Repurposing Disulfiram as an Antimicrobial Agent in Topical Infections

Antimicrobial drugs applied topically offer several advantages. However, the widespread use of antibiotics has led to increasing antimicrobial resistance. One interesting approach in the drug discovery process is drug repurposing. Disulfiram, which was originally approved as an anti-alcoholism drug, offers an attractive alternative to treat topical multidrug resistance bacteria in skin human infections. This study aimed to evaluate the biopharmaceutical characteristics of the drug and the effects arising from its topical application in detail. Microdilution susceptibility testing showed antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes. Dermal absorption revealed no permeation in pig skin. The quantification of the drug retained in pig skin demonstrated concentrations in the stratum corneum and epidermis, enough to treat skin infections. Moreover, in vitro cytotoxicity and micro-array analyses were performed to better understand the mechanism of action and revealed the importance of the drug as a metal ion chelator. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic to treat superficial human skin infections

Lepton Flavor Violating Process in Bi-maximal texture of Neutrino Mixings

We investigate the lepton flavor violation in the framework of the MSSM with right-handed neutrinos taking the large mixing angle MSW solution in the quasi-degenerate and the inverse-hierarchical neutrino masses. We predict the branching ratio of $\mu \to e+\gamma$ and $\tau \to \mu+\gamma$ processes assuming the degenerate right-handed Majorana neutrino masses. We find that the branching ratio in the quasi-degenerate neutrino mass spectrum is 100 times smaller than the ones in the inverse-hierarchical and the hierarchical neutrino spectra. We emphasize that the magnitude of $U_{e3}$ is one of important ingredients to predict BR($\mu \to e +\gamma$). The effect of the deviation from the complete-degenerate right-handed Majorana neutrino masses are also estimated. Furtheremore, we examine the S_{3\sL}\times S_{3\sR} model, which gives the quasi-degenerate neutrino masses, and the Shafi-Tavartkiladze model, which gives the inverse-hierarchical neutrino masses. Both predicted branching ratios of $\mu\to e+\gamma$ are smaller than the experimantal bound.Comment: Latex file, 38 pages, 10 figures, revised versio

The TELE-DD project on treatment nonadherence in the population with type 2 diabetes and comorbid depression

Diabetic patients have increased depression rates, diminished quality of life, and higher death rates due to depression comorbidity or diabetes complications. Treatment adherence (TA) and the maintenance of an adequate and competent self-care are crucial factors to reach optimal glycaemic control and stable quality of life in these patients. In this report, we present the baseline population analyses in phase I of the TELE-DD project, a three-phased population-based study in 23 Health Centres from the Aragonian Health Service Sector II in Zaragoza, Spain. The objectives of the present report are: (1) to determine the point prevalence of T2D and clinical depression comorbidity and treatment nonadherence; (2) to test if HbA1c and LDL-C, as primary DM outcomes, are related to TA in this population; and (3) to test if these DM primary outcomes are associated with TA independently of shared risk factors for DM and depression, and patients’ health behaviours. A population of 7,271 patients with type-2 diabetes and comorbid clinical depression was investigated for inclusion. Individuals with confirmed diagnoses and drug treatment for both illnesses (n = 3340) were included in the current phase I. A point prevalence of 1.9% was found for the T2D-depression comorbidity. The prevalence of patients nonadherent to treatment for these diseases was 35.4%. Multivariate analyses confirmed that lower diabetes duration, increased yearly PCS visits, HbA1c and LDL-C levels were independently related to treatment nonadherence. These findings informed the development of a telephonic monitoring platform for treatment of nonadherence for people with diabetes and comorbid depression and further trial, cost-effectiveness, and prognostic studies (phases II and III)

Lepton Flavor Violation in the SUSY-GUT Models with Lopsided Mass Matrix

The tiny neutrino masses measured in the neutrino oscillation experiments can be naturally explained by the supersymmetric see-saw mechanism. If the supersymmetry breaking is mediated by gravity, the see-saw models may predict observable lepton flavor violating effects. In this work, we investigate the lepton flavor violating process $\mu\to e\gamma$ in the kind of neutrino mass models based on the idea of the ``lopsided'' form of the charged lepton mass matrix. The constraints set by the muon anomalous magnetic moment are taken into account. We find the present models generally predict a much larger branching ratio of $\mu\to e\gamma$ than the experimental limit. Conversely, this process may give strong constraint on the lepton flavor structure. Following this constraint we then find a new kind of the charged lepton mass matrix. The feature of the structure is that both the elements between the 2-3 and 1-3 generations are ``lopsided''. This structure produces a very small 1-3 mixing and a large 1-2 mixing in the charged lepton sector, which naturally leads to small $Br(\mu\to e\gamma)$ and the LMA solution for the solar neutrino problem.Comment: 24 pages, 8 figure

Fixed and drifting buoys around the national Spanish waters

Joint Technical Commission for Oceanography and Marine Meteorology (JCOMM) Marine Technical Conference, The Technical Conference (TECO) Toward an Integrated Met-ocean Monitoring, Forecasting and Services System, 25-29 October 2017, Geneva, SwitzerlandImproving the knowledge of the ocean and seas surrounding the Iberian Peninsula and Balearic and Canary islands is an objective of the Spanish oceanography. For that purpose, a number of fixed and drifting floats have been established in the last 25 years. Data buoys measure sea surface temperature and salinity, ocean current velocity, air temperature, humidity, wave characteristic and wind velocity across seas and ocean. The objective is increase the quantity, quality, coverage and timeliness of atmospheric and oceanographic data. These observations are used immediately to improve forecast and therefore increase marine safety. The main group of fixed buoys is formed by the Puertos del Estado deep and shallow buoy networks, but a series of well instrumented new platforms has been established in later times. The RAIA Project (Xunta de Galicia), PLOCAN, SOCIB, IEO, Euskalmet-AZTI, ICM and UTM (CSIC) and University and Polytechnic of Barcelona have completed the Observing System. Most of the buoys are transmitting data by GTS for using in atmospheric and ocean prediction models. Multidisciplinary sensors as Dissolved Oxygen, Fluorescence Chlorophyll or pCO2 has been mounted in the buoys and calibration/validation procedures has been developed for improve data quality. Antifouling systems recently developed have also been included and quality of the optical sensors measurements has improved. Drifting floats has increase its number and importance, from Argo floats to traditional deriving ones improving the Spanish contribution to IOC and WWO and JCOMM. Spain is member of EuroArgo ERIC. SOCIB and IEO are the main contributors. Also multidisciplinary work has been done associated to Argo buoys. BGQ ARGO incorporate O2 sensor. ICM, SMOS Barcelona Expert Center, and SOCIB are the main contributors to the drifting buoys group. Main objectives are improving Technological development as well as data management. Tropical and Southern Atlantic Ocean are the main studying areasPeer Reviewe

Leptogenesis and rescattering in supersymmetric models

The observed baryon asymmetry of the Universe can be due to the $B-L$ violating decay of heavy right handed (s)neutrinos. The amount of the asymmetry depends crucially on their number density. If the (s)neutrinos are generated thermally, in supersymmetric models there is limited parameter space leading to enough baryons. For this reason, several alternative mechanisms have been proposed. We discuss the nonperturbative production of sneutrino quanta by a direct coupling to the inflaton. This production dominates over the corresponding creation of neutrinos, and it can easily (i.e. even for a rather small inflaton-sneutrino coupling) lead to a sufficient baryon asymmetry. We then study the amplification of MSSM degrees of freedom, via their coupling to the sneutrinos, during the rescattering phase which follows the nonperturbative production. This process, which mainly influences the (MSSM) $D-$flat directions, is very efficient as long as the sneutrinos quanta are in the relativistic regime. The rapid amplification of the light degrees of freedom may potentially lead to a gravitino problem. We estimate the gravitino production by means of a perturbative calculation, discussing the regime in which we expect it to be reliable.Comment: (20 pages, 6 figures), references added, typos corrected. Final version in revte

Exploring flavor structure of supersymmetry breaking from rare B decays and unitarity triangle

We study effects of supersymmetric particles in various rare B decay processes as well as in the unitarity triangle analysis. We consider three different supersymmetric models, the minimal supergravity, SU(5) SUSY GUT with right-handed neutrinos, and the minimal supersymmetric standard model with U(2) flavor symmetry. In the SU(5) SUSY GUT with right-handed neutrinos, we consider two cases of the mass matrix of the right-handed neutrinos. We calculate direct and mixing-induced CP asymmetries in the b to s gamma decay and CP asymmetry in B_d to phi K_S as well as the B_s--anti-B_s mixing amplitude for the unitarity triangle analysis in these models. We show that large deviations are possible for the SU(5) SUSY GUT and the U(2) model. The pattern and correlations of deviations from the standard model will be useful to discriminate the different SUSY models in future B experiments.Comment: revtex4, 36 pages, 10 figure

Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy

Background: Since December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection. Methods: This work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality. Results: Of 13, 932 patients, antibiotics were used in 12, 238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21–1.62; p <.001) except macrolides, which had a higher survival rate (OR 0.70, 95% CI 0.64–0.76; p <.001). The decision to start antibiotics was influenced by presence of increased inflammatory markers and any kind of infiltrate on an x-ray. Patients receiving antibiotics required respiratory support and were transferred to intensive care units more often. Conclusions: Bacterial co-infection was uncommon among COVID-19 patients, yet use of antibiotics was high. There is insufficient evidence to support widespread use of empiric antibiotics in these patients. Most may not require empiric treatment and if they do, there is promising evidence regarding azithromycin as a potential COVID-19 treatment. © 2021, The Author(s)