"I never had the money for blood testing" – Caretakers' experiences of care-seeking for fatal childhood fevers in rural Uganda – a mixed methods study

<p>Abstract</p> <p>Background</p> <p>The main killer diseases of children all manifest as acute febrile illness, yet are curable with timely and adequate management. To avoid a fatal outcome, three essential steps must be completed: caretakers must recognize illness, decide to seek care and reach an appropriate source of care, and then receive appropriate treatment. In a fatal outcome some or all of these steps have failed and it remains to be elucidated to what extent these fatal outcomes are caused by local disease perceptions, inappropriate care-seeking or inadequate resources in the family or health system. This study explores caretakers' experiences of care-seeking for childhood febrile illness with fatal outcome in rural Uganda to elucidate the most influential barriers to adequate care.</p> <p>Methods</p> <p>A mixed methods approach using structured Verbal/Social autopsy interviews and in-depth interviews was employed with 26 caretakers living in Iganga/Mayuge Demographic Surveillance Site who had lost a child 1–59 months old due to acute febrile illness between March and June 2006. In-depth interviews were analysed using content analysis with deductive category application.</p> <p>Results</p> <p>Final categories of barriers to care were: 1) "Illness interpretation barriers" involving children who received delayed or inappropriate care due to caretakers' labelling of the illness, 2) "Barriers to seeking care" with gender roles and household financial constraints hindering adequate care and 3) "Barriers to receiving adequate treatment" revealing discontents with providers and possible deficiencies in quality of care. Resource constraints were identified as the underlying theme for adequate management, both at individual and at health system levels.</p> <p>Conclusion</p> <p>The management of severely ill children in this rural setting has several shortcomings. However, the majority of children were seen by an allopathic health care provider during the final illness. Improvements of basic health care for children suffering from acute febrile illness are likely to contribute to a substantial reduction of fatal outcomes. Health care providers at all levels and private as well as public should receive training, support, equipment and supplies to enable basic health care for children suffering from common illnesses.</p

Design and Organization of the Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT) Trial: a factorial trial evaluating the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery

<p>Abstract</p> <p>Background</p> <p>The perioperative period is characterized by an intense inflammatory response. Perioperative inflammation promotes postoperative morbidity and increases mortality. Blunting the inflammatory response to surgical trauma might thus improve perioperative outcomes. We are studying three interventions that potentially modulate perioperative inflammation: corticosteroids, tight glucose control, and light anesthesia.</p> <p>Methods/Design</p> <p>The DeLiT Trial is a factorial randomized single-center trial of dexamethasone vs placebo, intraoperative tight vs. conventional glucose control, and light vs deep anesthesia in patients undergoing major non-cardiac surgery. Anesthetic depth will be estimated with Bispectral Index (BIS) monitoring (Aspect medical, Newton, MA). The primary outcome is a composite of major postoperative morbidity including myocardial infarction, stroke, sepsis, and 30-day mortality. C-reactive protein, a measure of the inflammatory response, will be evaluated as a secondary outcome. One-year all-cause mortality as well as post-operative delirium will be additional secondary outcomes. We will enroll up to 970 patients which will provide 90% power to detect a 40% reduction in the primary outcome, including interim analyses for efficacy and futility at 25%, 50% and 75% enrollment.</p> <p>Discussion</p> <p>The DeLiT trial started in February 2007. We expect to reach our second interim analysis point in 2010. This large randomized controlled trial will provide a reliable assessment of the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery. The factorial design will enable us to simultaneously study the effects of the three interventions in the same population, both individually and in different combinations. Such a design is an economically efficient way to study the three interventions in one clinical trial vs three.</p> <p>Trial registration</p> <p><b>This trial is registered at </b>Clinicaltrials.gov <b>#</b>: NTC00433251</p

Solution structure analysis of the periplasmic region of bacterial flagellar motor stators by small angle X-ray scattering

© 2017 Elsevier Inc. The bacterial flagellar motor drives the rotation of helical flagellar filaments to propel bacteria through viscous media. It consists of a dynamic population of mechanosensitive stators that are embedded in the inner membrane and activate in response to external load. This entails assembly around the rotor, anchoring to the peptidoglycan layer to counteract torque from the rotor and opening of a cation channel to facilitate an influx of cations, which is converted into mechanical rotation. Stator complexes are comprised of four copies of an integral membrane A subunit and two copies of a B subunit. Each B subunit includes a C-terminal OmpA-like peptidoglycan-binding (PGB) domain. This is thought to be linked to a single N-terminal transmembrane helix by a long unstructured peptide, which allows the PGB domain to bind to the peptidoglycan layer during stator anchoring. The high-resolution crystal structures of flagellar motor PGB domains from Salmonella enterica (MotBC2) and Vibrio alginolyticus (PomBC5) have previously been elucidated. Here, we use small-angle X-ray scattering (SAXS). We show that unlike MotBC2, the dimeric conformation of the PomBC5 in solution differs to its crystal structure, and explore the functional relevance by characterising gain-of-function mutants as well as wild-type constructs of various lengths. These provide new insight into the conformational diversity of flagellar motor PGB domains and experimental verification of their overall topology

Domain-swap polymerization drives the self-assembly of the bacterial flagellar motor.

Large protein complexes assemble spontaneously, yet their subunits do not prematurely form unwanted aggregates. This paradox is epitomized in the bacterial flagellar motor, a sophisticated rotary motor and sensory switch consisting of hundreds of subunits. Here we demonstrate that Escherichia coli FliG, one of the earliest-assembling flagellar motor proteins, forms ordered ring structures via domain-swap polymerization, which in other proteins has been associated with uncontrolled and deleterious protein aggregation. Solution structural data, in combination with in vivo biochemical cross-linking experiments and evolutionary covariance analysis, revealed that FliG exists predominantly as a monomer in solution but only as domain-swapped polymers in assembled flagellar motors. We propose a general structural and thermodynamic model for self-assembly, in which a structural template controls assembly and shapes polymer formation into rings