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We present preliminary results from follow-up observations of a carefully selected sample of subgiant stars from RAVE and Geneva-Copenhagen surveys. We find evidence of rapid saturation of the heating mechanism in the disk, with an abrupt increase of the velocity dispersion for stars older than 9 Gyr.

Miguel Angel Gonzalez-Torres,1,2 Miguel Angel Salazar,3 Manuel Imaz,4 Lucía Inchausti,1,2 Berta Ibañez,5 Aranzazu Fernandez-Rivas,1,2 Javier Pastor,3 Bosco Anguiano,3 Pedro Muñoz,3 Eduardo Ruiz,1,2 Rodrigo Oraa,3 Sonia Bustamante,1,2 Sofia Alvarez de Eulate,2 Ramón Cisterna4,61Department of Neuroscience, University of the Basque Country, 2Psychiatry Service, Basurto University Hospital, Bilbao, 3Mental Health Network of Biscay, Basque Health Service, Biscay, 4Microbiology Service, Basurto University Hospital, Bilbao, 5Navarra Biomed-Miguel Servet Foundation, Red de Investigación en Servicios Sanitarios y Enfermedades Crónicas (REDISSEC), Pamplona, 6Department of Microbiology, University of the Basque Country, Bilbao, SpainBackground: The aims of this study were to evaluate the prevalence of HIV and its associated demographic and clinical factors among psychiatric inpatients of a general hospital.Methods: This was a single-center, observational, cross-sectional study that included patients consecutively admitted to our unit aged 16 years or older and with no relevant cognitive problems. The patients were evaluated using a semistructured interview and an appropriate test for HIV infection.Results: Of the 637 patients who were screened, 546 (86%) who consented to participate were included in the analyses. Twenty-five (4.6%, 95% confidence interval [CI] 3.0–6.8) patients were HIV-positive. The prevalence was higher among patients with substance misuse (17.4%, 95% CI 9.7–28.8). All except one of the 25 patients knew of their seropositive condition prior to participation in the study. Only 14 (56%) of the 25 seropositive patients had previously received pharmacological treatment for their infection. According to the multiple logistic regression analysis, the likelihood of HIV infection was lower in patients with higher levels of education and higher among patients who were single, had history of intravenous drug use, and had an HIV-positive partner, particularly if they did not use condoms. Among the patients with HIV infection, 18 (72%) had a history of suicide attempts compared with 181 (34.7%) of the patients without HIV infection (relative risk 2.1, 95% CI 1.6–2.7; P

Using data from the GALAH pilot survey, we determine properties of the Galactic thin and thick discs near the solar neighbourhood. The data cover a small range of Galactocentric radius (7.9 ≤ RGC ≤ 9.5 kpc), but extend up to 4 kpc in height from the Galactic plane, and several kpc in the direction of Galactic anti-rotation (at longitude 260° ≤ ℓ ≤ 280°). This allows us to reliably measure the vertical density and abundance profiles of the chemically and kinematically defined 'thick' and 'thin' discs of the Galaxy. The thin disc (low-α population) exhibits a steep negative vertical metallicity gradient, at d[M/H]/dz = -0.18 ± 0.01 dex kpc-1, which is broadly consistent with previous studies. In contrast, its vertical α-abundance profile is almost flat, with a gradient of d[α/M]/dz = 0.008 ± 0.002 dex kpc-1. The steep vertical metallicity gradient of the low-α population is in agreement with models where radial migration has a major role in the evolution of the thin disc. The thick disc (high-α population) has a weaker vertical metallicity gradient d[M/H]/dz = -0.058 ± 0.003 dex kpc-1. The α- abundance of the thick disc is nearly constant with height, d[α/M]/dz = 0.007 ± 0.002 dex kpc-1. The negative gradient in metallicity and the small gradient in [α/M] indicate that the high-α population experienced a settling phase, but also formed prior to the onset of major Type Ia supernova enrichment. We explore the implications of the distinct α-enrichments and narrow [α/M] range of the sub-populations in the context of thick disc formation. [ABSTRACT FROM AUTHOR]

The Galactic Archaeology with HERMES (GALAH) survey is amassive observational project to trace the MilkyWay's history of star formation, chemical enrichment, stellar migration and minor mergers. Using high-resolution (R ≃ 28 000) spectra, taken with the High Efficiency and Resolution Multi-Element Spectrograph (HERMES) instrument at the Anglo-Australian Telescope, GALAH will determine stellar parameters and abundances of up to 29 elements for up to one million stars. Selecting targets from a colour-unbiased catalogue built from 2MASS, APASS and UCAC4 data, we expect to observe dwarfs at 0.3-3 kpc and giants at 1-10 kpc. This enables a thorough local chemical inventory of the Galactic thin and thick discs, and also captures smaller samples of the bulge and halo. In this paper, we present the plan, process and progress as of early 2016 for GALAH survey observations. In our first two years of survey observing we have accumulated the largest high-quality spectroscopic data set at this resolution, over 200 000 stars. We also present the first public GALAH data catalogue: stellar parameters (Teff, log(g), [Fe/H], [α/Fe]), radial velocity, distance modulus and reddening for 10 680 observations of 9860 Tycho-2 stars, 7894 of which are included in the first Gaia data release. [ABSTRACT FROM AUTHOR]

The age-metallicity relation (AMR) is a fundamental observational constraint for understanding how the Galactic disc formed and evolved chemically in time. However, there is not yet an agreement on the observational properties of the AMR for the solar neighbourhood, primarily due to the difficulty in obtaining accurate stellar ages for individual field stars. We have started an observational campaign for providing the much needed observational input by using wide white-dwarf-main-sequence (WDMS) binaries. White dwarfs are 'natural' clocks and can be used to derive accurate ages. Metallicities can be obtained from the main-sequence companions. Since the progenitors of white dwarfs and the main-sequence stars were born at the same time, WDMS binaries provide a unique opportunity to observationally constrain in a robust way the properties of the AMR. In this work we present the AMR derived from analysing a pilot sample of 23 WDMS binaries and provide clear observational evidence for the lack of correlation between age and metallicity at young and intermediate ages (0-7 Gyr). [ABSTRACT FROM AUTHOR]

We report the identification of extended tidal debris potentially associated with the globular cluster NGC 3201, using the RAdial Velocity Experiment (RAVE) catalogue. We find the debris stars are located at a distance range of 1-7 kpc based on the forthcoming RAVE distance estimates. The derived space velocities and integrals of motion show interesting connections to NGC 3201, modulo uncertainties in the proper motions. Three stars, which are among the four most likely candidates for NGC 3201 tidal debris, are separated by 80° on the sky yet are well matched by the 12 Gyr, [Fe/H] = -1.5 isochrone appropriate for the cluster. This is the first time tidal debris around this cluster has been reported over such a large spatial extent, with implications for the cluster's origin and dynamical evolution. [ABSTRACT FROM AUTHOR]

The Galactic Archaeology with HERMES (GALAH) survey is a large high-resolution spectro-scopic survey using the newly commissioned High Efficiency and Resolution Multi-Element Spectrograph (HERMES) on the Anglo-Australian Telescope. The HERMES spectrograph provides high-resolution (R ~ 28 000) spectra in four passbands for 392 stars simultaneously over a 2 deg field of view. The goal of the survey is to unravel the formation and evolution-ary history of the Milky Way, using fossil remnants of ancient star formation events which have been disrupted and are now dispersed throughout the Galaxy. Chemical tagging seeks to identify such dispersed remnants solely from their common and unique chemical signatures; these groups are unidentifiable from their spatial, photometric or kinematic properties. To carry out chemical tagging, the GALAH survey will acquire spectra for a million stars down to V ~ 14. The HERMES spectra of FGK stars contain absorption lines from 29 elements including light proton-capture elements, a-elements, odd-Z elements, iron-peak elements and n-capture elements from the light and heavy s-process and the r-process. This paper describes the motivation and planned execution of the GALAH survey, and presents some results on the first-light performance of HERMES. [ABSTRACT FROM AUTHOR]

The age-metallicity relation (AMR) is a fundamental observational constraint for understanding how the Galactic disc formed and evolved chemically in time. However, there is not yet an agreement on the observational properties of the AMR, primarily due to the difficulty in obtaining accurate ages for individual field stars. We have started an observational campaign for providing new observational input by using wide white dwarf-main sequence (WDMS) binaries. WDs are natural clocks and can be used to derive accurate ages. Metallicities can be obtained from the MS companions. Since the progenitors of WDs and the MS stars were born at the same time, WDMS provide a unique opportunity to constrain in a robust way the properties of the AMR. We present the AMR derived from analysing a pilot sample of 23 WDMS and provide clear evidence for the lack of correlation between age and metallicity at young and intermediate ages. [ABSTRACT FROM AUTHOR]

HERMES is a new high-resolution multi-object spectrograph on the Anglo Australian Telescope. The primary science driver for HERMES is the GALAH survey, GALactic Archaeology with HERMES. We are planning a spectroscopic survey of about a million stars, aimed at using chemical tagging techniques to reconstruct the star-forming aggregates that built up the disk, the bulge and halo of the Galaxy. This project will benefit greatly from the stellar distances and transverse motions from the Gaia mission. [ABSTRACT FROM PUBLISHER]

We use the Sloan Digital Sky Survey Data Release 12, which is the largest available white dwarf catalogue to date, to study the evolution of the kinematical properties of the population of white dwarfs of the Galactic disk. We derive masses, ages, photometric distances and radial velocities for all white dwarfs with hydrogen-rich atmospheres. For those stars for which proper motions from the USNO-B1 catalogue are available, the three-dimensional components of the velocity are obtained. This subset of the original sample comprises 20,247 stars, making it the largest sample of white dwarfs with measured three-dimensional velocities. The volume probed by our sample is large, allowing us to obtain relevant kinematical information. In particular, our sample extends from a Galactocentric radial distance R G = 7.8 to 9.3 kpc, and vertical distances from the Galactic plane ranging from Z = +0.5 to –0.5 kpc. [ABSTRACT FROM AUTHOR]

Using the chemical groups identified by Mitschang et al. (2014) on a local sample of around 700 stars by Bensby et al. (2014) and the new derived ages, I report some properties on the orbital parameters (Rmin, Rmax, e, Zmax, angular momentum) and their temporal evolution. We find that the < Rmax > is nearly independent of age with values from 9 to 11 kpc, while < Rmin > shows a clear trend with age. The < e > and < Zmax > for the chemical groups clearly increase with age. These preliminary results show a significant variety of orbits for the members inside a chemical group, that may support the idea of the identification of co-eval groups (born same time, not necessarily same place) rather than co-natal (Anguiano et al. in prep.). [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a multifactorial condition that involves oxidative alterations and dysbiosis of the microbiota associated with an imbalance in glucose metabolism. Therefore, the need to develop integrative therapies that are both effective and have fewer side effects has become evident in recent years. Molecular iodine (I 2 ) has antioxidant effects in preclinical hyperglycemic models. The present work analyzes the preventive and therapeutic effects of oral I 2 supplementation in a DM model induced by low doses of streptozotocin (STZ). Male CD1 mice (12 weeks old) were divided into the following groups: control, STZ (20 mg/kg/day, i.p., for five days), I 2 (0.2 mg/Kg in drinking water), preventive (STZ + I 2 ), and therapeutic (I 2 supplementation from day 35 to day 90; STZ + I 2(Ther) ). The supplementation with I 2 prevented and normalized hyperglycemia, hypercholesterolemia, and hypertriglyceridemia associated with STZ, preserving pancreatic, liver, muscle, and adipose tissue morphology and normalizing inflammatory gene induction (TLR2, TLR4, NFkβ, TNFα) in several tissues. Furthermore, compared to the STZ group, the presence of I 2 favored a more significant abundance of beneficial bacteria that support the integrity of the intestinal epithelial barrier and higher α-diversity. In conclusion, the I 2 supplement has preventive and therapeutic effects, reducing oxidative damage and reestablishing microbiota diversity following STZ exposure., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2024. Published by Elsevier Inc.)

Metronomic chemotherapy with cyclophosphamide (Cpp) has shown promising results in cancer protocols. These lower and prolonged doses have antiangiogenic, pro-cytotoxic, and moderate secondary effects. Molecular iodine (I 2 ) reduces the viability of cancer cells and, with chemotherapeutic agents, activates the antitumoral immune response and diminishes side effects. The present work evaluates the adjuvant of oral I 2 with Cpp using a murine model of mammary cancer. Female Sprague Dawley rats with 7,12-dimethylbenzantracene-induced tumors received Cpp intraperitoneal (50 and 70 mg/kg two times/week, iCpp50 and iCpp70) and oral (0.03%; 50 mg/Kg; oCpp50) doses. I 2 (0.05%, 50 mg/100 mL) and oCpp50 were offered in drinking water for three weeks. iCpp70 was the most efficient antitumoral dose but generated severe body weight loss and hemorrhagic cystitis (HC). I 2 prevented body weight loss, exhibited adjuvant actions with Cpp, decreasing tumor growth, and canceled HC mechanisms, including decreases in vascular endothelial growth factor (VEGF) and Survivin expression. oCpp50 + I 2 diminished angiogenic signals (CD34, vessel-length, and VEGF content) and proinflammatory cytokines (interleukin-10 and tumor necrosis factor-alpha) and increased cytotoxic (lymphocytic infiltration, CD8 + cells, Tbet, and interferon-gamma) and antioxidant markers (nuclear erythroid factor-2 and glutathione peroxidase). I 2 enhances the effectiveness of oCpp, making it a compelling candidate for a clinical protocol.

Exome and genome sequencing are clinically available, with many laboratories offering expedited testing (e.g., "rapid" and "ultra-rapid"). With the increase in uptake of expedited testing, there is a need for the development of inpatient protocols for best practices based on real-life data. A retrospective 2-year review (October 2019-November 2021) of the utilization of rapid exome and genome sequencing for inpatient cases at a tertiary care center using a utilization management tracking database with subsequent chart review was performed. Thirty-three expedited "rapid/priority" exome/genome tests were performed clinically. The average total turnaround time (TAT) was 17.88 days (5-43 days) with an average TAT of 13.97 days (3-41 days) for the performing laboratory. There were 5 positive diagnostic results (15.2%), 3 likely positive diagnostic results (9%), 2 noncontributory results (6%), and 26 nondiagnostic results (69.7%). Real-life data suggest that there is an approximately 3.91-day lag in getting samples to the performing laboratory. Although laboratories may advertise their expected TAT, a number of factors can potentially impact the actual time from test order placement to communication of the results for clinical use. Understanding the points of delay will enable the development of internal protocols and policies to improve time to diagnosis., (© 2023 Wiley Periodicals LLC.)

Pancreatic alterations such as inflammation and insulin resistance accompany hypothyroidism. Molecular iodine (I 2 ) exerts antioxidant and differentiation actions in several tissues, and the pancreas is an iodine-uptake tissue. We analyzed the effect of two oral I 2 doses on pancreatic disorders in a model of hypothyroidism for 30 days. Adult female rabbits were divided into the following groups: control, moderate oral dose of I 2 (0.2 mg/kg, M-I 2 ), high oral dose of I 2 (2.0 mg/kg, H-I 2 ), oral dose of methimazole (MMI; 10 mg/kg), MMI + M-I 2, , and MMI + H-I 2 . Moderate or high I 2 supplementation did not modify circulating metabolites or pancreatic morphology. The MMI group showed reductions of circulating thyroxine (T4) and triiodothyronine (T3), moderate glucose increments, and significant increases in cholesterol and low-density lipoproteins. Acinar fibrosis, high insulin content, lipoperoxidation, and overexpression of GLUT4 were observed in the pancreas of this group. M-I 2 supplementation normalized the T4 and cholesterol, but T3 remained low. Pancreatic alterations were prevented, and nuclear factor erythroid-2-related factor-2 (Nrf2), antioxidant enzymes, and peroxisome proliferator-activated receptor gamma (PPARG) maintained their basal values. In MMI + H-I 2, hypothyroidism was avoided, but pancreatic alterations and low PPARG expression remained. In conclusion, M-I 2 supplementation reestablishes thyronine synthesis and diminishes pancreatic alterations, possibly related to Nrf2 and PPARG activation.

Molecular iodine (I 2 ) prevents oxidative stress and prostate hyperplasia induced by hyperandrogenism and reduces cell viability in prostate cancer cell lines. Here, we aimed to evaluate the protective effect of I 2 and testosterone (T) on hyperestrogenism-induced prostate inflammation. Additionally, the effects of I 2 and/or tumor necrosis factor (TNF) on cell viability and interleukin 6 (IL6) secretion were evaluated in a prostate cancer cell line (DU145). We also investigated whether the effects of I 2 on viability are peroxisome proliferator-activated receptor gamma (PPARG)-dependent. Castrated (Cx) rats received pellets of either 17β estradiol (E 2 ) or E 2 and T and were treated with I 2 (0.05%) in the drinking water for four weeks. The experimental groups were sham, Cx, Cx + E 2 , Cx + E 2 +I 2 , Cx + E 2 +T, and Cx + E 2 +T + I 2 . As expected, inflammation was triggered in the Cx + E 2 group (high inflammation score; increase in TNF and transcriptional activity of RELA [nuclear factor-kappa B p65 subunit]), and this effect was diminished in the Cx + E 2 +T group (medium inflammation score and decrease in TNF). The lowest inflammation score (decrease of TNF and RELA and increase of PPARG) was obtained in the Cx + E 2 +T + I 2 group. In DU145 cells, I 2 (400 μM) and TNF (10 ng/ml) additively reduced cell viability, and I 2 reduced the production of TNF-stimulated IL6. The PPARG antagonist (GW9662) did not inhibit the effects of I 2 on the loss of cell viability. In summary, our data suggest that I 2 and T exert a synergistic anti-inflammatory action on the normal prostate, and the interrelationship between I 2 and TNF leads to anti-proliferative effects in DU145 cells. PPARG does not seem to participate in the I 2 -induced cell viability loss in the prostate., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The diagnostic yield of exome sequencing (ES) has primarily been evaluated in individuals of European ancestry, with less focus on underrepresented minority (URM) and underserved (US) patients. We evaluated the diagnostic yield of ES in a cohort of predominantly US and URM pediatric and prenatal patients suspected to have a genetic disorder. Eligible pediatric patients had multiple congenital anomalies and/or neurocognitive disabilities and prenatal patients had one or more structural anomalies, disorders of fetal growth, or fetal effusions. URM and US patients were prioritized for enrollment and underwent ES at a single academic center. We identified definitive positive or probable positive results in 201/845 (23.8%) patients, with a significantly higher diagnostic rate in pediatric (26.7%) compared to prenatal patients (19.0%) (P = 0.01). For both pediatric and prenatal patients, the diagnostic yield and frequency of inconclusive findings did not differ significantly between URM and non-URM patients or between patients with US status and those without US status. Our results demonstrate a similar diagnostic yield of ES between prenatal and pediatric URM/US patients and non-URM/US patients for positive and inconclusive results. These data support the use of ES to identify clinically relevant variants in patients from diverse populations., (© 2023. The Author(s).)

Purpose: Despite recent attention to increasing diversity in clinical genomics research, researchers still struggle to recruit participants from varied sociodemographic backgrounds. We examined the experiences of parents from diverse backgrounds with enrolling their children in clinical genomics research on rare diseases. We explored the barriers and facilitators parents encountered and possible impacts of sociodemographic factors on their access to research. Methods: We utilized semi-structured interviews with parents of children participating in the Undiagnosed Diseases Network. Interview data were analyzed using comparative content analysis. Results: We interviewed 13 Hispanic, 11 non-Hispanic White, four Asian, and two biracial parents. Participants discussed different pathways to clinical genomics research for rare disease as well as how sociodemographic factors shaped families' access. Themes focused on variation in: 1) reliance on providers to access research; 2) cultural norms around health communication; 3) the role of social capital in streamlining access; and 4) the importance of language-concordant research engagement. Conclusion: Our findings suggest that variables beyond race/ethnicity may influence access in clinical genomics research. Future efforts to diversify research participation should consider utilizing varied recruitment strategies to reach participants with diverse sociodemographic characteristics., Competing Interests: The 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., (Copyright © 2022 Young, Halley, Anguiano, Fernandez, Bernstein, Wheeler and Tabor.)

Even in the absence of significant valvular disease, patients with Marfan syndrome (MFS) have evidence of impaired left ventricular (LV) performance, suggestive of a primary cardiomyopathy. However, the true prevalence and long-term outcomes of this disease process remain largely unknown. We performed a retrospective analysis of all adult patients with confirmed MFS followed at Stanford Health Care. Those with significant valvular regurgitation, coronary artery disease, or previous cardiac surgery were excluded. LV systolic dysfunction was defined as a LV ejection fraction (LVEF) <55% on transthoracic echocardiography. A total of 753 patients with confirmed MFS were followed up over a median duration of 8 years (interquartile range 4 to 13). Of those, 241 patients (53% women, 71% White) met inclusion criteria and comprised the study cohort. LV systolic dysfunction was present in 30 patients (12%), with a median age of onset of 25 years (interquartile range 19 to 37), median EF of 52% (interquartile range 48 to 54), and evidence of clinical heart failure (New York Heart Association functional class ≥II) in 10% of patients. LV systolic dysfunction was more common in patients with larger aortic root diameters (≥4.0 cm: Odds ratio = 4.5, 95% confidence interval = 1.2 to 17.1) but was not associated with other cardiovascular manifestations of MFS or traditional atherosclerotic risk factors. In conclusion, apart from significant valvular pathology, LV systolic dysfunction was prevalent in MFS from a young age, suggestive of a primary cardiomyopathy. LV dysfunction was typically mild and subclinical and occurred more commonly in patients with more pronounced aortopathies., Competing Interests: Disclosures The authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Patients undergoing clinical exome sequencing (ES) are routinely offered the option to receive secondary findings (SF). However, little is known about the views of individuals from underrepresented minority pediatric or prenatal populations regarding SF., Methods: We explored the preferences for receiving hypothetical categories of SF (H-SF) and reasons for accepting or declining actual SF through surveying (n = 149) and/or interviewing (n = 47) 190 families undergoing pediatric or prenatal ES., Results: Underrepresented minorities made up 75% of the probands. In total, 150 families (79%) accepted SF as part of their child/fetus's ES. Most families (63%) wanted all categories of H-SF. Those who declined SF as part of ES were less likely to want H-SF across all categories. Interview findings indicate that some families did not recall their SF decision. Preparing for the future was a major motivator for accepting SF, and concerns about privacy, discrimination, and psychological effect drove decliners., Conclusion: A notable subset of families (37%) did not want at least 1 category of H-SF, suggesting more hesitancy about receiving all available results than previously reported. The lack of recollection of SF decisions suggests a need for alternative communication approaches. Results highlight the importance of the inclusion of diverse populations in genomic research., Competing Interests: Conflict of Interest The first author, S.R., completed most of the work on this manuscript while being an employee of the University of California San Francisco and has since moved to a role as a full-time employee and shareholder of AllStripes Research. She has no conflicts of interest to disclose in either role. The other authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Thyroid hormones (THs) are involved in the development and function of the male reproductive system, but their effects on the prostate have been poorly studied. This work reviews studies related to the interrelationship between the thyroid and the prostate. The information presented here is based upon bibliographic searches in PubMed using the following search terms: prostate combined with thyroid hormone or triiodothyronine, thyroxine, hypothyroidism, hyperthyroidism, or deiodinase. We identified and searched 49 articles directly related to the issue, and discarded studies related to endocrine disruptors. The number of publications has grown in the last 20 years, considering that one of the first studies was published in 1965. This review provides information based on in vitro studies, murine models, and clinical protocols in patients with thyroid disorders. Studies indicate that THs regulate different aspects of growth, metabolism, and prostate pathology, whose global effect depends on total and/or free concentrations of THs in serum, local bioavailability, and the endocrine androgen/thyronine context.

Pancreatitis has been implicated in the development and progression of type 2 diabetes and cancer. The pancreas uptakes molecular iodine (I 2 ), which has anti-inflammatory and antioxidant effects. The present work analyzes whether oral I 2 supplementation prevents the pancreatic alterations promoted by low doses of streptozotocin (STZ). CD1 mice (12 weeks old) were divided into the following groups: control; STZ (20 mg/kg/day, i.p. for five days); I 2 (0.2 mg/Kg/day in drinking water for 15 days); and combined (STZ + I 2 ). Inflammation (Masson's trichrome and periodic acid-Schiff stain), hyperglycemia, decreased β-cells and increased α-cells in pancreas were observed in male and female animals with STZ. These animals also showed pancreatic increases in immune cells and inflammation markers as tumor necrosis factor-alpha, transforming growth factor-beta and inducible nitric oxide synthase with a higher amount of activated pancreatic stellate cells (PSCs). The I 2 supplement prevented the harmful effect of STZ, maintaining normal pancreatic morphometry and functions. The elevation of the nuclear factor erythroid-2 (Nrf2) and peroxisome proliferator-activated receptor type gamma (PPARγ) contents was associated with the preservation of normal glycemia and lipoperoxidation. In conclusion, a moderated supplement of I 2 prevents the deleterious effects of STZ in the pancreas, possibly through antioxidant and antifibrotic mechanisms including Nrf2 and PPARγ activation.

Individual differences in coping with stress may determine either a vulnerable or resilient phenotype. Therefore, it is important to better understand the biology underlying the behavioral phenotype. We assessed whether individual behavioral phenotype to acute stress is related with the hippocampal expression of glucocorticoid receptor (GR), Nurr1, interleukin-1 beta (IL-1β) or brain-derived neurotrophic factor (BDNF). Wistar male rats were exposed to forced swimming for 15 min and sacrificed at different times. Behavioral response was analyzed, and it was compared with the gene and protein expression of GR, Nurr1, IL-1β and BDNF in the hippocampus for each time point. Behavioral phenotyping showed a group with high immobility (vulnerable) while another had low immobility (resilient). No significant differences were found in the Nurr1 , IL-1β and BDNF mRNA levels between resilient and vulnerable rats at different recovery times except for Nr3c1 (gene for GR). However, exposure to stress caused significantly higher levels of GR, Nurr1 and IL-1β proteins of vulnerable compared to resilient rats. This variability of behavioral phenotypes is associated with a differential molecular response to stress that involves GR, Nurr1, and IL-1β as mediators in coping with stress. This contributes to identifying biomarkers of susceptibility to stress.

Molecular iodine (I 2 ) induces apoptotic, antiangiogenic, and antiproliferative effects in breast cancer cells. Little is known about its effects on the tumor immune microenvironment. We studied the effect of oral (5 mg/day) I 2 supplementation alone (I 2 ) or together with conventional chemotherapy (Cht+I 2 ) on the immune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I 2 and Cht+I 2 samples showed significant increases in the expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I 2 groups. Real-time RT-PCR showed that I 2 tumors overexpress T-BET ( p = 0.019) and interferon-gamma (IFNγ; p = 0.020) and silence tumor growth factor-beta (TGFβ; p = 0.049), whereas in Cht+I 2 tumors, GATA3 is silenced ( p = 0.014). Preliminary methylation analysis shows that I 2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFβ in Cht+I 2 . In conclusion, our data showed that I 2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also participate.

Aim: To increase Spanish speakers' representation in genomics research, accessible study materials on genetic topics must be made available in Spanish. Materials & methods: The Clinical Sequencing Evidence-Generating Research consortium is evaluating genome sequencing for underserved populations. All sites needed Spanish translation of recruitment materials, surveys and return of results. Results: We describe our process for translating site-specific materials, as well as shared measures across sites, to inform future efforts to engage Spanish speakers in research. Conclusion: In translating and adapting study materials for roughly 1000 Spanish speakers across the USA, and harmonizing translated measures across diverse sites, we overcame numerous challenges. Translation should be performed by professionals. Studies must allocate sufficient time, effort and budget to translate and adapt participant materials.

Neuroblastoma (Nb), the most common extracranial tumor in children, exhibited remarkable phenotypic diversity and heterogeneous clinical behavior. Tumors with MYCN overexpression have a worse prognosis. MYCN promotes tumor progression by inducing cell proliferation, de-differentiation, and dysregulated mitochondrial metabolism. Cyclophosphamide (CFF) at minimum effective oral doses (metronomic therapy) exerts beneficial actions on chemoresistant cancers. Molecular iodine (I 2 ) in coadministration with all-trans retinoic acid synergizes apoptosis and cell differentiation in Nb cells. This work analyzes the impact of I 2 and CFF on the viability (culture) and tumor progression (xenografts) of Nb chemoresistant SK-N-BE(2) cells. Results showed that both molecules induce dose-response antiproliferative effects, and I 2 increases the sensibility of Nb cells to CFF, triggering PPARγ expression and acting as a mitocan in mitochondrial metabolism. In vivo oral I 2 /metronomic CFF treatments showed significant inhibition in xenograft growth, decreasing proliferation (Survivin) and activating apoptosis signaling (P53, Bax/Bcl-2). In addition, I 2 decreased the expression of master markers of malignancy (MYCN, TrkB), vasculature remodeling, and increased differentiation signaling (PPARγ and TrkA). Furthermore, I 2 supplementation prevented loss of body weight and hemorrhagic cystitis secondary to CFF in nude mice. These results allow us to propose the I 2 supplement in metronomic CFF treatments to increase the effectiveness of chemotherapy and reduce side effects.

Most investigations of iodine metabolism in humans and animals have focused on its role in thyroid function. However, considerable evidence indicates that iodine could also be implicated in the physiopathology of other organs. We review the literature that shows that molecular iodine (I 2 ) exerts multiple and complex actions on the organs that capture it, not including its effects as part of thyroid hormones. This chemical form of iodine is internalized by a facilitated diffusion system that is evolutionary conserved, and its effects appear to be mediated by a variety of mechanisms and pathways. As an oxidized component, it directly neutralizes free radicals, induces the expression of type II antioxidant enzymes, or inactivates proinflammatory pathways. In neoplastic cells, I 2 generates iodolipids with nuclear actions that include the activation of apoptotic pathways and the inhibition of markers related to stem cell maintenance, chemoresistance, and survival. Recently, I2 has been postulated as an immune modulator that depending on the cellular context, can function as an inhibitor or activator of immune responses. We propose that the intake of molecular iodine is increased in adults to at least 1 mg/day in specific pathologies to obtain the potential extrathyroid benefits described in this review.

Neuroblastoma (NB) is the most common solid childhood tumor, and all-trans retinoic acid (ATRA) is used as a treatment to decrease minimal residual disease. Molecular iodine (I2) induces differentiation and/or apoptosis in several neoplastic cells through activation of PPARγ nuclear receptors. Here, we analyzed whether the coadministration of I2 and ATRA increases the efficacy of NB treatment. ATRA-sensitive (SH-SY5Y), partially-sensitive (SK-N-BE(2)), and non-sensitive (SK-N-AS) NB cells were used to analyze the effect of I2 and ATRA in vitro and in xenografts (Foxn1 nu/nu mice), exploring actions on cellular viability, differentiation, and molecular responses. In the SH-SY5Y cells, 200 μM I2 caused a 100-fold (0.01 µM) reduction in the antiproliferative dose of ATRA and promoted neurite extension and neural marker expression (tyrosine hydroxylase (TH) and tyrosine kinase receptor alpha (Trk-A)). In SK-N-AS, the I2 supplement sensitized these cells to 0.1 μM ATRA, increasing the ATRA-receptor (RARα) and PPARγ expression, and decreasing the Survivin expression. The I2 supplement increased the mitochondrial membrane potential in SK-N-AS suggesting the participation of mitochondrial-mediated mechanisms involved in the sensibilization to ATRA. In vivo, oral I2 supplementation (0.025%) synergized the antitumor effect of ATRA (1.5 mg/kg BW) and prevented side effects (body weight loss and diarrhea episodes). The immunohistochemical analysis showed that I2 supplementation decreased the intratumoral vasculature (CD34). We suggest that the I2 + ATRA combination should be studied in preclinical and clinical trials to evaluate its potential adjuvant effect in addition to conventional treatments.

Thyroxine (T4) promotes cell proliferation and tumor growth in prostate cancer models, but it is unknown if the increase in the triiodothyronine (T3)/T4 ratio could attenuate prostate tumor development. We assessed T3 effects on thyroid response, histology, proliferation, and apoptosis in the prostate of wild-type (WT) and TRAMP (transgenic adenocarcinoma of the mouse prostate) mice. Physiological doses of T3 were administered in the drinking water (2.5, 5 and 15 µg/100 g body weight) for 6 weeks. None of the doses modified the body weight or serum levels of testosterone, but all of them reduced serum T4 levels by 50%, and the highest dose increased the T3/T4 ratio in TRAMP. In WT, the highest dose of T3 decreased cyclin D1 levels (immunohistochemistry) but did not modify prostate weight or alter the epithelial morphology. In TRAMP, this dose reduced tumor growth by antiproliferative mechanisms independent of apoptosis, but it did not modify the intraluminal or fibromuscular invasion of tumors. In vitro, in the LNCaP prostate cancer cell line, we found that both T3 and T4 increased the number of viable cells (Trypan blue assay), and only T4 response was fully blocked in the presence of an integrin-binding inhibitor peptide (RGD, arginine-glycine-aspartate). In summary, our data show that the prostate was highly sensitive to physiological T3 doses and suggest that in vivo, an increase in the T3/T4 ratio could be associated with the reduced weight of prostate tumors. Longitudinal studies are required to understand the role of thyroid hormones in prostate cancer progression.