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Introduction: Despite national policy changes, perspective changes on pregnancy and parenting in training are often lacking. We evaluated current viewpoints regarding pregnancy, parenthood, leave needs, and perceptions of support across trainees at our institution., Methods: A cross-sectional survey was sent to all residents and fellows at a tertiary care academic center with >700 trainees. Demographic information, opinions on maternity and paternity leave, and opinions on institutional support and career goals were collected. The survey was sent via the Graduate Medical Education Office listserv -- 66 Accreditation Council for Graduate Medical Education (ACGME) programs and 40 non-ACGME programs., Results: Seven hundred and forty-seven house officers received the survey with a response rate of 21.9% (n = 164). Of respondents, 81% were residents and 99 respondents were female (representing 31% of female trainees at our institution). Thirty-seven point two percent of respondents reported being parents. Twenty-five point three percent of respondents had been pregnant while a trainee with no statistical difference by specialty type (P = 0.0817). Statistically significant difference was noted in having children based on sex with men becoming parents at twice the rate of women (56% vs 26%, P < 0.001). No difference was noted between specialties on perceived support while pregnant and peripartum. Thirty percent of parent respondents reported thinking about leaving medical training after having children given family stressors. Statistical difference in thoughts of leaving medicine overall between females (46%) and males (17.6%; P = 0.0238)., Conclusions: Men and women need support as they navigate becoming parents at a naturally stressful transition period. Females consider leaving medicine at twice the rate of males after becoming parents. Our institution and other ACGME programs need greater transparency and consistent leave practices that reflect changing times., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Despite the promising potential of hydrogel-based therapeutic approaches for spinal cord injury (SCI), the need for new biomaterials to design effective strategies for SCI treatment and the outstanding properties of silk-elastin-like polymers (SELP), the potential use of SELPs in SCI is currently unknown. In this context, we assessed the effects elicited by the in vivo acute intraparenchymal injection of an SELP named (EIS) 2 -RGD6 in a clinically relevant model of SCI. After optimization of the injection system, the distribution, structure, biodegradability, and cell infiltration capacity of (EIS) 2 -RGD6 were assessed. Finally, the effects exerted by the (EIS) 2 -RGD6 injection-in terms of motor function, myelin preservation, astroglial and microglia/macrophage reactivity, and fibrosis-were evaluated. We found that (EIS) 2 -RGD6 can be acutely injected in the lesioned spinal cord without inducing further damage, showing a widespread distribution covering all lesioned areas with a single injection and facilitating the formation of a slow-degrading porous scaffold at the lesion site that allows for the infiltration and/or proliferation of endogenous cells with no signs of collapse and without inducing further microglial and astroglial reactivity, as well as even reducing SCI-associated fibrosis. Altogether, these observations suggest that (EIS) 2 -RGD6-and, by extension, SELPs-could be promising polymers for the design of therapeutic strategies for SCI treatment.

In this chapter we describe two unconventional strategies for the formulation of new nanovaccines. Both strategies are based on obtaining chimeric genes that code for proteins in which the major antigens of the pathogens are fused to an elastin-like recombinamer (ELR) as carrier. ELRs are a family of synthetic protein biopolymers obtained using DNA recombinant techniques. The ELRs employed in the present chapter are block copolymers that are able to assemble, under controlled conditions, into nanoparticles similar to virus-like particles and to provoke an immune response. We describe the biosynthesis of ELRs genetically fused to an antigenic sequence from Mycobacterium tuberculosis and a simple procedure for obtaining stable nanoparticles displaying the antigen in the first strategy. The second approach describes the production of a DNA vaccine library consisting of plasmids codifying for major antigens from Rift Valley fever virus fused to different ELR-based block copolymer architectures.The procedures described can be adapted for the production of other chimeric DNA-protein vaccines based on protein polymer carriers., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Biomaterials science is one of the most rapidly evolving fields in biomedicine. However, although novel biomaterials have achieved well-defined goals, such as the production of devices with improved biocompatibility and mechanical properties, their development could be more ambitious. Indeed, the integration of active targeting strategies has been shown to allow spatiotemporal control of cell-material interactions, thus leading to more specific and better-performing devices. This manuscript reviews recent advances that have led to enhanced biomaterials resulting from the use of natural structural macromolecules. In this regard, several structural macromolecules have been adapted or modified using biohybrid approaches for use in both regenerative medicine and therapeutic delivery. The integration of structural and functional features and aptamer targeting, although still incipient, has already shown its ability and wide-reaching potential. In this review, we discuss aptamer-functionalized hybrid protein-based or polymeric biomaterials derived from structural macromolecules, with a focus on bioresponsive/bioactive systems.

Unlabelled: Individual vulnerability to drug-induced liver injury (DILI) might result from deficiencies in the detoxification process, which determines the level of exposure to the reactive metabolite. We evaluated whether a genetically determined reduction in the ability to detoxify electrophilic compounds, such as that expected among individuals with glutathione S-transferase (GST) null genotypes, might play a role in determining the risk for DILI and its clinical expression. Genomic DNA from 154 patients (74 men, 80 women; mean age, 53 years) with a diagnosis of DILI as assessed with the Council for International Organizations of Medical Science scale and 250 sex- and age-matched healthy controls were analyzed. A multiplex polymerase chain reaction-based method was used to detect GSTM1 and GSTT1 gene deletions. Carriers of double GSTT1-M1 null genotypes had a 2.70-fold increased risk of developing DILI compared with noncarriers (odds ratio 2.70, 95% confidence interval 1.45-5.03; P = 0.003). The odds ratio for DILI patients receiving antibacterials, and NSAIDs were 3.52 (P = 0.002), and 5.61 (P = 0.001), respectively. Patients with amoxicillin-clavulanate hepatotoxicity (n = 32) had a 2.81-fold increased risk (P = 0.037). Patients classified by the combined GSTT1 and GSTM1 null genotypes did not differ with regard to the type of injury, clinical presentation, or outcome, except for the predominance of women in the combined null genotype (P < 0.001)., Conclusion: The double-null genotype for GSTT1 and GSTM1 might play a role in determining the susceptibility to develop DILI, as a general mechanism that occurs regardless of the type of drug involved, and predominantly in women.

Introduction: reexposure to a causal agent represents a potentially serious event in hepatotoxicity., Objectives: to assess the characteristics and outcome of cases with positive reexposure., Material and Methods: a retrospective study of cases with evidence of positive reexposure included in Registro Español de Hepatopatías Asociadas a Medicamentos, and an analysis of their relation to demographic and clinical variables, causality, course, and consequences., Results: of a total of 520 cases 31 (6%) met reexposure criteria. Fatal outcomes, needs for admission, and mean recovery time were all higher for hepatocellular-type toxic injury. The most commonly identified drug class was antibiotics. On most occasions (73%) reexposure to the causal compound escaped notice because of: absence of index case diagnosis, lack of information to patients and their physicians, and (12%) development of cross reactions between structurally similar drugs., Conclusions: accidental reexposure to a drug or a structurally-related compound after an initial hepatotoxicity event is common and may have serious consequences, particularly in hepatocellular-type toxicity. Careful history taking and reflecting diagnostic suspicion in the initial episode s record may reduce the incidence of this iatrogenic event.