in IR, lack of ethnic diversity in training was a significant deterrent. Increasing numbers and visibility of female and URiM interventional radiologists in mentoring and clinical practice may improve recruitment of medical students from these underrepresented groups.

Submandibular gland abscess in a kidney transplant recipient: a diagnostic and therapeutic enigma.

A renal allograft transplant recipient presented to our emergency department with pus discharging right-sided cheek swelling. She had the same presentation 1 year after kidney transplant surgery. The abscess was incised and drained, and a sample was sent for culture and sensitivity. The culture initially grew Aspergillus fumigatus for which she was started on itraconazole. While the patient was on antifungal therapy, immunohistochemistry revealed diffuse large B-cell lymphoma to be the primary disease, and rituximab chemotherapy was initiated. The patient is being followed up and is currently in remission.We are reporting this rare case to raise awareness so that clinicians consider the possibility of post-transplant lymphoproliferative disorder when they see a similar presentation.

Clinical Problem Solving: A 38-year-Old Woman With Systemic Lupus Erythematosus Presenting With Headache, Nausea, and Vomiting.

A 38-year-old woman with migraine headaches and systemic lupus erythematosus with recent cessation of her immunosuppressive therapy presents with prolonged headache and hypertensive emergency. Her examination is notable for a peripheral right facial palsy and stable malar rash. There are no signs of systemic infection nor systemic symptoms of a lupus flare. Initial CT head reveals bilateral hypodensities in the basal ganglia. Within 8 hours of presentation, she develops right hemiplegia and becomes encephalopathic. MRI shows multifocal acute infarcts (most notably in the left basal ganglia), enhancement of the right facial nerve, and multifocal vessel wall enhancement in the anterior and posterior circulation. We discuss the differential diagnosis, comprehensive workup, and subsequent treatment decisions in the management of this immunocompromised patient with encephalopathy, headache, and rapidly progressing focal neurologic deficits.

Bridging the Divide: Unintended Consequences of the Shift to Home-Based Telemedicine.

OBJECTIVE: To evaluate the impact on health care access of the change in telemedicine delivery from a clinic-based model, in which patients connect with their healthcare provider from local telemedicine clinics, to a home-based model, in which patients independently connect from their homes. STUDY DESIGN: In this retrospective analysis, we compared relative uptake in telemedicine services in Period 1 (01/01/2019 to 03/15/2020, prepandemic, clinic-based model) vs Period 2 (03/16/2020 to 06/30/2022, home-based model) within a tertiary pediatric hospital system. Using multivariable logistic regression, we investigated the influence of telemedicine delivery model on patient sociodemographic characteristics of completed telemedicine visits. RESULTS: We analyzed 400 539 patients with 1 406 961 completed outpatient encounters (52% White, 35% Black), of which 62 920 (4.5%) were telemedicine. In the clinic-based model (Period 1), underserved populations had greater likelihoods of accessing telemedicine: Hispanic ethnicity (OR = 1.41, P = .028) vs reference group non-Hispanic, Medicaid (OR = 2.62, P < .001) vs private insurance, and low-income neighborhood (OR = 3.40, P < .001) vs medium-income. In aggregate, telemedicine utilization rapidly increased from Period 1 (1.5 encounters/day) to Period 2 (107.9 encounters/day). However, underserved populations saw less relative increase (Medicaid [OR = 0.28, P < .001], Hispanic [OR = 0.53, P < .001], low-income [OR = 0.23, P < .001]). CONCLUSIONS: We observe that the clinic-based model offers more equitable access, while the home-based model offers more absolute access, suggesting that a hybrid model that offers both home-based and clinic-based services may result in more absolute and equitable access to telemedicine.

"External Iliac Artery Injury After Total Hip Arthroplasty in an Infected Intrapelvic Hemiarthroplasty": A Case Report.

CASE: We report a patient with intrapelvic prosthetic protrusion associated with infection after hemiarthroplasty for a fracture neck of the femur. We discuss the challenges involved in the management of this complex case with recommendations to manage a vascular injury. CONCLUSION: In patients with an intrapelvic prosthesis, thorough preoperative vascular evaluation and vigilant postoperative check are required to prevent a vascular injury. In a suspected vessel injury after primary or revision total hip arthroplasty, it is imperative to get proximal control of the vessel before re-exploration. A combined arterial Doppler and computerized tomography angiogram is more reliable in picking up arterial impingement by acetabular screws.

Nutritional Recovery of Children With HIV and Severe Acute Malnutrition Attending an Outpatient Therapeutic Care Program.

BACKGROUND: Despite significant morbidity and mortality from HIV and severe acute malnutrition (SAM) among children in sub-Saharan Africa, research is lacking in these children. We describe the proportion of children living with HIV with SAM achieving recovery, the factors associated with recovery, and time to recovery in an outpatient therapeutic care program. SETTING AND METHODS: This is a retrospective observational study of children with SAM and HIV on antiretroviral therapy (6 months-15 years), enrolled in outpatient therapeutic care from 2015 to 2017 at a pediatric HIV clinic in Kampala, Uganda. SAM diagnosis and recovery by 120 days after enrollment were determined per World Health Organization guidelines. Cox-proportional hazards models were used to determine predictors of recovery. RESULTS: Data from 166 patients were analyzed (mean age 5.4 years, SD 4.7). Outcomes showed 36.1% recovered, 15.6% were lost to follow-up, 2.4% died, and 45.8% failed. Average time to recovery was 59.9 days (SD 27.8). Patients 5 years or older were less likely to recover (crude hazard ratio [CHR] = 0.33, 95% CI: 0.18 to 0.58). In multivariate analysis, febrile patients were less likely to recover (adjusted hazard ratio = 0.53, 95% CI: 0.12 to 0.65). Patients with CD4 count of 200 or less at enrollment were less likely to recover (CHR = 0.46, 95% CI: 0.22 to 0.96). CONCLUSIONS: Despite treatment with antiretroviral therapy for children living with HIV, we observed poor rates of recovery from SAM, below the international target of >75%. Moreover, patients 5 years and older, fever, or low CD4 at diagnosis of SAM may require more intense therapy or closer monitoring than their counterparts.

Randomized, Double-Blind, Active Comparator Pharmacodynamic Study of Platelet Inhibition with Crushed and Integral Formulations of Clopidogrel and Ticagrelor in Acute Coronary Syndrome.

BACKGROUND: Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. OBJECTIVES: We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). METHODS: Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8 h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12 reaction units (PRUs) 1 h after the medication loading dose was also determined. RESULTS: The PRU and percentage inhibition median (interquartile range) at 1 h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p = 0.990, p = 0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p < 0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p = 0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. CONCLUSIONS: The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.