Abstract Femoral cannulation in pediatric patients requiring extracorporeal membrane oxygenation (ECMO) is commonly associated with distal limb ischemia. Authors have previously reported successful ...lower limb perfusion using various open techniques to cannulate a distal lower extremity artery at the time of initial ECMO cannulation. These procedures include open femoral artery antegrade cannulation and distal posterior tibial artery retrograde cannulation in older children and adults. Such approaches require ample vessel diameters to accommodate an arteriotomy and catheter insertion and, therefore, are of limited use in smaller children. We hypothesized that after femoral artery cannulation for ECMO, a percutaneous technique of distal limb perfusion might offer unique advantages when treating lower extremity ischemia in small pediatric patients. We report a technique for percutaneous antegrade cannulation in a 4-year-old patient shortly after her primary cannulation for venoarterial ECMO via the femoral artery.
Neonatal deaths account for 40% of global under-five mortality and are ever more important if we are to achieve the Millennium Development Goal 4 (MDG 4) on child survival. We applied a results ...framework to evaluate global and national changes for neonatal mortality rates (NMR), healthy behaviours, intervention coverage, health system change, and inputs including funding, while considering contextual changes. The average annual rate of reduction of NMR globally accelerated between 2000 and 2010 (2.1% per year) compared with the 1990s, but was slower than the reduction in mortality of children aged 1-59 months (2.9% per year) and maternal mortality (4.2% per year). Regional variation of NMR change ranged from 3.0% per year in developed countries to 1.5% per year in sub-Saharan Africa. Some countries have made remarkable progress despite major challenges. Our statistical analysis identifies inter-country predictors of NMR reduction including high baseline NMR, and changes in income or fertility. Changes in intervention or package coverage did not appear to be important predictors in any region, but coverage data are lacking for several neonatal-specific interventions. Mortality due to neonatal infection deaths, notably tetanus, decreased, and deaths from complications of preterm birth are increasingly important. Official development assistance for maternal, newborn and child health doubled from 2003 to 2008, yet by 2008 only 6% of this aid mentioned newborns, and a mere 0.1% (US$4.56m) exclusively targeted newborn care. The amount of newborn survival data and the evidence based increased, as did recognition in donor funding. Over this decade, NMR reduction seems more related to change in context, such as socio-economic factors, than to increasing intervention coverage. High impact cost-effective interventions hold great potential to save newborn lives especially in the highest burden countries. Accelerating progress requires data-driven investments and addressing context-specific implementation realities. Adapted from the source document.
India's population exhibits diverse dietary habits and chronic disease patterns. Nutritional epidemiologic studies in India are primarily of cross-sectional or case-control design and subject to ...biases, including differential recall of past diet. The aim of this feasibility study was to evaluate whether a diet-focused cohort study of cancer could be established in India, providing insight into potentially unique diet and lifestyle exposures.
Field staff contacted 7,064 households within three regions of India (New Delhi, Mumbai, and Trivandrum) and found 4,671 eligible adults aged 35-69 years. Participants completed interviewer-administered questionnaires (demographic, diet history, physical activity, medical/reproductive history, tobacco/alcohol use, and occupational history), and staff collected biological samples (blood, urine, and toenail clippings), anthropometric measurements (weight, standing and sitting height; waist, hip, and thigh circumference; triceps, sub-scapula and supra-patella skin fold), and blood pressure measurements.
Eighty-eight percent of eligible subjects completed all questionnaires and 67% provided biological samples. Unique protein sources by region were fish in Trivandrum, dairy in New Delhi, and pulses (legumes) in Mumbai. Consumption of meat, alcohol, fast food, and soft drinks was scarce in all three regions. A large percentage of the participants were centrally obese and had elevated blood glucose levels. New Delhi participants were also the least physically active and had elevated lipids levels, suggesting a high prevalence of metabolic syndrome.
A high percentage of participants complied with study procedures including biological sample collection. Epidemiologic expertise and sufficient infrastructure exists at these three sites in India to successfully carry out a modest sized population-based study; however, we identified some potential problems in conducting a cohort study, such as limited number of facilities to handle biological samples.
The species specificity of a small molecule antagonist for the human CCR1 chemokine receptor, 2-2-diphenyl-5-(4-chlorophenyl)piperidin-1-yl)valeronitrile (CCR1 antagonist 1), has been examined using ...cloned CCR1 receptors from various species. The compound was able to bind to rabbit, marmoset, and human CCR1, and was able to block the functional activation of these receptors. However, it failed to significantly displace radiolabeled macrophage inflammatory protein-1α (MIP-1α) binding to mouse CCR1 at concentrations up to 10 μM. These data suggested that the antagonist binding site is well-conserved in rabbit, marmoset and human CCR1, but not in mouse CCR1. The functional selectivity and mechanism of action for CCR1 antagonist 1 were further characterized. CCR1 antagonist 1 blocked the increase in intracellular Ca
2+ stimulated by CCR1 agonists, but had no effect on
N-formyl-Met–Leu–Phe (FMLP), monocyte chemotactic protein-1 (MCP-1) and stromal-derived factor 1α (SDF1α)-induced Ca
2+ mobilization, demonstrating functional selectivity for CCR1. Since CCR1 antagonist 1 is a functional antagonist of marmoset and rabbit CCR1 receptors, it should be possible to test its efficacy in animal models of disease.
The aim of this study was to examine the potential of using a lux-tagged Cronobacter sakazakii strain to monitor growth of the bacterium in various liquids. C. sakazakii was transformed with plasmid ...p16S lux, and integration of the plasmid at the desired site on the chromosome was confirmed by PCR. The growth of the lux-tagged strain was similar to that of the non-lux-tagged strain, and the integrated plasmid was stable when cells were cultured in the absence of antibiotic. Growth of the lux-tagged strain was monitored in real time in Luria-Bertani broth, skim milk, and infant milk formula by using both the Luminoskan luminometer and the Xenogen IVIS imager. Bioluminescence could be detected when the lux-tagged strain was cocultured with other bacteria. The effect of monocaprylin and nisin on the growth of C. sakazakii in milk was monitored by measuring bioluminescence. In conclusion, growth of a lux-tagged C. sakazakii can be monitored in real time in both clear and opaque liquids by measuring bioluminescence. lux-tagged C. sakazakii strains could be potentially used in high-throughput assays to monitor the effects of various infant milk formula compositions on growth of the bacterium.
Background: An urgent need exists to rapidly screen potential therapeutics for severe COVID-19 or other emerging pathogens associated with high morbidity and mortality. Methods: Using an adaptive ...platform design created to rapidly evaluate investigational agents, hospitalised patients with severe COVID-19 requiring ≥6 L/min oxygen were randomised to either a backbone regimen of dexamethasone and remdesivir alone (controls) or backbone plus one open-label investigational agent. Patients were enrolled to the arms described between July 30, 2020 and June 11, 2021 in 20 medical centres in the United States. The platform contained up to four potentially available investigational agents and controls available for randomisation during a single time-period. The two primary endpoints were time-to-recovery (<6 L/min oxygen for two consecutive days) and mortality. Data were evaluated biweekly in comparison to pre-specified criteria for graduation (i.e., likely efficacy), futility, and safety, with an adaptive sample size of 40–125 individuals per agent and a Bayesian analytical approach. Criteria were designed to achieve rapid screening of agents and to identify large benefit signals. Concurrently enrolled controls were used for all analyses. https://clinicaltrials.gov/ct2/show/NCT04488081. Findings: The first 7 agents evaluated were cenicriviroc (CCR2/5 antagonist; n = 92), icatibant (bradykinin antagonist; n = 96), apremilast (PDE4 inhibitor; n = 67), celecoxib/famotidine (COX2/histamine blockade; n = 30), IC14 (anti-CD14; n = 67), dornase alfa (inhaled DNase; n = 39) and razuprotafib (Tie2 agonist; n = 22). Razuprotafib was dropped from the trial due to feasibility issues. In the modified intention-to-treat analyses, no agent met pre-specified efficacy/graduation endpoints with posterior probabilities for the hazard ratios HRs for recovery ≤1.5 between 0.99 and 1.00. The data monitoring committee stopped Celecoxib/Famotidine for potential harm (median posterior HR for recovery 0.5, 95% credible interval CrI 0.28–0.90; median posterior HR for death 1.67, 95% CrI 0.79–3.58). Interpretation: None of the first 7 agents to enter the trial met the prespecified criteria for a large efficacy signal. Celecoxib/Famotidine was stopped early for potential harm. Adaptive platform trials may provide a useful approach to rapidly screen multiple agents during a pandemic. Funding: Quantum Leap Healthcare Collaborative is the trial sponsor. Funding for this trial has come from: the COVID R&D Consortium, Allergan, Amgen Inc., Takeda Pharmaceutical Company, Implicit Bioscience, Johnson & Johnson, Pfizer Inc., Roche/Genentech, Apotex Inc., FAST Grant from Emergent Venture George Mason University, The DoD Defense Threat Reduction Agency (DTRA), The Department of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA), and The Grove Foundation. Effort sponsored by the U.S. Government under Other Transaction number W15QKN-16-9-1002 between the MCDC, and the Government.
Abstract Background/Objective We examined seasonality and winter seasonal affective disorder (SAD) in the Old Order Amish of Lancaster County, Pennsylvania, a unique population that prohibits use of ...network electric light in their homes. Methods We estimated SAD using the seasonal pattern assessment questionnaire (SPAQ) in 1306 Amish adults and compared the frequencies of SAD and total SAD (i.e., presence of either SAD or subsyndromal-SAD) between men and women, young and old, and awareness of (ever vs. never heard about) SAD. Heritability of global seasonality score (GSS) was estimated using the maximum likelihood method, including a household effect to capture shared environmental effects. Results The mean (±SD) GSS was 4.36 (±3.38). Prevalence was 0.84% (95% CI: 0.36–1.58) for SAD and 2.59% (95% CI: 1.69–3.73) for total SAD. Heritability of GSS was 0.14±0.06 (SE) ( p =0.002) after adjusting for age, gender, and household effects. Limitations Limitations include likely overestimation of the rates of SAD by SPAQ, possible selection bias and recall bias, and limited generalizability of the study. Conclusions In the Amish, GSS and SAD prevalence were lower than observed in earlier SPAQ-based studies in other predominantly Caucasian populations. Low heritability of SAD suggests dominant environmental effects. The effects of awareness, age and gender on SAD risk were similar as in previous studies. Identifying factors of resilience to SAD in the face of seasonal changes in the Amish could suggest novel preventative and therapeutic approaches to reduce the impact of SAD in the general population.
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