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Objective: To understand the feelings of pediatrics residents early in the COVID-19 pandemic and to offer insights still relevant today., Methods: We performed a thematic analysis exploring resident feelings early in the pandemic using free-text responses on a national survey distributed between May and June 2020. We analyzed responses from the following multi-part free text question embedded in the larger survey, "Which of the following feelings have you experienced in your role as a pediatric resident during the COVID-19 pandemic" with response prompts including relief, guilt, pride, sadness, worry, fear, and other., Results: While many feelings that respondents shared were common to society at large, some were specific to their intersecting roles as health care workers, pediatricians, and trainees. Some issues uncovered have continued relevance today including varied interactions with program and institutional leadership, training away from established support networks and during an important life stage, and societal concerns., Conclusions: This study uncovered vulnerabilities inherent to being a trainee such as limited control over one's own schedule or institutional policies and training away from established supports. Their feelings shine light on the moral distress experienced in residency and the role program and institutional leadership can play in the experiences of residents., Competing Interests: Declaration of Competing Interest Dr. Schumacher is funded by the American Board of Pediatrics Foundation and serves as the chair of the American Board of Pediatrics Competency-Based Medical Education Committee for which he receives honoraria and travel reimbursement. Dr. Schwartz serves as Director of APPD Longitudinal Educational Assessment Research Network through a contract from APPD to his institution. Dr. Winn is funded by the American Board of Pediatrics Foundation and serves on the American Board of Pediatrics Competency-Based Medical Education Committee for which she receives honoraria and travel reimbursement. In addition, Dr. Winn receives compensation for her role as a medical advisor for Goode Health. Dr. Unaka is faculty for the Institute for Healthcare Improvement focused on supporting a collaborative sponsored by Department of Healthcare Services (DHCS). All other authors report no conflicts of interest or disclosures., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurogenetic disorder caused by duplications of the maternal copy of this region. In addition to hypotonia, motor deficits, and language impairments, patients with Dup15q commonly meet the criteria for autism spectrum disorder and have a high prevalence of seizures. It is known from mouse models that synaptic impairments are a strong component of Dup15q pathophysiology; however, cellular phenotypes that relate to seizures are less clear. The development of patient-derived induced pluripotent stem cells provides a unique opportunity to study human neurons with the exact genetic disruptions that cause Dup15q., Methods: Here, we explored electrophysiological phenotypes in induced pluripotent stem cell-derived neurons from 4 patients with Dup15q compared with 6 unaffected control subjects, 1 patient with a 15q11-q13 paternal duplication, and 3 patients with Angelman syndrome., Results: We identified several properties of Dup15q neurons that could contribute to neuronal hyperexcitability and seizure susceptibility. Compared with control neurons, Dup15q neurons had increased excitatory synaptic event frequency and amplitude, increased density of dendritic protrusions, increased action potential firing, and decreased inhibitory synaptic transmission. Dup15q neurons also showed impairments in activity-dependent synaptic plasticity and homeostatic synaptic scaling. Finally, Dup15q neurons showed an increased frequency of spontaneous action potential firing compared with control neurons, in part due to disruption of KCNQ2 potassium channels., Conclusions: Together, these data point to multiple electrophysiological mechanisms of hyperexcitability that may provide new targets for the treatment of seizures and other phenotypes associated with Dup15q., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

We report two cases of embryonal rhabdomyosarcoma (ERMS) of the cervix in teenagers presenting to Komfo Anokye Teaching Hospital in Kumasi, Ghana within one month of each other. Between October and November 2019, two patients presented with ERMS of the cervix. They both underwent fertility-sparing surgery followed by chemotherapy with vincristine, actinomycin-D, and cyclophosphamide. Preoperative workup for the two patients was minimal due to limited availability and high cost of imaging in a low-resource setting. Both patients were discussed at a multidisciplinary tumor board meeting to guide best management practices. Both patients had local surgical resection with histological confirmation of ERMS and negative margins, followed by six cycles of vincristine, actinomycin-D, and cyclophosphamide. Neither of the patients had perioperative complications or received radiation therapy. At the time of publication, both patients are currently alive and without evidence of recurrence. Fertility-sparing surgery followed by chemotherapy for patients with ERMS of the cervix is accessible in low-income countries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

It has long been suggested that NO may inhibit an early stage in viral replication. Furthermore, in vitro tests have shown that NO inhibits the replication cycle of severe acute respiratory syndrome coronavirus. Despite smoking being listed as a risk factor to contract Covid-19, only a low proportion of the smokers suffered from SARS-corona infection in China 2003, and from Covid-19 in China, Europe and the US. We hypothesize, that the intermittent bursts of high NO concentration in cigarette smoke may be a mechanism in protecting against the virus. Mainstream smoke from cigarettes contains NO at peak concentrations of between about 250 ppm and 1350 ppm in each puff as compared to medicinal use of no more than 80 to a maximum of 160 ppm. The diffusion of NO through the cell wall to reach the virus should be significantly more effective at the very high NO concentration in the smoke, according to classic laws of physics. The only oxide of nitrogen in the mainstream smoke is NO, and the NO 2 concentration that is inhaled is very low or undetectable, and methemoglobin levels are lower in smokers than non-smokers, reasonably explained by the breaths of air in between the puffs that wash out the NO. Specialized iNO machines can now be developed to provide the drug intermittently in short bursts at high concentration dose, which would then provide both a preventative drug for those at high risk, as well as an effective treatment, without the health hazards associated with smoking., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Cardiac tamponade is a severe complication of cardiac resynchronization therapy (CRT) implantations. We provide a contemporary large-scale study evaluating the incident trends, predictors and impact of cardiac tamponade in patients undergoing CRT., Method: Data were obtained from the Nationwide Inpatient Sample (NIS) of 2007 through 2014. Trends in the annual rates of tamponades in CRT implantation were assessed using negative binomial regressions. Hierarchical mixed-effects logistic regression models were built to determine the independent predictors of tamponade in CRT implantation and 1:1 propensity-matched analysis performed to examine the impact of tamponade on outcomes., Result: An estimated 310,704 CRT implantations were performed in the United States between 2007 and 2014, out of which 536 patients (0.17%) developed procedure-related cardiac tamponade. A significant increasing trend in the tamponade incidence was observed over the 8-year study period [1.65 per 10,000 CRT implantation in 2007 to 38.16 in 2014 (p < 0.001)]. After multivariable adjustment, female sex and coagulation disorder were found to be independently associated with higher odds of tamponade. Conversely, prior history of CABG procedure was associated with lower odds of tamponade. CRT complicated with tamponade had significantly increased in-hospital mortality, bleeding requiring transfusion, prolonged hospital stay and increased cost., Conclusion: We found an increasing trend in the incidence of post CRT tamponade among hospitalized patients between 2007 and 2014. Female gender and coagulation disorder were associated with the development of tamponade among recipients of CRT. Risk stratification of patients who are undergoing CRT is crucial to improving outcome in CRT implantation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: New treatment options are needed for second-line therapy in patients with NSCLC., Patients and Methods: This was a phase Ib/II study in patients with nonsquamous NSCLC in whom 1 previous platinum-based chemotherapy regimen had failed. Fifteen patients were enrolled in a dose escalation of eribulin mesylate in combination with pemetrexed (E+P). In phase II (n = 80), E+P at the maximum tolerated dose was compared with P., Results: In phase Ib, the maximum tolerated dose of E+P was defined as eribulin 0.9 mg/m(2) with pemetrexed (500 mg/m(2)) each on day 1 of a 21-day cycle. In phase II, adverse events were comparable between groups. PFS and OS were similar between treatment groups. Median PFS was 21.4 weeks for E+P (n = 26; 95% confidence interval [CI], 12.7-39.6) and 23.4 weeks for P (n = 29; 95% CI, 17.1-29.9), with a hazard ratio of 1.0 (95% CI, 0.6-1.7)., Conclusion: During phase Ib, E+P was tolerated only at a markedly lower dosing intensity relative to the eribulin monotherapy regimen approved for breast cancer and used in phase II studies of NSCLC. At the selected phase II dosing regimen, E+P was generally safe and well tolerated but provided no therapeutic advantage for the second-line treatment of locally advanced or metastatic nonsquamous NSCLC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Streptococcus agalactiae (GBS) is an important cause of chorioamnionitis. This study characterizes GBS colonization and stimulation of antimicrobial responses in human extraplacental membranes using an ex vivo transwell two-compartment system of full-thickness membranes and live GBS., Study Design: Human extraplacental membranes were affixed to transwell frames (without synthetic membranes). Live GBS was added to the decidual side of membranes in transwell cultures, and cocultures were incubated for 4, 8 and 24 h. GBS recovery from homogenized membranes and culture medium was determined by enumerating colony forming units (CFU) on blood agar. Antimicrobial peptide expression was identified using immunohistochemistry and ELISA. GBS killing by HBDs was assessed in vitro by incubating GBS with different human beta defensins (HBDs) for 3 h, then enumerating CFU., Results: GBS recovery from membranes markedly decreased over time (P < 0.05). The antimicrobial peptides HBD-1, HBD-2, HBD-3, and lactoferrin were expressed in both GBS-exposed and non-exposed tissues. Notably, a pattern of localized increased HBD-2 in the amnion of GBS-infected tissue was observed. Moreover, GBS-treated membranes released increased amounts of HBD-2 into the amniotic and decidual compartments of the transwell cultures after 24 h (P < 0.05). In bacterial cultures, HBD-2 decreased GBS viability in a concentration-dependent manner (P < 0.05)., Conclusion: Innate immune responses in ex vivo human extraplacental membranes suppress GBS growth. HBD-2 was implicated in this GBS suppression with evidence of signal transduction across the tissue. Antimicrobial peptides may be important for innate immune defense against intrauterine GBS infections during pregnancy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this study was to evaluate the efficacy of a totally subcutaneous, anteroposterior defibrillation shock pathway using a long time-constant shock waveform that emulates a proposed device having approximately twice the capacitance and thus twice the available energy of traditional transvenous devices., Background: A non-transvenous defibrillation system potentially offers advantages over a transvenous system including simplification of the implant procedure and reduction of the impact of device complications by eliminating the need to place a lead within the heart. Previous non-transvenous defibrillation efficacy studies have been reported using anterolateral and anterior-anterior shock vectors. An external anteroposterior shock vector has demonstrated superior efficacy compared to anterolateral shock vectors but a prospective study on an anteroposterior shock vector with implanted electrodes has not been previously reported., Methods: The non-transvenous shock vector consisted of an anterior low pectorally-placed active can emulator electrode and a posterior subcutaneous coil electrode. The shock waveform was a biphasic with 50% tilt per phase and a time constant of decay of 12 ms. Defibrillation efficacy was characterized using a step-down defibrillation threshold protocol (35 J, 25 J, 15 J)., Results: A total of 33 patients with standard ICD indications were enrolled in the study with 32 fully completing the protocol. The patient population was 69% male, with a mean age of 59 +/- 12 years. Mean ejection fraction was 27 +/- 12%. Of the 32 patients tested, 26 patients (81%) were successfully defibrillated at 35 J or less, 18 patients were defibrillated at 25 J or less and 9 patients were successfully defibrillated at 15 J., Conclusions: Defibrillation using a long time-constant waveform delivered through an anteroposterior non-transvenous pathway including a pectoral active can emulator electrode and a posterior subcutaneous coil electrode is feasible with over 80% of patients defibrillated successfully using 35 J or less.

Because of their safety and the fact that they are not perceived as "medicine," food-derived products are highly interesting for development as chemopreventive agents that may find widespread, long-term use in populations at normal risk. Numerous diet-derived agents are included among the >40 promising agents and agent combinations that are being evaluated clinically as chemopreventive agents for major cancer targets including breast, prostate, colon and lung. Examples include green and black tea polyphenols, soy isoflavones, Bowman-Birk soy protease inhibitor, curcumin, phenethyl isothiocyanate, sulforaphane, lycopene, indole-3-carbinol, perillyl alcohol, vitamin D, vitamin E, selenium and calcium. Many food-derived agents are extracts, containing multiple compounds or classes of compounds. For developing such agents, the National Cancer Institute (NCI) has advocated codevelopment of a single or a few putative active compounds that are contained in the food-derived agent. The active compounds provide mechanistic and pharmacologic data that may be used to characterize the chemopreventive potential of the extract, and these compounds may find use as chemopreventives in higher risk subjects (patients with precancers or previous cancers). Other critical aspects to developing the food-derived products are careful analysis and definition of the extract to ensure reproducibility (e.g., growth conditions, chromatographic characteristics or composition), and basic science studies to confirm epidemiologic findings associating the food product with cancer prevention.

Early randomized Phase II cancer chemoprevention trials which assess short-term biological activity are critical to the decision process to advance to late Phase II/Phase III trials. We have adapted published Bayesian interim analysis methods (Spiegelhalter et al., J. R. Statist. Soc A, 1994; 157: 357-416) which give greater flexibility and simplicity of inference to the monitoring of randomized controlled Phase II trials using intermediate endpoints. The Bayesian stopping rule is designed to stop the trial more quickly when the evidence suggests ineffectiveness rather than when it suggests biological activity, thus allowing resources to be concentrated on those agents that show the most promise in this early stage of testing. We investigate frequentist performance characteristics of the proposed method through simulation of randomized placebo controlled trials with a growth factor intermediate end-point using mean and variance values derived from the literature. Simulation results show expected error rates and trial size similar to other commonly used group sequential methods for this setting. These results suggest that the Bayesian approach to interim analysis is well suited for monitoring small randomized controlled Phase II chemoprevention trials for early detection of either inactive or promising agents.

The authors show here that progesterone suppresses apoptosis, and its antagonist RU 486 induces it in rabbit uterine epithelium, as assessed by morphologic and biochemical studies. The authors' studies demonstrate that internucleosomal DNA fragments are identifiable as early as 24 hours after ovariectomy of pseudopregnant rabbits, and become undetectable 6 days after ovariectomy. Maximal levels of DNA fragmentation (about 74% of total isolated DNA) were observed 36 hours after ovariectomy. The number of apoptotic cells appeared to increase parallel to the increased DNA breakdown, and accounted for approximately 26% of the uterine epithelial cells at 48 hours after ovariectomy. Levels of progesterone in serum dropped precipitously 6 hours after ovariectomy and remained very low for several days. Administration of progesterone, more than any other steroid hormone, to pseudopregnant ovariectomized rabbits, prevented the increase in apoptotic cell death. By contrast, administration of the anti-progestin RU 486 to pseudopregnant rabbits triggered apoptosis, which attained levels similar to those observed in ovariectomized animals. The authors' findings establish that uterine epithelium apoptosis occurs in a time-dependent fashion and provides strong evidence that the actions of progesterone in that tissue are not only to stimulate cell proliferation and differentiation, but also to suppress apoptosis.

Thirty-nine eyes from 31 patients with retinal detachment due to cytomegalovirus (CMV) retinitis were treated by either laser photocoagulation (22 eyes), scleral buckle (9 eyes), pars plana vitrectomy (5 eyes), or no therapy (3 eyes). The success rates for photocoagulation (77.2%), scleral buckle (77.7%), and vitrectomy (with gas or oil, 80%) were similar. The median survival time was 95 days (range, of 7 to 280 days). The extent of detachment, the presence of active disease in either the periphery or the posterior pole, and overall health served to determine what type of therapy was best suited for each patient. Although silicone oil appears to be best for patients with a total retinal detachment and active disease, this small series suggests that conservative modes of therapy such as laser photocoagulation and scleral buckles can be used successfully to treat these patients if there is an absence of active retinitis.

To investigate the potential role of magnetic resonance imaging and duplex scanning in the diagnosis of catheter-induced subclavian vein thrombosis, we correlated the results of 43 arm phlebograms with duplex scans; 28 of these phlebograms were also correlated with magnetic resonance imaging scans of the thoracic veins. Eighteen of the 43 phlebograms were normal, and all had normal magnetic resonance imaging and duplex studies. Eleven subclavian veins were totally occluded on phlebography; all had duplex scans, and five were also scanned with magnetic resonance imaging. Duplex scans detected 6 of 11 occlusions, whereas magnetic resonance imaging detected 4 of the 5 occlusions scanned. The five occlusions that were not detected by either magnetic resonance imaging or duplex scans were short segmental occlusions of the medial one third of the left subclavian vein. Of 14 nonocclusive thrombi seen on phlebography, duplex scans correctly identified 8. Magnetic resonance imaging was done on eight nonocclusive thrombi but identified only two. All abnormal findings on duplex scanning and magnetic resonance imaging were confirmed by phlebography. Short occlusions of the proximal portion of the left subclavian vein were often undetected by duplex scanning but occasionally seen with magnetic resonance imaging. Neither modality was sensitive to the presence of nonocclusive mural thrombi. Magnetic resonance imaging is highly reliable in ruling out the presence of a thrombotic process in the subclavian vein, but it may on occasion fail to detect the presence of subclavian thrombi. For this reason, in cases with suspected subclavian vein thrombosis magnetic resonance imaging cannot be used as the only diagnostic modality.(ABSTRACT TRUNCATED AT 250 WORDS)

A method is described for preparing derivatives of alkali-stable polysaccharides for coupling to immunogen carriers or to sheep red blood cells (SRBC) for use in hemagglutination (HA) and plaque-forming cell (PFC) assays. Inulin, a beta (2 leads to 1)-linked polyfructosan was partially derivatized with carboxyl, aminoethyl or (p-aminophenyl)butyryl groups; the latter derivative was coupled to SRBC following diazotization. Optimal conditions for the sensitization of SRBC with inulin were given. The immunological reactivity of the inulin molecule was unaffected by the derivatization reactions, and high, reproducible anti-inulin HA titers for inulin-binding myeloma proteins were found using these specifically sensitized SRBC. The sensitized SRBC were stable for assays for over 2 weeks. Problems with spontaneous agglutination or distortion of sensitized SRBC, normally seen in other procedures, e.g., methods using stearoyl-inulin, were not encountered.