The translational repressors Nanos and Pumilio have divergent effects on presynaptic terminal growth and postsynaptic glutamate receptor subunit composition

Pumilio (Pum) is a translational repressor that binds selectively to target mRNAs and recruits Nanos (Nos) as a corepressor. In the larval neuromuscular system, Pum represses expression of the translation factor eIF-4E and the glutamate receptor subunit GluRIIA. Here, we show that Nos, like Pum, is expressed at the neuromuscular junction (NMJ) and in neuronal cell bodies. Surprisingly, however, Nos and Pum have divergent functions on both the presynaptic and postsynaptic sides of the NMJ. In nos mutant and nos RNA interference larvae, the number of NMJ boutons is increased, whereas loss of Pum reduces the bouton number. On the postsynaptic side, Nos acts in opposition to Pum in regulating the subunit composition of the glutamate receptor. NMJ active zones are associated with GluRIIA- and GluRIIB-containing receptor clusters. Loss of Nos causes downregulation of GluRIIA and increases the levels of GluRIIB. Consistent with this finding, the electrophysiological properties of NMJs lacking postsynaptic Nos suggest that they use primarily GluRIIB-containing receptors. Nos can regulate GluRIIB in the absence of GluRIIA, suggesting that the effects of Nos on GluRIIB levels are at least partially independent of synaptic competition between GluRIIA and GluRIIB. Nos is a target for Pum repression, and Pum binds selectively to the 3' untranslated regions of the nos and GluRIIA mRNAs. Our results suggest a model in which regulatory interplay among Pum, Nos, GluRIIA, and GluRIIB could cause a small change in Pum activity to be amplified into a large shift in the balance between GluRIIA and GluRIIB synapses

NEBULIZED GLYCOPYRRONIUM AND FORMOTEROL, BUDESONIDE AEROSOL AERODYNAMIC ASSESSMENT WITH VIBRATING MESH AND COMPRESSOR AIR NEBULIZER: ANDERSON CASCADE IMPACTOR STUDY

Vibrating mesh nebulizers (VMN) demonstrate improved efficiency for delivery of inhaled aerosol solutions or suspensions as compared to compressor devices. The added advantages of compactness, portability and functioning as noise-free device makes them of incremental value in Home or Ambulatory settings while managing Severe Obstructive airway disease or delivery of maintenance medications in these cases. This further circumvents the need for multiple devices thereby further improving patient compliance and convenience while delivering acute or maintenance formulations including Glycopyrronium (GLY) and Formoterol (FRM)/Budesonide(BUD) nebulizing solution formulations. To further assess the clinical role and feasibility of FRM-BUD formulation delivery kinetics  with or without GLY nebulizing solution through VMN and jet  nebulizers for In- & outpatient settings, 2 comparative in-vitro lung deposition studies were carried out utilizing Anderson Cascade impactor at 30 L/min; deposited drug concentrations in different stages were suitably collected and estimated by HPLC. Post-hoc analyses with p<0.05 was considered statistically significant for intergroup differences on FRM/BUD and GLY delivered through VMN or Compressor devices.  The calculated mean fine particle dose for FRM & BUD delivered by VMN or jet nebulizer showed no statistical difference. However the mean fine particle fraction for BUD delivered by VMN was significantly better compared to jet nebulizer than that for FRM. The Residual volume at 10 mins was significantly higher with jet nebulizer. The optimal APSD for GLY nebulizing solution admixture with FRM/BUD suspension delivered through VMN and Jet nebulizer offers a clinically relevant strategy for High risk COPD cases in Acute or Home settings

Physicochemical properties of various alginate-based raft-forming antacid products: a comparative study

Background: Alginate-based, raft-forming antacid products with reflux suppressant activity are complex formulations expected to achieve effective raft formation and cause elimination or displacement of the acid pocket, which is typically manifested in gastroesophageal reflux disease (GERD).Methods: In the present study, six alginate-based raft-forming products commercially available in the Indian market were compared in terms of their acid neutralization properties, strength, resilience and structural and thermal properties of their rafts. Percent alginate content was also determined.Results: Rafts of products containing calcium-based antacids formed voluminous, porous and floating rafts within seconds of addition to the simulated gastric fluid (SGF) compared with the products that contained aluminium and magnesium-based antacids. Marked differences were not evident in the ANC (acid neutralization capacity) values of the various products. No correlation was observed between ANC and raft-forming capacity or duration of neutralization. Raft structures affected their neutralization profiles. Rafts of porous and absorbent nature could retain their ANC probably due to release of trapped antacids. Further, raft strengths of only two products were above the British Pharmacopoeia specification of not less than 7.5 g. Sodium alginate content was within specifications (85-115%) for three of the six products.Conclusions: Raft-forming formulations with higher alginate content and calcium-based antacids have better physicochemical properties such as ANC, neutralization profiles, raft strength and raft resilience than those with lower alginate content or those containing aluminium or magnesium-based antacids

Topical Formulations of Serratiopeptidase: Development and Pharmacodynamic Evaluation

Serratiopeptidase, an enzyme derived from Serratia marcescences strain E-15 (ATCC 21074), present in the gut wall of the silk worm possesses anti-inflammatory properties, and can prove to be a suitable alternative to commonly used non steroidal antiinflammatory agents. Being sensitive to gastric degradation, serratiopeptidase is conventionally given orally in the form of enteric coated tablet formulations. Topical formulations of serratiopeptidase would be useful to treat local inflammations and may prove to be more effective compared to non steroidal antiinflammatory agents. The present study investigates the feasibility of developing topical preparations of serratiopeptidase in the form of ointments and gels. Excipient compatibility of serratiopeptidase with various excipients and polymers, formulation development, characterization and stability studies have been carried out. Stable formulation was evaluated for anti-inflammatory activity by oxazolone induced ear edema method in mice and allergenic potential by passive cutaneous anaphylaxis

Njagala ekyo

This is a story narrated about a child who liked particular Items.This is a story narrated about a child who liked particular Items

Development and Evaluation of Dry Powder Inhalation System of Terbutaline Sulphate for Better Management of Asthma

Terbutaline sulphate (TBS), a bronchodilator (β2 agonist) has a short half-life, hence frequent administration (4-6 times a day) is necessary, resulting in patient compliance problems. Therefore long acting TBS inhalation formulations are desirable to improve patient compliance, reduce toxicity and hence achieve better management of asthma. Microparticulate dry powder inhalation delivery systems for sustained pulmonary drug delivery have been particularly attractive. In the present investigation, TBS loaded chitosan microspheres for pulmonary delivery were prepared by emulsification and ionotropic gelation method. The microspheres were characterized for drug content, particle size, densities, flow properties, moisture content and surface topography by SEM; in vitro drug release was evaluated in simulated lung fluid at 370 at pH 7.4. The respirable or fine particle fraction (FPF) was determined by using twin stage impinger (TSI). Further stability evaluation of TBS loaded DPI systems was carried out at 250/ 60% RH and at 400C/ 75% RH.Keywords: Turbutaline sulphate, microspheres, pulmonary delivery, Dry powder inhalation

Early enteral nutrition therapy in congenital cardiac repair postoperatively: A randomized, controlled pilot study

Background and Objectives: Adequate nutritional supplementation in infants with cardiac malformations after surgical repair is a challenge. Critically ill infants in the early postoperative period are in a catabolic stress. The mismatch between estimated energy requirement (EER) and the intake in the postoperative period is multifactorial, predisposing them to complications such as immune deficiency, more infection, and growth failure. This study aimed to assess the feasibility and efficacy of enriched breast milk feed on postoperative recovery and growth of infants after open heart surgery. Methodology: Fifty infants <6 months of age were prospectively randomized in the trial for enteral nutrition (EN) postoperatively from day 1 to 10, after obtaining the Institute Ethics Committee's approval. They were equally divided into two groups on the basis of the feed they received: Control group was fed with expressed breast milk (EBM; 0.65 kcal/ml) and intervention group was fed with EBM + energy supplementation/fortification with human milk fortifier (7.5 kcal/2 g)/Simyl medium-chain triglyceride oil (7.8 kcal/ml). Energy need for each infant was calculated as per EER at 90 kcal/kg/day, as the target requirement. The intra- and post-operative variables such as cardiopulmonary bypass and aortic cross-clamp times, ventilation duration, Intensive Care Unit (ICU), and hospital length of stay and mortality were recorded. Anthropometric and hematological parameters and infection control data were recorded in a predesigned pro forma. Data were analyzed using Stata 14.1 software. Results: The duration of mechanical ventilation, length of ICU stay (LOIS), length of hospital stay (LOHS), infection rate, and mortality rate were lower in the intervention group compared to the control group although none of the differences were statistically significant. Infants in control group needed mechanical ventilation for about a day more (i.e., 153.6 ± 149.0 h vs. 123.2 ± 107.0 h; P = 0.20) than those in the intervention group. Similarly, infants in control group stayed for longer duration in the ICU (13.2 ± 8.9 days) and hospital (16.5 ± 9.8 days) as compared to the intervention group (11.0 ± 6.1 days; 14.1 ± 7.0 days) (P = 0.14 and 0.17, respectively). The LOIS and LOHS were decreased by 2.2 and 2.4 days, respectively, in the intervention group compared to control group. The infection rate (3/25; 5/25) and mortality rate (1/25; 2/25) were lower in the intervention group than those in the control group. The energy intake in the intervention group was 40 kcal more (i.e., 127.2 ± 56.1 kcal vs. 87.1 ± 38.3 kcal) than the control group on the 10th postoperative day. Conclusions: Early enteral/oral feeding after cardiac surgery is feasible and recommended. In addition, enriching the EBM is helpful in achieving the maximum possible calorie intake in the postoperative period. EN therapy might help in providing adequate nutrition, and it decreases ventilation duration, infection rate, LOIS, LOHS, and mortality

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial

Objectives: To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. Design: Economic evaluation from healthcare system and societal perspectives. Setting: Ten diverse urban clinics in India and Pakistan. Participants: 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. Intervention: Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. Outcome measures: Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c \u3c7% (53 mmol/mol) and SBP \u3c130/80 mmHg or LDLc \u3c2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$4847.6). Results: Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and$1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was$33,399.6 from a societal perspective. Conclusions: In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMIC

Factors affecting achievement of glycemic targets among type 2 diabetes patients in south Asia: Analysis of the CARRS trial

Objective: To assess the predictors of achieving and maintaining guideline-recommended glycemic control in people with poorly controlled type 2 diabetes.Methods: We analyzed data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) Trial (n=1146), to identify groups that achieved guideline-recommended glycemic control (HbA1c\u3c7%) and those that remained persistently poorly controlled (HbA1c\u3e9%) over a median of 28 months of follow-up. We used generalized estimation equations (GEE) analysis for each outcome i.e. achieving guideline-recommended control and persistently poorly controlled and constructed four regression models (demographics, disease-related, self-care, and other risk factors) separately to identify predictors of HbA1c\u3c7% and HbA1c\u3e9% at the end of the trial, adjusting for trial group assignment and site.Results: In the final multivariate model, adherence to prescribed medications (RR: 1.46, 95%CI: 1.09, 1.95), adherence to diet plans (RR: 1.79, 95% CI: 1.43, 2.23) and middle-aged: 50-64 years (RR: 1.32; 95% CI: 1.02-1.71) were associated with achieving guideline-recommended control (HbA1c \u3c7%). Presence of microvascular complications (RR: 0.70; 95%CI: 0.53-0.92) reduced the probability of achieving guideline-recommended glycemic control (HbA1c 7%). Further, longer duration of diabetes (\u3e15 years), RR: 1.41; 95% CI: 1.15, 1.72, hyperlipidemia, RR: 1.19; 95% CI: 1.06, 1.34 and younger age group (35-49 years vs. \u3e64 years: RR: 0.61; 95% CI: 0.47-0.79) were associated with persistently poor glycemic control (HbA1c\u3e9%).Conclusion: To achieve and maintain guideline-recommended glycemic control, care delivery models must put additional emphasis and effort on patients with longer disease duration, younger people and those having microvascular complications and hyperlipidemia