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1.
Heliyon ; 10(13): e33449, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39071562

RESUMEN

Climate change still adversely affects agriculture in the sub-Saharan Africa. There is need to strengthen early action to bolster livelihoods and food security. Most governments use pre- and post-harvest field surveys to capture statistics for National Food Balance Sheets (NFBS) key in food policy and economic planning. These surveys, though accurate, are costly, time consuming, and may not offer rapid yield estimates to support governments, emergency organizations, and related stakeholders to take advanced strategic decisions in the face of climate change. To help governments in Kenya (KEN), Zambia (ZMB), and Malawi (MWI) adopt digitally advanced maize yield forecasts, we developed a hybrid model based on the Regional Hydrologic Extremes Assessment System (RHEAS) and machine learning. The framework is set-up to use weather data (precipitation, temperature, and wind), simulations from RHEAS model (soil total moisture, soil temperature, solar radiation, surface temperature, net transpiration from vegetation, net evapotranspiration, and root zone soil moisture), simulations from DSSAT (leaf area index and water stress), and MODIS vegetation indices. Random Forest (RF) machine learning model emerged as the best hybrid setup for unit maize yield forecasts per administrative boundary scoring the lowest unbiased Root Mean Square Error (RMSE) of 0.16 MT/ha, 0.18 MT/ha, and 0.20 MT/ha in Malawi's Karonga district, Kenya's Homa Bay county, and Zambia's Senanga district respectively. According to relative RMSE, RF outperformed other hybrid models attaining the lowest score in all countries (ZMB: 25.96%, MWI: 28.97%, and KEN: 27.54%) followed by support vector machines (ZMB: 26.92%, MWI: 31.14%, and KEN: 29.50%), and linear regression (ZMB: 29.44%, MWI: 31.76%, and KEN: 47.00%). Lastly, the integration of VI and RHEAS information using hybrid models improved yield prediction. This information is useful for NFBS bulletins forecasts, design and certification of maize insurance contracts, and estimation of loss and damage in the advent of climate justice.

2.
J Adolesc Health ; 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39007788

RESUMEN

PURPOSE: To identify risk factors for relaxing a strict e-cigarette ban in households with adolescents. METHODS: Youth (ages 12-17) in the Population Assessment of Tobacco and Health (PATH) Study whose parents held a strict vaping ban in 2016 (n = 6,514; 51.5% male) and their parents provided follow-up data on up to four occasions through 2020 on whether the ban was relaxed. RESULTS: 13.5% of households with strict vaping bans relaxed them in a subsequent wave. Results from a logistic regression model showed that the odds of relaxing strict bans were higher if, at baseline, parents vaped (OR = 2.20; 95% CI: 1.22-3.97; p < .01), parents smoked tobacco (OR = 2.55; CI: 2.00-3.26; p < .001), youth smoked tobacco (OR = 2.27; CI: 1.29-4.00; p < .01), parents reported no smoking ban (OR = 2.68; CI: 1.88-3.81; p < .001), youth did not know that their household had a vaping ban (OR = 1.95; CI: 1.50-2.54; p < .001), and parents perceived low harm from vaping (OR = 1.60; CI: 1.16-2.19; p < .01). Although most sociodemographic controls were not independently associated, parents were less likely to relax bans if they had a college degree (OR = 0.71; CI: 0.51-0.998; p < .05), graduate degree (OR = 0.50; CI: 0.43-0.72; p < .001), or children who were non-Hispanic Black (OR = 0.69; CI: 0.49-0.96; p < .05) or Hispanic (OR = 0.62; CI: 0.47-0.81; p < .001). DISCUSSION: While most households with adolescents prohibited e-cigarette use indoors, nearly one in seven relaxed prior strict vaping bans. Parents need support to maintain clear, consistent, and continuous restrictions that communicate that vaping is not safe or permissible for youth.

3.
BMC Public Health ; 24(1): 1546, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849779

RESUMEN

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significantly costly and increasingly prevalent disease, with treatment focused on lifestyle intervention. Integrating education and behavioral health into clinical care offers opportunities to engage and empower patients to prevent progression of liver disease. We describe the design and implementation of Behavioral Resources and Intervention through Digital Group Education (BRIDGE), a 6-session group telehealth program led by advanced practice providers (APPs) in 90-min shared medical appointments (SMAs) with small groups of MASLD patients in an academic outpatient hepatology clinic. The program contains multi-component group interventions, with didactic education and behavioral coaching, while leveraging peer-based learning and support. METHODS: A mixed-methods exploratory pilot study was conducted. Feasibility and acceptability of the clinical intervention were assessed by tracking recruitment, attendance, and retention of BRIDGE participants, patient interviews, and debriefing of clinician and staff views of the clinical program. Implementation metrics included program development time, workflow and scheduling logistics, and billing compliance for sustainability. Finally, patient parameters including changes in liver enzymes, FIB-4, weight, and BMI from pre- to post-BRIDGE were retrospectively analyzed. RESULTS: We included 57 participants (median age 57, interquartile range (IQR) 50 - 65 years), 38 (67%) female, 38 (67%) white, and 40% had public insurance. Thirty-three (58%) participants completed all six sessions, while 43 (75%) attended at least five sessions. Patients who completed all sessions were older (median age 61 vs 53.5; p = 0.01). Gender, race/ethnicity, and insurance type were not significantly associated with missed sessions, and patients had similar rates of completion regardless of weight, BMI, or stage of liver disease. Barriers to completion included personal illness, family reasons, work commitments, or insurance issues. Prior to BRIDGE, median BMI was 31.9 (SD 29 - 36), with a median weight loss of 2 pounds (IQR -2 - 6) after BRIDGE. CONCLUSION: The BRIDGE telehealth SMA program was feasible, well-attended, and positively reviewed. This pilot study informs future iterations of program development and evaluation of outcome measures.


Asunto(s)
Educación del Paciente como Asunto , Citas Médicas Compartidas , Telemedicina , Humanos , Proyectos Piloto , Femenino , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Hígado Graso/terapia , Anciano , Estudios de Factibilidad , Adulto , Evaluación de Programas y Proyectos de Salud
4.
J Pers Med ; 14(6)2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38929862

RESUMEN

The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990's, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating the reversal of autism diagnoses, with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism symptoms among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD "requiring very substantial support" at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin's symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins' symptoms, which manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing modifiable environmental and lifestyle risk factors.

5.
J Clin Neurophysiol ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38857370

RESUMEN

PURPOSE: To identify and characterize events of deterioration in intraoperative neuromonitoring data during correction procedures for thoracic and lumbar abnormal spinal curvature in young patients. METHODS: Records of 1,127 cases were retrospectively reviewed to identify events with deterioration of the neuromonitoring data. General etiological and demographic variables were summarized, and neuromonitoring events were studied and characterized. RESULTS: Adolescent idiopathic cases were associated with female dominance and older age. Nonadolescent idiopathic cases were associated with a higher rate of neuromonitoring events. The neuromonitoring events evolved during the different procedural stages, were primarily reflected in the motor-evoked potential data and affected a range of neural structures to varying degrees. Most of the events were resolved, partially or completely, following a corresponding intervention by the surgical team, before the end of the procedure. Significant immediate weakness of the lower extremities was demonstrated in patients with unresolved neuromonitoring events, most of them were nonadolescent idiopathic patients. CONCLUSIONS: Neurophysiological monitoring enables the intraoperative assessment of the integrity of neural pathways and allows the detection of surgery-related impending neural injuries. Neuromonitoring contributes to intraoperative decision making, either when data are uneventful and allow confident continuation or when data deteriorate and lead to corresponding intervention. Further awareness should be paid to the vulnerable characteristics of the patient, surgery course, and neuromonitoring data. Proper interpretation of the neuromonitoring data, together with corresponding intervention by the surgeon when necessary, has the potential to reduce postoperative neurological insults and improve clinical outcomes.

6.
iScience ; 27(6): 109913, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38799557

RESUMEN

Here, we show that a NOT gated cell therapy (Tmod) can exploit antigens such as epidermal growth factor receptor (EGFR) and human leukocyte antigen-E (HLA-E) which are widely expressed on cancer cells. Noncancerous cells-despite high expression of these antigens-are protected from cytotoxicity by the action of an inhibitory receptor ("blocker") via a mechanism that involves blocker modulation of CAR surface expression. The blocker is triggered by the product of a polymorphic HLA allele (e.g., HLA-A∗02) deleted in a significant subset of solid tumors via loss of heterozygosity. Moreover, Tmod constructs that target mouse homologs of EGFR or HLA-E for activation, and a mouse-equivalent of HLA-A∗02 for inhibition, protect mice from toxicity caused by the CAR alone. The blocker also controls graft vs. host response in allogeneic T cells in vitro, consistent with the use of Tmod cells for off-the-shelf therapy without additional gene-editing.

7.
J Clin Oncol ; 42(21): 2599-2615, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38759122

RESUMEN

PURPOSE: To guide use of multigene panels for germline genetic testing for patients with cancer. METHODS: An ASCO Expert Panel convened to develop recommendations on the basis of a systematic review of guidelines, consensus statements, and studies of germline and somatic genetic testing. RESULTS: Fifty-two guidelines and consensus statements met eligibility criteria for the primary search; 14 studies were identified for Clinical Question 4. RECOMMENDATIONS: Patients should have a family history taken and recorded that includes details of cancers in first- and second-degree relatives and the patient's ethnicity. When more than one gene is relevant based on personal and/or family history, multigene panel testing should be offered. When considering what genes to include in the panel, the minimal panel should include the more strongly recommended genes from Table 1 and may include those less strongly recommended. A broader panel may be ordered when the potential benefits are clearly identified, and the potential harms from uncertain results should be mitigated. Patients who meet criteria for germline genetic testing should be offered germline testing regardless of results from tumor testing. Patients who would not normally be offered germline genetic testing based on personal and/or family history criteria but who have a pathogenic or likely pathogenic variant identified by tumor testing in a gene listed in Table 2 under the outlined circumstances should be offered germline testing.Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines.


Asunto(s)
Predisposición Genética a la Enfermedad , Pruebas Genéticas , Mutación de Línea Germinal , Neoplasias , Humanos , Pruebas Genéticas/normas , Pruebas Genéticas/métodos , Neoplasias/genética
8.
Fam Cancer ; 23(2): 141-145, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38748383

RESUMEN

The Precision Medicine Initiative was launched upon the potential of genomic information to tailor medical care. Cascade genetic testing represents a powerful application of precision medicine and involves the process of familial diffusion or the "cascade" of genomic risk information. When an individual (proband) is found to carry a cancer-associated germline pathogenic mutation, the information should be cascaded or shared with at-risk relatives. First degree relatives have a 50% likelihood of carrying the same cancer-associated mutation. This process of cascade testing offers at-risk relatives the opportunity for genetic testing and, for those who also carry the cancer-associated mutation, genetically targeted primary disease prevention through intensive cancer surveillance, chemoprevention and risk-reducing surgery, reducing morbidity and preventing mortality. Cascade testing has been designated by the Centers for Disease Control and Prevention as a Tier 1 genomic application for hereditary breast and ovarian cancer. In this manuscript we describe a cascade genetic testing and in particular focus on its potential to provide necessary care to medically underserved and vulnerable populations.


Asunto(s)
Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Femenino , Medicina de Precisión/métodos , Mutación de Línea Germinal , Asesoramiento Genético , Neoplasias/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & control , Neoplasias de la Mama/genética
9.
JCO Oncol Pract ; : OP2300817, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38815190

RESUMEN

PURPOSE: Patients with hereditary cancer syndromes face increased medical management recommendations to address their cancer risks. As multigene panels are the standard of testing today, more patients needing clinical intervention are being identified. This study calculates the downstream revenue (DSR) generated by patients ascertained by a genetic counselor (GC) with a hereditary cancer likely pathogenic/pathogenic variant (LPV/PV). METHODS: Retrospective chart review was performed for patients seen in a high-volume cancer genetics clinic between October 1, 2009, and December 31, 2021, with LPV/PVs in hereditary cancer predisposition genes. DSR and work relative value units (wRVUs) were calculated for each patient before and after they met with a GC. Subgroup analyses calculated DSR/wRVUs from patients affected and unaffected with cancer and those whose genetic counseling visit was the first at the institution (naїve). RESULTS: A total of 978 patients were available for analysis after exclusions were applied. Patients generated $73.06 million (M) in US dollars (USD) in DSR and 54,814 wRVUs after their initial genetic counseling visit. Unaffected patients (n = 370, 37.8%) generated $11.38M (USD) and 13,879 wRVUs; affected patients (n = 608, 62.2%) generated $61.68M (USD) and 40,935 wRVUs. Naïve patients (n = 367, 37.5%) generated $15.39M (USD) and 11,811 wRVUs; established patients (n = 611, 62.5%) generated $57.67M (USD) and 43,003 wRVUs. Unaffected, naïve patients (n = 204, 20.9%) generated $5.48M (USD) and 5,186 wRVUs. CONCLUSION: By identifying patients with hereditary cancer, GCs can bring in substantial DSR for their institution. Naïve and unaffected patients provide the greatest GC value-add as these patients represent new business and revenue sources to the institution. As multigene panels continue to expand, the number of patients needing downstream services will increase. Recognizing patients at increased cancer risk will improve patient outcomes while simultaneously providing DSR for institutions.

11.
J Clin Invest ; 134(5)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38227370

RESUMEN

Two coding variants of apolipoprotein L1 (APOL1), called G1 and G2, explain much of the excess risk of kidney disease in African Americans. While various cytotoxic phenotypes have been reported in experimental models, the proximal mechanism by which G1 and G2 cause kidney disease is poorly understood. Here, we leveraged 3 experimental models and a recently reported small molecule blocker of APOL1 protein, VX-147, to identify the upstream mechanism of G1-induced cytotoxicity. In HEK293 cells, we demonstrated that G1-mediated Na+ import/K+ efflux triggered activation of GPCR/IP3-mediated calcium release from the ER, impaired mitochondrial ATP production, and impaired translation, which were all reversed by VX-147. In human urine-derived podocyte-like epithelial cells (HUPECs), we demonstrated that G1 caused cytotoxicity that was again reversible by VX-147. Finally, in podocytes isolated from APOL1 G1 transgenic mice, we showed that IFN-γ-mediated induction of G1 caused K+ efflux, activation of GPCR/IP3 signaling, and inhibition of translation, podocyte injury, and proteinuria, all reversed by VX-147. Together, these results establish APOL1-mediated Na+/K+ transport as the proximal driver of APOL1-mediated kidney disease.


Asunto(s)
Apolipoproteína L1 , Enfermedades Renales , Compuestos Organotiofosforados , Ratones , Animales , Humanos , Apolipoproteína L1/genética , Células HEK293 , Variación Genética , Enfermedades Renales/genética , Ratones Transgénicos
12.
Prehosp Emerg Care ; 28(3): 515-530, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37477998

RESUMEN

OBJECTIVE: We sought to describe prehospital ultrasound (PHUS) use and trends in PHUS utilization over time using a national database. METHODS: Using the 2018 - 2021 National Emergency Medical Services Information System databases, we identified those EMS activations where PHUS was performed. We evaluated the association between year and number of PHUS exams performed using univariable and multivariable regression analysis. Analysis was performed on the overall group and various subgroups. RESULTS: In total, there were 148,709,000 EMS activations by 13,899 agencies over the 4 years. Of these, 3,291 unique activations (0.002%) involved PHUS, performed by 71 EMS agencies (0.5%). The annual rate of ultrasound evaluations per 1 million EMS activations significantly increased over the study period: 5.2 in 2018, 14.8 in 2019, 18.6 in 2020, and 38.9 in 2021 (p < 0.01). The number of agencies performing PHUS each year increased over the study period from 11 in 2018 to 54 in 2021 (p < 0.05). Each year after 2018 had an increased odds of PHUS use demonstrated with logistic regression (p < 0.01). PHUS was used in each US census region, and paramedics performed most of the PHUS exams (75.5%). We identified 1,060 out-of-hospital cardiac arrest, 820 trauma, and 427 respiratory PHUS cases. These three cohorts accounted for 70.1% of all PHUS cases. CONCLUSION: Prehospital ultrasound use in the United States increased significantly over the study period, but remains exceedingly rare. The performance of PHUS was recorded throughout the United States, with paramedics performing the majority of PHUS studies included in this database.


Asunto(s)
Servicios Médicos de Urgencia , Humanos , Estados Unidos/epidemiología , Incidencia , Ultrasonografía , Bases de Datos Factuales , Modelos Logísticos
13.
J Natl Cancer Inst ; 116(2): 334-337, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-37756683

RESUMEN

Current guidelines recommend single variant testing in relatives of patients with known pathogenic or likely pathogenic germline variants in cancer predisposition genes. This approach may preclude the use of risk-reducing strategies in family members who have pathogenic or likely pathogenic germline variants in other cancer predisposition genes. Cascade testing using multigene panels was performed in 3696 relatives of 7433 probands. Unexpected pathogenic or likely pathogenic germline variants were identified in 230 (6.2%) relatives, including 144 who were negative for the familial pathogenic or likely pathogenic variant but positive for a pathogenic or likely pathogenic variant in a different gene than the proband and 74 who tested positive for the familial pathogenic or likely pathogenic variant and had an additional pathogenic or likely pathogenic variant in a different gene than the proband. Of the relatives with unexpected pathogenic or likely pathogenic germline variants, 36.3% would have qualified for different or additional cancer screening recommendations. Limiting cascade testing to only the familial pathogenic or likely pathogenic variant would have resulted in missed, actionable findings for a subset of relatives.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/genética , Pruebas Genéticas/métodos , Mutación de Línea Germinal
14.
Food Chem ; 439: 138056, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38035492

RESUMEN

The effect of sheep milk and cow milk on the lipid composition of rat brain was investigated in two feeding experiments of 28-days duration. Total lipids of the rat brain were extracted using ethanol-hexane, and the fatty acids and phospholipid contents analysed using gas chromatography with flame ionization detection (GC-FID) and phosphorus-31 nuclear magnetic resonance (31P NMR). Furthermore, freeze-dried pooled samples were analysed using attenuated total reflectance Fourier Transform Infrared and Fourier Transform Raman Spectroscopy and analysed with multivariate methods. A significantly (P < 0.05) higher C18:2 content was found in the cow milk group compared with sheep milk-treated groups in Study one. In Study two, a significantly (P < 0.05) lower C16:0 content was present in the sheep milk-treated group compared to the control low Ca/P group. No significant (P > 0.05) differences were observed in the spectroscopy analyses. It is concluded that sheep and cow milks fed to rats for 28-days had a low effect on the brain lipidome.


Asunto(s)
Ácidos Grasos , Leche , Bovinos , Femenino , Ratas , Animales , Ovinos , Leche/química , Ácidos Grasos/análisis , Fosfolípidos/análisis , Espectroscopía Infrarroja por Transformada de Fourier , Cromatografía de Gases
15.
Curr Biol ; 33(24): 5478-5487.e5, 2023 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-38065097

RESUMEN

The ability to recognize others is a frequent assumption of models of the evolution of cooperation. At the same time, cooperative behavior has been proposed as a selective agent favoring the evolution of individual recognition abilities. Although theory predicts that recognition and cooperation may co-evolve, data linking recognition abilities and cooperative behavior with evidence of selection are elusive. Here, we provide evidence of a selective link between individual recognition and cooperation in the paper wasp Polistes fuscatus through a combination of clinal, common garden, and population genomics analyses. We identified latitudinal clines in both rates of cooperative nesting and color pattern diversity, consistent with a selective link between recognition and cooperation. In behavioral experiments, we replicated previous results demonstrating individual recognition in cooperative and phenotypically diverse P. fuscatus from New York. In contrast, wasps from a less cooperative and phenotypically uniform Louisiana population showed no evidence of individual recognition. In a common garden experiment, groups of wasps from northern populations formed more stable and individually biased associations, indicating that recognition facilitates group stability. The strength of recent positive selection on cognition-associated loci likely to mediate individual recognition is substantially greater in northern compared with southern P. fuscatus populations. Collectively, these data suggest that individual recognition and cooperative nesting behavior have co-evolved in P. fuscatus because recognition helps stabilize social groups. This work provides evidence of a specific cognitive phenotype under selection because of social interactions, supporting the idea that social behavior can be a key driver of cognitive evolution.


Asunto(s)
Reconocimiento en Psicología , Avispas , Animales , Cognición , Conducta Social , Fenotipo , Conducta Cooperativa , Avispas/genética , Evolución Biológica
16.
Microbiol Spectr ; 11(6): e0302923, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37975661

RESUMEN

IMPORTANCE: Even though the coronavirus disease 2019 (COVID-19) pandemic is slowly developing into a conventional infectious disease, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection are still not well understood. One of the problems is that many COVID-19 cases develop acute kidney injuries. Still, it is heavily debated whether SARS-CoV-2 virus enters and actively replicates in kidney tissue and if SARS-CoV-2 virus particles can be detected in kidney during or post-infection. Here, we demonstrated that nucleocapsid N protein was detected in kidney tubular epithelium of patients that already recovered form COVID-19. The presence of the abundantly produced N protein without signs of viral replication could have implications for the recurrence of kidney disease and have a continuing effect on the immune system.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Proteínas de la Nucleocápside , Replicación Viral , Epitelio
17.
Sci Adv ; 9(46): eadi8716, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37976362

RESUMEN

Recent studies have identified increasing levels of nanoplastic pollution in the environment. Here, we find that anionic nanoplastic contaminants potently precipitate the formation and propagation of α-synuclein protein fibrils through a high-affinity interaction with the amphipathic and non-amyloid component (NAC) domains in α-synuclein. Nanoplastics can internalize in neurons through clathrin-dependent endocytosis, causing a mild lysosomal impairment that slows the degradation of aggregated α-synuclein. In mice, nanoplastics combine with α-synuclein fibrils to exacerbate the spread of α-synuclein pathology across interconnected vulnerable brain regions, including the strong induction of α-synuclein inclusions in dopaminergic neurons in the substantia nigra. These results highlight a potential link for further exploration between nanoplastic pollution and α-synuclein aggregation associated with Parkinson's disease and related dementias.


Asunto(s)
Enfermedad de Parkinson , alfa-Sinucleína , Ratones , Animales , alfa-Sinucleína/metabolismo , Enfermedad de Parkinson/metabolismo , Microplásticos , Cuerpos de Inclusión/metabolismo , Neuronas Dopaminérgicas/metabolismo
18.
J Bone Miner Res ; 38(12): 1846-1855, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37877440

RESUMEN

Postnatally, severe vitamin D deficiency commonly results in rickets as well as potential defects in tooth mineralization. The effects of milder deficiency on oral health outcomes later in life are still unclear. This study used micro-computed tomography (µCT), energy dispersive X-ray analysis (EDX), and Raman spectroscopy to investigate mineral density, total density, and elemental composition of enamel and dentine in 63 exfoliated primary incisors from participants with known 25-hydroxyvitamin D levels (25-OHD) at birth. No differences in mineralization and chemical composition using µCT and EDX analysis were observed irrespective of 25-OHD status. Subtle structural differences were observed via Raman spectroscopy, with more crystalline enamel observed in those with sufficient 25-OHD at birth. Although subtle, the differences seen suggest further attention should be given to children with known milder levels of vitamin D deficiency in early life. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Asunto(s)
Deficiencia de Vitamina D , Vitamina D , Niño , Recién Nacido , Humanos , Microtomografía por Rayos X , Minerales , Diente Primario , Densidad Ósea
19.
Res Sq ; 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37886561

RESUMEN

Recent studies have identified increasing levels of nanoplastic pollution in the environment. Here we find that anionic nanoplastic contaminants potently precipitate the formation and propagation of α-synuclein protein fibrils through a high-affinity interaction with the amphipathic and non-amyloid component (NAC) domains in α-synuclein. Nanoplastics can internalize in neurons through clathrin-dependent endocytosis, causing a mild lysosomal impairment that slows the degradation of aggregated α-synuclein. In mice, nanoplastics combine with α-synuclein fibrils to exacerbate the spread of α-synuclein pathology across interconnected vulnerable brain regions, including the strong induction of α-synuclein inclusions in dopaminergic neurons in the substantia nigra. These results highlight a potential link for further exploration between nanoplastic pollution and α-synuclein aggregation associated with Parkinson's disease and related dementias.

20.
JCO Oncol Pract ; 19(11): 1069-1079, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37733980

RESUMEN

PURPOSE: Germline genetic testing (GT) is recommended for men with prostate cancer (PC), but testing through traditional models is limited. The ProGen study examined a novel model aimed at providing access to GT while promoting education and informed consent. METHODS: Men with potentially lethal PC (metastatic, localized with a Gleason score of ≥8, persistent prostate-specific antigen after local therapy), diagnosis age ≤55 years, previous malignancy, and family history suggestive of a pathogenic variant (PV) and/or at oncologist's discretion were randomly assigned 3:1 to video education (VE) or in-person genetic counseling (GC). Participants had 67 genes analyzed (Ambry), with results disclosed via telephone by a genetic counselor. Outcomes included GT consent, GT completion, PV prevalence, and survey measures of satisfaction, psychological impact, genetics knowledge, and family communication. Two-sided Fisher's exact tests were used for between-arm comparisons. RESULTS: Over a 2-year period, 662 participants at three sites were randomly assigned and pretest VE (n = 498) or GC (n = 164) was completed by 604 participants (VE, 93.1%; GC, 88.8%), of whom 596 participants (VE, 98.9%; GC, 97.9%) consented to GT and 591 participants completed GT (VE, 99.3%; GC, 98.6%). These differences were not statistically significant although subtle differences in satisfaction and psychological impact were. Notably, 84 PVs were identified in 78 participants (13.2%), with BRCA1/2 PV comprising 32% of participants with a positive result (BRCA2 n = 21, BRCA1 n = 4). CONCLUSION: Both VE and traditional GC yielded high GT uptake without significant differences in outcome measures of completion, GT uptake, genetics knowledge, and family communication. The increased demand for GT with limited genetics resources supports consideration of pretest VE for patients with PC.


Asunto(s)
Asesoramiento Genético , Neoplasias de la Próstata , Humanos , Masculino , Persona de Mediana Edad , Proteína BRCA1/genética , Proteína BRCA2/genética , Estrógenos Conjugados (USP) , Asesoramiento Genético/métodos , Asesoramiento Genético/psicología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia
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