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1.
Nat Commun ; 15(1): 3379, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643180

RESUMEN

Transition from traditional high-fiber to Western diets in urbanizing communities of Sub-Saharan Africa is associated with increased risk of non-communicable diseases (NCD), exemplified by colorectal cancer (CRC) risk. To investigate how urbanization gives rise to microbial patterns that may be amenable by dietary intervention, we analyzed diet intake, fecal 16 S bacteriome, virome, and metabolome in a cross-sectional study in healthy rural and urban Xhosa people (South Africa). Urban Xhosa individuals had higher intakes of energy (urban: 3,578 ± 455; rural: 2,185 ± 179 kcal/d), fat and animal protein. This was associated with lower fecal bacteriome diversity and a shift from genera favoring degradation of complex carbohydrates (e.g., Prevotella) to taxa previously shown to be associated with bile acid metabolism and CRC. Urban Xhosa individuals had higher fecal levels of deoxycholic acid, shown to be associated with higher CRC risk, but similar short-chain fatty acid concentrations compared with rural individuals. Fecal virome composition was associated with distinct gut bacterial communities across urbanization, characterized by different dominant host bacteria (urban: Bacteriodota; rural: unassigned taxa) and variable correlation with fecal metabolites and dietary nutrients. Food and skin microbiota samples showed compositional differences along the urbanization gradient. Rural-urban dietary transition in South Africa is linked to major changes in the gut microbiome and metabolome. Further studies are needed to prove cause and identify whether restoration of specific components of the traditional diet will arrest the accelerating rise in NCDs in Sub-Saharan Africa.


Asunto(s)
Neoplasias Colorrectales , Microbioma Gastrointestinal , Pueblo del Sur de África , Humanos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/microbiología , Estudios Transversales , Dieta , Dieta Occidental , Heces/microbiología , Metaboloma , Sudáfrica/epidemiología , Urbanización
2.
Front Nutr ; 11: 1332765, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38321991

RESUMEN

Cell-cultured meat (CM) is a novel meat product grown in vitro from animal cells, widely framed as equivalent to conventional meat but presented as produced in a more sustainable way. Despite its limited availability for human consumption, consumer acceptance of CM (e.g., willingness to purchase and consume) has been extensively investigated. A key but under-investigated assumption of these studies is that CM's sensory qualities are comparable to conventional, equivalent meat products. Therefore, the current review aims to clarify what is actually known about the sensory characteristics of CM and their potential impact on consumer acceptance. To this end, a structured scoping review of existing, peer-reviewed literature on the sensory evaluation of CM was conducted according to the PRISMA-ScR and Joanna Briggs Institute guidelines. Among the included studies (N = 26), only 5 conducted research activities that could be termed "sensory evaluation," with only 4 of those 5 studies evaluating actual CM products in some form. The remaining 21 studies based their conclusions on the sensory characteristics of CM and consequent consumer acceptance to a set of hypothetical CM products and consumption experiences, often with explicitly positive information framing. In addition, many consumer acceptance studies in the literature have the explicit goal to increase the acceptance of CM, with some authors (researchers) acting as direct CM industry affiliates; this may be a source of bias on the level of consumer acceptance toward these products. By separating what is known about CM sensory characteristics and consumer acceptance from what is merely speculated, the current review reported realistic expectations of CM's sensory characteristics within the promissory narratives of CM proponents.

3.
AJNR Am J Neuroradiol ; 44(3): 261-267, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36797031

RESUMEN

BACKGROUND AND PURPOSE: Automated volumetric analysis of structural MR imaging allows quantitative assessment of brain atrophy in neurodegenerative disorders. We compared the brain segmentation performance of the AI-Rad Companion brain MR imaging software against an in-house FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. MATERIALS AND METHODS: T1-weighted images of 45 participants with de novo memory symptoms were selected from the OASIS-4 database and analyzed through the AI-Rad Companion brain MR imaging tool and the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. Correlation, agreement, and consistency between the 2 tools were compared among the absolute, normalized, and standardized volumes. Final reports generated by each tool were used to compare the rates of detection of abnormality and the compatibility of radiologic impressions made using each tool, compared with the clinical diagnoses. RESULTS: We observed strong correlation, moderate consistency, and poor agreement between absolute volumes of the main cortical lobes and subcortical structures measured by the AI-Rad Companion brain MR imaging tool compared with FreeSurfer. The strength of the correlations increased after normalizing the measurements to the total intracranial volume. Standardized measurements differed significantly between the 2 tools, likely owing to differences in the normative data sets used to calibrate each tool. When considering the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline as a reference standard, the AI-Rad Companion brain MR imaging tool had a specificity of 90.6%-100% and a sensitivity of 64.3%-100% in detecting volumetric abnormalities. There was no difference between the rate of compatibility of radiologic and clinical impressions when using the 2 tools. CONCLUSIONS: The AI-Rad Companion brain MR imaging tool reliably detects atrophy in cortical and subcortical regions implicated in the differential diagnosis of dementia.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Corteza Cerebral , Programas Informáticos , Atrofia/patología , Procesamiento de Imagen Asistido por Computador/métodos , Reproducibilidad de los Resultados
4.
Artículo en Inglés | MEDLINE | ID: mdl-36058835

RESUMEN

OBJECTIVE: This study attempted to understand the specific motivations of patients who undergo orthognathic surgery and determine their satisfaction with the surgery. The study also assessed the prevalence of complications and how they may impact patient satisfaction. STUDY DESIGN: Patients who underwent orthognathic surgery at the University of California between 2016 and 2019 and had completed postoperative orthodontic treatment for ≥9 months were interviewed. They responded to an open-ended telephone interview regarding their motivations, satisfaction, and complications. RESULTS: The patients showed a high level of satisfaction with the surgery, but there were persistent complications that affected satisfaction. The predominant complication was paresthesia over the distribution of the inferior alveolar nerve. The majority of patients who reported prior headaches and temporomandibular joint problems described improvement in those areas. Comparing the patients' motivations before and after surgery showed that before surgery, patients reported functional concerns, whereas postoperatively they were much more likely to recall aesthetic reasons for the surgery. CONCLUSION: This study showed that although patients are generally satisfied after orthognathic surgery, patients need to be realistically informed of their expectations and adequately informed of possible complications.


Asunto(s)
Cirugía Ortognática , Procedimientos Quirúrgicos Ortognáticos , Humanos , Satisfacción del Paciente , Motivación , Estética Dental , Cefalea
5.
Child Neuropsychol ; 28(5): 671-688, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35073818

RESUMEN

Learning disorders are common neurodevelopmental conditions, occurring both idiopathically and in the context of other medical conditions. They are frequently comorbid with other neurodevelopmental and psychiatric conditions. Delayed identification and treatment have been associated with significant negative psychosocial consequences. The need for pediatric neuropsychologists to efficiently screen for learning disorders is likely to increase in the months and years following the COVID-19 pandemic, which has severely disrupted access to educational services, especially for children who also face racial and economic disparities. In this paper, we describe a consultation model that can be used to screen for learning disorders and can be completed using both in-person and telemedicine visits. Implementation may result in earlier intervention for struggling children, increase access to neuropsychological services without increasing wait times for comprehensive evaluations, and provide opportunities for collaborations with other health professionals (e.g., pediatricians, therapists, psychiatrists, and neurologists).


Asunto(s)
COVID-19 , Discapacidades para el Aprendizaje , Telemedicina , Adolescente , Niño , Humanos , Discapacidades para el Aprendizaje/diagnóstico , Neuropsicología , Pandemias , Derivación y Consulta
6.
Br J Dermatol ; 186(3): 520-531, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34528236

RESUMEN

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, which in the early patch/plaque stages runs an indolent course. However, ~25% of patients with MF develop skin tumours, a hallmark of progression to the advanced stage, which is associated with high mortality. The mechanisms involved in stage progression are poorly elucidated. OBJECTIVES: We sought to address the hypothesis of MF cell trafficking between skin lesions by comparing transcriptomic profiles of skin samples in different clinical stages of MF. METHODS: We performed whole-transcriptome and whole-exome sequencing of malignant MF cells from skin biopsies obtained by laser-capture microdissection. We compared three types of MF lesions: early-stage plaques (ESP, n = 12) as well as plaques and tumours from patients in late-stage disease [late-stage plaques (LSP, n = 10) and tumours (TMR, n = 15)]. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine pathway changes specific for different lesions which were linked to the recurrent somatic mutations overrepresented in MF tumours. RESULTS: The key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt-mTOR), T helper cell (Th)2/Th9 signalling [interleukin (IL)4, STAT3, STAT5, STAT6], meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, REC8) and DNA repair (PARP1, MYCN, OGG1). Principal coordinate clustering of the transcriptome revealed extensive gene expression differences between early (ESP) and advanced-stage lesions (LSP and TMR). LSP and TMR showed remarkable similarities at the level of the transcriptome, which we interpreted as evidence of cell percolation between lesions via haematogenous self-seeding. CONCLUSIONS: Stage progression in MF is associated with Th2/Th9 polarization of malignant cells, activation of proliferation, survival, as well as increased genomic instability. Global transcriptomic changes in multiple lesions may be caused by haematogenous cell percolation between discrete skin lesions.


Asunto(s)
Linfoma Cutáneo de Células T , Micosis Fungoide , Neoplasias Cutáneas , Antígenos de Neoplasias , Proteínas de Ciclo Celular/genética , Progresión de la Enfermedad , Humanos , Linfoma Cutáneo de Células T/patología , Micosis Fungoide/genética , Micosis Fungoide/patología , Piel/patología , Neoplasias Cutáneas/patología , Transcriptoma
7.
BMJ Open ; 10(3): e035153, 2020 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-32234744

RESUMEN

OBJECTIVE: Implementation of a novel, rapid, high-volume, see-and-treat cervical cancer screening programme using self-swab human papillomavirus (HPV) testing and digital colposcopy in underserved regions of Yunnan China. DESIGN: 480-980 women per day self-swabbed for high-risk HPV (hrHPV+). Four careHPV machines (Qiagen) were run simultaneously to test the specimens. All hrHPV+ patients were contacted the same day and digital colposcopy was performed with the enhanced visual assessment system (MobileODT). Digital images were obtained, and all suspected lesions were biopsied and then treated. SETTING: Rural and underserved areas of the Yunnan province, Kunming municipality. PARTICIPANTS: 3600 women, mean age 50.2 years, who had never been screened for cervical cancer. The women were of the Yi, Hui, Dai and Han ethnicities. INTERVENTIONS: Cryotherapy was performed on all lesions suspicious for cervical intraepithelial neoplasia (CIN) 1 and loop electrosurgical excision procedure was performed on all lesions suspicious for ≥CIN2. Endocervical curettage was performed if the transformation zone was not fully visualised. RESULTS: 216 women (6%) were hrHPV+. 168 underwent same-day colposcopy (23 CIN1, 17≥CIN2). Digital colposcopy was able to identify 15 of 16 (93.8%)≥CIN2 lesions. CONCLUSIONS: This study illustrates a high-volume, rapid and practical strategy that can be used to screen and treat an ethnically diverse group of Chinese women. First, HPV self-sampling allows large numbers of women to be screened rapidly and relatively inexpensively. Only hrHPV+ women will then require further evaluation. Digital colposcopy is then performed on hrHPV+ women with a portable digital colposcope. The high-resolution images obtained can facilitate appropriate same-day treatment as they are able to accurately distinguish between CIN1 and ≥CIN2 lesions.


Asunto(s)
Colposcopía/métodos , Detección Precoz del Cáncer/métodos , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Anciano , China , Crioterapia , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Población Rural , Manejo de Especímenes , Neoplasias del Cuello Uterino/terapia , Displasia del Cuello del Útero/terapia
8.
Ann Oncol ; 30(7): 1080-1087, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31046082

RESUMEN

BACKGROUND: Advanced recurrent ovarian cancer (ROC) is the leading cause of gynecologic cancer-related death in developed countries and new treatments are needed. Previous studies of immune checkpoint blockade showed low objective response rates (ORR) in ROC with no identified predictive biomarker. PATIENTS AND METHODS: This phase II study of pembrolizumab (NCT02674061) examined two patient cohorts with ROC: cohort A received one to three prior lines of treatment with a platinum-free interval (PFI) or treatment-free interval (TFI) between 3 and 12 months and cohort B received four to six prior lines with a PFI/TFI of ≥3 months. Pembrolizumab 200 mg was administered intravenously every 3 weeks until cancer progression, toxicity, or completion of 2 years. Primary end points were ORR by Response Evaluation Criteria in Solid Tumors version 1.1 per blinded independent central review by cohort and by PD-L1 expression measured as combined positive score (CPS). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Cohort A enrolled 285 patients; the first 100 served as the training set for PD-L1 biomarker analysis. Cohort B enrolled 91 patients. ORR was 7.4% for cohort A and 9.9% for cohort B. Median DOR was 8.2 months for cohort A and not reached for cohort B. DCR was 37.2% and 37.4%, respectively, in cohorts A and B. Based on the training set analysis, CPS 1 and 10 were selected for evaluation in the confirmation set. In the confirmation set, ORR was 4.1% for CPS <1, 5.7% CPS ≥1, and 10.0% for CPS ≥10. PFS was 2.1 months for both cohorts. Median OS was not reached for cohort A and was 17.6 months for cohort B. Toxicities were consistent with other single-agent pembrolizumab trials. CONCLUSIONS: Single-agent pembrolizumab showed modest activity in patients with ROC. Higher PD-L1 expression was correlated with higher response. CLINICAL TRIAL NUMBER: Clinicaltrials.gov, NCT02674061.


Asunto(s)
Adenocarcinoma de Células Claras/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adenocarcinoma de Células Claras/patología , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Estudios de Cohortes , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/patología , Pronóstico , Tasa de Supervivencia
9.
Nutr Cancer ; 71(8): 1313-1324, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31007075

RESUMEN

The incidence of colorectal cancer (CRC) is gradually rising in sub-Saharan Africa. This may be due to dietary changes associated with urbanization, which may induce tumor-promoting gut microbiota composition and function. We compared fecal microbiota composition and activity in 10 rural and 10 urban Zimbabweans for evidence of a differential CRC risk. Dietary intake was assessed by a food frequency questionnaire. Fecal microbiota composition, metabolomic profile, functional microbial genes were analyzed, and bile acids and short chain fatty acids quantified. Animal protein intake was higher among urban volunteers, but carbohydrate and fiber intake were similar. Bacteria related to Blautia obeum, Streptococcus bovis, and Subdoligranulum variabile were higher in urban residents, whereas bacteria related to Oscillospira guillermondii and Sporobacter termitidis were higher in rural volunteers. Fecal levels of primary bile acids, cholic acid, and chenodeoxycholic acid (P < 0.05), and secondary bile acids, deoxycholic acid (P < 0.05) and ursodeoxycholic acid (P < 0.001) were higher in urban residents. Fecal levels of acetate and propionate, but not butyrate, were higher in urban residents. The gut microbiota composition and activity among rural and urban Zimbabweans retain significant homogeneity (possibly due to retention of dietary fiber), but urban residents have subtle changes, which may indicate a higher CRC risk.


Asunto(s)
Ácidos y Sales Biliares/efectos adversos , Neoplasias Colorrectales/etiología , Ácidos Grasos Volátiles/efectos adversos , Heces/microbiología , Microbioma Gastrointestinal , Población Urbana/estadística & datos numéricos , Urbanización/tendencias , Anciano , Ácidos y Sales Biliares/análisis , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Fibras de la Dieta/estadística & datos numéricos , Ácidos Grasos Volátiles/análisis , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Población Rural/estadística & datos numéricos , Zimbabwe
10.
Sci Total Environ ; 668: 867-880, 2019 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-30870754

RESUMEN

In many aquatic environments, municipal wastewater treatment facility (WWTF) effluent discharges influence local hydrologic and chemical connectivity between the surface-water and adjacent alluvial shallow-groundwater systems. Fourmile Creek located in Polk County, Iowa received effluent from the Ankeny WWTF for nearly forty years before it was shut down in November 2013. The decommissioning of the municipal WWTF provided a unique opportunity to characterize the recovery from impacts of treated wastewater discharge on water quality at the surface-water/groundwater interface in a shallow, unconfined alluvial aquifer. Dissolved major element and trace element concentrations in Fourmile Creek surface water, hyporheic-zone water, and shallow, unconfined groundwater were monitored upstream and downstream from the WWTF discharge before and after the shutdown. Multivariate statistical techniques including principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) were used to differentiate source-water contributions, characterize elemental components, and describe surface-water/groundwater interaction dynamics. During the post-closure assessment, there was subsurface attenuation of wastewater constituents including Al, B, Cu, Gd, K, Mo, Na, P, Pb, Sb, and Zn. During the same time, groundwater concentrations increased for As, Ba, Ca, Fe, Mg, Mn, SiO2, Sr, and U and represented a profile characteristic of the shallow alluvial aquifer. Hydrologic conditions transitioned from predominantly wastewater infiltration and hyporheic exchange before the WWTF shutdown, to predominantly discharge of native groundwater. Precipitation-driven streamflow events created fluctuations in the groundwater water-table elevations, resulting in variable contact between the saturated and unsaturated zones within the unconfined, alluvial aquifer and intermittent exposure to constituents stored in the sediments. The inorganic fingerprint of municipal wastewater was flushed relatively quickly (≤19 weeks) from the hyporheic zone indicating that processes like diffusion or sorption/desorption that might extend recovery may not be important for many trace elements in this system.

11.
J Dairy Sci ; 102(6): 4972-4977, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30904309

RESUMEN

Natamycin has been used as a natural antimicrobial in dairy products, but the poor light stability of natamycin can limit usefulness in food products. Mycosporine-like amino acids are strong UV absorbers and might be useful as an additive to decrease light-induced degradations. Therefore, the objective of this study was to evaluate the photoprotective effect of mycosporine-like amino acids (MAA) in cow milk stored under 2 lighting conditions in retail commercial display cabinets with fluorescent and high intensity light-emitting diode illumination. When milk was exposed to both fluorescent and light-emitting diode light, natamycin degradation was very fast, and only 17.1 ± 0.9% of its original concentration was observed after 8 d at 4.0°C. On the other hand, by adding MAA into milk, natamycin was retained at 82.2 ± 0.9% and 92.2 ± 0.9% when low and high MAA levels were used, respectively. However, high MAA levels resulted in color changes. Therefore, MAA at low levels had a photoprotective effect for natamycin stability in cow milk exposed to light in refrigerated glass containers.


Asunto(s)
Aminoácidos/farmacología , Antifúngicos/química , Leche/química , Natamicina/química , Animales , Bovinos , Iluminación , Leche/efectos de la radiación , Fotólisis/efectos de los fármacos , Protectores contra Radiación/farmacología
12.
Ann Oncol ; 29(8): 1807-1813, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29992241

RESUMEN

Background: Patients with castration-resistant prostate cancer derive only modest clinical benefit from available therapies. Blockade of the inhibitory programmed death 1 (PD-1) receptor by monoclonal antibodies has been effective in several malignancies. Results from the prostate adenocarcinoma cohort of the nonrandomized phase Ib KEYNOTE-028 trial of pembrolizumab in advanced solid tumors are presented. Materials and methods: Key eligibility criteria included advanced prostate adenocarcinoma, unsuccessful standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), and PD-1 ligand (PD-L1) expression in ≥1% of tumor or stromal cells. Patients received pembrolizumab 10 mg/kg every 2 weeks until disease progression or intolerable toxicity for up to 24 months. Primary end point was objective response rate (ORR) per RECIST v1.1 by investigator review. Results: Median patient age in this cohort (n = 23) was 65 years; 73.9% of patients received at least two prior therapies for metastatic disease. There were four confirmed partial responses, for an ORR of 17.4% [95% confidence interval (CI) 5.0%-38.8%]; 8 of 23 (34.8%) patients had stable disease. Median duration of response was 13.5 months. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 7.9 months, respectively; 6-month PFS and OS rates were 34.8% and 73.4%, respectively. One patient remained on treatment at data cutoff. After a median follow-up of 7.9 months, 14 (60.9%) patients experienced treatment-related adverse events (TRAEs), most commonly nausea (n = 3, 13.0%). Four (17.3%) experienced grade 3/4 TRAEs: grade 3 peripheral neuropathy, grade 3 asthenia, grade 3 fatigue, and grade 4 lipase increase. No pembrolizumab-related deaths or discontinuations occurred. Conclusion: Pembrolizumab resulted in durable objective response in a subset of patients with heavily pretreated, advanced PD-L1-positive prostate cancer, and its side effect profile was favorable. ClinicalTrials.gov Identifier: NCT02054806.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/epidemiología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Supervivencia sin Progresión , Próstata/patología , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Criterios de Evaluación de Respuesta en Tumores Sólidos
14.
Ann Oncol ; 27(8): 1579-85, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27457310

RESUMEN

BACKGROUND: Anti-angiogenic therapies are effective in metastatic renal cell carcinoma (mRCC), but resistance is inevitable. A dual-inhibition strategy focused on hypoxia-inducible factor (HIF) is hypothesized to be active in this refractory setting. CRLX101 is an investigational camptothecin-containing nanoparticle-drug conjugate (NDC), which durably inhibits HIF1α and HIF2α in preclinical models and in gastric cancer patients. Synergy was observed in the preclinical setting when combining this NDC and anti-angiogenic agents, including bevacizumab. PATIENTS AND METHODS: Patients with refractory mRCC were treated every 2 weeks with bevacizumab (10 mg/kg) and escalating doses of CRLX101 (12, 15 mg/m(2)) in a 3 + 3 phase I design. An expansion cohort of 10 patients was treated at the recommended phase II dose (RP2D). Patients were treated until progressive disease or prohibitive toxicity. Adverse events (AEs) were assessed using CTCAE v4.0 and clinical outcome using RECIST v1.1. RESULTS: Twenty-two patients were response-evaluable in an investigator-initiated trial at two academic medical centers. RCC histologies included clear cell (n = 12), papillary (n = 5), chromophobe (n = 2), and unclassified (n = 3). Patients received a median of two prior therapies, with at least one prior vascular endothelial tyrosine kinase inhibitor therapy (VEGF-TKI). No dose-limiting toxicities were observed. Grade ≥3 AEs related to CRLX101 included non-infectious cystitis (5 events), fatigue (3 events), anemia (2 events), diarrhea (2 events), dizziness (2 events), and 7 other individual events. Five of 22 patients (23%) achieved partial responses, including 3 of 12 patients with clear cell histology and 2 of 10 patients (20%) with non-clear cell histology. Twelve of 22 patients (55%) achieved progression-free survival (PFS) of >4 months. CONCLUSIONS: CRLX101 combined with bevacizumab is safe in mRCC. This combination fulfilled the protocol's predefined threshold for further examination with responses and prolonged PFS in a heavily pretreated population. A randomized phase II clinical trial in mRCC of this combination is ongoing.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Camptotecina/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Ciclodextrinas/administración & dosificación , Adulto , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/química , Bevacizumab/efectos adversos , Camptotecina/efectos adversos , Carcinoma de Células Renales/patología , Ciclodextrinas/efectos adversos , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nanopartículas/administración & dosificación , Nanopartículas/química , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos
15.
J Dairy Sci ; 98(4): 2205-14, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25660743

RESUMEN

The effectiveness of titanium dioxide (TiO2)-loaded high-density polyethylene (HDPE) to reduce light-induced oxidation of extended-shelf-life milk (2% total fat) was studied. The objective was to determine differences over time in sensory quality, vitamin retention, and oxidative chemistry as a function of packaging and retail light exposure duration. Effectiveness of packaging for protecting milk quality was assessed by sensory evaluation (triangle tests, untrained panel), changes in volatile compounds, thiobarbituric reactive substances (TBARS), and riboflavin concentration. Milk (2%) was stored in HDPE packages consisting of TiO2 at 3 levels (low: 0.6%; medium: 1.3%; high: 4.3%) at 3 °C for up to 43 d. Light-protected (translucent, foil-wrapped) and light-exposed (translucent) HDPE packages served as controls. The high TiO2-HDPE package provided protection similar to light-protected control package through d 22 of light exposure, with less consistent performance by the medium TiO2 package. The TBARS increased in all treatments during storage. Under the experimental conditions used, a TBARS value of 1.3mg/L could be considered the limiting sensory threshold for differentiating oxidized milk from light-protected milk. Riboflavin concentration decreased 10.5% in the light-protected control and 28.5% in the high TiO2 packaged milk past 29 d of light exposure, but losses were greater than 40% for all other packages. The high TiO2 package protected riboflavin concentration from degradation and controlled aldehyde concentration throughout the test period.


Asunto(s)
Embalaje de Alimentos/métodos , Conservación de Alimentos/métodos , Luz/efectos adversos , Leche/química , Gusto , Animales , Grasas de la Dieta/análisis , Manipulación de Alimentos , Microbiología de Alimentos , Almacenamiento de Alimentos , Cromatografía de Gases y Espectrometría de Masas , Leche/microbiología , Oxidación-Reducción , Polietileno/química , Control de Calidad , Riboflavina/análisis , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Titanio/química , Compuestos Orgánicos Volátiles
16.
QJM ; 108(1): 27-31, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24996769

RESUMEN

BACKGROUND: It is difficult to obtain informed consent for thrombolysis in stroke patients given the emergency setting, the need for a speedy decision and the effects of neurological deficits. AIM: To determine the advance preferences for thrombolysis of patients at risk for stroke following discussion of the potential risks and benefits. DESIGN: Cross-sectional survey. METHODS: Data on benefits and risks of thrombolysis within 3 h and between 3 and 4.5 h after stroke were presented orally, in writing and pictorially to patients attending geriatric and stroke services in a teaching hospital with specified stroke risk factors and preferences for thrombolysis were recorded. RESULTS: Of the 121 participants, 108 (89.3%; 95% confidence interval [CI] 82.4-93.7) would opt for thrombolysis within the 3-h period and 100 (82.6%; 95% CI 74.9-88.4) within the 3- to 4.5-h period after acute stroke (P = 0.04, McNemar's test for correlated proportions). Previous stroke or transient ischaemic attack was more common among those who agreed to thrombolysis (54.1% vs. 30.4%, P = 0.04) and those who opted for thrombolysis were significantly more likely to agree to have their preferences recorded and used in the event of a stroke than those who refused thrombolysis (88.8% vs. 30.4%, P = 0.002). CONCLUSION: Advance discussion of the potential risks and benefits of thrombolysis in at-risk patients may improve decision making if thrombolysis is being considered and the patient can no longer make a decision.


Asunto(s)
Directivas Anticipadas , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/psicología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Toma de Decisiones , Femenino , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Prioridad del Paciente , Medición de Riesgo , Accidente Cerebrovascular/etiología , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Factores de Tiempo
17.
Ir Med J ; 106(7): 214-6, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24218751

RESUMEN

Following a consultation and review process, the interRAI suite of assessment tools was chosen as the most suitable instrument for assessment of the care needs of older people in Ireland. We used previously validated questionnaires to examine the usability, practicality and acceptability of these tools to professionals, carers and clients in rural and urban acute, long-term care and community settings. Of the 45 professionals, 42-44 (93-98%) agreed or strongly agreed with 14 of 15 positive statements regarding the acceptability, clinical value and ease of use of the interRAl tools; 39 (87%) felt the terminology was consistent and familiar, although 35 (78%) felt some areas would require further explanation. Responses from carers (n = 15) and clients (n = 68) were similarly overwhelmingly positive regarding the experience of being assessed using these tools. These results support the clinical utility and practicality of using this approach to assess older people in Irish clinical practice.


Asunto(s)
Actitud del Personal de Salud , Encuestas de Atención de la Salud/métodos , Servicios de Salud para Ancianos , Evaluación de Necesidades , Encuestas y Cuestionarios/normas , Anciano , Humanos , Irlanda , Enfermeras y Enfermeros , Médicos , Proyectos Piloto
18.
J Dairy Sci ; 96(12): 7478-89, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24140329

RESUMEN

The composition of water given to dairy cattle is often ignored, yet water is a very important nutrient and plays a major role in milk synthesis. The objective of this study was to study effects of elevated levels of iron in bovine drinking water on milk quality. Ferrous lactate treatments corresponding to 0, 2, 5, and 12.5mg/kg drinking water concentrations were delivered through the abomasum at 10 L/d to 4 lactating dairy cows over 4 periods (1 wk infusion/period) in a Latin square design. On d 6 of infusion, milk was collected, processed (homogenized, pasteurized), and analyzed. Mineral content (Fe, Cu, P, Ca) was measured by inductively coupled plasma mass spectrometry. Oxidative stability of whole processed milk was measured by the thiobarbituric acid reactive substances (TBARS) assay for malondialdehyde (MDA) and sensory analysis (triangle test) within 72 h of processing and after 7d of storage (4°C). Significant sensory differences between processed milks from cows receiving iron and the control infusion were observed. No differences in TBARS (1.46±0.04 mg of MDA/kg) or mineral content (0.22±0.01 mg/kg Fe) were observed. A 2-way interaction (iron treatment by cow) for Ca, Cu, and Fe concentrations was seen. While iron added directly to milk causes changes in oxidation of milk, high levels of iron given to cattle have subtle effects that initially may not be obvious.


Asunto(s)
Agua Potable/química , Hierro/análisis , Leche/química , Leche/normas , Animales , Calcio/análisis , Bovinos , Cobre/análisis , Relación Dosis-Respuesta a Droga , Femenino , Compuestos Ferrosos/farmacología , Lactatos/farmacología , Malondialdehído/análisis , Espectrometría de Masas , Fósforo/análisis , Sustancias Reactivas al Ácido Tiobarbitúrico
19.
J Dairy Sci ; 95(11): 6242-51, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22981572

RESUMEN

Skim milk, butter-derived aqueous phase, butter oil, and fish oil (3 levels) were used to produce UHT pasteurized n-3 fatty acid-fortified beverages (3.1% fat, 3.9% protein, and 11.5% total solids) with targeted deliveries of 200, 500, and 800 mg of eicosapentaenoic acid and docosahexaenoic acid (combined total) per 250 mL (8 fl oz) serving. Microbial quality, emulsion stability, and oxidation of lipids over 35 d of storage at 4 °C were evaluated. Conjugated diene hydroperoxides were below 1% throughout storage and were found at highest concentrations around d 21 of storage for all formulations. Volatile analysis indicated an increase in 1-penten-3-ol in the n-3 fortified dairy-based beverage systems during storage. Triangle tests were conducted to determine if consumers could detect a difference in aroma, compared with commercially processed aseptically packaged milk. The beverage system with targeted delivery of 500 mg of eicosapentaenoic acid + docosahexaenoic acid per 250-mL serving was not different in aroma compared with commercially available UHT processed milk. This formulation delivered 432 mg of heart-healthy n-3 fatty acids per 250-mL serving on d 35 and was microbiologically and physically stable throughout the 35-d refrigerated storage period.


Asunto(s)
Productos Lácteos , Leche/química , Animales , Bovinos , Productos Lácteos/análisis , Ácidos Docosahexaenoicos/análisis , Ácido Eicosapentaenoico/análisis , Ácidos Grasos Omega-3/análisis , Aceites de Pescado/análisis , Calidad de los Alimentos , Almacenamiento de Alimentos , Alimentos Fortificados/análisis , Alimentos Fortificados/normas , Oxidación-Reducción , Pasteurización/métodos
20.
J Dairy Sci ; 95(4): 1690-8, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22459817

RESUMEN

The objective of this study was to determine the effects of different oils (butter, fish, and oxidized fish) on sensory characteristics of a savory [chile-lime (CL)] low-fat yogurt using descriptive (unstructured line scales, 5 attributes) and affective (hedonic) sensory testing methods. Yogurts were each manufactured at low [1.1-1.2% total fat; 0.43% added oil (wt/wt)] or high [1.6% total fat; 1% added oil (wt/wt)] levels of fish oil, with high levels of fish oil targeted to deliver 145 mg of docosahexaenoic acid+eicosapentaenoic acid/170 g of yogurt. In a preliminary study, untrained panelists (n=31), using triangle tests, did not discriminate between low levels of fish and butter oils in unflavored yogurts but could discern yogurt with oxidized fish oil, even at the low level. Trained panelists (n=12) described lower lime and acid flavor characteristics in CL-flavored yogurts containing 1% oxidized fish oil compared with yogurts containing low levels of oxidized fish oil and low or high levels of butter and fish oils. Oxidized flavor was higher in CL-flavored yogurts with oxidized fish oil (low and high) and with the high level of fish oil. Consumer ratings (n=100; 9-point hedonic scale; 9="like extremely) of overall acceptability and flavor acceptability were bimodally distributed, with overall means between 4 and 5 ("neither like nor dislike") for CL-flavored yogurt with butter or fish oils (high level). The upper 50% of responses for yogurt with butter or fish oil were 6.51 and 6.31, respectively, for overall acceptability ("like slightly"), and 7.02 and 6.56, respectively, for flavor acceptability. A large segment of consumers may be interested in incorporating heart-healthy n-3 lipids in their diets through frequent consumption of a savory yogurt enriched with n-3 fatty acids.


Asunto(s)
Comportamiento del Consumidor , Grasas Insaturadas en la Dieta/administración & dosificación , Ácidos Grasos Omega-3 , Alimentos Fortificados/análisis , Gusto , Yogur/análisis , Actitud Frente a la Salud , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/análisis , Aceites de Pescado/administración & dosificación , Humanos , Oxidación-Reducción , Percepción
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