This paper combines new experimental data for electrokinetic characterization of hydrophobic polymers with a detailed discussion of the putative origins of charge at water-hydrophobe interfaces. Complexities in determining the origin of charge are discussed in the context of design and modeling challenges for electrokinetic actuation in hydrophobic microfluidic devices with aqueous working fluids. Measurements of interfacial charge are complicated by slip and interfacial water structuring phenomena (see Part 2, this issue). Despite these complexities, it is shown that (i) several hydrophobic materials, such as Teflon and Zeonor, have predictable electrokinetic properties and (ii) electrokinetic data for hydrophobic microfluidic systems is most consistent with the postulate that hydroxyl ion adsorption is the origin of charge.
Aim:The aim was to evaluate the extent and factors responsible for underreporting (UR) of adverse drug reactions (ADRs) in India.Materials and Methods:A retrospective observational, cross-sectional prospective questionnaire-based analysis was undertaken to evaluate the extent and factors for UR of ADRs in pharmacovigilance.Results:At the time, this report was prepared, 90 ADR Monitoring Centers (AMC) were operational in India. Indian AMC functional rate was 56.45%. The average number of Individual Case Safety Reports reported by our center via VigiFlow per month was 48.038. In a period of the 3 years the total number of ADRs reported was 3024. The average number of reports per month was 80.08. Active surveillance versus spontaneous reporting contributed 66.13% versus 33.86% of the total ADRs (P < 0.0001). Outpatient Department (OPD) contribution was 76.05% and indoor contribution was 23.94% of total reports (P < 0.0001). Department of Medicine (33%), followed by oncology (19.27%) and chest disease (13.49%) contributed maximally. The contribution of Pharmacology ADR monitoring OPD was 16.20%. Eye, ear, nose and throat and surgery, private Medical Colleges, hospitals in periphery, sub-district and district contributed no ADRs. ADR detection rates by clinical presentation, biochemical investigation and diagnostic tools were 84.33%, 14.57%, and 1.09% respectively (P < 0.0001). Reporting by postgraduate, registrars, consultants and nurses were 72.65%, 6.58%, 16.56% and 4.19% respectively (P < 0.0001). PG students in Pharmacology contributed an average number of 5.61 ADR reports/month. The lack of knowledge and awareness about Pharmacovigilance Programme of India (PvPI), lethargy, indifference, insecurity, complacency, workload, lack of training were the common factors responsible for UR. Major academic activity, exams, thesis and synopsis submission time influenced reporting of ADRs by postgraduate students.Conclusion:UR is a matter of concern PvPI. Multiple interventions are needed to improve ADR reporting.
96 microfluidic devices with independent electrical readouts are coupled with 192 micropumps to make a high-throughput organ-on-chip platform.
Implementation of gene editing technologies such as CRISPR/Cas9 in the manufacture of novel cell-based therapeutics has the potential to enable highly-targeted, stable, and persistent genome modifications without the use of viral vectors. Electroporation has emerged as a preferred method for delivering gene-editing machinery to target cells, but a major challenge remaining is that most commercial electroporation machines are built for research and process development rather than for large-scale, automated cellular therapy manufacturing. Here we present a microfluidic continuous-flow electrotransfection device designed for precise, consistent, and high-throughput genetic modification of target cells in cellular therapy manufacturing applications. We optimized our device for delivery of mRNA into primary human T cells and demonstrated up to 95% transfection efficiency with minimum impact on cell viability and expansion potential. We additionally demonstrated processing of samples comprising up to 500 million T cells at a rate of 20 million cells/min. We anticipate that our device will help to streamline the production of autologous therapies requiring on the order of 10$$^8$$ 8 –10$$^9$$ 9 cells, and that it is well-suited to scale for production of trillions of cells to support emerging allogeneic therapies.
Aim:The present observational, cross-sectional prospective study was conducted during the period of 1 year in one of the rural health centers to study prevalence of conventional cardiovascular disease risk factors (CVRFs) in postmenopausal women.Materials and Methods:Five hundred consecutive postmenopausal women were screened for detailed information regarding common menopausal symptoms, the presence or absence of conventional CVRFs. Physical activity was measured, and dietary lifestyle was also assessed. Use of hormone replacement therapy (HRT) and other drugs were also noted. Knowledge regarding their menopause was also evaluated.Results:Mean age at menopause was 49.35 years, Mean number of menopausal symptoms was 6.70 ± 5.76, and mean duration since menopause was (MDSM = 4.70 years)). Fatigue, lack of energy (70%), cold hand and feet, rheumatology-related symptoms (60%) cold sweats, weight gain, irritability, and nervousness (50%), palpitation of heart, excitable/anxiety (30%) each were common complaints. Hypertension was diagnosed or a person was a known hypertensive (56%). Diabetes was diagnosed or a person was known diabetic in 21%, and BMI was found to be 25 kg/m2 in 78%. Truncal obesity with waist-hip ratio >0.8 in 68% females, whereas abdominal obesity with waist size >88 cm was in 60% women. Dyslipidemia was seen in 39%. It was defined by the presence of high TC (=200 mg/dL) in 30%, high LDL-c (=130 mg/dL) in 27%, low HDLc (<40 mg/dL) in 21% or high TG (=150 mg/dL) in 31%. Metabolic syndrome was present in 13% of cases. CRP was found positive in 12 out of 39 total evaluated women, and serum uric acid was found >6.5 mg/dL in 4%. Smoking (0.5%), alcohol (0%,), tobacco chewing (4%), and family history of premature heart disease (9%) were recorded. Lifestyle was active in 35%, hectic in 10%, and sedentary in 55% of postmenopausal women (PMWs). Only 5% of women were receiving HRT, 0.5% isoflavone-containing phytoestrogens, 0.4% tibolone, 24% anti-HT, 9% anti-diabetic, 8% lipid-lowering drugs, and only three patients were on anti-obesity along with dietary and lifestyle management. Out of 68 patients, who were advised for electrocardiography (ECG), 23 were found positive for ischemic changes on ECG and out of 12 women advised for treadmill test (TMT), only four were found positive for ischemic heart disease (IHD). Risk factor count of more than four was found in 11%. Over all 96% of women were affected by menopause or related problems. Only 9% were aware about their menopause, 3% for importance of lifestyle modification, weight and dietary management programs to ameliorate menopause or menopause-compounded CVRFs.Conclusion:This study showed alarmingly high prevalence of most of the conventional CVRFs, especially diabetes, hypertension, dyslipidemia, obesity, and other risk factors in postmenopausal women from rural areas.
antioxidant actions and ability to provide plaque stability, favorable coagulation profile, preventing platelet aggregation and normalizing sympathetic outflow as well as their antiproliferative and immunosuppressive properties suggest a new face of statin therapy which make them very important ABSTRACTThe lipid-lowering actions of statins are well known. However, recent studies provide compelling evidence that the clinical benefits of statin therapy may also be attributed to mechanisms independent of their cholesterol-lowering effects. These non-lipid-lowering (pleiotropic) effects of statin therapy are believed to include antiinflammatory actions, property to reverse endothelial dysfunction by decreasing LDL oxidation and increasing nitric oxide bioavailability. Their antioxidant actions, ability to provide plaque stability, favorable coagulation profile, ability to prevent platelet aggregation and normalize sympathetic outflow as well as their antiproliferative and immunosuppressive properties also contribute to the non-lipid-lowering effects. These pleiotropic effects shown by statin therapy offer many advantages over the currently available drugs for dyslipidemias. These additional benefits not only find therapeutic application in cardiovascular disorders but also in many other disease states.
We discuss the structure of water at hydrophobic interfaces from the standpoint of its impact on electrokinetic phenomena in microfluidic devices fabricated from hydrophobic polymers such as Teflon or Zeonor. Water structuring at hydrophobic interfaces has been described as a source of interfacial charge (see Part 1, this issue), and dewetting phenomena, whether via depletion layers or nanobubbles, contribute to slip and enhanced apparent electrokinetic potentials. Issues concerning the impact of hydrodynamic slip and the role of diffuse interfacial structures are discussed. These issues are coupled with each other and with interfacial charge concerns, providing challenges for measurements of individual parameters.
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