Stem Cell Antigen CD34 In Native And Engineered Form Alter Its Binding Ability To Stromal Cells And Ligands: A Classical Example Of Clinical Benefits Of Therapeutic Genetic Engineering Of Stem Cells In Transplantation

CD34 is a highly glycosylated surface-expressed sialomucin and, because it is present on hematopoietic stem cells (HSCs), has demonstrated immense clinical utility in their enumeration in aphaeresis products, immunoaffinity purification for transplantation, and disease monitoring. The success of CD34 based reagents in identifying hematopoietic progenitors led to the assumption that CD34 is expressed on cells with regenerative potential and is sufficient for hematopoietic reconstitution in marrow-ablated recipients. However, its role has not been identified in substantial detail. 

With the advent of the fact that CD34 binds adapter protein like CRK-L in cytosol and CD34 knock out studies identified a a signaling role, CD34 antigen has been proposed to play a signaling function. Since it is a sialomucin, a member of the group adhesion molecules, we attempted to identify a role by over-expreesing its gene in cell lines. We report here that CD34 and engineered forms (Ser306 & Tyr318) significantly regulates adhesion to stromal cells, like mesenchymal stem cells and bone marrow ligands. These enhance binding of cells overexpressing CD34 by upregulating integrins and we therefore propose that such cells may effectively potentiate the success of transplantation through greater homing if they are used for transfusion

Association of ADAM33 gene polymorphisms with adult-onset asthma and its severity in an Indian adult population

ADAM33, a member of the ADAM(a disintegrin and metalloprotease) gene family, is an asthma susceptibility gene originally identified by positional cloning. In the present study, we investigated the possible association of five single-nucleotide polymorphisms (SNPs) in the ADAM33 (rs511898, rs528557, rs44707, rs597980 and rs2787094) with adult-onset asthma in an Indian population. The study included 175 patients with mild intermittent (n=44), mild persistent (n=108) or moderate persistent (n=23) subgroups of asthma, and 253 nonasthmatic control individuals. SNPs were genotyped with the help of restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) method, and data were analysed using chi-square test and logistic regression model. Bonferroni’s correction for multiple comparisons was applied for each hypothesis. Genotypes and allele frequencies of SNPs rs511898 and rs528557 were significantly associated with adult-onset asthma(P=0.010-<0.001). A significant association of the homozygous mutant genotype and mutant alleles of SNPs rs2787094, rs44707 and rs597980 with the asthma was also observed (P=0.020-<0.001). A positive association between asthma and haplotypes AGCCT, GGCCT, AGACT, GCAGT, GGACT, ACCCC and AGACC were also found (P=0.036-<0.001,OR=2.07–8.49). Haplotypes AGCGT, GCAGC, ACAGC, ACAGT, GGAGC and GGCGT appear to protect against asthma (P=0.013-<0.0001, OR=0.34–0.10). Our data suggest that ADAM33 gene polymorphisms serve as genetic risk factors for asthma in Indian adult population

Gum Exudation in Relation to Depth of Incisions on Stem-Bark of \u3cem\u3eButea monosperma\u3c/em\u3e L.: A Dominant Interspersed Tree Species in Grazing Lands

Butea monosperma (Palas), a medium-sized deciduous tree belonging to the family Leguminosae-Papilioneae (family Fabaceae), is a native to tropical South Asia, especially from the regions of India (Indo-Gangetic plains). B. monosperma is a gum yielding tree, found naturally in most of the rangelands and grasslands particularly in arid and semi-arid regions. It is an important multipurpose tree for the rural population providing fodder, fibre, fuel wood, gum, medicine and shade. In Bundelkhand it is most widespread species and mainly found in open woodlands, degraded/ pasture lands and forest and farmer’s lands. It is adapted to survive under harsh environmental conditions such as low and erratic rainfall, and intense solar radiation. The green leaves are lopped for fodder and the yield of milk in buffaloes fed with Butea leaves has reportedly improved. The digestibility of butea leaves is comparable to that of straw and caloric content is reported to be 3.761 cal/g dry weights. Gums and resins are almost ubiquitous in plant Kingdom and many of them continue to play an important role in our daily lives. Numerous plants produce some kind of gum and resin, but only a few are commercially important. They have been used as adhesives, emulsifiers, thickening agents, added to varnishes, paint and ink; for aromas added to perfumes and cosmetics and even play a role in pharmacy and medicine (Howes, 1959; Fernandes, 1964; Kaushik and Dhiman, 2000). India is the producer of different gums in international market. Gum-butea is a minor gum. Traditionally, tapping of gumbutea (known as kamarkas) is one of the key livelihood option for tribes particularly the Saharia community in Central India. The gum is collected by Saharia tribe by making incisions or cuts on stem-bark of butea trees (Prasad et al., 2014). They collect the gum and sell it at very nominal price in local market. It has been found that on an average 10-15 trees/ha of B. monosperma are available in farmer’s field which are used by saharia tribe for collecting gum (Prasad et al., 2014). Traditionally, tribal collects gum during November to February, once in a year. The selection of trees for gum collection is done judiciously and only those trees which have at least 25-30 cm girth are marked for gum tapping. For inducing gum oozing, tribal first remove bark or dead bark from the stem. Thereafter, with the help of a special designed bill hook (having three side sharp edges) incision or cuts or tapping are made to depth 1 to 2 cm. After two days of tapping, trees are visited again for collecting gum. The juice or tears are removed from bark with hand or with the help of small knife. The complete process of gum collection is a labour intensive as the tribal family has to visit every tree twice in a season. However, much information is not available about the tapping possibilities of B. monosperma for gum production. Therefore, study was conducted at Central Agroforestry Research Institute, Jhansi to investigate the effect of different depths (0.5 cm, 1.0 cm and 1.5 cm) of incision or cuts made on stem-bark on yield of exuded gum from B. monosperma

Performance of \u3cem\u3eAcacia senegal\u3c/em\u3e L.: Untapped Wealth of Gum Arabic in Rangelands and Grasslands in Arid and Semi-Arid Region of India

Acacia senegal (Linn) Wild a member of Mimosaceae is a small tree of 3-6m in height with umbrella-shaped crown. It is a typical tree of Sahel in Africa from Senegal to red sea and essentially limited to the area between 110 and 160 North, with a wide range of rainfall 100 to 800mm. It spread widely in tropical Africa from Mozambique, Zambia to Somalia, Sudan, Ethiopia, Kenya, Tanzania and Nigeria, and in South Asia in India and Pakistan. In India it is a typical tree of arid regions with a low rainfall of 100-250mm. It is drought resistant and tolerates prolonged dry period of 10-11 months, with maximum temperature reaching 500C with strong winds, but susceptible to frost. It occurs mostly on sand stones and skeletal soils and widely distributed as interspersed species in most of the rangelands and grasslands in arid and semi-arid regions of India. World’s 90% gum Arabic is produced from Acacia senegal. The quality of gum is very superior as compared to gum from any other species of Acacia (Andreson, 1990). Nearly 90% of gum Arabic is produced by Republic of Sudan especially from (Kordafan). Production of gum Arabic is meagre in India, and contribution to the world production is negligible. The total annual output of gum Arabic is only 800 Mt compared to world production and consumption of 60,000-70,000 Mt. The domestic production is insufficient even for domestic consumption and more of it is imported from Sudan and Nigeria to meet India\u27s requirements. Gum exudes from cracks in bark of trees, mostly in the dry season. In Sudan the annual yields from young trees ranges from 188 to 2856 g (av. 0.9 kg), and from older trees, 379 to 6754 g (av. 2.0 kg). In India, however, the productivity is low varying from 175 to 550g tree-1 year-1. The main gum producing regions of India where natural as well as planted stands of A. senegal occur are in desert and arid region of Rajasthan, Gujarat, Haryana, and Punjab. The gum yield from various Acacia trees in their natural habitat is very poor. In arid and semi-arid region of India, particularly in Rajasthan, Gujarat, Haryana, Punjab and Bundelkahand, there is a good scope for extending area for large- scale plantation for production of gum Arabic. The area covered under forest, barren and uncultivable, pasture, oren (temple lands) and community grazing land etc, can be used for commercial plantation of A. senegal. The arid zone of Western Rajasthan is prone to frequent drought and famine and cultivation of gum Arabic can provide livelihood security to desert dwellers. A farmer who has planted 100 trees/ ha at spacing of 10 x 10 m can harvest about 25kg gum assuming average yield of 250g per tree. This would generate revenue of Rs 10000 ha-1 year-1 if, gum is sold at a minimum price of Rs. 400 kg-1. In addition, systematic commercial plantation of Acacia senegal can also provide employment to millions of people towards various planting activities and gum collection. According to an estimate of FAO, gum collection sustains about 0.3 million people and has huge potential of employment. Integration of Acacia senegal in traditional grazing grounds such as orens and gochars, systematically raised silvopastoral systems and other agroforestry landuse for production of gum Arabic can be a profitable proposition. It will not only provide alternative livelihood options to local people but also increase economic viability and sustainability grasslands and pastures. In consideration of wide variations in gum production in respect to sites, annual rainfall and geographical locations, it imperative to study growth performance of A. senegal in different eco-regions and develop site specific models for optimizing production of gum Arabic. This study is a part of research efforts being made at Central Agroforestry Research Institute, Jhansi, which is one of the co-ordinating centres in the ICAR-network project on Natural Resin and Gums headquartered at Indian Institute of Natural Resin and Gums, Ranchi. The main objective is to develope suitable agroforestry models based on gums and resins yielding trees for Bundelkhand region. This paper presents growth performance of A. senegal in semi-arid region of Bundelkhand, Central India

Role of Apoptotic Proteins in REC-2006 Mediated Radiation Protection in Hepatoma Cell Lines

The present study was carried out to evaluate the role of apoptotic proteins in REC-2006-mediated radiation protection in hepatoma cell lines. REC-2006 treatment 2 h before irradiation strongly inhibited the cleavage of ATM and PARP-1 in HepG2 cells. The expression of nuclear apoptosis inducing factor (AIF) was found to be more inhibited (~17%) in HepG2 cells in REC-2006 + radiation-treated group. More inhibition (~33%) of cytochrome c was observed in HepG2 cells upon REC-2006 treatment 2 h prior irradiation. Similarly, significantly more (P<.05) inhibition of Apaf-1, caspase-9 and caspase-3 was observed in REC-2006 + radition-treated group in HepG2 cells. REC-2006 treatment restored the expression of ICAD in HepG2 cells; however, no restoration was observed in Hep3B cells. Lower nuclear to cytoplasmic CAD ratio was observed in HepG2 cells (~0.6) as compared with Hep3B cells (~1.2) in REC-2006 + radiation-treated group. In conclusion, REC-2006 rendered higher protection in HepG2 cells by inhibiting the expression and translocation of AIF, inhibiting the cleavage of ATM and PARP-1, restoring the expression of ICAD, inhibiting the release of cytochrome c and thus modulating the expression of Apaf-1 caspase-9 and activity of caspase-3

Bronchiectasis in India:results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients ( 6518 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p&lt;0\ub70001]) and more likely to be men (1249 [56\ub79%] of 2195). Previous tuberculosis (780 [35\ub75%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13\ub77%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1\ub717, 95% CI 1\ub703-1\ub732; p=0\ub7015), P aeruginosa infection (1\ub729, 1\ub710-1\ub750; p=0\ub7001), a history of pulmonary tuberculosis (1\ub720, 1\ub707-1\ub734; p=0\ub7002), modified Medical Research Council Dyspnoea score (1\ub732, 1\ub725-1\ub739; p&lt;0\ub70001), daily sputum production (1\ub716, 1\ub703-1\ub730; p=0\ub7013), and radiological severity of disease (1\ub703, 1\ub701-1\ub704; p&lt;0\ub70001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Copyright © 2018 The Author(s). Published by Elsevier Ltd. Background A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8-98·1) in Iceland, followed by 96·6 (94·9-97·9) in Norway and 96·1 (94·5-97·3) in the Netherlands, to values as low as 18·6 (13·1-24·4) in the Central African Republic, 19·0 (14·3-23·7) in Somalia, and 23·4 (20·2-26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1-93·6) in Beijing to 48·0 (43·4-53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6-68·8) in Goa to 34·0 (30·3-38·1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view - and subsequent provision - of quality health care for all populations

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016

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

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016.

BACKGROUND: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. METHODS: Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita