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1.
Menopause ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38595203

RESUMO

OBJECTIVE: This study aimed to evaluate the association between daily spiritual experiences and allostatic load (AL) trajectories in midlife African American women. METHODS: A longitudinal analysis of public-use data from 727 African American women in the Study of Women's Health Across the Nation (SWAN) was performed. We included African American women who completed the Daily Spiritual Experiences Scale at SWAN visit 4 (2000-2001) and had AL data at three or more study visits over 7 years. AL was calculated at each visit using 10 biomarkers: systolic and diastolic blood pressure, body mass index, C-reactive protein, high-density lipoprotein cholesterol, total cholesterol, waist-to-hip ratio, fasting serum glucose, triglycerides, and dehydroepiandrosterone. Group-based trajectory modeling identified women with similar patterns of AL. We used multinomial logistic regression to estimate associations between daily spiritual experiences (some days or less, most days, daily, many times a day) and AL trajectories. FINDINGS: Our sample had a mean ± SD age of 49.9 ± 2.66 years, 47% were early perimenopausal, and 17% earned <$19,999 annually. The mean ± SD AL score was 2.52 ± 1.68. Three AL trajectories were identified: low (35.1%), moderate (44.7%), and high (20.2%). In age-adjusted models, women who reported daily comfort in religion and spirituality were less likely to follow a high AL trajectory (odds ratio, 0.41; 95% CI, 0.18-0.93); the association was attenuated when controlling for depressive symptoms (odds ratio, 0.48; 95% CI, 0.19-1.21). CONCLUSIONS: Findings from this study do not support an independent association between spirituality in African American women and AL trajectories in midlife. Studies with a larger sample and additional measures of spirituality are warranted in this population.

2.
Chemosphere ; 356: 141887, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583530

RESUMO

Microplastics pose risks to marine organisms through ingestion, entanglement, and as carriers of toxic additives and environmental pollutants. Plastic pre-production pellet leachates have been shown to affect the development of sea urchins and, to some extent, mussels. The extent of those developmental effects on other animal phyla remains unknown. Here, we test the toxicity of environmental mixed nurdle samples and new PVC pellets for the embryonic development or asexual reproduction by regeneration of animals from all the major animal superphyla (Lophotrochozoa, Ecdysozoa, Deuterostomia and Cnidaria). Our results show diverse, concentration-dependent impacts in all the species sampled for new pellets, and for molluscs and deuterostomes for environmental samples. Embryo axial formation, cell specification and, specially, morphogenesis seem to be the main processes affected by plastic leachate exposure. Our study serves as a proof of principle for the potentially catastrophic effects that increasing plastic concentrations in the oceans and other ecosystems can have across animal populations from all major animal superphyla.

3.
Prostate ; 84(7): 623-635, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38450798

RESUMO

BACKGROUND: There are relatively few widely used models of prostate cancer compared to other common malignancies. This impedes translational prostate cancer research because the range of models does not reflect the diversity of disease seen in clinical practice. In response to this challenge, research laboratories around the world have been developing new patient-derived models of prostate cancer, including xenografts, organoids, and tumor explants. METHODS: In May 2023, we held a workshop at the Monash University Prato Campus for researchers with expertise in establishing and using a variety of patient-derived models of prostate cancer. This review summarizes our collective ideas on how patient-derived models are currently being used, the common challenges, and future opportunities for maximizing their usefulness in prostate cancer research. RESULTS: An increasing number of patient-derived models for prostate cancer are being developed. Despite their individual limitations and varying success rates, these models are valuable resources for exploring new concepts in prostate cancer biology and for preclinical testing of potential treatments. Here we focus on the need for larger collections of models that represent the changing treatment landscape of prostate cancer, robust readouts for preclinical testing, improved in vitro culture conditions, and integration of the tumor microenvironment. Additional priorities include ensuring model reproducibility, standardization, and replication, and streamlining the exchange of models and data sets among research groups. CONCLUSIONS: There are several opportunities to maximize the impact of patient-derived models on prostate cancer research. We must develop large, diverse and accessible cohorts of models and more sophisticated methods for emulating the intricacy of patient tumors. In this way, we can use the samples that are generously donated by patients to advance the outcomes of patients in the future.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Reprodutibilidade dos Testes , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Próstata/patologia , Organoides/patologia , Xenoenxertos , Microambiente Tumoral
4.
Clin Nephrol Case Stud ; 12: 22-25, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444903

RESUMO

Acetaminophen ingestion is routinely managed with the antidote, N-acetylcysteine (NAC). Massive acetaminophen poisoning has been treated successfully with adjunctive therapies such as fomepizole and hemodialysis. Fomepizole functions by inhibiting cytochrome p560, which prevents tylenol from forming its toxic metabolite, NAPQI. Prior cases have demonstrated favorable outcomes and a significant drop in acetaminophen levels after a single session of intermittent hemodialysis and continuous veno-venous hemofiltration (CVVH). However, the recommended dosage adjustments of NAC and fomepizole while a patient is undergoing CVVH has not been well reported. We present a case of an 18-year-old male who presented after ingesting 125 g of tylenol. His 4-hour acetaminophen level was 738.6 µg/mL. He was treated with NAC, fomepizole, and a single 4-hour session of hemodialysis. His acetaminophen level remained elevated at 730 µg/mL despite the hemodialysis session. CVVH was initiated, and he was given intravenous NAC at 12.5 mg/kg/h, oral NAC at 70 mg/kg every 4 hours, and intravenous fomepizole at 10 mg/kg every 6 hours. His tylenol levels became undetectable 57 hours after ingestion, and he did not develop permanent liver toxicity. This case encourages the use of CVVH for massive tylenol ingestion when a single run of intermittent hemodialysis is not effective in lowering the tylenol level. NAC, fomepizole, and CVVH can prevent unfavorable outcomes in massive acetaminophen ingestion when provided at an appropriate dose and frequency.

5.
Healthcare (Basel) ; 12(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38470644

RESUMO

This paper investigates the planning of virtual ward (VW) capacity including the remote monitoring of frail and elderly patients. The main objective is to optimize VW hub locations across a region in the United Kingdom. Furthermore, assigning the optimal number of clinicians to different regions needs to be considered. We develop a mathematical model that minimizes the setup and travel costs of VW hubs and staff. Our experimental analysis evaluates different levels of demand considering postcode areas within different Trusts, also known as Health Boards, in the National Health Service (NHS). Furthermore, our experiments provide insights into how many hub locations should be deployed and staffed. This can be used to individually find the number of remote monitors and clinicians for each facility as well as the system overall.

6.
Am Fam Physician ; 109(2): 119-129, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38393796

RESUMO

Foot fractures account for about one-third of lower extremity fractures in adults. They are typically caused by a crush injury or an axial or twisting force on the foot. Patients usually present with bony point tenderness and swelling of the affected area. Weight-bearing varies based on the extent of the fracture and the patient's pain tolerance. When a foot or toe fracture is suspected, anteroposterior, lateral, and oblique radiography with weight-bearing should be obtained. The Ottawa foot and ankle rules can help determine the need for radiography after an acute ankle inversion injury. Many foot fractures can be managed with a short leg cast or boot or a hard-soled shoe. Weight-bearing and duration of immobilization are based on the stability of the fracture and the patient's pain level. Most toe fractures can be managed nonsurgically with a hard-soled shoe for two to six weeks. Close attention should be paid to the great toe because of its role in weight-bearing, and physicians should follow specific guidelines for orthopedic referral. Meta-tarsal shaft fractures are managed with a boot or hard-soled shoe for three to six weeks. The proximal aspect of the fifth metatarsal has varied rates of healing due to poor blood supply, and management is based on the fracture zone. Lis-franc fractures are often overlooked; radiography with weight-bearing should be obtained, and physicians should look for widening of the tarsometatarsal joint. Other tarsal bone fractures can be managed with a short leg cast or boot for four to six weeks when nonsurgical treatment is indicated. Common foot fracture complications include arthritis, infection, malunion or nonunion, and compartment syndrome.


Assuntos
Traumatismos do Pé , Fraturas Ósseas , Traumatismos do Joelho , Ossos do Metatarso , Adulto , Humanos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/terapia , Ossos do Metatarso/lesões , Ossos do Metatarso/cirurgia , Traumatismos do Pé/diagnóstico por imagem , Traumatismos do Pé/terapia , Extremidade Inferior , Dor
7.
Dig Dis Sci ; 69(4): 1444-1453, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38332211

RESUMO

BACKGROUND: Spleen stiffness measurement (SSM) correlates with the severity of portal hypertension. AIMS: We investigated the utility of SSM in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) for detecting cirrhosis, esophageal varices (EV), and high-risk EV. METHODS: 154 study participants with MASLD underwent simultaneous liver stiffness measurement (LSM) and SSM. 96 (62%) participants had an upper endoscopy (73 participants, i.e., 47% undergoing within a year). The diagnostic performance of SSM, as well as the BAVENO VII proposed SSM cutoffs (≥ 21 kPa, > 40 kPa, and > 50 kPa), was examined. RESULTS: The failure rate for SSM was 19% compared to 5% for LSM. An invalid SSM was statistically significantly associated with a higher body mass index, a larger waist circumference, and a lower fibrosis stage. The area under the receiver operating characteristics for SSM to diagnose cirrhosis, EV, and high-risk EV was 0.78 (95% CI 0.70-0.85), 0.74 (95% CI 0.61-0.84), and 0.82 (95% CI 0.75-0.98), respectively. SSM ≥ 21 kPa cutoff had a sensitivity > 96% for all three outcomes, with a positive predictive value (PPV) of 88% for cirrhosis. In contrast, SSM > 40 kPa and SSM > 50 kPa cutoffs had better diagnostic abilities for identifying EV, particularly high-risk EV (sensitivity of 100% and 93% with NPV of 100% and 96%, respectively). CONCLUSION: SSM has a higher failure rate in individuals who are non-cirrhotic or have a higher BMI, or larger waist circumference. Although useful for diagnosing NASH cirrhosis, SSM is most reliable in excluding EV and high-risk EV.


Assuntos
Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Fígado Gorduroso , Hipertensão Portal , Humanos , Baço/diagnóstico por imagem , Cirrose Hepática/complicações , Hipertensão Portal/complicações , Fígado Gorduroso/patologia , Endoscopia Gastrointestinal , Fígado/patologia
8.
Neural Dev ; 19(1): 3, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383501

RESUMO

BACKGROUND: The evolutionary origins of animal nervous systems remain contentious because we still have a limited understanding of neural development in most major animal clades. Annelids - a species-rich group with centralised nervous systems - have played central roles in hypotheses about the origins of animal nervous systems. However, most studies have focused on adults of deeply nested species in the annelid tree. Recently, Owenia fusiformis has emerged as an informative species to reconstruct ancestral traits in Annelida, given its phylogenetic position within the sister clade to all remaining annelids. METHODS: Combining immunohistochemistry of the conserved neuropeptides FVamide-lir, RYamide-lir, RGWamide-lir and MIP-lir with gene expression, we comprehensively characterise neural development from larva to adulthood in Owenia fusiformis. RESULTS: The early larval nervous system comprises a neuropeptide-rich apical organ connected through peripheral nerves to a prototroch ring and the chaetal sac. There are seven sensory neurons in the prototroch. A bilobed brain forms below the apical organ and connects to the ventral nerve cord of the developing juvenile. During metamorphosis, the brain compresses, becoming ring-shaped, and the trunk nervous system develops several longitudinal cords and segmented lateral nerves. CONCLUSIONS: Our findings reveal the formation and reorganisation of the nervous system during the life cycle of O. fusiformis, an early-branching annelid. Despite its apparent neuroanatomical simplicity, this species has a diverse peptidergic nervous system, exhibiting morphological similarities with other annelids, particularly at the larval stages. Our work supports the importance of neuropeptides in animal nervous systems and highlights how neuropeptides are differentially used throughout development.


Assuntos
Anelídeos , Neuropeptídeos , Poliquetos , Animais , Filogenia , Anelídeos/anatomia & histologia , Anelídeos/genética , Sistema Nervoso/metabolismo , Poliquetos/anatomia & histologia , Poliquetos/genética , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Larva
9.
Int J Cancer ; 154(5): 873-885, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37855394

RESUMO

Urinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B2 are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB2 were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB2 levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤ .001] and 8% [P ≤ .05] reduction in median 11-d-TXB2 values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB2 level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB2 level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB2 values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB2 synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB2 is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB2 measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation.


Assuntos
Aspirina , Pólipos do Colo , Humanos , Aspirina/farmacologia , Aspirina/uso terapêutico , Ácido Eicosapentaenoico , Prostaglandina-Endoperóxido Sintases , Tromboxano B2/urina , Biomarcadores , Prostaglandinas , Ativação Plaquetária
10.
Differentiation ; 135: 100743, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38147763

RESUMO

The fovea centralis (fovea) is a specialized region of the primate retina that plays crucial roles in high-resolution visual acuity and color perception. The fovea is characterized by a high density of cone photoreceptors and no rods, and unique anatomical properties that contribute to its remarkable visual capabilities. Early histological analyses identified some of the key events that contribute to foveal development, but the mechanisms that direct the specification of this area are not understood. Recently, the expression of the retinoic acid-metabolizing enzyme CYP26A1 has become a hallmark of some of the retinal specializations found in vertebrates, including the primate fovea and the high-acuity area in avian species. In chickens, the retinoic acid pathway regulates the expression of FGF8 to then direct the development of a rod-free area. Similarly, high levels of CYP26A1, CDKN1A, and NPVF expression have been observed in the primate macula using transcriptomic approaches. However, which retinal cells express these genes and their expression dynamics in the developing primate eye remain unknown. Here, we systematically characterize the expression patterns of CYP26A1, FGF8, CDKN1A, and NPVF during the development of the rhesus monkey retina, from early stages of development in the first trimester until the third trimester (near term). Our data suggest that some of the markers previously proposed to be fovea-specific are not enriched in the progenitors of the rhesus monkey fovea. In contrast, CYP26A1 is expressed at high levels in the progenitors of the fovea, while it localizes in a subpopulation of macular Müller glia cells later in development. Together these data provide invaluable insights into the expression dynamics of several molecules in the nonhuman primate retina and highlight the developmental advancement of the foveal region.


Assuntos
Galinhas , Retina , Animais , Macaca mulatta/genética , Ácido Retinoico 4 Hidroxilase/genética , Ácido Retinoico 4 Hidroxilase/metabolismo , Células Fotorreceptoras Retinianas Cones , Tretinoína
11.
bioRxiv ; 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37961575

RESUMO

The clinical manifestations of acute severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and COVID-19 suggest a dysregulation of the host immune response that leads to inflammation, thrombosis, and organ dysfunction. It is less clear whether these dysregulated processes persist during the convalescent phase of disease or during long COVID. We investigated the effects of SARS-CoV-2 infection on the proportions of classical, intermediate, and non-classical monocytes, their activation status, and their functional properties in convalescent COVID-19 patients and uninfected control subjects. We found that the percentage of total monocytes was decreased in convalescent COVID-19 patients compared to uninfected controls. This was due to decreased intermediate and non-classical monocytes. Classical monocytes from convalescent COVID-19 patients demonstrated a decrease in activation markers, such as CD56, in response to stimulation with bacterial lipopolysaccharide (LPS). In addition, classical monocytes from convalescent COVID-19 patients showed decreased expression of CD142 (tissue factor), which can initiate the extrinsic coagulation cascade, in response to LPS stimulation. Finally, we found that monocytes from convalescent COVID-19 patients produced less TNF-α and IL-6 in response to LPS stimulation, than those from uninfected controls. In conclusion, SARS-CoV-2 infection exhibits a clear effect on the relative proportions of monocyte subsets, the activation status of classical monocytes, and proinflammatory cytokine production that persists during the convalescent phase of disease.

12.
Curr Oncol ; 30(11): 9437-9447, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37999103

RESUMO

Patient-derived xenograft (PDX) models have been established as important preclinical cancer models, overcoming some of the limitations associated with the use of cancer cell lines. The utility of prostate cancer PDX models has been limited by an inability to genetically manipulate them in vivo and difficulties sustaining PDX-derived cancer cells in culture. Viable, short-term propagation of PDX models would allow in vitro transfection with traceable reporters or manipulation of gene expression relevant to different studies within the prostate cancer field. Here, we report an organoid culture system that supports the growth of prostate cancer PDX cells in vitro and permits genetic manipulation, substantially increasing the scope to use PDXs to study the pathobiology of prostate cancer and define potential therapeutic targets. We have established a short-term PDX-derived in vitro cell culture system which enables genetic manipulation of prostate cancer PDXs LuCaP35 and BM18. Genetically manipulated cells could be re-established as viable xenografts when re-implanted subcutaneously in immunocompromised mice and were able to be serially passaged. Tumor growth of the androgen-dependent LuCaP35 PDX was significantly inhibited following depletion of the androgen receptor (AR) in vivo. Taken together, this system provides a method to generate novel preclinical models to assess the impact of controlled genetic perturbations and allows for targeting specific genes of interest in the complex biological setting of solid tumors.


Assuntos
Neoplasias da Próstata , Receptores Androgênicos , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Xenoenxertos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/deficiência , Receptores Androgênicos/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Oncol Nurs Forum ; 50(6): 679-691, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37874753

RESUMO

OBJECTIVES: To examine associations between a history of adverse childhood experiences (ACEs) and receiving preventive cervical cancer screening and to investigate whether number and type of ACE exposures were predictive of cervical cancer screening uptake. SAMPLE & SETTING: Data were from 11,042 adults who completed the 2020 Texas Behavioral Risk Factor Surveillance System survey. The U.S. Preventive Services Task Force guidelines were used to indicate whether individuals had received cervical cancer screening at recommended intervals. METHODS & VARIABLES: Multiple logistic regression analysis was used to predict the likelihood of not having received the recommended preventive cancer screening by number and type of ACE exposures. Chi-square analysis was used to determine associations among demographic characteristics, cancer screening uptake, and ACE number and type. RESULTS: Individuals with one to three ACEs and those with six or more ACEs were statistically more likely not to have received the recommended cervical cancer screenings compared to those with zero ACEs. A history of physical ACEs was associated with 3.88 times the likelihood of not having received the recommended cervical cancer screening. IMPLICATIONS FOR NURSING: To promote timely cervical cancer screening and prevent retraumatization of patients with a history of ACEs, providers should implement trauma-informed care principles in their healthcare settings.


Assuntos
Experiências Adversas da Infância , Neoplasias do Colo do Útero , Adulto , Feminino , Humanos , Detecção Precoce de Câncer , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Inquéritos e Questionários , Sistema de Vigilância de Fator de Risco Comportamental
14.
Nat Commun ; 14(1): 5758, 2023 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-37717006

RESUMO

Cells within the tumour microenvironment (TME) can impact tumour development and influence treatment response. Computational approaches have been developed to deconvolve the TME from bulk RNA-seq. Using scRNA-seq profiling from breast tumours we simulate thousands of bulk mixtures, representing tumour purities and cell lineages, to compare the performance of nine TME deconvolution methods (BayesPrism, Scaden, CIBERSORTx, MuSiC, DWLS, hspe, CPM, Bisque, and EPIC). Some methods are more robust in deconvolving mixtures with high tumour purity levels. Most methods tend to mis-predict normal epithelial for cancer epithelial as tumour purity increases, a finding that is validated in two independent datasets. The breast cancer molecular subtype influences this mis-prediction. BayesPrism and DWLS have the lowest combined numbers of false positives and false negatives, and have the best performance when deconvolving granular immune lineages. Our findings highlight the need for more single-cell characterisation of rarer cell types, and suggest that tumour cell compositions should be considered when deconvolving the TME.


Assuntos
Neoplasias Mamárias Animais , Música , Animais , Microambiente Tumoral , Linhagem da Célula , RNA-Seq
16.
Cancer Prev Res (Phila) ; 16(11): 621-629, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37756582

RESUMO

Aspirin and eicosapentaenoic acid (EPA) reduce colorectal adenomatous polyp risk and affect synthesis of oxylipins including prostaglandin E2. We investigated whether 35 SNPs in oxylipin metabolism genes such as cyclooxygenase (PTGS) and lipoxygenase (ALOX), as well as 7 SNPs already associated with colorectal cancer risk reduction by aspirin (e.g., TP53; rs104522), modified the effects of aspirin and EPA on colorectal polyp recurrence in the randomized 2 × 2 factorial seAFOod trial. Treatment effects were reported as the incidence rate ratio (IRR) and 95% confidence interval (CI) by stratifying negative binomial and Poisson regression analyses of colorectal polyp risk on SNP genotype. Statistical significance was reported with adjustment for the false discovery rate as the P and q value. 542 (of 707) trial participants had both genotype and colonoscopy outcome data. Reduction in colorectal polyp risk in aspirin users compared with nonaspirin users was restricted to rs4837960 (PTGS1) common homozygotes [IRR, 0.69; 95% confidence interval (CI), 0.53-0.90); q = 0.06], rs2745557 (PTGS2) compound heterozygote-rare homozygotes [IRR, 0.60 (0.41-0.88); q = 0.06], rs7090328 (ALOX5) rare homozygotes [IRR 0.27 (0.11-0.64); q = 0.05], rs2073438 (ALOX12) common homozygotes [IRR, 0.57 (0.41-0.80); q = 0.05], and rs104522 (TP53) rare homozygotes [IRR, 0.37 (0.17-0.79); q = 0.06]. No modification of colorectal polyp risk in EPA users was observed. In conclusion, genetic variants relevant to the proposed mechanism of action on oxylipins are associated with differential colorectal polyp risk reduction by aspirin in individuals who develop multiple colorectal polyps. SNP genotypes should be considered during development of personalized, predictive models of colorectal cancer chemoprevention by aspirin. PREVENTION RELEVANCE: Single-nucleotide polymorphisms in genes controlling lipid mediator signaling may modify the colorectal polyp prevention activity of aspirin. Further investigation is required to determine whether testing for genetic variants can be used to target cancer chemoprevention by aspirin to those who will benefit most.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Humanos , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Pólipos do Colo/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/epidemiologia , Ciclo-Oxigenase 2 , Ácido Eicosapentaenoico , Genes p53 , Lipoxigenase/genética , Oxilipinas , Polimorfismo de Nucleotídeo Único , Comportamento de Redução do Risco , Proteína Supressora de Tumor p53/genética
17.
EJHaem ; 4(3): 587-594, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37601884

RESUMO

Sexual and reproductive healthcare standards for adolescents and young adults with sickle cell disease (SCD) are not established. A total of 50 young adults entering adult SCD care completed a Family Planning Survey assessing sexual and reproductive health needs from March 2019 to July 2020. Clinical data were abstracted from respondents' electronic medical records. Linear and logistic regression was applied to explore associations between clinical characteristics and survey results. Few respondents (8%) wished to be pregnant in the coming year, and 46% answered yes to at least one of four needs assessment questions. Those who were not employed full time were more likely to endorse needing help with getting sickle cell trait testing for a partner (ORadj = 9.59, p-value = 0.05). Contraceptive use was associated with having an obstetrician-gynecologist (OR = 6.8, p-value = 0.01). Young adults with SCD entering adult care have diverse reproductive health needs, highlighting opportunities to provide multidisciplinary, SCD-specific reproductive healthcare.

18.
Nutrients ; 15(15)2023 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-37571413

RESUMO

Smartphone apps might provide an opportunity to support the Dietary Approaches to Stop Hypertension (DASH) diet, a healthy diet designed to help lower blood pressure. This study evaluated DASH diet self-management apps based on their quality, likely effectiveness, and data privacy/security to identify the most suitable app(s). A systematic search and content analysis were conducted of all DASH diet apps available in Google Play and the Apple App Store in the UK in November 2022. Apps were included if they provided DASH diet tracking. A previous systematic literature review found some commercial apps not found in the app store search, and these were also included in this review. Three reviewers used the App Quality Evaluation Tool (AQEL) to assess each app's quality across seven domains: knowledge acquisition, skill development, behaviour change, purpose, functionality, and appropriateness for adults with hypertension. Domains with a score of 8 or higher were considered high-quality. Two reviewers assessed the apps' data privacy and security and then coded Behaviour change techniques (BCTs) linked to the Theoretical Domain Framework (TDF) underpinning the likely effectiveness of the apps. Seven DASH diet apps were assessed, showing the limited availability of apps supporting DASH diet self-management. The AQEL assessment showed that three apps scored higher than eight in most of the AQEL domains. Nineteen BCTs were used across the apps, linked to nine TDF action mechanisms that may support DASH diet self-management behaviours. Four apps met standards for privacy and security. All seven apps with self-monitoring functionality had sufficient theoretical basis to demonstrate likely effectiveness. However, most had significant quality and data security shortcomings. Only two apps, NOOM and DASH To TEN, were found to have both adequate quality and security and were thus deemed suitable to support DASH diet self-management.


Assuntos
Abordagens Dietéticas para Conter a Hipertensão , Aplicativos Móveis , Autogestão , Humanos , Dieta , Terapia Comportamental/métodos , Autogestão/métodos
20.
Aliment Pharmacol Ther ; 58(6): 562-572, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37518954

RESUMO

BACKGROUND: The seAFOod polyp prevention trial was a randomised, placebo-controlled, 2 × 2 factorial trial of aspirin 300 mg and eicosapentaenoic acid (EPA) 2000 mg daily in individuals who had a screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Aspirin treatment was associated with a 20% reduction in colorectal polyp number at BCSP surveillance colonoscopy 12 months later. It is unclear what happens to colorectal polyp risk after short-term aspirin use. AIM: To investigate colorectal polyp risk according to the original trial treatment allocation, up to 6 years after trial participation. METHODS: All seAFOod trial participants were scheduled for further BCSP surveillance and provided informed consent for the collection of colonoscopy outcomes. We linked BCSP colonoscopy data to trial outcomes data. RESULTS: In total, 507 individuals underwent one or more colonoscopies after trial participation. Individuals grouped by treatment allocation were well matched for clinical characteristics, follow-up duration and number of surveillance colonoscopies. The polyp detection rate (PDR; the number of individuals who had ≥1 colorectal polyp detected) after randomization to placebo aspirin was 71.1%. The PDR was 80.1% for individuals who had received aspirin (odds ratio [OR] 1.13 [95% confidence interval 1.02, 1.24]; p = 0.02). There was no difference in colorectal polyp outcomes between individuals who had been allocated to EPA compared with its placebo (OR for PDR 1.00 [0.91, 1.10]; p = 0.92). CONCLUSION: Individuals who received aspirin in the seAFOod trial demonstrated increased colorectal polyp risk during post-trial surveillance. Rebound elevated neoplastic risk after short-term aspirin use has important implications for aspirin cessation driven by age-related bleeding risk. ISRCTN05926847.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Humanos , Aspirina/uso terapêutico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/epidemiologia , Pólipos do Colo/diagnóstico , Pólipos do Colo/tratamento farmacológico , Colonoscopia
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