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Black soldier fly larvae (BSFL) (Hermetia illucens) reared on food waste streams are considered a sustainable source of protein in feed livestock diets. Recently, portable near-infrared spectroscopy (NIR) instruments have been assessed to monitor the consistency and quality of food waste streams used to feed black soldier fly larvae. During the application of NIR spectroscopy, sample presentation (e.g., drying, processing, particle size) plays an important role in the accuracy of the models developed (quantitative or qualitative analysis). The objective of this study was to evaluate the effect of sample presentation (number of larvae used during the scanning of BSFL) on the accuracy of classification models developed to trace the food waste stream (e.g., supermarket of childcare) used to feed the larvae. BSFL samples were sourced from two waste streams and scanned as half, 1, 2, or 3 larvae using an NIR portable instrument (MicroNIR, Viavi, Milpitas, California, USA). Principal component analysis (PCA) and linear discriminant analysis (LDA) were used to analyze the NIR data and to classify the samples according to the waste stream. The main differences in the NIR spectra of the BSFL samples associated with the number of larvae scanned were observed around 1200 nm, mainly associated with the C-H overtones (lipids). The classification results showed that high classification rates (>93%) were obtained regardless of the number of larvae scanned, ranging from 93% (using 0.5 larvae) to 100% (using 1, 2, or 3 larvae samples). Overall, the number of larvae scanned had minimal to no effect on the accuracy of the LDA classification models. The present study demonstrated that a portable NIR instrument can be suitable for an initial rapid classification or determination of the origin of the waste stream used to feed the BSFL.

Introduction: A picture version of the Free and Cued Selective Reminding Test (FCSRT) would assist in the assessment of memory function in patients with low levels of schooling. A shortened version would improve the test's applicability. Objectives: To analyse the diagnostic usefulness of a shortened picture version of the FCSRT for distinguishing patients with amnestic mild cognitive impairment (aMCI) from controls, without excluding participants with a low level of schooling. Methods: Phase I study of a diagnostic evaluation (convenience sampling; pre-test prevalence 50%). A blinded researcher independently administered the FCSRT to 30 patients with aMCI and 30 controls matched for age, sex, level of schooling and literacy, using images and omitting the usual 30-minutes delayed recall item. Three variables were recorded: free recall, total recall, and cue efficiency. Diagnostic accuracy was calculated using receiver operating characteristic curves and the area under the curve. The Youden index was used to identify optimal cut-off points. Results: Of all participants, 41.7% had not completed primary education. There were no differences between groups as regards sociodemographic variables. Area under the curve was excellent for free recall (0.99), total recall (0.95), and cue efficiency (0.93). The optimal cut-off points were 21/22, 43/44, and < 0.77, respectively. Conclusions: This preliminary analysis shows that a shortened picture version of the FCSRT may be useful and applicable for the diagnosis of aMCI without excluding individuals with a low level of schooling. Resumen: Introducción: Una versión pictórica del Free and Cued Selective Reminding Test (FCSRT) facilitaría la evaluación de la memoria en pacientes con bajo nivel educativo. Una forma abreviada mejoraría la aplicación. Objetivo: Analizar la utilidad diagnóstica de una versión pictórica y abreviada del FCSRT para distinguir pacientes con deterioro cognitivo leve amnésico (DCLa) de controles, sin excluir a individuos con un nivel educativo bajo. Método: Estudio en fase i de evaluación de prueba diagnóstica (muestreo de conveniencia, prevalencia pretest del 50%). El FCSRT fue administrado, de forma independiente y ciega al diagnóstico, a 30 pacientes con DCLa (recomendaciones NIA-AA 2011) y a 30 controles emparejados por edad, género, nivel educativo y grado de alfabetización, utilizando imágenes y obviando el ensayo diferido. Tres variables resultado fueron registradas: recuerdo libre total, recuerdo total e índice de sensibilidad a la pista. La utilidad diagnóstica fue calculada mediante el área bajo la curva ROC. El índice Youden fue usado para seleccionar los mejores puntos de corte. Resultados: El 41,7% de los participantes no habían completado estudios primarios. No hubo diferencias entre los 2 grupos respecto a las variables sociodemográficas. Las áreas bajo la curva fueron óptimas para recuerdo libre total (0,99), recuerdo total (0,95) e índice de sensibilidad a la pista (0,93). Los mejores puntos de corte fueron 21/22, 43/44 y

Black soldier fly larvae (BSFL) (Hermetia illucens) reared on food waste streams are considered a sustainable source of protein in feed livestock diets. Recently, portable near-infrared spectroscopy (NIR) instruments have been assessed to monitor the consistency and quality of food waste streams used to feed black soldier fly larvae. During the application of NIR spectroscopy, sample presentation (e.g., drying, processing, particle size) plays an important role in the accuracy of the models developed (quantitative or qualitative analysis). The objective of this study was to evaluate the effect of sample presentation (number of larvae used during the scanning of BSFL) on the accuracy of classification models developed to trace the food waste stream (e.g., supermarket of childcare) used to feed the larvae. BSFL samples were sourced from two waste streams and scanned as half, 1, 2, or 3 larvae using an NIR portable instrument (MicroNIR, Viavi, Milpitas, California, USA). Principal component analysis (PCA) and linear discriminant analysis (LDA) were used to analyze the NIR data and to classify the samples according to the waste stream. The main differences in the NIR spectra of the BSFL samples associated with the number of larvae scanned were observed around 1200 nm, mainly associated with the C-H overtones (lipids). The classification results showed that high classification rates (>93%) were obtained regardless of the number of larvae scanned, ranging from 93% (using 0.5 larvae) to 100% (using 1, 2, or 3 larvae samples). Overall, the number of larvae scanned had minimal to no effect on the accuracy of the LDA classification models. The present study demonstrated that a portable NIR instrument can be suitable for an initial rapid classification or determination of the origin of the waste stream used to feed the BSFL. [ABSTRACT FROM AUTHOR]

In this paper, we use photometric data from the Southern Photometric Local Universe Survey Data Release 4 survey to identify isolated galaxy pairs and analyse their characteristics and properties. Our results align with previous spectroscopic studies, particularly in luminosity function parameters, suggesting a consistent trait among galaxy systems. Our findings reveal a high fraction of red galaxies across all samples, irrespective of projected distance, velocity difference, or luminosity ratio. We found that the proximity of a neighbour to its central galaxy influences its colour due to environmental effects. We also found that central and neighbour have different behaviours: central galaxies maintain a stable red colour regardless of luminosity, while neighbour colours vary based on luminosity ratios. When the central is significantly brighter, the neighbour tends to be less red. According to our division in red, blue, and mixed pairs, we found evidence of galactic conformity. The red pair fractions increase in closer pairs and in pairs of similar luminosity, indicating shared environments promoting red galaxy formation. Analysing local density, the expected colour–density relation is of course recovered, but it is strongly determined by the stellar mass of the pair. In denser environments, the red pair fractions increase, blue pairs decrease, and for the mixed pairs it depends on their stellar mass: more massive mixed pairs decrease their fraction, whereas the less massive ones increase it. These results shed light on the intricate relationship between galaxy pairs, their characteristics, and environmental influences on colour, providing insights into their evolutionary histories. [ABSTRACT FROM AUTHOR]

Holocene environmental changes in Patagonia were mostly shaped by fluctuating ice cover recession. Consequently, environmental reconstructions are largely based on discontinuous moraine chronologies from valley deposits. Here, we present a 3 m long continuous sediment record recovered from Laguna Meseta (LME), a lake located on Meseta Chile Chico. Its altitude and location relative to the North Patagonian Icefield provide a unique opportunity to reconstruct the glacial history and related environmental dynamics. Our radiocarbon chronology constrains sedimentation to the last ∼10 000 years and provides a minimum age for postglacial ice-free lacustrine conditions, due to a westward retreat of the ice cap. Lacustrine productivity reached its maximum at the start of the lake phase and decreased afterwards. Between 5500 and 4600 cal yr BP, a major shift towards allochthonous sediment accumulation occurred, caused by an abrupt increase in clastic deposition from basaltic lithologies of the Meseta Chile Chico. This episode correlates with the precipitation-driven Mid-Holocene glacier advance of Patagonian glaciers and suggests that conditions were colder and/or wetter on Meseta Chile Chico at that time. After 4600 cal yr BP, these conditions continued to supply LME with clastic sediments until a stepped decrease around 900 cal yr BP. Thereupon, lacustrine productivity distinctly increased and stabilized around 300 cal yr BP. Our findings indicate that changes in sedimentation on Meseta Chile Chico were mainly controlled by regional variability in the precipitation. Furthermore, strong correlation between our records and available proxies for oscillations of the Southern Hemisphere Westerly Winds suggest a pronounced climatic control by this prominent wind system for central west Patagonia during the last 10 000 years.

Metal accumulation in brain is associated with toxic proteins, like amyloid-proteins (Aß), formation, accumulation, and aggregation, leading to neurodegeneration. Metals downregulate the correct folding, disaggregation, or degradation mechanisms of toxic proteins, as heat shock proteins (HSPs) and proteasome. The 7-aminophenanthridin-6(5H)-one derivatives (APH) showed neuroprotective effects against metal-induced cell death through their antioxidant effect, independently of their chelating activity. However, additional neuroprotective mechanisms seem to be involved. We tested the most promising APH compounds (APH1-5, 10-100 µM) chemical ability to prevent metal-induced Aß proteins aggregation; the APH1-5 effect on HSP70 and proteasome 20S (P20S) expression, the metals effect on Aß formation and the involvement of HSP70 and P20S in the process, and the APH1-5 neuroprotective effects against Aß proteins (1 µM) and metals in SN56 cells. Our results show that APH1-5 compounds chemically avoid metal-induced Aß proteins aggregation and induce HSP70 and P20S expression. Additionally, iron and cadmium induced Aß proteins formation through downregulation of HSP70 and P20S. Finally, APH1-5 compounds protected against Aß proteins-induced neuronal cell death, reversing partially or completely this effect. These data may help to provide a new therapeutic approach against the neurotoxic effect induced by metals and other environmental pollutants, especially when mediated by toxic proteins. [ABSTRACT FROM AUTHOR]

Ion acceleration from gaseous targets driven by relativistic-intensity lasers was demonstrated as early as the late 1990s, yet most of the experiments conducted to date have involved picosecond-duration, Nd:glass lasers operating at low repetition rate. Here, we present measurements on the interaction of ultraintense (≈10^{20}Wcm^{−2}, 1 PW), ultrashort (≈70fs) Ti:Sa laser pulses with near-critical (≈10^{20}cm^{−3}) helium gas jets, a debris-free targetry with the potential for future compatibility with high (≈1 Hz) repetition rate operation. We provide evidence of α particles being forward accelerated up to ≈2.7-MeV energy with a total flux of ≈10^{11}sr^{−1} as integrated over >0.1-MeV energies and detected within a 0.5-mrad solid angle. We also report on on-axis emission of relativistic electrons with an exponentially decaying spectrum characterized by a ≈10-MeV slope, i.e., five times larger than the standard ponderomotive scaling. The total charge of these electrons with energy above 2 MeV is estimated to be of ≈1nC, corresponding to ≈0.1% of the laser drive energy. In addition, we observe the formation of a plasma channel, extending longitudinally across the gas density maximum and expanding radially with time. These results are well captured by large-scale particle-in-cell simulations, which reveal that the detected fast ions most likely originate from reflection off the rapidly expanding channel walls. The latter process is predicted to yield ion energies in the MeV range, which compare well with the measurements. Finally, direct laser acceleration is shown to be the dominant mechanism behind the observed electron energization.

Aunque existe un creciente interés social y académico por comprender por qué se cometen delitos de odio, hay muy pocos estudios empíricos sobre esta tipología delictiva. Este estudio pretende superar dichas limitaciones, profundizando en las características de una muestra de personas condenadas por delitos de odio. Para ello, se ha comparado a 33 delincuentes que cometieron delitos de odio con 38 personas condenadas por otras tipologías delictivas. Los resultados muestran que aquellos que cometieron delitos de odio son mayoritariamente varones, más jóvenes que otros delincuentes y solteros. En la mayoría de los casos vivían con su familia de origen, careciendo de una relación de pareja o de estabilidad laboral. Finalmente, en comparación con el grupo de delincuentes comunes, los delitos de odio parecen estar relacionados con la pertenencia a bandas organizadas. Las intervenciones para reducir la reincidencia en este tipo de delitos deberían basarse en las características específicas del colectivo.

Introduction: Neuropsychological symptoms and cortical atrophy patterns show similarities between typical Alzheimer’s Disease (AD) and its variants. Thus, correct diagnosis is difficult, leading to errors in the therapeutic process. Indeed, the challenge in cognitive neuroscience focuses on identifying key features of cognitive-linguistic profiles and improving the knowledge of neural correlates for accurate differential diagnosis between the heterogeneous profiles of typical and atypical AD. Aim: This systematic review aims to describe different AD profiles, considering their neuropsychological symptoms and neural correlates. Methods: The present study followed the PRISMA guidelines and included studies from the PubMed, ScienceDirect, Scopus, and Web of Science databases, published between 2011 and 2021. Results: Thirty-one articles were included in this systematic review for critical analysis. Results suggest significant declines in episodic and working memory and executive function. Likewise, in all groups, verbal fluency and visuospatial/visuoconstructive skills declined. However, these symptoms overlap between typical AD, logopenic variant primary progressive aphasia, posterior cortical atrophy, behavioural/dysexecutive or frontal variant AD, and corticobasal syndrome. On the other hand, the neural correlate showed a pattern of atrophy in frontal, temporal, parietal, and occipital areas, even compromising the cuneus and precuneus. Conclusion: Spontaneous language and semantic and phonological verbal fluency could be an important biomarker for differential diagnosis between typical AD and its atypical variants. Likewise, clinical assessment should consider using advanced neuroimaging techniques to establish early associations between brain dysfunction and neuropsychological performance, with particular attention to brain areas such as the cuneus and precuneus. Resumen: Introducción: En la Enfermedad de Alzheimer (EA) la sintomatología neuropsicológica y el patrón de atrofia muestran similitudes entre sus variantes atípicas, conduciendo a errores diagnósticos e intervenciones no atingentes a los déficits en sus perfiles típico y atípicos. Así, el desafío en neurociencia cognitiva se centra en poder identificar los elementos neuropsicológicos y las bases neurales para un diagnóstico diferencial certero entre esta heterogeneidad de perfiles. Objetivo: Caracterizar los distintos perfiles de la EA considerando sus manifestaciones neuropsicológicas y correlato neural. Metodología: La revisión sistemática cualitativa se realizó bajo los criterios de la declaración PRISMA, considerando estudios de las bases de datos PubMed, ScienceDirect, Scopus y Web of Science, entre los años 2011 y 2021. Resultados: La búsqueda dio como resultado 31 artículos finales. Los hallazgos sugieren declives significativos en memoria episódica y de trabajo, función ejecutiva, lenguaje y habilidades visuoespaciales/visuoconstructivas, síntomas que se superponen en EA típica, Afasia Progresía Primaria variante logopénica, Atrofia Cortical Posterior, EA variante frontal y Síndrome Corticobasal. Por otra parte, el correlato neural en estos perfiles sugiere un patrón de atrofia frontal, témporoparietal y occipital, comprometiendo adicionalmente el cuneus y precuneus. Conclusión: El lenguaje espontáneo y la fluidez verbal semántica y fonológica se proponen como claves en el diagnóstico diferencial. Asimismo, la valoración clínica debe considerar el uso de técnicas de neuroimagen avanzadas para establecer asociaciones en etapas tempranas entre la función cerebral afectada y el desempeño neuropsicológico, dando especial atención a áreas como el cuneus y precuneus.

Resumen: Introducción: El proceso de neurorrehabilitación es clave para mejorar la funcionalidad en pacientes tanto post ictus como con enfermedades neurodegenerativas, específicamente con cuadros de demencia. Durante los últimos años, el uso de recursos musicales por medio de la terapia musical (TM) se ha impuesto como una herramienta terapéutica alternativa que logra avances significativos tanto a nivel cognitivo como motor en pacientes post ictus y con demencias. Sin embargo, su uso no está generalizado en la comunidad terapéutica, por lo cual es necesario explorar evidencia favorable sobre los efectos en la rehabilitación y los cambios cerebrales que produce la TM, especialmente en pacientes post ictus y con cuadros de demencia. Metodología: La revisión de la literatura se llevó a cabo utilizando los criterios y diagrama de flujo establecidos en la declaración PRISMA, considerando estudios entre los años 2010 a 2019 en las bases de datos PubMed, ScienceDirect y Web of Science. Resultados: El proceso de búsqueda tras considerar criterios de filtrado y elegibilidad dio como resultado 29 artículos para análisis crítico. La literatura resultante de esta revisión confirma que la TM promueve beneficios cognitivos sobre la memoria, atención y lenguaje en pacientes con afasia post ictus y demencia. Mediante su uso se logra incrementar la conectividad y el grosor cortical en zonas frontales, parietales, temporales e incluso insulares. Conclusión: La TM genera cambios estructurales a nivel cerebral que impactan de manera favorable sobre la cognición. En pacientes post ictus las mejoras cognitivas se producen en etapas agudas y crónicas; no obstante, en pacientes con demencia los efectos de la TM se limitan a grados de severidad leve a moderada. Abstract: Introduction: Neurorehabilitation therapy is crucial to improving functionality in patients with stroke or with such neurodegenerative diseases as dementia. In recent years, music therapy (i.e., the use of music for therapeutic purposes) has been described as an alternative tool that significantly improves motor and cognitive functions in patients with stroke or dementia. However, it has not yet been routinely implemented in clinical practice. Therefore, there is a need to review the current evidence on the positive effects of music therapy in rehabilitation and the changes it causes in the brain, particularly in patients with stroke or dementia. Methods: We conducted a literature review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and included studies published between 2010 and 2019 on the PubMed, ScienceDirect, and Web of Science databases. Results: A total of 29 articles met the inclusion and exclusion criteria and were included in this literature review. The studies selected confirm that music therapy has a positive impact on such cognitive domains as memory, attention, and language in patients with aphasia due to stroke or dementia. This therapy increases neural connectivity and cortical thickness in frontal, parietal, and temporal regions, and even in the insular cortex. Conclusion: Music therapy causes structural changes in the brain that have a favourable impact on cognition. In patients with stroke, these improvements occur during both acute and chronic stages. In the case of dementia, in contrast, the effects of music therapy are only observed in patients with mild to moderate dementia.

Resumen: Introducción: En el estudio de enfermedades neurodegenerativas, se ha considerado clásicamente a la enfermedad de Alzheimer (EA) con una presentación típica de síntomas cognitivos y cambios neuroanatómicos. No obstante, existen fenotipos clínicos de EA cuyas bases neurobiológicas presentan similitud con la demencia frontotemporal (DFT). En este sentido, la heterogeneidad de estos cuadros conlleva a procesos de evaluación y diagnóstico poco certeros, debido al escaso conocimiento sobre sus síntomas neurocognitivos. El objetivo de esta revisión sistemática es establecer características y similitudes neuropsicológicas en pacientes con EA y DFT, identificando elementos clave para su diagnóstico diferencial. Metodología: La revisión sistemática se realizó bajo los criterios y diagrama de flujo establecidos en la declaración PRISMA, considerando estudios de las bases de datos Pubmed, Scopus y Web of Science entre los años 2005 y 2020. Resultados: La búsqueda dio como resultado 41 artículos finales para llevar a cabo el análisis crítico. La evidencia sugiere que existen diferencias claves en dominios cognitivos como el lenguaje (por ejemplo: fluidez verbal), la memoria, la cognición social, el funcionamiento ejecutivo y la conducta; debiendo ser estos aspectos considerados como fundamentales en todo proceso de evaluación y diagnóstico neuropsicológico. Conclusiones: Existen aspectos lingüísticos que prometen ser biomarcadores potentes para el diagnóstico diferencial entre EA y DFT, siendo estos la fluidez verbal tanto semántica como fonémica y las alteraciones semánticas-gramaticales. Abstract: Introduction: Alzheimer's disease (AD) has classically been considered to present typical cognitive symptoms and neuroanatomical changes. However, the neurobiological basis of some clinical phenotypes of AD is similar to that of frontotemporal dementia (FTD). Therefore, the heterogeneity of these diseases leads to uncertain evaluation and diagnosis processes, due to limited understanding of the associated neurocognitive symptoms. This systematic review aims to describe neuropsychological characteristics and similarities in patients with AD and FTD, and to identify critical points for their differential diagnosis. Methods: The present study followed the PRISMA guidelines and included studies from the PubMed, Scopus, and Web of Science databases, published between 2005 and 2020. Results: The search returned a total of 41 articles eligible for critical analysis. The available evidence points to key differences in such cognitive domains as language (eg, verbal fluency), memory, social cognition, executive functioning, and behaviour; these should be considered in all neuropsychological assessments and diagnostic processes. Conclusion: Such language domains as verbal fluency (semantic and phonemic) and semantic/grammar alterations seem to be useful markers for differential diagnosis between AD and FTD.

We have studied the temporal effects on ultra-short pulses during their propagation in air below the collapse threshold where spontaneous self-channelling is observed. A rich dynamics in the spatio-temporal properties of the pulse has been obtained both in the theory and experiment. We have shown that different parts of the pulse do not have the same temporal properties because they do not propagate in the same way. Experimental measurements confirm the dependence of the temporal pulse width with the propagation as well as with the transversal coordinate predicted by the theoretical calculations. In particular, this study has lead us to identify the conditions for which an important reduction of the temporal width as well as a clear pedestal cleaning can be achieved. [ABSTRACT FROM AUTHOR]

The lower reaches of the Coatzacoalcos River in southeast Mexico is an area of intense industrial development. The physico-chemical characteristics of the area have exhibited differences over the years. Apparently from the associated outcroppings of limestone in the Uxpanapa River Basin, the major elements that are dissolved show higher concentrations of Ca, Mg and HCO3- in the waters supplied by this river. The water in the Calzadas River contains high concentrations of Ca, SO4 and HCO3- that are associated with the saline domes crossed by this river. Due to industrial discharges, the sulfate concentration is very high in the water and air during April. Nitrate concentration diminishes with salinity. Higher nitrate as well as nitrite and ammonia levels are present during flood season. Phosphate concentration, associated with high oxygen levels, is higher in January. Zn, Cu and Cr are higher during the dry season (April) when dilution is minimal and low levels of TOC are present. The smaller concentrations of Zn and Cu observed in January are associated with high TOC values in water. The lower levels of Cr present in August are associated with high amounts of suspended matter. Pajaritos Lagoon and Teapa-L, with large industrial discharges, have the highest nutrient and dissolved metal concentrations in the area. Air particles smaller than 2.5 μm contain Fe, V, Ti, Cu, Zn, and high amounts of S. These anomalous concentrations of sulfates and metals are attributed to anthropogenic sources. [ABSTRACT FROM AUTHOR]

Abstract Background Emerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor. Methods One hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes. Discussion SABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making. Trial registration Clinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023).

Multi-millennial environmental and climatic changes in central Chilean Patagonia (44–49° S) during the Last Glacial–Interglacial cycle have been of particular interest as changes in the position and strength of the southern westerlies are the major forcing factor conditioning the environmental dynamics. Recent attempts to reconstruct regional environmental and climatic signals from central Chilean Patagonia reveal some discrepancies and unclear issues among the records. This paper presents the 13 ka pollen and charcoal records from Mallín El Embudo (44° 40' S, 71° 42' W) located in the deciduous Nothofagus forest in the middle Río Cisnes valley. The paper aims to (1) establish the timing and magnitude of local vegetation changes and fire activity since the Late Glacial and (2) integrate these results at the regional scale in order to discuss the discrepancies and depict the environmental and climatic dynamics in central Chilean Patagonia since the Late Glacial. Open landscapes dominated by grasses associated with scattered Nothofagus forest patches dominated the middle Río Cisnes valley between 13 and 11.2 ka suggesting low effective moisture but also indicating that landscape configuration after glacial retreat was still ongoing. At 11.2 ka, the sudden development of an open and quite dynamic Nothofagus forest probably associated with the synchronous high fire activity occurred, suggesting a rise in effective moisture associated with dry summers. Since 9.5 ka, the record reflects the presence of a closed Nothofagus forest related to higher effective moisture conditions than before combined with moderate dry summers that may have triggered a high frequency of low-magnitude crown fires that did not severely affect the forest. The forest experienced a slight canopy opening after 5.7 ka, probably due to slightly drier conditions than before followed by a sudden change to open forest conditions around 4.2 ka associated with fire and volcanic disturbances. Around 2 ka, the recovery of a closed Nothofagus forest related to slightly wetter conditions (similar to present) occurred and persisted under highly variable climatic conditions up to 0.1 ka when massive forest burning and logging due to European settlements occurred. Central Chilean Patagonian climatic and environmental changes at millennial–centennial timescales since the Late Glacial were driven by changes in the southern westerlies latitudinal position and/or intensity, but during the late Holocene fire, volcanism and humans arose as forces contributing to environmental dynamics.

Abstract High dose-rate brachytherapy is a treatment technique for gynecologic cancers where intracavitary applicators are placed within the patient’s pelvic cavity. To ensure accurate radiation delivery, localization of the applicator at the time of insertion is vital. This study proposes a novel method for acquiring, registering, and fusing three-dimensional (3D) trans-abdominal and 3D trans-rectal ultrasound (US) images for visualization of the pelvic anatomy and applicators during gynecologic brachytherapy. The workflow was validated using custom multi-modal pelvic phantoms and demonstrated during two patient procedures. Experiments were performed for three types of intracavitary applicators: ring-and-tandem, ring-and-tandem with interstitial needles, and tandem-and-ovoids. Fused 3D US images were registered to magnetic resonance (MR) and computed tomography (CT) images for validation. The target registration error (TRE) and fiducial localization error (FLE) were calculated to quantify the accuracy of our fusion technique. For both phantom and patient images, TRE and FLE across all modality registrations (3D US versus MR or CT) resulted in mean ± standard deviation of 4.01 ± 1.01 mm and 0.43 ± 0.24 mm, respectively. This work indicates proof of concept for conducting further clinical studies leveraging 3D US imaging as an accurate, accessible alternative to advanced modalities for localizing brachytherapy applicators.

The tejocote (Crataegus spp.) is a tree considered to be native to Mexico. The aim of this study was to identify the causal agent of tejocote rust in the State of Puebla. Tejocote fruits were sampled in 2012 and 2013. The fungus was studied morphologically using light and scanning electron microscopy and molecularly using phylogenetic analysis of 18S and 28S rDNA genes. The fungus was identified as Gymnosporangium clavipes on tejocote fruits. To our knowledge, this is the first confirmed report of Gymnosporangium clavipes Cooke & Peck affecting Crataegus mexicana var. Chapeado and C. gracilior in Puebla Mexico.

Abstract Background Isolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues. Methods ROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment. Discussion ROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy. Trial registration NCT05230251 (ClinicalTrials.gov).

Abstract Searching for new bioactive molecules to design insecticides is a complex process since pesticides should be highly selective, active against the vector, and bio-safe for humans. Aiming to find natural compounds for mosquito control, we evaluated the insecticidal activity of essential oils (EOs) from 20 American native plants against Aedes aegypti larvae using bioassay, biochemical, and in silico analyses. The highest larvicide activity was exhibited by EOs from Steiractinia aspera (LC50 = 42.4 µg/mL), Turnera diffusa (LC50 = 70.9 µg/mL), Piper aduncum (LC50 = 55.8 µg/mL), Lippia origanoides (chemotype thymol/carvacrol) (LC50 = 61.9 µg/mL), L. origanoides (chemotype carvacrol/thymol) (LC50 = 59.8 µg/mL), Hyptis dilatata (LC50 = 61.1 µg/mL), Elaphandra quinquenervis (LC50 = 61.1 µg/mL), and Calycolpus moritzianus (LC50 = 73.29 µg/mL) after 24 h. This biological activity may be related to the disruption of the electron transport chain through the mitochondrial protein complexes. We hypothesized that the observed EOs' effect is due to their major components, where computational approaches such as homology modeling and molecular docking may suggest the possible binding pose of secondary metabolites that inhibit the mitochondrial enzymes and acetylcholinesterase activity (AChE). Our results provided insights into the possible mechanism of action of EOs and their major compounds for new insecticide designs targeting the mitochondria and AChE activity in A. aegypti for effective and safe insecticide.

Background: Localized Gleason Grade Group 5 (GG5) prostate cancer has a poor prognosis and is associated with a higher risk of treatment failure, metastases, and death. Treatment intensification with the addition of a brachytherapy (BT) boost to external beam radiation (EBRT) maximizes local control, which may translate into improved survival outcomes. Methods: A systematic review and meta-analysis was performed to compare survival outcomes for Gleason GG5 patients treated with androgen deprivation therapy (ADT) and either EBRT or EBRT + BT. The MEDLINE (PubMed), EMBASE and Cochrane databases were searched to identify relevant studies. Survival probabilities for distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were extracted and pooled to create a summary survival curve for each treatment modality, which were then compared at fixed points in time. An additional analysis was performed among studies directly comparing EBRT and EBRT + BT using a random-effects model. Results: Eight retrospective studies were selected for inclusion, representing a total of 1393 EBRT patients and 877 EBRT + BT patients. EBRT + BT was associated with higher DMFS starting at 6 years (86.8 % vs 78.8 %; p = 0.018) and extending out to 10 years (81.8 % vs 66.1 %; p

: Objectives The aim of the study was to analyse the evolution of antibiotic non-susceptibility in Spanish invasive Streptococcus pneumoniae after licensure of respiratory-quinolones for adults and 7-valent pneumococcal conjugate vaccine (PCV-7) for immunization of children. : Methods All invasive pneumococci received in the Reference Laboratory (January 2000–August 2007; n = 12 957 isolates) were serotyped, and susceptibility to penicillin/erythromycin/levofloxacin was determined. Antibiotic consumption and PCV-7 doses/year were provided by IMS and the manufacturer, respectively. : Results In 2000–07, PCV-7 distribution (doses/1000 inhabitants ≤59 months age/year) increased from 0.0 to 411.90, and antibiotic consumption (DDD/1000 inhabitants/day) was maintained for β-lactams (&ap;16), decreased for macrolides (from 4.4 to 2.7) and increased for respiratory fluoroquinolones (from 0.3 to 2.7). The increase in PCV-7 distribution correlated with a decrease in PCV-7 serotypes prevalence among invasive isolates in children (r = −0.976; P < 0.001) and adults (r = −0.905; P = 0.002). This decrease in PCV-7 serotypes correlated with a decrease in penicillin non-susceptibility in children (r = 0.929; P < 0.001) and adults (r = 0.905; P = 0.002) and with erythromycin non-susceptibility in children (r = 0.833; P = 0.010). Penicillin/erythromycin non-susceptibility in 2000 was significantly higher in paediatric versus adult isolates (penicillin: 51.4% versus 29.2%; erythromycin: 39.5% versus 20.4%), but similar in 2006–07 (20% to 24%). The increase in respiratory quinolones consumption correlated with the increase in levofloxacin non-susceptibility in adults (r = 0.926; P = 0.008) but not in children, with different non-susceptibility rates in 2007 (1.6% versus 0.0%; P = 0.013). : Conclusions This ecological analysis suggests that PCV-7 vaccination in children had a herd effect in adults, but consumption of respiratory quinolones in adults had no effect on pneumococcal susceptibility to levofloxacin in children. Penicillin/erythromycin non-susceptibility decreased along the studied period among paediatric invasive S. pneumoniae isolates to a level similar to that seen in adults. [ABSTRACT FROM AUTHOR]

Objective. Evaluate the efficacy of acupuncture associated with physiotherapy for patients with painful shoulder. Methods. In a multicentre controlled randomized study, participants were recruited with a clinical diagnosis of unilateral subacromial syndrome from six rehabilitation medicine departments belonging to the Public Health System in two Spanish regions. All participants received 15 sessions of physiotherapy during the 3 weeks that the treatment lasted and were randomized to additionally receive, once a week, acupuncture or mock TENS (transcutaneous electrical nerve stimulation). The primary outcome measure was the change in the Constant–Murley Score (CMS) for functional assessment of the shoulder, at 4 weeks after randomization. This study is registered as an International Standard Randomized Controlled Trial, number ISRCTN28687220. Results. A total of 425 patients were recruited. The mean score (s.d.) on the CMS had increased by 16.6 (15.6) points among the acupuncture group, compared with 10.6 (13.5) points in the control group, and the mean difference between the two groups was statistically significant (6.0 points; 95% CI 3.2, 8.8 points; P < 0.001). By the end of the treatment, 53% of the patients in the acupuncture group had decreased their consumption of analgesics, compared with a corresponding 30% among the control group (P < 0.001). Conclusions. Single-point acupuncture in association with physiotherapy improves shoulder function and alleviates pain, compared with physiotherapy as the sole treatment. This improvement is accompanied by a reduction in the consumption of analgesic medicaments. [ABSTRACT FROM AUTHOR]

Abstract Mosquito borne diseases are on the rise because of their fast spread worldwide and the lack of effective treatments. Here we are focusing on the development of a novel anti-malarial and virucidal agent with biocidal effects also on its vectors. We have synthesized a new quinoline (4,7-dichloroquinoline) derivative which showed significant larvicidal and pupicidal properties against a malarial and a dengue vector and a lethal toxicity ranging from 4.408 µM/mL (first instar larvae) to 7.958 µM/mL (pupal populations) for Anopheles stephensi and 5.016 µM/mL (larva 1) to 10.669 µM/mL (pupae) for Aedes aegypti. In-vitro antiplasmodial efficacy of 4,7-dichloroquinoline revealed a significant growth inhibition of both sensitive strains of Plasmodium falciparum with IC50 values of 6.7 nM (CQ-s) and 8.5 nM (CQ-r). Chloroquine IC50 values, as control, were 23 nM (CQ-s), and 27.5 nM (CQ-r). In vivo antiplasmodial studies with P. falciparum infected mice showed an effect of 4,7-dichloroquinoline compared to chloroquine. The quinoline compound showed significant activity against the viral pathogen serotype 2 (DENV-2). In vitro conditions and the purified quinoline exhibited insignificant toxicity on the host system up to 100 µM/mL. Overall, 4,7-dichloroquinoline could provide a good anti-vectorial and anti-malarial agent.

Background: Vitiligo is an autoimmune disorder involving inflammatory damage to melanocytes. STAT3 genetic variant (rs744166 T > C) increases inflammatory signaling via JAK/STAT pathway. Aim: The purpose of this study was to check whether this translates into an association between vitiligo and STAT3 gene variant (rs744166 T > C). Materials and Methods: This is a case-control study. A total of 56 vitiligo patients and 90 healthy, age and gender-matched volunteers were recruited for the study. The STAT3 gene variant (rs744166 T > C) was genotyped using the restriction fragment length polymorphism method. Results: The frequency of the minor allele 'C' was higher in vitiligo patients (72.3%) than in healthy volunteers (57.8%). The difference between the two groups was statistically significant (P = 0.006; OR = 1.9 with 95% CI). The genotypic variant showed the highest association with vitiligo in the dominant model (P = 0.001). Conclusion: This study shows that the STAT3 gene variant (rs744166 T > C) is associated with vitiligo. This observation underlines the importance of the JAK/STAT signaling pathway in vitiligo pathogenesis.

CRISPR-based engineering can be used to bias sex ratios. Here the authors develop a transgenic line of Drosophila melanogaster expressing Cas9 from the Y chromosome and functionally characterize the utility of this strain for both sex selection and gene drive.

Continuous ultrasound is recognized for its thermal effect and use in the tissue repair process. However, there is controversy about its dosage and efficacy. This study used infrared thermography, a non-invasive technique, to measure the short-term thermal effect of 3 MHz continuous ultrasound vs. a placebo, referencing the intensity applied. It was a single-blind, randomized clinical trial of 60 healthy volunteers (19–24 years old) divided into three equal groups. Group 1:1 W/cm2 for 5 min; Group 2: 0.5 W/cm2 for 10 min; and Group 3: the placebo for 5 min. The temperature was recorded through five thermographic images per patient: pre- and post-application, 5, 10, and 15 min later. After statistical analysis, a more significant decrease in temperature (p<0.05 ) was observed in the placebo group compared with the remaining groups after the application of continuous ultrasound. Group 1 was the one that generated the highest significant thermal effect (p<0.001), with an increase of 3.05 °C at 15 min, compared with the other two groups. It is concluded that to generate a thermal effect in the muscle, intensities of ≥1 W/cm2 are required, since the dosage maintained a temperature increase for more than 5 min.

Abstract Background Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy alone (RT) or chemoradiotherapy (CRT), often reducing treatment compliance. However, no standard currently exists for the treatment of RIM, and high dose opioid therapy, with its associated side effects and increased risk for chronic opioid use, remains the cornerstone of HNC pain management. The goal of this randomized clinical trial is to compare multimodal analgesia using analgesic medications with different mechanisms of action, to the institutional standard of opioid analgesia alone, in order to ascertain the optimal analgesic regimen for the management of RIM pain in HNC patients. Methods In this open-label, single-institution, non-inferiority, randomized clinical trial, sixty-two patients with mucosal head and neck malignancies treated with curative-intent radiation will be randomized in a 1:1 ratio, stratified by RT or CRT, between Arm 1: opioid analgesia alone as per the institutional standard, or Arm 2: multimodal analgesia using Pregabalin, Acetaminophen, and Naproxen, in addition to opioids, if required. The primary endpoint is the average 11-Numeric Rating Scale (11-NRS) score for pain during the last week of radiation treatment. Secondary endpoints include: average weekly opioid use, duration of opioid requirement, average daily 11-NRS score for pain, average weekly opioids dispensed, quality of life, hospitalizations for analgesic medication-induced complications, time to feeding tube insertion, weight loss, toxicity, treatment interruptions, and death within 3 months of completing RT treatment. Patients are eligible once analgesia is required for moderate 4/10 pain. Discussion This study will assess the efficacy and safety of multimodal analgesia and its impact on opioid requirements, clinical outcomes, and quality of life, as a potential new standard treatment for RIM pain in HNC patients undergoing definitive RT or CRT. Trial registration ClinicalTrials.gov Identifier: NCT04221165 . Date of registration: January 9, 2020. Appendix 2 reports the World Health Organization trial registration dataset.

In machine learning, a natural way to represent an instance is by using a feature vector. However, several studies have shown that this representation may not accurately characterize an object. For classification problems, the dissimilarity paradigm has been proposed as an alternative to the standard feature-based approach. Encoding each object by pairwise dissimilarities has been demonstrated to improve the data quality because it mitigates some complexities such as class overlap, small disjuncts, and low-sample size. However, its suitability and performance when applied to regression problems have not been fully explored. This study redefines the dissimilarity representation for regression. To this end, we have carried out an extensive experimental evaluation on 34 datasets using two linear regression models. The results show that the dissimilarity approach decreases the error rates of both the traditional linear regression and the linear model with elastic net regularization, and it also reduces the complexity of most regression datasets.

Abstract Background Transoral surgery (TOS), particularly transoral robotic surgery (TORS) has become the preferred modality in the United States for the treatment of early stage oropharyngeal cancer, largely due to assumptions of fewer toxicities and improved quality of life compared to primary radiotherapy (RT). However, these assumptions are based on retrospective analysis, a subset of which utilize primary RT groups not limited to T1-2 stage tumors for which transoral robotic surgery is FDA approved. Thus, there is potential for underestimating survival and overestimating toxicity, including treatment related mortality, in primary RT. Methods Consecutive cases of early T-stage (T1–T2) oropharyngeal cancer presenting to the London Health Sciences Centre between 2014 and 2018 treated with RT or chemoradiation (CRT) were reviewed. Patient demographics, treatment details, survival outcomes and toxicity were collected. Toxicities were retrospectively graded using the Common Terminology Criteria for Adverse Events criteria. Results A total of 198 patients were identified, of which 82% were male and 73% were HPV-positive. Sixty-eight percent of patients experienced a grade 2 toxicity, 48% a grade 3 and 4% a grade 4. The most frequent toxicities were dysphagia, neutropenia and ototoxicity. The rates of gastrostomy tube dependence at 1 and 2 years were 2.5% and 1% respectively. There were no grade 5 (fatal) toxicities. HPV-positive patients experienced improved 5-year overall survival (86% vs 64%, p = 0.0026). Conclusions Primary RT or CRT provides outstanding survival for early T-stage disease, with low rates of severe toxicity and feeding tube dependence. This study provides a reference for comparison for patients treated with primary transoral surgery.

Abstract Background Patients with high-risk prostate cancer are at increased risk of lymph node metastasis and are thought to benefit from whole pelvis radiotherapy (WPRT). There has been recent interest in the use of hypofractionated radiotherapy in treating prostate cancer. However, toxicity and cancer outcomes associated with hypofractionated WPRT are unclear at this time. This phase II study aims to investigate the impact in quality of life associated with hypofractionated WPRT compared to conventionally fractionated WPRT. Methods Fifty-eight patients with unfavourable intermediate-, high- or very high-risk prostate cancer will be randomized in a 1:1 ratio between high-dose-rate brachytherapy (HDR-BT) + conventionally fractionated (45 Gy in 25 fractions) WPRT vs. HDR-BT + hypofractionated (25 Gy in 5 fractions) WPRT. Randomization will be performed with a permuted block design without stratification. The primary endpoint is late bowel toxicity and the secondary endpoints include acute and late urinary and sexual toxicity, acute bowel toxicity, biochemical failure-, androgen deprivation therapy-, metastasis- and prostate cancer-free survival of the hypofractionated arm compared to the conventionally fractionated arm. Discussion To our knowledge, this is the first study to compare hypofractionated WPRT to conventionally fractionated WPRT with HDR-BT boost. Hypofractionated WPRT is a more attractive and convenient treatment approach, and may become the new standard of care if demonstrated to be well-tolerated and effective. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04197141 on December 12, 2019.

Purpose: Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT. Methods and Materials: A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation. Results: Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (α/β = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ≥grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS. Conclusions: Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.

Abstract Background Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck. Methods This is a multicentre phase II study randomizing 90 patients with T1–4 N0–2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL. Discussion This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials. Trial registration Clinicaltrials.gov identifier: NCT03997643 . Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Abstract Purpose To compare CTVHR and OAR dimensions and inter-rater agreement between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) images in IB cervical cancer patients. Methods IB cervical cancer patients treated with (chemo)radiotherapy plus MR-guided brachytherapy (BT) were prospectively enrolled in this study. Radiation oncologists contoured CTVHR and OARs in pre-BT MR images (MRI) and intra-operative TRUS images. These contours were subsequently compared in regard to volume and dimension. Contour inter-rater agreement analysis was also investigated using kappa index (KI). Stata 15.0 was used for statistical analysis and a p-value

Aedes albopictus mosquitoes are important vectors for a number of human pathogens including the Zika, dengue, and chikungunya viruses. Capable of displacing Aedes aegypti populations, this mosquito adapts to cooler environments which increases its geographical range and transmission potential. There are limited control strategies for Aedes albopictus mosquitoes which is likely attributed to the lack of comprehensive biological studies on this emerging vector. To fill this void, here using RNAseq we characterized Aedes albopictus mRNA expression profiles at 34 distinct time points throughout development providing the first high-resolution comprehensive view of the developmental transcriptome of this worldwide human disease vector. This enabled us to identify several patterns of shared gene expression among tissues as well as sex-specific expression patterns. To illuminate the similarities and differences with Aedes aegypti, a related human disease vector, we also performed a comparative analysis between the two developmental transcriptomes, identifying life stages where the two species exhibit similar and distinct gene expression patterns. These findings provide insights into the similarities and differences between Aedes albopictus and Aedes aegypti mosquito biology. In summary, the results generated from this study should form the basis for future investigations on the biology of Aedes albopictus and provide a gold mine resource for the development of transgene-based vector control strategies.

Abstract Objective: Methicillin-resistant Staphylococcus aureus (MRSA) infection is highly unlikely when nasal-swab results are negative. We evaluated the impact of an electronic prompt regarding MRSA nasal screening on the length of vancomycin therapy for respiratory indications. Design: Retrospective, single-center cohort study. Setting: Tertiary-care academic medical center (Mayo Clinic) in Jacksonville, Florida. Patients: Eligible patients received empiric treatment with vancomycin for suspected or confirmed respiratory infections from January through April 2019 (preimplementation cohort) and from October 2019 through January 2020 (postimplementation cohort). Intervention: The electronic health system software was modified to provide a best-practice advisory (BPA) prompt to the pharmacist upon order verification of vancomycin for patients with suspected or confirmed respiratory indications. Pharmacists were prompted to order a MRSA nasal swab if it was not already ordered by the provider. Methods: We reviewed patient records to determine the time from vancomycin prescription to de-escalation. The secondary end point was incidence of acute kidney injury. Results: The study included 120 patients (preimplementation, n = 61; postimplementation, n = 59). Median time to de-escalation was significantly shorter for the postimplementation cohort: 76 hours (interquartile range [IQR], 52–109) versus 42 hours (IQR, 37–61; P = .002). Acute kidney injury occurred in 11 patients (18%) in the preimplementation cohort and in 3 patients (5%) in the postimplementation cohort (P = .01; number needed to treat, 8). Conclusions: Implementation of a BPA notification for MRSA nasal screening helped decrease the time to de-escalation of vancomycin.

Purpose: Opioid addiction is a major public health concern. Chronic opioid use (COU) patterns after radiation for head and neck cancer (HNC) remain poorly understood. The aim of this study was to estimate the prevalence of COU and to identify its risk factors in patients with HNC undergoing curative-intent radiation therapy (RT) or chemoradiotherapy (CRT). Methods and Materials: We performed a systematic review and meta-analysis using the PubMed (Medline), EMBASE, and Cochrane Library databases, queried from dates of inception until January 2020. COU was defined as persistent use of opioids ≥ 3 months after treatment completion. Meta-analyses were performed using random effects models. Heterogeneity was assessed using the I2 value. Results: Seven retrospective studies, reporting on 1841 patients, met the inclusion criteria. Median age was 59.4 (range: 56.0-62.0) years with 1343 (72.9%) men and 498 (27.1%) women. Primary tumor locations included oropharynx (n = 891, 48.4%), oral cavity (n = 533, 29.0%), larynx (n = 93, 5.1%), hypopharynx (n = 32, 1.7%), and nasopharynx (n = 29, 1.6%). Eight hundred fifty-four (46.0%) patients had stage I/II and 952 (50.3%) had stage III-IV disease. Three hundred one (16.3%) patients had RT alone, 738 (40.1%) received CRT, and 594 (32.3%) underwent surgery followed by adjuvant RT/CRT. The proportion of patients with HNC who developed COU post-RT/CRT was 40.7% at 3 months (95% confidence interval [CI]: 22.6%-61.7%; I2 = 97.1%) and 15.5% at 6 months (95% CI: 7.3%-29.7%; I2 = 94.3%). Oropharyngeal malignancies had the highest rate of COU based on primary tumor location (46.6%; 95% CI: 30.8%-63.1%; P < .0001). High proportions of COU were found in patients with a history of psychiatric disorder(s) (61.7%), former/current alcohol abuse (53.9%), and opioid requirements before radiation treatment (51.6%; P = .035). Conclusions: A significant proportion of patients who undergo RT for HNC suffer from COU. High-risk factors for COU include an oropharyngeal primary, history of psychiatric disorder, former/current alcohol abuse, and pre-treatment opioid use. New strategies to mitigate COU are needed.

Although there are existing vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), new COVID-19 cases are increasing due to low immunization coverage and the emergence of new variants. For this reason, new drugs to treat and prevent severe COVID-19 are needed. Here, we provide four different FDA-approved drugs against SARS-CoV-2 proteins involved in the entry and replication process, aiming to identify potential drugs to treat COVID-19. We use the main protease (Mpro), the spike glycoprotein (S protein), and RNA-dependent RNA polymerase (RdRp) as protein targets for anti- SARS-CoV-2 drugs. In our constructed database, we selected different drugs against each target (Mpro, S protein, and RdRp) based on their common interactions with relevant residues involved in viral entry at the host cell and replication. Furthermore, their stability inside the binding pocket, as well as their predicted binding-free energy, allow us to provide new insight into the possible drug repurposing of viomycin (interacting with Mpro) due to its interactions with key residues, such as Asn 143, Glu 166, and Gln 189 at the same time as hesperidin (interacting with the S protein) is interacting with residues Tyr 449, Ser 494, and Thr 500, keeping inside the predicted binding pocket, as well as interacting with residues in different variants of concern. Finally, we also suggest nystatin and elvitegravir (interacting with RdRp) as possible drugs due to their stability within the predicted pocket along the simulation and their interaction with key residues, such as Asp 760, Asp 761, and Asp 618. Altogether our results provide new knowledge about the possible mechanism of the inhibition of viomycin, hesperidin, elvitegravir, and nystatin to inhibit the viral life cycle of SARS-CoV-2 and some of its variants of concern (VOC). Additionally, some iodide-based contrast agents were also found to bind the S protein strongly, i.e., iohexol (−58.99 Kcal/mol), iotrolan (−76.19 Kcal/mol), and ioxilan (−62.37 Kcal/mol). Despite the information we report here as the possible strong interaction between these contrast agents and the SARS-CoV-2′s S protein, Mpro, and RdRp, we believe that further investigation, including chemical modifications in their structures, are needed for COVID-19 treatment.

Abstract Background Sexually transmitted Human Papilloma Virus (HPV) infection is a known risk factor for cancer of the anal canal in both men and women. Case presentation We describe a report of synchronous carcinoma of the anal canal in a heterosexual couple. High risk type 16 HPV DNA was detected in both tumors. Conclusion Longstanding sexual partners may share risk of HPV-associated anal canal cancer.

Abstract Background Heart-sparing techniques are time and resource intensive, although not all patients require the use of these strategies. This study evaluates the performance of different distance metrics in predicting the need for breath-hold radiotherapy in left-sided breast cancer patients receiving adjuvant radiotherapy. Methods Fifty left-sided breast cancer patients treated with breast conserving surgery and adjuvant radiotherapy to the breast from a single institution were retrospectively studied. The left breast and organs at risk were contoured in accordance to guidelines and a plan with tangents was obtained using the free-breathing CT in supine position. Heart (mean heart dose (MHD), heart V25 Gy) and left anterior descending artery dosimetry were computed and compared against distance metrics under investigation (Contact Heart, 4th Arch and 5th Arch). Recursive partitioning analysis (RPA) was used to determine optimal cut-points for distance metrics for dosimetric end points. Receiver operating characteristic curves and Pearson correlation coefficients were used to evaluate the association between distance metrics and dosimetric endpoints. Univariable and multivariable logistic regression analysis was performed to identify significant predictors of dosimetric end points. Results The mean MHD and heart V25 Gy were 2.3 Gy and 10.4 cm3, respectively. With tangents, constraints for MHD (

Abstract Background To evaluate the dosimetric performance of multi-channel vaginal cylinder (MCVC) against interstitial brachytherapy (ISBT) for the treatment of vaginal tumors. Methods Vaginal tumors with extension of > 0.5 cm and ≤ 2 cm from the lateral vaginal wall and/or ≤ 1 cm in height above the vaginal vault were retrospectively selected from a ISBT registry trial database. The selected patients were treated with ISBT and targets included the intermediate (IRCTV) or high-risk (HRCTV) clinical target volumes. For technique comparison, a 35 mm MCVC was registered with the interstitial intra-vaginal cylinder. Bladder and rectum contours were transferred from the ISBT to the MCVC-BT plans. Vaginal mucosa was achieved by 3 mm uniform expansion from cylinder surface. Both the ISBT and MCVC-BT plans were optimized using the Inverse Planning Simulated Annealing optimization algorithm. After normalizing target D90 to 700 cGy, dose to organs at risk were measured and compared between ISBT and MCVC plans. Results Six interstitial patient plans met the inclusion criteria for this study. Four patients had vaginal primaries and two recurrent cancers in the vagina. Lower doses to bladder and rectum were seen with ISBT plans. In half of the MCVC plans, the rectal dose met the recommended constraints. For plans in which the rectal constraint was not met, the target volumes were abutting the rectum and had a cranial-caudal length ≥ 5 cm. Dose to vaginal mucosa was lower in ISBT plans directed to the HRCTVs, although no difference was seen in circumferential IRCTVs. Conclusions Overall, ISBT results in decreased dose to OARs as compared to MCVC. However, MCVC BT results in acceptable doses to OARs with possible improvement in vaginal doses for circumferential targets. Careful consideration to tumor geometry and location may help guide optimal techniques in vaginal tumor brachytherapy.

Anti-tumor mAbs are the most widely used and characterized cancer immunotherapy. Despite having a significant impact on some malignancies, most cancer patients respond poorly or develop resistance to this therapy. A known mechanism of action of these therapeutic mAbs is antibody-dependent cell-mediated cytotoxicity (ADCC), a key effector function of human NK cells. CD16A on human NK cells has an exclusive role in binding to tumor-bound IgG antibodies. Though CD16A is a potent activating receptor, it is also a low affinity IgG Fc receptor (FcγR) that undergoes a rapid downregulation in expression by a proteolytic process involving ADAM17 upon NK cell activation. These regulatory processes are likely to limit the efficacy of tumor-targeting therapeutic mAbs in the tumor environment. We sought to enhance NK cell binding to anti-tumor mAbs by engineering these cells with a recombinant FcγR consisting of the extracellular region of CD64, the highest affinity FcγR expressed by leukocytes, and the transmembrane and cytoplasmic regions of CD16A. This novel recombinant FcγR (CD64/16A) was expressed in the human NK cell line NK92 and in induced pluripotent stem cells from which primary NK cells were derived. CD64/16A lacked the ADAM17 cleavage region in CD16A and it was not rapidly downregulated in expression following NK cell activation during ADCC. CD64/16A on NK cells facilitated conjugation to antibody-treated tumor cells, ADCC, and cytokine production, demonstrating functional activity by its two components. Unlike NK cells expressing CD16A, CD64/16A captured soluble therapeutic mAbs and the modified NK cells mediated tumor cell killing. Hence, CD64/16A could potentially be used as a docking platform on engineered NK cells for therapeutic mAbs and IgG Fc chimeric proteins, allowing for switchable targeting elements and a novel cancer cellular therapy.

Objective: To present a case of a double ectopic thyroid gland in a 10-year old boy and discuss the pros and cons of the different management options that were available. Methods Design: Case Report Setting: Tertiary Hospital in Metro Manila Subject: One (1) Results: A 10-year-old boy presented with hoarseness and easy fatigability for 6 years. Rigid endoscopy and CT scan showed an infraglottic mass originating from the anterior tracheal wall causing obstruction. Biopsy revealed thyroid tissue with atypia. Thyroid scintigraphy showed uptake in the submental and midline anterior neck. Thyroid hormone levels were consistent with hypothyroidism. Levothyroxine returned hormone levels to normal and resulted in complete regression of the mass with no symptoms of dyspnea, stridor or bleeding. Conclusion: The management of ectopic thyroid presents a challenge as there are no guidelines for optimal treatment. Thyroid hormone insufficiency is a frequent occurrence, and emphasis must be given to its monitoring. Surgery in a critical airway lesion such as this may be reserved for cases where the patient experiences dyspnea and stridor or lack of response to thyroid hormone treatment. Keywords: Ectopic thyroid, direct laryngoscopy, thyroid hormone, levothyroxine

Con el fin de contribuir al conocimiento de su actividad a nivel celular, se evaluó el mecanismo de acción del aceite esencial de Eucalyptus citriodora (Fam. Myrtaceae) sobre la bioenergética mitocondrial, su efecto sobre la velocidad de consumo de oxígeno de mitocondrias energizadas (estados 3 y 4) y su coeficiente de control respiratorio (CCR). Además, se analizó la actividad de los complejos de la cadena respiratoria usando técnicas espectrofotométricas. Los resultados obtenidos indican que el aceite esencial de E. citriodora aumenta la velocidad del consumo de oxígeno en los estados 3 y 4, disminuye el CCR, desacopla la fosforilación oxidativa, aumenta la actividad de la citocromo c oxidasa y aumenta la actividad ATPasa en mitocondrias íntegras, a partir de la concentración de 10 μg/mL. Estos resultados sugieren que el aceite esencial o sus metabolitos afectan el funcionamiento normal del transporte de electrones de la cadena respiratoria y la síntesis de ATP.