Epicure: a European epidemiological study of patients with an advanced or metastatic Urothelial Carcinoma (UC) having progressed to a platinum-based chemotherapy.

BACKGROUND: Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. METHODS: Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. RESULTS: A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin-unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status ≥ 2 in 17 %, hemoglobinemia < 10 g/dL in 16 %, hepatic metastases in 13 %. 80 % of these patients received further anticancer therapy. Immediately after failure of adjuvant/neoadjuvant chemotherapy, most subsequent anticancer treatments were chemotherapy doublets (35/58), whereas after therapy failure in the advanced setting most patients receiving further anticancer drugs were treated with a single agent (80/114). After first progression to chemotherapy, treatment decisions were mainly driven by Performance Status and prior response to chemotherapy (>30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. CONCLUSION: In this daily practice experience, a majority of patients with urothelial carcinoma previously treated with a platinum-based therapy received a second chemotherapy regimen, most often a single agent after an initial chemotherapy in the advanced setting and preferably a cytotoxic combination after a neoadjuvant or adjuvant chemotherapy. Performance Status and prior response to chemotherapy were the main drivers of further treatment decisions.

Neurosteroids increase tonic GABAergic inhibition in the lateral section of the central amygdala in mice.

Neurosteroids are formed de novo in the brain and can modulate both inhibitory and excitatory neurotransmission. Recent evidence suggests that the anxiolytic effects of neurosteroids are mediated by the amygdala, a key structure for emotional and cognitive behaviors. Tonic inhibitory signaling via extrasynaptic type A γ-aminobutyric acid receptors (GABA(A)Rs) is known to be crucially involved in regulating network activity in various brain regions including subdivisions of the amygdala. Here we provide evidence for the existence of tonic GABAergic inhibition generated by the activation of δ-subunit-containing GABA(A)Rs in neurons of the lateral section of the mouse central amygdala (CeAl). Furthermore, we show that neurosteroids play an important role in the modulation of tonic GABAergic inhibition in the CeAl. Taken together, these findings provide new mechanistic insights into the effects of pharmacologically relevant neurosteroids in the amygdala and might be extrapolated to the regulation of anxiety.

Substance P excites GABAergic neurons in the mouse central amygdala through neurokinin 1 receptor activation.

Substance P (SP) is implicated in stress regulation and affective and anxiety-related behavior. Particularly high expression has been found in the main output region of the amygdala complex, the central amygdala (CE). Here we investigated the cellular mechanisms of SP in CE in vitro, taking advantage of glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) knockin mice that yield a reliable labeling of GABAergic neurons, which comprise 95% of the neuronal population in the lateral section of CE (CEl). In GFP-positive neurons within CEl, SP caused a membrane depolarization and increase in input resistance, associated with an increase in action potential firing frequency. Under voltage-clamp conditions, the SP-specific membrane current reversed at -101.5 ± 2.8 mV and displayed inwardly rectifying properties indicative of a membrane K(+) conductance. Moreover, SP responses were blocked by the neurokinin type 1 receptor (NK1R) antagonist L-822429 and mimicked by the NK1R agonist [Sar(9),Met(O2)(11)]-SP. Immunofluorescence staining confirmed localization of NK1R in GFP-positive neurons in CEl, predominantly in PKCδ-negative neurons (80%) and in few PKCδ-positive neurons (17%). Differences in SP responses were not observed between the major types of CEl neurons (late firing, regular spiking, low-threshold bursting). In addition, SP increased the frequency and amplitude of GABAergic synaptic events in CEl neurons depending on upstream spike activity. These data indicate a NK1R-mediated increase in excitability and GABAergic activity in CEl neurons, which seems to mostly involve the PKCδ-negative subpopulation. This influence can be assumed to increase reciprocal interactions between CElon and CEloff pathways, thereby boosting the medial CE (CEm) output pathway and contributing to the anxiogenic-like action of SP in the amygdala.

Interaction networks and the use of floral resources by male orchid bees (Hymenoptera: Apidae: Euglossini) in a primary rain forests of the Chocó Region (Colombia).

Orchid bees are important keystone pollinators from the Neotropics. With the aim to study the relationships between orchid bees and their nectar and aromatic host species, we made systematic samplings of males across two conservation areas in the biogeographic Choc6 Region of Colombia. We used chemical baits to collect 352 male bees during five months. The pollen attached to their bodies was extracted for palynological identification and to estimate interaction networks. The euglossine community consisted of at least 22 species including Eg. maculilabris, Eg. orellana, Eg. championi and Eg. ignita. The male bees were associated with 84 plants but depended on a small group of them (Peperomia spp. and Anthurium spp, as well as species of Solanaceae, Ericaceae and Malpighiaceae) which were widely distributed across the altitudinal gradient, and were available through the year. The resulting interaction networks revealed a typical nested pattern usually found in plant-pollinator interactions, with several rare bee and plant species interaction with a small group of generalist bees and plant species. Albeit, we found variation within networks related to species composition. Such variation may be a consequence of specific differences in plant flowering phenology.

Design and optimization methodology for different 3D processed materials (PLA, ABS and carbon fiber reinforced nylon PA12) subjected to static and dynamic loads.

This research presents a methodology for the design and optimization of 3D printed parts with material extrusion (MEX) technology with three different commercial materials: PLA, ABS and N + CF (PA12) subjected to tensile and fatigue stresses, which included three stages: pretreatment, design of experiments and sequential optimization by statistical modeling. In the pretreatment stage, mainly the printing control factors (inner layer and contour height, printing speed, extrusion temperature, nozzle, infill arrangement and printing orientation) were determined; then, factors to optimize tensile strength as a function of printing pattern (linear, 3D, hexagonal), infill percentage (33%, 66%, 100°) and printing orientation (+45°/-45°, 0°/90°) were evaluated. Fatigue analysis was performed as a function of impression orientation using 100% infill, linear impression pattern, 5 Hz and a load range between 90 and 50% UTS. Optimization of tensile strength resulted in parts that exceeded the UTS of their corresponding filament, leading to infinite life relative to fatigue tests. Results were presented for fatigue life prediction based on Weibull analysis, Basquins model and a multivariate response surface correlation analysis. The best fatigue behavior was related to the optimized tensile strength, the infill pattern applied to the printing orientation and the intrinsic properties of ABS (1 × 107cycles, stress up to 20 MPa). With respect to the other materials, a good fatigue behavior was highlighted at the number of cycles achieved 1 × 106 (stress up to 18 MPa) and 1 × 105 (stress up to 24 MPa) for N + CF and PLA, respectively. This study contributes to a better understanding of how printing parameters correlate with tensile and fatigue properties.

First large-scale study reveals important losses of managed honey bee and stingless bee colonies in Latin America.

Over the last quarter century, increasing honey bee colony losses motivated standardized large-scale surveys of managed honey bees (Apis mellifera), particularly in Europe and the United States. Here we present the first large-scale standardized survey of colony losses of managed honey bees and stingless bees across Latin America. Overall, 1736 beekeepers and 165 meliponiculturists participated in the 2-year survey (2016-2017 and 2017-2018). On average, 30.4% of honey bee colonies and 39.6% of stingless bee colonies were lost per year across the region. Summer losses were higher than winter losses in stingless bees (30.9% and 22.2%, respectively) but not in honey bees (18.8% and 20.6%, respectively). Colony loss increased with operation size during the summer in both honey bees and stingless bees and decreased with operation size during the winter in stingless bees. Furthermore, losses differed significantly between countries and across years for both beekeepers and meliponiculturists. Overall, winter losses of honey bee colonies in Latin America (20.6%) position this region between Europe (12.5%) and the United States (40.4%). These results highlight the magnitude of bee colony losses occurring in the region and suggest difficulties in maintaining overall colony health and economic survival for beekeepers and meliponiculturists.

Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma.

BACKGROUND: The aim of this open label phase II study (NCT00407459) was to assess the activity of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab combined with pemetrexed and carboplatin in patients with previously untreated, unresectable malignant pleural mesothelioma (MPM). METHODS: Eligible patients received pemetrexed 500 mg m(-2), carboplatin area under the plasma concentration-time curve (AUC) 5 mg ml(-1) per minute and bevacizumab 15 mg kg(-1), administered intravenously every 21 days for six cycles, followed by maintenance bevacizumab. The primary end point of the study was progression-free survival (PFS). A 50% improvement in median PFS in comparison with standard pemetrexed/platinum combinations (from 6 to 9 months) was postulated. RESULTS: Seventy-six patients were evaluable for analysis. A partial response was achieved in 26 cases (34.2%, 95% CI 23.7-46.0%). Forty-four (57.9%, 95% CI 46.0-69.1%) had stable disease. Median PFS and overall survival were 6.9 and 15.3 months, respectively. Haematological and non-haematological toxicities were generally mild; however, some severe adverse events were reported, including grade 3-4 fatigue in 8% and bowel perforation in 4% of patients. Three toxic deaths occurred. CONCLUSION: The primary end point of the trial was not reached. However, due to the limitation of a non-randomised phase II design, further data are needed before drawing any definite conclusion on the role of bevacizumab in MPM.

Phase II prospective study with sorafenib in advanced soft tissue sarcomas after anthracycline-based therapy.

INTRODUCTION: We investigated the activity and safety of sorafenib, a multitargeted tyrosine-kinase inhibitor, in patients with advanced soft tissue sarcomas (STS). PATIENTS AND METHODS: An open-label nonrandomised multicentre phase II study was conducted in advanced STS patients pre-treated with anthracycline-based chemotherapy. Patients received sorafenib 400 mg twice daily for 28 days. The primary end point was the progression-free survival (PFS) rate at 6 months. Toxicity was assessed. Clinical outcomes were evaluated in all histologies and in leiomyosarcoma (L) and angiovascular sarcomas (A). RESULTS: Between November 2006 and January 2010, 101 patients (36 L, 19 A, and 46 others) were enrolled; 76 patients per-protocol (PP) and 100 per intention-to-treat (ITT) were assessable for the primary end point. In the PP analysis, 11 (14.5%) achieved partial response and 25 (32.9%) stable disease; 6-month PFS rates were all histologies, 34.5%; L, 38.4%; and A, 56.3%. In the ITT analysis, 6-month PFS results were 27.1, 35, and 35.5% in all histologies, L, and A, respectively. When stratified by histology, we observed a better PFS favouring leiomyosarcoma versus other histologies (P = 0.033). Treatment was well tolerated. CONCLUSIONS: Sorafenib appears to be a promising option in leiomyosarcoma patients. This finding warrants further evaluation in histology-driven trials.

Evaluation of results after 112 radioembolizations with 90Y-microspheres.

AIM: To determine the results of radioembolization transarterial (TARE), in the treatment of liver tumors, a retrospective evaluation was performed after 112 TARE with 90Y-microspheres administered in 82 patients in a single hospital, analyzing efficacy and safety, after a follow-up greater than or equal to 1 year post-TARE in all patients, and evaluating the possible relationship between treatment response and patient survival. MATERIAL AND METHODS: We have administered 57 single TARE and 55 multiple TARE in patients with hepatocellular carcinoma (53), liver metastases (25) and cholangiocarcinoma (4), with prior multidisciplinary evaluation, clinical, angiographic and gammagraphic (planar/SPECT/SPECT-CT with 99mTc-MAA), multicompartment model (MIRD equations), post-TARE screening (planar/SPECT/SPECT-CT), clinical and radiological follow-up, tumor response evaluation (mRECIST criteria) and Kaplan-Meier analysis to determine progression-free survival (PFS) and overall survival (OS). RESULTS: Therapeutic intention was palliative (82%) and as bridge to liver transplantation/surgical resection (17%). We obtained response (R), complete or partial, in 65.9% of cases. One year after TARE 34.7% of patients with R and 19.2% of non-R were progression-free (P: .003), with OS of 80% for R and 37.5% for non-R (P: .001). Survival analysis showed median OS of 18 months (95% CI 15.7-20.3) for R and 9 months (95% CI 6.1-11.8) for non-R (P: .03). We found mild (27.6%) and severe (5.3%) side effects, all of them resolved, without higher incidence after multiple TARE. CONCLUSION: TARE with 90Y-microspheres, in appropriately selected patients with liver tumors, provides therapeutic efficacy and low rate of toxicity, with higher PFS and OS in patients with TARE response compared to those who did not respond.

[Report of the 4th International Conference on Envenomations by Snakebites and Scorpion Stings in Africa, Dakar, April 25-29, 2011]. / 4(e) Conférence internationale sur les envenimations par morsures de serpent et piqûres de scorpion en Afrique : Dakar, 25-29 avril 2011.

The authors present a summary of the proceedings and the recommendations of the Fourth International Conference on Envenomations by Snakebites and Scorpion Stings in Africa, held from 25 to 29 April 2011 in Dakar. After a two-day workshop for Senegalese health personnel on the most relevant aspects of the management of envenomations, about 270 participants met to share their experiences in the field. Nearly a hundred oral and poster presentations were made on the epidemiology of snakebites and scorpion stings in Africa, the composition and action of venoms and the manufacture and use of antivenoms. The last day was devoted to an institutional debate involving experts, representatives of national health authorities and concerned professionals (physicians, pharmacists, nurses and traditional healers) as well as members of the pharmaceutical industry to discuss and elaborate a set of recommendations. It was agreed that it is necessary to improve knowledge of the epidemiological situation by case reporting. Quality control of antivenoms and procedures for their registration at the level of national health authorities should aim at improving the distribution of safe and effective antivenoms in peripheral health centers for the better assessment of victims. It was also recommended that adequate training should be provided for health personnel in all aspects of medical management of envenomations. Equitable distribution of funding and the establishment of a network of African experts were also discussed in the conference.

[Pathogenic mechanisms of SARS-CoV-2 infection and kidney disease: a clinical and molecular perspective].

The SARS-CoV-2 infection has become as a worldwide public health emergency. It exhibits a variety of clinical presentations, ranging from benign to acute respiratory distress syndrome, systemic involvement, and multiorganic failure. The severity of the clinical picture depends on host and virus biological features and the presence of comorbidities such as chronic kidney disease. In addition, the interaction between the virus, angiotensin-converting enzyme 2, and the exacerbated immune response could lead to the development of acute kidney injury. However, the implications of SARS-CoV-2 infection on renal cells, the prognosis of patients with chronic kidney disease, and the long-term behavior of renal function are not entirely understood. This review aims to explore the role of SARS-CoV-2 in acute and chronic kidney disease and the possible pathogenic mechanisms of renal involvement.

Regulation of adult hippocampal neurogenesis exerted by sexual, cognitive and physical activity: An update.

In 1962, Joseph Altman described that the brain generates neurons after the postnatal period, and this continues throughout your life (Altman, 1962). This was a breakthrough in the neuroscience field because before this the accepted paradigm was that the brain only generated neurons during the embryonal development. This discovery has been controversial ever since, especially since one of the areas of the brain with neurogenic properties is the hippocampus, which is the area involved in memory storage and neurodegenerative processes. The adult hippocampal neurogenesis modulates in response to different environmental factors. In this article, we review how exercise and cognitive and sexual activity can regulate the generation of new neurons in the hippocampal in an adult brain and the impact of these new neurons in the brain circuitry.

Treponema species enrich the gut microbiota of traditional rural populations but are absent from urban individuals.

There is a significant gap in our knowledge of the microbe-host relationship between urban and traditional rural populations. We conducted a large-scale study to examine the gut microbiota of different traditional rural and urban lifestyles in human populations. Using high-throughput 16S ribosomal RNA gene amplicon sequencing, we tested urban French, Saudi, Senegalese, Nigerian and Polynesian individuals as well as individuals living in traditional rural societies, including Amazonians from French Guiana, Congolese Pygmies, Saudi Bedouins and Algerian Tuaregs. The gut microbiota from individuals living in traditional rural settings clustered differently and presented significantly higher diversity than those of urban populations (p 0.01). The bacterial taxa identified by class analysis as contributing most significantly to each cluster were Phascolarctobacterium for traditional rural individuals and Bifidobacterium for urban individuals. Spirochaetae were only present in the gut microbiota of individuals from traditional rural societies, and the gut microbiota of all traditional rural populations was enriched with Treponema succinifaciens. Cross-transmission of Treponema from termites or swine to humans or the increased use of antibiotics in nontraditional populations may explain why Treponema is present only in the gut microbiota of traditional rural populations.

[Report of the 3rd International Conference on Envenomations in Africa]. / Troisième Conférence internationale sur les envenimations en Afrique. Brazzaville, 15-17 novembre 2007.

The 3rd International Conference on Envenomations was held in Brazzaville from 15 to 17 November; 2007. At this meeting, updating of epidemiological and treatment information on envenomations in Africa were presented. A round table concluded the conference drawing contributors' main recommendations. One of these recommendation pointed out the need to treat the problem of envenimations at a regional level by creating a group of experts in charge of considering the priorities as well as identifying relevant strategies of management, ensuring the plea and finding the financing.

[Effect of landscape change on the structure of the sting-less bee community (Hymenoptera: Apidae) in Meta, Colombia]. / Efecto del cambio del paisaje en la estructura de la comunidad de abejas sin aguijón (Hymenoptera: Apidae) en Meta, Colombia.

Stingless bees represent one of the most diversified components of the natural Apoidea fauna of pollinators in the tropics. They use diverse kinds of substrates and inhabit varied habitats. Some species are typical for some natural either artificial place. The landscape alteration were this group of bees nests, has and important impact on the natural composition of its community structure, fact which is reflected in the nest density. We analyzed the structure composition of the stingless bees' community in three environments in the Colombian Ilanos piedmont, an important region that represents the transition between Andean ecosystems and a savannah that is seriously threatened by cattle practices. We made systematic samples in secondary forest, agro-ecosystems and urban areas, recording the presence of 204 nests from 11 genera (24 species). The nest density per landscape was heterogeneous and never higher than 16 nests/Ha. We observed two nesting patterns and an effect of sampling criterion on the measured biodiversity.

[A brief history of marijuana in the western world]. / Breve historia sobre la marihuana en Occidente.

Marijuana is a substance with a long and controversial history. At different times in its history, which goes back over 5,000 years, this plant has been used for different purposes, ranging from recreational and leisure to its use in the treatment of several diseases or to offer relief in processes that entail a certain type of malaise, and including its consideration as a means of relaxation and meditation. Although it was supposed that the roots of marijuana lay in Central America, it is now known that this is but an urban legend with little credibility and that its origins can be found recorded in Chinese medical references dating back to the year 2737 BC. Although this plant was not originally from Central America, it has aroused interest around the world, and above all in Mexico. It is in this country where the use of cannabis has gone from applications in textiles and medicine to its free sale, the bans on its use due to political and social pressures, its tolerance and, recently, its decriminalisation for recreational and medicinal use. Unfortunately there are few references on the history of this plant in Mexico, and thus we have considered it interesting to present some data about the generalities of marijuana, a brief history in the world, the development of decriminalisation in North America, its medicinal uses and its course through Mexico to the present day.

TITLE: Breve historia sobre la marihuana en Occidente.La marihuana es una sustancia con una extensa y controvertida historia. A lo largo del tiempo, esta planta, y desde hace mas de 5.000 años, ha sido utilizada para diferentes fines, que van desde el uso ludico y recreativo, pasando por un medio de relajacion y meditacion, hasta su uso en el tratamiento de varias enfermedades o el alivio de procesos vinculados a cierto tipo de malestares. Aunque se supuso que la marihuana tenia su origen en Mesoamerica, ahora se sabe que es solo una leyenda urbana de poca credibilidad y que sus origenes los podemos registrar en referencias medicas chinas datadas alrededor del año 2737 a. de C. Si bien esta planta no tiene un origen mesoamericano, si ha generado interes en el mundo, y sobre todo en Mexico. Es en este pais donde el uso del cannabis ha ido desde intereses textiles y medicinales hasta el consumo ludico, pasando por su venta libre, la prohibicion por presiones politicas y sociales, su tolerancia y, recientemente, su despenalizacion para uso ludico y medicinal. Desgraciadamente existen pocas referencias de la historia de esta planta en Mexico, por lo que ha sido de nuestro interes presentar algunos datos sobre las generalidades de la marihuana, una breve historia en el mundo, el desarrollo de la despenalizacion en Norteamerica, sus usos medicinales y su paso por Mexico hasta nuestros dias.

[Variation of the orchid bees community (Hymenoptera: Apidae) in three altered habitats of the Colombian "llano" piedmont]. / Variación de la comunidad de abejas de las orquídeas (Hymenoptera: Apidae) en tres ambientes perturbados del piedemonte llanero colombiano.

Orchid bees subsist in vast tropical forest areas because they maintain close relationships with particular plant species in diverse micro-habitats. Based on the relationships among the environment and biological features (food preference, morphologic and ethologic diversity), it is possible to determine habitat quality using the euglossine array. This work proposes the use of this ecological information, in addition to diversity indices, for the evaluation of environmental quality. Fifteen localities in three landscape types (urban, rural and conserved) were sampled in the eastern llanos foothill (Meta, Colombia), between March and December of 2003 using entomological nets, and Cineol and Metil Salicylate as baits. Of the 26 species known to occur in the area, 17 were registered. Eulaema nigrita was the most frequent, while E. speciosa E. bombiformis, Euglossa magnipes, E. cybelia, E. heterosticta, E. singularis and Exaerete frontalis were mostly found in habitats rated "good to acceptable". The vegetation composition and proximity of forest fragments seem to favor some species in disturbed habitats. Relative diversity of bee body shapes and sizes is proportional to habitat quality.

Mecanismos patogénicos de infección por SARS-CoV-2 y enfermedad renal: una perspectiva clínico-molecular / Pathogenic mechanisms of SARS-CoV-2 infection and kidney disease: a clinical and molecular perspective

La infección por SARS-CoV-2 se ha convertido en unproblema mundial de salud pública. Su presentaciónclínica es variada, desde benigna hasta un síndrome dedistrés respiratorio agudo, afectación sistémica y fallomultiorgánico. La severidad del cuadro clínico depen-de de factores biológicos del virus y del huésped y decomorbilidades como la enfermedad renal. Además, lainteracción entre el virus, la enzima convertidora deangiotensina 2 y la respuesta inmunológica exacerbadapodría conducir al desarrollo de lesión renal aguda. Sinembargo, las implicaciones de la infección por SARS-CoV-2 sobre las células renales, las repercusiones pro-nósticas en los pacientes con enfermedad renal crónicay su efecto a largo plazo sobre la función renal no estándel todo claras. El objetivo es revisar el papel del SARS-CoV-2 en la enfermedad renal aguda y crónica, y sus po-sibles mecanismos patogénicos en la afectación renal.

The SARS-CoV-2 infection has become as a worldwidepublic health emergency. It exhibits a variety of clinicalpresentations, ranging from benign to acute respira-tory distress syndrome, systemic involvement, andmultiorganic failure. The severity of the clinical picturedepends on host and virus biological features and thepresence of comorbidities such as chronic kidney dis-ease. In addition, the interaction between the virus,angiotensin-converting enzyme 2, and the exacerbatedimmune response could lead to the development ofacute kidney injury. However, the implications of SARS-CoV-2 infection on renal cells, the prognosis of patientswith chronic kidney disease, and the long-term behav-ior of renal function are not entirely understood. Thisreview aims to explore the role of SARS-CoV-2 in acuteand chronic kidney disease and the possible pathogen-ic mechanisms of renal involvement.(AU)