CLINICAL PROFILE, PRESCRIPTION PATTERNS, AND ADVERSE DRUG REACTIONS IN PATIENTS WITH VITILIGO: A PROSPECTIVE STUDY

Objectives: The objectives of the study were to assess clinical profile (age of onset, age of presentation, gender, site of involvement, severity (stage), type of vitiligo, triggering factors, and associated diseases), prescription patterns (monotherapy, combination therapy, oral, topical, and therapeutic categories of drugs prescribed) and to monitor and report adverse drug reactions (based on World Health Organization [WHO] causality assessment scale) in vitiligo patients. Methods: A hospital-based prospective observational study was carried out by evaluating and assessing the clinical profile and prescription patterns of 85 patients who attended dermatology venereology and leprosy (DVL) outpatient department at Sri Padmavathi Medical College for Women, SVIMS, Tirupati, over a period of 6 months from June 2019 to December 2019. Results: In our study, forty four (51.77%) patients were female, vitiligo vulgaris is the most common morphological type observed in twenty seven (31.76%) patients. 31–50 years was the predominant age group. The mean age of onset and presentation was 38.35 (standard deviation of 18.37) and 43.27 (standard deviation of 17.96) years, respectively. Forty-one (48.23%) patients were having Stage 1 vitiligo. Fifty (58.85%) patients were having vitiligo at more than 1 site. Twelve (14.11%) patients were having a positive family history of vitiligo. Thirty-seven (43.53%) patients had triggering factors. Associated diseases were found in thirty (35%) patients. Combination therapy was given to sixty one (71.77%) patients. Topical medications were given to fifty two (61.18%) patients. During the study, we did not have a single patient complaining of any adverse drug reaction. Conclusion: Longer the time after appearance of vitiligo, lesser the number of patients attending follow-up. If vitiligo is diagnosed at the earliest stage, more are the chances for complete repigmentation. Patients with a poor economic background are less bothered about their skin condition and are not using medications properly

Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B <em>Streptococcus</em>

ABSTRACT: Several bacterial pathogens decorate their surfaces with sialic acid (Sia) residues within cell wall components or capsular exopolysaccharides. Sialic acid expression can promote bacterial virulence by blocking complement activation or by engagement of inhibitory sialic acid-binding immunoglobulin-like lectins (Siglecs) on host leukocytes. Expressed at high levels on splenic and lymph node macrophages, sialoadhesin (Sn) is a unique Siglec with an elongated structure that lacks intracellular signaling motifs. Sialoadhesin allows macrophage to engage certain sialylated pathogens and stimulate inflammatory responses, but the in vivo significance of sialoadhesin in infection has not been shown. We demonstrate that macrophages phagocytose the sialylated pathogen group B Streptococcus (GBS) and increase bactericidal activity via sialoadhesin-sialic-acid-mediated recognition. Sialoadhesin expression on marginal zone metallophillic macrophages in the spleen trapped circulating GBS and restricted the spread of the GBS to distant organs, reducing mortality. Specific IgM antibody responses to GBS challenge were also impaired in sialoadhesin-deficient mice. Thus, sialoadhesin represents a key bridge to orchestrate innate and adaptive immune defenses against invasive sialylated bacterial pathogens. KEY MESSAGE: Sialoadhesin is critical for macrophages to phagocytose and clear GBS. Increased GBS organ dissemination in the sialoadhesin-deficient mice. Reduced anti-GBS IgM production in the sialoadhesin-deficient mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-014-1157-y) contains supplementary material, which is available to authorized users

Hampered Foraging and Migratory Performance in Swans Infected with Low-Pathogenic Avian Influenza A Virus

It is increasingly acknowledged that migratory birds, notably waterfowl, play a critical role in the maintenance and spread of influenza A viruses. In order to elucidate the epidemiology of influenza A viruses in their natural hosts, a better understanding of the pathological effects in these hosts is required. Here we report on the feeding and migratory performance of wild migratory Bewick's swans (Cygnus columbianus bewickii Yarrell) naturally infected with low-pathogenic avian influenza (LPAI) A viruses of subtypes H6N2 and H6N8. Using information on geolocation data collected from Global Positioning Systems fitted to neck-collars, we show that infected swans experienced delayed migration, leaving their wintering site more than a month after uninfected animals. This was correlated with infected birds travelling shorter distances and fuelling and feeding at reduced rates. The data suggest that LPAI virus infections in wild migratory birds may have higher clinical and ecological impacts than previously recognised

Understanding How Social Entrepreneurs Fit into the Tourism Discourse

This chapter discusses how social entrepreneurs fit into the existing tourism discourse. It examines four areas of literature in particular, tourism entrepreneurs, sustainability, destination development and intrapreneurship, and analyzes how introducing the concept of social entrepreneurs into these discussions is useful, and contributes to our understanding. Furthermore the paper illustrates that as social entrepreneurs are relevant to a broad range of issues in the tourism literature this should prevent the development of research silos where social entrepreneurship scholars seek out their own vein of research. The nexus of common ground and interests, as displayed in this chapter, should enhance the development of research, thought and understanding of social entrepreneurs within the field as a whole The key argument is that research on social entrepreneurs is not just relevant for those interested in entrepreneurs it also effects our thinking on issues such as destination development, relationships between stakeholders, tourism policy and sustainability. The chapter concludes with a wide range of questions for further research

Highly polymorphic microsatellite markers for the assessment of male reproductive skew and genetic variation in Critically Endangered crested macaques (Macaca nigra)

Genetic analyses based on non-invasively collected samples have become an important tool for evolutionary biology and conservation. Crested macaques (Macaca nigra), endemic to Sulawesi, Indonesia, are important for our understanding of primate evolution as Sulawesi macaques represent an exceptional example of primate adaptive radiation. Crested macaques are also Critically Endangered. However, to date we know very little about their genetics. The aim of our study was to find and validate microsatellite markers useful for evolutionary, conservation and other genetic studies on wild crested macaques. Using faecal samples of 176 wild macaques living in the Tangkoko Reserve, Sulawesi, we identified 12 polymorphic microsatellite loci through cross-species PCR amplification with later modification of some of these primers. We tested their suitability by investigating and exploring patterns of paternity, observed heterozygosity and evidence for inbreeding. We assigned paternity to 63 of 65 infants with high confidence. Among cases with solved paternity, we found no evidence of extra-group paternity and natal breeding. We found a relatively steep male reproductive skew B index of 0.330±0.267; mean±SD) and mean alpha paternity of 65% per year with large variation across groups and years (29-100%). Finally, we detected an excess in observed heterozygosity and no evidence of inbreeding across our three study groups, with an observed heterozygosity of 0.766±0.059 and expected heterozygosity of 0.708±0.059, and an inbreeding coefficient of -0.082±0.035. Our results indicate that the selected markers are useful for genetic studies on wild crested macaques, and possible also other Sulawesi and closely related macaques. They further suggest that the Tangkoko population of crested macaques is still genetically variable despite its small size, isolation and the species’ reproductive patterns. This gives us hope that other endangered primate species living in small, isolated populations may also retain a healthy gene pool, at least in the short term

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Hick and Radhakrishnan on Religious Diversity: Back to the Kantian Noumenon

We shall examine some conceptual tensions in Hick’s ‘pluralism’ in the light of S. Radhakrishnan’s reformulation of classical Advaita. Hick himself often quoted Radhakrishnan’s translations from the Hindu scriptures in support of his own claims about divine ineffability, transformative experience and religious pluralism. However, while Hick developed these themes partly through an adaptation of Kantian epistemology, Radhakrishnan derived them ultimately from Śaṁkara (c.800 CE), and these two distinctive points of origin lead to somewhat different types of reconstruction of the diversity of world religions. Our argument will highlight the point that Radhakrishnan is not a ‘pluralist’ in terms of Hick’s understanding of the Real. The Advaitin ultimate, while it too like Hick’s Real cannot be encapsulated by human categories, is, however, not strongly ineffable, because some substantive descriptions, according to the Advaitic tradition, are more accurate than others. Our comparative analysis will reveal that they differ because they are located in two somewhat divergent metaphysical schemes. In turn, we will be able to revisit, through this dialogue between Hick and Radhakrishnan, the intensely vexed question of whether Hick’s version of pluralism is in fact a form of covert exclusivism.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11841-015-0459-

Transthoracic coronary flow reserve and dobutamine derived myocardial function: a 6-month evaluation after successful coronary angioplasty

After percutaneous transluminal coronary angioplasty (PTCA), stress-echocardiography and gated single photon emission computerized tomography (g-SPECT) are usually performed but both tools have technical limitations. The present study evaluated results of PTCA of left anterior descending artery (LAD) six months after PTCA, by combining transthoracic Doppler coronary flow reserve (CFR) and color Tissue Doppler (C-TD) dobutamine stress. Six months after PTCA of LAD, 24 men, free of angiographic evidence of restenosis, underwent standard Doppler-echocardiography, transthoracic CFR of distal LAD (hyperemic to basal diastolic coronary flow ratio) and C-TD at rest and during dobutamine stress to quantify myocardial systolic (S(m)) and diastolic (E(m )and A(m), E(m)/A(m )ratio) peak velocities in middle posterior septum. Patients with myocardial infarction, coronary stenosis of non-LAD territory and heart failure were excluded. According to dipyridamole g-SPECT, 13 patients had normal perfusion and 11 with perfusion defects. The 2 groups were comparable for age, wall motion score index (WMSI) and C-TD at rest. However, patients with perfusion defects had lower CFR (2.11 ± 0.4 versus 2.87 ± 0.6, p < 0.002) and septal S(m )at high-dose dobutamine (p < 0.01), with higher WMSI (p < 0.05) and stress-echo positivity of LAD territory in 5/11 patients. In the overall population, CFR was related negatively to high-dobutamine WMSI (r = -0.50, p < 0.01) and positively to high-dobutamine S(m )of middle septum (r = 0.55, p < 0.005). In conclusion, even in absence of epicardial coronary restenosis, stress perfusion imaging reflects a physiologic impairment in coronary microcirculation function whose magnitude is associated with the degree of regional functional impairment detectable by C-TD

Chemical intervention in plant sugar signalling increases yield and resilience

The pressing global issue of food insecurity due to population growth, diminishing land and variable climate can only be addressed in agriculture by improving both maximum crop yield potential and resilience. Genetic modification is one potential solution, but has yet to achieve worldwide acceptance, particularly for crops such as wheat. Trehalose-6-phosphate (T6P), a central sugar signal in plants, regulates sucrose use and allocation, underpinning crop growth and development. Here we show that application of a chemical intervention strategy directly modulates T6P levels in planta. Plant-permeable analogues of T6P were designed and constructed based on a ‘signalling-precursor’ concept for permeability, ready uptake and sunlight-triggered release of T6P in planta. We show that chemical intervention in a potent sugar signal increases grain yield, whereas application to vegetative tissue improves recovery and resurrection from drought. This technology offers a means to combine increases in yield with crop stress resilience. Given the generality of the T6P pathway in plants and other small-molecule signals in biology, these studies suggest that suitable synthetic exogenous small-molecule signal precursors can be used to directly enhance plant performance and perhaps other organism function