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Meconium, the first stool produced by neonates, has been used as an analyte for exogenous fetal exposures. However, few studies have investigated the relationship between meconium and androgen exposure in utero. Here, we examine the associations of testosterone and dehydroepiandrosterone (DHEA) across maternal antenatal salivary testosterone, cord blood, meconium, and infant salivary testosterone. A total of 47 women with singleton, uncomplicated pregnancies, and their infants were included in this study. Participants were recruited from an academic obstetric clinic. Maternal saliva was collected at 36-weeks' gestation. Cord blood and meconium were collected at birth. Infant salivary testosterone was collected at 1 and 4 weeks of age. Multivariate model results showed that meconium testosterone was associated with neonatal testosterone at 1 (F = 5.62, p = 0.029) and 4 weeks (F = 4.28, p = 0.048) postnatal age; no sex differences were detected. This study suggests meconium is a valuable tool for evaluating endogenous androgen exposure and should be used in future studies to investigate the fetal hormonal milieu., (© 2024 Wiley Periodicals LLC.)

Brown macroalgae synthesize large amounts of fucoidans, sulfated fucose-containing polysaccharides, in the ocean. Fucoidans are of importance for their recently discovered contribution to marine carbon dioxide sequestration and due to their potential applications in biotechnology and biomedicine. However, fucoidans have high intra- and intermolecular diversity that challenges assignment of structure to biological function and the development of applications. Fucoidan-active enzymes may be used to simplify this diversity by producing defined oligosaccharides more applicable for structural refinement, characterization, and structure to function assignment for example via bioassays. In this study, we combined MALDI mass spectrometry with biocatalysis to show that the endo-fucoidanases P5AFcnA and Wv323 can produce defined oligosaccharide structures directly from unrefined macroalgal biomass. P5AFcnA released oligosaccharides from seven commercial fucoidan extracts in addition to unrefined biomass of three macroalgae species indicating a broadly applicable approach reproducible across 10 species. Both MALDI-TOF/TOF and AP-MALDI-Orbitrap systems were used, demonstrating that the approach is not instrument-specific and exploiting their combined high-throughput and high-resolution capabilities. Overall, the combination of MALDI-MS and endo-fucoidanase assays offers high-throughput evaluation of fucoidan samples and also enables extraction of defined oligosaccharides of known structure from unrefined seaweed biomass., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Objective: Iodine fortification (IF) induces an initial increase followed by a decrease in the incidence of hyperthyroidism in the general population. Within the population of hyperthyroid patients, the sex-, age- and subtype distribution changes after IF. The risk of atrial fibrillation (AF) in hyperthyroid patients may be influenced by these factors. Therefore, we aimed to examine how the association between incident hyperthyroidism and AF was affected by IF increasing the population iodine intake from moderate-mild iodine deficiency to low adequacy. DESIGN, PATIENTS AND MEASUREMENTS: Incident hyperthyroid patients were included at the date of first inpatient or outpatient diagnosis, and AF diagnoses within 3 months before to 6 months after the index date were identified in Danish nationwide registers, 1997-2018. The relative risk (RR) of AF each calendar year (reference: 1997; IF introduced: 2000) was analyzed in Poisson regression models adjusted for age, sex, educational level, geographic region, and comorbidities., Results: Overall, in 62,201 patients with incident hyperthyroidism 7.9% were diagnosed with AF. There was a minor nonsignificantly increased risk of AF during the first years after IF followed by a gradual decrease to RR 0.76 (0.62-0.94) in 2017. There were no statistically significant differences in the development in the risk of AF by sex, age group, or geographic region., Conclusions: Results indicate that IF may reduce the risk of concomitant AF in hyperthyroid patients. If these results are confirmed, IF may not only reduce the population incidence of hyperthyroidism but also reduce the burden of morbidity in the remaining hyperthyroid patients., (© 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Foot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzootic areas, underscoring the need to develop new fast-acting therapies for FMD control during outbreaks. Interferons (IFNs) are among the immune system's first line of defense against viral infections. Bovine type III IFN delivered by a replication defective adenovirus (Ad) vector has effectively blocked FMD in cattle. However, the limited duration of protection-usually only 1-3 days post-treatment (dpt)-diminishes its utility as a field therapeutic. Here, we test whether polyethylene glycosylation (PEGylation) of recombinant bovine IFNλ3 (PEGboIFNλ3) can extend the duration of IFN-induced prevention of FMDV infection in both vaccinated and unvaccinated cattle. We treated groups of heifers with PEGboIFNλ3 alone or in combination with an adenovirus-based FMD O1Manisa vaccine (Adt-O1M) at either 3 or 5 days prior to challenge with homologous wild type FMDV. We found that pre-treatment with PEGboIFNλ3 was highly effective at preventing clinical FMD when administered at either time point, with or without co-administration of Adt-O1M vaccine. PEGboIFNλ3 protein was detectable systemically for >10 days and antiviral activity for 4 days following administration. Furthermore, in combination with Adt-O1M vaccine, we observed a strong induction of FMDV-specific IFNγ+ T cell response, demonstrating its adjuvanticity when co-administered with a vaccine. Our results demonstrate the promise of this modified IFN as a pre-exposure prophylactic therapy for use in emergency outbreak scenarios., Competing Interests: PC was employed by VetBio Partners, LLC., and LS, JN, and NK were employed by Ambrx BioPharma, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor DG declared a shared affiliation with the authors SaA, CS, MR-C, AM, SoA, PA, GM, TS, and FD-S at the time of review., (Copyright © 2024 Attreed, Silva, Rodriguez-Calzada, Mogulothu, Abbott, Azzinaro, Canning, Skidmore, Nelson, Knudsen, Medina, de los Santos and Díaz-San Segundo.)

ARX788 is an anti-HER2 antibody drug conjugate (ADC) developed using Ambrx proprietary Engineered Precision Biologics technology. The manufacturing process of ARX788 has been optimized during the course of early to late-phase clinical development. A comprehensive evaluation of side-by-side comparability between pre- and post-change process for ARX788 drug substance and drug product from a quality perspective was conducted based on ICH Q5E guidelines consisting of batch release assays, physicochemical and biophysical characterization, biological characterization, and forced degradation studies. All results have substantiated a high degree of similarity between the pre- and post-change ARX788 drug substance batches and drug product lots, demonstrating that the process manufacturing changes did not impact product quality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: To evaluate the impact of early vs late palliative care on (1) length of stay (LOS) in the context of expected LOS measures and (2) total cost of care to the hospital for each patient. Methods: A prospective cohort study was performed at a single large academic medical center on patients who received an inpatient palliative care consultation. The two cohorts were early palliative care (within 3 days of admission) and late palliative care (after 3 days of admission). Comparisons were made between patients' actual LOS, expected LOS, and total hospital costs between both cohorts. Results: Compared to the late palliative care cohort (N = 126), patients who received early palliative care (N = 68) had a significantly shorter LOS ( P < .001) and also performed better compared to CMS-Expected LOS standards (Observed/Expected 3.1 vs 1.5 respectively; P < .001). Early palliative care patients also saw an average decline of $1431 in total costs 1-day pre/post consult as opposed to a more modest $403 decline in the later palliative care cohort ( P < .001). Similarly, patients who received early palliative care had a $5839 decline in aggregated total 3-day costs, as opposed to a $1478 decline in those who received late palliative care ( P < .001). Conclusions: In the competitive and rapidly evolving healthcare system, the opportunity to suppress costs and lower patient LOS has increasing importance. Our study strongly supports the implementation of earlier palliative care intervention to assist hospitals in approaching LOS targets and reducing patient costs.

Fucoidans are fucose rich sulfated polysaccharides that are found in the cell wall of brown seaweeds and have been shown to have several beneficial bioactivities. In the present study, we report a new enzymatic extraction technique for the production of pure and intact fucoidans from the two brown seaweeds Saccharina latissima and Alaria esculenta. This new extraction protocol uses the commercial cellulase blend Cellic® CTec2 in combination with endo- and exo-acting thermophilic alginate lyases. The fucoidans obtained by this extraction technique are compared to traditionally extracted fucoidans in terms of chemical compositions and molecular weights and are shown to contain significantly higher amounts of fucose and sulfate, the main components of fucoidans, while cellulose, laminarin, and alginate contamination is low. Thus, by using this combination of enzymes, the extracted fucoidans do not undergo depolymerization during extraction and additional purification steps are not needed. The high purity fucoidans isolated by this new enzymatic extraction technique can be used to provide insight into the different fucoidan structures and biological activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Self-control plays an essential role in children's emotional and behavioral adjustment. A central behavioral indicator of self-control is the ability to delay gratification. Few studies have focused on understanding the heterogeneity of self-control behaviors that underlie children's ability to delay gratification. Therefore, we examined the role of spontaneous self-control behaviors (fidgeting, vocalizations, and anticipation/attentional focus toward a reward) in relation to 5-year old children's delay ability using Mischel's delay task (N = 144; M age  = 5.4 years, SD = 0.29). Latent mixture modeling was used to derive three distinct classes of self-control behaviors observed during the delay task: (1) Passive (low fidgeting, low vocalizations, but moderate anticipation), (2) Active (moderate fidgeting, moderate vocalizations, but high anticipation), and (3) Disruptive (high fidgeting, high vocalizations, and high anticipation). Children in the Passive class were more likely to delay the full task time compared with children in the Active class (odds ratio = 1.50, 95 % confidence interval = 1.28-1.81). There were no other differences in delay ability by self-control class. Children whose level of fidgeting and vocalizations matched their level of anticipation (i.e., Passive and Disruptive regulators) were able to delay more successfully than children who were mostly driven by anticipation (Active regulators). Some variation in children's delay ability and use of self-control strategies was explained by sociodemographic differences, specifically maternal age. Findings suggest probing processes underlying children's self-control to identify potential targets for intervention., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Children continually encounter situations where they must regulate impulsive responses to achieve a goal, requiring both self-control (SC) and delay of gratification. We examined concurrent behavioral SC strategies (fidgeting, vocalizations, anticipation) and physiological regulation (heart rate [HR], respiratory sinus arrhythmia [RSA]) in 126 children (M (SD) = 5.4 (0.29) years) during a standard delay of gratification task. Latent variable models derived latent SC classes and examined the moderating role of HR/RSA on SC and delay ability. Three classes of SC were identified: passive: low fidgeting and vocalizations, moderate anticipation; active: moderate fidgeting, low vocalizations, and high anticipation; and disruptive: moderate fidgeting, high vocalizations, and high anticipation. Children in the active class had the lowest odds of delaying full task time, compared to children in the passive (OR = 0.67, z = -5.25, p < .001) and disruptive classes (OR = 0.76, z = -2.03, p = .04). RSA changes during the task moderated the relationship between SC class and delay ability for children in the active class (aOR = 0.92, z = -3.1, p < .01). Within the group who struggled to delay gratification (active class), a subset exhibiting appropriate autonomic regulation was able to delay. The findings suggest probing congruency of observed behavioral and unobserved physiological regulation., (© 2022 The Authors. Developmental Psychobiology published by Wiley Periodicals LLC.)