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1.
Ann Oncol ; 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38408508

RESUMEN

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) ß, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.

2.
J Oncol Pharm Pract ; 30(1): 127-141, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37122190

RESUMEN

PURPOSE: Oncology care continues to evolve at a rapid pace including provision of infusion-based care. There is currently a lack of robust metrics around oncology infusion centers and pharmacy practice. The workgroup completed a nationwide survey to learn about oncology-based infusion pharmacy services offered. The objective was to highlight consistent, measureable oncology-based infusion pharmacy metrics that will provide a foundation to describe overall productivity including emphasis on high patient-safety standards. METHODS: A nationwide survey was developed via a workgroup within the Vizient Pharmacy Cancer Care Group beginning in April 2019 and conducted electronically via the Vizient Pharmacy Network from September to November 2020. The survey was designed to capture a number of key metrics related to oncology-based infusion pharmacy services. RESULTS: Forty-one sites responded to the survey. Responses highlighted hours of operation (median = 11.5), number of infusion chairs (median = 45). Staffing metrics included 7.1 pharmacist full-time equivalent (FTE) and 7.6 technician FTE per week. 80.5% of sites had cleanrooms and 95.1% reported both hazardous and nonhazardous compounding hoods. 68.3% of sites reported using intravenous (IV) technology, 50.0% measured turnaround time, and 31.4% prepared treatment medications in advance. CONCLUSION: There was variability among oncology infusion pharmacy practices in regard to survey responses among sites. The survey results highlight the need for standardization of established productivity metrics across oncology infusion pharmacies in order to improve efficiency and contain costs in the changing oncology landscape. The survey provides insight into oncology infusion pharmacy practices nationwide and provides information for pharmacy leaders to help guide their practices.


Asunto(s)
Servicios Farmacéuticos , Farmacias , Farmacia , Humanos , Oncología Médica , Farmacéuticos , Encuestas y Cuestionarios , Bombas de Infusión
4.
Psychiatr Psychol Law ; 28(2): 274-285, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34712096

RESUMEN

In March 2019, a mass shooting at two Christchurch mosques, livestreamed to Facebook, resulted in the deaths of 51 people. Psychologically, this served as a focusing event with high threat salience, shocking a country unused to gun violence despite its comparatively lax firearm legislation. The unprecedented reluctance by the New Zealand media to feature the shooter as a protagonist or even publish his name, concentrating instead on victims and societal issues, helped promote a sense of collective responsibility for change. This was strongly modeled by political leaders. Within weeks, new gun control laws were introduced with bipartisan support. We present this as a national case study, considering psychological and societal enablers for legislative reform in response to extreme gun violence. The shooting also raised the intractable problem of the internet allowing terrorists to promulgate violent content and extremist ideology with regulation in this area harder to achieve than gun control.

5.
Cancer Epidemiol ; 75: 102036, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34562747

RESUMEN

PURPOSE: The incidence of renal cell carcinoma (RCC) is rising. Use of analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol may affect renal function. The aim of this study was to assess associations between analgesic use and risk of RCC. METHODS: A population-based case-control family design was used. Cases were recruited via two Australian state cancer registries. Controls were siblings or partners of cases. Analgesic use was captured by self-completed questionnaire. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for RCC risk associated with regular analgesic use (at least 5 times per month for 6 months or more) and duration and frequency of use. RESULTS: The analysis included 1064 cases and 724 controls. Regular use of paracetamol was associated with an increased risk of RCC (OR 1.41, 95%CI 1.13-1.77). Regular use of NSAIDs was associated with increased risk of RCC for women (OR 1.71, 95% CI 1.23-2.39) but not men (OR 0.83, 95% CI 0.58-1.18; p-interaction=0.003). There was no evidence of a dose-response for duration of use of paracetamol (linear trend p = 0.77) and weak evidence for non- aspirin NSAID use by women (linear trend p = 0.054). CONCLUSION: This study found that regular use of paracetamol was associated with increased risk of RCC. NSAID use was associated with increased risk only for women.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Acetaminofén/efectos adversos , Analgésicos/efectos adversos , Australia/epidemiología , Carcinoma de Células Renales/inducido químicamente , Carcinoma de Células Renales/epidemiología , Femenino , Humanos , Neoplasias Renales/inducido químicamente , Neoplasias Renales/epidemiología
6.
Anaesthesia ; 76(10): 1377-1391, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33984872

RESUMEN

The need to evacuate an ICU or operating theatre complex during a fire or other emergency is a rare event but one potentially fraught with difficulty: Not only is there a risk that patients may come to harm but also that staff may be injured and unable to work. Designing newly-built or refurbished ICUs and operating theatre suites is an opportunity to incorporate mandatory fire safety features and improve the management and outcomes of such emergencies: These include well-marked manual fire call points and oxygen shut off valves (area valve service units); the ability to isolate individual zones; multiple clear exit routes; small bays or side rooms; preference for ground floor ICU location and interconnecting routes with operating theatres; separate clinical and non-clinical areas. ICUs and operating theatre suites should have a bespoke emergency evacuation plan and route map that is readily available. Staff should receive practical fire and evacuation training in their clinical area of work on induction and annually as part of mandatory training, including 'walk-through practice' or simulation training and location of manual fire call points and fire extinguishers, evacuation routes and location and operation of area valve service units. The staff member in charge of each shift should be able to select and operate fire extinguishers and lead an evacuation. Following an emergency evacuation, a network-wide response should be activated, including retrieval and transport of patients to other ICUs if needed. A full investigation should take place and ongoing support and follow-up of staff provided.


Asunto(s)
Desastres , Incendios , Unidades de Cuidados Intensivos , Quirófanos , Administración de la Seguridad/métodos , Urgencias Médicas , Inundaciones , Humanos
7.
Nat Commun ; 12(1): 505, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33479217

RESUMEN

The Rustenburg Layered Suite of the Bushveld Complex of South Africa is a vast layered accumulation of mafic and ultramafic rocks. It has long been regarded as a textbook result of fractional crystallization from a melt-dominated magma chamber. Here, we show that most units of the Rustenburg Layered Suite can be derived with thermodynamic models of crustal assimilation by komatiitic magma to form magmatic mushes without requiring the existence of a magma chamber. Ultramafic and mafic cumulate layers below the Upper and Upper Main Zone represent multiple crystal slurries produced by assimilation-batch crystallization in the upper and middle crust, whereas the chilled marginal rocks represent complementary supernatant liquids. Only the uppermost third formed via lower-crustal assimilation-fractional crystallization and evolved by fractional crystallization within a melt-rich pocket. Layered intrusions need not form in open magma chambers. Mineral deposits hitherto attributed to magma chamber processes might form in smaller intrusions of any geometric form, from mushy systems entirely lacking melt-dominated magma chambers.

8.
Front Cell Dev Biol ; 9: 720798, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35087825

RESUMEN

How does the information in the genome program the functions of the wide variety of cells in the body? While the development of biological organisms appears to follow an explicit set of genomic instructions to generate the same outcome each time, many biological mechanisms harness molecular noise to produce variable outcomes. Non-deterministic variation is frequently observed in the diversification of cell surface molecules that give cells their functional properties, and is observed across eukaryotic clades, from single-celled protozoans to mammals. This is particularly evident in immune systems, where random recombination produces millions of antibodies from only a few genes; in nervous systems, where stochastic mechanisms vary the sensory receptors and synaptic matching molecules produced by different neurons; and in microbial antigenic variation. These systems employ overlapping molecular strategies including allelic exclusion, gene silencing by constitutive heterochromatin, targeted double-strand breaks, and competition for limiting enhancers. Here, we describe and compare five stochastic molecular mechanisms that produce variety in pathogen coat proteins and in the cell surface receptors of animal immune and neuronal cells, with an emphasis on the utility of non-deterministic variation.

11.
Br J Dermatol ; 182(5): 1262-1268, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31378928

RESUMEN

BACKGROUND: Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk. OBJECTIVES: To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors. METHODS: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case-Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age- and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer-Lemeshow test. RESULTS: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71-4·54] in the Australian study and 2·56 (95% CI 2·23-2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76-0·83) in the Australian study and 0·73 (95% CI 0·70-0·75) in the Leeds study. The Hosmer-Lemeshow test P-value was 0·30 in the Australian study and < 0·001 in the Leeds study. CONCLUSIONS: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self-assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically-assessed whole-body naevi and solar lentigines, and self-assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions.


Asunto(s)
Lentigo , Melanoma , Neoplasias Cutáneas , Adolescente , Australia/epidemiología , Estudios de Casos y Controles , Humanos , Lentigo/epidemiología , Melanoma/diagnóstico , Melanoma/epidemiología , Melanoma/etiología , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología
12.
J Eur Acad Dermatol Venereol ; 33(10): 1874-1885, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31087403

RESUMEN

BACKGROUND: People at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes. OBJECTIVE: We examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population-based, case-control studies with comparable ancestry but different ambient sun exposure. METHODS: Data were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case-control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders. RESULTS: Hair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self-reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk. CONCLUSIONS: Classifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self-reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development.


Asunto(s)
Exposición a Riesgos Ambientales , Melanoma/etnología , Nevo Pigmentado/etnología , Neoplasias Cutáneas/etnología , Pigmentación de la Piel , Luz Solar , Adolescente , Adulto , Anciano , Australia/epidemiología , Estudios de Casos y Controles , Extremidades , Femenino , Color del Cabello , Humanos , Masculino , Persona de Mediana Edad , Nevo Pigmentado/patología , Fenotipo , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Neoplasias Cutáneas/patología , Carga Tumoral , Reino Unido/epidemiología , Población Blanca , Adulto Joven
13.
J Parasit Dis ; 43(1): 75-82, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30956449

RESUMEN

The purpose of this study was to optimize primary and nested polymerase chain reaction (PCR) assays for detecting the microsporidia Encephalitozoon intestinalis and Enterocytozoon bieneusi in fecal samples from dairy calves. PCR for these microsporidia were compared to immunofluorescence assays (IFA) based on commercially available monoclonal antibodies specific for outer wall proteins of Enc. intestinalis or Ent. bieneusi. Fecal samples were collected from 15 dairy calves and processed by molecular sieving followed by salt floatation to recover Enc. intestinalis and Ent. bieneusi spores. An aliquot of the final supernatant was applied to glass slides for IFA testing; another aliquot was extracted for total DNA using a QIAamp Stool Mini-Kit for primary and nested Enc. intestinalis- and Ent. bieneusi-specific PCR analysis. Internal standards were generated for both Enc. intestinalis and Ent. bieneusi PCR assays to control for false negative reactions due to the presence of inhibitors commonly found in fecal samples. Using the commercial MicrosporIFA (Waterborne, Inc.) as the gold standard, the optimized Enc. intestinalis PCR method provided 85.7% sensitivity and 100% specificity with a kappa value = 0.865. Likewise, using the commercial BienusiGlo IFA (Waterborne, Inc.) as the gold standard, the optimized Ent. bieneusi PCR method provided 83.3% sensitivity and 100% specificity with a kappa value = 0.857. Sequencing of amplicons from both PCR assays confirmed the presence of Enc. intestinalis or Ent. bieneusi. In conclusion, our optimized assays for recovering and detecting Enc. intestinalis or Ent. bieneusi in feces from dairy calves provides a valuable alternative to traditional IFA methods that require expertise to identify extremely small microsporidia spores (~ 2.0 µm). Our assays also improve upon existing molecular detection techniques for these microsporidia by incorporating an internal standard to control for false negative reactions.

14.
Poult Sci ; 98(8): 3176-3180, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-30953077

RESUMEN

The purpose of this study was to determine if Eimeria oocysts recovered from litter at the time of chick placement in commercial broiler houses contained oocysts that were infectious for chickens. Over 100 litter samples were collected from 30 poultry farms representing a total of 60 different broiler houses with 9 houses sampled more than once over 1.5 yr. The samples were collected just before the placement of newly hatched chicks and after an anticoccidial drug (ACD) or Eimeria vaccine (VAC) program, and processed for counting oocysts followed by Eimeria species determination using ITS1 PCR. Broiler chicks were inoculated with recovered Eimeria oocysts to determine if the litter oocysts were viable and capable of causing patent infection. At placement, E. maxima (Emax) oocysts were detected in 70 of 75 houses after ACD program and 46 of 47 houses after VAC program. Eimeria acervulina, E. praecox, and/or E. tenella (Eapt) were detected in 75 of 75 houses after ACD program and 47 of 47 houses after VAC program. Viability testing revealed that 33.0% of broiler houses contained viable Emax oocysts, while 46.9% contained viable Eapt oocysts. During VAC programs, the concentration of Emax oocysts at placement and the total number of Emax oocysts shed by chickens in viability studies showed a very strong correlation (r = 0.83). Likewise, during ACD programs, the concentration of Eapt oocysts at placement and the total number of Eapt oocysts shed by chickens in the viability study showed a strong correlation (r = 0.62). In general, Eimeria oocyst levels at placement and number of viable oocysts shed by chickens in the viability study were similar among houses on the same farm. However, the number of Eimeria oocysts shed in the viability studies was considerably less than expected based on the number of oocysts given. These data suggest that nearly 100% of all poultry houses contain Emax and Eapt oocysts at placement with 30 to 50% of the houses containing viable Eimeria oocysts, thus possibly representing a source of the protozoa to newly hatched chicks.


Asunto(s)
Coccidiosis/veterinaria , Eimeria/aislamiento & purificación , Oocistos/aislamiento & purificación , Enfermedades de las Aves de Corral/transmisión , Animales , Animales Recién Nacidos , Pollos , Coccidiosis/prevención & control , Coccidiosis/transmisión , Coccidiostáticos/administración & dosificación , Vivienda para Animales , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/prevención & control , Vacunas Antiprotozoos/administración & dosificación , Vacunación/veterinaria
15.
Ann Oncol ; 30(4): 510-519, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30721924

RESUMEN

Despite significant progress in our understanding of the etiology, biology and genetics of colorectal cancer, as well as important clinical advances, it remains the third most frequently diagnosed cancer worldwide and is the second leading cause of cancer death. Based on demographic projections, the global burden of colorectal cancer would be expected to rise by 72% from 1.8 million new cases in 2018 to over 3 million in 2040 with substantial increases anticipated in low- and middle-income countries. In this meeting report, we summarize the content of a joint workshop led by the National Cancer Institute and the International Agency for Research on Cancer, which was held to summarize the important achievements that have been made in our understanding of colorectal cancer etiology, genetics, early detection and treatment and to identify key research questions that remain to be addressed.


Asunto(s)
Neoplasias Colorrectales , Congresos como Asunto , Carga Global de Enfermedades/tendencias , Cooperación Internacional , Carga Global de Enfermedades/estadística & datos numéricos , Humanos , Oncología Médica/organización & administración , Oncología Médica/estadística & datos numéricos , Oncología Médica/tendencias , National Cancer Institute (U.S.)/estadística & datos numéricos , Estados Unidos
16.
BMC Neurol ; 19(1): 20, 2019 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-30738426

RESUMEN

BACKGROUND: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for ß-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures. METHODS: This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician's Global Impression of Change (CGIC). Secondary measures will include the Parkinson's disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson's disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes. DISCUSSION: If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.


Asunto(s)
Ambroxol/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Proyectos de Investigación , Anciano , Encéfalo/efectos de los fármacos , Demencia/etiología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/psicología
17.
IEEE Trans Neural Syst Rehabil Eng ; 26(9): 1823-1834, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30047891

RESUMEN

Recent progress in wearable technology has made wearable tremor suppression devices (WTSDs) for Parkinson's patients a potentially viable alternative solution for tremor management. So far, in contrast to wrist and elbow tremor, finger tremors have not been studied in depth despite the huge impact that they have on a patient's daily life. In addition, more evidence has been found showing that the performance of current tremor estimators may be limited by their model order due to the multiple harmonics present in tremor. The aim of this paper is to characterize finger and wrist tremor in both the time and frequency domains, and to propose a high-order tremor estimation algorithm. Tremor magnitudes are reported in the forms of linear acceleration, angular velocity, and angular displacement. The activation of forearm flexor and extensor muscles is also investigated. The frequency analysis shows that Parkinsonian tremors produce oscillations of the hand with pronounced harmonics. At last, a high-order weighted-frequency Fourier linear combiner (WFLC)-based Kalman filter is proposed. The percentage estimation accuracy achieved from the proposed estimator is 96.3 ± 1.7%, showing average improvements of 28.5% and 48.9% over its lower-order counterpart and the WFLC. The proposed estimator shows promise for use in a WTSD.


Asunto(s)
Mano/fisiopatología , Trastornos Parkinsonianos/fisiopatología , Temblor/diagnóstico , Temblor/fisiopatología , Anciano , Anciano de 80 o más Años , Algoritmos , Fenómenos Biomecánicos , Codo/fisiopatología , Femenino , Dedos/fisiopatología , Análisis de Fourier , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Dispositivos Electrónicos Vestibles , Muñeca/fisiopatología
18.
Poult Sci ; 97(12): 4392-4400, 2018 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-30007365

RESUMEN

Fayoumi chickens are believed to be more disease resistant compared to commercial broiler chickens. The objective of this study was to compare mRNA expression of intestinal nutrient transporters, digestive enzymes, and host defense peptides (HDP) between Eimeria maxima-challenged Fayoumi and Ross broiler chickens. At 21 d of age, Ross broilers and Fayoumi lines M5.1 and M15.2 were challenged with 1,000 E. maxima oocysts. Control birds were not challenged. Duodenum, jejunum, and ileum were sampled (n = 6) at 7 d post challenge. Gene expression was analyzed using relative quantification PCR. Data were analyzed by ANOVA and significance level was set at P < 0.05. There was numerical, but not statistically significant, differential weight gain depression for Ross (15%) and Fayoumi lines M5.1 (21%) and M15.2 (22%) and significant line-specific changes in gene expression. For nutrient transporters, there was downregulation of mRNA for the brush border membrane, amino acid transporters b0,+AT/rBAT, BoAT, and EAAT3 in different segments of the small intestine of Ross and both lines of Fayoumi chickens, indicating that E. maxima challenge likely caused a decrease in nutrient uptake. For HDP, there was downregulation of avian beta defensin (AvBD) 1, 6, 10, 12, and 13 mRNA in the jejunum of the 2 Fayoumi lines, but no change in the Ross broilers. In the duodenum, there was upregulation of AvBD10 mRNA in the Ross and both Fayoumi lines and additionally upregulation of AvBD11, 12, and 13 mRNA in only Fayoumi line M15.2. Liver expressed antimicrobial peptide 2 (LEAP2) mRNA was downregulated in the duodenum and jejunum of Ross and Fayoumi line M5.1 but not in Fayoumi line M15.2. The homeostatic, non-challenged levels of AvBD mRNA were greater in Fayoumi line M15.2 than Ross and Fayoumi line M5.1 in the duodenum and ileum. This study demonstrates tissue- and genetic line-specific transcriptional responses to E. maxima, highlights novel potential candidate genes for response to coccidiosis, and confirms a role for several previously reported genes in response to coccidiosis.


Asunto(s)
Proteínas Aviares/genética , Proteínas Aviares/inmunología , Pollos/genética , Pollos/inmunología , Regulación de la Expresión Génica/inmunología , Inmunidad Innata/genética , Enfermedades de las Aves de Corral/inmunología , Animales , Coccidiosis/inmunología , Coccidiosis/veterinaria , Eimeria/fisiología , Perfilación de la Expresión Génica/veterinaria , Análisis de Secuencia de ADN/veterinaria
19.
Br J Surg ; 105(4): 315-327, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29488648

RESUMEN

BACKGROUND: Recent advances in endovascular technology have enabled minimally invasive repair of the aortic arch, with specifically designed stent-grafts. This article reviews hybrid and total endovascular repair in the management of aortic arch pathology. METHODS: Studies relating to aortic arch management were identified using MEDLINE and Embase, focusing on endovascular repair. RESULTS: Hybrid arch repair is associated with an early mortality rate of some 12 per cent, and carries significant risk of stroke (up to 15 per cent), paraplegia (up to 6 per cent), retrograde dissection (up to 6·5 per cent) and proximal endoleak (6 per cent). Despite patients being of overall higher perioperative risk, hybrid repair has morbidity and early mortality rates comparable to those of open arch replacement. However, rates of freedom from aortic rupture or reintervention are significantly lower in the longer term, owing to the incidence of endoleak. Total endovascular arch repair may be achieved by the use of parallel stents or in situ fenestration in the emergency setting, or use of custom-made devices (scalloped, fenestrated or branched stent-grafts) in the elective setting. Reports of these relatively novel technologies suggest acceptable short-term outcomes, but long-term data are still awaited. CONCLUSION: Repair of aortic arch pathology presents a formidable challenge for endovascular technology. Open aortic arch repair remains the standard in younger, fitter patients, but endovascular technology and experience continue to evolve with encouraging early outcomes and expanding indications.


Asunto(s)
Aorta Torácica/cirugía , Enfermedades de la Aorta/cirugía , Implantación de Prótesis Vascular/métodos , Procedimientos Endovasculares/métodos , Enfermedades de la Aorta/mortalidad , Humanos , Resultado del Tratamiento
20.
Ann R Coll Surg Engl ; 100(4): 316-321, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29484940

RESUMEN

Objective Despite centralisation of the provision of vascular care, not all areas in England and Wales are able to offer emergency treatment for patients with acute conditions affecting the aorta proximal to the renal arteries. While cardiothoracic centres have made network arrangements to coordinate care for the repair of type A dissections, a similar plan for vascular care is lacking. This study investigates early outcomes in patients with ruptured suprarenal aortic aneurysm or dissection (rSRAD) transferred to a specialist centre. Methods Retrospective observational study over a five-year period (2009-2014) assessing outcomes of patients with ruptured sRAD diagnosed at their local hospital and then transferred to a tertiary centre capable of offering such treatment. Results Fifty-two patients (median age 73 years, 32 male) with rSRAD were transferred and a further four died during transit. The mean distance of patient transfer was 35 miles (range 4-211 miles). One patient did not undergo intervention due to frailty and two died before reaching the operating theatre. A total of 23 patients underwent endovascular repair, 9 hybrid repair and 17 open surgery. Median follow-up was 12 months (range 1-43 months). Complications included paraplegia (n = 3), stroke (n = 2), type IA endoleak (n = 4); 30-day and in-hospital mortality were 16% and 27%. For patients discharged alive from hospital, one-year survival was 67%. Conclusions Although the number of patients with rSRAD is low and those who are transferred alive are a self-selecting group, this study suggests that transfer of such patients to a specialist vascular centre is associated with acceptable mortality rates following emergency complex aortic repair.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Rotura de la Aorta/cirugía , Tratamiento de Urgencia/métodos , Procedimientos Endovasculares/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Disección Aórtica/etiología , Disección Aórtica/mortalidad , Aorta/cirugía , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/mortalidad , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/mortalidad , Rotura de la Aorta/etiología , Rotura de la Aorta/mortalidad , Tratamiento de Urgencia/estadística & datos numéricos , Endofuga/epidemiología , Endofuga/etiología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/métodos , Inglaterra/epidemiología , Femenino , Estudios de Seguimiento , Anciano Frágil , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Paraplejía/epidemiología , Paraplejía/etiología , Transferencia de Pacientes/estadística & datos numéricos , Periodo Perioperatorio , Estudios Prospectivos , Estudios Retrospectivos , Stents , Centros de Atención Terciaria/estadística & datos numéricos , Resultado del Tratamiento , Gales/epidemiología
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