Role of female birth attendants to enhance breastfeeding rates and essential newborn care

Background: Women who received support during labor are more likely to give birth “spontaneously.” The role of the female birth attendant (FBA) has not been very well established; hence, this study was planned. Objective: The objective of the study was to train, educate, assess, and evaluate the role of FBA before, during and after labor in terms of mother’s satisfaction, early initiation and continuation of breastfeeding and providing essential newborn care. Methods: In this prospective cohort study, 400 pregnant women, 200 cases and 200 controls in their third trimester were enrolled. FBAs were given training using flipchart. Thesenewborns were followed up at 1½ month at an immunization clinic. Data were collected and analyzed. Results: 88% (176) of cases initiated breastfeeding in the 1st h of birth compared to 14.5% (29) in controls. 57 (28.5%) of controls had given prelacteal feeds to newborns compared to 7% (14) of cases. 108 (59%) of cases put the baby skin-to-skin contact following delivery compared to none in controls. There was more number of hospital visits in neonates of controls 26.25% (52) compared to cases 12.5% (25). Conclusion: The presence of FBAs improves early initiation of breastfeeding, decreases prelacteal feeds, improves skin-to-skin contact indirectly preventing hypothermia, and decreases the number of hospital visits

Analysis of fixed dose combinations of expectorants, antitussives, decongestants, antihistamines and mucolytics available in the Indian market for rationality and cost variation

Background: Aim of the current study was to analyze the FDCs of expectorants, antitussives, decongestants, antihistamines and mucolytics available in the Indian market for their rationality, cost, and dosage forms. Methods: FDCs involving expectorants, antitussives, decongestants, antihistamines and mucolytics listed on Drug Today and Jan Aushadhi online portal were analysed for rationality according to the list of banned FDCs by CDSCO published on 01 Jan 2018. The FDCs with EADAM available in Jan Aushadhi online portal are compared with cost of different brands with same composition, strength and dosage form available in the Indian market as per the latest drug today. The cost ratio and percentage cost variation were calculated for each FDC. Results: Out of total 340 oral formulations, 268 were liquid and 72 were solid formulations. 228 were Syrups, 67 were Tablets, 23 were Drops, 17 were Suspension and 5 were Capsules. Out of 47 banned FDCs, branded FDC with Ammonium chloride 50mg, Bromhexine 4mg, Dextromethorphan 5mg and Menthol in syrup form was still available for over-the-counter purchase and for online purchase with prescription. Percentage cost variation between branded and generic FDCs ranged from 99% for Terbutaline 2.5 mg and Bromhexine 8 mg to 1081% for Terbutaline 1.25 mg, Bromhexine 4mg, Guaiphenesin 50 mg and Menthol 2.5 mg. Conclusions: One among 47 Banned FDCs was available at both online apps and drug stores. These irrational FDCs can be risk to human lives. The drug authorities need to tune the price of these FDCs as there is a huge percentage cost variation between generic and branded products

Homocystinuria with Cerebral Venous Sinus Thrombosis: Excellent Recovery with Intravenous Recombinant Tissue Plasminogen Activator

How to Cite This Article: Gowda VK, Nanjundappa RC, Pendharkar H, Benakappa N. Homocystinuria with Cerebral Venous Sinus Thrombosis: Excellent Recovery with Intravenous Recombinant Tissue Plasminogen Activator. Iran J Child Neurol. Summer 2017; 11(3):48-52. AbstractHyperhomocysteinemia can cause cerebral venous thrombosis. Recombinant tissue plasminogen activator is one of the treatment options for cerebral venous thrombosis in selected cases. We present here a 7-year-old boy with homocysteinuria with stroke. MRI of brain showed cerebral venous sinus thrombosis. We successfully treated with intravenous recombinant tissue plasminogen activator. He recovered completely without any complications.Recombinant tissue plasminogen activator can be considered one of the treatment options in cerebral venous thrombosis in homocystinura.References1. Fernando D. Testai, MD, PhD; Philip B. Gorelick, MD,MPH. Inherited Metabolic disorders and stroke part 2-Homocystinuria, organic acidurias, and urea cycle disorders. Arch Neurol 2010; 67 (2):148-153.2. Herrmann E, Lorenzl S, Obeid R. Review of the role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric disorders-current evidence and preliminary recommendations. Fortschr Neurol Psychiatr 2007; 75: 515-527.3. Online Mendelian Inheritance in Man. Homocystinuria. http://www.ncbi.nlm.nih.gov/entrez/dispomim. cgi?id=236200. Accessed March 27, 2009.4. udd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, et al. The natural history of homocysteinuria due to cystathionine beta synthase deficiency. Am J Hum Genet 1985; 37: 1-31.5. Hacke W, Doonnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, et al. Association of outcome with early stroke treatment: Pooled analysis of ATLANTIS, ECASS, and NINDS rt –PA stroke trials. Lancet 2004; 363: 768-774.,6. Roach ES, Golomb MR, Adams R, Biller J, Daniels S, Deveber G. et al. Management of stroke in infants and children: a scientific statement from a special writing group of the American Heart Association Stroke Council and the Council on cardiovascular disease in young. Stroke 2008; 39:2644-2691.7. Soleau SW, Schmidt R, Stevens S, Osborn A, MacDonald JD. Extensive experience with dural sinus thrombosis. Neurosurgery 2003; 52: 534-544; discussion 542-544.8. Janjua N, Nasar A, Lynch JK, Qureshi AI. Thrombolysis for ischemic stroke in children: data from the nationwide inpatient sample. Stroke 2007; 38:1850-1854.9. Amlie-Lefond C, deVeber G, Chan AK, Benedict S, Bernard T, Carpenter J et al. Use of alteplase in childhood arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol 2008; 8:530-536

Prediction of Compressive Strength of Corncob Ash Concrete for Environmental Sustainability Using an Artificial Neural Network: A Soft Computing Techniques

Agricultural waste materials are increasingly being used as partial replacements for cement in concrete. Several experimental studies are available to evaluate the mechanical properties of plastic waste reinforced concrete but there are limited evaluations on agricultural waste material. In this study, an attempt is made to investigate the compressive strength of Corn Cob Ash (CCA) concrete at different replacement levels by implementing an Artificial Neural Network (ANN). As the percentage of CCA increases, workability, density and compressive strength decreases, hence the developed ANN model consists of 3 input parameters (cement content, CCA content, and curing ages) in the input layer, 4 hidden neurons in the hidden layer and 3 output parameters (slump, density, and compressive strength) in the output layer. Training is done by adopting Levenberg-Marquardt back-propagation algorithm by considering 80% of experimental data with log-sigmoid activation function for both hidden and output layers. The developed model has a high correlation coefficient of 0.999 for both the training and testing data sets. It has low MSE and MAPE values of 2.2768x10-5 and 1.25 for training data respectively and 3.0463x10-5 and 1.37 for testing data respectively. Hence, it is concluded that the developed model predicts the output at an average rate of 98% accuracy. The predicted 2.5% replaced CCA concrete shows the best performance at all curing ages. Therefore, this percentage level is considered as an optimum replacement level which does not much affect the hardened properties of concrete

FMRP Interacts with C/D Box snoRNA in the Nucleus and Regulates Ribosomal RNA Methylation

Summary: FMRP is an RNA-binding protein that is known to localize in the cytoplasm and in the nucleus. Here, we have identified an interaction of FMRP with a specific set of C/D box snoRNAs in the nucleus. C/D box snoRNAs guide 2’O methylations of ribosomal RNA (rRNA) on defined sites, and this modification regulates rRNA folding and assembly of ribosomes. 2’O methylation of rRNA is partial on several sites in human embryonic stem cells, which results in ribosomes with differential methylation patterns. FMRP-snoRNA interaction affects rRNA methylation on several of these sites, and in the absence of FMRP, differential methylation pattern of rRNA is significantly altered. We found that FMRP recognizes ribosomes carrying specific methylation patterns on rRNA and the recognition of methylation pattern by FMRP may potentially determine the translation status of its target mRNAs. Thus, FMRP integrates its function in the nucleus and in the cytoplasm. : Molecular Interaction; Stem Cells Research; Omics Subject Areas: Molecular Interaction, Stem Cells Research, Omic

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Regulation of Hsp70 function by nucleotide-exchange factors

Protein folding is the process in which polypeptides in their non-native states attain the unique folds of their native states. Adverse environmental conditions and genetic predisposition challenge the folding process and accelerate the production of proteotoxic misfolded proteins. Misfolded proteins are selectively recognized and removed from the cell by processes of protein quality control (PQC). In PQC molecular chaperones of the Heat shock protein 70 kDa (Hsp70) family play important roles by recognizing and facilitating the removal of misfolded proteins. Hsp70 function is dependent on cofactors that regulate the intrinsic ATPase activity of the chaperone. In this thesis I have used yeast genetic, cell biological and biochemical experiments to gain insight into the regulation of Hsp70 function in PQC by nucleotide-exchange factors (NEFs). Study I shows that the NEF Fes1 is a key factor essential for cytosolic PQC. A reverse genetics approach demonstrated that Fes1 NEF activity is required for the degradation of misfolded proteins associated with Hsp70 by the ubiquitin-proteasome system. Specifically, Fes1 association with Hsp70-substrate complexes promotes interaction of the substrate with downstream ubiquitin E3 ligase Ubr1. The consequences of genetic removal of FES1 (fes1Δ) are the failure to degrade misfolded proteins, the accumulation of protein aggregates and constitutive induction of the heat-shock response. Taken the experimental data together, Fes1 targets misfolded proteins for degradation by releasing them from Hsp70. Study II describes an unusual example of alternative splicing of FES1 transcripts that leads to the expression of the two alternative splice isoforms Fes1S and Fes1L. Both isoforms are functional NEFs but localize to different compartments. Fes1S is localized to the cytosol and is required for the efficient degradation of Hsp70-associated misfolded proteins. In contrast, Fes1L is targeted to the nucleus and represents the first identified nuclear NEF in yeast. The identification of distinctly localized Fes1 isoforms have implications for the understanding of the mechanisms underlying nucleo-cytoplasmic PQC. Study III reports on the mechanism that Fes1 employs to regulate Hsp70 function. Specifically Fes1 carries an N-terminal domain (NTD) that is conserved throughout the fungal kingdom. The NTD is flexible, modular and is required for the cellular function of Fes1. Importantly, the NTD forms ATP-sensitive complexes with Hsp70 suggesting that it competes substrates of the chaperone during Fes1-Hsp70 interactions. Study IV reports on methodological development for the efficient assembly of bacterial protein-expression plasmids using yeast homologous recombination cloning and the novel vector pSUMO-YHRC. The findings support the notion that Fes1 plays a key role in determining the fate of Hsp70-associated misfolded substrates and thereby target them for proteasomal degradation. From a broader perspective, the findings provide information essential to develop models that describe how Hsp70 function is regulated by different NEFs to participate in protein folding and degradation.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p

A Two-dimensional Modeling Study of a Planar SOFC using Actual Cell Testing Geometry and Operating Conditions

This paper reports a new electrochemical performance study performed on a planar SOFC cell. This study consists of a 2D model developed using a commercial software, namely Comsol Multiphysics. The model includes fluid dynamics, electrochemistry, electrical conduction, and diffusion physics. This model was built using the actual button cell testing geometry and using experimental data for validation purposes. The objective of this study is to understand the effects of the testing setup used on the cell performance and to recommend an improved design or geometry where the cell performance is independent of any flow maldistribution in both the air and fuel side of the SOFC cell. The air and fuel flow rates are studied to determine the effects on the cell performance. The effects of electrode porosities are studied together with the fuel and air flow rates. The distance from the SOFC cell to the discharge fuel feed tube and air chamber geometry are studied as well. The modeling results indicate that the SOFC electrochemical performance becomes independent of any flow maldistribution at relatively high flow rates for both fuel and air. Reduced electrode porosities play a role in the cell performance, and larger flow rates are required in order to achieve a cell performance independent of flow rates. The cell performance is also affected by the distance from the SOFC cell to the fuel discharge tube and the air chamber geometry. The behavior seen in the cell performance can be explained by a non-uniform mole fraction of reactants near the electrode surface