Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 88
Filtrar
1.
Artículo en Inglés | MEDLINE | ID: mdl-38831121

RESUMEN

Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field.

2.
Nat Ecol Evol ; 8(5): 1021-1034, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38361161

RESUMEN

Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mitochondrial genome in different tissues throughout ageing. We used ultrasensitive duplex sequencing to profile ~2.5 million mitochondrial genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloguing ~1.2 million mitochondrial somatic and ultralow-frequency inherited mutations, of which 81,097 are unique. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the light strand origin of replication, which consistently exhibits the highest mutation frequency. We show that rodents exhibit a distinct mitochondrial somatic mutational spectrum compared with primates with a surfeit of reactive oxygen species-associated G > T/C > A mutations, and that somatic mutations in protein-coding genes exhibit signatures of negative selection. Lastly, we identify an extensive enrichment in somatic reversion mutations that 're-align' mito-nuclear ancestry within an organism's lifespan. Together, our findings demonstrate that mitochondrial genomes are a dynamically evolving subcellular population shaped by somatic mutation and selection throughout organismal lifetimes.


Asunto(s)
Envejecimiento , Genoma Mitocondrial , Haplotipos , Mutación , Selección Genética , Animales , Envejecimiento/genética , Ratones , ADN Mitocondrial/genética , Núcleo Celular/genética , Femenino , Mitocondrias/genética , Ratones Endogámicos C57BL , Masculino
3.
Haematologica ; 109(2): 401-410, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37534515

RESUMEN

The presence of measurable residual disease (MRD) is strongly associated with treatment outcomes in acute myeloid leukemia (AML). Despite the correlation with clinical outcomes, MRD assessment has yet to be standardized or routinely incorporated into clinical trials and discrepancies have been observed between different techniques for MRD assessment. In 62 patients with AML, aged 18-60 years, in first complete remission after intensive induction therapy on the randomized phase III SWOG-S0106 clinical trial (clinicaltrials gov. Identifier: NCT00085709), MRD detection by centralized, high-quality multiparametric flow cytometry was compared with a 29-gene panel utilizing duplex sequencing (DS), an ultrasensitive next-generation sequencing method that generates double-stranded consensus sequences to reduce false positive errors. MRD as defined by DS was observed in 22 (35%) patients and was strongly associated with higher rates of relapse (68% vs. 13%; hazard ratio [HR] =8.8; 95% confidence interval [CI]: 3.2-24.5; P<0.001) and decreased survival (32% vs. 82%; HR=5.6; 95% CI: 2.3-13.8; P<0.001) at 5 years. DS MRD strongly outperformed multiparametric flow cytometry MRD, which was observed in ten (16%) patients and marginally associated with higher rates of relapse (50% vs. 30%; HR=2.4; 95% CI: 0.9-6.7; P=0.087) and decreased survival (40% vs. 68%; HR=2.5; 95% CI: 1.0-6.3; P=0.059) at 5 years. Furthermore, the prognostic significance of DS MRD status at the time of remission for subsequent relapse was similar on both randomized arms of the trial. These findings suggest that next-generation sequencing-based AML MRD testing is a powerful tool that could be developed for use in patient management and for early anti-leukemic treatment assessment in clinical trials.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Resultado del Tratamiento , Pronóstico , Recurrencia , Neoplasia Residual/diagnóstico , Citometría de Flujo/métodos
4.
Artículo en Inglés | MEDLINE | ID: mdl-37770135

RESUMEN

Duplex sequencing (DS) is an error-corrected next-generation sequencing method in which molecular barcodes informatically link PCR-copies back to their source DNA strands, enabling computational removal of errors in consensus sequences. The resulting background of less than one artifactual mutation per 107 nucleotides allows for direct detection of somatic mutations. TwinStrand Biosciences, Inc. has developed a DS-based mutagenesis assay to sample the rat genome, which can be applied to genetic toxicity testing. To evaluate this assay for early detection of mutagenesis, a time-course study was conducted using male Hsd:Sprague Dawley SD rats (3 per group) administered a single dose of 40 mg/kg N-ethyl-N-nitrosourea (ENU) via gavage, with mutation frequency (MF) and spectrum analyzed in stomach, bone marrow, blood, and liver tissues at 3 h, 24 h, 7 d, and 28 d post-exposure. Significant increases in MF were observed in ENU-exposed rats as early as 24 h for stomach (site of contact) and bone marrow (a highly proliferative tissue) and at 7 d for liver and blood. The canonical, mutational signature of ENU was established by 7 d post-exposure in all four tissues. Interlaboratory analysis of a subset of samples from different tissues and time points demonstrated remarkable reproducibility for both MF and spectrum. These results demonstrate that MF and spectrum can be evaluated successfully by directly sequencing targeted regions of DNA obtained from various tissues⁠, a considerable advancement compared to currently used in vivo gene mutation assays.


Asunto(s)
Etilnitrosourea , Compuestos de Nitrosourea , Ratas , Masculino , Animales , Etilnitrosourea/toxicidad , Reproducibilidad de los Resultados , Ratas Sprague-Dawley , Mutagénesis , Mutación , Mutágenos/toxicidad
5.
JAAPA ; 36(9): 17-23, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37561653

RESUMEN

ABSTRACT: Females spend a third to half of their life in menopause, and the number of US females in menopause is growing. A high percentage of postmenopausal females experience bothersome, sometimes debilitating genitourinary symptoms, which can affect quality of life. The genitourinary syndrome of menopause (GSM) describes the condition previously referred to as vulvovaginal atrophy, atrophic vaginitis, or urogenital atrophy. Of concern, many patients with symptoms of GSM have never been asked about nor have they initiated conversations about these concerns with a healthcare provider. This article addresses the need to improve screening, identification, and patient-centered management in primary care of females with GSM.


Asunto(s)
Calidad de Vida , Vagina , Femenino , Humanos , Vulva/patología , Síndrome , Menopausia , Atrofia/patología , Atención Primaria de Salud
6.
Artículo en Inglés | MEDLINE | ID: mdl-37491114

RESUMEN

Error-corrected duplex sequencing (DS) enables direct quantification of low-frequency mutations and offers tremendous potential for chemical mutagenicity assessment. We investigated the utility of DS to quantify induced mutation frequency (MF) and spectrum in human lymphoblastoid TK6 cells exposed to a prototypical DNA alkylating agent, N-ethyl-N-nitrosourea (ENU). Furthermore, we explored appropriate experimental parameters for this application, and assessed inter-laboratory reproducibility. In two independent experiments in two laboratories, TK6 cells were exposed to ENU (25-200 µM) and DNA was sequenced 48, 72, and 96 h post-exposure. A DS mutagenicity panel targeting twenty 2.4-kb regions distributed across the genome was used to sample diverse, genome-representative sequence contexts. A significant increase in MF that was unaffected by time was observed in both laboratories. Concentration-response in the MF from the two laboratories was strongly positively correlated (r = 0.97). C:G>T:A, T:A>C:G, T:A>A:T, and T:A>G:C mutations increased in consistent, concentration-dependent manners in both laboratories, with high proportions of C:G>T:A at all time points. The consistent results across the three time points suggest that 48 h may be sufficient for mutation analysis post-exposure. The target sites responded similarly between the two laboratories and revealed a higher average MF in intergenic regions. These results, demonstrating remarkable reproducibility across time and laboratory for both MF and spectrum, support the high value of DS for characterizing chemical mutagenicity in both research and regulatory evaluation.


Asunto(s)
ADN , Mutágenos , Humanos , Reproducibilidad de los Resultados , Mutación , Mutágenos/toxicidad , Mutagénesis , Etilnitrosourea
7.
Gynecol Oncol Rep ; 47: 101199, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37251786

RESUMEN

Objective: Endometrial cancer is the most common gynecological malignancy in the United States. Despite the high prevalence amongst cisgender females the prevalence of this gynecological malignancy in transgender men has not been clearly identified. To date, only four reported cases have been described in the literature. Case: A 36-year-old nulliparous assigned female at birth, transgender premenopausal male underwent a laparoscopic total hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node mapping and omental biopsy after having an endometrial biopsy that demonstrated well differential endometroid adenocarcinoma. He had been on testosterone therapy for at least five years prior to presenting to his gynecologist with the chief complaint of vaginal bleeding. Final pathology showed FIGO Stage 1A endometroid endometrial carcinoma. Conclusion: This case report adds to the body of literature demonstrating that transgender men can develop endometrial carcinoma while on exogenous testosterone therapy. In addition, this report illustrates the importance of routine gynecological care in the transgender patient population.

8.
bioRxiv ; 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37214853

RESUMEN

Duplex sequencing (DuplexSeq) is an error-corrected next-generation sequencing (ecNGS) method in which molecular barcodes informatically link PCR-copies back to their source DNA strands, enabling computational removal of errors by comparing grouped strand sequencing reads. The resulting background of less than one artifactual mutation per 10 7 nucleotides allows for direct detection of somatic mutations. TwinStrand Biosciences, Inc. has developed a DuplexSeq-based mutagenesis assay to sample the rat genome, which can be applied to genetic toxicity testing. To evaluate this assay for early detection of mutagenesis, a time-course study was conducted using male Hsd:Sprague Dawley SD rats (3 per group) administered a single dose of 40 mg/kg N-ethyl-N-nitrosourea (ENU) via gavage, with mutation frequency (MF) and spectrum analyzed in stomach, bone marrow, blood, and liver tissues at 3 h, 24 h, 7 d, and 28 d post-exposure. Significant increases in MF were observed in ENU-exposed rats as early as 24 h for stomach (site of contact) and bone marrow (a highly proliferative tissue) and at 7 d for liver and blood. The canonical, mutational signature of ENU was established by 7 d post-exposure in all four tissues. Interlaboratory analysis of a subset of samples from different tissues and time points demonstrated remarkable reproducibility for both MF and spectrum. These results demonstrate that MF and spectrum can be evaluated successfully by directly sequencing targeted regions of DNA obtained from various tissues, a considerable advancement compared to currently used in vivo gene mutation assays. HIGHLIGHTS: DuplexSeq is an ultra-accurate NGS technology that directly quantifies mutationsENU-dependent mutagenesis was detected 24 h post-exposure in proliferative tissuesMultiple tissues exhibited the canonical ENU mutation spectrum 7 d after exposureResults obtained with DuplexSeq were highly concordant between laboratoriesThe Rat-50 Mutagenesis Assay is promising for applications in genetic toxicology.

9.
medRxiv ; 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37034683

RESUMEN

The presence of measurable residual disease (MRD) is strongly associated with treatment outcomes in acute myeloid leukemia (AML). Despite the correlation with clinical outcomes, MRD assessment has yet to be standardized or routinely incorporated into clinical trials. Discrepancies have been observed between different techniques for MRD assessment and there remains a need to compare centralized, high-quality multiparametric flow cytometry (MFC) and ultrasensitive next-generation sequencing (NGS) in AML patients with diverse mutational profiles. In 62 patients with AML, aged 18-60, in first complete remission after intensive induction therapy on the randomized phase 3 SWOG-S0106 clinical trial, MRD detection by MFC was compared with a 29 gene panel utilizing duplex sequencing (DS), an NGS method that generates double-stranded consensus sequences to reduce false positive errors. Using DS, detection of a persistent mutation utilizing defined criteria was seen in 22 (35%) patients and was strongly associated with higher rates of relapse (68% vs 13% at year 5; HR, 8.8; 95% CI, 3.2-24.5; P<0.001) and decreased survival (32% vs 82% at year 5; HR, 5.6; 95% CI, 2.3-13.8; P<0.001). MRD as defined by DS strongly outperformed MFC, which was observed in 10 (16%) patients and marginally associated with higher rates of relapse (50% vs 30% at year 5; HR, 2.4; 95% CI, 0.9-6.7; P=0.087) and decreased survival (40% vs 68% at year 5; HR, 2.5; 95% CI, 1.0-6.3; P=0.059). Furthermore, the prognostic significance of DS MRD status at the time of remission was similar on both randomized arms of the trial, predicting S0106 clinical trial outcomes. These findings suggest that DS is a powerful tool that could be used in patient management and for early treatment assessment in clinical trials.

10.
bioRxiv ; 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-36945529

RESUMEN

Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here, we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mt-genome in different tissues throughout aging. We used ultra-sensitive Duplex Sequencing to profile ~2.5 million mt-genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloging ~1.2 million mitochondrial somatic and ultra low frequency inherited mutations, of which 81,097 are unique. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the Light Strand Origin of Replication, which consistently exhibits the highest mutation frequency. We show that rodents exhibit a distinct mitochondrial somatic mutational spectrum compared to primates with a surfeit of reactive oxygen species-associated G>T/C>A mutations, and that somatic mutations in protein coding genes exhibit signatures of negative selection. Lastly, we identify an extensive enrichment in somatic reversion mutations that "re-align" mito-nuclear ancestry within an organism's lifespan. Together, our findings demonstrate that mitochondrial genomes are a dynamically evolving subcellular population shaped by somatic mutation and selection throughout organismal lifetimes.

11.
Contraception ; 123: 110024, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36934955

RESUMEN

OBJECTIVES: Studies have illustrated crisis pregnancy centers' (CPC) disingenuous practices regarding abortion services. We evaluated the proportion of patients who visited a CPC before their abortion in Los Angeles. STUDY DESIGN: Patients attending one of two abortion clinics between July 2019 and March 2020 were recruited for a survey that examined patient characteristics and locations of care. RESULTS: Five hundred eleven respondents participated (62% response rate). Less than 1% of individuals visited a CPC before their abortion. Fifty-three percent of survey respondents obtained their abortion within one visit, 39% within two unique clinic visits, and eight percent visited three or more clinics. CONCLUSION: CPC visits before abortion were uncommon in our patient population.


Asunto(s)
Aborto Inducido , Embarazo , Femenino , Humanos , Los Angeles , Instituciones de Atención Ambulatoria
12.
Metabolites ; 13(3)2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36984838

RESUMEN

The purpose of this trial was to evaluate serum levels of oxidative stress biomarkers and biochemical analytes in crossbred lambs during the rearing phase in an integrated crop-livestock system (ICLS) to control gastrointestinal parasites. The experiment used 36 crossbred lambs (cross: Ile de France × White Dorper × Texel) divided into two groups. The WCS group was supplemented with whole cottonseed (WCS), and controls had no supplementation. Body weight, blood collection, and fecal analysis of nematode eggs and Eimeria oocysts counting per gram of feces were performed for each animal within 84 days of experiment. The following serum analytes were determined: total protein, albumin, globulin, cholesterol, haptoglobin, and 10 oxidative stress biomarkers: cupric reducing antioxidant capacity, ferric reducing ability of plasma, trolox equivalent antioxidant capacity, thiol, uric acid, paraoxonase-1, total oxidant status, ferric-xylenol orange, advanced oxidation protein products, and reactive oxygen metabolites derived compounds. The inclusion of WCS suggested the benefit in controlling infection as well as inducing an increase in antioxidants and a decrease in oxidants in lambs naturally infected by gastrointestinal parasites. The combination of WCS and ICLS could be a useful tool in controlling gastrointestinal parasite infection without affecting the production performance.

13.
PLoS One ; 17(9): e0274510, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36137129

RESUMEN

In chronic kidney disease dogs, the inflammatory process increases C-reactive protein concentrations. This study aimed to determine C-reactive protein serum concentrations in stage IV chronic kidney disease dogs treated with intermittent hemodialysis. A prospective cohort study was conducted with 23 dogs allocated into three groups: control group (CG, n = 7), intermittent hemodialysis group (IHG, n = 8) and clinical treatment group (CTG, n = 8), both comprised of stage IV chronic kidney disease dogs. One blood sample from CG (initial evaluation) and two samples from IHG and CTG (first- and last-moment) were obtained to determine C-reactive protein concentration, total leukocytes, platelets, erythrocytes, total plasma protein, serum albumin, urea, creatinine, and phosphorus. C-reactive protein was higher in IHG compared to CG in the first- and last-moments (p <0.001) and compared to CTG in the first-moment (p = 0.0406). C-reactive protein presented moderate positive correlation with leukocytes (r = 0.5479; p = 0.01), and moderate negative correlation with albumin (r = - 0.5974; p = 0.006) and red blood cells (r = - 0.5878, p = 0.01). A high correlation coefficient was observed in the tests' evaluation (CI = 0.59-0.78; r = 0.70; P<0.0001). In conclusion, both assays used in this study to measure C-reactive protein have provided safe and reliable quantification of the results. Additionally, despite IHG dogs presented an active inflammatory profile, intermittent hemodialysis has proven to be beneficial, leading to a clinical improvement in life quality of patients, and thus being recommended for stage IV CKD dogs when performed by trained professionals.


Asunto(s)
Enfermedades de los Perros , Insuficiencia Renal Crónica , Animales , Proteína C-Reactiva/metabolismo , Creatinina , Enfermedades de los Perros/terapia , Perros , Humanos , Fósforo , Estudios Prospectivos , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/veterinaria , Albúmina Sérica , Urea
14.
Am J Ther ; 29(5): e553-e567, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35998109

RESUMEN

BACKGROUND: The UN Commission on Life-Saving Commodities for Women and Children identified emergency contraceptive pills as 1 of the 13 essential underused, low-cost, and high-impact commodities that could save the lives of millions of women and children worldwide. In the US, 2 emergency contraceptive regimens are currently approved, and their most plausible mechanism of action involves delaying and/or inhibiting ovulation. AREAS OF UNCERTAINTY: Abortion and contraception are recognized as essential components of reproductive health care. In the US, in the wake of the Dobbs v. Jackson Women's Health Organization Supreme Court decision on June 24, 2022, 26 states began to or are expected to severely restrict abortion. It is anticipated that these restrictions will increase the demand for emergency contraception (EC). Several obstacles to EC access have been described, and these include cost, hurdles to over-the-counter purchase, low awareness, myths about their mechanisms of action, widespread misinformation, and barriers that special populations face in accessing them. The politicization of EC is a major factor limiting access. Improving sex education and health literacy, along with eHealth literacy, are important initiatives to improve EC uptake and access. DATA SOURCES: PubMed, The Guttmacher Institute, Society of Family Planning, American College of Obstetricians and Gynecologists, the World Health Organization, The United Nations. THERAPEUTIC ADVANCES: A randomized noninferiority trial showed that the 52 mg levonorgestrel intrauterine device was noninferior to the copper intrauterine device when used as an EC method in the first 5 days after unprotected intercourse. This is a promising and highly effective emergency contraceptive option, particularly for overweight and obese patients, and a contraceptive option with a different bleeding profile than the copper intrauterine device. CONCLUSIONS: EC represents an important facet of medicine and public health. The 2 medical regimens currently approved in the US are very effective, have virtually no medical contraindications, and novel formulations are actively being investigated to make them more convenient and effective for all patient populations. Barriers to accessing EC, including the widespread presence of contraception deserts , threaten to broaden and accentuate the already existing inequities and disparities in society, at a time when they have reached the dimensions of a public health crisis.


Asunto(s)
Anticoncepción Postcoital , Anticonceptivos Poscoito , Dispositivos Intrauterinos de Cobre , Niño , Anticoncepción , Anticoncepción Postcoital/métodos , Femenino , Humanos , Levonorgestrel , Embarazo , Incertidumbre
15.
Am J Ther ; 29(5): e534-e543, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35994387

RESUMEN

BACKGROUND: The U.S. Supreme Court's Dobbs v. Jackson Women's Health Organization decision on June 24, 2022 effectively overturned federal constitutional protections for abortion that have existed since 1973 and returned jurisdiction to the states. Several states implemented abortion bans, some of which banned abortion after 6 weeks and others that permit abortion under limited exceptions, such as if the health or the life of the woman is in danger. Other states introduced bills that define life as beginning at fertilization. As a result of these new and proposed laws, the future availability of mifepristone, one of two drugs used for medical abortion in the United States, has become the topic of intense debate and speculation. AREAS OF UNCERTAINTY: Although its safety and effectiveness has been confirmed by many studies, the use of mifepristone has been politicized regularly since its approval. Areas of future study include mifepristone for induction termination and fetal demise in the third trimester and the management of leiomyoma. DATA SOURCES: PubMed, Society of Family Planning, American College of Obstetricians and Gynecologists, the World Health Organization. THERAPEUTIC ADVANCES: The use of no-touch medical abortion, which entails providing a medical abortion via a telehealth platform without a screening ultrasound or bloodwork, expanded during the COVID-19 pandemic, and studies have confirmed its safety. With the Dobbs decision, legal abortion will be less accessible and, consequently, self-managed abortion with mifepristone and misoprostol will become more prevalent. CONCLUSIONS: Mifepristone and misoprostol are extremely safe medications with many applications. In the current changing political climate, physicians and pregnancy-capable individuals must have access to these medications.


Asunto(s)
Aborto Inducido , Tratamiento Farmacológico de COVID-19 , Misoprostol , Automanejo , Aborto Inducido/métodos , Femenino , Humanos , Mifepristona/efectos adversos , Misoprostol/efectos adversos , Pandemias , Embarazo , Estados Unidos
16.
BMC Genomics ; 23(1): 542, 2022 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-35902794

RESUMEN

Exposure to environmental mutagens increases the risk of cancer and genetic disorders. We used Duplex Sequencing (DS), a high-accuracy error-corrected sequencing technology, to analyze mutation induction across twenty 2.4 kb intergenic and genic targets in the bone marrow of MutaMouse males exposed to benzo(a)pyrene (BaP), a widespread environmental pollutant. DS revealed a linear dose-related induction of mutations across all targets with low intra-group variability. Heterochromatic and intergenic regions exhibited the highest mutation frequencies (MF). C:G > A:T transversions at CCA, CCC and GCC trinucleotides were enriched in BaP-exposed mice consistent with the known etiology of BaP mutagenesis. However, GC-content had no effect on mutation susceptibility. A positive correlation was observed between DS and the "gold-standard" transgenic rodent gene mutation assay. Overall, we demonstrate that DS is a promising approach to study in vivo mutagenesis and yields critical insight into the genomic features governing mutation susceptibility, spectrum, and variability across the genome.


Asunto(s)
Benzo(a)pireno , Mutágenos , Animales , Benzo(a)pireno/toxicidad , Genómica , Masculino , Ratones , Mutación
17.
Am J Occup Ther ; 76(3)2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-35648121

RESUMEN

IMPORTANCE: Occupational therapy practitioners are expected to translate promising discoveries from empirical research into routine practice with their clients. However, complex barriers can influence practitioners' knowledge translation (KT) efforts, leading the American Occupational Therapy Association's Evidence-Based Practice (EBP) group to develop the KT Toolkit tailored to the perceived needs of occupational therapists and occupational therapy assistants. OBJECTIVE: To identify common barriers to implementing EBPs and potential strategies to support EBP uptake. DESIGN: Cross-sectional survey. SETTING: United States. PARTICIPANTS: Occupational therapy practitioners. OUTCOMES AND MEASURES: Data underwent descriptive and directed content analysis, the latter of which was guided by the Consolidated Framework for Implementation Research. RESULTS: Occupational therapy survey respondents (N = 818) identified common EBP implementation barriers (e.g., lack of time and resources, difficulty understanding research findings). Initial KT Toolkit content was developed to address these barriers and included resources for searching for, analyzing, and applying evidence in practice. CONCLUSIONS AND RELEVANCE: Survey findings have informed the development of the KT Toolkit, which includes resources designed to support occupational therapy practitioners' EBP implementation efforts. This KT Toolkit is available at AOTA.org and will be continuously revised and updated on an ongoing basis. What This Article Adds: Several barriers limit the extent to which occupational therapy practitioners can implement evidence with their client populations. The KT Toolkit is directly informed by practitioner input and provides resources to support practitioners in their efforts to translate knowledge into real-world practice.


Asunto(s)
Terapia Ocupacional , Estudios Transversales , Práctica Clínica Basada en la Evidencia , Humanos , Terapeutas Ocupacionales , Ciencia Traslacional Biomédica , Estados Unidos
18.
Artículo en Inglés | MEDLINE | ID: mdl-35586753

RESUMEN

Identification of pathogens with pulmonary presentation in patients with hematologic malignancies may be challenging due to diagnostic difficulty related to the underlying malignancy and limitations of conventional microbiologic methods. Herein, we present a case series of three patients with pulmonary consolidations due to Legionella bozemanae necrotizing pneumonia, Pneumocystis jirovecii pneumonia, and disseminated Scedosporium infection, who were diagnosed by microbial cell-free DNA next-generation sequencing. We observed that this new sequencing modality was in agreement with gold-standard diagnostics, posing a potential solution to the problem of limited capability in diagnosing infections in hematological malignancy patients.

19.
Vet Clin Pathol ; 51(1): 77-83, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35191061

RESUMEN

BACKGROUND: Feline obstructive disease of the lower urinary tract (FLUTD) is a common pathologic condition of cats. It can be related to sterile inflammation, which leads to acute impairment of renal function and the accumulation of electrolytes and acid-base imbalance. Acute-phase proteins (APPs) are biomarkers of tissue damage from inflammation that assist in monitoring treatment and prognosis. OBJECTIVE: Monitoring the inflammatory processes of obstructive feline lower urinary tract disease through the determination of plasma fibrinogen concentrations and serum concentrations of the acute-phase proteins, serum amyloid A (SAA), alpha-1-acid glycoprotein (AGP), and albumin. METHODOLOGY: Twenty-five male cats were included in this study. They were divided into two experimental groups: a control group (CG) and an obstruction group (OG). There were 8 healthy cats in the CG group and 17 cats with obstructive FLUTD in the OG group. APP measurements were conducted using ELISA kits. Samples were collected for APP analyses, serum biochemical assays, urinalyses, and urine protein: creatinine ratio calculations at diagnosis, before urethral clearance (H0), and 12 (H12), 24 (H24), and 48 (H48) hours after urethral clearance from cats in the OG group. Samples were collected once from cats in the CG group cats. RESULTS: At H0, we found positive correlations of SAA, AGP, and fibrinogen with urea and creatinine, and negative correlations of albumin with hematuria, SAA, and potassium. At H48, we found positive correlations between SAA and AGP, AGP and urea, fibrinogen and urea, fibrinogen and creatinine, fibrinogen and AGP, and fibrinogen and SAA. In addition, a negative correlation of albumin with urea and creatinine was observed. CONCLUSIONS: Serum amyloid A, AGP, fibrinogen, and albumin could be used as biomarkers of inflammatory processes in cats with obstructive FLUTD.


Asunto(s)
Enfermedades de los Gatos , Enfermedades Urológicas , Proteínas de Fase Aguda/análisis , Animales , Biomarcadores , Enfermedades de los Gatos/diagnóstico , Gatos , Masculino , Orosomucoide/análisis , Orosomucoide/metabolismo , Proteína Amiloide A Sérica/análisis , Enfermedades Urológicas/veterinaria
20.
J Appl Res Intellect Disabil ; 35(4): 1019-1027, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33527499

RESUMEN

BACKGROUND: Individuals with intellectual and developmental disabilities demonstrate disparities in sexual and reproductive health (SRH) compared to individuals without disabilities (e.g., lack of sexual education and knowledge, increased rates of abuse, unplanned pregnancies and sexually transmitted infections). Therefore, the purpose of this study was to identify topics healthcare providers address and perceived barriers and supports to SRH education. METHODS: We conducted semi-structured interviews with healthcare providers (N = 12). RESULTS: Providers address relationships, safety, protection and appropriate sexual behaviours with clients with intellectual and developmental disabilities. Parent education and client-centred care were identified as supports, while the patient's level of understanding, the provider's lack of knowledge or access to resources and to appropriate referrals were identified as barriers to SRH education. CONCLUSION: Future studies are needed to link providers to resources they can use to provide comprehensive, accessible SRH education for clients with intellectual and developmental disabilities.


Asunto(s)
Discapacidad Intelectual , Salud Sexual , Niño , Discapacidades del Desarrollo , Femenino , Personal de Salud , Humanos , Embarazo , Salud Reproductiva , Conducta Sexual
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...