Relationship between cardiovascular risk and lipid testing in one health care system: a retrospective cohort study.

BackgroundThe US Preventive Services Taskforce (USPSTF) recommends routine lipid screening beginning age 35 for men [1]. For women age 20 and older, as well as men age 20-34, screening is recommended if cardiovascular risk factors are present. Prior research has focused on underutilization but not overuse of lipid testing. The objective is to document over- and under-use of lipid testing in an insured population of persons at low, moderate and high cardiovascular disease (CVD) risk for persons not already on statins.MethodsThe study is a retrospective cohort study that included all adults without prior CVD who were continuously enrolled in a large integrated healthcare system from 2005 to 2010. Measures included lipid test frequency extracted from administrative data and Framingham cardiovascular risk equations applied using electronic medical record data. Five year lipid testing patterns were examined by age, sex and CVD risk. Generalized linear models were used to estimate the relative risk for over testing associated with patient characteristics.ResultsAmong males and females for whom testing is not recommended, 35.8 % and 61.5 % received at least one lipid test in the prior 5 years and 8.4 % and 24.4 % had two or more. Over-testing was associated with age, race, comorbidity, primary care use and neighborhood income. Among individuals at moderate and high-risk (not already treated with statins) and for whom screening is recommended, between 21.4 % and 25.1 % of individuals received no screening in the prior 5 years.ConclusionsBased on USPSTF lipid screening recommendations, this study documents substantial over-testing among individuals with low CVD risk and under-testing among individuals with moderate to high-risk not already on statins. Opportunity exists to better focus lipid screening efforts appropriate to CVD risk

Length of Stay After Childbirth in 92 Countries and Associated Factors in 30 Low- and Middle-Income Countries: Compilation of Reported Data and a Cross-sectional Analysis from Nationally Representative Surveys

Background: Following childbirth, women need to stay sufficiently long in health facilities to receive adequate care. Little is known about length of stay following childbirth in low- and middle-income countries or its determinants. Methods and Findings: We described length of stay after facility delivery in 92 countries. We then created a conceptual framework of the main drivers of length of stay, and explored factors associated with length of stay in 30 countries using multivariable linear regression. Finally, we used multivariable logistic regression to examine the factors associated with stays that were “too short” (<24 h for vaginal deliveries and <72 h for cesarean-section deliveries). Across countries, the mean length of stay ranged from 1.3 to 6.6 d: 0.5 to 6.2 d for singleton vaginal deliveries and 2.5 to 9.3 d for cesarean-section deliveries. The percentage of women staying too short ranged from 0.2% to 83% for vaginal deliveries and from 1% to 75% for cesarean-section deliveries. Our conceptual framework identified three broad categories of factors that influenced length of stay: need-related determinants that required an indicated extension of stay, and health-system and woman/family dimensions that were drivers of inappropriately short or long stays. The factors identified as independently important in our regression analyses included cesarean-section delivery, birthweight, multiple birth, and infant survival status. Older women and women whose infants were delivered by doctors had extended lengths of stay, as did poorer women. Reliance on factors captured in secondary data that were self-reported by women up to 5 y after a live birth was the main limitation. Conclusions: Length of stay after childbirth is very variable between countries. Substantial proportions of women stay too short to receive adequate postnatal care. We need to ensure that facilities have skilled birth attendants and effective elements of care, but also that women stay long enough to benefit from these. The challenge is to commit to achieving adequate lengths of stay in low- and middle-income countries, while ensuring any additional time is used to provide high-quality and respectful care

Gene transfer and expression in human neutrophils. The phox homology domain of p47(phox )translocates to the plasma membrane but not to the membrane of mature phagosomes

BACKGROUND: Neutrophils are non-dividing cells with poor survival after isolation. Consequently, exogenous gene expression in neutrophils is challenging. We report here the transfection of genes and expression of active proteins in human primary peripheral neutrophils using nucleofection. RESULTS: Exogenous gene expression in human neutrophils was achieved 2 h post-transfection. We show that neutrophils transfected by nucleofection are functional cells, able to respond to soluble and particulate stimuli. They conserved the ability to undergo physiological processes including phagocytosis. Using this technique, we were able to show that the phox homology (PX) domain of p47(phox )localizes to the plasma membrane in human neutrophils. We also show that RhoB, but not the PX domain of p47(phox), is translocated to the membrane of mature phagosomes. CONCLUSION: We demonstrated that cDNA transfer and expression of exogenous protein in human neutrophils is compatible with cell viability and is no longer a limitation for the study of protein function in human neutrophils

Rehabilitation of hand function after spinal cord injury using a novel handgrip device: a pilot study

BackgroundActivity-based therapy (ABT) for patients with spinal cord injury (SCI), which consists of repetitive use of muscles above and below the spinal lesion, improves locomotion and arm strength. Less data has been published regarding its effects on hand function. We sought to evaluate the effects of a weekly hand-focused therapy program using a novel handgrip device on grip strength and hand function in a SCI cohort.MethodsPatients with SCI were enrolled in a weekly program that involved activities with the MediSens (Los Angeles, CA) handgrip. These included maximum voluntary contraction (MVC) and a tracking task that required each subject to adjust his/her grip strength according to a pattern displayed on a computer screen. For the latter, performance was measured as mean absolute accuracy (MAA). The Spinal Cord Independence Measure (SCIM) was used to measure each subject's independence prior to and after therapy.ResultsSeventeen patients completed the program with average participation duration of 21.3&nbsp;weeks. The cohort included patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A (n = 12), AIS B (n = 1), AIS C (n = 2), and AIS D (n = 2) injuries. The average MVC for the cohort increased from 4.1&nbsp;N to 21.2&nbsp;N over 20&nbsp;weeks, but did not reach statistical significance. The average MAA for the cohort increased from 9.01 to 21.7% at the end of the study (p = .02). The cohort's average SCIM at the end of the study was unchanged compared to baseline.ConclusionsA weekly handgrip-based ABT program is feasible and efficacious at increasing hand task performance in subjects with SCI

Reconstitution of Rab11-FIP4 Expression Rescues Cellular Homeostasis in Cystinosis

Rab11 family interacting protein 4 (Rab11-FIP4) regulates endocytic trafficking. A possible role for Rab11-FIP4 in the regulation of lysosomal function has been proposed, but its precise function in the regulation of cellular homeostasis is unknown. By mRNA array and protein analysis, we found that Rab11-FIP4 is downregulated in the lysosomal storage disease cystinosis, which is caused by genetic defects in the lysosomal cystine transporter, cystinosin. Rescue of Rab11-FIP4 expression in Ctns-/- fibroblasts re-established normal autophagosome levels and decreased LC3B-II expression in cystinotic cells. Furthermore, Rab11-FIP4 reconstitution increased the localization of the chaperone-mediated autophagy receptor LAMP2A at the lysosomal membrane. Treatment with genistein, a phytoestrogen that upregulates macroautophagy, or the CMA activator QX77 (CA77) restored Rab11-FIP4 expression levels in cystinotic cells supporting a cross-regulation between two independent autophagic mechanisms, lysosomal function and Rab11-FIP4. Improved cellular homeostasis in cystinotic cells rescued by Rab11-FIP4 expression correlated with decreased endoplasmic reticulum stress, an effect that was potentiated by Rab11 and partially blocked by expression of a dominant negative Rab11. Restoring Rab11-FIP4 expression in cystinotic proximal tubule cells increased the localization of the endocytic receptor megalin at the plasma membrane, suggesting that Rab11-FIP4 reconstitution has the potential to improve cellular homeostasis and function in cystinosis

A competitive integration model of exogenous and endogenous eye movements

We present a model of the eye movement system in which the programming of an eye movement is the result of the competitive integration of information in the superior colliculi (SC). This brain area receives input from occipital cortex, the frontal eye fields, and the dorsolateral prefrontal cortex, on the basis of which it computes the location of the next saccadic target. Two critical assumptions in the model are that cortical inputs are not only excitatory, but can also inhibit saccades to specific locations, and that the SC continue to influence the trajectory of a saccade while it is being executed. With these assumptions, we account for many neurophysiological and behavioral findings from eye movement research. Interactions within the saccade map are shown to account for effects of distractors on saccadic reaction time (SRT) and saccade trajectory, including the global effect and oculomotor capture. In addition, the model accounts for express saccades, the gap effect, saccadic reaction times for antisaccades, and recorded responses from neurons in the SC and frontal eye fields in these tasks. © The Author(s) 2010