Implementation of Bedaquiline, Pretomanid, and Linezolid in the United States: Experience Using a Novel All-Oral Treatment Regimen for Treatment of Rifampin-Resistant or Rifampin-Intolerant Tuberculosis Disease.

BACKGROUND: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. METHODS: Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. RESULTS: Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. CONCLUSIONS: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

Novel 6-Month Treatment for Drug-Resistant Tuberculosis, United States.

The US Food and Drug Administration approved a 6-month regimen of pretomanid, bedaquiline, and linezolid for extensively drug-resistant or multidrug-intolerant tuberculosis after a trial in South Africa demonstrated 90% effectiveness 6 months posttreatment. We report on a patient who completed the regimen using a lower linezolid dose.

Observation of unexpected uniaxial magnetic anisotropy in La2/3Sr1/3MnO3 films by a BaTiO3 overlayer in an artificial multiferroic bilayer.

We studied in detail the in-plane magnetic properties of heterostructures based on a ferroelectric BaTiO3 overlayer deposited on a ferromagnetic La2/3Sr1/3MnO3 film grown epitaxially on pseudocubic (001)-oriented SrTiO3, (LaAlO3)0.3(Sr2TaAlO6)0.7 and LaAlO3 substrates. In this configuration, the combination of both functional perovskites constitutes an artificial multiferroic system with potential applications in spintronic devices based on the magnetoelectric effect. La2/3Sr1/3MnO3 single layers and BaTiO3/La2/3Sr1/3MnO3 bilayers using the pulsed-laser deposition technique. We analyzed the films structurally through X-ray reciprocal space maps and high-angle annular dark field microscopy, and magnetically via thermal demagnetization curves and in-plane magnetization versus applied magnetic field loops at room temperature. Our results indicate that the BaTiO3 layer induces an additional strain in the La2/3Sr1/3MnO3 layers close to their common interface. The presence of BaTiO3 on the surface of tensile-strained La2/3Sr1/3MnO3 films transforms the in-plane biaxial magnetic anisotropy present in the single layer into an in-plane uniaxial magnetic anisotropy. Our experimental evidence suggests that this change in the magnetic anisotropy only occurs in tensile-strained La2/3Sr1/3MnO3 film and is favored by an additional strain on the La2/3Sr1/3MnO3 layer promoted by the BaTiO3 film. These findings reveal an additional mechanism that alters the magnetic behavior of the ferromagnetic layer, and consequently, deserves further in-depth research to determine how it can modify the magnetoelectric coupling of this hybrid multiferroic system.

Experimental realisation of tunable ferroelectric/superconductor [Formula: see text] 1D photonic crystals in the whole visible spectrum.

Emergent technologies that make use of novel materials and quantum properties of light states are at the forefront in the race for the physical implementation, encoding and transmission of information. Photonic crystals (PCs) enter this paradigm with optical materials that allow the control of light propagation and can be used for optical communication, and photonics and electronics integration, making use of materials ranging from semiconductors, to metals, metamaterials, and topological insulators, to mention but a few. Here, we show how designer superconductor materials integrated into PCs fabrication allow for an extraordinary reduction of electromagnetic waves damping, making possible their optimal propagation and tuning through the structure, below critical superconductor temperature. We experimentally demonstrate, for the first time, a successful integration of ferroelectric and superconductor materials into a one-dimensional (1D) PC composed of [Formula: see text] bilayers that work in the whole visible spectrum, and below (and above) critical superconductor temperature [Formula: see text]. Theoretical calculations support, for different number of bilayers N, the effectiveness of the produced 1D PCs and may pave the way for novel optoelectronics integration and information processing in the visible spectrum, while preserving their electric and optical properties.

Ex Vivo Cardiotoxicity of Antineoplastic Casiopeinas Is Mediated through Energetic Dysfunction and Triggered Mitochondrial-Dependent Apoptosis.

Casiopeinas are a group of copper-based antineoplastic molecules designed as a less toxic and more therapeutic alternative to cisplatin or Doxorubicin; however, there is scarce evidence about their toxic effects on the whole heart and cardiomyocytes. Given this, rat hearts were perfused with Casiopeinas or Doxorubicin and the effects on mechanical performance, energetics, and mitochondrial function were measured. As well, the effects of Casiopeinas-triggered cell death were explored in isolated cardiomyocytes. Casiopeinas III-Ea, II-gly, and III-ia induced a progressive and sustained inhibition of heart contractile function that was dose- and time-dependent with an IC50 of 1.3 ± 0.2, 5.5 ± 0.5, and 10 ± 0.7 µM, correspondingly. Myocardial oxygen consumption was not modified at their respective IC50, although ATP levels were significantly reduced, indicating energy impairment. Isolated mitochondria from Casiopeinas-treated hearts showed a significant loss of membrane potential and reduction of mitochondrial Ca2+ retention capacity. Interestingly, Cyclosporine A inhibited Casiopeinas-induced mitochondrial Ca2+ release, which suggests the involvement of the mitochondrial permeability transition pore opening. In addition, Casiopeinas reduced the viability of cardiomyocytes and stimulated the activation of caspases 3, 7, and 9, demonstrating a cell death mitochondrial-dependent mechanism. Finally, the early perfusion of Cyclosporine A in isolated hearts decreased Casiopeinas-induced dysfunction with reduction of their toxic effect. Our results suggest that heart cardiotoxicity of Casiopeinas is similar to that of Doxorubicin, involving heart mitochondrial dysfunction, loss of membrane potential, changes in energetic metabolites, and apoptosis triggered by mitochondrial permeability.

Body Packer y Body Stuffer: Serie de Casos. Revisión / Body Packer y Body Stuffer: serie de casos. Revision

"Body packing", "Body pushing" y "Body stuffing" son distintas formas de transportar sustancias ilegales dentro del cuerpo humano. Frente al ingreso en la unidad de emergencias de un "Body Packer", conocido como "tragador de paquetes" con fines de contrabando o un "Body Stuffer" llamados "tragadores rápidos", quienes ingieren en forma compulsiva paquetes manufacturados para la venta de sustancias ante la posibilidad de ser sorprendidos por agentes de la ley; se plantean una serie de desafíos en cuanto al tratamiento que al día de hoy permanecen en debate. Generalmente se prefiere mantener una conducta conservadora facilitando la expulsión de los paquetes. En aquellos casos en los que los pacientes presenten paquetes atascados o rotos o no mejoren con el tratamiento conservador, se recomienda el tratamiento quirúrgico.El presente trabajo tiene por objetivo reportar una serie de casos internados por ingesta de paquetes potencialmente peligrosos que se sometieron a una evacuación farmacológica y/o quirúrgica en 8 pacientes y una revisión bibliográfica sobre el tema.

"Body packing", "Body pushing", and "Body stuffing" are different ways to use the interior of the human body to transport illegal substances. In the face of a "Body Packer" or a "Body Stuffer" known as "fast swallowers", which are those cases in which they compulsively swallow manufactured packages for the sale of substances before the possibility of being surprised by law enforcement officers, a series of challenges present themselves regarding the treatment, which is currently up for debate. Generally, a conservative conduct is preferred, facilitating the expulsion of the packages. In those cases, in which patients have stuck or broken packages or do not improve with conservative treatment, surgical treatment is recommended.The present paper aims to report a series of cases in which the patients were admitted due to an intake of potentially dangerous packages and put through a pharmacological evacuation and/or surgical evacuation of 8 patients, and a bibliographical revision on the subject.

Concordance between qualitative and quantitative cultures in burned patients. Analysis of 2886 cultures.

OBJECTIVE: To determine the concordance between superficial cultures (SC) and quantitative cultures (QC) in the diagnosis of wound infection in burn patients. SAMPLE: All SC and QC taken from the same patient, site and during the same surgery were analysed. VARIABLES: On the SC, the microorganism (MO) and its amount defined subjectively by the microbiologist was recorded (negative, very low, low, regular and abundant). On the QC, the MO and its amount were expressed as colony forming units per gram of tissue (CFUs/g). STATISTICS: Kappa index of agreement beyond chance; Wilcoxon and Kruskall-Wallis for continuous variables and chi(2) for categorical variables were used with a p<0.05 indicating statistical significance. RESULTS: One thousand four hundred and forty three pairs of cultures were analyzed. The concordance between SC and QC (Kappa index) was 52%. On the SC, only when the microbiologist subjectively informed "abundant" MOs there was a significant difference (p<0.0001). There were 6.1% of QCs with more than 10(5) CFUs/g and the most frequent MOs isolated were: S. aureus (27.9%), E. coli (11.6%), P. aeruginosa (11.6%), E. faecalis (11.6%) and S. epidermidis (7.0%). CONCLUSIONS: SC has a moderate concordance with the QC showing a low reliability between the two methods. The subjective information given by the microbiology technician in the SC is not precise. A study in which the two methods be compared blindly against the reference standard, in a prospective cohort of patients, it is needed to discriminate which of two methods it is the most accurate one determining sensitivity and specificity.

Presence of impaired insulin secretion and insulin resistance in normoglycemic male subjects with family history of type 2 diabetes.

In order to demonstrate the effect of family history (FH) coexisting with obesity in insulin resistance (IR) and secretion in subjects at risk for type 2 diabetes, fasting and 2 h post-glucose load serum glucose and insulin concentrations were measured in 143 individuals, 66 men and 77 women, ages ranging from 18 to 68 years, who were considered at risk but were normoglycemic following ADA criteria. Insulin resistance was estimated using HOMA(IR), basal hyperinsulinemia and I(0)/G(0) ratio. Insulin secretion was estimated by means of HOMA(beta-cell), DeltaI(30-0)/DeltaG(30-0) ratio and the insulin concentration at 30 min post-glucose load (I(30)). Disposition index (DI) was calculated to verify if insulin secretion compensate IR. Obesity in males produced an increase in all the parameters indicative of IR in both groups of individuals, with (FH(+)) or without (FH(-)) family history of diabetes, increase that was more pronounced in those FH(-). This effect was not observed in women. The parameters indicative of insulin secretion showed that only in males the presence of FH(+) was responsible for a significant decrease in insulin secretion, mainly expressed as lower values of HOMA(beta-cell) in obese as well as in non-obese. The I(30) and the ratio DeltaI(30-0)/DeltaG(30-0), although lower, did not reach statistical significance. The DI showed that only when obesity and FH were associated the decrease in insulin secretion was not a compensatory response to the IR present in those individuals. In conclusion, normoglycemic obese and non-obese male subjects of Hispanic (Latinos) origin with a family history of type 2 diabetes present not only IR but impaired insulin secretion, having the obese FH(+) and additional risk like low DI.

[The environment and its impact on health: old risks, new risks]. / El medio ambiente y su impacto en la salud: riesgos tradicionales, nuevos riesgos.

The objective of this article is to investigate three representative elements of environmental health from a geographical perspective taking the Autonomous Community as the unit of analysis: legionnaire's disease, chemical safety and food safety. Legionnaire's disease is a pathology with a specific epidemiological profile; males, adults, and with previous chronic pathologies and habits. The official response, with regard to recent outbreaks and the increase in the incidence of legionnaire's disease, has differed between autonomous communities due to peculiarities and different organizational cultures. Both the sinking of the ship Prestige and the accident at the oil refinery at Puertollano (Ciudad Real) have increased concern in the population about chemical substances, so familiar in our environment. However it is not only the big accidents which are relevant: it is surprising to learn that most of the registered poisonings are due to domestic cleaning goods. The pending challenge from the Public Health point of view is to elaborate the Report on Human Exposure to Environmental Chemical Agents which, undoubtedly, will help to establish differences between type and class. Finally, the number of outbreaks of food poisoning continues to be of concern; this should lead us to think about the effectiveness of food safety programmes and to focus on the home, being place where most of the outbreaks occur. The General Sanitary Inspection of Food ought to be a good tool to help improve food safety.