Comparative Genomics of the First Resistant Candida auris Strain Isolated in Mexico: Phylogenomic and Pan-Genomic Analysis and Mutations Associated with Antifungal Resistance.

Candida auris is an emerging multidrug-resistant and opportunistic pathogenic yeast. Whole-genome sequencing analysis has defined five major clades, each from a distinct geographic region. The current study aimed to examine the genome of the C. auris 20-1498 strain, which is the first isolate of this fungus identified in Mexico. Based on whole-genome sequencing, the draft genome was found to contain 70 contigs. It had a total genome size of 12.86 Mbp, an N50 value of 1.6 Mbp, and an average guanine-cytosine (GC) content of 45.5%. Genome annotation revealed a total of 5432 genes encoding 5515 proteins. According to the genomic analysis, the C. auris 20-1498 strain belongs to clade IV (containing strains endemic to South America). Of the two genes (ERG11 and FKS1) associated with drug resistance in C. auris, a mutation was detected in K143R, a gene located in a mutation hotspot of ERG11 (lanosterol 14-α-demethylase), an antifungal drug target. The focus on whole-genome sequencing and the identification of mutations linked to the drug resistance of fungi could lead to the discovery of new therapeutic targets and new antifungal compounds.

Streptomyces albidoflavus Q antifungal metabolites inhibit the ergosterol biosynthesis pathway and yeast growth in fluconazole-resistant Candida glabrata: phylogenomic and metabolomic analyses.

There is an urgent need to develop new antifungals due to the increasing prevalence of multidrug-resistant fungal infections and the recent emergence of COVID-19-associated candidiasis. A good study model for evaluating new antifungal compounds is Candida glabrata, an opportunistic fungal pathogen with intrinsic resistance to azoles (the most common clinical drugs for treating fungal infections). The aim of the current contribution was to conduct in vitro tests of antifungal metabolites produced by the bacteria Streptomyces albidoflavus Q, identify their molecular structures, and utilize several techniques to provide evidence of their therapeutic target. S. albidoflavus was isolated from maize rhizospheric soil in Mexico and identified by phylogenomic analysis using a 92-gene core. Of the 66 metabolites identified in S. albidoflavus Q by a liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomic analysis of the lyophilized supernatant, six were selected by the Way2drug server based on their in silico binding to the likely target, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR, the key enzyme in the ergosterol biosynthesis pathway). Molecular modeling studies show a relatively high binding affinity for the CgHMGR enzyme by two secondary metabolites: isogingerenone B (diaryl heptanoid) and notoginsenoside J (polycyclic triterpene). These secondary metabolites were able to inhibit ergosterol synthesis and affect yeast viability in vitro. They also caused alterations in the ultrastructure of the yeast cytoplasmic membrane, as evidenced by transmission electron microscopy. The putative target of isogingerenone B and notoginsenoside J is distinct from that of azole drugs (the most common clinical antifungals). The target for the latter is the lanosterol 14 alpha-demethylase enzyme (Erg11). IMPORTANCE Multidrug resistance has emerged among yeasts of the genus Candida, posing a severe threat to global health. The problem has been exacerbated by the pandemic associated with COVID-19, during which resistant strains of Candida auris and Candida glabrata have been isolated from patients infected with the SARS-CoV-2 virus. To confront this challenge, the World Health Organization has invoked scientists to search for new antifungals with alternative molecular targets. This study identified 66 metabolites produced by the bacteria Streptomyces albidoflavus Q, 6 of which had promising properties for potential antifungal activity. The metabolites were tested in vitro as inhibitors of ergosterol synthesis and C. glabrata growth, with positive results. They were also found to damage the cytoplasmic membrane of the fungus. The corresponding molecular structures and their probable therapeutic target were established. The target is apparently distinct from that of azole drugs.

The distribution of COVID-19 mortality.

We estimate the distribution of COVID-19 mortality (measured as daily deaths) from the start of the pandemic until July 31st, 2022, for six European countries and the USA. We use the Pareto, the stretched exponential, the log-normal and the log-logistic distributions as well as mixtures of the log-normal and log-logistic distributions. The main results are that the Pareto does not describe well the data and that mixture distributions tend to offer a very good fit to the data. We also compute Value-at-Risk measures as well as mortality probabilities with our estimates. We also discuss the implications of our results and findings from the point of view of public health planning and modelling.

Characterization and Modeling of Free Volume and Ionic Conduction in Multiblock Copolymer Proton Exchange Membranes.

Free volume plays a key role on transport in proton exchange membranes (PEMs), including ionic conduction, species permeation, and diffusion. Positron annihilation lifetime spectroscopy and electrochemical impedance spectroscopy are used to characterize the pore size distribution and ionic conductivity of synthesized PEMs from polysulfone/polyphenylsulfone multiblock copolymers with different degrees of sulfonation (SPES). The experimental data are combined with a bundle-of-tubes model at the cluster-network scale to examine water uptake and proton conduction. The results show that the free pore size changes little with temperature in agreement with the good thermo-mechanical properties of SPES. However, the free volume is significantly lower than that of Nafion®, leading to lower ionic conductivity. This is explained by the reduction of the bulk space available for proton transfer where the activation free energy is lower, as well as an increase in the tortuosity of the ionic network.

Quasi-Static Variation of Power-Law and Log-Normal Distributions of Urban Population.

We analytically derived and confirmed by empirical data the following three relations from the quasi-time-reversal symmetry, Gibrat's law, and the non-Gibrat's property observed in the urban population data of France. The first is the relation between the time variation of the power law and the quasi-time-reversal symmetry in the large-scale range of a system that changes quasi-statically. The second is the relation between the time variation of the log-normal distribution and the quasi-time-reversal symmetry in the mid-scale range. The third is the relation among the parameters of log-normal distribution, non-Gibrat's property, and quasi-time-reversal symmetry.

Cancer and SARS-CoV-2 Infection: A Third-Level Hospital Experience.

INTRODUCTION: Madrid has been the epicenter of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Spain. We analyzed our experience with SARS-CoV-2 infected and cancer patients. PATIENTS AND METHODS: We included patients from March 1 to April 30 2020 at Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain). The inclusion criteria were diagnosis of SARS-CoV-2 infection made by reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in cancer patients who were admitted to the hospital due to the need for respiratory support. The exclusion criteria were suspected cases not confirmed. The primary objective was to analyze the mortality rates of patients with cancer, especially those with lung cancer and COVID-19. RESULTS: Overall in-hospital mortality of cancer patients with coronavirus disease 2019 (COVID-19) was 15.2% similar to 12.7% of the global COVID-19 hospitalized population (p=0.615) and greater than that of patients admitted without SARS-CoV-2 infection during the same period 4.3% (p<0.001). Among 653 patients receiving active cancer therapy during the study period, 24 (3.7%) developed COVID-19 and required admission, 4.2% of those receiving chemotherapy, 9.5% immunotherapy and 2.1% targeted therapies. Lung and breast cancer were the most frequent cancer types (26.1%), followed by colorectal cancer (19.6%). Mortality in patients with lung cancer was 25%. The univariate analysis comparing patients who developed a serious event to those who did not showed that the higher Brescia index, CURB-65 scale, lactate dehydrogenase (LDH) or C-reactive protein (CRP) were the risk factors of developing severe complications. CONCLUSION: Patients with cancer, especially lung cancer, and SARS-CoV-2 infection have a worse overall prognosis than the general population.

First report of a catheter-related bloodstream infection by Candida haemulonii in a children's hospital in Mexico City.

BACKGROUND: Candida haemulonii is an emergent, multi-resistant opportunistic pathogenic yeast that like Candida auris, can be misidentified when conventional diagnostic methods are used. Timely molecular identification using DNA sequence analysis variation in the internal transcriber spacer region, ITS1-ITS4 and the 28S ribosomal DNA gene (28S rDNA), and in vitro antifungal susceptibility assessment can lead to rapid therapeutic success. CASE REPORT: A case of Candida haemulonii candidiasis suffered by a male paediatric patient attended at Federico Gómez Children's Hospital of México City in September 2016 is reported. The isolate was yielded from peripheral blood and central catheter blood specimens. From in vitro antifungal susceptibility data, caspofungin was administered to the patient, who showed clear improvements at the end of antimicrobial administration, and the removal of the central venous catheter. Using a molecular phylogenetic approach, we identified the clinical isolate as C. haemulonii. The clinical isolate has been named as Candida haemulonii ENCB-87 from now on. C. haemulonii ENCB-87 grew well between the temperatures, 28 °C and 35 °C but not at 37 °C in YPD culture medium. The clinical isolate was susceptible to caspofungin, which resulted in therapeutic success for the patient. CONCLUSIONS: C. haemulonii is an emergent, opportunistic pathogen, closely related to C. auris, therefore, the timely and accurate identification and antifungal susceptibility assessments are paramount in generating a robust epidemiology of this emerging Candida species.

Discordance between bioelectrical impedance vector analysis and the new ESPEN definition of malnutrition for the diagnosis of hospital malnutrition.

BACKGROUND & AIMS: No universally accepted diagnostic criteria for malnutrition are available to date. The aim was to assess the concordance for the diagnosis of hospital malnutrition between the bioelectrical impedance vector analysis (BIVA) and the new definition of malnutrition proposed by the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: A total of 140 adult hospitalized patients were included. The malnutrition risk was assessed by the Nutritional Risk Screening. The ESPEN malnutrition criteria (body mass index (BMI) <18.5 kg/m2, weight loss (WL) + low BMI, and WL + low fat free mass index (FFMI) were applied to each patient. The bioelectrical impedance of each patient was measured, and malnutrition was diagnosed using the BIVA method. Diagnostic concordance between the BIVA and the new ESPEN definition was assessed with the Kappa coefficient. RESULTS: The malnutrition prevalence was higher with the BIVA vs ESPEN definition (22.1% vs 13.6%) in the global population and was similar (12.8% vs 12.1%) in the population at risk of malnutrition. The diagnostic performance of the BIVA was acceptable, with higher sensitivity in patients with fluid overload (FO) and more specificity in euvolemic patients. Diagnostic concordance between the BIVA and the ESPEN definition was poor for the global population (kappa = 0.56) and the population at risk of malnutrition (kappa = 0.67) but was acceptable in patients with FO (kappa = 0.78). However, the discordant BIVA+/ESPEN- patients classified as false positives for BIVA showed clinical and body composition data (low FFMI, low phase angle) consistent with malnutrition. CONCLUSIONS: According to the clinical and bioelectrical characteristics of the discordant BIVA+/ESPEN- patients, the BIVA could perform better that the new ESPEN definition for the diagnosis of hospital malnutrition, which should be confirmed with other studies.

Tratamiento de la leishmaniasis cutánea con rayos láser CO2 / Treatment of cutaneous leishmaniasis with CO2 laser rays

Se presentan 10 pacientes con diferentes formas clínicas de leishmaniasis cutánea a los que se les aplicó una exposición única de rayos láser de CO2. Se evaluaron evolutivamente hasta 2 años posteriores al tratamiento, sin que presentaran recidivas en ningún caso. La curación total de la lesión ocurrió sin efectos colaterales. Se recomienda el método descrito para el tratamiento de esta enfermedad siempre que sea posible su aplicación en lugar de los otros métodos descritos en la literatura

Tratamiento de la leishmaniasis cutánea con rayos láser CO2 / Treatent of cutaneous leishmaniasis with CO2 laser rays

Se presentan 10 pacientes con diferentes formas clínicas de leishmaniasis cutánea a los que se les aplicó una exposición única de rayos láser de CO2. Se evaluaron evolutivamente hasta 2 años posteriores al tratamiento, sin que presentaran recidivas en ningún caso. La curación total de la lesión ocurrió sin efectos colaterales. Se recomienda el método descrito para el tratamiento de esta enfermedad siempre que sea posible su aplicación en lugar de los otros métodos descritos en la literatura

Dengue en Cuba: historia de una epidemia / Dengue in Cuba: the history of an epidemic

Se muestra una panorámica del trabajo realizado por el Departamento de Arbovirus del IPK, con respecto al estudio del virus del dengue, agente causal de la epidemia de FDH/SSD, que afectó al país en el año 1981. Se incluyen no sólo los trabajos realizados en el transcurso de la epidemia, relacionados directamente con el diagnóstico, sino también otros efectuados posteriormente que abarcan aspectos clínicos, virológicos y epidemiológicos, todos aquellos de gran interés y vigencia, al tener en cuenta que la epidemia cubana ha sido la única ocurrida fuera del contexto del Sudeste Asiático y en la cual se conocen con suficiente exactitud las condiciones epidemiológicas que permitieron su aparición

Dengue en Cuba: historia de una epidemia / Dengue in Cuba: the history of an epidemic

Se muestra una panorámica del trabajo realizado por el Departamento de Arbovirus del IPK, con respecto al estudio del virus del dengue, agente causal de la epidemia de FDH/SSD, que afectó al país en el año 1981. Se incluyen no sólo los trabajos realizados en el transcurso de la epidemia, relacionados directamente con el diagnóstico, sino también otros efectuados posteriormente que abarcan aspectos clínicos, virológicos y epidemiológicos, todos aquellos de gran interés y vigencia, al tener en cuenta que la epidemia cubana ha sido la única ocurrida fuera del contexto del Sudeste Asiático y en la cual se conocen con suficiente exactitud las condiciones epidemiológicas que permitieron su aparición

Patología del cuello uterino: experiencia lograda en el Hospital Central de la Sanidad de las Fuerzas Policiales / Pathology of the uterine cervix: experience of the Central Hospital of Policial Forces Health

Se presenta la casuística de la Patología del Cuello Uterino en un lapso de 30 años (1954-1983), realizado en el Departamento de Anatomia Patológica del Hospital Central de Sanidad de las Fuerzas Policiales. En este período se procesaron 4,369 muestras de cuello uterino. La patología más frecuente es la Cervicitis crónica con 2,972 casos (68.0%). El Carcinoma epidermoide es el tumor maligno más frecuente del cuello uterino con 591 casos (92.6%). De ellos 229 corresponde al Carcinoma in Situ y 362 al Carcinoma Infiltrante. Los casos de Displasia y Carcinoma In Situ, son bajos en la primera década (1954-1963), debido a que fundamentalmente en esos años eran escasos los exámenes de despistaje. El grupo de edad de mayor presentación del Carcinoma Epidermoide es de 40 a 49 años. El Carcinoma In Situ, se presenta con mayor tendencia en los grupos de 40 a 60 años. En este tipo de lesión el síntoma principal, motivo de la consulta, es la ginecorragia, siendo varios de ellos asintomáticos especialmente el Carcinoma In Situ. El síntoma dolor es raro en los portadores de esta enfermedad

Brucellosis en el medio policial: pruebas serológicas para su seguimiento; importancia del 2-mercaptoetanol / Brucellosis in police milieu: serological tests for its follow-up; importance of 2-mercaptoethanol

Se presenta un estudio de 25 pacientes atendidos en el Hospital Central de la Sanidad de las Fuerzas Policiales con síntomas y signos de PIG., en las que las aglutinaciones para Brucellas presentaron títulos superiores a 1.100 por los métodos de placa y de tubo; asimismo a todos los pacientes se les hizo un seguimiento con 2 Mercaptoetanol. En los primeros 15 días de la enfermedad los Ac. aglutinantes fueron del tipo IgM; los Ac. IgG (2ME) aparecen después de los 15 días. Se demuestra que la evolución de los Ac. aglutinantes son independientes a la respuesta del tto, los títulos aumentan y se mantienen durante los 2 primeros meses, su disminución es en forma lenta. La prueba de aglutinación con 2ME es innecesario para la evolución y control del enfermo, el aumento de su título mínimo indicará recaída. Un buen número de enfermos presentan resultados paradojales en sus títulos aglutinantes

Incidencia de variente del antígeno Du en el medio policial / Variant of Du antigen incidence en police forces

Se revisaron 16,765 fichas de hemodonadores en el Archivo de la Sección Hemoterapia HCSFP en un lapso de cinco años 1980 a 1984; endontrándose 1,067 Rh negativos (6.3) de éstos, 20 fueron variante Du (1.8%). El estudio demuestra la importancia de hacer la determinación correcta del antígeno Du en los Rh negativos puesto que produce peligrosas sensibilizaciones al usarse en las transfusiones

Utilización de hematíes humanos "O" en la prueba de Waaler-Rose / Use of human hematies \"O\" in Waaler-Rose test

La obtención de una hemolisina anticarnero de alto poder es una necesidad para mejorar el sistema hemolítico; y, la posibilidad de los laboratorios pequeños para contar con un bioterio adecuado de donde obtener fácilmente los glóbulos rojos de carnero a motivado que el personal del Laboratorio Clínico del Hospital Central de la Sanidad de las Fuerzas Policiales se preocupe por la solución de este problema y llegar a implementar y mejorar la calidad de este tipo de análisis. En el presente trabajo se expone una técnica sencilla y fácil de realizar por personal capacitado, con la cual nos permite obtner altos títulos de suero hemolítico, al inyectar a un conejo, primero sangre humana total del grupo "O" por vía intracutánea, en dosis crecientes para luego continuar inyectando por vía endovenosa glóbulos rojos "O" al 20%. Obtuvimos un suero hemolítico con un título aglutinante de 1/3200. Posteriormente se realizó una técnica distinta utilizando glóbulos rojos "O" humanos sensibilizados con el suero hemolítico obtenido, obteniéndose resultados idénticos

Niveles de colesterol, triglicéridos y amilasa séricos en sujetos con dosaje etílico positivo / Cholesterol, triglycerides and serum amylase levels in subjects with positive ethylic dosage

El presente trabajo se realizó en el Laboratorio Clínico del Hospital Central de la Sanidad de las Fuerzas Policiales y Centro de Reconocimiento Médico SFP., con la finalidad de investigar los efectos del alcohol sobre los valores del colesterol, triglicéridos y amilasa séricos. Se evaluó a personas que por accidentes de tránsito fueron conducidos al Centro de Reconocimiento Médico por personal G.C. y que presentaron prueba cualitativa de alcoholemia positiva. Se seleccionaron 100 muestras con alcoholemia a partir de 0.61 gr/lt. Los sujetos se agruparon de acuerdo a tres niveles de alcoholemia y tres grupos etarios. Para el dosaje de colesterol se usó el método de Libermann-Burchard, triglicéridos por el método colorimétrico de Handel y la amilasa por método de Caraway modificado; así como el método de Sheftel para el dosaje de alcohol etílico. Se evalúan resultados y se encuentra incrementos leves y/o moderados en los valores de los triglicéridos. No se observó variaciones anormales en las cifras de colesterol y amilasa

La tomografía computada de abdómen en la estadificación de los linfomas / Computed tomography of abdomen in the staging of lymphoma

En la revisión de 100 pacientes con linfoma (19 con enfermedad de Hodgkin y 81 con linfoma no Hodgkin), la Tomografía Axial Computada (TAC) cambió el estadio clínico inicial en 34% de los casos, demostrando ser un estudio de gran valor para la estadificación de la enfermedad y por lo tanto eliminando la necesidad de realizar urografía excretora, cavografía y linfografía en muchos de los casos. La linfografía se recomienda particularmente cuando la tomografía computada muestra ganglios retroperitoneales de dimensiones normales, ya que la ausencia de adenomegalias no descarta la posibilidad de infiltración linfomatosa y la linfografía es el único método de estudio que permite valorar la arquitectura interna del ganglio. Se hace una revisión de los hallazgos en tomografía computada de la infiltración linfomatosa en ganglios retroperitoneales, mesentéricos, bazo, hígado y del tubo digestivo

Giardiasis en el medio policial / Giardiasis in polices force

Se examinaron 15,381 muestras en un período de dos años (1982 y 1983) en el Departamento de Laboratorio Clínico del Hospital Central de Sanidad de las Fuerzas Policiales. Se encontró 4,150 muestras positivas a parásitos en general (26,9%) de las cuales 1,687 correspondieron a Giardia lamblia (40.6%). Se demuestra una mayor incidencia en el personal subalterno y familiares 1,205 (71.4%), mientras que el personal oficial y familiares presentaron 482 casos (28.5%)