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1.
Int J Obes (Lond) ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39152336

RESUMEN

BACKGROUND: The association between body mass index (BMI) and mortality among individuals with renal cell cancer (RCC) is debated, with some observational studies suggesting a lower mortality associated with higher BMI. However, methodological issues such as confounding and reverse causation may bias these findings. Using BMI-associated genetic variants can avoid these biases and generate more valid estimates. METHODS: In this prospective cohort study, we included 1264 RCC patients (446 deaths) from the UK Biobank. We created a BMI polygenic score (PGS) based on 336 BMI-associated genetic variants. The association between the PGS and mortality (all-cause and RCC-specific) was evaluated by logistic regression (all RCC cases) and Cox regression (906 incident cases). For comparison, the associations of measured pre-diagnostic BMI and waist-to-hip ratio (WHR) with mortality were quantified by Cox regression among incident cases. We stratified these analyses by time between anthropometric measurement and RCC diagnosis to assess the influence of reverse causation. RESULTS: We did not observe an association between the BMI PGS and all-cause mortality among RCC patients (hazard ratio (HR) per SD increase = 0.98, 95% CI: 0.88,1.10). No association was found for pre-diagnostic BMI (HR per 5 kg/m2 increase = 0.93, 95% CI: 0.83,1.04) or WHR (HR per 0.1 increase = 0.97, 95% CI: 0.83,1.13) with mortality. In patients with anthropometrics measured within 2 years before RCC diagnosis, we observed associations of higher BMI (HR per 5 kg/m2 = 0.76, 95% CI: 0.59,0.98) and WHR (HR = 0.67 per 0.1 increase, 95% CI: 0.45,0.98) with a lower risk of death. Similar patterns were observed for RCC-specific mortality. CONCLUSION: We found no association between either genetic variants for high BMI or measured pre-diagnostic body adiposity and mortality among RCC patients, and our results suggested a role for reverse causation in the association of obesity with lower mortality. Future studies should be designed carefully to produce unbiased estimates that account for confounding and reverse causation.

2.
Front Oncol ; 14: 1420333, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39070148

RESUMEN

Background: Cardiovascular disease (CVD) is a major concern of morbidity and mortality among cancer survivors. However, few evidence exists on the short- and long-term risk of CVD in kidney cancer (KCa) survivors. Methods: In this nationwide, large population-based retrospective cohort study, we used the Korean national health insurance and medical checkup survey linkage database (2007-2021), drawn from the entire Korean population. We included adults diagnosed with KCa as the first primary cancer and matched them to an individual without KCa at a 1:5 ratio. The primary outcome was CVD incidence, including myocardial infarction, stroke, atrial fibrillation, heart failure, peripheral arterial occlusion, and venous thromboembolism (VTE). We evaluated CVD risk at 6 months, 1 year, and 5 years following cancer diagnosis, using Fine-Gray competing risk models that accounted for death as a competing factor. Results: A total of 149,232 participants were included (KCa survivors: N=20,093 and matched non-KCa individuals: N=129,139). After 6-month follow-up, KCa survivors showed an increased risk of CVD compared to the general population (subdistribution hazard ratio (HR) 2.70, 95% confidence interval (CI) 2.31-3.15). After 1 year, KCa survivors had a higher risk of CVD (HR=1.77, 95% CI: 1.56-2.00). After 5 years, this elevated CVD risk remained (HR=1.10, 95% CI: 1.03-1.18), with VTE identified as the primary contributing disease (HR=3.05, 95% CI:2.59-3.59). Conclusion: KCa survivors had an increased risk of CVD up to 5 years after cancer diagnosis compared to the general population. Our findings emphasize the importance of comprehensive healthcare management for both CVD and KCa throughout cancer survivorship.

3.
Neurotoxicology ; 104: 20-35, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39002649

RESUMEN

Air pollution (AP) exposures have been associated with numerous neurodevelopmental and psychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder and schizophrenia, all male-biased disorders with onsets from early life to late adolescence/early adulthood. While prior experimental studies have focused on effects of AP exposures during early brain development, brain development actually extends well into early adulthood. The current study in mice sought to extend the understanding of developmental brain vulnerability during adolescence, a later but significant period of brain development and maturation to the ultrafine particulate (UFPs) component of AP, considered its most reactive component. Additionally, it examined adolescent response to UFPs when preceded by earlier developmental exposures, to ascertain the trajectory of effects and potential enhancement or mitigation of adverse consequences. Outcomes focused on shared features associated with multiple neurodevelopmental disorders. For this purpose, C57Bl/6 J mice of both sexes were exposed to ambient concentrated UFPs or filtered air from PND (postnatal day) 4-7 and PND10-13, and again at PND39-42 and 45-49, resulting in 3 exposure postnatal/adolescent treatment groups per sex: Air/Air, Air/UFP, and UFP/UFP. Features common to neurodevelopmental disorders were examined at PND50. Mass exposure concentration from postnatal exposure averaged 44.34 µg/m3 and the adolescent exposure averaged 49.18 µg/m3. Male brain showed particular vulnerability to UFP exposures in adolescence, with alterations in frontal cortical and striatal glutamatergic and tryptophan/serotonergic neurotransmitters and concurrent reductions in levels of astrocytes in corpus callosum and in serum cytokine levels, with combined exposures resulting in significant reductions in corpus callosum myelination and serum corticosterone. Reductions in serum corticosterone in males correlated with reductions in neurotransmitter levels, and reductions in striatal glutamatergic function specifically correlated with reductions in corpus callosum astrocytes. UFP-induced changes in neurotransmitter levels in males were mitigated by prior postnatal exposure, suggesting potential adaptation, whereas reductions in corticosterone and in corpus callosum neuropathological effects were further strengthened by combined postnatal and adolescent exposures. UFP-induced changes in females occurred primarily in striatal dopamine systems and as reductions in serum cytokines only in response to combined postnatal and adolescent exposures. Findings in males underscore the importance of more integrated physiological assessments of mechanisms of neurotoxicity. Further, these findings provide biological plausibility for an accumulating epidemiologic literature linking air pollution to neurodevelopmental and psychiatric disorders. As such, they support a need for consideration of the regulation of the UFP component of air pollution.

4.
Nat Commun ; 15(1): 5116, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879581

RESUMEN

Exposure to ambient air pollution has significant adverse health effects; however, whether air pollution is associated with urological cancer is largely unknown. We conduct a systematic review and meta-analysis with epidemiological studies, showing that a 5 µg/m3 increase in PM2.5 exposure is associated with a 6%, 7%, and 9%, increased risk of overall urological, bladder, and kidney cancer, respectively; and a 10 µg/m3 increase in NO2 is linked to a 3%, 4%, and 4% higher risk of overall urological, bladder, and prostate cancer, respectively. Were these associations to reflect causal relationships, lowering PM2.5 levels to 5.8 µg/m3 could reduce the age-standardized rate of urological cancer by 1.5 ~ 27/100,000 across the 15 countries with the highest PM2.5 level from the top 30 countries with the highest urological cancer burden. Implementing global health policies that can improve air quality could potentially reduce the risk of urologic cancer and alleviate its burden.


Asunto(s)
Contaminación del Aire , Material Particulado , Neoplasias Urológicas , Humanos , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Neoplasias Urológicas/epidemiología , Neoplasias Urológicas/etiología , Material Particulado/efectos adversos , Material Particulado/análisis , Masculino , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/efectos adversos , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias Renales/epidemiología , Neoplasias Renales/etiología , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/etiología , Femenino
5.
Viruses ; 16(5)2024 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-38793659

RESUMEN

Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by the FDA. Recently, N6-methyladenosine (m6A) RNA methylation has been implicated in the regulation of the viral life cycle and replication of many viruses, including RSV. m6A methylation of RSV RNA has been demonstrated to promote replication and prevent anti-viral immune responses by the host. Whether m6A is also involved in viral entry and whether m6A can also affect RSV infection via different mechanisms than methylation of viral RNA is poorly understood. Here, we identify m6A reader YTH domain-containing protein 1 (YTHDC1) as a novel negative regulator of RSV infection. We demonstrate that YTHDC1 abrogates RSV infection by reducing the expression of RSV entry receptor CX3C motif chemokine receptor 1 (CX3CR1) on the cell surface of lung epithelial cells. Altogether, these data reveal a novel role for m6A methylation and YTHDC1 in the viral entry of RSV. These findings may contribute to the development of novel treatment options to control RSV infection.


Asunto(s)
Receptor 1 de Quimiocinas CX3C , Regulación hacia Abajo , Factores de Empalme de ARN , Infecciones por Virus Sincitial Respiratorio , Humanos , Células A549 , Adenosina/análogos & derivados , Adenosina/metabolismo , Línea Celular , Receptor 1 de Quimiocinas CX3C/metabolismo , Receptor 1 de Quimiocinas CX3C/genética , Células Epiteliales/virología , Células Epiteliales/metabolismo , Interacciones Huésped-Patógeno , Metilación , Proteínas del Tejido Nervioso , Infecciones por Virus Sincitial Respiratorio/virología , Infecciones por Virus Sincitial Respiratorio/metabolismo , Virus Sincitial Respiratorio Humano/fisiología , Factores de Empalme de ARN/metabolismo , Factores de Empalme de ARN/genética , ARN Viral/genética , ARN Viral/metabolismo , Internalización del Virus , Replicación Viral
7.
Sci Total Environ ; 930: 172688, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38663627

RESUMEN

With allergic rhinitis (AR) on the rise globally, there has been a growing focus on the role of environmental pollutants in the onset of AR. However, the potential mechanisms by how and which these pollutants exacerbate AR conditions remain unknown. This panel study of 49 patients diagnosed with AR over one year aimed to assess the individual and combined effects of short-term exposure to multiple ambient pollutants on oxidative stress, symptoms, and quality of life among patients with AR. All participants underwent four repeated assessments of health conditions and personal environmental exposures (PM2.5, O3, SO2, and NO2) over warm and cold seasons during 2017-2018. We evaluated two oxidative stress biomarkers (malondialdehyde [MDA], and superoxide dismutase [SOD]) via nasal lavage. We collected information on self-reported symptoms and quality of life using the Rhinitis Symptom Scale (SRS), the Visual Analog Scale (VAS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) through in-person interviews. Bayesian kernel machine regression (BKMR) was used to evaluate the joint effects of pollutant mixture and identify key contributors. The results revealed a significant association of the pollutant mixture when all four pollutants were at or above their median levels, with increased oxidative stress. This was evidenced by elevated MDA and reduced SOD. We found a joint detrimental effect of the pollutant mixture on AR symptoms with a strong association with increased SRS scores, but a non-significant positive association with VAS and RQLQ scores. PM2.5, O3, and SO2 presented as the potentially primary contributors to the adverse health effects associated with the pollutant mixture in Taiyuan city. Patients with AR exposed to short-term air pollutant mixture are more likely to have greater nasal symptoms and worse quality of life from increased oxidative stress and reduced antioxidant capacity. Further research is warranted to better elucidate the underlying mechanisms.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Estrés Oxidativo , Rinitis Alérgica , Humanos , Contaminación del Aire/efectos adversos , Contaminación del Aire/estadística & datos numéricos , Contaminantes Atmosféricos/efectos adversos , Masculino , Femenino , Adulto , Calidad de Vida , Exposición a Riesgos Ambientales/estadística & datos numéricos , Exposición a Riesgos Ambientales/efectos adversos , Persona de Mediana Edad , Material Particulado
8.
Eur J Vasc Endovasc Surg ; 68(1): 30-38, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38428671

RESUMEN

OBJECTIVE: Registry data suggest that centralising abdominal aortic aneurysm (AAA) surgery decreases the mortality rate after AAA repair. However, the impact of higher elective volumes on ruptured AAA (rAAA) repair associated mortality rates remains uncertain. This study aimed to examine associations between intact AAA (iAAA) repair volume and post-operative rAAA death. METHODS: Using data from official national registries between 2015 - 2019, all iAAA and rAAA repairs were separately analysed across 10 public hospitals. The following were assessed: 30 day and 12 month mortality rate following open surgical repair (OSR) and endovascular aneurysm repair (EVAR). Associations between the 5 year hospital iAAA repair volumes (organised into tertiles) and rAAA associated mortality rate were analysed, regardless of treatment modality. Receiver operating characteristic (ROC) curves were generated to identify iAAA volume thresholds for decreasing the rAAA mortality rate. Subanalysis by treatment type was conducted. Threshold analysis was repeated with the Markov chain Monte Carlo (MCMC) procedure to confirm the findings. RESULTS: A total of 1 599 iAAAs (80.2% EVAR, 19.8% OSR) and 196 rAAAs (66.3% EVAR, 33.7% OSR) repairs were analysed. The median and interquartile range of the volume/hospital/year for all iAAA repairs were 39.2 (31.2, 47.4). The top volume iAAA tertile exhibited lower rAAA associated 30 day (odds ratio [OR] 0.374; p = .007) and 12 month (OR 0.264; p < .001) mortality rates. The ROC analysis revealed a threshold of 40 iAAA repairs/hospital/year (EVAR + OSR) for a reduced rAAA mortality rate. Middle volume hospitals for open iAAA repair had reduced 30 day (OR 0.267; p = .033) and 12 month (OR 0.223; p = .020) mortality rates, with a threshold of five OSR procedures/year. The MCMC procedure found similar thresholds. No significant association was found between elective EVAR volumes and ruptured EVAR mortality. CONCLUSION: Higher iAAA repair volumes correlated with a lower rAAA mortality rate, particularly for OSR. The recommended iAAA repair threshold is 40 procedures/year and five procedures/year for OSR. These findings support high elective volumes for improving the rAAA mortality rate, especially for OSR.


Asunto(s)
Aneurisma de la Aorta Abdominal , Rotura de la Aorta , Procedimientos Quirúrgicos Electivos , Procedimientos Endovasculares , Hospitales de Alto Volumen , Hospitales de Bajo Volumen , Sistema de Registros , Humanos , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/mortalidad , Rotura de la Aorta/cirugía , Rotura de la Aorta/mortalidad , Masculino , Femenino , Anciano , Procedimientos Quirúrgicos Electivos/mortalidad , Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Hospitales de Alto Volumen/estadística & datos numéricos , Procedimientos Endovasculares/mortalidad , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/estadística & datos numéricos , Hospitales de Bajo Volumen/estadística & datos numéricos , Factores de Riesgo , Anciano de 80 o más Años , Implantación de Prótesis Vascular/mortalidad , Implantación de Prótesis Vascular/efectos adversos , Medición de Riesgo , Resultado del Tratamiento , Factores de Tiempo , Mortalidad Hospitalaria , Estudios Retrospectivos
9.
Chemosphere ; 346: 140582, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38303402

RESUMEN

Particulate matter (PM) exposure may be associated with male semen quality. Besides, PM exposure induces up and down levels of trace metals in tissues or organs. The levels of trace metals in semen are critical for adverse male semen quality. This study aims to evaluate the concentrations of seminal-level trace metals in fertile men and assess its associations with PM exposure and to explore the mediation role of trace metals in seminal plasma plays in the relationship between PM exposure and semen quality. Total 1225 fertile men who participated in a cohort study from 2014 to 2016 were finally recruited. Multivariate linear regression was applied to explore associations between each two of PM exposure, trace metals and semen parameters. 1-year PM2.5 and PM10 exposure levels were positively associated with arsenic (As), mercury (Hg), lanthanum (La), praseodymium (Pr), neodymium (Nd) but negatively associated with vanadium (V), magnesium (Mg), strontium (Sr), barium (Ba) in semen. It was also found that most of the elements were associated with total sperm number, followed by sperm concentration. Redundancy analysis (RDA) also determined several strong positive correlations or negative correlations between 1-year PM exposure and trace metals. Mediation analysis found that trace metals had a potentially compensatory or synergetic indirect effect on the total effect of the association between 1-year PM exposure and semen quality. The retrospective cohort study provides long-term PM exposure that may cause abnormal semen quality by affecting seminal plasma element levels.


Asunto(s)
Infertilidad Masculina , Oligoelementos , Humanos , Masculino , Análisis de Semen , Semen/química , Material Particulado/análisis , Estudios de Cohortes , Estudios Retrospectivos , Espermatozoides , Infertilidad Masculina/inducido químicamente , Motilidad Espermática , Oligoelementos/análisis
10.
Artículo en Inglés | MEDLINE | ID: mdl-38195151

RESUMEN

BACKGROUND: Lower urinary tract symptoms (LUTS) in older men are associated with an increased risk of mobility limitations. Lower extremity muscle quality may represent a novel shared mechanism of both LUTS and mobility limitations. METHODS: We evaluated associations of thigh skeletal muscle measures (strength, area, and specific force) with total LUTS severity (American Urologic Association Symptom Index; AUASI) and voiding and storage subscores among 352 men aged ≥60 years enrolled in the Baltimore Longitudinal Study of Aging. Thigh muscle strength (Nm) was defined as maximum concentric 30°/s knee extensor torque, area (cm2), and specific force (Nm/cm2) defined as strength/area. Associations with AUASI score were estimated using multivariable linear regression and linear mixed models. RESULTS: Mean thigh muscle strength at baseline was 139.7Nm. In cross-sectional multivariable models, each 39Nm increment in thigh muscle strength and 0.28Nm/cm2 increment in specific force was associated with -1.17 point (95% CI: -1.93 to -.41) and -0.95 point (95% CI: -1.63 to -0.27) lower AUASI score, respectively. Similar associations were observed for voiding and storage subscores, although somewhat attenuated. In longitudinal analyses, baseline muscle measures were not associated with annual change in AUASI, and current changes in muscle measures and AUASI were unrelated. CONCLUSIONS: Cross-sectionally, higher thigh muscle strength and specific force were associated with decreased LUTS severity in older men. However, we did not observe concurrent worsening LUTS severity with declining thigh muscle strength, area, or specific force in longitudinal analyses.


Asunto(s)
Extremidad Inferior , Síntomas del Sistema Urinario Inferior , Fuerza Muscular , Humanos , Masculino , Síntomas del Sistema Urinario Inferior/fisiopatología , Fuerza Muscular/fisiología , Anciano , Estudios Longitudinales , Baltimore/epidemiología , Persona de Mediana Edad , Extremidad Inferior/fisiopatología , Envejecimiento/fisiología , Estudios Transversales , Músculo Esquelético/fisiopatología , Muslo , Índice de Severidad de la Enfermedad
12.
Sci Rep ; 13(1): 20611, 2023 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-37996453

RESUMEN

The recently observed FLASH effect describes the observation of normal tissue protection by ultra-high dose rates (UHDR), or dose delivery in a fraction of a second, at similar tumor-killing efficacy of conventional dose delivery and promises great benefits for radiotherapy patients. Dedicated studies are now necessary to define a robust set of dose application parameters for FLASH radiotherapy and to identify underlying mechanisms. These studies require particle accelerators with variable temporal dose application characteristics for numerous radiation qualities, equipped for preclinical radiobiological research. Here we present the DRESDEN PLATFORM, a research hub for ultra-high dose rate radiobiology. By uniting clinical and research accelerators with radiobiology infrastructure and know-how, the DRESDEN PLATFORM offers a unique environment for studying the FLASH effect. We introduce its experimental capabilities and demonstrate the platform's suitability for systematic investigation of FLASH by presenting results from a concerted in vivo radiobiology study with zebrafish embryos. The comparative pre-clinical study was conducted across one electron and two proton accelerator facilities, including an advanced laser-driven proton source applied for FLASH-relevant in vivo irradiations for the first time. The data show a protective effect of UHDR irradiation up to [Formula: see text] and suggests consistency of the protective effect even at escalated dose rates of [Formula: see text]. With the first clinical FLASH studies underway, research facilities like the DRESDEN PLATFORM, addressing the open questions surrounding FLASH, are essential to accelerate FLASH's translation into clinical practice.


Asunto(s)
Neoplasias , Protones , Animales , Humanos , Dosificación Radioterapéutica , Pez Cebra , Neoplasias/radioterapia , Radiobiología
13.
ACS Nano ; 17(20): 20179-20193, 2023 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-37791900

RESUMEN

Single-molecule fluorescence imaging experiments generally require sub-nanomolar protein concentrations to isolate single protein molecules, which makes such experiments challenging in live cells due to high intracellular protein concentrations. Here, we show that single-molecule observations can be achieved in live cells through a drastic reduction in the observation volume using overmilled zero-mode waveguides (ZMWs- subwavelength-size holes in a metal film). Overmilling of the ZMW in a palladium film creates a nanowell of tunable size in the glass layer below the aperture, which cells can penetrate. We present a thorough theoretical and experimental characterization of the optical properties of these nanowells over a wide range of ZMW diameters and overmilling depths, showing an excellent signal confinement and a 5-fold fluorescence enhancement of fluorescent molecules inside nanowells. ZMW nanowells facilitate live-cell imaging as cells form stable protrusions into the nanowells. Importantly, the nanowells greatly reduce the cytoplasmic background fluorescence, enabling the detection of individual membrane-bound fluorophores in the presence of high cytoplasmic expression levels, which could not be achieved with TIRF microscopy. Zero-mode waveguide nanowells thus provide great potential to study individual proteins in living cells.


Asunto(s)
Microscopía , Nanotecnología , Nanotecnología/métodos , Imagen Individual de Molécula , Espectrometría de Fluorescencia/métodos
14.
Nat Microbiol ; 8(11): 2115-2129, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37814072

RESUMEN

Antiviral signalling, which can be activated in host cells upon virus infection, restricts virus replication and communicates infection status to neighbouring cells. The antiviral response is heterogeneous, both quantitatively (efficiency of response activation) and qualitatively (transcribed antiviral gene set). To investigate the basis of this heterogeneity, we combined Virus Infection Real-time IMaging (VIRIM), a live-cell single-molecule imaging method, with real-time readouts of the dsRNA sensing pathway to analyse the response of human cells to encephalomyocarditis virus (EMCV) infection. We find that cell-to-cell heterogeneity in viral replication rates early in infection affect the efficiency of antiviral response activation, with lower replication rates leading to more antiviral response activation. Furthermore, we show that qualitatively distinct antiviral responses can be linked to the strength of the antiviral signalling pathway. Our analyses identify variation in early viral replication rates as an important parameter contributing to heterogeneity in antiviral response activation.


Asunto(s)
Virosis , Replicación Viral , Humanos , Transducción de Señal , Virus de la Encefalomiocarditis/fisiología , Antivirales
15.
J Natl Med Assoc ; 115(5): 475-481, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37550160

RESUMEN

OBJECTIVE: Children with sickle cell disease (SCD) are at risk for neurocognitive deficits that can affect school performance, and psychosocial functioning. The aim of this study was to assess the academic performance of school-aged children with SCD in Jamaica compared to their school peers. METHOD: A cross-sectional survey of academic performance was done in a group of children 11 to 13 years of age, using a standardized state administered examination, the Grade Six Achievement Test (GSAT), covering 5 subjects. Scores were obtained from the Ministry of Education (MOE) for eligible children with SCD, as well as mean scores with standard deviation for unaffected classmates by gender. Socio-demographic and clinical data were obtained from our sickle cell clinic database and an interview administered questionnaire. RESULTS: Sixty-four children satisfied eligibility criteria. Children with SCD had lower percentage scores and significantly lower mean z-scores for 4 of 5 subjects (p < 0.05). Males had significantly lower mean z-scores compared with females. Thirty-seven children (57.8%) were classified as underperformers. Haemoglobin level was a significant predictor of subject score rank. CONCLUSION: Children with SCD in Jamaica perform worse in standardized school examinations than their class peers with boys being particularly vulnerable.


Asunto(s)
Rendimiento Académico , Anemia de Células Falciformes , Masculino , Femenino , Humanos , Niño , Jamaica/epidemiología , Estudios Transversales , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología , Escolaridad
16.
Phys Med Biol ; 68(18)2023 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-37579761

RESUMEN

Objective.Laser plasma-based accelerators (LPAs) of protons can contribute to research of ultra-high dose rate radiobiology as they provide pulse dose rates unprecedented at medical proton sources. Yet, LPAs pose challenges regarding precise and accurate dosimetry due to the high pulse dose rates, but also due to the sources' lower spectral stability and pulsed operation mode. Forin vivomodels, further challenges arise from the necessary small field dosimetry for volumetric dose distributions. For these novel source parameters and intended applications, a dosimetric standard needs to be established.Approach.In this work, we present a dosimetry and beam monitoring framework forin vivoirradiations of small target volumes with LPA protons, solving aforementioned challenges. The volumetric dose distribution in a sample (mean dose value and lateral/depth dose inhomogeneity) is provided by combining two independent dose measurements using radiochromic films (dose rate-independent) and ionization chambers (dose rate-dependent), respectively. The unique feature of the dosimetric setup is beam monitoring with a transmission time-of-flight spectrometer to quantify spectral fluctuations of the irradiating proton pulses. The resulting changes in the depth dose profile during irradiation of anin vivosample are hence accessible and enable pulse-resolved depth dose correction for each dose measurement.Main results.A first successful small animal pilot study using an LPA proton source serves as a testcase for the presented dosimetry approach and proves its performance in a realistic setting.Significance.With several facilities worldwide either setting up or already using LPA infrastructure for radiobiological studies with protons, the importance of LPA-adapted dosimetric frameworks as presented in this work is clearly underlined.


Asunto(s)
Protones , Radiometría , Animales , Proyectos Piloto , Radiometría/métodos , Rayos Láser , Radiobiología , Dosimetría por Película/métodos
17.
Cancer Epidemiol Biomarkers Prev ; 32(11): 1651-1659, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37624040

RESUMEN

BACKGROUND: Body mass index (BMI) is a known risk factor for renal cell cancer (RCC), but data are limited as to the effect of lifetime exposure to excess body weight. METHODS: Using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 138,614, 527 incident RCCs), we identified several anthropometric measures to capture the lifetime BMI patterns: (i) BMI at specific ages; (ii) adulthood BMI trajectories; (iii) cumulative exposure to overweight/obesity denoted as weighted years of living overweight/obese (WYO); and (iv) weight change during each age span. We conducted multivariable Cox model to quantify the association between each anthropometric metric and incident RCC. RESULTS: A higher BMI at ages 20 and 50 and at baseline was associated with a greater hazard of RCC. Compared with individuals who retained normal BMI throughout adulthood, we observed an increased hazard of RCC for BMI trajectory of progressing from normal BMI to overweight [HR, 1.49; 95% confidence interval (CI), 1.19-1.87], from normal BMI to obesity (HR, 2.22; 95% CI, 1.70-2.90), and from overweight to obesity (HR, 2.78; 95% CI, 1.81-4.27). Compared with individuals who were never overweight (WYO = 0), elevated HRs were observed among individuals who experienced low (HR, 1.31; 95% CI, 0.99-1.74), medium (HR, 1.57; 95% CI, 1.20-2.05), and high (HR, 2.10; 95% CI, 1.62-2.72) WYO tertile. Weight gain of ≥10 kg was associated with increased RCC incidence for each age span. CONCLUSIONS: Across the lifespan, being overweight/obese, weight gain, and higher cumulative exposure to excess weight were all associated with increased RCC risk. IMPACT: It is important to avoid weight gain and assess BMI from a life-course perspective to reduce RCC risk.


Asunto(s)
Trayectoria del Peso Corporal , Carcinoma de Células Renales , Neoplasias Renales , Adulto , Femenino , Humanos , Masculino , Índice de Masa Corporal , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/etiología , Neoplasias Renales/epidemiología , Neoplasias Renales/etiología , Obesidad/complicaciones , Obesidad/epidemiología , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Estudios Prospectivos , Factores de Riesgo , Aumento de Peso , Ensayos Clínicos como Asunto , Adulto Joven , Persona de Mediana Edad
18.
Artículo en Inglés | MEDLINE | ID: mdl-37490995

RESUMEN

BACKGROUND: Blunt traumatic thoracic aortic injuries (BTAIs) are associated with a high mortality rate. Thoracic endovascular aortic repair (TEVAR) is the most frequently used surgical strategy in patients with BTAI, as it offers good short- and middle-term results. Previous studies have reported an abnormally high prevalence of hypertension (HT) in these patients. This work aimed to describe the long-term prevalence of HT and provide a comprehensive evaluation of the biomechanical, clinical, and functional factors involved in HT development. METHODS: Twenty-six patients treated with TEVAR following BTAI with no history of HT at the time of trauma were enrolled. They were matched with 37 healthy volunteers based on age, sex, and body surface area and underwent a comprehensive follow-up study, including cardiovascular magnetic resonance, 24-hour ambulatory blood pressure monitoring, and assessment of carotid-femoral pulse wave velocity (cfPWV, a measure of aortic stiffness) and flow-mediated vasodilation. RESULTS: The mean patient age was 43.5 ± 12.9 years, and the majority were male (23 of 26; 88.5%). At a mean of 120.2 ± 69.7 months after intervention, 17 patients (65%) presented with HT, 14 (54%) had abnormal nighttime blood pressure dipping, and 6 (23%) high cfPWV. New-onset HT was related to a more proximal TEVAR landing zone and greater distal oversizing. Abnormal nighttime blood pressure was related to high cfPWV, which in turn was associated with TEVAR length and premature arterial aging. CONCLUSIONS: HT frequently occurs otherwise healthy subjects undergoing TEVAR implantation after BTAI. TEVAR stiffness and length, the proximal landing zone, and distal oversizing are potentially modifiable surgical characteristics related to abnormal blood pressure.

19.
Artículo en Inglés | MEDLINE | ID: mdl-37372707

RESUMEN

Sexual minorities (SM) have higher chronic physiologic stress as indicated by allostatic load (AL), which may be explained in part by consistent experiences of discriminatory practices. This is one of the first studies to examine the joint effects of SM status and AL on the association with long-term risk for cancer death. Retrospective analyses were conducted on 12,470 participants using National Health and Nutrition Examination Survey (NHANES) from years 2001 through 2010 linked with the National Death Index through December 31, 2019. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) of cancer deaths between groups of SM (those reporting as gay, lesbian, bisexual, or having same-sex sexual partners) status and AL. SM adults living with high AL (n = 326) had a 2-fold increased risk of cancer death (aHR: 2.55, 95% CI: 1.40-4.65) when compared to straight/heterosexual adults living with low AL (n = 6674). Among those living with high AL, SM (n = 326) had a 2-fold increased risk of cancer death (aHR: 2.26, 95% CI: 1.33-3.84) when compared to straight/heterosexual adults with high AL (n = 4957). SM with high AL have an increased risk of cancer mortality. These findings highlight important implications for promoting a focused agenda on cancer prevention with strategies that reduce chronic stress for SM adults.


Asunto(s)
Alostasis , Neoplasias , Minorías Sexuales y de Género , Femenino , Adulto , Humanos , Encuestas Nutricionales , Estudios Retrospectivos , Neoplasias/epidemiología
20.
J Hand Surg Am ; 2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37294238

RESUMEN

PURPOSE: Recent studies examining the implementation of clinic-based procedure rooms (PRs) for wide-awake hand surgery have reported cost reduction, decreased burden on hospital systems, and improved patient satisfaction. This study evaluates other resource savings, primarily time spent by patients in the hospital. METHODS: Thirty-two patients were enrolled in a PR or the operating room group for prospective evaluation. Time spent in the hospital on the day of surgery, several preprocedure appointments, complications, and cost comparisons were evaluated between the two groups. Patient-reported outcomes were also evaluated with postoperative surveys assessing anxiety, pain, and satisfaction. RESULTS: Significant time savings were noted between the groups. The median time spent in the hospital on the day of surgery for the patients in the operating room group was 256 minutes versus 90 minutes for the PR group, a time savings of approximately 3 hours. Eight additional preoperative clinic visits for operating room patients were generated compared with no additional preoperative visits for PR patients. Cost savings for surgeries performed in the clinic-based procedure amounted to $232,411. No postoperative complications were observed in the clinic setting. CONCLUSIONS: Continued utilization of the clinical PR for select hand surgery procedures will reduce the cost and time burdens for procedures while maintaining satisfaction and safety. CLINICAL RELEVANCE: A clinic-based PR for performing minor hand surgeries saves the patient time and ostensibly allows the operating room to be used for more complex surgeries that are not easily amenable to a wide-awake in-clinic procedure.

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