Design, Synthesis, and Biomedical Applications of Glycotripods for Targeting Trimeric Lectins

In the last decades, various efforts have been made to synthesize optimal glycotripods for targeting trimeric glycoproteins like asialoglycoprotein receptor, hemagglutinin, and langerin. All these trimeric glycoproteins have sugar binding pockets which are highly selective for a particular carbohydrate ligand. Optimized glycotripods are high affinity binders and have been used for delivering drugs or even applied as drug candidates. The selection of the tripodal base scaffold together with the length and flexibility of the linker between the scaffold and sugar residue, as important design parameters are discussed in this review

Effect of epidural volume extension with colloid on dose requirement for intrathecal spinal block: a double blind prospective study

Background: Epidural volume extension (EVE) is a modification of combined- spinal epidural anaesthesia (CSEA) in which fluid is injected in epidural space after the intrathecal block. Fluid in epidural space compress subarachnoid space and causes cephalic spread of intrathecal drug to increase block height. Purpose of study is to determine efficacy of EVE on dose requirement of intrathecal bupivacaine when colloid was used for EVE.Methods: Sixty patients of ASA physical status I or II, scheduled for elective caesarean sections were recruited and randomized into two groups (30 each group). Group 1: CSEA in which spinal block is followed by 10 ml Colloid (HES 6%) in epidural space; Group 2: CSEA but no fluid in epidural space. Onset of sensory block and hemodynamic variables were measured at 5 min. intervals up to 40 minutes then at 10 min. intervals till end of surgery. Ineffective block was top- up by epidural 0.5% bupivacaine in incremental doses.Results: Median effective dose of intrathecal bupivacaine was significantly lower, 4.0 mg (95% CI 4.40-5.60) in group 1 versus 7.0 mg (95% CI 6.93-7.61) in group 2. Only 11 patients required ephedrine in group 1 versus 20 in group 2. Requirement of ephedrine was significantly lower 2.20 (±2.94) mg in group 1 versus 4.0 (±2.88) mg groups 2. Changes in haemodynamic variables from baseline were significantly lower in group 1 than those in group 2.Conclusions: EVE with colloid was effective in lowering dose requirement of spinal bupivacaine while patients hemodynamically were more stable.

A STUDY OF RECOVERY FROM GENERAL ANAESTHESIA AFTER PREOPERATIVE ADMINISTRATION OF ANTIMICROBIAL

ABSTRACT Antimicrobials are used prophylactily in any major surgery to cover perioperative wound infection and other infectious complication ,that may have interaction with muscle relaxant used for general anesthesia and the aim of our study is drug interaction and behavioural response of newly introduced antibiotics used with rocuronium. Gentamicin shortened onset and duration of block after intubating dose of rocuronium and also prolonged duration of extubation after last dose of rocuronium where as meropenem and ceftriaxone did not alter onset, duration and recovery characterstics of rocuronium. . From our study we can conclude that meropenem and ceftriaxone but not gentamicin, can be used safely during general anesthesia. The near ideal muscle relaxant must span the range of short, intermediate and long acting duration (as required by surgical procedure),have rapid onset, be highly metabolized, have no cumulative or cardiovascular effect, to be independent of kidney for elimination, and be easily antagonized. The most commonly used clinical agentsatracurium, doxacurium, vecuronium, pancuronium and pipecuronium-demonstrate some, but not all, of these properties. KEYWORDS : Rocuronium bromide is a relatively new nondepolarizing muscle relaxant. It is the first of these agents to have an onset time possibly as brief as that of suxamethonium without adverse side effect. Rocuronium bromide is mono-quaternary, aminosteroidal, nondepolarizing neuromuscular blocking agent with a rapid onset of actio

Complementary feeding at 4 versus 6 months of age for preterm infants born at less than 34 weeks of gestation: a randomised, open-label, multicentre trial

Background Evidence on the optimal time to initiation of complementary feeding in preterm infants is scarce. We examined the effect of initiation of complementary feeding at 4 months versus 6 months of corrected age on weight for age at 12 months corrected age in preterm infants less than 34 weeks of gestation. Methods In this open-label, randomised trial, we enrolled infants born at less than 34 weeks of gestation with no major malformation from three public health facilities in India. Eligible infants were tracked from birth and randomly assigned (1:1) at 4 months corrected age to receive complementary feeding at 4 months corrected age (4 month group), or continuation of milk feeding and initiation of complementary feeding at 6 months corrected age (6 month group), using computer generated randomisation schedule of variable block size, stratified by gestation (30 weeks or less, and 31–33 weeks). Iron supplementation was provided as standard. Participants and the implementation team could not be masked to group assignment, but outcome assessors were masked. Primary outcome was weight for age Z-score at 12 months corrected age (WAZ12) based on WHO Multicentre Growth Reference Study growth standards. Analyses were by intention to treat. The trial is registered with Clinical Trials Registry of India, number CTRI/2012/11/003149. Findings Between March 20, 2013, and April 24, 2015, 403 infants were randomly assigned: 206 to receive complementary feeding from 4 months and 197 to receive complementary feeding from 6 months. 22 infants in the 4 month group (four deaths, two withdrawals, 16 lost to follow-up) and eight infants in the 6 month group (two deaths, six lost to follow-up) were excluded from analysis of primary outcome. There was no difference in WAZ12 between two groups: –1·6 (SD 1·2) in the 4 month group versus –1·6 (SD 1·3) in the 6 month group (mean difference 0·005, 95% CI –0·24 to 0·25; p=0·965). There were more hospital admissions in the 4 month group compared with the 6 month group: 2·5 episodes per 100 infant-months in the 4 month group versus 1·4 episodes per 100 infant-months in the 6 month group (incidence rate ratio 1·8, 95% CI 1·0–3·1, p=0·03). 34 (18%) of 188 infants in the 4 month group required hospital admission, compared with 18 (9%) of 192 infants in the 6 month group. Interpretation Although there was no evidence of effect for the primary endpoint of WAZ12, the higher rate of hospital admission in the 4 month group suggests a recommendation to initiate complementary feeding at 6 months over 4 months of corrected age in infants less than 34 weeks of gestation

The impact of different fertiliser management options and cultivars on nitrogen use efficiency and yield for rice cropping in the Indo-Gangetic Plain: two seasons of methane, nitrous oxide and ammonia emissions

This study presents detailed crop and gas flux data from two years of rice production at the experimental farm of the ICAR-Indian Agricultural Research Institute, New Delhi, India. In comparing 4 nitrogen (N) fertiliser regimes across 4 rice cultivars (CRD 310, IR-64, MTU 1010, P-44), we have added to growing evidence of the environmental costs of rice production in the region. The study shows that rice cultivar can impact yields of both grain, and total biomass produced in given circumstances, with the CRD 310 cultivar showing consistently high nitrogen use efficiency (NUE) for total biomass compared with other tested varieties, but not necessarily with the highest grain yield, which was P-44 in this experiment. While NUE of the rice did vary depending on experimental treatments (ranging from 41% to 73%), 73%), this did not translate directly into the reduction of emissions of ammonia (NH3) and nitrous oxide (N2O). Emissions were relatively similar across the different rice cultivars regardless of NUE. Conversely, agronomic practices that reduced total N losses were associated with higher yield. In terms of fertiliser application, the outstanding impact was of the very high methane (CH4) emissions as a result of incorporating farmyard manure (FYM) into rice paddies, which dominated the overall effect on global warming potential. While the use of nitrification and urease inhibiting substances decreased N2O emissions overall, NH3 emissions were relatively unaffected (or slightly higher). Overall, the greatest reduction in greenhouse gas (GHG) emissions came from reducing irrigation water added to the fields, resulting in higher N2O, but significantly less CH4 emissions, reducing net GHG emission compared with continuous flooding. Overall, genetic differences generated more variation in yield and NUE than agronomic management (excluding controls), whereas agronomy generated larger differences than genetics concerning gaseous losses. This study suggests that a mixed approach needs to be applied when attempting to reduce pollution and global warming potential from rice production and potential pollution swapping and synergies need to be considered. Finding the right balance of rice cultivar, irrigation technique and fertiliser type could significantly reduce emissions, while getting it wrong can result in considerably poorer yields and higher pollution

Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia

Leukemia stem cells (LSCs) in individuals with chronic myelogenous leukemia (CML) (hereafter referred to as CML LSCs) are responsible for initiating and maintaining clonal hematopoiesis. These cells persist in the bone marrow (BM) despite effective inhibition of BCR–ABL kinase activity by tyrosine kinase inhibitors (TKIs). Here we show that although the microRNA (miRNA) miR-126 supported the quiescence, self-renewal and engraftment capacity of CML LSCs, miR-126 levels were lower in CML LSCs than in long-term hematopoietic stem cells (LT-HSCs) from healthy individuals. Downregulation of miR-126 levels in CML LSCs was due to phosphorylation of Sprouty-related EVH1-domain-containing 1 (SPRED1) by BCR–ABL, which led to inhibition of the RAN–exportin-5–RCC1 complex that mediates miRNA maturation. Endothelial cells (ECs) in the BM supply miR-126 to CML LSCs to support quiescence and leukemia growth, as shown using mouse models of CML in which Mir126a (encoding miR-126) was conditionally knocked out in ECs and/or LSCs. Inhibition of BCR–ABL by TKI treatment caused an undesired increase in endogenous miR-126 levels, which enhanced LSC quiescence and persistence. Mir126a knockout in LSCs and/or ECs, or treatment with a miR-126 inhibitor that targets miR-126 expression in both LSCs and ECs, enhanced the in vivo anti-leukemic effects of TKI treatment and strongly diminished LSC leukemia-initiating capacity, providing a new strategy for the elimination of LSCs in individuals with CML

Patient Safety in the Cardiac Operating Room: Human Factors and Teamwork: A Scientific Study from the American Heart Association

The cardiac surgical operating room (OR) is a complex environment in which highly trained subspecialists interact with each other using sophisticated equipment to care for patients with severe cardiac disease and significant comorbidities. Thousands of patient lives have been saved or significantly improved with the advent of modern cardiac surgery. Indeed, both mortality and morbidity for coronary artery bypass surgery have decreased during the past decade. Nonetheless, the highly skilled and dedicated personnel in cardiac ORs are human and will make errors. Refined techniques, advanced technologies, and enhanced coordination of care have led to significant improvements in cardiac surgery outcomes

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo