A simple three-dimensional-focusing, continuous-flow mixer for the study of fast protein dynamics

We present a simple, yet flexible microfluidic mixer with a demonstrated mixing time as short as 80 μs that is widely accessible because it is made of commercially available parts. To simplify the study of fast protein dynamics, we have developed an inexpensive continuous-flow microfluidic mixer, requiring no specialized equipment or techniques. The mixer uses three-dimensional, hydrodynamic focusing of a protein sample stream by a surrounding sheath solution to achieve rapid diffusional mixing between the sample and sheath. Mixing initiates the reaction of interest. Reactions can be spatially observed by fluorescence or absorbance spectroscopy. We characterized the pixel-to-time calibration and diffusional mixing experimentally. We achieved a mixing time as short as 80 μs. We studied the kinetics of horse apomyoglobin (apoMb) unfolding from the intermediate (I) state to its completely unfolded (U) state, induced by a pH jump from the initial pH of 4.5 in the sample stream to a final pH of 2.0 in the sheath solution. The reaction time was probed using the fluorescence of 1-anilinonaphthalene-8-sulfonate (1,8-ANS) bound to the folded protein. We observed unfolding of apoMb within 760 μs, without populating additional intermediate states under these conditions. We also studied the reaction kinetics of the conversion of pyruvate to lactate catalyzed by lactate dehydrogenase using the intrinsic tryptophan emission of the enzyme. We observe sub-millisecond kinetics that we attribute to Michaelis complex formation and loop domain closure. These results demonstrate the utility of the three-dimensional focusing mixer for biophysical studies of protein dynamics

Plasma proteome correlates of lipid and lipoprotein: biomarkers of metabolic diversity and inflammation in children of rural Nepal.

Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = -0.43∼0.70), triglycerides (r = -0.39∼0.53), and HDL-C (r = -0.49∼0.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 4∼40%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 3∼20%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease

Investigation of Performance Envelope for Phenolic Impregnated Carbon Ablator (PICA)

The present work provides the results of a short exploratory study on the performance of Phenolic Impregnated Carbon Ablator, or PICA, at high heat flux and pressure in an arcjet facility at NASA Ames Research Center. The primary objective of the study was to explore the thermal response of PICA at cold-wall heat fluxes well in excess of 1500 W/cm (exp 2). Based on the results of a series of flow simulations, multiple PICA samples were tested at an estimated cold wall heat flux and stagnation pressure of 1800 W/cm (exp 2) and 130 kPa, respectively. All samples survived the test, and no failure was observed either during or after the exposure. The results indicate that PICA has a potential to perform well at environments with significantly higher heat flux and pressure than it has currently been flown

Do ACE inhibitors or ARBs help prevent kidney disease in patients with diabetes and normal BP?

Q: Do ACE inhibitors or ARBs help prevent kidney disease in patients with diabetes and normal BP? Evidence-based answer: Yes for angiotensin-converting enzyme (ACE) inhibitors, no for angiotensin receptor blockers (ARBs). In normotensive patients with type 1 and type 2 diabetes, ACE inhibitor therapy reduces the risk of developing diabetic kidney disease, defined as new-onset microalbuminuria or macroalbuminuria, by 18% (strength of recommendation [SOR]: C, meta-analysis of randomized controlled trials [RCTs], disease-oriented evidence). ACE inhibitor treatment improves all-cause mortality by 16% in patients with diabetes, including patients with and without hypertension. Patients on ACE inhibitor therapy are at increased risk of cough (SOR: A, meta-analysis of RCTs). ARB therapy doesn't lower the risk of developing kidney disease in normotensive patients with type 2 diabetes (SOR: C, meta-analysis of RCTs, disease-oriented evidence); nor does it reduce all-cause mortality in patients with or without hypertension (SOR: A, meta-analysis of RCTs). ARBs aren't associated with significant adverse events (SOR: A, meta-analysis of RCTs)

Prospective study on outcomes of postpartum intrauterine contraceptive device including safety, efficacy and expulsion at GMERS Medical College, Dharpur-Patan, Gujarat, India

Background: Evaluation of PPIUCD in terms of incidence of failure, expulsion, bleeding p\v and other complication. Present study is aimed at determining the safety, efficacy, expulsion of post placental and intra cesarean insertion of intrauterine device.Methods: Prospective analysis was carried out to collect information regarding IUCD insertion and outcome at tertiary care center for the period of three years using the hospital record that a total number of 600 mothers had postpartum intrauterine contraceptive device.Results: Total women opted for PPIUCD 600, Followed up 560 after 1 week, 580 after 6 weeks and 400 after 6 months. Complications after 6 months 228. (pain 66, bleeding 37, expulsion 17, strings problem 7, discharge p/v 101).Conclusions: The insertion of PPIUCD is safe and effective method of contraception in the means of complication though it is a new concept for the population it is well accepted by the community though expulsion rate is somewhat high compare to conventional IUCD. it can be reduced with practice

Study of maternal mortality in a tertiary care hospital (GMERS-Dharpur, Patan, Gujarat, India): a three-year review

Background: Epidemiological data related to maternal mortality is valuable in each set up to design the progress to maternal mortality. This study was done to evaluate maternal death over period of 3 years at tertiary care centre of North Gujarat, India.Methods: This was retrospective study conducted at department of Obstetrics and Gynecology at GMERS medical college Dharpur, Patan (N.G.), India. Epidemiological data was collected from hospital register from January-15 to Dec-17 of maternal death in the hospital maternal age, parity, educational status, ANC registration, mode of delivery, admission death interval and direct and indirect causes and maternal deaths were noted and analyzed statistically.Results: There were 41 maternal deaths from Jan-15 to Dec-17. Maximum deaths were in 21-30 age group with multipara, unbooked and illiterate patients. Majority of maternal deaths are due to hemorrhage, eclampsia and sepsis.Conclusions: Many different factors interact in a complex way to increase the risk of death of pregnant women. Regular ANC, early identification of complication and timely referral, delivery by skill birth attendant and adequate post-partum case and follow up are required. To avoid maternal death unwanted pregnancy, too early pregnancy should be avoided adequate counseling and contraception facility also required for sepsis prevention, safe abortion services according to the law and quality post abortion care. There is a wide scope of improvement as most of the maternal deaths are preventable

Use of MTP kit (Mifepristone and Misoprostol combination pack) for 1st trimester MTP (up to 63 days) at GMERS Dharpur, Patan, Gujarat, India

Background: MTP has been legalized in India since 1971. MTP pill (Medical abortion) refers for early pregnancy termination (usually before 9 week gestation) performed without any primary surgical interventions. This study was called out to measure its effectiveness and safety as an abortificiant drug.Methods: This is a prospective study of 57 cases, conducted at OBSTETRIC and GYNECOLOGY Department, GMERS Medical College, Dharpur, Patan (N.G.) from April 2017 to April 2018.Results: In present study,61.4% women are of 20-30 years of age. Majority of women are (82.5%) of 2nd and 3rd para. Complete abortion was found in 91.2%. Incomplete abortion was in 7%. And there was no effect in 1.8%. Major side effects were bleeding (84.2%), abdominal pain (85.9%). Misoprostol related side effects are minimal.Conclusions: The present observational study demonstrates that mifepristone and misoprostol combined therapy is an effective and well tolerated medication in Indian adult women (≥18 years) requiring medical termination of intrauterine pregnancy (MTP) up to 63 days’ gestation