Molecular identification of Borrelia and SFG Rickettsia spp. in hard ticks parasitizing domestic and wild animals in southeastern Spain.

Lyme disease and the spotted fever group rickettsiosis, involve bacteria belonging to the genus Borrelia and Rickettsia, respectively. These infections are the most important tick-borne zoonotic diseases involving ticks as vectors. Descriptive and epidemiological studies are essential to determine the animal hosts involved in the maintenance of these diseases. In the present study, 94 tick pool samples from 15 different host species located in the Region of Murcia (southeastern, Spain) were analysed. Ticks were morphologically identified as: Dermacentor marginatus, Hyalomma lusitanicum, Ixodes Ricinus, and Rhipicephalus sanguineus. Our results showed that 5.3% of the tick pool samples carried Borrelia spp. DNA, and 20.2% carried SFG Rickettsia DNA. In every hard tick pool Spot Fever Group (SFG) Rickettsia spp. DNA were detected, except for H. lusitanicum. Likewise, D. marginatum was the only species in which Borrelia spp. DNA was not detected. Barbary sheep and wild boar were the host species in which tick pools showed DNA presence of both pathogens. This study increases the knowledge about the presence of Borrelia spp. DNA and SFG Rickettsia spp. DNA in different hard tick species from this geographical area.

Leader-follower formation control based on non-inertial frames for non-holonomic mobile robots.

A chain formation strategy based on mobile frames for a set of n differential drive mobile robots is presented. Considering two consecutive robots in the formation, robots Ri and Ri+1. It is intended that robot Ri+1 follows the delayed trajectory, τ units of time, of the leader robot Ri. In this way, the follower robot Ri+1 becomes the leader robot for robot Ri+ 2 in the formation and so on. With this formation policy, the trailing distance between two consecutive robots varies accordingly to the velocity of the Ri leader robot. Mobile frames are located on the body of the vehicles, in such a way that the position of robot Ri is determined with respect to the frame located on Ri+1 robot. The strategy relies on the fact that the general leader robot R1 describes any trajectory generated by bounded linear v1(t) and angular ω1(t) velocities. For the remaining vehicles in the string, the strategy considers a desired trajectory for the follower robot Ri+1 obtained by an estimation of the delayed trajectory of the leader robot Ri. This desired estimated trajectory is obtained under the knowledge of the actual and past input velocities of the Ri robot. To formally prove the convergence of the formation strategy, the equations describing the time variation of the relative posture between any pair of consecutive vehicles in the formation are obtained, and a feedback law based on local measurements is proposed to get the convergence of robot Ri+1 to the delayed trajectory, τ units of time, of the trajectory previously described by robot Ri. Lyapunov techniques are considered for this fact. The effectiveness of the chain formation solution is evaluated by means of numerical simulations and real time experiments showing an adequate convergence.

Conjugate treatment with high concentration normobaric oxygen and hyaluronic acid for vaginal atrophy: a prospective study.

OBJECTIVE: Vulvovaginal atrophy is a condition closely related to low circulating estrogen levels, with post-menopause being the main cause. However, patients of childbearing age may also present with these symptoms due to treatments that reduce estrogen production. Local estrogen therapy is the causal treatment of local symptoms, but it is not always accepted and is often abandoned by patients. In recent years, alternative therapies have been proposed: fractional CO2 laser or the conjugate treatment with normobaric oxygen and hyaluronic acid, the latter being the subject of this study. The study aimed to evaluate the effectiveness of conjugate topical treatment with normobaric oxygen and hyaluronic acid. PATIENTS AND METHODS: 50 patients were evaluated and treated with 5 applications of 15 minutes each, every 15 days, with Caressflow®. All patients presented at least one of the symptoms related to vulvovaginal atrophy: dryness, burning, and dyspareunia. In all cases, vulvoscopy, colposcopy, and cervicovaginal cytology were performed. The patients were interviewed with an analogic scale (VAS) concerning the severity of symptoms before and after the treatment. Colposcopy and PAP-smear were assessed by mean of Vaginal Health Index Score (VHI) at baseline and at the end of the treatment. RESULTS: All patients completed the treatment scheme and presented with a significant improvement in subjective symptoms. The colposcopy and PAP-smear performed 10 days after the end of the last treatment showed a significant improvement in the appearance and elasticity of the vaginal epithelium and the cytological picture, which showed, in the sample taken after treatment, hyaluronic acid vesicles within the cell cytoplasm. CONCLUSIONS: This study corroborates the data presented in the latest published papers on the effectiveness of treatment with normobaric O2 and hyaluronic acid on vaginal atrophy. Efficacy has been confirmed both in terms of subjective symptoms reported by the patients and objective improvement at colposcopy and PAP-smear cytology.

Strengthening preparedness against global health threats: A paradigm shift based on One Health approaches.

The implementation of preparedness strategies to prevent and mitigate the impact of global health threats poses several challenges. It should promptly identify cross-cutting drivers of pandemic threats, assess context-specific risks, engage multiple stakeholders, and translate complex data from multiple sources into accessible information for action. This requires a coordinated, multidisciplinary and multisectoral effort engaging systems that, most of the time, work in isolation. The One Health (OH) approach promotes the collaboration and communication among different disciplines and sectors, and could be applied across the preparedness phases at national and international level. We discuss here gaps and needs in preparedness strategies, which can benefit from the OH approach, and a set of actionable recommendations, as shared with the G20-2021 with a dedicated Policy Brief. The discussion adds to the current debate about OH operationalization and promotes a paradigm shift towards coordinated prevention and preparedness strategies for early assessment and management of global health threats.

New ABO intron 1 variant alleles.

Unusual and discrepant ABO phenotypes are often due to genetic variants that lead to altered levels or activity of ABO transferases and consequently to altered expression of ABO antigens. This report describes eight genetic alterations found in 15 cases with reduced or undetectable expression of ABO antigens. Forward and reverse ABO grouping was performed by standard gel or tube methods. Adsorption-heat elution and saliva testing for H and A substances followed the AABB technical manual procedures. Genomic DNA extracted from whole blood was PCR-amplified to cover the entire ABO coding sequence, splice junctions, proximal promoter, and intron 1 enhancer. Amplification products were sequenced by next-generation or Sanger dideoxy methods, either directly or after cloning into a bacterial plasmid vector. Eight unreported alleles were found in the 15 cases analyzed. Alleles ABO*A(28+1C) and ABO*A(29-5G) harbor variants that alter the consensus sequence at the intron 1 donor and acceptor splice sites, respectively. The other alleles harbor variants that alter the consensus sequence at transcription factor-binding sites in the intron 1 enhancer: specifically, ABO*A(28+5792T), ABO*A(28+5859A), and ABO*A(28+5860G) at GATA-1 sites; ABO*B(28+5877T) and ABO*B(28+5878G) at a RUNX1 site; and ABO*A(28+5843A) at or near a C/EBP site. Molecular and serologic characterization of ABO alleles can help in their future identification and in the resolution of discrepancies.Unusual and discrepant ABO phenotypes are often due to genetic variants that lead to altered levels or activity of ABO transferases and consequently to altered expression of ABO antigens. This report describes eight genetic alterations found in 15 cases with reduced or undetectable expression of ABO antigens. Forward and reverse ABO grouping was performed by standard gel or tube methods. Adsorption-heat elution and saliva testing for H and A substances followed the AABB technical manual procedures. Genomic DNA extracted from whole blood was PCR-amplified to cover the entire ABO coding sequence, splice junctions, proximal promoter, and intron 1 enhancer. Amplification products were sequenced by next-generation or Sanger dideoxy methods, either directly or after cloning into a bacterial plasmid vector. Eight unreported alleles were found in the 15 cases analyzed. Alleles ABO*A(28+1C) and ABO*A(29­5G) harbor variants that alter the consensus sequence at the intron 1 donor and acceptor splice sites, respectively. The other alleles harbor variants that alter the consensus sequence at transcription factor­binding sites in the intron 1 enhancer: specifically, ABO*A(28+5792T), ABO*A(28+5859A), and ABO*A(28+5860G) at GATA-1 sites; ABO*B(28+5877T) and ABO*B(28+5878G) at a RUNX1 site; and ABO*A(28+5843A) at or near a C/EBP site. Molecular and serologic characterization of ABO alleles can help in their future identification and in the resolution of discrepancies.

Hypersensitivity to platinum salts according to BRCA status in ovarian cancer: A retrospective analysis of clinical outcomes and systematic review of literature.

BACKGROUND: Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status. PATIENTS AND METHODS: We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series. RESULTS: Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. [9% vs 18%, p = 0.019] and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00-3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004-0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant. CONCLUSIONS: In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.

ANOVA to Compare Three Methods to Track COVID-19 in Nine Countries / ANOVA en la comparación de tres métodos para rastrear COVID-19 en nueve países

ABSTRACT A new coronavirus denominated first 2019-nCoV and later SARS-CoV-2 was found in Wuhan, China in December of 2019. This paper compares three mathematical methods: nonlinear regression, SIR, and SEIR epidemic models, to track the covid-19 disease in nine countries affected by the SARS-CoV-2 virus, to help epidemiologists to know the disease trajectory, considering initial data in the pandemic, mainly 100 days from the beginning. To evaluate the results obtained with the three methods one-way ANOVA is applied. The average of predicted infected cases with SARS-CoV-2, obtained with the mentioned methods was: for United States of America 1,098,508, followed by Spain with 226,721, Italy with 202,953, France with 183,897 United Kingdom with 182,190, Germany with 159,407, Canada with 58,696, Mexico with 50,366 and Argentina with 4,860 in average. The one-way ANOVA does not show a significant difference among the results of the projected infected cases by SARS-CoV-2, using nonlinear regression, SIR, and SEIR epidemic methods. The above could mean that initially any method can be used to model the pandemic course.

RESUMEN Un nuevo coronavirus denominado primero 2019-nCoV y más tarde SARS-CoV-2 fue encontrado en Wuhan, China en diciembre de 2019. El objetivo de este trabajo es comparar tres métodos matemáticos: regresión no lineal, modelos epidemiológicos SIR y SEIR, para rastrear la enfermedad del COVID-19 en nueve países infectados por el virus SARS-CoV-2, con el propósito de ayudar al epidemiólogo a conocer el curso de la pandemia, considerando principalmente sus primeros 100 días. Para evaluar los resultados obtenidos de la aplicación de los tres métodos, se aplicó ANOVA de una vía. El número promedio de casos infectados con SARS-CoV-2, obtenidos con los tres métodos descritos son: para Estados Unidos 1,098,508, seguido de España con 226,721, Italia con 202,953, Francia con 183,897 Reino Unido con 182,190, Alemania con 159,407, Canadá con 58,696, México con 50,366 y Argentina con 4,860 en promedio. El ANOVA de una vía no muestra diferencias significativas entre los resultados de los casos infectados proyectados por SARS-CoV-2, utilizando la regresión no lineal y los métodos SIR and SEIR. Lo anterior podría señalar que cualquiera de los tres métodos estudiados puede modelar el curso de la pandemia en las condiciones descritas para cada uno.

The transmission-blocking effects of antimalarial drugs revisited: fitness costs and sporontocidal effects of artesunate and sulfadoxine-pyrimethamine.

Assays used to evaluate the transmission-blocking activity of antimalarial drugs are largely focused on their potential to inhibit or reduce the infectivity of gametocytes, the blood stages of the parasite that are responsible for the onward transmission to the mosquito vector. For this purpose, the drug is administered concomitantly with gametocyte-infected blood, and the results are evaluated as the percentage of reduction in the number of oocysts in the mosquito midgut. We report the results of a series of experiments that explore the transmission-blocking potential of two key antimalarial drugs, artesunate and sulfadoxine-pyrimethamine, when administered to mosquitoes already infected from a previous blood meal. For this purpose, uninfected mosquitoes and mosquitoes carrying a 6 day old Plasmodium relictum infection (early oocyst stages) were allowed to feed either on a drug-treated or an untreated host in a fully factorial experiment. This protocol allowed us to bypass the gametocyte stages and establish whether the drugs have a sporontocidal effect, i.e. whether they are able to arrest the ongoing development of oocysts and sporozoites, as would be the case when a mosquito takes a post-infection treated blood meal. In a separate experiment, we also explored whether a drug-treated blood meal impacted key life history traits of the mosquito relevant for transmission, and if this depended on their infection status. Our results showed that feeding on an artesunate- or sulfadoxine-pyrimethamine-treated hosts has no epidemiologically relevant effects on the fitness of infected or uninfected mosquitoes. In contrast, when infected mosquitoes fed on an sulfadoxine-pyrimethamine-treated host, we observed both a significant increase in the number of oocysts in the midgut, and a drastic decrease in both sporozoite prevalence (-30%) and burden (-80%) compared with the untreated controls. We discuss the potential mechanisms underlying these seemingly contradictory results and contend that, provided the results are translatable to human malaria, the potential epidemiological and evolutionary consequences of the current preventive use of sulfadoxine-pyrimethamine in malaria-endemic countries could be substantial.

Aurore: A platform for ultrafast sciences.

We present the Aurore platform for ultrafast sciences. This platform is based on a unique 20 W, 1 kHz, 26 fs Ti:sapphire laser system designed for reliable operation and high intensity temporal contrast. The specific design ensures the high stability in terms of pulse duration, energy, and beam pointing necessary for extended experimental campaigns. The laser supplies 5 different beamlines, all dedicated to a specific field: attosecond science (Aurore 1), ultrafast phase transitions in solids (Aurore 2 and 3), ultrafast luminescence in solids (Aurore 4), and femtochemistry (Aurore 5). The technical specifications of these five beamlines are described in detail, and examples of the recent results are given.

Neurological outcome and modifiable events after out-of-hospital cardiac arrest in patients managed in a tertiary cardiac centre: A ten years register / Desenlaces neurológicos y acontecimientos modificables tras parada cardíaca extrahospitalaria en pacientes tratados en un centro de atención cardíaca terciaria: registro de 10 años

OBJECTIVE: A study was made of the events occurring in the early post-resuscitation phase that may help to improve the outcomes at hospital discharge. DESIGN: A retrospective cohort study (2007-2017) of a prospective Utstein type registry database was carried using multivariate logistic regression analysis. Pre- and post-hospital admission events were investigated. SETTING: A tertiary cardiac centre. PARTICIPANTS: Unconscious victims of out-of-hospital cardiac arrest (OHCA) with documented ventricular tachycardia or fibrillation. MAIN VARIABLES OF INTEREST: Events occurring before and within 72h after intensive care unit (ICU) admission were recorded. The variables were analyzed to determine their impact on hospital survival and poor neurological outcome. One-year follow-up survival was also considered. Results are presented as odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: Of 245 patients admitted to our ICU after OHCA, 152 (62%) were alive and 131 (86.2%) presented good neurological outcomes (cerebral performance categories≤2) at hospital discharge. The one-year follow-up survival rate was 95.9%. Age >70 years (OR 2.0; 95%CI 1.1-4.1), previous myocardial infarction (OR 2.7; 95%CI 1.2-6.1), shock upon hospital admission (OR 2.9; 95%CI 1.3-6.2), time from call to return of spontaneous circulation (ROSC) >25min (OR 3.1; 95%CI 1.6-6.0) and anticonvulsant therapy (OR 18.2; 95%CI 5.5-60) were independent predictors of poor neurological outcome. Immediate admission to the cardiac centre (OR 0.5; 95%CI 0.3-0.9) and lactate clearance reaching plasma levels <2.5mmol/l at 12h (OR 0.4; 95%CI 0.2-0.8) were associated with better outcomes. CONCLUSIONS: Unconscious OHCA patients with documented ventricular tachycardia or fibrillation may benefit from direct admission to a reference cardiac centre. Initial haemodynamic support, urgent coronary angiography and targeted management in the cardiac ICU seem to increase the likelihood of good neurological outcomes

OBJETIVO: Llevar a cabo un estudio de los acontecimientos ocurridos en la fase inmediatamente posterior a la reanimación que puedan ayudar a mejorar los desenlaces en el momento del alta hospitalaria. DISEÑO: Se realizó un estudio retrospectivo (2007-2017) de cohorte de una base de datos de registro de tipo Utstein prospectivo mediante un análisis de regresión logística multivariable. Se investigaron los acontecimientos previos y posteriores al ingreso hospitalario. Ámbito: Un centro de atención cardíaca terciaria. PARTICIPANTES: Víctimas inconscientes de parada cardíaca extrahospitalaria (OHCA) con fibrilación o taquicardia ventricular documentada. VARIABLES PRINCIPALES DE INTERÉS: Se registraron los acontecimientos ocurridos antes y durante las 72h posteriores al ingreso en la unidad de cuidados intensivos (UCI). Se analizaron las variables para determinar su impacto en la supervivencia hospitalaria y los malos desenlaces neurológicos. También se tuvo en consideración la supervivencia en el seguimiento a lo largo de un año. Los resultados se presentan con valores de oportunidad relativa (OR) e intervalo de confianza del 95% (IC del 95%). RESULTADOS: De los 245 pacientes ingresados en nuestra UCI tras una OHCA, 152 (62%) seguían vivos y 131 (86,2%) presentaban unos buenos desenlaces neurológicos (categorías de rendimiento cerebral≤2) en el momento del alta hospitalaria. La tasa de supervivencia en el seguimiento a lo largo de un año fue del 95,9%. La edad>70 años (OR: 2,0; IC del 95%: 1,1-4,1), los antecedentes de infarto de miocardio (OR: 2,7; IC del 95%: 1,2-6,1), el choque en el momento del ingreso hospitalario (OR: 2,9; IC del 95%: 1,3-6,2), el tiempo transcurrido entre la llamada y el regreso a la circulación espontánea (ROSC)>25min (OR: 3,1; IC del 95%: 1,6-6,0) y la administración de tratamiento anticonvulsivo (OR: 18,2; IC del 95%: 5,5-60) fueron factores predictivos independientes de un mal desenlace neurológico. El ingreso inmediato en un centro de cuidados cardíacos (OR: 0,5; IC del 95%: 0,3-0,9) y el hecho de que el aclaramiento de lactato alcanzase unos niveles plasmáticos<2,5mmol/l al cabo de 12h (OR: 0,4; IC del 95%: 0,2-0,8) se asociaron con unos mejores desenlaces. CONCLUSIONES: Los pacientes inconscientes tras OHCA y con fibrilación o taquicardia ventricular documentada podrían beneficiarse del ingreso directo en un centro cardíaco de referencia. El apoyo hemodinámico inicial, la angiografía coronaria urgente y el tratamiento dirigido en la UCI cardíaca parecen aumentar la probabilidad de obtener unos buenos desenlaces neurológicos

Análisis comparativo de costes directos e indirectos de dos técnicas mínimamente invasivas, para el tratamiento de la litiasis renoureteral menor de 2 cm / Comparative analysis of direct and indirect costs of two minimally invasive techniques for the treatment of renal/ureteral calculi smaller than 2 cm

OBJETIVO: Analizar de forma comparativa los costes indirectos y directos de dos técnicas mínimamente invasivas (litotricia extracorpórea (LEOC) vs. ureterorrenoscopia-láser holmium (URS/RIRS)) para el tratamiento de la litiasis reno-ureteral menor de 2 cm. MATERIAL Y MÉTODOS: Estudio prospectivo y comparativo, no aleatorizado de 84 pacientes tratados por litiasis reno-ureteral menor de 2 cm entre enero y diciembre de 2016. De estos, 38 (45,67%) se trataron con LEOC (18 litiasis renales y 20 litiasis ureterales) y 46 (54,32%) con URS/RIRS (22 litiasis renal y 24 litiasis ureteral). Un total de 19 (41,3%) pacientes estaban activos laboralmente en el grupo de URS/RIRS y 15 (39,5%) pacientes en el grupo de LEOC. Las variables analizadas fueron sexo, edad, número y tamaño de las litiasis, días de baja laboral debido al tratamiento, estimación del coste indirecto por la pérdida de productividad laboral y el coste directo del tratamiento aplicado incluyendo el seguimiento (número total de procedimientos, procedimientos auxiliares, visitas y pruebas diagnósticas). Para la estimación del coste indirecto se empleó la Encuesta de Estructura Salarial 2015 (INE). Además, también se utilizó el cuestionario «Work Productivity and Activity Impairment» (WPAI) para determinar el grado de percepción de pérdida de productividad. RESULTADOS: El número medio de sesiones hasta la resolución de la litiasis fue de 2,57 para el grupo de LEOC y de 1,04 para la URS. El promedio de días de baja laboral en el grupo de la URS fue de 7,16 días, mientras que en el caso de la LEOC fue de 3,18 (p = 0,034). Los costes indirectos totales derivados de la pérdida de productividad fueron de 621,55 € y de 276,05 € para la URS y LEOC, respectivamente. Los costes directos en el grupo de la LEOC fueron de 1.382,9 € y 2.317,71 € en el grupo de la URS. El grado de afectación en el trabajo percibido por los pacientes sometidos a URS fue del 18,88% y del 21,33% en el grupo de LEOC. El grado de afectación para realizar actividades cotidianas fue del 24,44% en URS y del 15% en LEOC. CONCLUSIONES: La LEOC es una técnica que precisa de un mayor número medio de sesiones para la resolución de la litiasis reno-ureteral menor de 2 cm, pero con una menor repercusión en los costes totales y en la percepción del grado de afectación

OBJECTIVE: To perform a comparative analysis of indirect and direct costs of two minimally invasive techniques (extracorporeal shock wave lithotripsy (ESWL) vs. ureteroscopy with holmium laser (URS/RIRS)) for the treatment of renal/ureteral calculi smaller than 2 cm. MATERIAL AND METHODS: Prospective, comparative, non-randomized study of 84 patients treated for kidney stones smaller than 2 cm between January and December 2016. Of these, 38 (45.67%) were treated with ESWL (18 renal lithiasis and 20 ureteral lithiasis) and 46 (54.32%) with URS/RIRS (22 renal lithiasis and 24 ureteral lithiasis). A total of 19 (41.3%) patients in the URS/RIRS group and 15 (39.5%) patients in the ESWL group were actively working before treatment. The variables analyzed were sex, age, number and size of lithiasis, time (days) off from work due to treatment, estimate of indirect cost due to labor productivity loss and direct treatment costs including follow-up (total number of procedures, ancillary care, visits and diagnostic tests). The 2015 Wage Structure Survey (INE) was used to estimate the indirect cost. In addition, the «Work Productivity and Activity Impairment» (WPAI) questionnaire was also used to determine the level of perceived productivity loss. RESULTS: The mean number of sessions until lithiasis resolution was achieved was 2.57 for the ESWL group and 1.04 for the URS. The mean number of days off from work in the URS group was 7.16 days and 3.18 (p = 0.034) in the ESWL group. The total indirect costs resulting from productivity loss were EUR 621.55 and EUR 276.05 for the URS and ESWL, respectively. Direct costs in the ESWL group were EUR 1,382.9 and EUR 2,317.71 in the URS group. The level of work impairment perceived by patients undergoing URS was 18.88% and 21.33% in the ESWL group. The degree of impairment for performing activities of daily living was 24.44% in the URS and 15% in ESWL. CONCLUSIONS: The ESWL technique requires a higher number of sessions for the resolution of kidney stones under 2 cm, but it has a lower impact on total costs and on the perceived degree of affectation

Comparative analysis of direct and indirect costs of two minimally invasive techniques for the treatment of renal/ureteral calculi smaller than 2 cm. / Análisis comparativo de costes directos e indirectos de dos técnicas mínimamente invasivas, para el tratamiento de la litiasis renoureteral menor de 2 cm.

OBJECTIVE: To perform a comparative analysis of indirect and direct costs of two minimally invasive techniques (extracorporeal shock wave lithotripsy (ESWL) vs. ureteroscopy with holmium laser (URS/RIRS)) for the treatment of renal/ureteral calculi smaller than 2 cm. MATERIAL AND METHODS: Prospective, comparative, non-randomized study of 84 patients treated for kidney stones smaller than 2 cm between January and December 2016. Of these, 38 (45.67%) were treated with ESWL (18 renal lithiasis and 20 ureteral lithiasis) and 46 (54.32%) with URS/RIRS (22 renal lithiasis and 24 ureteral lithiasis). A total of 19 (41.3%) patients in the URS/RIRS group and 15 (39.5%) patients in the ESWL group were actively working before treatment. The variables analyzed were sex, age, number and size of lithiasis, time (days) off from work due to treatment, estimate of indirect cost due to labor productivity loss and direct treatment costs including follow-up (total number of procedures, ancillary care, visits and diagnostic tests). The 2015 Wage Structure Survey (INE) was used to estimate the indirect cost. In addition, the «Work Productivity and Activity Impairment¼ (WPAI) questionnaire was also used to determine the level of perceived productivity loss. RESULTS: The mean number of sessions until lithiasis resolution was achieved was 2.57 for the ESWL group and 1.04 for the URS. The mean number of days off from work in the URS group was 7.16 days and 3.18 (p = 0.034) in the ESWL group. The total indirect costs resulting from productivity loss were EUR 621.55 and EUR 276.05 for the URS and ESWL, respectively. Direct costs in the ESWL group were EUR 1,382.9 and EUR 2,317.71 in the URS group. The level of work impairment perceived by patients undergoing URS was 18.88% and 21.33% in the ESWL group. The degree of impairment for performing activities of daily living was 24.44% in the URS and 15% in ESWL. CONCLUSIONS: The ESWL technique requires a higher number of sessions for the resolution of kidney stones under 2 cm, but it has a lower impact on total costs and on the perceived degree of affectation.

Quantification of neutrophil and monocyte CD64 expression: a predictive biomarker for active tuberculosis.

SETTING: QuantiFERON TB assay (QFT) is used to screen tuberculosis (TB) infection, but it cannot distinguish active TB from latent TB infection (LTBI).OBJECTIVE: To evaluate the quantitative expression of the high-affinity FCgamma receptor I (CD64) on neutrophils (NE) and monocytes (MO) in peripheral blood using flow cytometry, measured in antibody binding capacity (ABC) units as a predictive biomarker of TB.DESIGN: Fifty-two patients were enrolled (45 QFT-positive and 7 QFT-indeterminate). Cultures and molecular analyses were performed.RESULTS: Of the 45 QFT-positive patients, 29 were culture-positive (active TB) and 16 were negative (LTBI). The median NE CD64 ABC and MO CD64 ABC expression was significantly higher (P < 0.001) in culture-positive patients. The NE CD64 and MO CD64 area under the receiver operating characteristic curve values were respectively 0.948 (95%CI 0.838-0.992) and 0.989 (0.901-1.000). By setting the cut-off NE CD64 value at >2400 ABC or MO CD64 value >25 800 the assay sensitivity increased to 95.5% with 100% specificity and 100% positive predictive value. In the QFT-indeterminate group, five culture-positive cases had NE CD64 >2400 ABC or MO CD64 value >25 800; two culture-negative cases had lower values.CONCLUSION: The CD64 quantitative expression on peripheral blood cells may be used as a predictive biomarker for active TB.

Neurological outcome and modifiable events after out-of-hospital cardiac arrest in patients managed in a tertiary cardiac centre: A ten years register.

OBJECTIVE: A study was made of the events occurring in the early post-resuscitation phase that may help to improve the outcomes at hospital discharge. DESIGN: A retrospective cohort study (2007-2017) of a prospective Utstein type registry database was carried using multivariate logistic regression analysis. Pre- and post-hospital admission events were investigated. SETTING: A tertiary cardiac centre. PARTICIPANTS: Unconscious victims of out-of-hospital cardiac arrest (OHCA) with documented ventricular tachycardia or fibrillation. MAIN VARIABLES OF INTEREST: Events occurring before and within 72h after intensive care unit (ICU) admission were recorded. The variables were analyzed to determine their impact on hospital survival and poor neurological outcome. One-year follow-up survival was also considered. Results are presented as odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: Of 245 patients admitted to our ICU after OHCA, 152 (62%) were alive and 131 (86.2%) presented good neurological outcomes (cerebral performance categories≤2) at hospital discharge. The one-year follow-up survival rate was 95.9%. Age >70 years (OR 2.0; 95%CI 1.1-4.1), previous myocardial infarction (OR 2.7; 95%CI 1.2-6.1), shock upon hospital admission (OR 2.9; 95%CI 1.3-6.2), time from call to return of spontaneous circulation (ROSC) >25min (OR 3.1; 95%CI 1.6-6.0) and anticonvulsant therapy (OR 18.2; 95%CI 5.5-60) were independent predictors of poor neurological outcome. Immediate admission to the cardiac centre (OR 0.5; 95%CI 0.3-0.9) and lactate clearance reaching plasma levels <2.5mmol/l at 12h (OR 0.4; 95%CI 0.2-0.8) were associated with better outcomes. CONCLUSIONS: Unconscious OHCA patients with documented ventricular tachycardia or fibrillation may benefit from direct admission to a reference cardiac centre. Initial haemodynamic support, urgent coronary angiography and targeted management in the cardiac ICU seem to increase the likelihood of good neurological outcomes.

Mangiferin glycethosomes as a new potential adjuvant for the treatment of psoriasis.

Mangiferin, a natural compound isolated from Mangifera indica L, was incorporated in glycerosomes, ethosomes and alternatively in glycerol-ethanol phospholipid vesicles (glycethosomes). Actually, only glycethosomes were able to stably incorporate the mangiferin that was loaded at increasing concentrations (2, 4, 6, 8 mg/mL). The morphology, size distribution, rheological properties, surface charge and entrapment efficiency of prepared vesicles were deeply measured. All vesicles were mainly spherical, oligolamellar, small in size (~145 nm) and negatively charged (~-40 mV), as confirmed by cryo-TEM observation and dynamic laser light scattering measurements. The higher concentration of mangiferin (8 mg/mL) allowed an increase of vesicle mean diameter up to ~288 nm. The entrapment efficiency was inversely proportional to the amount of loaded mangiferin. In vitro studies performed by using human abdominal skin, underlined that, the dose-dependent ability of vesicles to promote mangiferin retention in epidermis. In addition, glycethosomes were highly biocompatible and showed a strong ability to protect in vitro the fibroblasts against damages induced by hydrogen peroxide. In vivo results underlined the superior ability of mangiferin loaded glycethosomes respect to the mangiferin dispersion to promote the heal of the wound induced by TPA, confirming their potential application for the treatment of psoriasis or other skin disorders.

Linear IgA Bullous Dermatosis: A Series of 17 Cases. / Dermatosis ampollar IgA lineal: serie de 17 casos.

Linear IgA bullous dermatosis is an acquired subepidermal immunoglobulin-mediated vesiculobullous disease. In this retrospective, observational, descriptive study, we describe the clinical characteristics, treatments, and outcomes of 17 patients with linear IgA bullous dermatosis. Two children had been vaccinated 2 weeks before the onset of symptoms, 2 had had bronco-obstructive respiratory symptoms, and 1 had received intravenous antibiotic therapy. We also observed an association with autoimmune hepatitis in one patient and alopecia areata in another. One boy had VACTERL association. Diagnosis was confirmed by histopathology and direct immunofluorescence. Sixteen patients were treated with dapsone, which was combined with oral corticosteroids in 8 cases and topical corticosteroids in two. Of note in this series was the occurrence of relapses in the perioral area coinciding with infections and vaccination, and the association between linear IgA bullous dermatosis and autoimmune hepatitis and VACTERL association.

Factores predictores de complicaciones infecciosas en el postoperatorio de la nefrolitotomía percutánea / Predictive factors of infectious complications in the postoperative period of percutaneous nephrolithotomy

Objetivo: Las complicaciones infecciosas (CI) tras la nefrolitotomía percutánea (NLPC) pueden llegar a ser de gravedad. Nuestro objetivo fue analizar factores predictores preoperatorios de CI tras la NLPC. Materiales y métodos: Se incluyó en un estudio prospectivo a un total de 203 pacientes que se trataron con NLPC entre enero de 2013 y febrero de 2016. Se definió CI postoperatoria como infección urinaria/pielonefritis, síndrome de respuesta inflamatoria sistémica o sepsis. Las variables analizadas fueron: edad, sexo, número, lado y tamaño (cm) de la litiasis; unidades Hounsfield, diabetes (insulinodependiente o no), cultivo de orina preoperatorio, bacteria aislada, multitrayecto, índice de masa corporal y tiempo quirúrgico (min). Se llevó a cabo un análisis multivariante (regresión logística). Resultados: Se produjeron CI en 30 pacientes (14,8%): en 9 de ellos (4,4%) se presentó infección urinaria, en 14 (6,9%) síndrome de respuesta inflamatoria sistémica y en 7 (3,5%) sepsis. Además, 13 (43,3%) tenían un cultivo de orina preoperatorio negativo, 15 (50%) positivo y en 2 (6,7%) no estaba disponible. En la regresión logística, el tamaño de la litiasis, la diabetes insulinodependiente y el sexo femenino resultaron factores predictores independientes de CI (OR: 1,03; 14,6 y 7,8, respectivamente; p = 0,0001). Conclusiones: Pacientes con litiasis de mayor tamaño, diabéticos insulinodependientes y mujeres deberían ser aconsejados de forma preoperatoria sobre el riesgo de CI tras la NLPC, y ser estrechamente seguidos tras la cirugía. Además, un cultivo de orina preoperatorio negativo no ofrece fiabilidad suficiente para excluir el riesgo de CI

Objective: Infectious complications (IC) following percutaneous nephrolithotomy surgery (PCNL) can be life-threatening. Our objective was to analyze preoperative predictors of IC in PCNL. Materials and methods: A total of 203 patients who underwent PCNL were included in a prospective study between January 2013 and February 2016. A postoperative IC was defined as urinary infection/pyelonephritis, systemic inflammatory response syndrome or sepsis. The variables analyzed were age, gender, number, size (cm) and side of stone; Hounsfield units, diabetes (insulin dependent or not), preoperative culture, isolated bacteria, multitract, body mass index and surgical time (min). A multivariate forward stepwise (logistic regression) was performed. Results: IC occurred in 30 patients (14.8%): 9 (4.4%) had urinary infection, 14 (6.9%) systemic inflammatory response syndrome and 7 (3.5%) sepsis. In addition, 13 (43.3%) had negative preoperative urine culture, 15 (50%) positive and in 2 (6.7%) was not available. On the logistic regression analysis, stone size (cm), insulin dependent diabetes and female sex were independently associated with increased risk of IC (odds ratio [OR] 1.03, 14.6 and 7.8, respectively; p = 0.0001). Conclusions: Patients with large stone burdens, insulin-dependentdiabetes condition and female gender, should be counselled properly regarding postoperative infection risks and closely followed up to diagnose IC (specially sepsis) soon enough. Negative preoperative urine culture seems not reliable enough to exclude an infectious complication according to our results

Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1α in NSCLC which can be overcome by OXPHOS inhibition.

BACKGROUND: Platinum-based chemotherapy remains the standard of care for most lung cancer cases. However chemoresistance is often developed during the treatment, limiting clinical utility of this drug. Recently, the ability of tumor cells to adapt their metabolism has been associated to resistance to therapies. In this study, we first described the metabolic reprogramming of Non-Small Cell Lung Cancer (NSCLC) in response to cisplatin treatment. METHODS: Cisplatin-resistant versions of the A549, H1299, and H460 cell lines were generated by continuous drug exposure. The long-term metabolic changes, as well as, the early response to cisplatin treatment were analyzed in both, parental and cisplatin-resistant cell lines. In addition, four Patient-derived xenograft models treated with cisplatin along with paired pre- and post-treatment biopsies from patients were studied. Furthermore, metabolic targeting of these changes in cell lines was performed downregulating PGC-1α expression through siRNA or using OXPHOS inhibitors (metformin and rotenone). RESULTS: Two out of three cisplatin-resistant cell lines showed a stable increase in mitochondrial function, PGC1-α and mitochondrial mass with reduced glycolisis, that did not affect the cell cycle. This phenomenon was confirmed in vivo. Post-treatment NSCLC tumors showed an increase in mitochondrial mass, PGC-1α, and a decrease in the GAPDH/MT-CO1 ratio. In addition, we demonstrated how a ROS-mediated metabolism reprogramming, involving PGC-1α and increased mitochondrial mass, is induced during short-time cisplatin exposure. Moreover, we tested how cells with increased PGC-1a induced by ZLN005 treatment, showed reduced cisplatin-driven apoptosis. Remarkably, the long-term metabolic changes, as well as the metabolic reprogramming during short-time cisplatin exposure can be exploited as an Achilles' heel of NSCLC cells, as demonstrated by the increased sensitivity to PGC-1α interference or OXPHOS inhibition using metformin or rotenone. CONCLUSION: These results describe a new cisplatin resistance mechanism in NSCLC based on a metabolic reprogramming that is therapeutically exploitable through PGC-1α downregulation or OXPHOS inhibitors.

Predictive factors of infectious complications in the postoperative of percutaneous nephrolithotomy. / Factores predictores de complicaciones infecciosas en el postoperatorio de la nefrolitotomía percutánea.

OBJECTIVE: Infectious complications (IC) following percutaneous nephrolithotomy surgery (PCNL) can be life-threatening. Our objective was to analyse preoperative predictors of IC in PCNL. MATERIALS AND METHODS: A total of 203 patients who underwent PCNL were included in a prospective study between January 2013 and February 2016. A postoperative IC was defined as urinary infection/pyelonephritis, systemic inflammatory response syndrome or sepsis. The variables analysed were age, gender, number, size(cm) and side of stone; Hounsfield units,diabetes (insulin dependent or not), preoperative culture, isolated bacteria, multitract, bodymass index and surgical time (min). A multivariate forward stepwise (logistic regression) was performed. RESULTS: IC occurred in 30 patients (14.8%): 9 (4.4%) had urinary infection, 14 (6.9%) systemic inflammatory response syndrome and 7 (3.5%) sepsis. In addition, 13 (43.3%) had negative preoperative urine culture, 15 (50%) positive and in 2 (6.7%) was not available. On the logistic regression analysis, stone size (cm), insulin dependent diabetes and female sex were independently associated with increased risk of IC (odds ratio [OR] 1.03, 14.6 and 7.8, respectively; P=.0001). CONCLUSIONS: Patients with large stone burdens, insulin diabetes condition and female gender, should be counselled properly regarding postoperative infection risks and closely followed up to diagnose IC (specially sepsis) soon enough. Negative preoperative urine culture seems not reliable enough to exclude an infectious complication according to our results.