New Pharmacological Strategies against Pancreatic Adenocarcinoma: The Multifunctional Thiosemicarbazone FA4.

A new sigma-2 (σ2) receptor ligand (FA4) was efficiently synthesized and evaluated for cytotoxic, proapoptotic, and antimigratory activity on pancreatic ductal adenocarcinoma (PDAC) primary cell cultures, which restrained the aggressive and chemoresistant behavior of PDAC. This compound showed relevant antiproliferative activity with half maximal inhibitory concentration (IC50) values ranging from 0.701 to 0.825 µM. The cytotoxic activity was associated with induction of apoptosis, resulting in apoptotic indexes higher than those observed after exposure to a clinically relevant concentration of the gemcitabine, the first-line drug used against PDAC. Interestingly, FA4 was also able to significantly inhibit the migration rate of both PDAC-1 and PDAC-2 cells in the scratch wound-healing assay. In conclusion, our results support further studies to improve the library of thiosemicarbazones targeting the σ-2 receptor for a deeper understanding of the relationship between the biological activity of these compounds and the development of more efficient anticancer compounds against PDAC.

Mercury in birds (aquatic and scavenger) from the Western Amazon.

In the Amazon rainforest, methylmercury (MeHg) is easily biomagnified and bio-accumulated in the aquatic food chain. This unique biome has been studied for occupational and environmental issues related to human health and contamination through fish consumption; however, wildlife studies have not yet addressed fish-eating birds. Different species of birds categorized by foraging strategies and life-stages were studied in the Madeira River Basin (Western Amazon rainforest). Feather and tissue (muscle, liver, kidneys, lungs, heart, brain, and blood) samples were collected opportunistically from six bird species feeding on fish and aquatic fauna and a scavenger (a saprophagous species) during the low-water season (July 2017). All collected samples were analyzed for total Hg (THg); methyl-Hg (MeHg) was determined only in feathers. The mean THg concentrations in feathers (dw) were as follows: Ardea cocoi (4.05 µg g-1, n = 51) > Egretta thulla (3.94 µg g-1, n = 5) > Ardea alba (3.80 µg g-1, n = 61) > Anhinga anhinga (3.69 µg g-1, n = 8) > Nannopterum brasilianus (3.07 µg g-1, n = 10). The scavenger Coragyps atratus showed mean THg in feathers (9.93 µg g-1, n = 30) to be significantly higher than in fish-eating birds. Across species, THg levels in feathers correlated significantly with THgmuscle (p = 0.022) and THgbrain (p = 0.002). THg concentrations varied in tissues (feather > liver > kidneys > lungs > heart > muscle > blood > brain). The Hgbrain:Hgfeather, Hgbrain:Hgmuscle, and Hgbrain:Hgblood ratios were 0.031, 0.503 and 0.516, respectively. The mean [MeHg:THg] ratio in feathers from aquatic birds varied between species from 14 to 74% with a mean of 38%. Scavenger birds that forage in the terrestrial Amazonian environments concentrate more THg than species that forage in the aquatic environment. None of the aquatic species showed THg concentration in internal organs that were above threshold for risk of Hg toxicity; additionally, they are not listed in the categories of threat by the International Union for Conservation of Nature (IUCN).

Dynamics of Hg and MeHg in the Madeira River basin (Western Amazon) before and after impoundment of a run-of-river hydroelectric dam.

The impact of a hydroelectric run-of-river (RoR) dam construction on the dynamics of total mercury (THg) and methylmercury (MeHg) is of interest to the environment and health of human and wild life. We monitored (May 2010 to October 2018) THg and MeHg in the waters and in the suspended particulate matter (SPM) of the Madeira River and its tributaries (before and after dam construction) to evaluate changes upstream and downstream from the Santo Antonio Hydroelectric Dam (SAHD). We collected 2826 samples of water and SPM at sampling stations upstream (UPMD-01, UPMD-02 and UPMD-03) and downstream the Madeira River (DWMD-04, DWMD-05 and DWMD-06), and Tributaries upstream (Branco River, Jaci-Parana River, Jatuarana-I Igarapé, Contra River, Caripunas Igarapé, Ceara Igarapé, and Teotonio Igarapé) and downstream (Jatuarana-II Igarapé and Belmont Igarapé) from the SAHD and monitored water and the total load of SPM. SPM was significantly higher in the Madeira River (median: 178.63 mg.L-1) than in upstream and downstream tributaries (median: 15.30 mg.L-1); however, the THg and MeHg concentrations were significantly higher in the tributaries (median: 161.14 ng g-1 and 9.03 ng g-1, respectively) than in the mainstream Madeira River (median = 57.06 ng g-1 and 1.63 ng g-1, respectively). THg concentration in the water was significantly higher in the mainstream Madeira River (median = 6.51 ng.L-1) than in the tributaries (median = 2.57 ng.L-1). However, the percentage of methylation in the tributaries (median = 4.9%) was 4-times higher than in the Madeira River (median: 1.3%). The significantly higher MeHg percentages in the tributaries may indicate natural (hydro-bio-geochemical factors) still predominant in this changing landscape of the Western Amazon. So far, the data suggest that this RoR has not yet impacted the THg and MeHg concentrations.

Mercury biomagnification and the trophic structure of the ichthyofauna from a remote lake in the Brazilian Amazon.

The present study assesses mercury biomagnification and the trophic structure of the ichthyofauna from the Puruzinho Lake, Brazilian Amazon. In addition to mercury determination, the investigation comprised the calculation of Trophic Magnification Factor (TMF) and Trophic Magnification Slope (TMS), through the measurements of stable isotopes of carbon (δ13C) and nitrogen (δ15N) in fish samples. These assessments were executed in two different scenarios, i.e., considering (1) all fish species or (2) only the resident fish (excluding the migratory species). Bottom litter, superficial sediment and seston were the sources used for generating the trophic position (TP) data used in the calculation of the TMF. Samples from 84 fish were analysed, comprising 13 species, which were categorized into four trophic guilds: iliophagous, planktivorous, omnivorous and piscivorous fish. The δ13C values pointed to the separation of the ichthyofauna into two groups. One group comprised iliophagous and planktivorous species, which are linked to the food chains of phytoplankton and detritus. The other group was composed by omnivorous and piscivorous fish, which are associated to the trophic webs of phytoplankton, bottom litter, detritus, periphyton, as well as to food chains of igapó (blackwater-flooded Amazonian forests). The TP values suggest that the ichthyofauna from the Puruzinho Lake is part of a short food web, with three well-characterized trophic levels. Mercury concentrations and δ13C values point to multiple sources for Hg input and transfer. The similarity in Hg levels and TP values between piscivorous and planktivorous fish suggests a comparable efficiency for the transfer of this metal through pelagic and littoral food chains. Regarding the two abovementioned scenarios, i.e., considering (1) the entire ichthyofauna and (2) only the resident species, the TMF values were 5.25 and 4.49, as well as the TMS values were 0.21 and 0.19, respectively. These findings confirm that Hg biomagnifies through the food web of Puruzinho Lake ichthyofauna. The migratory species did not significantly change mercury biomagnification rate in Puruzinho Lake; however, they may play a relevant role in Hg transport. The biomagnification rate (TMS value) in Puruzinho Lake was higher than the average values for its latitude, being comparable to TMS values of temperate and polar systems (marine and freshwater environments).

Polydimethylsiloxane films doped with NdFeB powder: magnetic characterization and potential applications in biomedical engineering and microrobotics.

This work reports the fabrication, magnetic characterization and controlled navigation of film-shaped microrobots consisting of a polydimethylsiloxane-NdFeB powder composite material. The fabrication process relies on spin-coating deposition, powder orientation and permanent magnetization. Films with different powder concentrations (10 %, 30 %, 50 % and 70 % w/w) were fabricated and characterized in terms of magnetic properties and magnetic navigation performances (by exploiting an electromagnet-based platform). Standardized data are provided, thus enabling the exploitation of these composite materials in a wide range of applications, from MEMS/microrobot development to biomedical systems. Finally, the possibility to microfabricate free-standing polymeric structures and the biocompatibility of the proposed composite materials is demonstrated.

Liver allografts from donors with peritoneal contamination: report of two cases.

Organs from deceased donors with traumatic abdominal injury, peritoneal contamination and open abdomen are usually discarded due to risks of transmission of severe infections to the recipient. There are no specific recommendations regarding organ utilization from these donors, but they might be an unexplored source able to attenuate organ shortage. Herein, the first successful report of a case involving liver transplantation using a liver allograft procured from a deceased donor with an open abdomen is outlined. This donor was a young trauma patient in which peritoneal contamination had occurred following a gunshot wound. Also included in this the report is liver transplant from a donor, who also was a trauma victim with an enteric perforation. The decision-making process to accept liver allografts from donors with a greater risk of peritoneal infection involved the absence of uncontrolled sepsis or visible contamination of the cavity. Appropriate donor-recipient matching and adequate anti-infectious management might have contributed to a favorable outcome, which suggest that these donors can be used as alternatives to reduce organ shortage.

Annual activity density of groundbeetles (Coleoptera: Carabidae) of a Celtis ehrenbergiana (Rosales: Celtidaceae) forest of Buenos Aires province, Argentina.

The aim of this study was to describe the annual activity cycle, the sex ratio, and the relationship between the weather variables and activity density of the 16 most abundant carabid species of a typical southeastern region of Pampasia, Argentina. The study focused on the southernmost Celtis ehrenbergiana (Klotzsch) Liebmann ( = C. tala Guillies ex Planch) native forest of the region, from March 2008 to March 2009, a period during which there was a marked draught associated with the La Niña phenomenon. Forty-five pitfall traps were emptied once every 2 wk, and the occurrence of larvae, tenerals, and subtenerals was recorded. Photoperiod, temperature, and precipitations explained 35% of the total variation in the catch. Total carabid activity was high in early autumn and late spring. Eight species reached their maximum activity in spring, five in winter, two in summer, and one in autumn. Possible reproductive strategies, the influence of different variables involved in the life cycles of the species, and the sex ratio and their limitations are discussed.

Trends of Mansonia (Diptera, Culicidae, Mansoniini) in Porto Velho: Seasonal patterns and meteorological influences.

Entomological research is vital for shaping strategies to control mosquito vectors. Its significance also reaches into environmental management, aiming to prevent inconveniences caused by non-vector mosquitoes like the Mansonia Blanchard, 1901 mosquito. In this study, we carried out a five-year (2019-2023) monitoring of these mosquitoes at ten sites in Porto Velho, Rondônia, using SkeeterVac SV3100 automatic traps positioned between the two hydroelectric complexes on the Madeira River. Throughout this period, we sampled 153,125 mosquitoes, of which the Mansonia genus accounted for 54% of the total, indicating its prevalence in the region. ARIMA analysis revealed seasonal patterns of Mansonia spp., highlighting periods of peak density. Notably, a significant decreasing trend in local abundance was observed from July 2021 (25th epidemiological week) until the end of the study. Wind speed was observed to be the most relevant meteorological factor influencing the abundance of Mansonia spp. especially in the Joana D'Arc settlement, although additional investigation is needed to comprehensively analyze other local events and gain a deeper understanding of the ecological patterns of this genus in the Amazon region.

A bioinspired autonomous swimming robot as a tool for studying goal-directed locomotion.

The bioinspired approach has been key in combining the disciplines of robotics with neuroscience in an effective and promising fashion. Indeed, certain aspects in the field of neuroscience, such as goal-directed locomotion and behaviour selection, can be validated through robotic artefacts. In particular, swimming is a functionally important behaviour where neuromuscular structures, neural control architecture and operation can be replicated artificially following models from biology and neuroscience. In this article, we present a biomimetic system inspired by the lamprey, an early vertebrate that locomotes using anguilliform swimming. The artefact possesses extra- and proprioceptive sensory receptors, muscle-like actuation, distributed embedded control and a vision system. Experiments on optimised swimming and on goal-directed locomotion are reported, as well as the assessment of the performance of the system, which shows high energy efficiency and adaptive behaviour. While the focus is on providing a robotic platform for testing biological models, the reported system can also be of major relevance for the development of engineering system applications.

A novel robotic system for single-port laparoscopic surgery: preliminary experience.

BACKGROUND: The concept of single-access procedures has gained greater attention from general surgeons during the past 5 years. Despite this wide momentum, these procedures pose several changes for the surgeon, such as impaired eye-hand coordination and restricted manipulation. In this context, robotic-assisted surgery represents a promising technology to enhance the dexterity of laparoscopic surgeons. METHODS: A novel teleoperated robotic system for minimally invasive surgery (MIS) called SPRINT (Single-Port lapaRoscopy bImaNual roboT) has been developed. SPRINT is a master-slave robotic platform designed for bimanual interventions through a single-access port. The system is basically composed by two main arms having a maximum diameter of 18 mm and a stereoscopic-camera (Karl-Storz, Tuttlingen, Germany). The arms may be inserted into a cylindrical introducer that has a maximum diameter of 30 mm. The surgeon console is composed of two master manipulators, a foot-switch, and a 3D full-HD display. RESULTS: In an animal study, a small-bowel enteroenterostomy and the ligation of a mesenteric vessel bundle have been performed. As preliminary experience, the system has been placed within the peritoneal cavity through an incision of approximately 10 cm: the robot has been suspended in an open fashion, due to some mechanical constraints of the current prototype. The procedures have been performed in an authorized laboratory on a female pig of approximately 50 Kg. CONCLUSIONS: Two typical surgical maneuvers have been performed successfully with the SPRINT surgical platform: an intestinal anastomosis and a vessel ligation. Moreover, the speed, precision, and force with which the SPRINT robot executed the commands by the surgeon controlling the master console have been subjectively described as adequate to the tasks. Based on this preliminary demonstration, bimanual robot solutions, such as the SPRINT robot, may offer more dexterity and precision to single-port techniques in the next future.

Autocrine 17-ß-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

PURPOSE: The response to immune checkpoint inhibitors (ICI) often differs between genders in non-small cell lung cancer (NSCLC), but metanalyses results are controversial, and no clear mechanisms are defined. We aim at clarifying the molecular circuitries explaining the differential gender-related response to anti-PD-1/anti-PD-L1 agents in NSCLC. EXPERIMENTAL DESIGN: We prospectively analyzed a cohort of patients with NSCLC treated with ICI as a first-line approach, and we identified the molecular mechanisms determining the differential efficacy of ICI in 29 NSCLC cell lines of both genders, recapitulating patients' phenotype. We validated new immunotherapy strategies in mice bearing NSCLC patient-derived xenografts and human reconstituted immune system ("immune-PDXs"). RESULTS: In patients, we found that estrogen receptor α (ERα) was a predictive factor of response to pembrolizumab, stronger than gender and PD-L1 levels, and was directly correlated with PD-L1 expression, particularly in female patients. ERα transcriptionally upregulated CD274/PD-L1 gene, more in females than in males. This axis was activated by 17-ß-estradiol, autocrinely produced by intratumor aromatase, and by the EGFR-downstream effectors Akt and ERK1/2 that activated ERα. The efficacy of pembrolizumab in immune-PDXs was significantly improved by the aromatase inhibitor letrozole, which reduced PD-L1 and increased the percentage of antitumor CD8+T-lymphocytes, NK cells, and Vγ9Vδ2 T-lymphocytes, producing durable control and even tumor regression after continuous administration, with maximal benefit in 17-ß-estradiol/ERα highfemale immune-xenografts. CONCLUSIONS: Our work unveils that 17-ß-estradiol/ERα status predicts the response to pembrolizumab in patients with NSCLC. Second, we propose aromatase inhibitors as new gender-tailored immune-adjuvants in NSCLC. See related commentary by Valencia et al., p. 3832.

Bacterial diversity on larval and female Mansonia spp. from different localities of Porto Velho, Rondonia, Brazil.

Studies based on the bacterial diversity present in Mansonia spp. are limited; therefore, the aim of this study was to investigate the bacterial diversity in females and larvae of Mansonia spp., describe the differences between the groups identified, and compare the microbiota of larvae from different collection sites. Sequences of the 16S rRNA region from the larvae and females of Mansonia spp. were analyzed. Diversity analyzes were performed to verify the possible bacterial differences between the groups and the collection sites. The results showed Pseudomonas was the most abundant genus in both females and larvae, followed by Wolbachia in females and Rikenellaceae and Desulfovibrio in larvae. Desulfovibrio and Sulfurospirillum, sulfate- and sulfur-reducing bacteria, respectively, were abundant on the larvae. Aminomonas, an amino acid-degrading bacterium, was found only in larvae, whereas Rickettsia was identified in females. Bacterial diversity was observed between females and larvae of Mansonia and between larvae from different collection sites. In addition, the results suggest that the environment influenced bacterial diversity.

Magnetic air capsule robotic system: proof of concept of a novel approach for painless colonoscopy.

BACKGROUND: Despite being considered the most effective method for colorectal cancer diagnosis, colonoscopy take-up as a mass-screening procedure is limited mainly due to invasiveness, patient discomfort, fear of pain, and the need for sedation. In an effort to mitigate some of the disadvantages associated with colonoscopy, this work provides a preliminary assessment of a novel endoscopic device consisting in a softly tethered capsule for painless colonoscopy under robotic magnetic steering. METHODS: The proposed platform consists of the endoscopic device, a robotic unit, and a control box. In contrast to the traditional insertion method (i.e., pushing from behind), a "front-wheel" propulsion approach is proposed. A compliant tether connecting the device to an external box is used to provide insufflation, passing a flexible operative tool, enabling lens cleaning, and operating the vision module. To assess the diagnostic and treatment ability of the platform, 12 users were asked to find and remove artificially implanted beads as polyp surrogates in an ex vivo model. In vivo testing consisted of a qualitative study of the platform in pigs, focusing on active locomotion, diagnostic and therapeutic capabilities, safety, and usability. RESULTS: The mean percentage of beads identified by each user during ex vivo trials was 85 ± 11%. All the identified beads were removed successfully using the polypectomy loop. The mean completion time for accomplishing the entire procedure was 678 ± 179 s. No immediate mucosal damage, acute complications such as perforation, or delayed adverse consequences were observed following application of the proposed method in vivo. CONCLUSIONS: Use of the proposed platform in ex vivo and preliminary animal studies indicates that it is safe and operates effectively in a manner similar to a standard colonoscope. These studies served to demonstrate the platform's added advantages of reduced size, front-wheel drive strategy, and robotic control over locomotion and orientation.

Splicing deregulation, microRNA and notch aberrations: fighting the three-headed dog to overcome drug resistance in malignant mesothelioma.

INTRODUCTION: Malignant mesothelioma (MMe) is an aggressive rare cancer of the mesothelium, associated with asbestos exposure. MMe is currently an incurable disease at all stages mainly due to resistance to treatments. It is therefore necessary to elucidate key mechanisms underlying chemoresistance, in an effort to exploit them as novel therapeutic targets. AREAS COVERED: Chemoresistance is frequently elicited by microRNA (miRNA) alterations and splicing deregulations. Indeed, several miRNAs, such as miR-29c, have been shown to exert oncogenic or oncosuppressive activity. Alterations in the splicing machinery might also be involved in chemoresistance. Moreover, the Notch signaling pathway, often deregulated in MMe, plays a key role in cancer stem cells formation and self-renewal, leading to drug resistance and relapses. EXPERT OPINION: The prognosis of MMe in patients varies among different tumors and patient characteristics, and novel biomarkers and therapies are warranted. This work aims at giving an overview of MMe, with a special focus on state-of-the-art treatments and new therapeutic strategies against vulnerabilities emerging from studies on epigenetics factors. Besides, this review is also the first to discuss the interplay between miRNAs and alternative splicing as well as the role of Notch as new promising frontiers to overcome drug resistance in MMe.

Seasonality and Biting Behavior of Mansonia (Diptera, Culicidae) in Rural Settlements Near Porto Velho, State of Rondônia, Brazil.

Mansonia (Diptera: Culicidae) are known to cause discomfort to the local populations of Amazon. Considering the fact that the effective control of these mosquitoes can only be obtained by understanding their ecology and behavior, entomological monitoring becomes essential. In view of this, mosquitoes of the genus Mansonia were collected by human landing catches (HLC) from 2015 to 2019, in four locations of Porto Velho, Rondônia, Brazil. The collections were performed inside and outside the homes, once in every four months, uninterrupted for 24 hr. Human bite indices/hour was used to analyze the hourly activity of the species for different seasons and environment (indoor and outdoor). Moreover, nonparametric Mann-Whitney tests were conducted to indicate if there were differences between exophagic and endophagic behavior. The seasonality of Mansonia species was also analyzed. Overall, 96,766 specimens were collected over five years of sampling. Mansonia titillans (Walker) was found to be the most abundant species (76.9%). The highest percentage of mosquitoes was collected in February (48.4%), followed by October (39.6%) and June (12.0%). The biting activity of the two most abundant species showed peak host seeking activity/behavior during twilight and night, more perceptible in the outdoor environment (peridomiciliary). In general, seasonality showed a tendency towards a reduction in the abundance of Mansonia in the years after 2015. Our results will be essential in the formulation of effective control methodology for Mansonia in the studied area.

Mucoadhesive film for anchoring assistive surgical instruments in endoscopic surgery: in vivo assessment of deployment and attachment.

BACKGROUND: Flexible endoscopic procedures in the gastric cavity are usually performed by operative instruments introduced through the working channels of a gastroscope. To enable additional functions and to widen the spectrum of possible surgical procedures, assistive internal surgical instruments (AISI) may be deployed through the esophagus and fixed onto the gastric wall for the entire duration of the procedure. This paper presents a solution for deploying, positioning, and anchoring AISI inside the stomach by exploiting a chemical approach. METHODS: A mucoadhesive polymer was synthesized and tested inside the stomach. In vivo trials were performed on a porcine model by introducing the AISI provided with mucoadhesive by means of an overtube through the mouth. Targeted deployment was achieved by a purposely developed delivery device, passed through the operative channel of a gastroscope. The total time for deployment, positioning, and anchoring of the AISI was evaluated by testing the procedure with passive modules (10, 12, 15, 20 mm in diameter) and active devices: e.g., a miniaturized wired camera and a wireless illumination module. The time and force required for the detachment of the modules were measured. RESULTS: The whole procedure of in vivo deployment, positioning, and attachment of an AISI was performed in approximately 6 min. A preload force of 5 N for 3 min was required for anchoring the modules. The stable adhesion was maintained for a maximum of 110 min. Thanks to the positioning of the camera in the fundus, a wide view of the gastric cavity was obtained. The force required to detach the modules reached 2.8 N. CONCLUSIONS: Mucoadhesive anchoring represents a completely biocompatible and safe solution for stable positioning of AISI onto mucosal tissue. This novel polymeric mechanism can be useful for designing intraluminal accessories and tools that enhance surgeons' performances in endoluminal procedures.

Mercury in blood, hair, and feces from subsistence fish-eating riverines of the Madeira River Basin (Western Amazon).

BACKGROUND: The Madeira River (Amazon Basin) has been impacted by activities related to artisanal and small-scale gold mining (ASGM), deforestation and burning (for timber, agriculture, and hydroelectric dam projects). All these activities contribute to environmental mercury (Hg) release and cycling into the Amazon ecosystem and thus to changing lifestyles. METHOD: We assessed exposure to total and MeHg in two small riverine communities of the Madeira River (Amazon): Lago Puruzinho (LP, n = 26 families) and São Sebastião do Tapurú (SST, n = 31 families). Samples of human hair (n = 137), blood (n = 39), and feces (n = 41) were collected from adults and children (0-15 years of age). RESULTS: In women of childbearing age from LP village, the mean blood total-Hg (THg) (45.54 ±â€¯24.76 µg.L-1) and MeHg (10.79 ±â€¯4.36 µg.L-1) concentrations were significantly (p = 0.0024; p < 0.0001, respectively) higher than in women from SST village (THg: 25.32 ±â€¯16.75 µg.L-1; MeHg: 2.32 ±â€¯1.56 µg.L-1) village; the trend in hair-Hg persisted but was statistically significant (p < 0.0145) only for THg (LP, 11.34 ±â€¯5.03 µg. g-1; SST, 7.97 ±â€¯3.51 µg. g-1). In women, the median hair:blood ratio of total Hg was 269. In children, the mean hair THg concentrations were 6.07 ±â€¯3.60 µg. g-1 and 6.47 ±â€¯4.16 µg. g-1 in LP and SST; thus, not significantly different (p = 0.8006). There was a significant association (p < 0.001) between hair-Hg concentrations of mothers and their respective children. The excretion of Hg in feces of women (0.52 µg. g-1 dw) was not significantly different from children (0.49 µg. g-1 dw). The only statistically significant correlation between Hg in feces and in hair was found in children, (n = 16, rs = 0.38, p = 0.005). Significant relationship was seen between the levels of THg in blood and hair of women from LP and SST. Based on hair-Hg concentrations, fish consumption rate ranged from 94.5 to 212.3 g.day-1. CONCLUSION: Women and children excrete THg in feces in comparable concentrations. However, the mean fish consumption rate and blood MeHg are higher in the most remote villagers. Mother`s hair-Hg concentration is a good predictor of children's hair-Hg.

Total mercury and methylmercury in river dolphins (Cetacea: Iniidae: Inia spp.) in the Madeira River Basin, Western Amazon.

In the Amazon, mercury (Hg) contamination comes from ASGM operations along with soil remobilization processes associated with deforestation. The objective of this study was to evaluate the exposure to methylmercury (MeHg) and total mercury (THg) in 88 samples of skin and blubber tissue obtained from live captured river dolphins (Inia boliviensis, Inia geoffrensis, and Inia spp.) in the Madeira River Basin. THg and MeHg measurements were performed by CV-AAS and GC-AFS, respectively. We also calculated the daily intake rate (DIR) of THg (wet weight) by Inia spp. THg levels in blubber tissue of adult river dolphins (Inia spp.) ranged from 0.015 to 3.804 mg kg-1, while MeHg concentrations in blubber tissue varied from 0.04 to 2.65 mg kg-1 and in skin tissue from 0.09 to 0.66 mg kg-1. There were no significant differences in MeHg concentration in blubber (p = 0.616) and skin (p = 0.498) tissue samples between adult males and females in the different sampling locations. The adult animals showed differences in THg and MeHg concentrations significantly higher than in the calves. The estimate of the DIR of the genus Inia ranged from 1.17 to 12.35 µg kg-1 day-1 (bw), from the consumption of fish species with herbivorous to piscivorous habits, respectively. More biological and ecological data, such as the precise determination of age, mediated length, weight, and diet of river dolphins, are necessary to verify the Hg biomagnification. However, our data indicate that bioaccumulation is an active process in the dolphins of the Madeira River Basin.

Evaluation of the Preclinical Efficacy of Lurbinectedin in Malignant Pleural Mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer generally diagnosed at an advanced stage and characterized by a poor prognosis. The absence of alterations in druggable kinases, together with an immune-suppressive tumor microenvironment, limits the use of molecular targeted therapies, making the treatment of MPM particularly challenging. Here we investigated the in vitro susceptibility of MPM to lurbinectedin (PM01183), a marine-derived drug that recently received accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. METHODS: A panel of primary MPM cultures, resembling the three major MPM histological subtypes (epithelioid, sarcomatoid, and biphasic), was characterized in terms of BAP1 status and histological markers. Subsequently, we explored the effects of lurbinectedin at nanomolar concentration on cell cycle, cell viability, DNA damage, genotoxic stress response, and proliferation. RESULTS: Stabilized MPM cultures exhibited high sensitivity to lurbinectedin independently from the BAP1 mutational status and histological classification. Specifically, we observed that lurbinectedin rapidly promoted a cell cycle arrest in the S-phase and the activation of the DNA damage response, two conditions that invariably resulted in an irreversible DNA fragmentation, together with strong apoptotic cell death. Moreover, the analysis of long-term treatment indicated that lurbinectedin severely impacts MPM transforming abilities in vitro. CONCLUSION: Overall, our data provide evidence that lurbinectedin exerts a potent antitumoral activity on primary MPM cells, independently from both the histological subtype and BAP1 alteration, suggesting its potential activity in the treatment of MPM patients.

Robotic versus manual control in magnetic steering of an endoscopic capsule.

BACKGROUND AND STUDY AIMS: Capsular endoscopy holds promise for the improved inspection of the gastrointestinal tract. However, this technique is limited by a lack of controlled capsule locomotion. Magnetic steering has been proposed by the main worldwide suppliers of commercial capsular endoscopes and by several research groups. The present study evaluates and discusses how robotics may improve diagnostic outcomes compared with manual magnetic steering of an endoscopic capsule. MATERIALS AND METHODS: An endoscopic capsule prototype incorporating permanent magnets was deployed in an ex vivo colon segment. An operator controlled the external driving magnet manually or with robotic assistance. The capsule was maneuvered through the colon, visualizing and contacting targets installed on the colon wall. Procedure completion time and number of targets reached were collected for each trial to quantitatively compare manual versus robotic magnetic steering ( T-test analysis with P = 0.01). Then, through a set of in vivo animal trials, the efficacy of both approaches was qualitatively assessed. RESULTS: In ex vivo conditions, robotic-assisted control was superior to manual control in terms of targets reached (87 % +/- 13 % vs 37 % +/- 14 %). Manual steering demonstrated faster trial completion time (201 +/- 24 seconds vs 423 +/- 48 seconds). Under in vivo conditions, the robotic approach confirmed higher precision of movement and better reliability compared with manual control. CONCLUSIONS: Robotic control for magnetic steering of a capsular endoscope was demonstrated to be more precise and reliable than manual operation. Validation of the proposed robotic system paves the way for automation of capsular endoscopy and advanced endoscopic techniques.