Spectrum of Skin Manifestations in CKD: A Tertiary Care Center Experience from North India

Introduction: Dermal manifestations in chronic kidney disease (CKD) patients may range from mild ones, like xerosis, skin pallor, pruritus, coated tongue, superficial infections and hair and nail changes, to severe life-threatening ones, like nephrogenic systemic fibrosis, which is a rare entity in current times. The present study was done to evaluate the spectrum of mucocutaneous manifestations in patients with CKD and to look for an association between them and various biochemical parameters and inflammatory markers. Material and methods: This study was a 1 year prospective, observational study conducted on adult patients with CKD who presented to the Nephrology clinic in Pt. BD Sharma PGIMS, Rohtak. Patients between the ages of 17 and 75 years with CKD stages II or more with dermatological conditions were included in this study. Each participant was subjected to detailed clinical, biochemical, radiological and dermatological examination by same consultants in order to avoid interpersonal variations. Various skin, mucosal, nail and hair manifestations along with cutaneous infections were analyzed across the spectrum of CKD. Results: Among cutaneous infections, fungal infections predominated, amongst which, onychomycosis was the most common. Xerosis was the most common dermatological disease and the prevalence of xerosis, skin pallor and pruritus was found to increase significantly from Stage II to Stage V and VD of CKD in a statistically significant manner. An association was found between xerosis and decreasing levels of hemoglobin and while ferritin was not different between patients with and without xerosis, high-sensitivity C-reactive protein (hs-CRP) was significantly higher in patients with xerosis. Similarly, hs-CRP levels were significantly elevated in patients with xerostomia and nail pallor as compared with those who did not have these conditions. Lastly, patients with nail pallor had significantly lower albumin. Conclusion: It was observed in our study that in CKD patients on hemodialysis and on conservative management, xerosis, pruritus, pigmentation, nail changes, oral mucosa changes and cutaneous infections were the predominant cutaneous manifestations. In patients with CKD, mucocutaneous manifestations progressively worsened as renal function deteriorated

Spectrum of Opportunistic Infections in People Living with HIV: A Tertiary Care Center Experience from North India

: Patients with human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) are proneto opportunistic infections (OIs) given their immunosuppressed state. OIs continue to cause morbidity and mortality in HIV/AIDS patients even after highly-active antiretroviral therapy (HAART); hence, attainment of the goals on health care programs,particularly in resource-poor countries, is hard to achieve. The prevalence of specific OIs varies in different countries and evenin different areas within the same country. Little information is available about the prevalence of OI in HIV patients fromdeveloping countries, especially India. Early diagnosis and prompt treatment contribute to increased life expectancy amonginfected patients delaying progression to AIDS. Hence, the present study was carried out to elucidate current frequencies andspectrum of OIs in HIV seropositive adult patients in Haryana and to evaluate the associated risk factors for OIs. Materialsand methods: This was a cross-sectional study carried out at the Dept. of General Medicine in a tertiary care hospital in NorthIndia. Basic demographic details, anthropometric measurements, symptoms of HIV/OI, clinical examination, biochemicalinvestigations and treatment details were recorded. Patients aged 18 to 70 years and HIV seropositive subjects were includedin the study. Results: The study found that about 53.21% of HIV/AIDS patients on ART had one or more OIs. Tuberculosis(TB) was the predominant OI identified, with a prevalence of 25.71%. Candidiasis and herpes zoster were the second and thethird most prevalent OIs at 13.8% (101/731) and 7.25% (53/731), respectively. Age (43.4 ± 10.7 years), low income, illiteracy,low socioeconomic status, initial 4 months since initiation of ART, CD4 count <200/mm3, body mass index of <18.5 kg/m², poorART adherence, hemoglobin, albumin were strongly associated with OIs. Conclusion: The present study shows that TB is thecommonest OI in adults and the overall population of people living with HIV (PLHIV) in Haryana and proves that OIs acrossdifferent patient groups vary significantly. Various factors like adherence to HAART, socioeconomic and education status ofpatients can influence the occurrence and outcome of these deadly infections

Utility of adzuki bean [Vigna angularis (Willd.) Ohwi & Ohashi] simple sequence repeat (SSR) markers in genetic analysis of mungbean and related Vigna spp.

In the present study, 78 mapped simple sequence repeat (SSR) markers representing 11 linkage groups of adzuki bean were evaluated for transferability to  mungbean and related Vigna spp. 41 markers amplified characteristic bands in at least one Vigna species. The transferability percentage across the genotypes ranged from 60.97 to 92.6% with 87.8% in Vigna radiata and Vigna mungo, 62.2% in Vigna unguiculata, 91.8% in Vigna umbellata, 78% in Vigna mungo var. sylvestris and 80% in Vigna trilobata, respectively. Five major clusters were observed using unweighted pair group method with an arithmetic mean (UPGMA) with each cluster representing a particular Vigna species. We have successfully utilized adzuki bean SSRs in amplifying microsatellite sequences in Vigna species and inferring phylogenetic relationships by correlating the rate of transfer among them. The polymorphic SSR markers identified in this study would be useful in the analysis of genetic diversity, gene mapping and other aspects of genetic studies in mungbean and related species.Key words: Adzuki bean, simple sequence repeat (SSR), inter-genomic marker transferability, genetic diversity, mungbean, Vigna spp

Cancer-selective, single agent chemoradiosensitising gold nanoparticles

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics

Mixed Mediation of Supersymmetry Breaking with Anomalous U(1) Gauge Symmetry

Models with anomalous U(1) gauge symmetry contain various superfields which can have nonzero supersymmetry breaking auxiliary components providing the origin of soft terms in the visible sector, e.g. the U(1) vector superfield, the modulus or dilaton superfield implementing the Green-Schwarz anomaly cancellation mechanism, U(1)-charged but standard model singlet matter superfield required to cancel the Fayet-Iliopoulos term, and finally the supergravity multiplet. We examine the relative strength between these supersymmetry breaking components in a simple class of models, and find that various different mixed mediations of supersymmetry breaking, involving the modulus, gauge, anomaly and D-term mediations, can be realized depending upon the characteristics of D-flat directions and how those D-flat directions are stabilized with a vanishing cosmological constant. We identify two parameters which represent such properties and thus characterize how the various mediations are mixed. We also discuss the moduli stabilization and soft terms in a variant of KKLT scenario, in which the visible sector K\"ahler modulus is stabilized by the D-term potential of anomalous U(1) gauge symmetry.Comment: 30 pages, 5 figure

Singlet-doublet Higgs mixing and its implications on the Higgs mass in the PQ-NMSSM

We examine the implications of singlet-doublet Higgs mixing on the properties of a Standard Model (SM)-like Higgs boson within the Peccei-Quinn invariant extension of the NMSSM (PQ-NMSSM). The SM singlet added to the Higgs sector connects the PQ and visible sectors through a PQ-invariant non-renormalizable K\"ahler potential term, making the model free from the tadpole and domain-wall problems. For the case that the lightest Higgs boson is dominated by the singlet scalar, the Higgs mixing increases the mass of a SM-like Higgs boson while reducing its signal rate at collider experiments compared to the SM case. The Higgs mixing is important also in the region of parameter space where the NMSSM contribution to the Higgs mass is small, but its size is limited by the experimental constraints on the singlet-like Higgs boson and on the lightest neutralino constituted mainly by the singlino whose Majorana mass term is forbidden by the PQ symmetry. Nonetheless the Higgs mixing can increase the SM-like Higgs boson mass by a few GeV or more even when the Higgs signal rate is close to the SM prediction, and thus may be crucial for achieving a 125 GeV Higgs mass, as hinted by the recent ATLAS and CMS data. Such an effect can reduce the role of stop mixing.Comment: 26 pages, 3 figures; published in JHE

Phase Ib study of CP-868,596, a PDGFR inhibitor, combined with docetaxel with or without axitinib, a VEGFR inhibitor

BACKGROUND: Tumoural interstitial hypertension, possibly modulated by platelet-derived and vascular endothelial growth factor receptors (PDGFR and VEGFR), may mediate resistance to chemotherapy. METHODS: Forty-eight patients with advanced solid tumours received oral PDGFR inhibitor CP-868,596 (60-100 mg twice daily (BID)) and docetaxel (75-100 mg m⁻²), or CP-868,596 (60 mg BID), docetaxel (75 mg m⁻²), and VEGFR inhibitor axitinib (5 mg BID). RESULTS: The CP-868,596/docetaxel was escalated as above. The CP-868,596/docetaxel/axitinib was not dose escalated because of increased incidence of mucositis-like adverse events (AEs) with concurrent neutropenia relative to that expected for docetaxel. All tested regimens were tolerable, including 100 mg BID CP-868,596 (recommended phase II dose) plus 100 mg m⁻² docetaxel (maximum approved dose). Most treatment-emergent AEs were mild-moderate and reversible, commonly including nausea, diarrhoea, vomiting, constipation, fatigue, and anaemia (CP-868,596/docetaxel), and hypertension, lethargy, diarrhoea, and fatigue (CP-868,596/docetaxel/axitnib). Pharmacokinetics were unaffected by co-administration. Twenty-one patients achieved stable disease, including all seven evaluable on CP-868,596/docetaxel/axitinib. All nine CP-868,596/docetaxel/axitinib patients received therapy for a median of six (range, 3-16) cycles. CONCLUSIONS: The CP-868,596/docetaxel was well tolerated, but increased efficacy was not observed. Addition of axitinib delivered greater benefits than expected in the number of patients achieving prolonged stable disease with a moderate increase in AEs

Traditional use of medicinal plants among the tribal communities of Chhota Bhangal, Western Himalaya

The importance of medicinal plants in traditional healthcare practices, providing clues to new areas of research and in biodiversity conservation is now well recognized. However, information on the uses for plants for medicine is lacking from many interior areas of Himalaya. Keeping this in view the present study was initiated in a tribal dominated hinterland of western Himalaya. The study aimed to look into the diversity of plant resources that are used by local people for curing various ailments. Questionnaire surveys, participatory observations and field visits were planned to illicit information on the uses of various plants. It was found that 35 plant species are commonly used by local people for curing various diseases. In most of the cases (45%) under ground part of the plant was used. New medicinal uses of Ranunculus hirtellus and Anemone rupicola are reported from this area. Similarly, preparation of "sik" a traditional recipe served as a nutritious diet to pregnant women is also not documented elsewhere. Implication of developmental activities and changing socio-economic conditions on the traditional knowledge are also discussed

Design of cohort studies in chronic diseases using routinely collected databases when a prescription is used as surrogate outcome

BACKGROUND: There has been little research on design of studies based on routinely collected data when the clinical endpoint of interest is not recorded, but can be inferred from a prescription. This often happens when exploring the effect of a drug on chronic diseases. Using the LifeLink claims database in studying the possible anti-inflammatory effects of statins in rheumatoid arthritis (RA), oral steroids (OS) were treated as surrogate of inflammatory flare-ups. We compared two cohort study designs, the first using time to event outcomes and the second using quantitative amount of the surrogate. METHODS: RA patients were extracted from the LifeLink database. In the first study, patients were split into two sub-cohorts based on whether they were using OS within a specified time window of the RA index date (first record of RA). Using Cox models we evaluated the association between time-varying exposure to statins and (i) initiation of OS therapy in the non-users of OS at RA index date and (ii) cessation of OS therapy in the users of OS at RA index date. In the second study, we matched new statin users to non users on age and sex. Zero inflated negative binomial models were used to contrast the number of days' prescriptions of OS in the year following date of statin initiation for the two exposure groups. RESULTS: In the unmatched study, the statin exposure hazard ratio (HR) of initiating OS in the 31451 non-users of OS at RA index date was 0.96(95% CI 0.9,1.1) and the statin exposure HR of cessation of OS therapy in the 6026 users of OS therapy at RA index date was 0.95 (0.87,1.05). In the matched cohort of 6288 RA patients the statin exposure rate ratio for duration on OS therapy was 0.88(0.76,1.02). There was digit preference for outcomes in multiples of 7 and 30 days. CONCLUSIONS: The 'time to event' study design was preferable because it better exploits information on all available patients and provides a degree of robustness toward confounding. We found no convincing evidence that statins reduce inflammation in RA patients

Health impact of US military service in a large population-based military cohort: findings of the Millennium Cohort Study, 2001-2008

<p>Abstract</p> <p>Background</p> <p>Combat-intense, lengthy, and multiple deployments in Iraq and Afghanistan have characterized the new millennium. The US military's all-volunteer force has never been better trained and technologically equipped to engage enemy combatants in multiple theaters of operations. Nonetheless, concerns over potential lasting effects of deployment on long-term health continue to mount and are yet to be elucidated. This report outlines how findings from the first 7 years of the Millennium Cohort Study have helped to address health concerns related to military service including deployments.</p> <p>Methods</p> <p>The Millennium Cohort Study was designed in the late 1990s to address veteran and public concerns for the first time using prospectively collected health and behavioral data.</p> <p>Results</p> <p>Over 150 000 active-duty, reserve, and National Guard personnel from all service branches have enrolled, and more than 70% of the first 2 enrollment panels submitted at least 1 follow-up survey. Approximately half of the Cohort has deployed in support of operations in Iraq and Afghanistan.</p> <p>Conclusion</p> <p>The Millennium Cohort Study is providing prospective data that will guide public health policymakers for years to come by exploring associations between military exposures and important health outcomes. Strategic studies aim to identify, reduce, and prevent adverse health outcomes that may be associated with military service, including those related to deployment.</p