Treatment of dermatophyte toenail onychomycosis with itraconazole

Background: Onychomycosis is fungal infection of nail. The prevalence of onychomycosis varies across the world. It is lower in tropical countries (3.8%) than in sub-tropical countries and countries in the temperate zone (23%). The risk of onychomycosis is higher in persons with diabetes mellitus and human immunodeficiency virus infection. Systemic antifungals are recommended for treatment. Topical antifungals are less effective. Different cure rates have been reported by different authors for terbinafine, itraconazole and fluconazole therapy. A variety of regimens (continuous or pulse) have also been suggested.Methods: Here in this study we report a prospective, observational, cohort study of pulse itraconazole therapy in toenail onychomycosis caused by dermatophytes over a period of one year in patients with SCIO scores between 6 to 9.Results: It was observed that mean age of patients was 38.96 years. 57.27 % study subjects had complete clinical improvement to oral itraconazole three pulses regimen. One pulse consisted of 200 mg twice per day given for one week, followed by a three weeks interval. Thus, this regimen was repeated thrice.Conclusions: This study shows the substantial benefit with itraconazole pulse regimen in toenail onychomycosis. The outcome this study is comparable with previously published data and may encourage the usage of itraconazole pulse regimen for the treatment of dermatophyte toenail onychomycosis in adults

Anti-nicotine vaccine: current status

Tobacco abuse has an enormous impact on health. Nicotine is the main substance responsible for dependence on tobacco-containing products. The vast majority of cigarette smokers who try to quit ultimately fail because of high relapse rates. Clearly, novel approaches are needed for the treatment and prevention of nicotine addiction. Having an efficient vaccine that would generate antibodies to sequester the drug and prevent its access to the brain could go a long way toward helping a motivated addict quit an addiction

A clinical trial of treatment of uncomplicated typhoid fever: efficacy of ceftriaxone-azithromycin combination

Background: Typhoid fever is a systemic infection caused by Gram-negative bacterium Salmonella enterica serovar typhi (S. typhi). It is a major health problem in India. It carries significant morbidity and mortality. Antimicrobial therapy is critical for the management of typhoid fever. Emergence of multidrug-resistant (MDR) and nalidixic acid-resistant (NAR) strains of S. typhi has complicated therapy by limiting treatment options. Hence, this study was conducted to evaluate the efficacy and safety profile of ceftriaxone and azithromycin combination therapy in uncomplicated typhoid fever.Methods: Adults patients of blood culture proven uncomplicated typhoid fever admitted in the medicine ward of Teerthanker Mahaveer Medical College and Research Centre were treated with ceftriaxone intravenously (2 g daily for 14 days) and azithromycin orally (500 mg daily for 7 days). Patients were clinically and bacteriologically evaluated during the study period and follow-up.Results: 96% cure rate was observed. No relapse was recorded.Conclusion: Ceftriaxone-azithromycin combination may be considered as an empirical therapy for treatment of uncomplicated typhoid fever in view of the emergence of MDR and NAR strains of S. typhi

Gadolinium free cardiovascular magnetic resonance with 2-point Cine balanced steady state free precession

BACKGROUND: Cardiovascular magnetic resonance (CMR) of ventricular structure and function is widely performed using cine balanced steady state free precession (bSSFP) MRI. The bSSFP signal of myocardium is weighted by magnetization transfer (MT) and T1/T2-relaxation times. In edematous and fibrotic tissues, increased T2 and reduced MT lead to increased signal intensity on images acquired with high excitation flip angles. We hypothesized that acquisition of two differentially MT-weighted bSSFP images (termed 2-point bSSFP) can identify tissue that would enhance with gadolinium similar to standard of care late gadolinium enhancement (LGE). METHODS: Cine bSSFP images (flip angles of 5° and 45°) and native-T1 and T2 maps were acquired in one mid-ventricular slice in 47 patients referred for CMR and 10 healthy controls. Afterwards, LGE images and post-contrast T1 maps were acquired and gadolinium partition coefficient (GPC) was calculated. Maps of ΔS/S(o) were calculated as (S(45)-S(5))/S(5)*100 (%), where S(flip_angle) is the voxel signal intensity. RESULTS: Twenty three patients demonstrated areas of myocardial hyper-enhancement with LGE. In enhanced regions, ΔS/S(o), native-T1, T2, and GPC were heightened (p < 0.05 vs. non-enhanced tissues). ΔS/S(o), native-T1, and T2 all demonstrated association with GPC, however the association was strongest for ΔS/S(o). Bland-Altman analysis revealed a slight bias towards larger volume of enhancement with ΔS/S(o) compared to LGE, and similar transmurality. Subjective analysis with 2-blinded expert readers revealed agreement between ΔS/S(o) and LGE of 73.4 %, with false positive detection of 16.7 % and false negative detection of 15.2 %. CONCLUSIONS: Gadolinium free 2-point bSSFP identified tissue that enhances at LGE with strong association to GPC. Our results suggest that with further development, MT-weighted CMR could be used similar to LGE for diagnostic imaging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12968-015-0194-1) contains supplementary material, which is available to authorized users

Quantum Backaction on kg-Scale Mirrors: Observation of Radiation Pressure Noise in the Advanced Virgo Detector

The quantum radiation pressure and the quantum shot noise in laser-interferometric gravitational wave detectors constitute a macroscopic manifestation of the Heisenberg inequality. If quantum shot noise can be easily observed, the observation of quantum radiation pressure noise has been elusive, so far, due to the technical noise competing with quantum effects. Here, we discuss the evidence of quantum radiation pressure noise in the Advanced Virgo gravitational wave detector. In our experiment, we inject squeezed vacuum states of light into the interferometer in order to manipulate the quantum backaction on the 42 kg mirrors and observe the corresponding quantum noise driven displacement at frequencies between 30 and 70 Hz. The experimental data, obtained in various interferometer configurations, is tested against the Advanced Virgo detector quantum noise model which confirmed the measured magnitude of quantum radiation pressure noise

The population of merging compact binaries inferred using gravitational waves through GWTC-3

We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 $\rm{Gpc^{-3} yr^{-1}}$ and 1700 $\rm{Gpc^{-3} yr^{-1}}$ and the NSBH merger rate to be between 7.8 $\rm{Gpc^{-3}\, yr^{-1}}$ and 140 $\rm{Gpc^{-3} yr^{-1}}$ , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 $\rm{Gpc^{-3}\, yr^{-1}}$ and 44 $\rm{Gpc^{-3}\, yr^{-1}}$ at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from $1.2^{+0.1}_{-0.2} M_\odot$ to $2.0^{+0.3}_{-0.3} M_\odot$. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 $M_\odot$. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above $\sim 60 M_\odot$. The rate of BBH mergers is observed to increase with redshift at a rate proportional to $(1+z)^{\kappa}$ with $\kappa = 2.9^{+1.7}_{-1.8}$ for $z\lesssim 1$. Observed black hole spins are small, with half of spin magnitudes below $\chi_i \simeq 0.25$. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate

Drug Prescribing Pattern in Dermatophytosis at the Medical Outpatient Clinic of a Tertiary Healthcare in Karnataka, India

Aim of this study is to ascertain the drug prescribing pattern of the patients with Tinea infections attending a tertiary care teaching centre. This retrospective study conducted at a tertiary care teaching hospital in the Dakshina Kannada district, Karnataka for a period of one year. 158 prescriptions were audited to find generic/ brand names of drugs, number of drugs, dosage, forms, frequency, and duration of treatment. The age and sex distributions of patients and disease distribution were also studied. 72 (45.57%) patients were males and 86 (54.43%) were females. Terbinafine, Ketoconazole, Sertaconazole were prescribed as topical monotherapy .Clobetasone butyrate, Sertaconazole and Miconazole were prescribed as topical polytherapy. Terbinafine, Fluconazole and anti histaminics were prescribed as systemic monotherapy and polytherapy. Statistical analysis revealed p-value was &gt; 0.05. Prescription patterns were in consensus with the general guidelines. [Med-Science 2015; 4(3.000): 2465-72

Retrospective Study of the Clinical Profile and Prognostic Indicators in Patients of Alcoholic Liver Disease Admitted to a Tertiary Care Teaching Hospital in Western Nepal

<b>Background/Aim:</b> Alcohol is the most common substance abused in Nepal. Liver disease caused by alcohol abuse, including its end stage, cirrhosis, is a major health care problem, which is difficult to treat. <b> Objectives:</b> To study the demographic profile, laboratory parameters, complications and their prognostic implications among patients of alcoholic liver disease (ALD). <b> Materials and Methods:</b> Records of all patients of ALD admitted from January1^, 2005 to December 31^, 2006 were studied and followed up to December 31, 2007. A total of 181 patients were analyzed. Their clinical profile and laboratory parameters were noted and analyzed using SPSS-10.0 software. <b> Results:</b> Among the 181 patients, 80.7&#x0025; were male, 30.9&#x0025; were army/ex-army and 65.2&#x0025; were documented smokers. The mean age of presentation was 52.08 years. Jaundice (57.5&#x0025;) was the most common presentation followed by hepatomegaly (51.4&#x0025;). Hypoalbuminemia (50.3) followed by ascites (48.1) were common complications. Death occurred in 19.1&#x0025; of the patients, the most common cause being hepatic encephalopathy (72.2&#x0025;) followed by variceal bleeding and hepatorenal syndrome. Jaundice, ascites and hepatic encephalopathy at presentation and female sex were significantly associated with increased mortality along with discriminant score&#62; 32, aspartate aminotransferase (AST): Alanine aminotranferase (ALT) &#8805; 2, ultrasonography (USG)-proven cirrhosis, rise in prothrombin time &#8805;5 s, total bilirubin &#8805; 4&#8197;mg/dL and ESR &#8805;34. <b> Conclusion:</b> ALD was predominantly seen among the productive age group with a high morbidity and mortality. Jaundice, ascites, hepatic encephalopathy at presentation and female sex are poor prognostic indicators along with discriminant score &gt; 32, AST:ALT &#8805; 2, USG-proven cirrhosis, coagulopathy, hyperbilirubenemia and high ESR