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

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

Order out of chaos: Sense of coherence and the mediating role of coping resources in explaining mental health during COVID-19 in 7 countries

In the midst of the COVID-19 pandemic and the universal chaos created by it, this study explores the role of sense of coherence (Soc, Antonovsky, 1979) and how it enables coping with a stressful situation and staying well. SOC is a generalized orientation which allows one to perceive the world as comprehensible, manageable, and meaningful. In an attempt to understand 'how does the SOC work' we employed the salutogenic assumption that a strong SOC allows one to reach out in any given situation and find those resources appropriate to the specific stressor. Thus, we hypothesized that the positive impact of SOC on mental health outcomes would be mediated through coping resources that are particularly salient in times of crisis. One resource is related to the micro level (perceived family support) and the other concerns the macro level (trust in leaders and social-political institutions). Data collection was conducted in different countries during May-June 2020 via online platforms. The data included 7 samples of adult participants (age 18-90) from Israel (n ​= ​669), Italy (n ​= ​899), Spain (n ​= ​476), Germany (n ​= ​708), Austria (n ​= ​1026), Switzerland (n ​= ​147), and the U.S. (n ​= ​506). The questionnaires included standard tools (MHC-SF, SOC-13) as well as questionnaires of perceived family support and trust that were adapted to the pandemic context. As expected, SOC was associated with mental health in all the samples. Perceived family support and trust in leaders and social-political institutions mediated the relationships between SOC and mental health, controlling for age, gender, and level of financial risk. It appears that SOC has a universal meaning, not limited by cultural and situational characteristics. The discussion focuses on the theoretical, social, and political applications of the salutogenic model - and its core concept of SOC - in the context of coping with a global pandemic across different cultural contexts and countries

It's not just what you say: Relationships of HIV dislosure and risk reduction among MSM in the post-HAART era

In the post-HAART era, critical questions arise as to what factors affect disclosure decisions and how these decisions are associated with factors such as high-risk behaviors and partner variables. We interviewed 1,828 HIV-positive men who have sex with men (MSM), of whom 46% disclosed to all partners. Among men with casual partners, 41.8% disclosed to all of these partners and 21.5% to none. Disclosure was associated with relationship type, perceived partner HIV status and sexual behaviors. Overall, 36.5% of respondents had unprotected anal sex (UAS) with partners of negative/unknown HIV status. Of those with only casual partners, 80.4% had >1 act of UAS and 58% of these did not disclose to all partners. This 58% were more likely to self-identify as gay (versus bisexual), be aware of their status for <5 years and have more partners. Being on HAART, viral load and number of symptoms were not associated with disclosure. This study—the largest conducted to date of disclosure among MSM and one of the few conducted post-HAART—indicates that almost 1/5th reported UAS with casual partners without disclosure, highlighting a public health challenge. Disclosure needs to be addressed in the context of relationship type, partner status and broader risk-reduction strategies

Disruption of Saccadic Adaptation with Repetitive Transcranial Magnetic Stimulation of the Posterior Cerebellum in Humans

Saccadic eye movements are driven by motor commands that are continuously modified so that errors created by eye muscle fatigue, injury, or—in humans—wearing spectacles can be corrected. It is possible to rapidly adapt saccades in the laboratory by introducing a discrepancy between the intended and actual saccadic target. Neurophysiological and lesion studies in the non-human primate as well as neuroimaging and patient studies in humans have demonstrated that the oculomotor vermis (lobules VI and VII of the posterior cerebellum) is critical for saccadic adaptation. We studied the effect of transiently disrupting the function of posterior cerebellum with repetitive transcranial magnetic stimulation (rTMS) on the ability of healthy human subjects to adapt saccadic eye movements. rTMS significantly impaired the adaptation of the amplitude of saccades, without modulating saccadic amplitude or variability in baseline conditions. Moreover, increasing the intensity of rTMS produced a larger impairment in the ability to adapt saccadic size. These results provide direct evidence for the role of the posterior cerebellum in man and further evidence that TMS can modulate cerebellar function

Nicotinamide Phosphoribosyltransferase/Visfatin Does Not Catalyze Nicotinamide Mononucleotide Formation in Blood Plasma

Nicotinamide (Nam) phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in mammalian NAD synthesis, catalyzing nicotinamide mononucleotide (NMN) formation from Nam and 5-phosphoribosyl 1-pyrophosphate (PRPP). NAMPT has also been described as an adipocytokine visfatin with a variety of actions, although physiological significance of this protein remains unclear. It has been proposed that possible actions of visfatin are mediated through the extracellular formation of NMN. However, we did not detect NMN in mouse blood plasma, even with a highly specific and sensitive liquid chromatography/tandem mass spectrometry. Furthermore, there is no or little ATP, the activator of NAMPT, in extracellular spaces. We thus questioned whether visfatin catalyzes the in situ formation of NMN under such extracellular milieus. To address this question, we here determined Km values for the substrates Nam and PRPP in the NAMPT reaction without or with ATP using a recombinant human enzyme and found that 1 mM ATP dramatically decreases Km values for the substrates, in particular PRPP to its intracellular concentration. Consistent with the kinetic data, only when ATP is present at millimolar levels, NAMPT efficiently catalyzed the NMN formation at the intracellular concentrations of the substrates. Much lower concentrations of Nam and almost the absence of PRPP and ATP in the blood plasma suggest that NAMPT should not efficiently catalyze its reaction under the extracellular milieu. Indeed, NAMPT did not form NMN in the blood plasma. From these kinetic analyses of the enzyme and quantitative determination of its substrates, activator, and product, we conclude that visfatin does not participate in NMN formation under the extracellular milieus. Together with the absence of NMN in the blood plasma, our conclusion does not support the concept of “NAMPT-mediated systemic NAD biosynthesis.” Our study would advance current understanding of visfatin physiology

Communicating genetic information: a difficult challenge for future pediatricians

<p>Abstract</p> <p>Background</p> <p>The role of the pediatrician as genetic counselor is ideal because pediatricians have medical knowledge and experience with genetic disorders (e.g. Down syndrome). Moreover, pediatricians can provide comprehensive care in a medical home to patients with genetic disorders. However, changes in the curriculum of the pediatric resident are necessary to address the future challenges of effectively communicating genetic information to patients. The objective of this study was to explore these challenges and make recommendations for training to adequately prepare pediatricians for their future role as genetic counselors.</p> <p>Methods</p> <p>Three reviewers independently searched PubMed, OVID, and Medline databases to identify articles describing the challenges of communicating genetic information to patients, published from 1960 to December 2005. After the publications were identified and reviewed, four major areas of interest were identified in order to categorize the findings.</p> <p>Results</p> <p>Twenty-five publications were identified during the literature search. From the review, the following categories were selected to organize the findings: (1) Inherent difficulties of communicating and comprehending genetic information; (2) Comprehension of genetic information by pediatricians; (3) Genetics training in residency programs; and (4) The effect of genetic information on the future role of pediatricians and potential legal implications.</p> <p>Conclusion</p> <p>Pediatricians and residents lack essential knowledge of genetics and communication skills for effective counseling of patients. The review indicated that successful communication of genetic information involves a number of important skills and considerations. It is likely that these skills and considerations are universally required for the communication of most complex specialized medical information. In the past, communication skills have not been considered a priority. Today, these skills have become a demanding professional and even legal obligation. However, the challenges involved in communicating complex medical information cannot be successfully addressed with universal, one-size-fits-all recommendations. Residency training programs require changes to adequately prepare future pediatricians for the growing challenge of communicating genetic information. Four important skills should be considered in the training of residents to improve the communication of complex information to patients. These skills are (1) discriminating, (2) understanding, (3) simplifying, and (4) explaining information.</p

Reduction of missed appointments at an urban primary care clinic: a randomised controlled study

<p>Abstract</p> <p>Background</p> <p>Missed appointments are known to interfere with appropriate care and to misspend medical and administrative resources. The aim of this study was to test the effectiveness of a sequential intervention reminding patients of their upcoming appointment and to identify the profile of patients missing their appointments.</p> <p>Methods</p> <p>We conducted a randomised controlled study in an urban primary care clinic at the Geneva University Hospitals serving a majority of vulnerable patients. All patients booked in a primary care or HIV clinic at the Geneva University Hospitals were sent a reminder 48 hrs prior to their appointment according to the following sequential intervention: 1. Phone call (fixed or mobile) reminder; 2. If no phone response: a Short Message Service (SMS) reminder; 3. If no available mobile phone number: a postal reminder. The rate of missed appointment, the cost of the intervention, and the profile of patients missing their appointment were recorded.</p> <p>Results</p> <p>2123 patients were included: 1052 in the intervention group, 1071 in the control group. Only 61.7% patients had a mobile phone recorded at the clinic. The sequential intervention significantly reduced the rate of missed appointments: 11.4% (n = 122) in the control group and 7.8% (n = 82) in the intervention group (p < 0.005), and allowed to reallocate 28% of cancelled appointments. It also proved to be cost effective in providing a total net benefit of 1846. - EUR/3 months. A satisfaction survey conducted with 241 patients showed that 93% of them were not bothered by the reminders and 78% considered them to be useful. By multivariate analysis, the following characteristics were significant predictors of missed appointments: younger age (OR per additional decade 0.82; CI 0.71-0.94), male gender (OR 1.72; CI 1.18-2.50), follow-up appointment >1year (OR 2.2; CI: 1.15-4.2), substance abuse (2.09, CI 1.21-3.61), and being an asylum seeker (OR 2.73: CI 1.22-6.09).</p> <p>Conclusion</p> <p>A practical reminder system can significantly increase patient attendance at medical outpatient clinics. An intervention focused on specific patient characteristics could further increase the effectiveness of appointment reminders.</p

AKT inhibition is associated with chemosensitisation in the pancreatic cancer cell line MIA-PaCa-2

Activation of the serine/threonine kinase AKT is common in pancreatic cancer; inhibition of which sensitises cells to the apoptotic effect of chemotherapy. Of the various downstream targets of AKT, we examined activation of the NF-kappaB transcription factor and subsequent transcriptional regulation of BCL-2 gene family in pancreatic cancer cells. Inhibition of either phosphatidylinositol-3 kinase or AKT led to a decreased protein level of the antiapoptotic gene BCL-2 and an increased protein level of the proapoptotic gene BAX. Furthermore, inhibition of AKT decreased the function of NF-kappaB, which is capable of transcriptional regulation of the BCL-2 gene. Inhibiting this pathway had little effect on the basal level of apoptosis in pancreatic cancer cells, but increased the apoptotic effect of chemotherapy. The antiapoptotic effect of AKT activation in pancreatic cancer cells may involve transcriptional induction of a profile of BCL-2 proteins that confer resistance to apoptosis; alteration of this balance allows sensitisation to the apoptotic effect of chemotherapy