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1.
JCO Precis Oncol ; 8: e2400167, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39102633

RESUMEN

PURPOSE: Approximately 5%-10% of patients with pancreatic ductal adenocarcinoma (PDAC) have an inherited basis, yet uptake of genetic testing remains low and subject to disparities. This study compared two genetic testing pathways available to patients referred to a provincial cancer center, BC Cancer: a traditional hereditary cancer clinic-initiated testing (HCT) pathway and a new oncology clinic-initiated testing (OCT) pathway. METHODS: Study subjects were patients with confirmed PDAC referred for genetic testing through the HCT or OCT pathway between June 1, 2020, and February 1, 2022. Charts were retrospectively reviewed for patient characteristics and testing outcomes. RESULTS: The study population was 397 patients (HCT, n = 279 and OCT, n = 118). OCT patients were more likely to have non-European ethnicity compared with HCT patients (41.9% v 25.6%, P = .004), to have earlier-stage disease (P = .012), and to have better Eastern Cooperative Oncology Group performance status than the HCT group (P = .001). A total of 306 patients completed testing (77%). OCT patients had higher test completion rates than HCT patients (odds ratio, 3.74 [95% CI, 1.66 to 9.62]). Median time for results was shorter in OCT than in HCT (53 days [IQR, 44-76] v 107 days [IQR, 63.8-158.3]). Pancreatic cancer susceptibility pathogenic gene variants were identified in 8.5% (26/306). CONCLUSION: The real-world observations in our study show that oncology clinic-initiated hereditary testing is more effective and faster than testing through hereditary cancer clinic referrals and reaches a more ethnically diverse population. This has important implications for publicly funded environments with limited resources for genetic counseling.


Asunto(s)
Carcinoma Ductal Pancreático , Pruebas Genéticas , Accesibilidad a los Servicios de Salud , Neoplasias Pancreáticas , Humanos , Femenino , Masculino , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/diagnóstico , Pruebas Genéticas/métodos , Pruebas Genéticas/estadística & datos numéricos , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Estudios Retrospectivos , Anciano , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Adulto
2.
Virol J ; 21(1): 153, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38972989

RESUMEN

Wild waterfowl serve as a reservoir of some astroviruses. Fecal samples from wild waterfowl collected at Hong Kong's Marshes were tested using pan-astrovirus reverse transcription-PCR. Positive samples underwent subsequent host identification using DNA barcoding. Based on deduced partial sequences, noteworthy samples from three astrovirus groups (mammalian, avian and unclassified astroviruses) were further analyzed by next-generation sequencing. One sample of Avastrovirus 4 clade, MP22-196, had a nearly complete genome identified. The results of ORF2 phylogenetic analysis and genetic distance analysis indicate that Avastrovirus 4 is classified as a distinct subclade within Avastrovirus. MP22-196 has typical astrovirus genome characteristics. The unique characteristics and potential differences of this genome, compared to other avian astrovirus sequences, involve the identification of a modified sgRNA sequence situated near the ORF2 start codon, which precedes the ORF1b stop codon. Additionally, the 3' UTR of MP22-196 is shorter than other avian astroviruses. This study expands our understanding of the Avastrovirus 4 clade.


Asunto(s)
Infecciones por Astroviridae , Aves , Heces , Variación Genética , Genoma Viral , Filogenia , Animales , Hong Kong , Aves/virología , Heces/virología , Infecciones por Astroviridae/veterinaria , Infecciones por Astroviridae/virología , Animales Salvajes/virología , Enfermedades de las Aves/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Avastrovirus/genética , Avastrovirus/clasificación , Avastrovirus/aislamiento & purificación , ARN Viral/genética , Sistemas de Lectura Abierta , Astroviridae/genética , Astroviridae/aislamiento & purificación , Astroviridae/clasificación
3.
J Am Med Dir Assoc ; : 105174, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39084598

RESUMEN

OBJECTIVE: To examine if the quality of care in Appalachian nursing homes in metropolitan, micropolitan, and rural areas differs from those in non-Appalachian regions of the United States. DESIGN: Retrospective analysis of Medicare Cost Reports, combined with data from Nursing Home Compare, LTCFocus, and Medicare, Post-Acute Care, and Hospice Public Use Form. Nursing homes were classified using Rural-Urban Commuting Area Codes. SETTING AND PARTICIPANTS: Data from 14,040 nursing homes reporting on staffing, costs, and quality of care metrics from 2013 to 2019 were analyzed. METHODS: Descriptive analyses compared resident and facility characteristics, quality, staffing, and cost outcomes between non-Appalachian and Appalachian nursing homes in metropolitan, micropolitan, and rural areas. Regressions compared quality, staffing, and cost outcomes among (1) Appalachian metropolitan and non-Appalachian nursing homes, (2) Appalachian micropolitan and non-Appalachian nursing homes, and (3) Appalachian rural and non-Appalachian nursing homes. Outcomes included health deficiency index scores, Medicare spending per beneficiary, staffing hours per resident day (registered nurse, licensed practical nurse, certified nursing assistant per resident day), and 5 Minimum Data Set metrics for short-stay and long-stay residents. RESULTS: Appalachian nursing homes are more likely to be hospital-based, for-profit, multifacility chain affiliated, and have higher proportions of White and Medicaid residents. Regression analyses revealed that Appalachian metropolitan nursing homes have 3.3% fewer certified nursing assistant hours per resident day, a 16.5% higher health deficiency score index, and 4.2% higher Medicare spending per beneficiary compared with non-Appalachian homes. Appalachian micropolitan nursing homes showed 7.4% fewer registered nurse hours per resident day and 6.9% higher Medicare spending per beneficiary. Appalachian rural nursing homes had 16.7% more registered nurse hours per resident day, 22.7% lower health deficiency index scores, and 10.7% higher Medicare spending per beneficiary. Minimum Data Set measures varied, with Appalachian nursing homes performing better on some metrics and worse on others. CONCLUSIONS AND IMPLICATIONS: Appalachia lags behind in staffing and Medicare spending per beneficiary. These disparities should be considered by policymakers advocating for Appalachia's senior citizens.

5.
Nat Commun ; 15(1): 5080, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871724

RESUMEN

The reconstruction of Cu catalysts during electrochemical reduction of CO2 is a widely known but poorly understood phenomenon. Herein, we examine the structural evolution of Cu nanocubes under CO2 reduction reaction and its relevant reaction conditions using identical location transmission electron microscopy, cyclic voltammetry, in situ X-ray absorption fine structure spectroscopy and ab initio molecular dynamics simulation. Our results suggest that Cu catalysts reconstruct via a hitherto unexplored yet critical pathway - alkali cation-induced cathodic corrosion, when the electrode potential is more negative than an onset value (e.g., -0.4 VRHE when using 0.1 M KHCO3). Having alkali cations in the electrolyte is critical for such a process. Consequently, Cu catalysts will inevitably undergo surface reconstructions during a typical process of CO2 reduction reaction, resulting in dynamic catalyst morphologies. While having these reconstructions does not necessarily preclude stable electrocatalytic reactions, they will indeed prohibit long-term selectivity and activity enhancement by controlling the morphology of Cu pre-catalysts. Alternatively, by operating Cu catalysts at less negative potentials in the CO electrochemical reduction, we show that Cu nanocubes can provide a much more stable selectivity advantage over spherical Cu nanoparticles.

7.
BMJ Mil Health ; 170(3): 212-215, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38777366

RESUMEN

OBJECTIVE: The selection process to the British Army's Brigade of Gurkhas is rigorous, demanding and competitive. The ethos of recruitment to the Gurkhas is grounded in an overarching tenant: that selection is free, fair and transparent. The aim of this study was to retrospectively review reasons for potential recruits (PRs) to be deemed medically unsuitable or deferred suitability on medical grounds for selection to the Brigade of Gurkhas. METHODS: A retrospective review was conducted by extracted data from published post-exercise reports for the past four years to ascertain numbers of PRs deemed medically fit, medically unsuitable or deferred suitability on medical grounds. The International Classification of Disease version 11 (ICD-11) codes were retrospectively assigned to code medical reasons for non-progression. Rates of medical non-progression were compared by year. RESULTS: A total of 3154 PRs were analysed between 2018 and 2021. There was no significant difference between PRs deemed medically fit and those deemed medically suitable or deferred on medical grounds over the study period (p=0.351). There was a significant difference in the ratio of PRs deferred on medical grounds and those deemed medically unsuitable over the study period (p<0.05). CONCLUSION: Selection to the Gurkhas is extremely competitive. These data demonstrate that, overall, reasons for medical deferral or unsuitability have remained constant despite the impact of a global pandemic. These data reinforce the central tenant of Gurkha selection; that it continues to be free, fair, and transparent.


Asunto(s)
Personal Militar , Humanos , Estudios Retrospectivos , Personal Militar/estadística & datos numéricos , Masculino , Estudios de Cohortes , Reino Unido , Selección de Personal/métodos , Selección de Personal/estadística & datos numéricos , Salud Laboral/estadística & datos numéricos , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Femenino , India/epidemiología , Adulto
8.
J Med Genet ; 61(8): 788-793, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38806232

RESUMEN

BACKGROUND: Variant classification in the setting of germline genetic testing is necessary for patients and their families to receive proper care. Variants are classified as pathogenic (P), likely pathogenic (LP), uncertain significance (VUS), likely benign (LB) and benign (B) using the standards and guidelines recommended by the American College of Medical Genetics and the Association for Molecular Pathology, with modifications for specific genes. As the literature continues to rapidly expand, and evidence continues to accumulate, prior classifications can be updated accordingly. In this study, we aim to characterise variant reclassifications in Ontario. METHODS: DNA samples from patients seen at hereditary cancer clinics in Ontario from January 2012 to April 2022 were submitted for testing. Patients met provincial eligibility criteria for testing for hereditary cancer syndromes or polycystic kidney disease. Reclassification events were determined to be within their broader category of significance (B to LB or vice versa, or P to LP or vice versa) or outside of their broader category as significance (ie, significant reclassifications from B/LB or VUS or P/LP, from P/LP to VUS or B/LB, or from VUS to any other category). RESULTS: Of the 8075 unique variants included in this study, 23.7% (1912) of variants were reassessed, and 7.2% (578) of variants were reclassified. Of these, 351 (60.7%) variants were reclassified outside of their broader category of significance. Overall, the final classification was significantly different for 336 (58.1%) variants. Importantly, most reclassified variants were downgraded to a more benign classification (n=245; 72.9%). Of note, most reclassified VUS was downgraded to B/LB (n=233; 84.7%). CONCLUSIONS: The likelihood for reclassification of variants on reassessment is high. Most reclassified variants were downgraded to a more benign classification. Our findings highlight the importance of periodic variant reassessment to ensure timely and appropriate care for patients and their families.


Asunto(s)
Pruebas Genéticas , Variación Genética , Humanos , Pruebas Genéticas/métodos , Ontario/epidemiología , Mutación de Línea Germinal/genética , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/clasificación , Femenino , Laboratorios Clínicos , Técnicas de Diagnóstico Molecular/métodos
9.
Aging Cell ; 23(7): e14164, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38637937

RESUMEN

Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. Ninety-eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24-86 years). We used nonlinear and penalized regression to model CA and time to all-cause mortality. We examined associations of four new and two previously published metabolomic age models, with aging risk factors and phenotypes. Within the UK Biobank (N ≈102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type-2 diabetes mellitus, cancer, dementia, and chronic obstructive pulmonary disease), and all-cause mortality. Seven-fold cross-validated Pearson's r between metabolomic age models and CA ranged between 0.47 and 0.65 in the training cohort set (mean absolute error: 8-9 years). Metabolomic age models, adjusted for CA, were associated with C-reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with CA were modest (r = 0.29-0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06/metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability.


Asunto(s)
Envejecimiento , Espectroscopía de Resonancia Magnética , Metabolómica , Humanos , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Metabolómica/métodos , Masculino , Femenino , Espectroscopía de Resonancia Magnética/métodos , Longevidad , Estudios de Cohortes , Adulto Joven , Factores de Riesgo , Finlandia/epidemiología
10.
BMC Health Serv Res ; 24(1): 512, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38659030

RESUMEN

BACKGROUND: It is known that many surgeons encounter intraoperative adverse events which can result in Second Victim Syndrome (SVS), with significant detriment to their emotional and physical health. There is, however, a paucity of Asian studies in this space. The present study thus aimed to explore the degree to which the experience of an adverse event is common among surgeons in Singapore, as well as its impact, and factors affecting their responses and perceived support systems. METHODS: A self-administered survey was sent to surgeons at four large tertiary hospitals. The 42-item questionnaire used a systematic closed and open approach, to assess: Personal experience with intraoperative adverse events, emotional, psychological and physical impact of these events and perceived support systems. RESULTS: The response rate was 57.5% (n = 196). Most respondents were male (54.8%), between 35 and 44 years old, and holding the senior consultant position. In the past 12 months alone, 68.9% recalled an adverse event. The emotional impact was significant, including sadness (63.1%), guilt (53.1%) and anxiety (45.4%). Speaking to colleagues was the most helpful support source (66.7%) and almost all surgeons did not receive counselling (93.3%), with the majority deeming it unnecessary (72.2%). Notably, 68.1% of the surgeons had positive takeaways, gaining new insight and improving vigilance towards errors. Both gender and surgeon experience did not affect the likelihood of errors and emotional impact, but more experienced surgeons were less likely to have positive takeaways (p = 0.035). Individuals may become advocates for patient safety, while simultaneously championing the cause of psychological support for others. CONCLUSIONS: Intraoperative adverse events are prevalent and its emotional impact is significant, regardless of the surgeon's experience or gender. While colleagues and peer discussions are a pillar of support, healthcare institutions should do more to address the impact and ensuing consequences.


Asunto(s)
Complicaciones Intraoperatorias , Cirujanos , Humanos , Singapur , Estudios Transversales , Masculino , Femenino , Adulto , Cirujanos/psicología , Cirujanos/estadística & datos numéricos , Encuestas y Cuestionarios , Complicaciones Intraoperatorias/epidemiología , Persona de Mediana Edad , Errores Médicos/estadística & datos numéricos , Errores Médicos/psicología , Emociones , Apoyo Social
11.
J Clin Endocrinol Metab ; 109(8): e1642-e1651, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38477463

RESUMEN

CONTEXT: Diabetes mellitus is associated with morbid complications such as diabetic foot ulcers (DFUs) that may lead to amputations or mortality if not managed adequately. OBJECTIVE: New adjunctive interventions to treat diabetic wounds include topical biologics and growth factors. This study aims to evaluate their efficacy in improving wound-healing outcomes and safety. METHODS: Comprehensive database searches of MEDLINE via PubMed, EMBASE, and Cochrane were performed from inception to December 2022. Three independent researchers selected the studies. Randomized controlled trials that compared the use of a topical biologic growth factor-containing regimen to other biologics or standard of care (SOC) were included. This review followed PRISMA guidelines. Risk of bias analysis was performed using the Jadad scale. Network meta-analysis was performed. Treatments were grouped into common nodes based on the type of biologic agent. Primary outcomes of interest were healing rate and time to wound closure. Secondary outcomes included wound infection, serious adverse events (AEs), and amputation rate. RESULTS: Human umbilical cord (HUC) was associated with the highest cure, followed by recombinant human epidermal growth factor (hEGF). A significantly greater reduction in the time to cure DFUs was seen in HUC, hEGF, and fibroblast growth factor (FGF). There was a significantly lower risk of AEs when platelet-rich plasma (PRP) was administered. CONCLUSION: HUC, hEGF, and FGF are promising topical biologics with statistically significant primary outcomes compared to SOC, while PRP is effective in reducing ulcer-related AEs. HUC has been found to be the most effective in terms of cure rate and a reduction in time to cure.


Asunto(s)
Administración Tópica , Pie Diabético , Péptidos y Proteínas de Señalización Intercelular , Cicatrización de Heridas , Humanos , Cicatrización de Heridas/efectos de los fármacos , Pie Diabético/tratamiento farmacológico , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Péptidos y Proteínas de Señalización Intercelular/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Factor de Crecimiento Epidérmico/administración & dosificación , Factor de Crecimiento Epidérmico/uso terapéutico
12.
Hum Vaccin Immunother ; 20(1): 2317446, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38436584

RESUMEN

Herpes zoster (HZ) is a prevalent disease characterized by a painful rash. A multi­country study was conducted to elicit public and physician knowledge, attitude, and practice (KAP) toward HZ disease and vaccination for the assessment of local factors influencing HZ vaccine perceptions in four Asian-Pacific countries/territories One-to-one qualitative interviews were conducted in 2022, among the public (people aged ≥ 50 years, adults with parents aged ≥ 50 years, zoster vaccine live-vaccinated individuals aged ≥ 50 years in Republic of Korea, and HZ patients; n = 78) and physicians (general practitioners and specialists; n = 24). Themes surrounding KAP toward HZ and HZ vaccination were summarized using a thematic analysis. A substantial knowledge gap related to HZ was observed among the public, including its causes, long-term impacts, and the at-risk population. There was a low perceived risk of HZ and low general awareness of HZ vaccine availability, although country/territory-specific differences existed. Fear of HZ-associated pain contributed toward vaccination intent among HZ patients and adults with parents aged ≥ 50 years. HZ-naïve adults who were encouraged to receive the vaccine by others were not motivated to do so due to optimism bias. Physicians were perceived to be a reliable source of information. However, physicians did not always proactively discuss HZ vaccination due to time constraints and a perceived need to prioritize other vaccinations including influenza and pneumococcal vaccines. Initiatives are needed to improve public awareness of HZ and its complications, in terms of overall impact on individuals and society, and highlight the important role of physicians in recommending vaccination.


Asunto(s)
Médicos Generales , Vacuna contra el Herpes Zóster , Herpes Zóster , Adulto , Humanos , Conocimientos, Actitudes y Práctica en Salud , Herpes Zóster/epidemiología , Herpes Zóster/prevención & control , Vacunación , Asia/epidemiología , Dolor
14.
Cancer Res ; 84(11): 1898-1914, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38503267

RESUMEN

Tobacco use is a major modifiable risk factor for adverse health outcomes, including cancer, and elicits profound epigenetic changes thought to be associated with long-term cancer risk. While electronic cigarettes (e-cigarettes) have been advocated as harm reduction alternatives to tobacco products, recent studies have revealed potential detrimental effects, highlighting the urgent need for further research into the molecular and health impacts of e-cigarettes. Here, we applied computational deconvolution methods to dissect the cell- and tissue-specific epigenetic effects of tobacco or e-cigarette use on DNA methylation (DNAme) in over 3,500 buccal/saliva, cervical, or blood samples, spanning epithelial and immune cells at directly and indirectly exposed sites. The 535 identified smoking-related DNAme loci [cytosine-phosphate-guanine sites (CpG)] clustered into four functional groups, including detoxification or growth signaling, based on cell type and anatomic site. Loci hypermethylated in buccal epithelial cells of smokers associated with NOTCH1/RUNX3/growth factor receptor signaling also exhibited elevated methylation in cancer tissue and progressing lung carcinoma in situ lesions, and hypermethylation of these sites predicted lung cancer development in buccal samples collected from smokers up to 22 years prior to diagnosis, suggesting a potential role in driving carcinogenesis. Alarmingly, these CpGs were also hypermethylated in e-cigarette users with a limited smoking history. This study sheds light on the cell type-specific changes to the epigenetic landscape induced by smoking-related products. SIGNIFICANCE: The use of both cigarettes and e-cigarettes elicits cell- and exposure-specific epigenetic effects that are predictive of carcinogenesis, suggesting caution when broadly recommending e-cigarettes as aids for smoking cessation.


Asunto(s)
Carcinogénesis , Fumar Cigarrillos , Metilación de ADN , Sistemas Electrónicos de Liberación de Nicotina , Epigénesis Genética , Humanos , Fumar Cigarrillos/efectos adversos , Fumar Cigarrillos/genética , Carcinogénesis/genética , Femenino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/patología , Vapeo/efectos adversos , Masculino , Receptor Notch1/genética , Adulto
15.
World Neurosurg ; 185: 224, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38401755

RESUMEN

Cystic craniopharyngiomas of the third ventricle can be challenging to treat because complete resection of the cyst wall can be associated with hypothalamic dysfunction and minimal rostral displacement of the optic chiasm leads to a small endonasal operative corridor. Various methods to overcome the frequent recurrences have been described, such as intracystic bleomycin or catheter placement, with mixed results.1-12 In Video 1, we describe a simple cystocisternal fenestration technique with preservation of the rostral cyst wall via an endoscopic endonasal approach where the solid portion of the tumor is resected, and the inferior wall of the cyst is opened into the prepontine cistern and the superior wall of the cyst and adjacent third ventricle are preserved. This allows for ventricular pressure to collapse the cyst cavity in the postoperative period. In select patients where safe complete resection of a cystic craniopharyngioma is prohibitive, this may provide a durable treatment and can be performed through a small endonasal corridor below a nondisplaced optic chiasm.


Asunto(s)
Craneofaringioma , Neuroendoscopía , Neoplasias Hipofisarias , Tercer Ventrículo , Humanos , Craneofaringioma/cirugía , Craneofaringioma/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/diagnóstico por imagen , Tercer Ventrículo/cirugía , Neuroendoscopía/métodos , Neoplasias del Ventrículo Cerebral/cirugía , Neoplasias del Ventrículo Cerebral/diagnóstico por imagen , Seno Esfenoidal/cirugía , Masculino
16.
Prenat Diagn ; 44(4): 443-453, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38279846

RESUMEN

OBJECTIVE: Chromosomal microarray (CMA), while considered the gold standard for detecting copy number variants (CNVs) in prenatal diagnostics, has its limitations, including the necessity to replace aging microarray equipment, low throughput, a static design, and an inefficient multi-day workflow. This study evaluates the feasibility of low-pass genome sequencing (LP-GS) as a potential replacement for CMA in prenatal diagnostics. METHODS: We comprehensively compared LP-GS at 10x and 5x average depths with CMA in a prenatal laboratory. We examined parameters, including concordance, sensitivity, specificity, workflow efficiency, and cost-effectiveness. RESULTS: We found a high degree of agreement between LP-GS and CMA for detecting CNVs and absence of heterozygosity. Furthermore, compared to CMA, LP-GS increased workflow efficiency and proved to be cost-neutral at 10x and cost-effective at 5x. CONCLUSION: Our study suggests that LP-GS is a promising alternative to CMA in prenatal diagnostics, offering advantages, including a more efficient workflow and scalability for larger testing volumes. Importantly, for clinical laboratories that have adopted next-generation sequencing in a separate capacity, LP-GS facilitates a unified NGS-centric approach, enabling workflow consolidation. By offering a single, streamlined platform for detecting a broad range of genetic variants, LP-GS may represent a critical step toward enhancing the diagnostic capabilities of prenatal laboratories.


Asunto(s)
Variaciones en el Número de Copia de ADN , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Mapeo Cromosómico , Análisis por Micromatrices
17.
J Neurol Neurosurg Psychiatry ; 95(8): 748-752, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38199813

RESUMEN

BACKGROUND: Consistent patterns of reduced cortical thickness have been identified in early Alzheimer's disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear. METHODS: Participants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral ß-amyloid (Aß) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years). RESULTS: In a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aß status did not. Among Aß positive participants (n=56), there was some evidence that greater global Aß standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08). CONCLUSIONS: Cortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aß-positivity, robust Aß-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Adelgazamiento de la Corteza Cerebral , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Sustancia Blanca , Humanos , Femenino , Masculino , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Estudios Longitudinales , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adelgazamiento de la Corteza Cerebral/diagnóstico por imagen , Adelgazamiento de la Corteza Cerebral/patología , Estudios Prospectivos , Glicoles de Etileno , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Corteza Cerebral/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/patología , Compuestos de Anilina
18.
Genome Biol ; 25(1): 22, 2024 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-38229171

RESUMEN

BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.


Asunto(s)
Diabetes Mellitus Tipo 2 , Estudio de Asociación del Genoma Completo , Adulto , Adolescente , Humanos , Niño , Preescolar , Pubertad/genética , Fenotipo , Estatura/genética , Evaluación de Resultado en la Atención de Salud , Estudios Longitudinales
19.
Sci Adv ; 10(4): eadj3880, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38266092

RESUMEN

Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here, we show that early-life thermal stress strongly up-regulates tsp-1, a gene encoding the conserved transmembrane tetraspanin in C. elegans. TSP-1 forms prominent multimers and stable web-like structures critical for membrane barrier functions in adults and during aging. Increased TSP-1 abundance persists even after transient early-life heat stress. Such regulation requires CBP-1, a histone acetyltransferase that facilitates initial tsp-1 transcription. Tetraspanin webs form regular membrane structures and mediate resilience-promoting effects of early-life thermal stress. Gain-of-function TSP-1 confers marked C. elegans longevity extension and thermal resilience in human cells. Together, our results reveal a cellular mechanism by which early-life thermal stress produces long-lasting memory-like impact on organismal resilience and longevity.


Asunto(s)
Experiencias Adversas de la Infancia , Proteínas de Caenorhabditis elegans , Resiliencia Psicológica , Adulto , Humanos , Animales , Longevidad , Trombospondina 1 , Caenorhabditis elegans , Tetraspaninas/genética , Factores de Transcripción , Proteínas de Caenorhabditis elegans/genética , Histona Acetiltransferasas
20.
Angew Chem Int Ed Engl ; 63(13): e202317256, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38289336

RESUMEN

Powdery hexagonal boron nitride (h-BN), as an important material for electrochemical energy storage, has been typically synthesized in bulk and one/two-dimensional (1/2D) nanostructured morphologies. However, until now, no method has been developed to synthesize powdery three-dimensional (3D) h-BN. This work introduces a novel NaCl-glucose-assisted strategy to synthesize micron-sized 3D h-BN with a honeycomb-like structure and its proposed formation mechanism. We propose that NaCl acts as the template of 3D structure and promotes the nitridation reaction by adsorbing NH3 . Glucose facilitates the homogeneous coating of boric acid onto the NaCl surface via functionalizing the NaCl surface. During the nitridation reaction, boron oxides (BO4 and BO3 ) form from a dehydration reaction of boric acid, which is then reduced to O2 -B-N and O-B-N2 intermediates before finally being reduced to BN3 by NH3 . When incorporated into polyethylene oxide-based electrolytes for Li metal batteries, 5 wt % of 3D h-BN significantly enhances ionic conductivity and mechanical strength. Consequently, this composite electrolyte demonstrates superior electrochemical stability. It delivers 300 h of stable cycles in the Li//Li cell at 0.1 mA cm-2 and retains 89 % of discharge capacity (138.9 mAh g-1 ) after 100 cycles at 1 C in the LFP//Li full cell.

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