Introduction: Neonatal mortality rates in resource-limited hospitals of Sub-Saharan Africa (SSA) remain disproportionately high and are likely underestimated due to misclassification of extremely preterm births as "stillbirths" or "abortions", incomplete death registries, fear of repercussions from hospital and governmental authorities, unrecorded village deaths, and cultural beliefs surrounding the viability of premature newborns. While neonatology partnerships exist between high income countries and hospitals in SSA, efforts have largely been directed toward improving newborn survival through neonatal resuscitation training and provision of equipment to nascent neonatal intensive care units (NICUs). These measures are incomplete and fail to address the challenges which NICUs routinely face in low-resource settings.
View Article and Find Full Text PDFMany marketed pharmaceuticals reach extremely high tissue concentrations due to accumulation in lysosomes (lysosomotropism). Quantitative prediction of intracellular concentrations of accumulating drugs is challenging, especially for macrocyclic compounds that mainly do not fit in current in silico models. We tested a unique library of 47 compounds (containing 39 macrocycles) specifically designed to cover the entire range of accumulation intensities observed with pharmaceuticals so far.
View Article and Find Full Text PDFDifferences in people's beliefs can substantially impact their interpretation of a series of events. In this functional MRI study, we manipulated subjects' beliefs, leading two groups of subjects to interpret the same narrative in different ways. We found that responses in higher-order brain areas-including the default-mode network, language areas, and subsets of the mirror neuron system-tended to be similar among people who shared the same interpretation, but different from those of people with an opposing interpretation.
View Article and Find Full Text PDFA Rh-catalyzed ortho-amidation of 2-aryloxazolines offers an efficient and direct route to a range of sulfonamides. The scope of the reaction is very broad with respect to sulfonamide substrate, but the position and electronic nature of the substituents on the aryl moiety of the oxazoline lead to a surprising modulation of reactivity. The reactivity of sulfonamides in comparison to trifluoroacetamide is compared, the latter undergoing Rh-catalyzed amidation more rapidly.
View Article and Find Full Text PDFThe first Rh-catalyzed C-H amidation of pyridines is reported. The incorporation of a substituent at the C2 position both is crucial to the success of this transformation and provides considerable scope for further elaboration of the resulting products. Among these compounds, 2-chloropyridines allow access to a selection of intermediates including a versatile azaquinazoline scaffold.
View Article and Find Full Text PDFA Rh-catalyzed ortho-amidation cyclocondensation sequence gave a range of 4-aminoquinazolines in high yield. The method features a remarkably mild C(sp(2) )H activation step and can be exploited to rapidly access compounds with established biological activity.
View Article and Find Full Text PDFA Cu-promoted cyclization of 2-nitrophenyl iodoacetylenes provides a direct route to a range of 2-iodoisatogens. These compounds represent useful intermediates for the late-stage elaboration of the C-I bond to furnish isatins and a range of alternative heterocyclic products.
View Article and Find Full Text PDFThe designation of E/Z-geometrical isomers in 3-acylidene 2-oxindoles by NMR spectroscopy can lead to erroneous assignment of alkene stereochemistry because of the narrow chemical shift range observed over a large series of analogues. In contrast, UV-Vis spectroscopy offers a convenient and more reliable method for alkene stereochemical assignment. A combination of X-ray crystallography and theoretical studies shows that the observed differences in UV-Vis spectroscopic behaviour relate to the twisted conformation of the Z-isomers that provides reduced conjugation and weaker hypsochromic (blue-shifted) absorbances relative to those of the E-isomers.
View Article and Find Full Text PDFIn this article, we describe a practical drug discovery project for third-year undergraduates. No previous knowledge of medicinal chemistry is assumed. Initial lecture workshops cover the basic principles; then students, in teams, seek to improve the profile of a weakly potent, insoluble phosphatidylinositide 3-kinase delta (PI3Kδ) inhibitor (1) through compound array design, molecular modelling, screening data analysis and the synthesis of target compounds in the laboratory.
View Article and Find Full Text PDFBackground: Beginning on May 1, 1999, the Centers for Disease Control and Prevention (CDC) recommended presumptive treatment of refugees for intestinal parasites with a single dose of albendazole (600 mg), administered overseas before departure for the United States.
Methods: We conducted a retrospective cohort study involving 26,956 African and Southeast Asian refugees who were screened by means of microscopical examination of stool specimens for intestinal parasites on resettlement in Minnesota between 1993 and 2007. Adjusted prevalence ratios for intestinal nematodes, schistosoma species, giardia, and entamoeba were calculated among refugees who migrated before versus those who migrated after the CDC recommendation of presumptive predeparture albendazole treatment.
Global mobility has shown a steady rise in recent years, with increased immigration and international travel. The VFR traveler is a traveler whose primary purpose of travel is to visit friends and relatives (VFR), where there is a gradient of risk between home and destination. Children are more likely to be VFR travelers than adults.
View Article and Find Full Text PDFThis study evaluated safety and efficacy of esterified estrogens and methyltestosterone administered alone or in combination for the treatment of hot flashes in menopausal women. The 0.30-mg esterified estrogens and 0.
View Article and Find Full Text PDFBackground: Although patients considered "successful" at longer-term follow-up no longer exhibited patellar instability, those with more severe malalignment issues had other, gradually worsening symptoms such as activity-related pain, crepitation, swelling with activities, and pain with weather changes.
Hypothesis: Improvement of patellar tracking by correction of the tubercle-sulcus angle and related ligament deficiencies will result in good to excellent results, regardless of the technique employed.
Study Design: Cohort study; Level of evidence, 3.
Background: An estimated 1.4 million salmonella infections occur annually in the United States. The majority of these infections are foodborne, but many are acquired by contact with animals.
View Article and Find Full Text PDFThe pathogens that cause Lyme disease (LD), human anaplasmosis, and babesiosis can coexist in Ixodes ticks and cause human coinfections. Although the risk of human coinfection differs by geographic location, the true prevalence of coinfecting pathogens among Ixodes ticks remains largely unknown for the majority of geographic locations. The prevalence of dually infected Ixodes ticks appears highest among ticks from regions of North America and Europe where LD is endemic, with reported prevalences of < or =28%.
View Article and Find Full Text PDFObjective: To demonstrate the safety and efficacy of tibolone (1.25 and 2.5 mg) in the treatment of moderate to severe vasomotor symptoms and symptoms associated with vaginal atrophy.
View Article and Find Full Text PDFIntroduction/purpose: Characterization of hamstring mechanics during sprinting is fundamental to understanding musculotendon injury mechanisms. The objective of this study was to use muscle-actuated forward dynamic simulations to investigate musculotendon mechanics of the biceps femoris long head during the swing phase of sprinting.
Methods: We used a three-dimensional linked segment model with 26 Hill-type musculotendon actuators to simulate swing phase dynamics.
Background: While hamstring strain injuries are common during sprinting, the mechanisms of injury are not well understood. In this study, we analyzed the running kinematics of an athlete obtained at the time of an acute hamstring strain injury. The purpose was to identify the period of the gait cycle during which the hamstring was likely injured, as well as to characterize the biomechanical conditions associated with the injury.
View Article and Find Full Text PDFObjective: To compare the effect of esterified estrogens and methyltestosterone versus esterified estrogens alone on diminished sexual interest in surgically menopausal women.
Design: This randomized, double-blind study compared the effect of combined esterified estrogens (1.25 mg) and methyltestosterone (2.
Introduction/purpose: The objective of this study was to characterize hamstring muscle kinematics during sprinting, so as to provide scientific data to better understand injury mechanisms and differences in injury rates between muscles.
Methods: We conducted three-dimensional motion analyses of 14 athletes performing treadmill sprinting at speeds ranging from 80 to 100% of maximum. Scaled musculoskeletal models were used to estimate hamstring muscle-tendon lengths throughout the sprinting gait cycle for each speed.