Prevalence and clinical characteristics of itch in epidemic-like scenario of dermatophytoses in India: a cross-sectional study.

BACKGROUND: Itch is an integral part of clinical picture of superficial dermatophytoses which constitute a common and growing problem in India. OBJECTIVES: The study aimed to evaluate the prevalence, intensity and clinical characteristics of itch in superficial dermatophytosis. METHODS: The data concerning disease history and clinical type of dermatophytosis were obtained. The presence and various characteristics of itch were documented. Numerical Rating Scale (NRS) was utilized to assess the worst intensity of itch during the last 3 days and during the course of the disease. 4-Item Itch Questionnaire was utilized to assess itch extent, intensity, frequency and associated sleep impairment, while quality of life (QoL) impairment was assessed via Dermatology Life Quality Index. RESULTS: Ninety-nine patients with direct microscopic confirmation of dermatophytosis were included in the study. In 46.5% of subjects, the coexistence of tinea corporis and tinea cruris was noted, followed by tinea cruris (25.2%) and tinea corporis (13.1%). The majority of patients reported itch in the last 3 days (99%) and complained of itch limited to skin lesions (89.9%). According to NRS, the mean intensity of worst itch in the last 3 days was 6.8 ± 1.8 points. Severe and very severe itch was reported by 74.7% of patients. Itch was an isolated sensation in 34.3% of subjects, while 46.9% reported associated burning sensation. Itch was frequently exacerbated by sweating, hot temperature and wearing tight clothes. Difficulties in falling asleep and sleep awakenings were reported by 34.3% and 54.6% of subjects, respectively. Itch negatively influenced the well-being of patients and its intensity correlated with QoL impairment. CONCLUSIONS: Itch is an important symptom in superficial dermatophytoses and is associated with negative impact on sleep and carries a significant psychosocial burden. Acknowledging its presence is necessary in a holistic approach to these patients.

Evaluating the role of dithiolane rich fraction of Ferula asafoetida (apiaceae) for its antiproliferative and apoptotic properties: in vitro studies.

Asafoetida resin has been reported for various biological activities but its use has been widely restricted owing to its pungent smell and pool water solubility. AIM: In vitro study of the anticancer potential of microwave-extracted essential oil (EO) of Ferula asafoetida. MATERIALS AND METHODS: The phytochemical investigation and in vitro cytotoxicity assessment was carried out in two human liver cancer cell lines. The expression of NFKB1, TGFB1, TNF, CASP3 was analyzed by reverse transcription polymerase chain reaction. RESULTS: Ferula asafoetida EO contains high concentrations of dithiolane, which possess antiproliferative activity in human liver carcinoma cell lines (HepG2 and SK-Hep1) in a dose-dependent manner. The bioactive compounds in F. asafoetida are capable of induction of apoptosis and altered NF-kB and TGF-ß signalling with increase in caspase-3 and TNF-α expression. CONCLUSION: Further elucidation of bioactive molecules and underlying mechanisms could lead to potential intervention in liver cancer in animal models. The safety and efficacy as well as the mode of EO action in animal models would be highly crucial.

Dynamic prediction of transition to psychosis using joint modelling.

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.

Medical assistance in dying for cancer patients one year after legalization: a collaborative approach at a comprehensive cancer centre.

Medical assistance in dying (maid) is a new medical service in Canada. Access to maid for patients with advanced cancer can be daunting during periods of declining health near the end of life. In this report, we describe a collaborative approach between the centralized coordination service and a regional cancer centre as an effective strategy for enabling interdisciplinary care delivery and enhancing patient-centred care at the end of the patient's cancer journey.

High correlation of clinical criteria in the diagnosis of drug-resistant TB and prevalence of ofloxacin resistance.

OBJECTIVE: To study the drug resistance profile of patients with suspected multidrug-resistant tuberculosis (MDR-TB). MATERIAL AND METHODS: This was a prospective study conducted among patients with suspected MDR-TB attending the Department of Respiratory Medicine, King George's Medical University, Lucknow, India, from August 2014 to April 2015. Sputum samples obtained from 50 such patients were subjected to drug susceptibility testing against first- and second-line drugs. Data on baseline characteristics were obtained from the patients and their previous medical records. RESULTS: Mycobacterium tuberculosis was detected in 47/50 (94%) and non-tuberculous mycobacteria (NTM) in 3/50 (6%). Of the 47 patients with M. tuberculosis, 36 (76.6%) had MDR-TB: 24 (66.7%) of these had pre-extensively drug-resistant TB (pre-XDR-TB) and 4 (11.1%) had XDR-TB. CONCLUSIONS: Among proven MDR-TB cases, approximately two thirds were pre-XDR-TB cases and more than 10% were XDR-TB cases. These form a sizeable proportion and may result in the failure of second-line treatment.

2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards, individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included in the Supplementary Material, and on the CCS Web site. The section on concomitant AF and coronary artery disease was developed in collaboration with the CCS Antiplatelet Guidelines Committee. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF Guidelines recommendations, from 2010 to the present 2016 Focused Update

Quercetin sensitizes fluconazole-resistant candida albicans to induce apoptotic cell death by modulating quorum sensing.

Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections.

Biophysicochemical evaluation of wild hilly biotypes of Jatropha curcas for biodiesel production and micropropagation study of elite plant parts.

Depleting reserves of fossil fuel and increasing effects of environmental pollution from petrochemicals demands eco-friendly alternative fuel sources. Jatropha curcas oil, an inedible vegetable oil, can be a substitute feedstock for traditional food crops in the production of environment-friendly and renewable fuel. Jatropha oil is looked up in terms of availability and cost and also has several applications and enormous economic benefits. The seed oils of various jatropha biotypes from hilly regions were screened out and evaluated for their physiochemical parameters, viz, seed index(520-600 g), oil content (15-42 %), biodiesel yield (71-98 %), moisture content (2.3-6.5 %), ash content (3.2-5.6 %), acid value (4.2-26), density (0.9172-0.9317 g/cm(3)), viscosity (5-37 mm(2)/s), saponification value (195.8-204.2 mg/g), iodine value (106.6-113.6 mg/g), flash point (162-235 °C), cetane value (46.70-50.06 °C), free fatty acid value (2.5-10.2 %), and refractive index (1.4600-1.4710). Fatty acid profiling of jatropha resembles as edible oilseeds. NAA with BAP was found to be superior for callus induction (up to 87 %), as well as for shoot regeneration (up to12 shoots). Root induction (90-100 %) was successfully obtained in MS medium with or without phytoregulators. Grown plantlets were successfully transferred from lab to field with a survival rate of 80 %.

Calcium and magnesium elimination enhances accumulation of cardenolides in callus cultures of endemic Digitalis species of Turkey.

Elimination of calcium (Ca), magnesium (Mg) or both from the medium of callus cultures of Digitalis davisiana Heywood, Digitalis lamarckii Ivanina, Digitalis trojana Ivanina and Digitalis cariensis Boiss. ex Jaub. et Spach increased cardenolides production. Callus was induced from hypocotyl segments from one-month old seedlings were cultured on MS medium containing 0.5 µg ml(-1) thidiazuron (TDZ) and 0.25 µg ml(-1) indole acetic acid (IAA). After 30 days of culture, callus was transferred in hormone-free MS medium (MSO) as well as Ca or Mg or both were completely eliminated from same medium. The amount of five cardenolides from D. davisiana Heywood, D. lamarckii Ivanina, D. trojana Ivanina and D. cariensis Boiss. ex Jaub. et Spach were compared. Higher amounts of five cardenolides and total cardenolides were obtained when callus of four Digitalis species were incubated on MS medium lacking both Ca and Mg. The mean contents of total cardenolides obtained were in the order of D. lamarckii (2017.97 µg g(-1))>D. trojana (1385.75 µg g(-1))>D. cariensis (1038.65 µg g(-1))>D. davisiana (899.86 µg g(-1)) when both Ca and Mg were eliminated from the medium, respectively. This protocol is useful for development of new strategies for the large-scale production of cardenolides.

Antibacterial and antioxidant activity of lichen species Ramalina roesleri.

Solvent extracts of Ramalina roesleri Nyl were assayed for antimicrobial and antioxidant activity. Hexane extract was highly active against Staphylococcus aureus and Streptococcus mutans. The 1,1-diphenyl-2-picryl-hydrazil (DPPH) radical scavenging activity of extracts ranged from 29.42% to 87.90%. Atranorin, protolichesterinic acid, usnic acid, 2-hydroxy-4-methoxy-6-propyl benzoic acid, homosekikaic acid, sekikaic acid, benzoic acid, 2,4-dihydroxy-6-propyl and 2,4-dihydroxy-3,6-dimethyl benzoate were isolated from the hexane extract. Maximum DPPH radical scavenging activity was exhibited by sekikaic acid followed by homosekikaic acid.

Heat shock protein 60 of filarial parasite Brugia malayi: cDNA cloning, expression, purification and in silico modeling and analysis of its ATP binding site.

We report here cloning and expression of full length mitochondrial HSP60 gene of Brugia malayi adult worm (mtHSP60bm), purification of the gene product by affinity chromatography, its in silico 3D structure and the sequence homology of the protein with Escherichia coli GroEL/ES and human HSP60. The ATP binding pocket of human HSP60 and mtHSP60bm were analyzed and compared using in silico models. The distribution of HSP60 in different life-stages of the parasite was determined using antibodies raised against recombinant mtHSP60bm (rmtHSP60bm). mtHSP60bm was present in all life-stages of the parasite except third stage infective larvae, in which it could be induced by heat-shock, and showed high degree of homology with E. coli GroEL/ES. The ATP binding pocket of HSP60 in humans, E. coli and B. malayi were also found structurally conserved. This similarity between human and mtHSP60bm might be useful in understanding the host-parasite interactions. This is the first ever report on distribution, cloning, sequence homology and ATP binding site of mtHSP60bm.

Membrane-damaging potential of natural L-(-)-usnic acid in Staphylococcus aureus.

The purpose of this investigation was to try to understand the antibacterial mechanism of L-(-)-usnic acid isolated for the first time from fruticose lichen Usnea subfloridana using clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of L-(-)-usnic acid against the clinical isolates of MRSA and reference strain S. aureus MTCC-96 (SA-96) was in the range 25-50 µg/ml. Treatment of both reference and clinical strains (MRSA-ST 2071) with four-fold MIC concentrations (100-200 µg/ml) of L-(-)-usnic acid reduced the viability of cells without damaging the cell wall. However, the loss of 260 nm absorbing material and increase in propidium iodide uptake was observed in both of the strains. Similarly, a combined effect of L-(-)-usnic acid (25-50 µg/ml) and 7.5 % NaCl resulted in a reduced number of viable cells within 24 h in comparison to the control. These observations clearly indicate that L-(-)-usnic acid exerts its action by disruption of the bacterial membrane. Further, in vivo efficacy showed that L-(-)-usnic acid significantly (p < 0.001) lowered the microbial load of spleen at doses ranging from 1 to 5 mg/kg. Further, toxicity studies in infected mice at doses 20 times higher than the efficacious dose indicated L-(-)usnic acid to be safe. Paradoxically, L-(-)usnic acid exhibited changes in serum triglycerides, alkaline phosphatase (ALKP) and liver organ weight in the healthy mice administered with only 25 mg/kg body weight. The results obtained in this study showed that natural L-(-)-usnic acid exerts its antibacterial activity against MRSA by disruption of the cell membrane. Further, the natural L-(-)-usnic acid was found to be safe up to 100 mg/kg body weight, thereby, making it a probable candidate for treating S. aureus infections.

Bioavailability, antioxidant and non toxic properties of a radioprotective formulation prepared from isolated compounds of Podophyllum hexandrum: a study in mouse model.

The current study was aimed to determine the stability, serum protein binding ability, biodistribution, antioxidant potential and tissue toxicity status of a novel radioprotective formulation (G-002M) from Podophyllum hexandrum. G-002M is the combination of a flavonoid, a lignan and its glucoside isolated from P. hexandrum rhizome that exhibit high radioprotective potential. Stability of G-002M tagged with 99mTc was observed in vitro and with mice serum till 24 hr of incubation. The formulation was investigated for its antioxidant status and its bioavailability and toxicity in different organs of mice. Biodistribution study of 99mTc-G-002M revealed its uptake by all the vital organs of mice. Higher absorbed dose was observed in lungs, liver, jejunum and kidney. Maximum retention of G-002M in kidney revealed that G-002M was excreted predominantly through renal route. G-002M was also observed to have high free radical scavenging and total reducing properties. Histopathological observations showed no significant alterations in tissue morphology of lungs, liver, jejunum and kidney by G-002M administration. The data conclusively demonstrate that high stability, multi organ availability, longer retention and non-toxic behavior of G-002M might help in exhibiting strong protective potential against lethal radiation.

Effect of Pueraria tuberosa DC. (Indian Kudzu) on blood pressure, fibrinolysis and oxidative stress in patients with stage 1 hypertension.

The Indian Kudzu (Pueraria tuberosa DC.) is an important medicinal plant widely used in Indian and Chinese traditional systems of medicine. The present study is an attempt to evaluate effect of its tubers on blood pressure, coagulation parameters and antioxidant status in patients with stage 1 (primary) hypertension. In a long-term, single blinded, placebo controlled study; 15 patients with stage 1 hypertension (group 1), were administered 3 g P. tuberosa in two divided doses while another 15 patients (group II) were administered matched placebo for a period of twelve weeks. A significant fall of 25, 11 and 16 mmHg was observed in systolic (p < 0.001), diastolic (p < 0.05) and mean (p < 0.001) blood pressure, respectively at the end of the study. Along with blood pressure reduction, there was a significant (p < 0.01) reduction in plasma fibrinogen and significant enhancement of plasma fibrinolytic activity (p < 0.001) and serum total antioxidant status (p < 0.05). It was tolerated well without any untoward side effects.

Inhibition in radiation mediated cellular toxicity by minimizing free radical flux: one of the possible mechanisms of biological protection against lethal ionizing radiation by a sub- fraction of Podophyllum hexandrum.

The study has focused on exploring the mechanism of action of Podophyllum hexandrum sub-fraction (G-001M) exhibiting >90% protection in lethally irradiated mice. Currently, G-001M was assessed for antioxidant characteristics by evaluating DPPH, superoxide and hydrogen peroxide radical formation, anti-lipid per oxidation, metal chelation and total flavonoid content. To affirm cytoprotective efficacy of G-001M, plasmid DNA protection, blood WBC counts, marker for lipid peroxidation (MDA) and antioxidant status (GSH) in mice splenocytes and thymocytes were studied. G-001M, having high amount of total phenolic contents (200±10mg, w/w), exhibited dose dependent inhibition in DPPH and superoxide radical formation. Hydrogen peroxide radical scavenging was higher than standards. With pre-treatment of G-001M, plasmid DNA was also maximally restored to supercoiled form. Radiation modulated MDA and GSH values in splenocytes and thymocytes of mice altered significantly after 24 hrs and at later intervals, values were close to the controls. Radiation mediated losses in WBC counts were significantly regained (p<0.001) in G-001M pre-treated irradiated mice. The above findings explicitly conveyed that G-001M has successfully minimized radiation inflicted free radicals generation and their multiplication. This activity of G-001M could be undoubtedly among one of the major modes of action in extending whole body survival in lethally irradiated mice.

Synthesis, anticonvulsant and toxicity screening of newer pyrimidine semicarbazone derivatives.

A number of N-(4,6-substituted diphenylpyrimidin-2-yl) semicarbazones (4a-t) were synthesized and tested for their anticonvulsant activity against the two seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). All the synthesized compounds possessed the four essential pharmacophoric elements for good anticonvulsant activity. Most of the compounds displayed good anticonvulsant activity with lesser neurotoxicity. To assess the unwanted effects of the compounds on liver, estimation of enzymes and proteins was carried out.

HIV: a raft-targeting approach for prevention and therapy using plant-derived compounds (review).

It has been widely accepted that HIV-1 enters into and buds out from microdomains known as lipid rafts/caveolae of plasma membranes of infected cells. Since lipid rafts are recognized sites for budding and entry of HIV-1, and since lipids in rafts (including composition/dynamic structure) play a crucial role in modulating the functions of raft-associated signaling proteins and receptors, it has been consistently shown that modulating the composition/structure of lipid rafts have influenced the life cycle of HIV-1 inhibiting its replication. Since anti-retroviral multi-drugs treatment has severe side effects, one of the strategies could be to block the HIV-1 entry and its replication using natural compounds that can target lipid rafts. Dietary and plant-derived compounds have advantage over synthetic drugs exhibiting minimum side effects and are available in cost effective manner. Studies exploring the effects of dietary and plant-derived compounds targeting lipid rafts could be an evolving strategy to control the progression of AIDS. This article is intended to review: (i) composition/structure and conditions for the formation of lipid rafts in plasma membranes, (ii) interaction of HIV-1 with lipid rafts and (iii) to introduce a novel concept that dietary and plant-derived compounds, which can target lipid rafts, could have potential preventive/therapeutic values against the progression of AIDS. More emphasis has been given to the roles of omega-3 fatty acids and plant-derived various triterpenes, especially euphane-types of triterpenes extracted from Neem tree, targeting lipid rafts and its major component cholesterol.

Oil and fatty acid diversity in genetically variable clones of Moringa oleifera from India.

The physico-chemical properties of oil from Moringa oleifera seeds from India were determined in the present study. The petroleum ether extracted oil ranged from 27.83 - 45.07% on kernel basis and 15.1-28.4% on whole seed basis in 20 different clones. Leaves and pods showed a good source of vitamin C. Oleic acid (C18:1) has been found to be the major fatty acid being 78.91-85.52% as compared to olive oil, which is considered to be richest source of oleic acid. All the clones from India did not show any presence of behenic acid (C 22:0). The oil was also found to contain high levels of beta-sitosterol ranged from 42.29-47.94% stigmasterol from 13.66-16.61%, campesterol from 12.53-16.63%. The gamma- and delta-tocopherol were found to be in the range of 128.0-146.95, 51.88-63.5 and 55.23-63.84 mg/kg, respectively.

A practical guide to the management of menopausal symptoms in breast cancer patients.

Breast cancer is the most frequently diagnosed cancer in Canadian women. As a result of increased screening and improved treatment, more women are becoming long-term breast cancer survivors. However, due to either their treatment or prolonged survival, many of these women now have to face the consequences of premature menopause and prolonged estrogen deprivation. Hormone replacement therapy/estrogen replacement therapy (HRT/ERT) has, in the past, been recommended to healthy women at menopause not only for relief of short-term menopausal changes, particularly hot flashes, but also for its benefits on bone density, fracture reduction, and genitourinary symptoms. Recent studies have demonstrated that not only is HRT associated with an increased risk of developing breast cancer, but it also has been shown to increase the risk of recurrence in those with a breast cancer history. Until the safety of HRT/ERT in breast cancer patients can be more fully clarified, it would be wise to develop alternative strategies for the management of menopausal symptoms in these patients. This paper will discuss nonestrogen-based therapies for hot flashes, osteoporosis, and genitourinary symptoms, with emphasis on efficacy and safety in breast cancer survivors.