Cation channels,cell volume and the death of an erythrocyte

Similar to a variety of nucleated cells, human erythrocytes activate a non-selective cation channel upon osmotic cell shrinkage. Further stimuli of channel activation include oxidative stress, energy depletion and extracellular removal of Cl^–. The channel is permeable to Ca²⁺ and opening of the channel increases cytosolic [Ca²⁺]. Intriguing evidence points to a role of this channel in the elimination of erythrocytes by apoptosis. Ca²⁺ entering through the cation channel stimulates a scramblase, leading to breakdown of cell membrane phosphatidylserine asymmetry, and stimulates Ca²⁺-sensitive K⁺ channels, thus leading to KCl loss and (further) cell shrinkage. The breakdown of phosphatidylserine asymmetry is evidenced by annexin binding, a typical feature of apoptotic cells. The effects of osmotic shock, oxidative stress and energy depletion on annexin binding are mimicked by the Ca²⁺ ionophore ionomycin (1 µM) and blunted in the nominal absence of extracellular Ca²⁺. Nevertheless, the residual annexin binding points to additional mechanisms involved in the triggering of the scramblase. The exposure of phosphatidylserine at the extracellular face of the cell membrane stimulates phagocytes to engulf the apoptotic erythrocytes. Thus, sustained activation of the cation channels eventually leads to clearance of affected erythrocytes from peripheral blood. Susceptibility to annexin binding is enhanced in several genetic disorders affecting erythrocyte function, such as thalassaemia, sickle-cell disease and glucose-6-phosphate dehydrogenase deficiency. The enhanced vulnerability presumably contributes to the shortened life span of the affected erythrocytes. Beyond their role in the limitation of erythrocyte survival, cation channels may contribute to the triggering of apoptosis in nucleated cells exposed to osmotic shock and/or oxidative stress.     

Treatment of infants with ureteropelvic junction obstruction: findings from the PURSUIT network

International Urology and Nephrology - Studies based on administrative databases show that infant pyeloplasty is associated with minority race/ethnicity but lack clinical data that may influence...     

Quality improvement in immunization delivery following an unsuccessful immunization recall.

OBJECTIVES: Within a clinic serving disadvantaged children, 1) to evaluate a multifaceted quality improvement (QI) project to improve immunization (IZ) up-to-date (UTD) rates and 2) to assess the efficacy of IZ reminder/recall performed following QI. METHODS: A year-long QI project followed by a trial of reminder/recall. QI interventions were targeted at previously identified barriers to IZ and were designed specifically to improve the efficacy of reminder/recall. QI interventions were designed to 1) increase the use of medical record releases to document IZs received elsewhere; 2) improve the accuracy of parental contact information; and 3) reduce missed opportunities by utilizing chart prompts, provider education, and provider reminders. Following QI, we conducted a randomized trial of reminder/recall. RESULTS: UTD rates for 7-11 month olds increased from 21% before the QI project to 52% after (P <.0001); rates for 12-18 month olds increased from 16% before QI to 44% after (P <.0001); 19-25 month olds 18% before to 33% after (P <.001). After QI, an average of 61 records per month were updated with IZs received elsewhere. However, the accuracy of parental contact information worsened (29% unreachable before QI vs 44% after, P <.001) and missed opportunities did not improve (8% before vs 6% after, P = not significant [NS]). A subsequent trial of reminder/recall did not increase UTD rates, with 17% of recalled children brought UTD vs 16% of controls (P = NS). CONCLUSIONS: Clinic-based QI increased documented UTD rates in a disadvantaged patient population. However, IZ reminder/recall did not further increase UTD rates above the rates achieved by the QI process.     

Less anticipatory guidance is associated with more subsequent injury visits among infants.

OBJECTIVE: To describe clinician delivery of injury prevention anticipatory guidance and injury visits in a birth cohort, and to describe the association of injury prevention anticipatory guidance with subsequent injury visits. METHODS: We performed a prospective cohort study of 2610 infants born from July 1, 1998 to June 30, 1999, at an urban safety-net hospital and seen subsequently for well child care (WCC, visits = 10558) and/or injury by 16 months of age. Injury guidance was defined as the proportion of recommended injury prevention anticipatory guidance items delivered to those expected, given the WCC visits the child attended. The outcome was a first injury visit to a clinic, emergency department, or hospital. RESULTS: The injury prevention items most discussed were car seats (84%-95% of all WCC visits) and rolling over at the 2-month WCC visit (80%). Other items were addressed at 36%-69% of visits. A total of 1931 (74%) of children received > or = 50% expected injury guidance. A total of 277 children (11%) had an injury visit, primarily for minor injuries. In unadjusted analysis, children receiving < 25% expected injury guidance were more likely to have a subsequent injury visit (unadjusted odds ratio 6.2; 95% confidence interval [95% CI] 3.2-9.7). In adjusted analysis, children who received < 25% and 25%-49% expected injury guidance were more likely to have a subsequent injury visits (adjusted odds ratio [AOR] 6.6; 95% CI 3.8-11.2; and AOR 2.9, 95% CI 2.0-4.3, respectively). CONCLUSIONS: Disadvantaged children whose families received less injury guidance than other children in their cohort were more likely to have a subsequent injury visit. Further studies are needed to determine whether increased injury prevention counseling reduces injury visits.     

Attacking Key Performance Indicators in Soccer: Current Practice and Perceptions from the Elite to Youth Academy Level

Key Performance Indicators (KPIs) are used to evaluate the offensive success of a soccer team (e.g. penalty box entries) or player (e.g. pass completion rate). However, knowledge transfer from research to applied practice is understudied. The current study queried practitioners (n = 145, mean ± SD age: 36 ± 9 years) from 42 countries across different roles and levels of competition (National Team Federation to Youth Academy levels) on various forms of data collection, including an explicit assessment of twelve attacking KPIs. 64.3% of practitioners use data tools and applications weekly (predominately) to gather KPIs during matches. 83% of practitioners use event data compared to only 52% of practitioners using positional data, with a preference for shooting related KPIs. Differences in the use and value of metrics derived from positional tracking data (including Ball Possession Metrics) were evident between job role and level of competition. These findings demonstrate that practitioners implement KPIs and gather tactical information in a variety of ways with a preference for simpler metrics related to shots. The low perceived value of newer KPIs afforded by positional data could be explained by low buy-in, a lack of education across practitioners, or insufficient translation of findings by experts towards practice.Key points

• Soccer practitioners collect data and evaluate performance in a variety of ways depending on the level of competition and their role within a club or federation.
• Practitioners reported a preference for shooting related metrics gathered by event data compared to KPIs offered by optical positional tracking technology.
• Despite increased interest and the capability to measure contextual aspects of passing performance with tracking technology, most practitioners still rely on more easily computed metrics (e.g. Pass Completion Percentage) and ball possession KPIs (e.g. Total Duration of Possession).
• This study highlights a gap in knowledge transfer between research and practice, encouraging increased education and collaborative efforts between data/sport scientists and practitioners to progress the field of analytics towards practical use in soccer.

Key words: Football, soccer, match analysis, performance analysis, applied data-science     

Gene Expression Analysis Using a High‐Resolution DNA Microarray of Peripheral Whole Blood Immediately Before and After Leukocytapheresis for Rheumatoid Arthritis

Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non‐woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high‐resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t‐test. Calculations were performed with a statistical software R.basic package: if the P‐value was less than 0.05, this was seen as a significant change. In a comparison of 25 370 gene expressions, the number of genes showing a P‐value < 0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.     

Failure of the platelet-activating-factor antagonist WEB 2086 BS for treatment of chronic autoimmune thrombocytopenia

Summary Thirteen patients with chronic autoimmune thrombocytopenia (AITP) were treated for 14 days with daily oral doses of 120 mg of the novel platelet-activating-factor (PAF) antagonist WEB 2086 BS. Clinical bleeding symptoms remained essentially unchanged in 9 patients and became more pronounced in the post-treatment period in 4 patients. In no case was an increase in platelet counts observed. While the PAF antagonist was well tolerated subjectively during treatment, most patients exhibited a prolongation of the sensitive hemostasis time (a modified bleeding time test) after treatment, but the Duke bleeding time was not changed. We conclude that the PAF antagonist WEB 2086 BS is ineffective for treatment of chronic AITP and should be used with caution in thrombocytopenic patients.