Is methotrexate safe for men with an immune-mediated inflammatory disease and an active desire to become a father? Results of a prospective cohort study (iFAME-MTX).

INTRODUCTION: Current scientific evidence guiding the decision whether men with an active desire to become a father should be treated with methotrexate (MTX) remains controversial. We aimed to prospectively evaluate the testicular toxicity profile of MTX focusing on several markers of male fertility, including semen parameters and sperm DNA fragmentation index (sDFI). As a secondary outcome, we aimed to evaluate whether MTX-polyglutamates can be detected in spermatozoa and seminal plasma and to evaluate the enzymatic activity in spermatozoa of folylpolyglutamate synthetase (FPGS). METHODS: In a prospective cohort study, men ≥18 years who started therapy with MTX were invited to participate (MTX-starters). Participants were instructed to produce two semen samples (a pre-exposure and a post-exposure sample after 13 weeks). Healthy men ≥18 years were invited to participate as controls. Conventional semen analyses, male reproductive endocrine axis and sDFI were compared between groups. FPGS enzymatic activity and MTX-PG1-5 concentrations were determined by mass spectrometry analytical methods. RESULTS: In total, 20 MTX-starters and 25 controls were included. The pre-exposure and postexposure semen parameters of MTX-starters were not statistically significant different. Compared with healthy controls, the conventional semen parameters and the sDFI of MTX-starters were not statistically significant different. These data were corroborated by the marginal accumulation of MTX-PGs in spermatozoa, consistent with the very low FPGS enzymatic activity associated with the expression of an alternative FPGS splice-variant. DISCUSSION: Treatment with MTX is not associated with testicular toxicity, consistent with the very low concentration of intracellular MTX-PG. Therefore, therapy with MTX can be safely started or continued in men and with a wish to become a father.

Biomedical Applications of Metal 3D Printing.

Additive manufacturing's attributes include print customization, low per-unit cost for small- to mid-batch production, seamless interfacing with mainstream medical 3D imaging techniques, and feasibility to create free-form objects in materials that are biocompatible and biodegradable. Consequently, additive manufacturing is apposite for a wide range of biomedical applications including custom biocompatible implants that mimic the mechanical response of bone, biodegradable scaffolds with engineered degradation rate, medical surgical tools, and biomedical instrumentation. This review surveys the materials, 3D printing methods and technologies, and biomedical applications of metal 3D printing, providing a historical perspective while focusing on the state of the art. It then identifies a number of exciting directions of future growth: (a) the improvement of mainstream additive manufacturing methods and associated feedstock; (b) the exploration of mature, less utilized metal 3D printing techniques; (c) the optimization of additively manufactured load-bearing structures via artificial intelligence; and (d) the creation of monolithic, multimaterial, finely featured, multifunctional implants.

Impaired fertility in men diagnosed with inflammatory arthritis: results of a large multicentre study (iFAME-Fertility).

OBJECTIVES: The impact of inflammatory arthritis (IA) on male fertility remains unexplored. Our objective was to evaluate the impact of IA on several male fertility outcomes; fertility rate (number of biological children per man), family planning, childlessness and fertility problems. METHODS: We performed a multicentre cross-sectional study (iFAME-Fertility). Men with IA 40 years or older who indicated that their family size was complete were invited to participate. Participants completed a questionnaire that included demographic, medical and fertility-related questions. To analyse the impact of IA on fertility rate, patients were divided into groups according to the age at the time of their diagnosis: ≤30 years (before the peak of reproductive age), between 31 and 40 years (during the peak) and ≥41 years (after the peak). RESULTS: In total 628 participants diagnosed with IA were included. Men diagnosed ≤30 years had a lower mean number of children (1.32 (SD 1.14)) than men diagnosed between 31 and 40 years (1.60 (SD 1.35)) and men diagnosed ≥41 years (1.88 (SD 1.14)).This was statistically significant (p=0.0004).The percentages of men diagnosed ≤30 and 31-40 years who were involuntary childless (12.03% vs 10.34% vs 3.98%, p=0.001) and who reported having received medical evaluations for fertility problems (20.61%, 20.69% and 11.36%, p=0.027) were statistically significant higher than men diagnosed ≥41 years. CONCLUSIONS: This is the first study that shows that IA can impair male fertility. Men diagnosed with IA before and during the peak of reproductive age had a lower fertility rate, higher childlessness rate and more fertility problems. Increased awareness and more research into the causes behind this association are urgently needed.

Fully 3D-printed carbon nanotube field emission electron sources with in-plane gate electrode.

We report the design, fabrication, and experimental characterization of the first fully additively manufactured carbon nanotube (CNT) field emission electron sources. The devices are created via direct ink writing (DIW)-one of the least expensive and most versatile additive manufacturing methods, capable of creating monolithic multi-material objects. The devices are 2.5 cm by 2.5 cm glass substrates coated with two imprints, i.e. a trace made of a CNT ink (the emitting electrode), symmetrically surrounded on both sides by a trace made of Ag microparticle ink (the in-plane extractor gate). The CNT ink is a mixture of (-COOH)-functionalized multiwalled CNTs (MWCNTs), N,N-Dimethylformamide, and ethyl cellulose. Optimization of the formulation of the CNT ink resulted in a MWCNT concentration equal to 0.82 wt% and in imprints with an electrical resistivity equal to 0.78 Ω cm. 3D-printed devices having CNT imprints with active length equal to 25 mm (a single, straight trace with 174.5 µm gap between adjacent Ag microparticle imprints) and 135 mm (a square-loop spiral with 499 µm gap between Ag microparticle adjacent imprints) were characterized in a triode configuration (i.e. using an external anode electrode) at ∼2.5 × 10-7 Torr, yielding emission currents as large as 120 µA (60 µA cm-2), start-up voltages as low as 62 V and gate transmission as high as 99%. The low-cost cold cathode technology is compatible with compact applications such as miniaturized mass spectrometry, handheld x-ray generation, and nanosatellite electric propulsion.

Comparison of the capture efficiency, prey processing, and nutrient extraction in a generalist and a specialist spider predator.

Predators are traditionally classified as generalists and specialists based on the presence of adaptations that increase efficiency of prey capture and consumption and selection of particular prey types. Nevertheless, empirical evidence comparing foraging efficiency between generalist and specialist carnivores is scarce. We compared the prey-capture and feeding efficiency in a generalist and a specialist (araneophagous) spider predator. By using two related species, the generalist Harpactea rubicunda (Dysderidae) and the specialist Nops cf. variabilis (Caponiidae), we evaluated their fundamental trophic niche by studying the acceptance of different prey. Then, we compared their predatory behavior, efficiency in capturing prey of varying sizes, feeding efficiency, and nutrient extraction. Nops accepted only spiders as prey, while Harpactea accepted all offered prey, confirming that Nops is stenophagous, while Harpactea is euryphagous. Further, Nops displayed more specialized (stereotyped) capture behavior than Harpactea, suggesting that Nops is a specialist, while Harpactea is a generalist. The specialist immobilized prey faster, overcame much larger prey, and gained more mass (due to feeding on larger prey) than the generalist. Both the specialist and the generalist spider extracted more proteins than lipids, but the extraction of macronutrients in the specialist was achieved mainly by consuming the prosoma of the focal prey. We show that the specialist has more efficient foraging strategy than the generalist.

A new species of Piaroa (Schizomida: Hubbardiidae) from Venezuela, with taxonomic notes on the genus.

A new species belonging to the schizomid genus Piaroa Villarreal, Giupponi and Tourinho, 2008 is described from north-western Venezuela. A complementary description of Piaroa guipongai Villarreal and Garcia, 2012 is provided including SEM pictures of relevant structures of both sexes. A key for males of Piaroa and Colombiazomus Armas and Delgado-Santa, 2012 is included. The presence of Dm3 setae on Hubbardiidae is discussed.

High-Performance, Low-Cost, Additively Manufactured Electrospray Ion Sources for Mass Spectrometry.

We report novel 3D-printed electrospray sources for mass spectrometry (MS) that produce twice the signal strength of their mainstream counterparts. Leveraging 3D printing to fabricate in bulk nano- and microscale-featured electrospray emitters, this work shows a path for scalable integration in clinically relevant diagnostics. This solution improves the device performance by simultaneously tuning the surface hydrophilicity, solvent evaporation, and geometry. The emitters are made of stainless-steel (SS) 316L via binder jetting and coated in a conformal, hydrothermally grown zinc oxide nanowire (ZnONW) forest. The printed emitters are designed as surface mount devices that can be directly soldered to printed circuit boards with built-in digital microfluidics as part of an automated device assembly. The electrospray sources use a novel extractor electrode design that enables operation at ∼24% larger bias voltages compared with conventional MS cylindrical inlets. The 3D-printed electrospray emitters were characterized against their state-of-the-art counterparts (coated blades and paper spray). MS data from the 3D-printed electrospray emitters show detection of therapeutically relevant targets at 1 µg/ml concentrations with a variety of solvents; for nicardipine, such emitters attain 116% higher signal-to-noise ratios and far greater stability than their counterparts.

Addressing the unspoken: sexual dysfunction in men with systemic lupus erythematosus, a call to action for rheumatologists.

INTRODUCTION: Sexual dysfunction (SD) is highly prevalent and multifactorial; nevertheless, recent research has shed light on a notable phenomenon: male patients with systemic lupus erythematosus (SLE) exhibit an elevated prevalence of sexual function disorders compared with the general population. Despite this recognition, the precise nature and extent of this association remain incompletely understood. OBJECTIVES: This comprehensive review aims to clarify the link by providing an overview of the fundamental components of normal male sexual function, delving into the pathogenesis of male SD and exploring the primary factors predisposing male SLE patients to SD. Additionally, the review offers insights into potential screening, diagnostic, and treatment strategies based on the current body of literature. METHODS: A meticulous search of relevant literature was conducted using the PubMed and Google Scholar databases. RESULTS: Studies exploring the correlation between SLE and SD in both genders have revealed a nearly 2-fold increased risk of SD among individuals with SLE compared with healthy counterparts. Moreover, these studies suggest that male SLE patients may have a higher susceptibility to SD, with reported prevalence ranging from 12% to 68%, compared with 0% to 22% in healthy individuals. Male patients with SLE are influenced by a spectrum of pathological factors, including pharmacological, psychological, and disease-related determinants, which, through their intricate interplay, elevate the likelihood of developing SD. CONCLUSION: Healthcare professionals must remain vigilant in understanding the intricacies of human sexuality and its dysfunction, particularly in males with SLE. The objective is to establish effective and potentially standardized methods for promptly diagnosing and optimally managing SD, recognizing its significant impact on the quality of life for males living with SLE. The pivotal role of rheumatologists in initiating discussions about sexual health, diagnosing SD, investigating causes, and implementing tailored strategies is underscored as crucial in addressing this multifaceted issue.

Evaluating the participation of junior members and patient and healthcare professionals representatives in EULAR task forces: results from an international survey.

OBJECTIVE: European Alliance of Associations for Rheumatology (EULAR) task forces (TF) requires participation of ≥2 junior members, a health professional in rheumatology (HPR) and two patient research partners for the development of recommendations or points to consider. In this study, participation of these junior and representative members was compared with the one of traditional TF members (convenor, methodologist, fellow and expert TF members). METHODS: An online survey was developed and emailed to previous EULAR TF members. The survey comprised multiple-choice, open-ended and 0-100 rating scale (fully disagree to fully agree) questions. RESULTS: In total, 77 responded, 48 (62%) women. In total, 46 (60%) had participated as a junior or representative TF member. Most junior/representative members reported they felt unprepared for their first TF (10/14, 71%). Compared with traditional members, junior/representative members expressed a significantly higher level of uncertainty about their roles within the TF (median score 23 (IQR 7.0-52.0) vs 7 (IQR 0.0-21.0)), and junior/representative members felt less engaged by the convenor (54% vs 71%). Primary factors that facilitated interaction within a TF were experience, expertise and preparation (54%), a supportive atmosphere (42%) and a clear role (12%). CONCLUSION: Juniors, patients and HPR experience various challenges when participating in a EULAR TF. These challenges differ from and are generally less pronounced than those experienced by traditional TF members. The convenor should introduce the participants to the tasks, emphasise the value of their contributions and how to prepare accordingly for the TF meeting.

Linking toxicity and predation in a venomous arthropod: the case of Tityus fuhrmanni (Scorpiones: Buthidae), a generalist predator scorpion.

BACKGROUND: Scorpions are arachnids that have a generalist diet, which use venom to subdue their prey. The study of their trophic ecology and capture behavior is still limited compared to other organisms, and aspects such as trophic specialization in this group have been little explored. METHODS: In order to determine the relationship between feeding behavior and venom toxicity in the scorpion species Tityus fuhrmanni, 33 specimens were offered prey with different morphologies and defense mechanisms: spiders, cockroaches and crickets. In each of the experiments we recorded the following aspects: acceptance rate, immobilization time and the number of capture attempts. The median lethal dose of T. fuhrmanni venom against the three different types of prey was also evaluated. RESULTS: We found that this species does not have a marked difference in acceptance for any of the evaluated prey, but the number of capture attempts of spiders is higher when compared to the other types of prey. The immobilization time is shorter in spiders compared to other prey and the LD50 was higher for cockroaches. CONCLUSIONS: These results indicate that T. fuhrmanni is a scorpion with a generalist diet, has a venom with a different potency among prey and is capable of discriminating between prey types and employing distinct strategies to subdue them.

Pinching or stinging? Comparing prey capture among scorpions with contrasting morphologies.

Background: Scorpions can use their pincers and/or stingers to subdue and immobilize their prey. A scorpion can thus choose between strategies involving force or venom, or both, depending on what is required to subdue its prey. Scorpions vary greatly in the size and strength of their pincers, and in the efficacy of their venom. Whether this variability is driven by their defensive or prey incapacitation functionis unknown. In this study, we test if scorpion species with different pincer morphologies and venom efficacies use these weapons differently during prey subjugation. To that end, we observed Opisthacanthus elatus and Chactas sp. with large pincers and Centruroides edwardsii and Tityus sp. with slender pincers. Methods: The scorpion pinch force was measured, and behavioral experiments were performed with hard and soft prey (Blaptica dubia and Acheta domesticus). Stinger use, sting frequency and immobilization time were measured. Results: We found that scorpions with large pincers such as O. elatus produce more force and use the stinger less, mostly subjugating prey by crushing them with the pincers. In C. edwardsii and Tityus sp. we found they use their slender and relatively weak pincers for holding the prey, but seem to predominantly use the stinger to subjugate them. On the other hand, Chactas sp. uses both strategies although it has a high pinch force. Conclusions: Our results show that scorpionspecies with massive pincers and high pinch force as O. elatus use the stinger less for prey subjugation than scorpionspecies with slenderpincers.

The pest-specific effects of glyphosate on functional response of a wolf spider.

Although glyphosate is widely used for weed pest control, it might have negative side effects on natural enemies. Wolf spiders are one of the most representative predators found on soybean crops in Uruguay, preying on a wide variety of potential pests. However, the sublethal effects that pesticides might have on this group have been poorly explored for South American species. Herein, we explored the sublethal effects of glyphosate on the functional response of the wolf spider Hogna cf. bivittata against three potential pest insects, namely ant (Acromyrmex sp.), caterpillar (Anticarsia gemmatalis), and cricket (Miogryllus sp.). We contaminated residually adult females of the species Hogna cf. bivittata with glyphosate (Roundup®) and compared their functional response against non-contaminated spiders. We did not observe any mortality during the study. We found that overall Hogna cf. bivittata showed a functional response type II against crickets and caterpillars but no functional response to ants. Contaminated spiders killed less ants and caterpillars in comparison to the control group, probably as a consequence of the irritating effects of glyphosate. We did not observe differences in functional response to crickets at the evaluated densities, probably as a consequence of the low capture rate against this prey. Although glyphosate does not specifically target spiders, it might have negative sublethal effects on native predators such as Hogna cf. bivittata. Further studies should explore effect of glyphosate on other native predators from South American crops.

Do predators react differently to dangerous and larger prey? The case of a mygalomorph generalist spider preying upon insects.

Prey morphology and size are known to influence a predator's decision to attack and consume particular prey; however, studies that evaluate both traits simultaneously are uncommon. Here, we first described the trophic niche in the mygalomorph spider Paratropis sp. These spiders have a narrow trophic niche and feed mainly on sympatric species such as larvae of lepidopterans and of beetles such as carabids, passalids and scarabeids. Second, we evaluated the effect of prey taxon and size on acceptance and immobilization duration, and built an ethogram of the predator's behaviors. For each prey taxa, we offered large (approximately same size than the spider) and small larvae (approximately half of the size of the spider) of the aforementioned prey. We classified carabid beetle larvae as the most dangerous prey because of their sharp mandibles and predatory habits, followed by scarabeid larvae; lepidopteran and passalids larvae were considered to be non-dangerous prey. We did not find a significant effect of prey taxon or size on spiders' acceptance. Prey size did not affect the time invested on each behavioral category, but prey taxon did. Moreover, although spiders used a similar strategy for capturing prey, they spent more time biting carabid larvae than other prey. Our results suggest that, at least in our study area, prey that are dangerous or the predator's size do not seem to affect Paratropis sp. acceptance per se, but can cause the predator to change the time budget allocated to each behavior.

Midterm outcomes of the covered endovascular reconstruction of the aortic bifurcation for aortoiliac occlusive disease in a latinoamerican population.

INTRODUCTION: Surgical approach of aortoiliac occlusive disease (AOD) with aorto-bi-femoral graft or endarterectomy, has been the first line treatment with patency rates up to 90%. Nevertheless, this procedure has an early mortality rate of 4%. Vascular complications of aorto-bi-femoral graft have an average incidence of 5-10% and development of incisional hernia in 10% of the cases. The Covered Endovascular Reconstruction of Aortic Bifurcation or CERAB technique, as a new approach is shaping up to be a promising approach. However, there are few studies in Latin America and the Caribbean. MATERIALS AND METHODS: Retrospective multicenter study. All patients treated with the CERAB technique between February 2015 and June 2021 in three hospitals. RESULTS: A total of 9 patients (5 male and 4 female) were treated with the CERAB technique. Only one patient died. Of the total number of patients, 41.2% had a TASC II - C classification, and 58.8% had a TASC II - D classification. Complications included dissection in only 2 patients, massive bleeding in 1 patient and hematoma in 3 patients. The average number of days in critical care was 1.2 days and 2.6 in hospitalization. Two patients required endovascular reintervention. Primary patency was present in 66.7% of the patients. DISCUSSION: The CERAB technique presents a low morbidity and mortality with an 88.9% of technical success rate. None of our patients needed Chimney CERAB procedure. Our results are similar to those reported in the literature, where they report primary patency rates between 82% and 97%.

3D Multicellular Spheroid for the Study of Human Hematopoietic Stem Cells: Synergistic Effect Between Oxygen Levels, Mesenchymal Stromal Cells and Endothelial Cells.

INTRODUCTION: The human bone marrow microenvironment is composed of biological, chemical and physical factors that act in a synergistic way to modulate hematopoietic stem cell biology, such as mesenchymal stromal cells (MSCs), endothelial cells (ECs) and low oxygen levels; however, it is difficult to mimic this human microenvironment in vitro. METHODS: In this work, we developed 3D multicellular spheroid (3D-MS) for the study of human hematopoietic stem cells (HSCs) with some components of perivascular niche. HSCs were isolated from umbilical cord blood, MSCs were isolated from human bone marrow and a microvasculature EC line (CC-2811, Lonza®) was used. For the formation of a 3D structure, a magnetic levitation culture system was used. Cultures were maintained in 21%, 3% and 1% O2 for 15 days. Culture volume, sphericity index and cell viability were determined. Also, human HSC proliferation, phenotype and production of reactive oxygen species were evaluated. RESULTS: After 15 days, 3D-MS exhibited viability greater than 80%. Histology results showed structures without necrotic centers, and higher cellular proliferation with 3% O2. An increase in the expression of the CD34 antigen and other hematopoietic antigens were observed to 1% O2 with MSCs plus ECs and low ROS levels. CONCLUSION: These findings suggest that 3D-MS formed by MSCs, ECs and HSCs exposed to low concentrations of oxygen (1-3% O2) modulate human HSC behavior and mimics some features of the perivascular niche, which could reduce the use of animal models and deepen the relationship between the microenvironment of HSC and human hematological diseases development.

It is not just about sex: viewpoints of men with inflammatory arthritis on the overall impact of the disease on their sexual health.

OBJECTIVES: Sexual health is defined as a state of physical, emotional, mental and social well-being in relation to sexuality. The impact of inflammatory arthritis (IA) on male sexual health has been mainly studied focusing on erectile function, one of the physical components of sexual health. Our objective was to describe the viewpoints among men with IA in the Netherlands on the overall impact of IA on their sexual health. METHODS: Q-methodology, a mixed methods approach to systematically study subjectivity was used. Adult men diagnosed with IA ranked 34 opinion statements about potential impacts of IA on their sexual health and were interviewed. By-person factor analysis was used to identify common patterns in the rankings, which were interpreted as viewpoints. Data from the interviews were used to verify and adjust the interpretations. RESULTS: 30 men (22-77 years) with IA were included. The analysis revealed three viewpoints. Men with the viewpoint 'Arthritis negatively affects my sexual health' experience a dramatic impact on all components of sexual health. In viewpoint 'I am keeping up appearances', IA negatively impacts sexual health but a distinguishing coping mechanism could mask a more serious negative impact. Men with the viewpoint 'I am satisfied with my sexual health'' experience no significant impact of IA on their sexual health. CONCLUSIONS: We identified three viewpoints on the impact of IA on male sexual health, two revealed a negative influence that goes beyond the physical act of sex. IA can severely affect the emotional, mental and social components of sexual health.

Koinobint life style of the spider wasp Minagenia (Hymenoptera, Pompilidae) and its consequences for host selection and sex allocation.

Spider wasps of the genus Minagenia have evolved koinobiontism as a relatively rare life strategy within the widely diversified hymenopteran family Pompilidae. In this study, we evaluated several aspects of the parasitic strategy of the wasp Minagenia sp. (hereafter, Minagenia) - namely host specificity, ontogeny, and sex determination as a function of host size. We found that Minagenia is highly host specific, being associated only with the genus Lycosa from the family Lycosidae, namely Lycosa u-album (Mello-Leitão, 1938), Lycosa erythrognatha (Lucas, 1836) and Lycosa poliostoma (Koch, 1847) with a parasitism incidence of 18.9%, 15.8% and 12.5%, respectively. Both ecological and taxonomical host traits determine the host selection and sex allocation of Minagenia female wasps. Charnov's host-size model explains Minagenia's host-size-dependent sex ratio in combination with the effect of host development stage, host species, and host foraging strategy. We also found that the final instar larva of Minagenia induces behavioural changes in spider hosts. The manipulated spider builds a protective silk chamber as a shelter for parasitoid pupation. Our results suggest that host manipulation seems to be narrowly connected with koinobiont life style throughout Hymenoptera. This study provides new information about the host-parasitoid koinobiont life strategy among spider wasps, which probably arose convergently in distant taxonomical groups within Pompilidae.

Correction: Selection on the Colombian paso horse's gaits has produced kinematic differences partly explained by the DMRT3 gene.

[This corrects the article DOI: 10.1371/journal.pone.0202584.].

Prey and Venom Efficacy of Male and Female Wandering Spider, Phoneutria boliviensis (Araneae: Ctenidae).

Spiders rely on venom to catch prey and few species are even capable of capturing vertebrates. The majority of spiders are generalist predators, possessing complex venom, in which different toxins seem to target different types of prey. In this study, we focused on the trophic ecology and venom toxicity of Phoneutria boliviensis F. O. Pickard-Cambridge, 1897, a Central American spider of medical importance. We tested the hypothesis that its venom is adapted to catch vertebrate prey by studying its trophic ecology and venom toxicity against selected vertebrate and invertebrate prey. We compared both trophic ecology (based on acceptance experiments) and toxicity (based on bioassays) among sexes of this species. We found that P. boliviensis accepted geckos, spiders, and cockroaches as prey, but rejected frogs. There was no difference in acceptance between males and females. The venom of P. boliviensis was far more efficient against vertebrate (geckos) than invertebrate (spiders) prey in both immobilization time and LD50. Surprisingly, venom of males was more efficient than that of females. Our results suggest that P. boliviensis has adapted its venom to catch vertebrates, which may explain its toxicity to humans.