Valor pronóstico de los parámetros hematológicos y los parámetros metabólicos de la PET/TC con [18F]FDG en el cáncer de cabeza y cuello / Prognostic value of haematological parameters and [18F]FDG PET/CT metabolic parameters in head and neck cancer

Objetivo Determinar la utilidad de los cocientes neutrófilos/linfocitos (N/L) y plaquetas/linfocitos (P/L), así como de parámetros cuantitativos de la PET/TC con [18F]FDG, como factores pronósticos para la supervivencia global (SG), la supervivencia cáncer específica (SCE) y la supervivencia libre de progresión (SLP) en pacientes con carcinoma escamoso de cabeza y cuello (CyC) Material y métodos Se valoraron retrospectivamente 66 pacientes (56 hombres) diagnosticados de CyC durante un intervalo de 8años. Se determinaron los parámetros SUV máximo (SUVmax), volumen metabólico tumoral (MTV) y glucólisis tumoral total (TLG) del estudio PET/TC al diagnóstico. Tras tratamiento con quimiorradioterapia, se valoró la supervivencia de los pacientes. El modelo de regresión de Cox y el método de Kaplan-Meier se utilizaron para analizar factores pronósticos y curvas de supervivencia. Resultados El seguimiento medio fue de 50,4meses, produciéndose 39 recurrencias-progresiones y 39 fallecimientos. En el análisis univariante los parámetros metabólicos, excepto el SUVmax, fueron factores predictivos para las tres supervivencias, y los dos parámetros sanguíneos lo fueron para la SG y la SCE. La TLG fue el único factor predictivo en el análisis multivariante. Las tres curvas de supervivencias fueron significativamente diferentes para los parámetros metabólicos y la curva de SG para el cociente N/L. Se apreciaron correlaciones entre el cociente N/L, el MTV y la TLG. No se demostraron correlaciones entre el cociente P/L y los parámetros metabólicos. Conclusión El uso de marcadores hematológicos y metabólicos permitiría identificar pacientes con un alto riesgo de recurrencias y pobre supervivencia e individualizar el tratamiento aplicando terapias más agresivas (AU)

Aim To determine the usefulness of neutrophil/lymphocyte (N/L) and platelet/lymphocyte (P/L) ratios as well as quantitative [18F]FDG PET/CT parameters as prognostic factors for overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) in patients with head and neck squamous cell carcinoma (HyN). Material and methods Sixty-six patients (56 men) diagnosed with HyN carcinoma were retrospectively assessed over an 8-year interval. Maximum SUV (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) parameters were determined from the PET/CT study at diagnosis. After treatment with chemoradiotherapy, patient survival was assessed. The Cox regression model and the Kaplan-Meier method were used to analyse prognostic factors and survival curves. Results Median follow-up was 50.4months, with 39 recurrences-progressions and 39 deaths. In the univariate analysis, metabolic parameters, except SUVmax, were predictive factors for all three survivals and the two blood parameters were predictive for OS and EFS. TLG was the only predictive factor in the multivariate analysis. The three survival curves were significantly different for the metabolic parameters and the OS curve for the N/L ratio. Correlations were seen between N/L ratio, MTV and TLG. No correlations were demonstrated between P/L ratio and metabolic parameters. Conclusion The use of haematological and metabolic markers would allow to identify patients with a high risk of recurrences and poor survival and to individualise treatment by applying more aggressive therapies (AU)

Cumplimentación del consentimiento informado en cirugía radioguiada por los servicios de Cirugía General y Medicina Nuclear de una unidad de cirugía radioguiada / Completion of the informed consent in radioguided surgery by the General Surgery and Nuclear Medicine services of a radioguided surgery unit

Objetivo Identificar la frecuencia de errores en los documentos de consentimiento informado en cirugía radioguiada en un hospital de tercer nivel y detectar posibles causas o factores asociados a un mayor riesgo de error. Material y método Se analizaron los consentimientos informados de un total de 369 intervenciones de cirugía radioguiada, cumplimentados por los servicios de Medicina Nuclear y Cirugía General, y se analizó el grado de cumplimentación de los mismos y su correlación con facultativos responsables, tipo de enfermedad e intervención, tiempo de espera y cumplimentación del consentimiento de la otra especialidad. Resultados Se identificaron errores en 22 consentimientos de Medicina Nuclear y 71 consentimientos de Cirugía General. El error más común fue la ausencia de identificación del facultativo responsable (17 en Medicina Nuclear, 51 en Cirugía General), y el segundo más común la ausencia de documento (2 en Medicina Nuclear, 20 en Cirugía General). Existieron diferencias significativas en los errores cometidos en función del médico responsable, sin encontrarse correlación significativa con el resto de las variables. Conclusiones Los médicos responsables fueron el principal factor asociado a un mayor riesgo de error en la cumplimentación de consentimientos informados. Serían recomendables nuevos estudios para analizar factores casuales y posibles intervenciones para minimizar errores (AU)

Objective To identify the frequency of errors in the informed consent documents in radioguided surgery in a third level hospital and to detect possible causes or factors associated with a greater risk of error. Material and method The informed consents of a total of 369 radioguided surgery interventions, completed by the Nuclear Medicine and General Surgery services, were analyzed, as well as their degree of completion and its correlation with responsible physicians, type of pathology and intervention, waiting time and completion of the consent of the other specialty. Results Errors were identified in 22 consent forms for Nuclear Medicine and 71 consent forms for General Surgery. The most common error was the absence of identification of the responsible physician (17 in Nuclear Medicine, 51 in General Surgery), and the second most common was the absence of a document (2 in Nuclear Medicine, 20 in General Surgery). There were significant differences in the errors made depending on the doctor in charge, without finding a significant correlation with the other variables. Conclusions The responsible physicians were the main factor associated with a greater risk of error in the completion of informed consent. New studies would be recommended to analyze causal factors and possible interventions to minimize errors (AU)

Criterios PERCIST, Hopkins y parámetros metabólicos de la PET/TC como factores pronósticos en el cáncer escamoso de cabeza y cuello / PERCIST and Hopkins criteria and PET/CT metabolic parameters as prognostic factors in squamous head and neck cancer

Objetivo Valorar la utilidad clínica de los criterios PERCIST, Hopkins y de los cambios en los parámetros cuantitativos de la PET/TC con [18F]FDG como factores pronósticos para la supervivencia libre de progresión (SLP) y la supervivencia cáncer específica (SCE) en pacientes con cáncer escamoso de cabeza y cuello tratados mediante quimiorradioterapia. Material y métodos Se valoraron retrospectivamente 40 pacientes (34 hombres) diagnosticados de cáncer escamoso de cabeza y cuello durante un intervalo de 8 años. Se utilizaron los criterios PERCIST y Hopkins para determinar la respuesta al tratamiento. Así mismo, se cuantificaron las variaciones de los parámetros metabólicos SUV máximo (ΔSUVmax), volumen metabólico tumoral (ΔMTV) y glicólisis tumoral total (ΔTLG) entre los estudios PET/TC pre- y postratamiento. El modelo de regresión de Cox, las curvas ROC y el método de Kaplan-Meier se aplicaron para el análisis de factores pronósticos y curvas de supervivencia. Resultado El seguimiento medio fue de 39,4 meses produciéndose 24 recidivas-progresiones y 22 muertes. Tanto los criterios PERCIST y Hopkins como los tres parámetros metabólicos fueron factores predictivos en análisis univariante y solo el ΔSUVmax en el multivariante. El análisis de supervivencia mostró curvas de SLP y SCE significativamente diferentes para los cinco parámetros considerados. Conclusión La aplicación de los criterios PERCIST y Hopkins, así como los ΔSUVmax, ΔMTV y ΔTLG de los estudios PET/TC demostraron ser factores pronósticos para la supervivencia en pacientes de nuestro entorno tratados por cáncer de cabeza y cuello. Los resultados podrían ayudar a personalizar el tratamiento (AU)

Aim To assess the clinical utility of PERCIST and Hopkins criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with head and neck squamous cell carcinoma treated by chemoradiotherapy. Material and methods Forty patients (34 men) diagnosed with head and neck squamous cell carcinoma were retrospectively assessed over an interval of 8 years. PERCIST and Hopkins criteria were used to assess response to treatment. Variations in the metabolic parameters maximum SUV (ΔSUVmax), metabolic tumor volume (ΔMTV) and total lesion glycolysis (ΔTLG) between pre- and post-treatment PET/CT studies were also determined. Cox regression model, ROC curves and Kaplan-Meier method were used for the analysis of prognostic factors and survival curves. Results The average follow-up was 39.4 months, with 24 progressions and 22 deaths. Both PERCIST and Hopkins criteria and the three metabolic parameters were predictive factors in the univariate analysis and only ΔSUVmax in the multivariate analysis. Survival analysis showed statistically significant differences in PFS and CSS curves for the five parameters considered. Conclusion Application of PERCIST and Hopkins criteria as well as ΔSUVmax, ΔMTV and ΔTLG from PET/CT studies proved to be prognostic factors for survival in patients in our setting treated for head and neck cancer. The results could help to personalize treatment (AU)

Completion of the informed consent in radioguided surgery by the General Surgery and Nuclear Medicine services of a radioguided surgery unit.

OBJECTIVE: To identify the frequency of errors in informed consent documents in radioguided surgery in a third level hospital and to detect possible causes or factors associated with a greater risk of error. MATERIAL AND METHODS: Informed consent forms of a total of 369 radioguided surgery interventions, completed by the Nuclear Medicine and General Surgery services, were analyzed, and the degree of completion of the forms and its correlation with the physicians responsible, type of pathology, intervention, and waiting time were compared with the completion of consent by another specialty. RESULTS: Errors were identified in 22 consent forms from Nuclear Medicine and 71 from General Surgery. The most common error was the absence of identification of the physician responsible (17 in Nuclear Medicine, 51 in General Surgery), and the second most common was the absence of a document (2 in Nuclear Medicine, 20 in General Surgery). There were significant differences in the errors made depending on the doctor in charge, with no significant correlation with the other variables. CONCLUSIONS: The physicians responsible were the main factor associated with a greater risk of error in the completion of informed consent forms. Further studies are needed to analyze the causal factors and possible interventions to minimize errors.

Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

PERCIST and Hopkins criteria and PET/CT metabolic parameters as prognostic factors in squamous head and neck cancer.

AIM: To assess the clinical utility of PERCIST and Hopkins criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with head and neck squamous cell carcinoma treated by chemoradiotherapy. MATERIAL AND METHODS: Forty patients (34 men) diagnosed with head and neck squamous cell carcinoma were retrospectively assessed over an interval of 8 years. PERCIST and Hopkins criteria were used to assess response to treatment. Variations in the metabolic parameters maximum SUV (ΔSUVmax), metabolic tumor volume (ΔMTV) and total lesion glycolysis (ΔTLG) between pre- and post-treatment PET/CT studies were also determined. The Cox regression model, ROC curves and the Kaplan-Meier method were used for the analysis of prognostic factors and survival curves. RESULTS: The mean follow-up was 39.4 months, with 24 progressions and 22 deaths. Both PERCIST and Hopkins criteria and the three metabolic parameters were predictive factors in the univariate analysis and only ΔSUVmax was in the multivariate analysis. Survival analysis showed statistically significant differences in PFS and CSS curves for the five parameters considered. CONCLUSION: Application of PERCIST and Hopkins criteria as well as ΔSUVmax, ΔMTV and ΔTLG from PET/CT studies proved to be prognostic factors for survival in patients in our setting for treating head and neck cancer. The results may help to personalize treatment.

Tumor uterino que recuerda a los tumores de los cordones sexuales del ovario (UTROSCT): un caso clinicopatológico / Uterine tumour resembling ovarian sex cord tumours (UTROSCT): A clinicopathological case

Introducción: El tumor uterino que recuerda al tumor de los cordones sexuales del ovario (UTROSCT) es un tumor muy infrecuente de histogénesis incierta, incluido en la actual clasificación de tumores del estroma endometrial de la Organización Mundial de la Salud. Principales síntomas y/o hallazgos clínicos: Mujer de 48 años, sin antecedentes de interés, acudió a consulta por hipermenorreas en los últimos ciclos. La exploración ginecológica era normal. Diagnósticos principales, intervenciones terapéuticas y resultados: El estudio ecográfico mostró una lesión nodular submucosa de 26×21mm. Se le realizó histeroscopia diagnóstica, identificándose un mioma submucoso no accesible para extirpación ambulatoria. Se llevó a cabo histeroscopia quirúrgica procediéndose a miomectomía con asa de diatermia. Histológicamente se observó tejido muscular liso masivamente infiltrado por células de poco citoplasma con diferenciación glandular positivas con citoqueratinas, interpretándose como fragmentos de pared miometrial infiltrados por carcinoma. Se le realizó estudio de extensión e histerectomía. En la pieza quirúrgica no se identificó neoplasia residual. Se revaluó la biopsia previa y se amplió el estudio inmunohistoquímico, observándose positividad para marcadores de los cordones sexuales, epiteliales y musculares lisos. Ante estos hallazgos, el diagnóstico definitivo fue UTROSCT. Conclusión: El UTROSCT muestra generalmente un comportamiento benigno. Sin embargo, se considera de potencial maligno incierto, debido a que presenta una baja tasa de recurrencias y metástasis excepcionales. Desde el punto de vista histopatológico es importante reconocer esta entidad, ya que su histológica es variada imitando una amplia gama de tumores tanto benignos como malignos, por lo que es necesario realizar estudio inmunohistoquímico para su correcto diagnóstico.(AU)

Introduction: Uterine tumour resembling ovarian sex cord tumour (UTROSCT) is a very rare tumour of uncertain histogenesis, included in the current classification of endometrial stromal tumours of the World Health Organization. Main symptoms and/or clinical findings: 48-year-old woman with no history of interest, consulted for hypermenorrhoea in recent cycles. The gynaecological examination was normal. Main diagnoses, therapeutic interventions, and results: The ultrasound study showed a submucosal nodular lesion of 26×21mm. A diagnostic hysteroscopy was performed, identifying a submucosal myoma not accessible for outpatient removal. Surgical hysteroscopy was performed, proceeding to myomectomy with loop diathermy. Histologically, smooth muscle tissue was observed massively infiltrated by cells with scant cytoplasm and positive glandular differentiation for cytokeratins, interpreted as fragments of the myometrial wall infiltrated by carcinoma. An extension study and hysterectomy were performed. No residual neoplasia was identified in the surgical piece. A previous biopsy was re-evaluated and an immunohistochemical study was extended, showing positivity for sexual cord, epithelial, and smooth muscle markers. Given these findings, the definitive diagnosis was UTROSCT. Conclusion: UTROSCT generally shows benign behaviour. However, it is considered to be of uncertain malignant potential, due to its low rate of recurrence and rare metastases. From the histopathological point of view, it is important to recognize this entity, since its histology is varied, mimicking a wide range of tumours, both benign and malignant, making it necessary to perform an immunohistochemical study for its correct diagnosis.(AU)

[Atlantoid assimilation: malformation, compensation or deformity. Is it part of basilar invagination?] / Asimilación atlantoidea: malformación, compensación o deformidad. ¿Es parte de la invaginación basilar?

INTRODUCTION: atlas assimilation can occur alone or in association with other craniocervical junction malformations and deformities. The etiological and pathological mechanisms are not clear. CASE PRESENTATION: patient in her sixth decade of life, who was treated at the "Eugenio Espejo" Hospital, with asymmetric pyramidal symptoms after a low-energy kinetic fall. The condition completely reverted with conservative management. The patient is currently under periodic observation. CONCLUSION: the atlas assimilation, a congenital malformation, often asymptomatic; it is part of an embryological compensation when it is associated with other malformations. The appearance of deformity is necessary to reach atlantoaxial instability that it is not early. The knowledge of the concepts and distinction of the craniocervical junction abnormalities allows to indicate the best treatment in order to obtain the most suitable results with the individualization of each case.

INTRODUCCIÓN: la asimilación atlantoidea puede presentarse sola o asociada a otras malformaciones y deformidades de la unión craneocervical, los mecanismos etiológicos y patológicos no están esclarecidos. PRESENTACIÓN DE CASO: paciente de la sexta década de vida, quien fue atendida en el Hospital de Especialidades "Eugenio Espejo", con datos clínicos piramidales asimétricos, posteriores a mecanismo de lesión de caída con cinética de baja energía. La sintomatología revirtió con manejo conservador. En la actualidad, la paciente está bajo observación periódica. CONCLUSIÓN: la asimilación atlantoidea es una malformación congénita muchas veces asintomática y parte de una compensación embriológica cuando está asociada a otras malformaciones. Es necesaria la aparición de deformidad para llegar a la inestabilidad atlantoaxoidea que no es temprana. El conocimiento y poder diferenciar los conceptos de las anormalidades de la unión craneocervical permiten indicar el mejor tratamiento y así obtener los resultados más adecuados con la individualización de cada caso.

Linezolid for infective endocarditis: A structured approach based on a national database experience.

ABSTRACT: Current data on the frequency and efficacy of linezolid (LNZ) in infective endocarditis (IE) are based on small retrospective series. We used a national database to evaluate the effectiveness of LNZ in IE.This is a retrospective study of IE patients in the Spanish GAMES database who received LNZ. We defined 3 levels of therapeutic impact: LNZ < 7 days, LNZ high-impact (≥ 7 days, > 50% of the total treatment, and > 50% of the LNZ doses prescribed in the first weeks of treatment), and LNZ ≥ 7 days not fulfilling the high-impact criteria (LNZ-NHI). Effectiveness of LNZ was assessed using propensity score matching and multivariate analysis of high-impact cases in comparison to patients not treated with LNZ from the GAMES database matched for age-adjusted comorbidity Charlson index, heart failure, renal failure, prosthetic and intracardiac IE device, left-sided IE, and Staphylococcus aureus. Primary outcomes were in-hospital mortality and one-year mortality. Secondary outcomes included IE complications and relapses.From 3467 patients included in the GAMES database, 295 (8.5%) received LNZ. After excluding 3 patients, 292 were grouped as follows for the analyses: 99 (33.9%) patients in LNZ < 7 days, 11 (3.7%) in LNZ high-impact, and 178 (61%) in LNZ-NHI. In-hospital mortality was 51.5%, 54.4%, and 19.1% respectively. In the propensity analysis, LNZ high-impact group presented with respect to matched controls not treated with LNZ higher in-hospital mortality (54.5% vs 18.2%, P = .04). The multivariate analysis showed an independent relationship of LNZ use with in-hospital mortality (odds ratio 9.06, 95% confidence interval 1.15--71.08, P = .03).Treatment with LNZ is relatively frequent, but most cases do not fulfill our high-impact criteria. Our data suggest that the use of LNZ as definitive treatment in IE may be associated with higher in-hospital mortality.

Beyond words: From jaguar population trends to conservation and public policy in Mexico.

The jaguar (Panthera onca) is one of the most threatened carnivores in the Americas. Despite a long history of research on this charismatic species, to date there have been few systematic efforts to assess its population size and status in most countries across its distribution range. We present here the results of the two National Jaguar Surveys for Mexico, the first national censuses in any country within the species distribution. We estimated jaguar densities from field data collected at 13 localities in 2008-2010 (2010 hereafter) and 11 localities in 2016-2018 (2018 hereafter). We used the 2010 census results as the basis to develop a National Jaguar Conservation Strategy that identified critical issues for jaguar conservation in Mexico. We worked with the Mexican government to implement the conservation strategy and then evaluated its effectivity. To compare the 2010 and 2018 results, we estimated the amount of jaguar-suitable habitat in the entire country based on an ecological niche model for both periods. Suitable jaguar habitat covered ~267,063 km2 (13.9% of the country's territory) in 2010 and ~ 288,890 km2 (~14.8% of the country's territory) in 2018. Using the most conservative density values for each priority region, we estimated jaguar densities for both the high and low suitable habitats. The total jaguar population was estimated in ~4,000 individuals for 2010 census and ~4,800 for the 2018 census. The Yucatan Peninsula was the region with the largest population, around 2000 jaguars, in both censuses. Our promising results indicate that the actions we proposed in the National Jaguar Conservation Strategy, some of which have been implemented working together with the Federal Government, other NGO's, and land owners, are improving jaguar conservation in Mexico. The continuation of surveys and monitoring programs of the jaguar populations in Mexico will provide accurate information to design and implement effective, science-based conservation measures to try to ensure that robust jaguar populations remain a permanent fixture of Mexico's natural heritage.

Environmental and anthropogenic factors synergistically affect space use of jaguars.

Large terrestrial carnivores have undergone some of the largest population declines and range reductions of any species, which is of concern as they can have large effects on ecosystem dynamics and function.1-4 The jaguar (Panthera onca) is the apex predator throughout the majority of the Neotropics; however, its distribution has been reduced by >50% and it survives in increasingly isolated populations.5 Consequently, the range-wide management of the jaguar depends upon maintaining core populations connected through multi-national, transboundary cooperation, which requires understanding the movement ecology and space use of jaguars throughout their range.6-8 Using GPS telemetry data for 111 jaguars from 13 ecoregions within the four biomes that constitute the majority of jaguar habitat, we examined the landscape-level environmental and anthropogenic factors related to jaguar home range size and movement parameters. Home range size decreased with increasing net productivity and forest cover and increased with increasing road density. Speed decreased with increasing forest cover with no sexual differences, while males had more directional movements, but tortuosity in movements was not related to any landscape factors. We demonstrated a synergistic relationship between landscape-scale environmental and anthropogenic factors and jaguars' spatial needs, which has applications to the conservation strategy for the species throughout the Neotropics. Using large-scale collaboration, we overcame limitations from small sample sizes typical in large carnivore research to provide a mechanism to evaluate habitat quality for jaguars and an inferential modeling framework adaptable to the conservation of other large terrestrial carnivores.

Depressive and anxiety symptomatology among people with asthma or atopic dermatitis: A population-based investigation using the UK Biobank data.

The present study investigated the association of depression and anxiety symptomatology (DAS) with asthma and atopic dermatitis (AD) diagnosis during mid-adult years. The study employed data from 502,641 participants in the UK Biobank. Neutrophils to Lymphocytes Ratios (NLRs) of patients with asthma and AD were calculated and evaluated in relation to DAS, measured via the Patient Health Questionnaire-4 (PHQ-4). Age of asthma or AD onset association with DAS were also estimated. Multivariable regression analyses were implemented among participants with asthma or AD, compared to those without these disorders. Out of 58,833 participants with asthma and 13,462 with AD, the prevalence of DAS was 11.7% and 2.7%, respectively. DAS increased among participants with either asthma or AD, being highest within patients having both (ß = 0.41, 95% confidence interval (95%CI), 0.34,0.49). NLR showed a linear increase with PHQ scores in asthma patients, (tertile 1, ß = 0.30, 95% CI, 0.27,0.34; tertile 2, ß = 0.36, 95%CI, 0.32,0.39, and tertile 3, ß = 0.43, 95%CI, 0.39,0.46). An inverted U-shaped association was seen between age of asthma onset and PHQ, with the 40-59 age group (ß = 0.54, 95%CI, 0.48,0.59) showing the highest risk followed by the 60+ (ß = 0.43, 95%CI, 0.34,0.51 and 20-39 groups (ß = 0.32, 95%CI, 0.27,0.38). Similar patterns emerged within AD. Asthma and AD were associated with increased DAS during mid-adult years, being strongest among participants reporting both disorders. A dose-response relationship between NLR and DAS was observed. Asthma or AD onset during mid-adult years (40-59) were associated with the highest increment in DAS.

Non-local viscosity from the Green-Kubo formula.

We study through MD simulations the correlation matrix of the discrete transverse momentum density field in real space for an unconfined Lennard-Jones fluid at equilibrium. Mori theory predicts this correlation under the Markovian approximation from the knowledge of the non-local shear viscosity matrix, which is given in terms of a Green-Kubo formula. However, the running Green-Kubo integral for the non-local shear viscosity does not have a plateau. By using a recently proposed correction for the Green-Kubo formula that eliminates the plateau problem [Español et al., Phys. Rev. E 99, 022126 (2019)], we unambiguously obtain the actual non-local shear viscosity. The resulting Markovian equation, being local in time, is not valid for very short times. We observe that the Markovian equation with non-local viscosity gives excellent predictions for the correlation matrix from a time at which the correlation is around 80% of its initial value. A local in space approximation for the viscosity gives accurate results only after the correlation has decayed to 40% of its initial value.

Effects of body size on estimation of mammalian area requirements.

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross-validation to quantify bias in empirical home-range estimates. Area requirements of mammals <10 kg were underestimated by a mean approximately15%, and species weighing approximately100 kg were underestimated by approximately50% on average. Thus, we found area estimation was subject to autocorrelation-induced bias that was worse for large species. Combined with the fact that extinction risk increases as body mass increases, the allometric scaling of bias we observed suggests the most threatened species are also likely to be those with the least accurate home-range estimates. As a correction, we tested whether data thinning or autocorrelation-informed home-range estimation minimized the scaling effect of autocorrelation on area estimates. Data thinning required an approximately93% data loss to achieve statistical independence with 95% confidence and was, therefore, not a viable solution. In contrast, autocorrelation-informed home-range estimation resulted in consistently accurate estimates irrespective of mass. When relating body mass to home range size, we detected that correcting for autocorrelation resulted in a scaling exponent significantly >1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum.

Efectos del Tamaño Corporal sobre la Estimación de los Requerimientos de Área de Mamíferos Resumen La cuantificación precisa de los requerimientos de área de una especie es un prerrequisito para que la conservación basada en áreas sea efectiva. Esto comúnmente implica la recolección de datos de rastreo de la especie de interés para después realizar análisis de la distribución local. De manera problemática, la autocorrelación en los datos de rastreo puede resultar en una subestimación grave de las necesidades de espacio. Con base en trabajos previos, formulamos una hipótesis en la que supusimos que la magnitud de la subestimación varía con la masa corporal, una relación que podría tener implicaciones serias para la conservación. Para probar esta hipótesis en mamíferos terrestres, estimamos las áreas de distribución local con las ubicaciones en GPS de 757 individuos de 61 especies de mamíferos distribuidas mundialmente con una masa corporal entre 0.4 y 4,000 kg. Después aplicamos una validación cruzada en bloque para cuantificar el sesgo en estimaciones empíricas de la distribución local. Los requerimientos de área de los mamíferos <10 kg fueron subestimados por una media ∼15% y las especies con una masa ∼100 kg fueron subestimadas en ∼50% en promedio. Por lo tanto, encontramos que la estimación del área estaba sujeta al sesgo inducido por la autocorrelación, el cual era peor para las especies de talla grande. En combinación con el hecho de que el riesgo de extinción incrementa conforme aumenta la masa corporal, el escalamiento alométrico del sesgo que observamos sugiere que la mayoría de las especies amenazadas también tienen la probabilidad de ser aquellas especies con las estimaciones de distribución local menos acertadas. Como corrección, probamos si la reducción de datos o la estimación de la distribución local informada por la autocorrelación minimizan el efecto de escalamiento que tiene la autocorrelación sobre las estimaciones de área. La reducción de datos requirió una pérdida de datos del ∼93% para lograr la independencia estadística con un 95% de confianza y por lo tanto no fue una solución viable. Al contrario, la estimación de la distribución local informada por la autocorrelación resultó en estimaciones constantemente precisas sin importar la masa corporal. Cuando relacionamos la masa corporal con el tamaño de la distribución local, detectamos que la corrección de la autocorrelación resultó en un exponente de escalamiento significativamente >1, lo que significa que el escalamiento de la relación cambió sustancialmente en el extremo superior del espectro de la masa corporal.

El papel de las intervenciones biomédicas en la prevención del VIH: la profilaxis preexposición (PrEP) / The role of biomedical interventions in HIV prevention: pre-exposure Prophylaxis (PrEP)

La transmisión del VIH sigue siendo un importante problema de salud pública en todo el mundo. Estrategias tradicionales de prevención como la educación sexual, el cribado y el inicio precoz de tratamiento antirretroviral, a pesar de ser efectivas, resultan insuficientes para el control de las nuevas infecciones. En este contexto, se ha propuesto la profilaxis preexposición (PrEP) como estrategia preventiva. Actualmente, se ha demostrado ampliamente que la administración de fármacos antirretrovirales en personas expuestas y no infectadas por VIH puede reducir el riesgo de transmisión sin asociarse a inconvenientes significativos. A pesar de haber demostrado su eficacia para la prevención de nuevas infecciones, la PrEP sigue siendo un tema controvertido, especialmente su coste-efectividad, y no se ha conseguido acceso unánime a los grupos de mayor riesgo de infección. Por ello, y basándonos en la evidencia actual, planteamos que el debate no debería ser si la PrEP es coste-eficaz, sino las posibles repercusiones de implementarla

HIV infection remains an important public health problem worldwide. The traditional preventive measures, such as sexual education, screening, and early antiretroviral treatment initiation, despite having shown their effectiveness, are not enough to control new infections. In this context, Pre-Exposure Prophylaxis (PrEP) has been investigated as a preventive measure. Currently, it has been extensively documented that the administration of antiretroviral treatment in an HIV exposed, but not infected population, could reduce the risk of transmission without significant drawbacks. Despite its high efficacy for HIV prevention, the use of PrEP remains a controversial measure, particularly its cost-effectiveness. For this reason, the access to PrEP is not available for all the HIV risk groups. Therefore, and based on the evidence found, the current approach must be the repercussions of not to implement PrEP, more than its cost or its effectiveness

[The role of biomedical interventions in HIV prevention: Pre-exposure Prophylaxis (PrEP)]. / El papel de las intervenciones biomédicas en la prevención del VIH: la profilaxis preexposición (PrEP).

HIV infection remains an important public health problem worldwide. The traditional preventive measures, such as sexual education, screening, and early antiretroviral treatment initiation, despite having shown their effectiveness, are not enough to control new infections. In this context, Pre-Exposure Prophylaxis (PrEP) has been investigated as a preventive measure. Currently, it has been extensively documented that the administration of antiretroviral treatment in an HIV exposed, but not infected population, could reduce the risk of transmission without significant drawbacks. Despite its high efficacy for HIV prevention, the use of PrEP remains a controversial measure, particularly its cost-effectiveness. For this reason, the access to PrEP is not available for all the HIV risk groups. Therefore, and based on the evidence found, the current approach must be the repercussions of not to implement PrEP, more than its cost or its effectiveness.

Effectiveness of Panama as an intercontinental land bridge for large mammals.

Habitat fragmentation is a primary driver of wildlife loss, and establishment of biological corridors is a common strategy to mitigate this problem. A flagship example is the Mesoamerican Biological Corridor (MBC), which aims to connect protected forest areas between Mexico and Panama to allow dispersal and gene flow of forest organisms. Because forests across Central America have continued to degrade, the functioning of the MBC has been questioned, but reliable estimates of species occurrence were unavailable. Large mammals are suitable indicators of forest functioning, so we assessed their conservation status across the Isthmus of Panama, the narrowest section of the MBC. We used large-scale camera-trap surveys and hierarchical multispecies occupancy models in a Bayesian framework to estimate the occupancy of 9 medium to large mammals and developed an occupancy-weighted connectivity metric to evaluate species-specific functional connectivity. White-lipped peccary (Tayassu pecari), jaguar (Panthera onca), giant anteater (Myrmecophaga tridactyla), white-tailed deer (Odocoileus virginianus), and tapir (Tapirus bairdii) had low expected occupancy along the MBC in Panama. Puma (Puma concolor), red brocket deer (Mazama temama), ocelot (Leopardus pardalis), and collared peccary (Pecari tajacu), which are more adaptable, had higher occupancy, even in areas with low forest cover near infrastructure. However, the majority of species were subject to ≥1 gap that was larger than their known dispersal distances, suggesting poor connectivity along the MBC in Panama. Based on our results, forests in Darien, Donoso-Santa Fe, and La Amistad International Park are critical for survival of large terrestrial mammals in Panama and 2 areas need restoration.

Efectividad de Panamá como un Puente Terrestre Intercontinental para Mamíferos Mayores Resumen La fragmentación del hábitat es un causante primario de la pérdida de biodiversidad, y el establecimiento de corredores biológicos es una estrategia común para mitigar este problema. El Corredor Biológico Mesoamericano (CBM) es un ejemplo notable que pretende conectar áreas boscosas protegidas entre México y Panamá para permitir la dispersión y flujo genético de organismos del bosque. El funcionamiento del CBM se ha cuestionado debido a que la degradación de los bosques en Centroamérica continúa, pero no se dispone de estimaciones confiables de la ocurrencia de especies. Los mamíferos grandes son indicadores adecuados del funcionamiento de los bosques tropicales Por lo tanto evaluamos su estado de conservación en el Istmo de Panamá, la sección más angosta del CBM. Utilizamos muestreos con cámaras trampa y modelos de ocupación para múltiples especies bajo un modelo Bayesiano para estimar la ocupación de 9 especies de mamíferos medianos a grandes, y desarrollamos una métrica de conectividad ponderada por la ocupación para evaluar la conectividad funcional para cada especie. El puerco de monte (Tayassu pecari), jaguar (Panthera onca), hormiguero gigante (Myrmecophaga tridactyla), venado cola blanca (Oidocoileus virginianus), y tapir (Tapirus bairdii) presentaron una ocupación baja en el CBM en Panamá. El puma (Puma concolor), venado corzo (Mazama temama), ocelote (Leopardus pardalis) y el saino (Pecari tajacu), que son más adaptables, presentaron mayor ocupación, aún en áreas con poca cobertura boscosa, cercanas a infraestructura. Sin embargo, la mayoría de las especies estuvo sujeta a ≥ 1 vacío que era mayor que sus distancias de dispersión conocidas, lo que sugiere una conectividad pobre a lo largo del CBM en Panamá. Basados en nuestros resultados, los bosques de Darién, Donoso-Santa Fé y el Parque Internacional La Amistad son críticos para la supervivencia de mamíferos terrestres grandes en Panamá mientras que 2 áreas requieren restauración.

Hydrodynamic Properties of Biomacromolecules and Macromolecular Complexes: Concepts and Methods. A Tutorial Mini-review.

This article is intended to be an overview of the current possibilities offered by hydrodynamic methods in the calculation of properties and prediction of the behavior of biomacromolecules in solution. First, we briefly cover the experimental techniques, mentioning their fundamentals and current status. Using a tutorial approach, we provide basic hints to understand conceptual aspects of macromolecular hydrodynamics which underlie the instrumental methods and the modeling and computational procedures. The description is focused on the bead model methodology as implemented in the HYDRO suite of computer programs. For rigid particles, we cover simple models, such as ellipsoids and cylinders, to the most detailed models with atomic resolution. The fundamentals and applicability of the basic random coil and wormlike models for flexible particles are also briefly described. In addition to the simple linear, more or less flexible chain, flexibility may appear in other more specific forms. These cases can be treated by Monte Carlo and Brownian simulation methods, for which computational tools are also available. Finally, we present in some detail the applicability of these tools for unfolded and intrinsically disordered proteins. For the particular case of partially disordered proteins comprising both globular domains and flexible linkers or tails, solution properties can be accurately predicted, and this validation makes the methodology quite promising for future work.

Population genetic structure and habitat connectivity for jaguar (Panthera onca) conservation in Central Belize.

BACKGROUND: Connectivity among jaguar (Panthera onca) populations will ensure natural gene flow and the long-term survival of the species throughout its range. Jaguar conservation efforts have focused primarily on connecting suitable habitat in a broad-scale. Accelerated habitat reduction, human-wildlife conflict, limited funding, and the complexity of jaguar behaviour have proven challenging to maintain connectivity between populations effectively. Here, we used non-invasive genetic sampling and individual-based conservation genetic analyses to assess genetic diversity and levels of genetic connectivity between individuals in the Cockscomb Basin Wildlife Sanctuary and the Maya Forest Corridor. We used expert knowledge and scientific literature to develop models of landscape permeability based on circuit theory with fine-scale landscape features as ecosystem types, distance to human settlements and roads to predict the most probable jaguar movement across central Belize. RESULTS: We used 12 highly polymorphic microsatellite loci to identify 50 individual jaguars. We detected high levels of genetic diversity across loci (HE = 0.61, HO = 0.55, and NA = 9.33). Using Bayesian clustering and multivariate models to assess gene flow and genetic structure, we identified one single group of jaguars (K = 1). We identified critical areas for jaguar movement that fall outside the boundaries of current protected areas in central Belize. We detected two main areas of high landscape permeability in a stretch of approximately 18 km between Sittee River Forest Reserve and Manatee Forest Reserve that may increase functional connectivity and facilitate jaguar dispersal from and to Cockscomb Basin Wildlife Sanctuary. Our analysis provides important insights on fine-scale genetic and landscape connectivity of jaguars in central Belize, an area of conservation concern. CONCLUSIONS: The results of our study demonstrate high levels of relatively recent gene flow for jaguars between two study sites in central Belize. Our landscape analysis detected corridors of expected jaguar movement between the Cockscomb Basin Wildlife Sanctuary and the Maya Forest Corridor. We highlight the importance of maintaining already established corridors and consolidating new areas that further promote jaguar movement across suitable habitat beyond the boundaries of currently protected areas. Continued conservation efforts within identified corridors will further maintain and increase genetic connectivity in central Belize.