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BACKGROUND: Iodinated contrast is commonly used for radiologic procedures, with one dose delivering several hundred-fold the daily requirements needed for normal thyroid hormone production. Risks of excess iodine include incident thyroid dysfunction, which is associated with adverse cardiac outcomes, yet there are no prospective studies investigating the changes in cardiac physiology following iodine contrast administration. This study was conducted to investigate the longitudinal relationships between the amount of iodinated contrast administration and changes in cardiac electrophysiology and structure. METHODS: A longitudinal cohort study was conducted with prospectively enrolled participants who received iodine contrast for elective computed tomography or coronary angiography. Serum thyroid function tests, electrocardiograms (EKG), and transthoracic echocardiograms (TTE) were obtained serially until 36 months. Trends of electrical and structural cardiac changes following iodine contrast administration were assessed using mixed effect models. RESULTS: The cohort was composed of 129 patients (median age, 70 [interquartile range: 63, 75] years; 98% male). Larger amounts of iodine exposure were associated with increases in QRS and QTc durations and decreased ejection fraction (EF), and these associations were still observed for follow-up EF after additionally adjusting for baseline values (the high-iodine contrast group vs the low-iodine contrast group, -4.23% [95%CI, -7.66% to -0.79%]). Dose-response analyses also showed lower EF with larger amounts of iodine received; these trends were not significant for the EKG parameters studied. CONCLUSIONS: Over a period of up to 36 months, a larger amount of administered iodine contrast was associated with lower EF among participants. Further investigation is needed to elucidate the long-term trends of electrical and structural cardiac function after iodine contrast administration.
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BACKGROUND: In the early 2020s, nearly half of New Zealand adults reported that cost of treatment had prevented them from accessing dental care, with higher rates among Maori, Pasifika and individuals living in the most deprived areas. Unaffordable dental care may be explained by a rise in dental service fees over time relative to personal income, as documented in New Zealand between 1978 and 1993. However, there have been no contemporary estimates in New Zealand of how the affordability of dental care has changed. The aims of this study were to analyse the change in dental treatment fees and the personal income of New Zealanders from 1978 to 2023 and to explore differences in affordability of dental care by ethnicity. METHODS: Average fees for dental treatments were sourced from surveys completed by practising New Zealand dentists. Earnings (from 1978) and personal income data (full population from 2000 and by ethnicity from 2008) were sourced from Statistics NZ and NZ Official Yearbooks. Inflation-adjusted changes in average fees, weekly personal earnings and income were calculated as a percentage change from 1978 levels for fees and earnings and from 2000 for personal income. RESULTS: For the five dental treatments with data available from 1978 to 2023, fees increased in the range of 75%-236%, while earnings increased by 46% over the same period. Fees for other treatments (with data available from 1981 to 2009) similarly increased and mostly surpassed changes in earnings. From 2008 to 2023 the overall increase in personal income (about 21% across all ethnic groups) kept pace with the rising cost of most treatments. However, due to persistent income inequalities, in 2023, Maori and Pasifika would need to spend a higher proportion of their weekly income (approximately 16% and 23% respectively) to receive the same dental treatments as NZ Europeans. CONCLUSIONS: Fees for dental treatments have risen markedly in recent decades, more sharply than the price of other goods and services.
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Kindler syndrome (KS) is a rare genodermatosis resulting from loss-of-function mutations in FERMT1, the gene that encodes Kindlin-1. KS patients have a high propensity to develop aggressive and metastatic cutaneous squamous cell carcinoma (cSCC). Here we show in non-KS-associated patients that elevation of FERMT1 expression is increased in actinic keratoses compared to normal skin, with a further increase in cSCC supporting a pro-tumorigenic role in this population. In contrast, we show that loss of Kindlin-1 leads to increased SCC tumor growth in vivo and in 3D spheroids, which was associated with the development of a hypoxic tumor environment and increased glycolysis. The metalloproteinase Mmp13 was upregulated in Kindlin-1-depleted tumors, and increased expression of MMP13 was responsible for driving increased invasion of the Kindlin-1-depleted SCC cells. These results provide evidence that Kindlin-1 loss in SCC can promote invasion through the upregulation of MMP13, and offer novel insights into how Kindlin-1 loss leads to the development of a hypoxic environment that is permissive for tumor growth.
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BACKGROUND: Technological burden and medical complexity are significant drivers of clinician burnout. Electronic health record(EHR)-based population health management tools can be used to identify high-risk patient populations and implement prophylactic health practices. Their impact on clinician burnout, however, is not well understood. Our objective was to assess the relationship between ratings of EHR-based population health management tools and clinician burnout. METHODS: We conducted cross-sectional analyses of 2018 national Veterans Health Administration(VA) primary care personnel survey, administered as an online survey to all VA primary care personnel (n = 4257, response rate = 17.7%), using bivariate and multivariate logistic regressions. Our analytical sample included providers (medical doctors, nurse practitioners, physicians' assistants) and nurses (registered nurses, licensed practical nurses). The outcomes included two items measuring high burnout. Primary predictors included importance ratings of 10 population health management tools (eg. VA risk prediction algorithm, recent hospitalizations and emergency department visits, etc.). RESULTS: High ratings of 9 tools were associated with lower odds of high burnout, independent of covariates including VA tenure, team role, gender, ethnicity, staffing, and training. For example, clinicians who rated the risk prediction algorithm as important were less likely to report high burnout levels than those who did not use or did not know about the tool (OR 0.73; CI 0.61-0.87), and they were less likely to report frequent burnout (once per week or more) (OR 0.71; CI 0.60-0.84). CONCLUSIONS: Burned-out clinicians may not consider the EHR-based tools important and may not be using them to perform care management. Tools that create additional technological burden may need adaptation to become more accessible, more intuitive, and less burdensome to use. Finding ways to improve the use of tools that streamline the work of population health management and/or result in less workload due to patients with poorly managed chronic conditions may alleviate burnout. More research is needed to understand the causal directional of the association between burnout and ratings of population health management tools.
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Agotamiento Profesional , Registros Electrónicos de Salud , Atención Dirigida al Paciente , Gestión de la Salud Poblacional , Atención Primaria de Salud , United States Department of Veterans Affairs , Humanos , Agotamiento Profesional/epidemiología , Estados Unidos/epidemiología , Estudios Transversales , United States Department of Veterans Affairs/organización & administración , Masculino , Femenino , Registros Electrónicos de Salud/estadística & datos numéricos , Persona de Mediana Edad , AdultoRESUMEN
CONTEXT: Iodinated contrast media (ICM) is a common source of excess iodine in medical settings, given the common use of iodinated radiologic procedures. OBJECTIVE: To determine the long-term risks of thyroid dysfunction following iodinated contrast administration in a prospective study. DESIGN, SETTING, PARTICIPANTS: A longitudinal cohort study was conducted of patients in the U.S. Veterans Affairs medical system who received ICM. MAIN OUTCOME MEASURES: Serum thyroid function, thyroid antibody, and inflammatory markers were measured at baseline. Thyroid function tests were repeated at 1 month, 3 months, and every 6 months thereafter until 36 months. Risk of thyroid dysfunction and longitudinal changes in thyroid hormone levels were assessed using mixed effect models. RESULTS: There were 122 participants (median age, 70.0 [IQR 62.2-74.0] years; 98.4% male). At baseline, six subjects had subclinical thyroid dysfunction prior to ICM receipt. During median follow-up of 18 months, iodine-induced thyroid dysfunction was observed in 11.5% (14/122); six (4.9%) developed hyperthyroidism (including one with overt hyperthyroidism) and eight (6.6%) subclinical hypothyroidism. At last follow-up, ten of 20 subjects with thyroid dysfunction (14 new-onset cases and six with preexisting thyroid dysfunction) had persistent subclinical hyperthyroidism or hypothyroidism. There were also subtle changes in thyroid hormones observed longitudinally within the reference ranges in the overall cohort. CONCLUSIONS: There is a rare long-term risk of an excess iodine load on thyroid dysfunction even among individuals from an overall iodine-sufficient region, supporting the need for targeted monitoring following iodinated contrast administration.
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Betaine has important roles in preimplantation mouse embryos, including as an organic osmolyte that functions in cell volume regulation in the early preimplantation stages and as a donor to the methyl pool in blastocysts. The origin of betaine in oocytes and embryos was largely unknown. Here, we found that betaine was present from the earliest stage of growing oocytes. Neither growing oocytes nor early preantral follicles could take up betaine, but antral follicles were able to transport betaine and supply the enclosed oocyte. Betaine is synthesized by choline dehydrogenase, and female mice lacking Chdh did not have detectable betaine in their oocytes or early embryos. Supplementing betaine in their drinking water restored betaine in the oocyte only when supplied during the final stages of antral follicle development but not earlier in folliculogenesis. Together with the transport results, this implies that betaine can only be exogenously supplied during the final stages of oocyte growth. Previous work showed that the amount of betaine in the oocyte increases sharply during meiotic maturation due to upregulated activity of choline dehydrogenase within the oocyte. This betaine present in mature eggs was retained after fertilization until the morula stage. There was no apparent role for betaine uptake via the SIT1 (SLC6A20) betaine transporter that is active at the 1- and 2-cell stages. Instead, betaine was apparently retained because its major route of efflux, the volume-sensitive organic osmolyte - anion channel, remained inactive, even though it is expressed and capable of being activated by a cell volume increase.
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Betaína , Blastocisto , Oocitos , Animales , Betaína/metabolismo , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Femenino , Ratones , Blastocisto/metabolismo , Blastocisto/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Desarrollo Embrionario/fisiología , Folículo Ovárico/metabolismo , Folículo Ovárico/efectos de los fármacos , Colina-Deshidrogenasa/metabolismoRESUMEN
Introduction: Cigarettes containing nicotine (Nic) are a risk factor for the development of cardiovascular and metabolic diseases. We reported that Nic delivered via injections or e-cigarette vapor led to hepatic steatosis in mice fed with a high-fat diet. High-fructose corn syrup (HFCS) is the main sweetener in sugar-sweetened beverages (SSBs) in the US. Increased consumption of SSBs with HFCS is associated with increased risks of non-alcoholic fatty liver disease (NAFLD). Nicotinamide riboside (NR) increases mitochondrial nicotinamide adenine dinucleotide (NAD+) and protects mice against hepatic steatosis. This study evaluated if Nic plus Coca-Cola™ (Coke) with HFCS can cause hepatic steatosis and that can be protected by NR. Methods: C57BL/6J mice received twice daily intraperitoneal (IP) injections of Nic or saline and were given Coke (HFCS), or Coke with sugar, and NR supplementation for 10 weeks. Results: Our results show that Nic+Coke caused increased caloric intake and induced hepatic steatosis, and the addition of NR prevented these changes. Western blot analysis showed lipogenesis markers were activated (increased cleavage of the sterol regulatory element-binding protein 1 [SREBP1c] and reduction of phospho-Acetyl-CoA Carboxylase [p-ACC]) in the Nic+Coke compared to the Sal+Water group. The hepatic detrimental effects of Nic+Coke were mediated by decreased NAD+ signaling, increased oxidative stress, and mitochondrial damage. NR reduced oxidative stress and prevented mitochondrial damage by restoring protein levels of Sirtuin1 (Sirt1) and peroxisome proliferator-activated receptor coactivator 1-alpha (PGC1) signaling. Conclusion: We conclude that Nic+Coke has an additive effect on producing hepatic steatosis, and NR is protective. This study suggests concern for the development of NAFLD in subjects who consume nicotine and drink SSBs with HFCS.
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Ratones Endogámicos C57BL , Niacinamida , Nicotina , Compuestos de Piridinio , Animales , Compuestos de Piridinio/farmacología , Ratones , Niacinamida/análogos & derivados , Niacinamida/farmacología , Masculino , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/etiología , Hígado Graso/prevención & control , Hígado Graso/metabolismo , Hígado Graso/inducido químicamente , Jarabe de Maíz Alto en Fructosa/efectos adversos , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Estrés Oxidativo/efectos de los fármacosRESUMEN
An exclusive human milk diet (EHMD) and standardized feeding protocols are two critical methods for safely feeding very low birth weight (VLBW) infants. Our institution initiated a standardized feeding protocol for all VLBW infants in 2018. In this protocol, a human milk fat modular was used only reactively when an infant had poor weight gain, fluid restriction, or hypoglycemia. As part of our NICU quality improvement program, internal utilization review data revealed a potential opportunity to improve growth and reduce costs. While maintaining the EHMD, a simple feeding guideline process change could provide cost savings without sacrificing caloric density or growth. We examined this process change in pre-post cohorts of VLBW infants. METHODS: Our revised feeding protocol, established in October 2021, called for a human milk fat modular (Prolact CR) to be added to all infant feeding when parenteral nutrition (PN) and lipids were discontinued. The human milk fat modular concentration is 4 mL per 100 mL feed, providing approximately an additional 2 kcal/oz. We tracked data to compare (1) the use of the human milk fat modular, (2) the use of the human milk +8 fortifier, (3) overall growth before and after feeding protocol changes, and (4) cost differences between protocols. RESULTS: Thirty-six VLBW infants were followed prospectively upon the introduction of the revised feeding protocol. In the revised era, the need for human milk +8 fortifier decreased from 43% to 14%. The decrease in the cost of a more costly fortifier provided a cost savings of USD 2967.78 on average per infant. Overall growth improved from birth to discharge, with severe malnutrition declining from 3.3% to 2.7% and moderate malnutrition declining from 37% to 8%. CONCLUSIONS: With the proactive use of a human milk fat modular in a standardized feeding protocol, our VLBW infants showed improved growth, lower malnutrition rates, and decreased use of higher caloric fortifiers.
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Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Leche Humana , Humanos , Recién Nacido , Recién Nacido de muy Bajo Peso/crecimiento & desarrollo , Masculino , Femenino , Aumento de Peso , Nutrición Parenteral , Grasas de la Dieta/administración & dosificación , Recien Nacido Prematuro/crecimiento & desarrolloRESUMEN
Precision engineering of the gut microbiome holds promise as an effective therapeutic approach for diseases associated with a disruption in this microbial community. Engrafting a live biotherapeutic product (LBP) in a predictable, controllable manner is key to the consistent success of this approach and has remained a challenge for most LBPs under development. We recently demonstrated high-level engraftment of Bifidobacterium longum subsp. infantis (B. infantis) in adults when co-dosed with a specific prebiotic, human milk oligosaccharides (HMO). Here, we present a cellular kinetic-pharmacodynamic approach, analogous to pharmacokinetic-pharmacodynamic-based analyses of small molecule- and biologic-based drugs, to establish how HMO controls expansion, abundance, and metabolic output of B. infantis in a human microbiota-based model in gnotobiotic mice. Our data demonstrate that the HMO dose controls steady-state abundance of B. infantis in the microbiome, and that B. infantis together with HMO impacts gut metabolite levels in a targeted, HMO-dependent manner. We also found that HMO creates a privileged niche for B. infantis expansion across a 5-log range of bacterial inocula. These results demonstrate remarkable control of both B. infantis levels and the microbiome community metabolic outputs using this synbiotic approach, and pave the way for precision engineering of desirable microbes and metabolites to treat a range of diseases.
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Bifidobacterium , Microbioma Gastrointestinal , Humanos , Animales , Ratones , Leche Humana/metabolismo , Oligosacáridos/metabolismo , Bifidobacterium longum subspecies infantisRESUMEN
Introduction: Telemedicine was an integral component in Singapore's COVID-19 management strategy, having been deployed at a national level in a centrally-administered program whereby patients at higher risk of developing severe COVID-19 disease were proactively assigned tele-consultations, whereas those at lower risk and seen by primary care physicians could request ad hoc tele-consultations. To better plan for fluctuations in telemedicine demand during the pandemic, the Telemedicine Demand Index (TDI) was developed. Methods: Three main factors influencing telemedicine demand were considered-characteristics of the Variant of Concern, prevailing health care policies, and the population's healthcare-seeking behaviour-from which 11 coefficients were derived for the TDI formula. The number of tele-consultations demanded is the product of the TDI and the total number of new COVID-19 cases for a given period. Results: Real-world data from January 31 to March 27, 2022 were compared with TDI estimates. A total of 148,485 tele-consultations were conducted against a backdrop of 723,675 new COVID-19 cases for the period. The TDI overestimated demand by an average 11.4%. Data from March 28 to May 1, 2022 were then used to derive new TDI values and applied to a 3-week period starting May 9, 2022, following a policy change. A total of 5,560 tele-consultations were conducted against a backdrop of 77,998 new COVID-19 cases. The TDI underestimated demand by an average of 7.2%. Conclusion: The TDI shows initial promise for quickly estimating telemedicine demand at a population level. By leveraging historical data and applying some informed assumptions, it allows for the estimation of current capabilities and future requirements. There remains scope for more research to refine the TDI's constituent components, as well as its applicability in different population contexts.
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COVID-19 , Telemedicina , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Derivación y Consulta , Aceptación de la Atención de SaludRESUMEN
Autophagy is a conserved cellular degradation process. While autophagy-related proteins were shown to influence the signaling and trafficking of some receptor tyrosine kinases, the relevance of this during cancer development is unclear. Here, we identify a role for autophagy in regulating platelet-derived growth factor receptor alpha (PDGFRA) signaling and levels. We find that PDGFRA can be targeted for autophagic degradation through the activity of the autophagy cargo receptor p62. As a result, short-term autophagy inhibition leads to elevated levels of PDGFRA but an unexpected defect in PDGFA-mediated signaling due to perturbed receptor trafficking. Defective PDGFRA signaling led to its reduced levels during prolonged autophagy inhibition, suggesting a mechanism of adaptation. Importantly, PDGFA-driven gliomagenesis in mice was disrupted when autophagy was inhibited in a manner dependent on Pten status, thus highlighting a genotype-specific role for autophagy during tumorigenesis. In summary, our data provide a mechanism by which cells require autophagy to drive tumor formation.
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Neoplasias Encefálicas , Transducción de Señal , Ratones , Animales , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , AutofagiaRESUMEN
The temperature dependent order parameter provides important information on the nature of magnetism. Using traditional methods to study this parameter in two-dimensional (2D) magnets remains difficult, however, particularly for insulating antiferromagnetic (AF) compounds. Here, we show that its temperature dependence in AF MPS3 (M(II) = Fe, Co, Ni) can be probed via the anisotropy in the resonance frequency of rectangular membranes, mediated by a combination of anisotropic magnetostriction and spontaneous staggered magnetization. Density functional calculations followed by a derived orbital-resolved magnetic exchange analysis confirm and unravel the microscopic origin of this magnetization-induced anisotropic strain. We further show that the temperature and thickness dependent order parameter allows to deduce the material's critical exponents characterising magnetic order. Nanomechanical sensing of magnetic order thus provides a future platform to investigate 2D magnetism down to the single-layer limit.
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OBJECTIVES: Although public efforts to reduce tobacco use have been successful, millions of US adults currently smoke tobacco. Reducing the public health burden of tobacco use disorder (TUD) and eliminating disparities experienced by underresourced communities requires increased accessibility to services. The goal of this study was to assess whether prescriptions for evidence-based medications for tobacco treatment showed steeper growth rates among community health clinics providing specialty TUD services as compared with treatment as usual. METHODS: Clinic-wide data on prescriptions for smoking cessation pharmacotherapy at 18 primary care or mental health community clinics operated by Los Angeles County were retrieved for 4 years of an ongoing implementation trial. Specialty services included behavioral counseling and medications for tobacco treatment. Descriptive statistics characterized prescriptions rates across clinics and time. Analyses compared the slopes of the changes between intervention groups across time for primary care and mental health sites. RESULTS: Within primary care clinics, the most commonly prescribed smoking cessation medications were nicotine patches, nicotine gum, and varenicline. Throughout the trial, all clinics displayed increased rates of prescribing smoking cessation medications. Analytic results supported overall steeper increases in prescription rates for these medications among clinics randomized to specialty services versus treatment as usual within primary care ( P = 0.020) and mental health sites ( P = 0.004). CONCLUSIONS: This work provides support for the effectiveness of community-based implementation interventions that promote prescribing smoking cessation medications with the potential to reduce health disparities among communities at greater risk for TUD and its consequences.
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Cese del Hábito de Fumar , Tabaquismo , Adulto , Humanos , Salud Pública , Nicotina , Uso de TabacoRESUMEN
Standardized approaches to phage susceptibility testing (PST) are essential to inform selection of phages for study in patients with bacterial infections. There is no reference standard for assessing bacterial susceptibility to phage. We compared agreement between PST performed at three centers: two centers using a liquid assay standardized between the sites with the third, a plaque assay. Four Pseudomonas aeruginosa phages: PaWRA01ø11 (EPa11), PaWRA01ø39 (EPa39), PaWRA02ø83 (EPa83), PaWRA02ø87 (EPa87), and a cocktail of all four phages were tested against 145 P. aeruginosa isolates. Comparisons were made within measurements at the two sites performing the liquid assay and between these two sites. Agreement was assessed based on coverage probability (CP8), total deviation index, concordance correlation coefficient (CCC), measurement accuracy, and precision. For the liquid assay, there was satisfactory agreement among triplicate measurements made on different days at site 1, and high agreement based on accuracy and precision between duplicate measurements made on the same run at site 2. There was fair accuracy between measurements of the two sites performing the liquid assay, with CCCs below 0.6 for all phages tested. When compared to the plaque assay (performed once at site 3), there was less agreement between results of the liquid and plaque assays than between the two sites performing the liquid assay. Similar findings to the larger group were noted in the subset of 46 P. aeruginosa isolates from cystic fibrosis. Results of this study suggest that reproducibility of PST methods needs further development.
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Bacteriófagos , Fibrosis Quística , Infecciones por Pseudomonas , Humanos , Pseudomonas aeruginosa , Reproducibilidad de los Resultados , Infecciones por Pseudomonas/tratamiento farmacológico , Fibrosis Quística/microbiología , Antibacterianos/uso terapéuticoRESUMEN
Vertical-external-cavity surface-emitting semiconductor lasers (VECSELs) are of increasing interest for applications requiring ultra-coherence and/or low noise at novel wavelengths; performance that is currently achieved via high-Q, air-spaced resonators to achieve long intra-cavity photon lifetimes (for the so-called class-A low noise regime), power scaling and high beam quality. Here, we report on the development of a compact, electronically tunable, monolithic-cavity, class-A VECSEL (monolithic VECSEL) for ultra-narrow free-running linewidths. A multi-quantum-well, resonant periodic gain structure with integrated distributed Bragg reflector (DBR) was optically-bonded to an air-gap-free laser resonator created inside a right-angle fused-silica prism to suppress the influence of environmental noise on the external laser oscillation, thus achieving high stability. Mode-hop-free wavelength tuning is performed via the stabilized temperature; or electronically, and with low latency, via a shear piezo-electric transducer mounted on the top of the prism. The free-running linewidth, estimated via the frequency power spectral density (PSD), is sub-kHz over ms timescales and <1.9 kHz for time sampling as long as 1s, demonstrating at least two orders-of-magnitude improvement in noise performance compared to previously reported single frequency VECSELs. The stable, total internal reflection resonator concept is akin to the prevalent monolithic non-planar ring oscillator (NPRO), however the monolithic VECSEL has several important advantages: tailored emission wavelength (via semiconductor bandgap engineering), no relaxation oscillations, no applied magnetic field, and low requirements on the pump beam quality. This approach is power-scalable in principle and could be applied to VECSELs at any of the wavelengths from the visible to the mid-infrared at which they are already available, to create a range of robust, ultra-coherent laser systems with reduced bulkiness and complexity. This is of particular interest for remote metrology and the translation of quantum technologies, such as optical clocks, from research laboratories into real world applications.
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Background Although most individuals can adapt to a large iodine load and remain euthyroid, hypothyroidism can develop after iodine exposure. Hypothyroidism is associated with adverse cardiovascular consequences, including heart failure. This study was performed to investigate the relationships between iodine-induced hypothyroidism and incident heart failure. Methods and Results This cohort study of the US Veterans Health Administration (1998-2021) included adults aged ≥18 years with a serum thyroid-stimulating hormone (thyrotropin) <60 days of iodine contrast administration, and <1 year of a baseline normal serum thyroid-stimulating hormone. Cox proportional hazards regression ascertained risk of incident heart failure following iodine-induced hypothyroidism, adjusting for age, sex, race and ethnicity, body mass index, and history of coronary heart disease, dyslipidemia, diabetes, and hypertension. Of 45 470 veterans (mean±SD age, 61.1±14.1 years; 88% men), 3361 (7.4%) developed iodine-induced hypothyroidism. Heart failure developed in 5685 (12.5%) individuals over a median follow-up of 3.6 years (interquartile range, 1.9-7.2 years). Adjusted for risk factors, iodine-induced hypothyroidism was associated with increased risk of heart failure, compared with those who remained euthyroid after iodine exposure (adjusted hazard ratio [HR], 1.11 [95% CI, 1.01-1.22]). Women were at greater risk than men (adjusted HR: women, 1.65 [95% CI, 1.13-2.40]; men, 1.08 [95% CI, 0.98-1.19]; P for interaction, 0.02). Conclusions In the largest US study of this topic, hypothyroidism following iodine exposure was associated with an increased risk of incident heart failure, particularly in women. These findings support the need for further research to address the clinical significance of this issue, including the possible sex-specific risks of incident heart failure in more diverse data sets and study populations.
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Insuficiencia Cardíaca , Hipotiroidismo , Yodo , Adulto , Masculino , Humanos , Femenino , Adolescente , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Hipotiroidismo/inducido químicamente , Hipotiroidismo/epidemiología , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/complicaciones , Tirotropina , Yodo/efectos adversosRESUMEN
We report for the first time a high performance, single frequency AlGaInP-based VECSEL (vertical-external-cavity surface-emitting-laser) with emission at 698â nm, targeting the clock transition of neutral strontium atoms. Furthermore, we present comprehensive noise characterization of this class-A semiconductor laser, including the residual fast phase noise in addition to the frequency and relative intensity noise. The low noise VECSEL has output power at around 135â mW with an estimated linewidth of 115â Hz when frequency stabilized via the Pound-Drever-Hall (PDH) technique to a high finesse reference cavity, without intermediate stabilization. The phase noise is measured to be below -126 dBc/Hz for frequencies between 10 kHz and 15â MHz with a total integrated phase noise of 3.2â mrad, suitable not only for ultra-cold neutral strontium-based quantum technologies, such as optical clocks, but also with potential for atom-interferometry applications.
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Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol sulfate, metabolites that impact host inflammatory status. Furthermore, Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts lactate produced by B. infantis to propionate, an important mediator of host physiology. These results suggest that the synbiotic reproducibly and predictably modulates recovery of a dysbiotic microbiome.