Control of proton transport and hydrogenation in double-gated graphene.

The basal plane of graphene can function as a selective barrier that is permeable to protons1,2 but impermeable to all ions3,4 and gases5,6, stimulating its use in applications such as membranes1,2,7,8, catalysis9,10 and isotope separation11,12. Protons can chemically adsorb on graphene and hydrogenate it13,14, inducing a conductor-insulator transition that has been explored intensively in graphene electronic devices13-17. However, both processes face energy barriers1,12,18 and various strategies have been proposed to accelerate proton transport, for example by introducing vacancies4,7,8, incorporating catalytic metals1,19 or chemically functionalizing the lattice18,20. But these techniques can compromise other properties, such as ion selectivity21,22 or mechanical stability23. Here we show that independent control of the electric field, E, at around 1 V nm-1, and charge-carrier density, n, at around 1 × 1014 cm-2, in double-gated graphene allows the decoupling of proton transport from lattice hydrogenation and can thereby accelerate proton transport such that it approaches the limiting electrolyte current for our devices. Proton transport and hydrogenation can be driven selectively with precision and robustness, enabling proton-based logic and memory graphene devices that have on-off ratios spanning orders of magnitude. Our results show that field effects can accelerate and decouple electrochemical processes in double-gated 2D crystals and demonstrate the possibility of mapping such processes as a function of E and n, which is a new technique for the study of 2D electrode-electrolyte interfaces.

Proton transport through nanoscale corrugations in two-dimensional crystals.

Defect-free graphene is impermeable to all atoms1-5 and ions6,7 under ambient conditions. Experiments that can resolve gas flows of a few atoms per hour through micrometre-sized membranes found that monocrystalline graphene is completely impermeable to helium, the smallest atom2,5. Such membranes were also shown to be impermeable to all ions, including the smallest one, lithium6,7. By contrast, graphene was reported to be highly permeable to protons, nuclei of hydrogen atoms8,9. There is no consensus, however, either on the mechanism behind the unexpectedly high proton permeability10-14 or even on whether it requires defects in graphene's crystal lattice6,8,15-17. Here, using high-resolution scanning electrochemical cell microscopy, we show that, although proton permeation through mechanically exfoliated monolayers of graphene and hexagonal boron nitride cannot be attributed to any structural defects, nanoscale non-flatness of two-dimensional membranes greatly facilitates proton transport. The spatial distribution of proton currents visualized by scanning electrochemical cell microscopy reveals marked inhomogeneities that are strongly correlated with nanoscale wrinkles and other features where strain is accumulated. Our results highlight nanoscale morphology as an important parameter enabling proton transport through two-dimensional crystals, mostly considered and modelled as flat, and indicate that strain and curvature can be used as additional degrees of freedom to control the proton permeability of two-dimensional materials.

Limits on gas impermeability of graphene.

Despite being only one-atom thick, defect-free graphene is considered to be completely impermeable to all gases and liquids1-10. This conclusion is based on theory3-8 and supported by experiments1,9,10 that could not detect gas permeation through micrometre-size membranes within a detection limit of 105 to 106 atoms per second. Here, using small monocrystalline containers tightly sealed with graphene, we show that defect-free graphene is impermeable with an accuracy of eight to nine orders of magnitude higher than in the previous experiments. We are capable of discerning (but did not observe) permeation of just a few helium atoms per hour, and this detection limit is also valid for all other gases tested (neon, nitrogen, oxygen, argon, krypton and xenon), except for hydrogen. Hydrogen shows noticeable permeation, even though its molecule is larger than helium and should experience a higher energy barrier. This puzzling observation is attributed to a two-stage process that involves dissociation of molecular hydrogen at catalytically active graphene ripples, followed by adsorbed atoms flipping to the other side of the graphene sheet with a relatively low activation energy of about 1.0 electronvolt, a value close to that previously reported for proton transport11,12. Our work provides a key reference for the impermeability of two-dimensional materials and is important from a fundamental perspective and for their potential applications.

Ferrozoles: Ferrocenyl derivatives of letrozole with dual effects as potent aromatase inhibitors and cytostatic agents.

In the treatment of hormone-dependent cancers, aromatase inhibitors (AI) are receiving increased attention due to some undesirable effects such as the risk of endometrial cancer and thromboembolism of SERMs (selective estrogen receptor modulators). Letrozole is the most active AI with 99% aromatase inhibition. Unfortunately, this compound also exhibits some adverse effects such as hot flashes and fibromyalgias. Therefore, there is an urgent need to explore new types of AIs that retain the same-or even increased-antitumor ability. Inspired by the letrozole structure, a set of new derivatives has been synthesized that include a ferrocenyl moiety and different heterocycles. The derivative that contains a benzimidazole ring, namely compound 6, exhibits a higher aromatase inhibitory activity than letrozole and it also shows potent cytostatic behavior when compared to other well-established aromatase inhibitors, as demonstrated by dose-response, cell cycle, apoptosis and time course experiments. Furthermore, 6 promotes the inhibition of cell growth in both an aromatase-dependent and -independent fashion, as indicated by the study of A549 and MCF7 cell lines. Molecular docking and molecular dynamics calculations on the interaction of 6 or letrozole with the aromatase binding site revealed that the ferrocene moiety increases the van der Waals and hydrophobic interactions, thus resulting in an increase in binding affinity. Furthermore, the iron atom of the ferrocene fragment can form a metal-acceptor interaction with a propionate fragment, and this results in a stronger coupling with the heme group-a possibility that is consistent with the strong aromatase inhibition of 6.

Boosting the photocatalytic properties of NaTaO3 by coupling with AgBr.

AgBr/NaTaO3 composites, with different molar % of NaTaO3 (Br/NTO(X%)), have been synthesized by simple precipitation methods; bare NaTaO3 was synthesized by hydrothermal procedure, while AgBr was synthesized by a precipitation procedure using cetyl-tri-methyl-ammonium bromide (CTAB) and AgNO3. Samples have been characterized by X-ray diffraction (XRD), N2 adsorption, UV-vis diffuse reflectance spectroscopy (DRS), Fourier-transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Photocatalytic activity of the as-prepared photo-catalysts was evaluated through photocatalytic degradation of rhodamine B (RhB), methyl orange (MO) and caffeic acid (CAFA) under UV and visible illumination. Single AgBr material and Br/NTO(X%) composites displayed the ability to absorb light in the visible region, while NaTaO3 is only photoactive under UV irradiation. Based on the position of conduction and valence bands of AgBr and NaTaO3, the heterojunction between these two photo-catalysts corresponds to a type II junction. In the case of photocatalytic degradation of RhB and CAFA, Br/NTO(x%) composites have highest photocatalytic activity than that obtained by both parental materials under the same operational conditions. AgBr and Br/NTO(x%) composites achieve a fast degradation of MO, together with a considerable adsorption capacity, attributed to the presence of a remaining amount of residual CTAB on the AgBr surface. In summary, coupling AgBr with NaTaO3 improves the photocatalytic activity under both UV and visible illumination with respect to the parental components, but the performance of the composites is highly dependent on the type of substrate to be degraded and the illumination conditions.

Molecular transport through capillaries made with atomic-scale precision.

Nanometre-scale pores and capillaries have long been studied because of their importance in many natural phenomena and their use in numerous applications. A more recent development is the ability to fabricate artificial capillaries with nanometre dimensions, which has enabled new research on molecular transport and led to the emergence of nanofluidics. But surface roughness in particular makes it challenging to produce capillaries with precisely controlled dimensions at this spatial scale. Here we report the fabrication of narrow and smooth capillaries through van der Waals assembly, with atomically flat sheets at the top and bottom separated by spacers made of two-dimensional crystals with a precisely controlled number of layers. We use graphene and its multilayers as archetypal two-dimensional materials to demonstrate this technology, which produces structures that can be viewed as if individual atomic planes had been removed from a bulk crystal to leave behind flat voids of a height chosen with atomic-scale precision. Water transport through the channels, ranging in height from one to several dozen atomic planes, is characterized by unexpectedly fast flow (up to 1 metre per second) that we attribute to high capillary pressures (about 1,000 bar) and large slip lengths. For channels that accommodate only a few layers of water, the flow exhibits a marked enhancement that we associate with an increased structural order in nanoconfined water. Our work opens up an avenue to making capillaries and cavities with sizes tunable to ångström precision, and with permeation properties further controlled through a wide choice of atomically flat materials available for channel walls.

Post-traumatic stress disorder prevalence and sleep quality in fire victims and rescue workers in southern Brazil: a cross-sectional study.

OBJECTIVES: This survey was conducted to evaluate the prevalence of post-traumatic stress disorder (PTSD) and the sleep quality in victims and rescue team of the third deadliest nightclub fire in the world. STUDY DESIGN: A cross-sectional study. METHODS: Participants were victims and rescue workers exposed to a fire at a nightclub, which occurred in January 2013 in Southern Brazil. The Pittsburgh Sleep Quality Index (PSQI), composed of seven subjective sleep variables (including daytime dysfunction), and PTSD Checklist - Civilian version (PCL-C) were applied to all people who sought medical attention at the local reference center in the first year after the event. Comprehensive information was obtained concerning sociodemographic factors, health status, and sleep complaints. RESULTS: A total of 370 individuals, 190 victims and 180 rescue workers, were included. Participants were 70% male, with an average age of 29 years. The prevalence of PTSD was 31.9%, ranging from 24.4% for rescue workers to 38.9% for victims. The prevalence of poor sleep quality was 65.9%, ranging from 56.1% for rescue workers to 75.3% for victims. Most of the participants with PTSD (91.5%) had PSQI scores >5 (poor sleepers), against 54.0% of the non-PTSD individuals. All seven PSQI subscores showed significant differences between PTSD and non-PTSD individuals, especially daytime dysfunction. Sex, shift work, previous psychiatric disease, and sleep quality remained associated with PTSD in adjusted models, with a prevalence ratio (95% CI) of 1.76 (1.28-2.43) in females, 1.73 (1.17-2.55) in shift workers, 1.36 (1.03-1.80) in individuals with psychiatric disease history, and 5.42 (2.55-11.52) in poor sleepers. CONCLUSIONS: The presence of daytime dysfunction increased by at least tenfold the prevalence of PTSD in this sample. Considering that daytime dysfunction was shown to be strongly associated with PTSD, sleep-related issues should be addressed in the assessment of individuals exposed to traumatic events, both victims and rescuers. Factors like shift work and female sex were also associated with PTSD, especially among victims.

Influence of sperm post-thaw subpopulations of angus and nelore bulls on pregnancy rates by fixed-time artificial insemination.

BACKGROUND: The heterogeneity of ejaculate indicates that fertility is still variable among bulls and that more stringent evaluation methods are needed to identify the ejaculates suitable for AI. OBJECTIVE: To identify and characterize the sperm subpopulations (SP) in thawed semen doses of Nelore and Angus bulls and to evaluate the influence of these sperm subpopulations on pregnancy rate in cows submitted to fixed-time AI (FTAI). MATERIALS AND METHODS: A dose of post-thawed semen from each bull (n=18; consisting of Angus n = 9 and Nelore n = 9) was analyzed for: sperm kinetics; morphology and plasma membrane integrity; and the determination of the sperm subpopulations. Differences between the groups were estimated with the t-test considering a significance level of <5%. RESULTS: There was no influence between breeding bulls for sperm morphology, plasma membrane integrity, and pregnancy rate (P > 0.05). Regarding the kinetic parameters evaluated by the CASA system, Nelore had greater values, for cells with slow velocity (Angus: 16.4 %; Nelore: 21.7%; P = 0.028). In contrast, ANGUS bulls had more static cells (Angus: 27.2%; Nelore: 9.3%; P = 0.048). Based on CASA system data and clustering procedures, four sperm subpopulations were statistically established. In Angus bulls, a higher level of fast and nonlinear spermatozoa were found in SP3 (33.3%), followed by SP1 (32.7%%) with fast and progressive spermatozoa. Whereas, SP1 of Nelore bulls had 33.8% fast and progressive spermatozoa, followed by 32.2% of SP3 with fast and nonlinear spermatozoa. CONCLUSION: Both breeds of bulls presented similar proportions of sperm SP. Consequently, no influence on the pregnancy rates was shown in cows submitted to the IATF programs on a large scale. doi.org/10.54680/fr22310110312.

Sexual orientation, gender: Where is the problem? Nowhere! Correct self-identification and minority stigma.

PURPOSE: Self-concept, at the core of minority stress, is associated with negative mental health outcomes. METHODS: We aimed to assess the effectiveness of a one-shot third-wave CBT intervention targeting correct self-identification to address suffering related to minority stress. The study population included 172 participants (n = 98 heterosexuals, n=13 transgenders). The intervention consisted of a 90 minutes conference including overview of LGBT's suffering related to distal and proximal factors, a wisdom understanding of the root of suffering (mistaken self-identification) followed by a Questions & Answers session. Participants completed online self-questionnaires assessing sociodemographic data, acceptance by others (external) and oneself (internal) for sexual orientation and gender variables before the conference, immediately after the conference, and three months later. RESULTS: The conference helped to improve external acceptance of transgender for the whole sample, especially among the majority group. Those belonging to the minority (LGBT) had a positive benefit from the conference by reducing their fear of judgment. Adding a Q&A session to the conference failed to show any additional benefits. CONCLUSION: A specific wisdom-based self-identification conference appears to be an effective and low-cost intervention to target minority stigma, and therefore mental health and social integration of LGBT people.

Trends in psychiatric hospitalization for alcohol and drugs in Castilla y León between 2005 and 2015. / Tendencias en la hospitalización psiquiátrica por alcohol y drogas en Castilla y León entre 2005 y 2015.

It has been estimated that alcohol, tobacco, and illicit drugs were responsible for more than 10 million deaths worldwide in 2016, and there are many opportunities for improvement. Regarding innovative data analysis, advances have been made in the extraction of information from administrative databases for analytics purposes. We studied trends in hospitalization rates for alcohol and drug abuse over eleven years with Joinpoint Trend Analysis software. This is a descriptive study of cross-associations in 3,758 hospital admissions of patients admitted with a main diagnosis of alcohol and drug abuse or dependence in psychiatry units of public health centres of Castilla y León (Spain) between 2005 and 2015. Hospitalization trends for alcohol and drug related conditions declined over the eleven-year period. Separately, there was a statistically significant decrease in alcohol and cocaine related conditions, but a strong upward trend in cannabis related conditions between 2013 and 2015. Alcohol was the main cause of admission to psychiatric units with a diagnosis of addiction. In the 11 years researched, there was a progressive and constant reduction in admissions for substance use except for cannabis. The innovative statistical methodology has already proven to be useful for identifying trends and changes in different pathologies over time.

A nivel mundial, se ha estimado que el alcohol, el tabaco y las drogas han sido responsables de más de 10 millones de muertes en 2016, y que existe mucho margen para reducir la mortalidad. Se han realizado avances en la extracción de información de bases de datos administrativas con el fin de analizar grandes volúmenes de datos sanitarios. Hemos estudiado las tendencias en las tasas de hospitalización con diagnóstico de adicción a alcohol y drogas durante once años con el software Joinpoint Trend Analysis. Se trata de un estudio descriptivo de asociación cruzada de 3.758 ingresos hospitalarios de pacientes con diagnóstico principal de abuso o dependencia de alcohol y drogas en unidades de Psiquiatría de centros públicos de Castilla y León entre 2005 y 2015. Las tendencias en la hospitalización por adicción al alcohol y/o drogas disminuyeron a lo largo de los once años. Además de una reducción estadísticamente significativa de los ingresos por alcohol y cocaína, se apreció una fuerte tendencia al alza en los ingresos por cannabis entre 2013 y 2015. El alcohol fue durante todo el periodo de estudio la principal causa de ingreso y el que más días de hospitalización ha generado. No obstante, en los 11 años se observó una reducción progresiva y constante en los ingresos por todas las sustancias a excepción del cannabis. La metodología utilizada ya ha demostrado ser muy útil para identificar cambios de tendencias en diferentes patologías.

Evaluation of the Freezability of the Bovine Epididymis Tail Sperm with the Addition of Antioxidants.

BACKGROUND: The cryopreservation and recovery of epididymis tail sperm is an important biotechnology dependent on the composition of the freezing medium. OBJETIVE: To evaluate the effect of melatonin, added to commercial freezing medium extender, on the kinetics and viability of bovine epididymis tail sperm. MATERIAL AND METHODS: Five routines were performed, each consisting of eight epididymis and the structures were sliced onto a glass plate containing a commercial diluting medium for Botubov. The samples were divided into four groups, with 80 x 106 spermatozoa per mL. Group 1: samples diluted in Botubov. Group 2: samples centrifuged (600 g, 10 min), and the pellet re-suspended in Botubov. Group 3, samples diluted in Botubov containing 100 pM melatonin. Group 4: samples centrifuged (600 g, 10 min) and the pellet resuspended in Botubov with 100 pM melatonin. The samples were transferred to 0.5 mL straws at 40 x 106 viable spermatozoa, stabilized at 5º C for 4 h, transferred to liquid nitrogen vapour for 20 min, dipped in liquid nitrogen and stored in a cryogenic cylinder. After thawing (46ºC, 15s), sperm kinetics and viability parameters were evaluated. RESULTS: There was no difference in the parameters of total motility (MT, %), progressive motility (MP, %), progressive linear velocity (VSL, µm/s), curvilinear velocity (VCL, µm/s), linearity (LIN, %), spermatozoa with rapid movement (RAP, %) and level of intact plasma membranes and acrosome (IPMA, %) among the groups studied. However, a difference was observed between the routines performed. CONCLUSION: The protocol for freezing bovine epididymis tail sperm is applicable; however, there is an influence of the epididymis used, for the best efficacy of this biotechnology.

Proton transport through one-atom-thick crystals.

Graphene is increasingly explored as a possible platform for developing novel separation technologies. This interest has arisen because it is a maximally thin membrane that, once perforated with atomic accuracy, may allow ultrafast and highly selective sieving of gases, liquids, dissolved ions and other species of interest. However, a perfect graphene monolayer is impermeable to all atoms and molecules under ambient conditions: even hydrogen, the smallest of atoms, is expected to take billions of years to penetrate graphene's dense electronic cloud. Only accelerated atoms possess the kinetic energy required to do this. The same behaviour might reasonably be expected in the case of other atomically thin crystals. Here we report transport and mass spectroscopy measurements which establish that monolayers of graphene and hexagonal boron nitride (hBN) are highly permeable to thermal protons under ambient conditions, whereas no proton transport is detected for thicker crystals such as monolayer molybdenum disulphide, bilayer graphene or multilayer hBN. Protons present an intermediate case between electrons (which can tunnel easily through atomically thin barriers) and atoms, yet our measured transport rates are unexpectedly high and raise fundamental questions about the details of the transport process. We see the highest room-temperature proton conductivity with monolayer hBN, for which we measure a resistivity to proton flow of about 10 Ω cm(2) and a low activation energy of about 0.3 electronvolts. At higher temperatures, hBN is outperformed by graphene, the resistivity of which is estimated to fall below 10(-3) Ω cm(2) above 250 degrees Celsius. Proton transport can be further enhanced by decorating the graphene and hBN membranes with catalytic metal nanoparticles. The high, selective proton conductivity and stability make one-atom-thick crystals promising candidates for use in many hydrogen-based technologies.

Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss.

Objective: This study aimed to compare the efficacy and safety of ossein-hydroxyapatite complex (OHC) versus calcium carbonate (CC) for preventing bone loss during perimenopause in current clinical practice.Methods: The prospective, comparative, non-randomized, open-label study included 851 perimenopausal women with basal bone mineral density (BMD) T-score ≥-2 standard deviations (SDs). Participants received either OHC (712 mg calcium/day) or CC (1000 mg calcium/day) over 3 years. BMD was evaluated by dual-energy X-ray absorptiometry at the lumbar spine (L2-L4) at baseline and after 18 and 36 months of follow-up. Adverse drug reactions (ADRs) were also recorded.Results: In women receiving OHC, BMD at the L2-L4 site remained stable over the 3-year follow-up period (mean [SD] change 0.00 [0.11] g/cm2). BMD in the CC arm decreased -3.1% (mean [SD] - 0.03 [0.11] g/cm2). Between-group differences were statistically significant (p < 0.001) and favored OHC. ADRs were more frequent in the CC group (7.7% vs. 2.7% in the OHC group; p = 0.001), affecting primarily the gastrointestinal system.Conclusion: OHC showed greater efficacy and tolerability than CC for bone loss prevention in perimenopausal women in real-world practice. As the daily dose of calcium was higher in the CC group, the differences might be linked to the ossein compound in OHC.

Maternal health among Venezuelan women migrants at the border of Brazil.

BACKGROUND: Guaranteeing the sexual and reproductive health and rights (SRHR) of populations living in fragile and humanitarian settings is essential and constitutes a basic human right. Compounded by the inherent vulnerabilities of women in crises, substantial complications are directly associated with increased risks of poor SRHR outcomes for displaced populations. The migration of Venezuelans, displaced due to current economic circumstances, is one of the largest in Latin America's history. This study aims to provide an overview of the sexual and reproductive health (SRH) issues affecting migrant Venezuelan women in the state of Roraima, Brazil. METHODS: Face-to-face interviews were conducted from 24 to 30 November 2019. Data collection covered various issues involving access to and use of SRH services by 405 migrant Venezuelan women aged 18-49 years. The Minimum Initial Service Package readiness assessment tools, available from the Inter-Agency Working Group on Reproductive Health in Crises, were used in the data collection. RESULTS: Most commonly, the women reported unmet family planning needs. Of these, a significant proportion reported being unable to obtain contraceptive methods, particularly long-acting reversible contraceptives, either due to the woman's inability to access them or their unavailability at healthcare centres. Although a significant proportion of women were largely satisfied with the attention received at the maternity hospital, both before and during childbirth, 24.0% of pregnant or postpartum women failed to receive any prenatal or postnatal care. CONCLUSION: Meeting the essential SRHR needs of migrant Venezuelan women in Roraima, Brazil is a challenge that has yet to be fully addressed. Given the size of this migrant population, the Brazilian healthcare system has failed to adapt sufficiently to meet their needs; however, problems with healthcare provision are similar for migrants and Brazilian citizens. Efforts need to be encouraged not only in governmental health sectors, but also with academic, non-governmental and international organisations, including a coordinated approach to ensure a comprehensive SRHR response. Given the current high risks associated with the SARS-CoV-2 pandemic, meeting the SRHR needs of migrant populations has become more critical than ever.

Effects of long-term exposure to an extremely low frequency magnetic field (15 µT) on selected blood coagulation variables in OF1 mice.

The long-term exposure of OF1 mice to an extremely low frequency magnetic field (ELF-MF; 50 Hz, 15 µT [rms]) has been associated with the appearance of leukaemia. Neoplasms are usually accompanied by changes in haemostatic processes but reports on changes in blood coagulation following exposure to an ELF-MF are scarce and rather fragmentary. The aim of the present work was to determine whether any global or partial coagulation variables are modified after such long-term exposure. A parental generation of six week-old OF1 mice was exposed to an artificial ELF-MF for 14 weeks. Mating was then allowed, and the resulting filial generation raised until the age of 31-35 weeks within the same ELF-MF. Control animals were subjected only to the magnetic field of the Earth. Whole blood samples were extracted from the anesthetised filial generation of mice by cardiac puncture. White blood cells (WBC) were counted, the activated partial thromboplastin time (APTT) and prothrombin time (PT) determined, and plasma fibrinogen, reptilase time (RT), and factor VIII activity examined. The similarity between the results for the present control animals and those recorded in the literature for human blood render OF1 mice a suitable study model. The differences in the studied coagulation variables were largely owed simply to sex. However, the females showed a very significant shortening of the PT time associated with ELF-MF exposure. Exposure also caused significant increases in the female APTT and RT values, and in general reduced the differences between the sexes.

Atlantic bluefin tuna spawn at suboptimal temperatures for their offspring.

Life-history traits such as spawning migrations and timing of reproduction are adaptations to specific environmental constraints and seasonal cycles in many organisms' annual routines. In this study we analyse how offspring fitness constrains spawning phenology in a large migratory apex predator, the Atlantic bluefin tuna. The reproductive schedule of Atlantic bluefin tuna varies between spawning sites, suggesting plasticity to local environmental conditions. Generally, temperature is considered to be the main constraint on tuna spawning phenology. We combine evidence from long-term field data, temperature-controlled rearing experiments on eggs and larvae, and a model of egg fitness, and show that Atlantic bluefin tuna do not spawn to optimize egg and larval temperature exposure. The timing of spawning leads to temperature exposure considerably lower than optimal at all spawning grounds across the Atlantic Ocean. The early spawning is constrained by thermal inhibition of egg hatching and larval growth rates, but some other factors must prevent later spawning. Matching offspring with ocean productivity and the prey peak might be an important driver for bluefin tuna spawning phenology. This finding is important for predictions of reproductive timing in future climate warming scenarios for bluefin tuna.

Vitrification in straws conserves motility features better than spheres in donkey sperm.

Sperm vitrification as alternative to conventional freezing is increasing in popularity in many species. It has been achieved by direct exposure of diluted semen to liquid nitrogen in spheres or straws. Both techniques have been successfully developed, but they had not been compared yet in donkeys. The aim of this study was to compare these two methods of vitrification for donkey semen. Ejaculates from six Andalusian donkeys were collected and extended in Gent without glycerol supplemented with sucrose 0.1 M (Molar). Samples were slowly cooled at 5°C. For vitrification, 30 µl suspensions (spheres) were dropped directly into liquid nitrogen (LN2 ) or filled in covered 0.25 ml straws and then plunged into the LN2 (straws). For warming, straws and spheres were directly immersed in 3 ml of INRA-96 at 43°C. Total (TM, %) and progressive motility (PM, %) were objectively evaluated by computer-assisted sperm analysis and plasma membrane integrity (PMI, %) by epifluorescence microscopy. Results showed the straw method resulted in significantly higher values than spheres for: TM (54.7% ± 10.1 vs. 28.6% ± 6.5) and PM (44.2% ± 9.4 vs. 17.7% ± 6.4), but no significant differences were found between straws or spheres for PMI (31.5 ± 10.7 vs. 41.6 ± 14.3) respectively. In conclusion, donkey sperm could be vitrified in straws obtaining better sperm motility parameters after warming in comparison to the sphere method.

Comparison of different sucrose-based extenders for stallion sperm vitrification in straws.

Vitrification of sperm is based on high-speed freezing by direct exposure to liquid nitrogen using non-permeable cryoprotectants, mainly disaccharides; yet, the concentration of cryoprotectants has a species-specific effect on the sperm cell. The aim of this study was to assess different sucrose concentrations for stallion sperm vitrification. Semen samples (n = 9) were collected from three stallions, centrifuged and resuspended to a concentration of 50 × 106  sperm/ml in a base extender (INRA96 + 1% of bovine serum albumin) with three different sucrose concentrations (Molar): 20 mM (S1), 100 mM (S2), or 200 mM (S3). Then, sperm were filled in covered 0.25 ml straws and directly plunged into liquid nitrogen. For warming, 0.25 ml straw was pulled out the covering straw and immersed in 3 ml of INRA96 at 43°C, with gentle pipetting to accelerate the melting. Total (TM, %) and progressive sperm motility (PM, %) were analysed using computer-assisted sperm analysis. Plasma (PMI, %) and acrosome membrane integrity (AIS, %) were assessed under epifluorescence microscopy. Post-warmed sperm parameters were compared between treatments by ANOVA. S2 showed significantly higher values in comparison with S1 and S3 for TM (S2 = 54.7 ± 5.5a ; S1 = 29.1 ± 3.3b ; S3 = 28.6 ± 3.0b ; p < 0.001) and PM (S2 = 31.3 ± 3.8a ; S1 = 18.5 ± 2.6b ; S3 = 17.7 ± 2.9b ; p < 0.01), respectively. No significant differences were found among treatments for PMI (S2 = 70.3 ± 5.2; S1 = 67.4 ± 4.3; S3 = 70.0 ± 3.7) neither for AIS (S2 = 57.1 ± 3.9; S1 = 53.9 ± 4.2; S3 = 57.0 ± 7.9). In conclusion, a concentration of 100 mM sucrose is recommended for stallion sperm vitrification in straws.

Patient-derived xenografts effectively capture responses to oncology therapy in a heterogeneous cohort of patients with solid tumors.

BACKGROUND: While patient-derived xenografts (PDXs) offer a powerful modality for translational cancer research, a precise evaluation of how accurately patient responses correlate with matching PDXs in a large, heterogeneous population is needed for assessing the utility of this platform for preclinical drug-testing and personalized patient cancer treatment. PATIENTS AND METHODS: Tumors obtained from surgical or biopsy procedures from 237 cancer patients with a variety of solid tumors were implanted into immunodeficient mice and whole-exome sequencing was carried out. For 92 patients, responses to anticancer therapies were compared with that of their corresponding PDX models. RESULTS: We compared whole-exome sequencing of 237 PDX models with equivalent information in The Cancer Genome Atlas database, demonstrating that tumorgrafts faithfully conserve genetic patterns of the primary tumors. We next screened PDXs established for 92 patients with various solid cancers against the same 129 treatments that were administered clinically and correlated patient outcomes with the responses in corresponding models. Our analysis demonstrates that PDXs accurately replicate patients' clinical outcomes, even as patients undergo several additional cycles of therapy over time, indicating the capacity of these models to correctly guide an oncologist to treatments that are most likely to be of clinical benefit. CONCLUSIONS: Integration of PDX models as a preclinical platform for assessment of drug efficacy may allow a higher success-rate in critical end points of clinical benefit.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.