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Sperm are transcriptionally and translationally quiescent and, therefore, rely on the seminal plasma microenvironment for function, survival and fertilization of the oocyte in the oviduct. The male reproductive system influences sperm function via the binding and fusion of secreted epididymal (epididymosomes) and prostatic (prostasomes) small extracellular vesicles (S-EVs) that facilitate the transfer of proteins, lipids and nucleic acids to sperm. Seminal plasma S-EVs have important roles in sperm maturation, immune and oxidative stress protection, capacitation, fertilization and endometrial implantation and receptivity. Supplementing asthenozoospermic samples with normospermic-derived S-EVs can improve sperm motility and S-EV microRNAs can be used to predict non-obstructive azoospermia. Thus, S-EV influence on sperm physiology might have both therapeutic and diagnostic potential; however, the isolation of pure populations of S-EVs from bodily fluids with current conventional methods presents a substantial hurdle. Many conventional techniques lack accuracy, effectiveness, and practicality; yet microfluidic technology has the potential to simplify and improve S-EV isolation and detection.

Sperm selection is an essential component of all assisted reproductive treatments (ARTs) and is by far the most neglected step in the ART workflow in regard to technological innovation. Conventional sperm selection methodologies typically produce a higher total number of sperm with variable motilities, morphologies, and levels of DNA integrity. Gold-standard techniques, including density gradient centrifugation (DGC) and swim-up (SU), have been shown to induce DNA fragmentation through introducing reactive oxygen species (ROS) during centrifugation. Here, we demonstrate a 3D printed, biologically inspired microfluidic sperm selection device (MSSP) that utilizes multiple methods to simulate a sperms journey toward selection. Sperm are first selected based on their motility and boundary-following behavior and then on their expression of apoptotic markers, yielding over 68% more motile sperm than that of previously reported methods with a lower incidence of DNA fragmentation and apoptosis. Sperm from the MSSP also demonstrated higher motile sperm recovery after cryopreservation than that of SU or neat semen. Experiments were conducted side-by-side against conventional SU methods using human semen (n = 33) and showed over an 85% improvement in DNA integrity with an average 90% reduction in sperm apoptosis. These results that the platform is easy-to-use for sperm selection and mimics the biological function of the female reproductive tract during conception.

Schnell wirksame Antidepressiva widerlegen das Dogma, dass es mehrere Wochen dauert, bis Antidepressiva klinisch wirken. Ketamin, der Prototyp eines schnell wirksamen Antidepressivums, blockiert N‑Methyl-D-Aspartat(NMDA)-Rezeptoren und fuhrt bereits nach einer einmaligen i.v. Gabe zu raschen Veranderungen des glutamatergen Neurotransmittersystems. Dadurch kommt es zu einer bevorzugten Aktivierung von Glutamatrezeptoren vom AMPA(„α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid“)-Typ. Dies bedingt die Aktivierung des Neurotrophins BDNF („brain-derived neurotrophic factor“) und verursacht innerhalb von 24 h plastische Veranderungen. Im prafrontalen Kortex fuhrt Ketamin zur Regeneration synaptischer Verbindungen, die zuvor durch chronischen Stress geschadigt wurden. Im Tiermodell korreliert dies mit der Verbesserung depressionsartiger Verhaltensweisen. Moglicherweise bewirken auch klassische, monoaminerge Antidepressiva solche Veranderungen, allerdings mit einer sehr viel groseren Latenz. Fur den klinischen Einsatz wurde eine als Nasenspray applizierbare Form des Ketaminenantiomers Esketamin entwickelt, weil selbiges die hochste Affinitat zu NMDA-Rezeptoren aufweist. Aber auch R‑Ketamin und bestimmte Ketaminmetabolite sind zumindest praklinisch antidepressiv wirksam und derzeit in der klinischen Erprobung. Auserdem sucht man nach spezifischen Substanzen, mit denen man das glutamaterge System entsprechend verandern kann, ohne die ketamintypischen Nebenwirkungen zu erzielen. Es gibt aber auch vielversprechende, potenziell schnell wirksame Antidepressiva, die nicht direkt uber das Glutamatsystem wirken, beispielsweise den GABA(γ-Amino-Buttersaure)-Rezeptor-Modulator Brexanolon oder den Serotoninrezeptor-Agonisten Psilocybin.

Data de publicació electrònica: 11 d'octubre de 2022 Overrepresentation of foreigners in prisons is a well-established fact in Spain. However, there is a lack of empirical studies exploring the causes of this overrepresentation. Based on focal concerns theory, this paper aims to explore one of the possible causes of this overrepresentation: sentencing disparities between Spanish and foreign citizens. For this purpose, two subsets of court records are used to study disparities in the odds of incarceration (n = 2310) and differences in the length of prison sentence (n = 1162). Due to alleged limitations of standard regression models to analyse disparities in sentencing when differences between groups are large, entropy re-weighting was used to achieve balance between group observations with regard to control variables. The analyses reveal, on the one hand that, even when controlling for relevant legal and other extra-legal factors, citizens from Africa have higher odds than Spanish citizens to be sentenced to prison. On the other hand, no differences in the length of the conviction have been found. Research funding provided thanks to Ministerio de Economía y Competitividad (Ref: PGC2018-099155-B-I00). Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.

Introduction The purpose of this paper is to present an analysis on the energy balance of the hybrid energy system and the mooring scheme for a container ship, as well as the energy balance of the electricity generating systems, from unconventional sources. The methods applied to achieve the main objective consist of analytical calculations and simulations in the ANSYS Fluent program for various positions of the analyzed system, as follows: a) technical characteristics of the container ship; b) elements of the hybrid energy system, which uses unconventional energy; c) energy balance of electricity generating systems from unconventional sources; d) connecting conventional and unconventional power sources to the ship's main power bar. Results Finally of researches, the results obtained are: a) the volume, mass and ascending force of the FLETTNER balloon with helium, assimilated with an airship; b) positioning scheme of large vertical wind turbines installed in the bow of the container ship and in the stern of the container ship; c) the energy balance of electricity generating systems from unconventional sources; d) schemes for connecting conventional and unconventional energy sources to the ship. Conclusions The calculation of the energy balance of the two types of wind energy capture systems depending on the speed of the ship, in ideal wind conditions and depending on the number of vertical wind turbines running, which use wind energy. Of course, it will never be necessary to turn on all wind power equipment at full capacity. The FLETTNER balloon can generate more power and for this reason, we must to present the number and diameter of cables needed to transmit electricity. Through this research, following the installation of the elements of the hybrid diesel-electric power system with energy from conventional (fossil fuels) and unconventional energy sources (a FLETTNER balloon with helium and four large vertical wind turbines) placed on a ship container portability, both the manoeuvrability and the stability of the ship, do not change fundamentally.

The alveolar ducts are connected to peripheral septal fibers which extend from the visceral pleura into interlobular septa, and are anchored to axial fibers in the small airways. Together these axial and septal fibers constitute a fiber continuum that provides tension and integrity throughout the lung. Building on the observations that alveolar ducts associated with sub-pleural alveoli are orientated perpendicular to the visceral pleura, and in parallel to each other, the goal of the present study was to investigate the nature of the collagen fiber organization within sub-pleural alveolar ducts in healthy control and elastase-induced emphysema murine lungs. Employing three-dimensional second harmonic generation imaging, the structural arrangement of fibrilar collagen fibers could be visualized in cleared murine lungs. In healthy control lungs, fibrilar collagen fibers within alveolar mouths formed the coiled collagen structure within the alveolar duct. In the elastase-treated emphysema lungs, there was loss of fibrilar collagen fibers (p

Current developments in fields such as quantum physics, fine arts, robotics, cognitive sciences or defense and security indicate the emergence of creative systems capable of producing new and innovative solutions through combinations of machine learning algorithms. These systems, called machine invention systems, challenge the established invention paradigm in promising the automation of – at least parts of – the innovation process. This paper’s main contribution is twofold. Based on the identified state-of-the-art examples in the above mentioned fields, key components for machine invention systems and their relations are identified, creating a conceptual model as well as proposing a working definition for machine invention systems. The differences and delimitations to other concepts in the field of machine learning and artificial intelligence, such as machine discovery systems are discussed as well. Furthermore, the paper briefly addresses the social and societal implications and limitations that come with the adoption of the technology. Because of their revolutionizing potential, there are widespread implications to consider from ethical and moral implications to policymaking and societal changes, like changes in the job structure. The discussion part approaches some of these implications, as well as solutions to some of the proposed challenges. The paper concludes by discussing some of the systemic benefits that can be accessed through machine invention.

Identifying high-grade valuable wood resources by the visible individual traits of trees is a challenge for foresters and a requirement for sustainable resource management. The aim of this study was to identify the most relevant phenotypic descriptors of the acoustic quality of Norway spruce standing timber. Two highly valuable Norway spruce (Picea abies) stands located in the Romanian Carpathians were selected for this purpose. A total of 27 tree, bole, bark, and crown variables and nine variables related to wood structure were statistically checked against the velocities of stress waves measured on standing trees at breast height, and the derived parameters: the radiation, the impedance, and the moduli of elasticity in L and R directions. Principal component analysis was used for exploratory data analysis as well as mixed linear models were involved in explaining these acoustics. There were consistent variations in the measured acoustics from tree to tree, according to the age and social class. Wood acoustical parameters measured in the R direction are better predicted by tree phenotype than the acoustical parameters measured in the L direction. Bark thickness and branch width were the best predictors, while tree ring features were less predictive. At a given age, trees with high velocity had thinner and reddisher bark, thinner branches, and a narrower crown. Trees with high velocity anisotropy had narrower branches and wider sapwood. Furthermore, the phenotypic traits used had a poor explanatory power of the radiation ratio. In conclusion, spruce standing trees from the studied area bring forward certain outside features that enable us the multitrait identification of highly valuable wood for string instruments.

Rapastinel is a novel psychoactive substance that acts as an N-methyl-D-aspartate-receptor (NMDAR) agonist and triggers antidepressant- and antipsychotic-like effects in animal models. However, it is unknown if rapastinel possesses a better side-effect profile than fast-acting glutamatergic antidepressants, like ketamine, which trigger neurotoxicity in the perinatal rodent cortex and protracted schizophrenia-like alterations. Here we found a remarkable neuroprotective effect of rapastinel against apoptosis induced by the NMDAR antagonist MK-801 in comparison to that elicited by clozapine and the mGlu2/3 agonist LY354740. These results suggest the potential therapeutic/prophylactic effect of rapastinel in ameliorating deleterious effects induced by NMDAR blockade during neurodevelopment.

This paper aims to review data regarding two determinants of comorbidity between depression and obesity, i.e., the role of disturbed gut microbiome in their genesis and of diets in their treatment. Obesity and major depressive disorders (MDD) are highly comorbid, the “metabolic” (obese) subtype of MDD affects about one third of all individuals with MDD. There is an urgent need for better therapies strategies, which may include specific dietary measures. A diet low in carbohydrates (low-carb), effective in obesity, may be beneficial also in MDD. However, the underlying mechanisms have not yet been elucidated. Recent data suggest a key role of gut microbiota, neuroplasticity, and neuroinflammation in obesity and MDD. We will focus on the brain-derived neurotrophic factor (BDNF), and microglial fractalkine, a main modulator of neuroinflammation. BDNF and fractalkine may be involved in “metabolic” depression. Future studies may uncover specific pathophysiological pathways in affected patients towards more efficient causal therapies.

Treating benign tumors of the pancreatic head by using duodenum-preserving total or subtotal pancreatic head resection (DPPHRt/s) has proven to reduce mortality and morbidity with a positive postoperative outcome, when compared with the standard approach which is represented by pancreaticoduodenectomy (PD). We present three cases of DPPHRs for benign tumors, in which pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG) were used. The long-term outcome of these patients was favorable; with a single case that presents a rapid onset of an acute pancreatitis, with postoperative pancreatic fistula that necessitate reoperation. The best results on early postoperative outcome were recorded in the case of pancreaticogastrostomy, with rapid onset of digestive tolerance and short period of hospital stay. These cases come in aiding modern surgery by ensuring an alternative to reintegrate the pancreatic remnant into the digestive tract after limited pancreatic head resection, with lower rates of postoperative complications.

Planar micromixers with repetitive units have received substantial research interest since they allow low cost, lab-on-a-chip (LOC), and point-of-care (POC) systems to achieve a proper level of mixing for any given process. This paper presents an efficient planar micromixer that combines four types of mixing units, including convergent–divergent, circular, rhombic, and G-shaped micromixers. Their combinations and resulting effects on the mixing efficiency are numerically and experimentally investigated. A comprehensive Taguchi design of experiment method was used to reduce the number of the combinations from 1024 to only 16, among which a micromixer made of rhombic and G-shaped units readily showed a mixing efficiency beyond 80% over a wide range of inlet Reynolds numbers 0.001–0.3 and 35–65; meanwhile, a pressure drop as low as 12 kPa was reported. The velocity and concentration fields and their gradients within the nominated micromixer were analyzed, providing a better understanding of the mixing mechanism. These results offer design insights for further development of planar micromixers with repetitive unites for low-cost LOC and POC devices.

Denoting by $\mathbb{M}$ the complexification of the quaternionic algebra $\mathbb{H}$, we characterize the family of those $\mathbb{M}$-valued functions, defined on subsets of $\H$, whose values are actually quaternions, using an intrinsic approach. In particular, we show that the slice quaternionic regularity can be characterized via a Cauchy type transform acting on the space of analytic $\mathbb{M}$-valued stem functions., Comment: arXiv admin note: text overlap with arXiv:1902.03850

The aim of the study is to assess the impact of the splenic hilar vasculature configuration on the amount of remnant splenic parenchyma volume after partial splenectomy for splenic cysts. The data of all patients receiving a splenectomy for a splenic cyst from 2002 to 2016 at the Center of General Surgery and Liver Transplantation of Fundeni Clinical Institute were retrospectively reviewed. The size and location in the splenic parenchyma of the cyst and the splenic hilar vasculature type were assessed for each patient with a splenectomy. Thirty-one patients with non-parasitic and 32 patients with hydatid cysts were recorded. In cases of centrally located cysts, a total splenectomy was performed for the majority of cases, while in peripheral cysts a spleen-preserving surgery was feasible for most of the patients (p = 0.001). The size of the cyst was significantly higher in the group of patients with a total splenectomy, compared with the group with a partial splenectomy (p = 0.003). In the subgroup with a distributed arterial pattern, preservation of more than 50% of the initial parenchyma was achieved in a significantly higher proportion of patients, compared with the subgroup of patients with a magistral pattern (p = 0.012). Besides cyst size or peripheral location in the splenic parenchyma, the vascular pattern is also considered another decisive factor that associates with successful conservative or minimally invasive approach.

The total number of retrieved and analyzed lymph nodes is known to impact on survival of patients with gastric cancer. Multiple factors are responsible for the high variability of total lymph node yields. Among these factors, the use of surgical ex vivo lymphodissection may be significant for optimizing the lymph node count. This article includes our personal experience regarding ex vivo lymphodissection and a meta-analysis which included all the articles related to this topic. We compared two groups of patients with gastric adenocarcinoma who underwent gastrectomy with at least D2 lymphodissection. In the first group, the lymph node count was performed by the pathologist. As for the second, the surgeon performed an ex vivo lymphodissection of the resected specimens before submitting these to the pathologist for further analysis. For the systematic literature review and the meta-analysis, the PubMed database was thoroughly searched, and in order to assess the inter-study heterogeneity, we used I2 and chi2 tests. The total lymph node yield proved to be significantly higher in the ex vivo lymphodissection group than in the non-ex vivo lymphodissection group (37.4 versus 23.2, p 58%, chi2 = 9.63, df = 4, p = 0.05). Surgical ex vivo lymphodissection increases the total lymph node yield and may lead not only to a more accurate staging of gastric cancer, but also to an improved clinical outcome.

A new Ti-20Zr-5Ta-2Ag alloy was elaborated and characterized regarding its microstructure, its native passive film composition and thickness, its surface wettability, its electrochemical behavior in Ringer solution of different pH values, and its ion release. The new alloy has a bi-phase, α + β, acicular, homogeneous microstructure (scanning electron microscopy (SEM)). Its native passive film (12-nm thicknesses) consists of the protective TiO2, ZrO2, and Ta2O5 oxides, Ti and Ta suboxides, and metallic Ag (X-ray photoelectron spectroscopy (XPS) data). The alloy possesses high hydrophilic properties. The main electrochemical parameters of the new alloy are superior to those of Ti as a result of the beneficial influence of Zr, Ta, and Ag alloying elements, which reinforce its native passive film. Electrochemical impedance spectroscopy (EIS) spectra in Ringer solutions for the new alloy displayed better values of impedances and phase angles, proving a more insulate passive film than that on the Ti surface. The main corrosion parameters for the new Ti-20Zr-5Ta-2Ag alloy are more favorable by about 25 to 38 times than those of Ti, confirming extremely resistant passive film. The new Ti-20Zr-5Ta-2Ag alloy releases into Ringer solution low quantities of Ti4+, Zr4+ metallic ions (inductively coupled plasma–mass spectroscopy (ICP-MS)). The Ag+ ions are released in low quantity, conferring to this alloy’s low antibacterial activity. All experimental results show that the new Ti-20Zr-5Ta-2Ag alloy fulfills the requirements for biocompatibility, corrosion resistance, and antibacterial protection.

In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic–and biologic-free–disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR)

Sodium alginate/ammonium lignosulfonate blend solutions and thin films with different compositions have been prepared and studied. The rheology of the film forming solutions was comparatively evaluated and was established the effect of lignosulfonate incorporation onto sodium alginate solution properties and partial compatibility of components was found. The shear-thinning behaviour of the ALG/LS solutions was better evidenced at high ALG content, suggesting that the time required for the reorganization of the network structure is longer for the samples containing predominantly ALG, because its structure is damaged by increasing shear rate. The structural, morphological, optical and antioxidant properties of the crosslinked ALG/LS blend films were investigated with the aim to identify their potential as new active materials with photoprotective and antioxidant properties. The ATR-FTIR spectroscopy revealed the hydrogen bonding interactions between the components and scanning electron microscopy showed the modified microstructure of the blend films depending on composition. The surface topography changes have been evidenced by atomic force microscopy, showing an increased average surface roughness when the increasing lignosulfonate amount was incorporated into ALG matrix. The optical properties measurements revealed the light barrier properties of the blend films and the antioxidant activity evaluation showed the enhanced radical scavenging activity of the films with higher lignosulfonate content.

The structural changes occurred in bioactive glass microspheres belonging to the system SiO2–Na2O–P2O5–CaO–K2O–MgO incorporating yttrium were investigated before and after soaking in simulated body fluid (SBF) by X-ray diffraction (XRD) and 31P and 29Si magic angle sample spinning nuclear magnetic resonance (MAS-NMR). The addition of yttrium to the bioactive glass composition induces changes in the behavior of the glass microspheres in SBF. The XRD analysis proves that after the immersion in SBF a crystalline hydroxyapatite-like phase is developed on the microspheres surface. The 29Si and 31P MAS-NMR results show that silicate species with two and three bridging oxygens per SiO4 tetrahedra and PO4 monomeric units are present in the glass structure. After immersion in SBF, new silicate species with four bridging oxygens appear as result of silica-gel layer formed on microspheres surface. The formation of crystalline hydroxyapatite-type layer is reflected by the occurrence of narrow components in 31P MAS-NMR spectra. The NMR results support the Hench model for bioactive glasses behavior in biological environments.

Peroxynitrite (PON for short) is a powerful nitrating, nitrosating and oxidative agent for cellular constituents. In vivo, PON is formed through the diffusion-controlled reaction between superoxide radical (O2•-) and nitric oxide (•NO). This critical review (with 67 refs.) covers the state of the art in nanomaterial-based (a) detection and imaging of PON inside cells and (b) monitoring of cellular events such as cellular oxidative burst by using optical or electrochemical methods. It starts with the formation, fate and pathophysiology of PON in vivo. The next part summarizes nanomaterial based electrochemical microsensors featuring nanofilms and nanostructured electrodes, nanospheres, 3D nanostructures and graphene-supported catalysts. A following chapter covers techniques based on optical nanoprobes, starting with nanomaterials used in optical detection of PON (including quantum dots, carbon dots, fluorescent organic polymer dots, rare earth nanocrystals including upconversion nanoparticles, iron oxide nanoparticles, gold nanoparticles, and fluorophore-modified nanoporous silicon). This is followed by subsections on strategies for optical detection of PON (including color changes, fluorescence quenching, activation and recovery), and on schemes for optimized spatial and temporal resolution, for improving sensitivity, selectivity, and (photo)stability. We then address critical issues related to biocompatibility, pharmacokinetics, give a number of representative practical applications and discuss challenges related to PON detection. The review concludes with a discussion of latest developments and future perspectives.