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1.
Health Qual Life Outcomes ; 22(1): 30, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561752

RESUMEN

BACKGROUND: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. METHODS: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. RESULTS: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. CONCLUSIONS: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Calidad de Vida , Humanos , Persona de Mediana Edad , Anciano , Calidad de Vida/psicología , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Medición de Resultados Informados por el Paciente , China , Psicometría/métodos
2.
J Dev Orig Health Dis ; 14(6): 711-718, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38234128

RESUMEN

We investigated the influence of maternal yellow-pea fiber supplementation in obese pregnancies on offspring metabolic health in adulthood. Sixty newly-weaned female Sprague-Dawley rats were randomized to either a low-calorie control diet (CON) or high calorie obesogenic diet (HC) for 6-weeks. Obese animals were then fed either the HC diet alone or the HC diet supplemented with yellow-pea fiber (HC + FBR) for an additional 4-weeks prior to breeding and throughout gestation and lactation. On postnatal day (PND) 21, 1 male and 1 female offspring from each dam were weaned onto the CON diet until adulthood (PND 120) for metabolic phenotyping. Adult male, but not female, HC offspring demonstrated increased body weight and feed intake vs CON offspring, however no protection was offered by maternal FBR supplementation. HC male and female adult offspring demonstrated increased serum glucose and insulin resistance (HOMA-IR) compared with CON offspring. Maternal FBR supplementation improved glycemic control in male, but not female offspring. Compared with CON offspring, male offspring from HC dams demonstrated marked dyslipidemia (higher serum cholesterol, increased number of TG-rich lipoproteins, and smaller LDL particles) which was largely normalized in offspring from HC + FBR mothers. Male offspring born to obese mothers (HC) had higher hepatic TG, which tended to be lowered (p = 0.07) by maternal FBR supplementation.Supplementation of a maternal high calorie diet with yellow-pea fiber in prepregnancy and throughout gestation and lactation protects male offspring from metabolic dysfunction in the absence of any change in body weight status in adulthood.


Asunto(s)
Pisum sativum , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Masculino , Embarazo , Ratas , Peso Corporal , Dieta Alta en Grasa , Suplementos Dietéticos , Lactancia , Obesidad/complicaciones , Obesidad/prevención & control , Obesidad/metabolismo , Efectos Tardíos de la Exposición Prenatal/etiología , Efectos Tardíos de la Exposición Prenatal/prevención & control , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas Sprague-Dawley
4.
Front Artif Intell ; 5: 872858, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860344

RESUMEN

We explore the use of deep convolutional neural networks (CNNs) trained on overhead imagery of biomass sorghum to ascertain the relationship between single nucleotide polymorphisms (SNPs), or groups of related SNPs, and the phenotypes they control. We consider both CNNs trained explicitly on the classification task of predicting whether an image shows a plant with a reference or alternate version of various SNPs as well as CNNs trained to create data-driven features based on learning features so that images from the same plot are more similar than images from different plots, and then using the features this network learns for genetic marker classification. We characterize how efficient both approaches are at predicting the presence or absence of a genetic markers, and visualize what parts of the images are most important for those predictions. We find that the data-driven approaches give somewhat higher prediction performance, but have visualizations that are harder to interpret; and we give suggestions of potential future machine learning research and discuss the possibilities of using this approach to uncover unknown genotype × phenotype relationships.

5.
JACC Cardiovasc Imaging ; 15(8): 1488-1501, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35331658

RESUMEN

Heart disease is the leading cause of death among men and women. Women have a unique phenotype of ischemic heart disease with less calcified lesions, more nonobstructive plaques, and a higher prevalence of microvascular disease compared with men, which may explain in part why current risk models to detect obstructive coronary artery disease (CAD) may not work as well in women. This paper summarizes the sex differences in the functional and anatomical assessment of CAD in women presenting with stable chest pain and provides an approach for using multimodality imaging for the evaluation of suspected ischemic heart disease in women in accordance to the recently published American Heart Association/American College of Cardiology guidelines for the evaluation and diagnosis of chest pain. A paradigm shift in the approach to imaging ischemic heart disease women is needed including updated risk models, a more profound understanding of CAD in women where nonobstructive disease is more prevalent, and algorithms focused on the evaluation of ischemia with nonobstructive CAD and myocardial infarction with nonobstructive CAD.


Asunto(s)
Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Dolor en el Pecho , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Humanos , Masculino , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/epidemiología , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Factores Sexuales
6.
J Am Coll Radiol ; 18(5S): S2-S12, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33958114

RESUMEN

Coronary atherosclerotic disease is a leading cause of mortality and morbidity due to major cardiovascular events in the United States and abroad. Risk stratification and early preventive measures can reduce major cardiovascular events given the long latent asymptomatic period. Imaging tests can detect subclinical coronary atherosclerosis and aid initiation of targeted preventative efforts based on patient risk. A summary of available imaging tests for low-, intermediate-, and high-risk asymptomatic patients is outlined in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Asunto(s)
Enfermedad de la Arteria Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Diagnóstico por Imagen , Humanos , Sociedades Médicas , Estados Unidos
7.
Clin Transl Sci ; 14(2): 497-501, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32702149

RESUMEN

Patients in the pediatric intensive care unit are exposed to multiple medications and are at high risk for adverse drug reactions. Pharmacogenomic (PGx) testing could help decrease their risk of adverse reactions. Although whole blood is preferred for PGx testing, blood volume in this population is often limited. However, for patients on mechanical ventilation, tracheal secretions are abundant, frequently suctioned, and discarded. Thus, the aim of this pilot study was to determine if tracheal aspirates could be used as a source of human genomic DNA for PGx testing. We successfully extracted DNA from tracheal secretions of all 23 patients in the study. The samples were successfully genotyped for 10 clinically actionable single nucleotide variants across 3 cytochrome P450 genes (CYP2D6, CYP2C19, and CYP3A5). Using DNA from whole blood samples in 11 of the patients, we confirmed the accuracy of the genotyping with 100% concordance. Therefore, our results support the use of tracheal aspirates from mechanically ventilated children as an adequate biospecimen for clinical genetic testing.


Asunto(s)
Secreciones Corporales/química , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Técnicas de Genotipaje/métodos , Pruebas de Farmacogenómica/métodos , Tráquea/metabolismo , Adolescente , Niño , ADN/análisis , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Estudios de Factibilidad , Femenino , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , Masculino , Variantes Farmacogenómicas , Proyectos Piloto , Respiración Artificial
8.
Mol Cancer Ther ; 19(10): 2155-2162, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32847973

RESUMEN

VEGF blockade does not uniformly result in clinical benefit. We evaluated safety, dose-limiting toxicities (DLT), recommended phase II dose (RP2D), antitumor efficacy, and exploratory biomarkers including pharmacogenomics and pharmacokinetics with sorafenib, bevacizumab, and paclitaxel in patients with refractory cancers. The study had a "3 + 3" design, using paclitaxel 80 mg/m2 every week for 3 weeks, in every 4 week cycles, bevacizumab 5 mg/kg every 2 weeks, and sorafenib 200 or 400 mg twice a day, 5 or 7 days/week (5/7, 7/7). The MTD cohort was expanded. Twenty-seven patients enrolled in 3 cohorts: sorafenib 200 mg twice a day 5/7, 200 mg twice a day 7/7, and 400 mg twice a day 5/7. DLTs were grade 3 neutropenia >7 days (cohort 1, 1), grade 3 hypertension (cohort 2, 1), grade 3 hand-foot skin reaction (HFSR; cohort 3, 2). MTD was sorafenib 200 mg twice a day 7/7. Six DLTs occurred in cohort 2 expansion: grade 3 HFSR (2), grade 2 HFSR with sorafenib delay >7 days (2), grade 4 cerebrovascular accident (1), grade 3 neutropenia >7 days (1). RP2D was sorafenib 200 mg twice a day 5/7. Most patients (62%) dose reduced sorafenib to 200 mg daily 5/7 after a median 3 (range, 2-17) cycles. Response rates were 48% overall (27) and 64% for ovarian cancers (14). VEGF-A-1154AA and -7TT recessive homozygous genotypes conferred worse overall survival versus alternative genotypes (7 vs. 22 months). Intermittent, low-dose sorafenib (200 mg twice a day 5/7) combined with bevacizumab and paclitaxel was tolerable and had high antitumor efficacy in patients with refractory cancer (NCT00572078).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias/tratamiento farmacológico , Paclitaxel/uso terapéutico , Farmacogenética/métodos , Sorafenib/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Bevacizumab/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/farmacología , Sorafenib/farmacología
9.
J Diet Suppl ; 17(6): 753-767, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31416362

RESUMEN

Dietary supplementation of α-lipoic acid, an 8-carbon organosulfur compound, has been widely reported to lower blood glucose concentration and/or improve insulin sensitivity in previous randomized controlled trials. Although animal model studies further report fairly consistent lipid lowering in both blood and tissue pools in response to α-lipoic acid supplementation, results from human studies are mixed. According to PRISMA guidelines, we conducted a systematic review of published randomized controlled studies (RCTs) to assess the efficacy of α-lipoic acid supplementation as a strategy to improve dyslipidemia, with a focus on serum lipid endpoints including TC, low density lipoprotein cholesterol (LDL-C), HDL-C, and TG. PubMed, EMBASE, Cochrane Evidence-Based Medicine Reviews, Proquest, Web of Science, and Scopus were searched to identify RCTs that reported the effects of α-lipoic acid on blood lipid concentrations from 1970 to 2017. We included RCTs reporting blood lipid responses in adults supplemented with oral α-lipoic acid versus a placebo or control for at least one month. Studies were reviewed and data were extracted by two independent study authors. Seventeen studies were deemed eligible for inclusion. Overall, mean percent changes in blood lipid endpoints in response to α-lipoic acid varied considerably between studies for total cholesterol (-10.5 to +13.9), low-density lipoprotein cholesterol (-19.67 to +9.06), high-density lipoprotein cholesterol (-12.5 to +29.20), and triglycerides (-38.57 to +17.0). Results of this systematic review suggest little consistent benefit on serum lipids in response to α-lipoic acid supplementation. Further well-controlled studies designed and powered to detect improvements in blood lipids in hypercholesterolemic individuals are warranted (PROSPERO registration number: CRD42018105933).


Asunto(s)
Hipolipemiantes/farmacología , Ácido Tióctico , Adulto , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Suplementos Dietéticos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido Tióctico/farmacología , Triglicéridos/sangre
10.
J Comp Neurol ; 528(6): 953-971, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31600836

RESUMEN

Acupuncture increasingly is accepted as a potential therapy for many diseases in the Western world. However, the mechanism of acupuncture is not well understood mechanistically. We have established that manual acupuncture (MA) at the Neiguan (P6) acupoint inhibits excitatory cardiovascular reflex responses through modulation of the autonomic nervous system in the brainstem. It is unclear whether P6 MA activates neurons in the brain regions beyond the brainstem. Thus, we mapped P6 specific neural activation by MA in the forebrain using the Fos-CreER; Ai9 mice model, which allows for enhanced sensitivity and efficiency compared to conventional immunohistochemical staining. Compared to sham-MA control without manual stimulation, we find that MA at P6 markedly increases c-Fos positive neurons in a number of the forebrain regions (n = 5 in each group). These activated regions include accumbens nucleus, caudate putamen, claustrum, bed nucleus of the stria terminalis, amygdaloid nucleus, ventral posterior division of the thalamic nucleus, paraventricular hypothalamic nucleus, arcuate hypothalamic nucleus, primary and secondary somatosensory cortex, ectorhinal cortex, and dorsolateral entorhinal cortex. As MA at P6 activates neurons in relatively broad brain networks beyond the brainstem, our data suggest that acupuncture at this acupoint has the potential to influence physiological functions associated with autonomic and non-autonomic nervous systems through its effects on multiple brain regions.


Asunto(s)
Terapia por Acupuntura , Mapeo Encefálico/métodos , Prosencéfalo/fisiología , Puntos de Acupuntura , Animales , Genes Reporteros , Genes fos , Integrasas , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos
11.
Food Funct ; 10(9): 5732-5738, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31453617

RESUMEN

Supplementation of health promoting nutraceuticals may be an effective adjunct strategy with other lifestyle and drug approaches to impede disease progression in prediabetic subjects. α-Lipoic acid, a naturally occurring short-chain fatty acid, has been extensively evaluated for its antioxidant and glycemic control properties but has rarely been investigated as a lipid-lowering strategy. We conducted a pilot study to examine the effects of α-lipoic acid supplementation on glycemic control and lipid profile in pre-diabetic, overweight/obese adults. The study was designed as a free-living, randomized, two-phase, placebo-controlled cross-over study with 12 pre-diabetic, dyslipidemic subjects. Eligible subjects completed two thirty-day phases (in random order) consisting of a placebo (600 mg cellulose per day) and α-lipoic acid treatment (600 mg day-1). Although no change (p < 0.05) in serum glucose was observed, α-lipoic acid-supplemented subjects demonstrated reduced fasting serum insulin (p = 0.04) and HOMA-IR (p = 0.07) compared with the placebo group. However, no change (p > 0.05) in serum lipids (including total cholesterol, LDL-C, HDL-C, triglycerides, LDL-C/HDL-C, and TC/HDL-C) were observed. Study results suggest that α-lipoic acid supplementation may be a useful strategy to improve insulin sensitivity in pre-diabetic subjects but is not effective in modulating serum lipids.


Asunto(s)
Estado Prediabético/tratamiento farmacológico , Ácido Tióctico/administración & dosificación , Adulto , Glucemia/metabolismo , HDL-Colesterol/sangre , Estudios Cruzados , Suplementos Dietéticos/análisis , Femenino , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estado Prediabético/sangre , Triglicéridos/sangre
12.
J Nutr Biochem ; 52: 10-17, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29107136

RESUMEN

In hypercholesterolemic pregnancies, the maternal environment is characterized by excessive levels of atherogenic lipids that may increase cardiovascular disease risk in mothers and their offspring. We examined the influence of maternal hypercholesterolemia and phytosterol (PS) intervention on the concentration and metabolism of oxysterols, bioactive oxygenated cholesterol derivatives that regulate arterial health and lesion progression, in mothers and their newly weaned offspring. Twenty-one female apoE-/- mice were randomly assigned to three different diets throughout gestation and lactation: (1) chow, (2) high cholesterol (CH; 0.15%) and (3) CH with added PS (2%, CH/PS). At the end of the lactation period, mothers and pups were euthanized for serum and hepatic oxysterol analyses, hepatic transcriptional profiling of hepatic sterol regulatory targets and atherosclerosis. Hypercholesterolemic dams and their pups demonstrated increased (P˂.05) serum oxysterols [including 24 hydroxycholesterol (HC), 25HC, 27HC, 7αHC, 7ßHC and 7 ketocholesterol)] compared with the chow group that were normalized by maternal PS supplementation. Hepatic oxysterol concentrations followed a similar pattern of response in mothers but were not altered in newly weaned pups. Hepatic mRNA expression suggested a pattern of enhanced abca1/g1 high-density-lipoprotein-mediated efflux but a reduction in biliary abcg5/g8 export in both dams and their pups. Although arterial lesions were not apparent in newly weaned pups, CH dams demonstrated enhanced atherosclerosis that was reduced upon PS intervention. These results demonstrate that offspring from hypercholesterolemic pregnancies have enhanced circulating oxysterol concentrations and highlight the potential utility of PS as a lipid-lowering option during hypercholesterolemic pregnancies for which there are currently limited options.


Asunto(s)
Hipercolesterolemia/metabolismo , Hígado/efectos de los fármacos , Oxiesteroles/metabolismo , Fitosteroles/farmacología , Placa Aterosclerótica/etiología , Animales , Animales Recién Nacidos , Apolipoproteínas E/genética , Citocinas/metabolismo , Suplementos Dietéticos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Hipercolesterolemia/complicaciones , Hipercolesterolemia/dietoterapia , Hígado/fisiología , Masculino , Fenómenos Fisiologicos Nutricionales Maternos , Ratones Mutantes , Oxiesteroles/sangre , Placa Aterosclerótica/patología , Embarazo , Destete
13.
BMC Res Notes ; 10(1): 529, 2017 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-29084592

RESUMEN

OBJECTIVE: An excessive rise in blood lipids during pregnancy may promote metabolic dysfunction in adult progeny. We characterized how maternal phytosterol (PS) supplementation affected serum lipids and the expression of lipid-regulatory genes in the intestine and liver of newly-weaned apo-E deficient offspring from dams fed a chow diet supplemented with cholesterol (0.15%, CH) or cholesterol and PS (2%) (CH/PS) throughout pregnancy and lactation. RESULTS: Serum lipid concentrations and lipoprotein particle numbers were exacerbated in offspring from cholesterol-supplemented mothers but normalized to chow-fed levels in pups exposed to PS through the maternal diet during gestation and lactation. Compared with the CH pups, pups from PS-supplemented mothers demonstrated higher (p < 0.05) expression of the primary intestinal cholesterol transport protein (Niemann-Pick C1-like 1) and the rate-limiting enzyme in hepatic cholesterol synthesis (HMG-CoAr), suggestive of a compensatory response to restore cholesterol balance. Furthermore, pups from PS-supplemented mothers exhibited a coordinated downregulation (p < 0.05) of several genes regulating fatty acid synthesis including PGC1ß, SREBP1c, FAS, and ACC compared with the CH group. These results suggest that maternal PS supplementation during hypercholesterolemic pregnancies protects against aberrant lipid responses in newly-weaned offspring and results in differential regulation of cholesterol and lipid regulatory targets within the enterohepatic loop.


Asunto(s)
Apolipoproteínas E/deficiencia , Colesterol/farmacología , Suplementos Dietéticos , Regulación de la Expresión Génica , Hipercolesterolemia/metabolismo , Hipercolesterolemia/prevención & control , Proteínas de Transporte de Membrana/metabolismo , Fitosteroles/farmacología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Animales , Colesterol/administración & dosificación , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Hipercolesterolemia/sangre , Mucosa Intestinal/metabolismo , Hígado/metabolismo , Ratones , Ratones Noqueados , Fitosteroles/administración & dosificación , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre
14.
Curr Pharm Des ; 23(34): 5077-5085, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28745211

RESUMEN

Phytosterols (PS) are plant-based structural analogous of mammalian cholesterol that have been shown to lower blood cholesterol concentrations by ~10%, although inter-individual response to PS supplementation due to subject-specific metabolic and genetic factors is evident. Recent work further suggests that PS may act as effective triglyceride (TG)-lowering agents with maximal TG reductions observed in hypertriglyceridemic subjects. Although PS have been demonstrated to interfere with cholesterol and perhaps TG absorption within the intestine, they also have the capacity to modulate the expression of lipid regulatory genes through liver X receptor (LXR) activation. Identification of single-nucleotide polymorphisms (SNP) in key cholesterol and TG regulating genes, in particular adenosine triphosphate binding cassette G8 (ABCG8) and apolipoprotein E (apoE) have provided insight into the potential of utilizing genomic identifiers as an indicator of PS responsiveness. While PS supplementation is deemed safe, expanding research into the atherogenic potential of oxidized phytosterols (oxyphytosterols) has emerged with their identification in arterial lesions. This review will highlight the lipid-lowering utility and associated mechanisms of PS and discuss novel applications and future research priorities for PS pertaining to in utero PS exposure for long-term cardiovascular disease risk protection and combination therapies with lipidlowering drugs.


Asunto(s)
Suplementos Dietéticos , Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Lípidos/sangre , Fitosteroles/administración & dosificación , Animales , Ensayos Clínicos como Asunto/métodos , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/tratamiento farmacológico , Lípidos/antagonistas & inhibidores
15.
Can J Urol ; 24(3): 8795-8801, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28646934

RESUMEN

INTRODUCTION: To compare visual analog scale (VAS) pain scores between patients with a 2-minute versus 10-minute delay of peri-prostatic lidocaine injection prior to transrectal ultrasound-guided prostate biopsies (TRUS-bx). MATERIALS AND METHODS: Eighty patients who underwent standard 12-core TRUS-bx by a single surgeon were prospectively randomized into four different treatment arms: bibasilar injection with a 2-minute delay, bibasilar injection plus a single apical injection with a 2-minute delay, bibasilar injection with a 10-minute delay, and bibasilar injection plus a single apical injection with a 10-minute delay. Patients were asked to report their level of pain on the VAS (0-10, with 10 indicating unbearable pain) at the following intervals: probe insertion (baseline), after each core, and post-procedure. The primary outcome measure was mean VAS score across all 12 cores minus baseline VAS score, which we refer to baseline-adjusted mean VAS score. RESULTS: Baseline-adjusted mean VAS score was significantly higher for the 2-minute delay group compared to the 10-minute delay group (mean: -0.7 versus -1.6, p = 0.025). Subset analysis of biopsies 1-3, 4-6, 7-9 and 10-12 also demonstrated higher baseline-adjusted mean VAS scores in the 2-minute delay group (all p ≤ 0.043). CONCLUSIONS: Lower TRUS-bx VAS scores can be achieved by extending the time from lidocaine injection to onset of prostate biopsy from 2 to 10 minutes.


Asunto(s)
Anestesia Local , Anestésicos Locales , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/efectos adversos , Lidocaína , Dolor Asociado a Procedimientos Médicos/prevención & control , Próstata/patología , Adulto , Anciano , Anciano de 80 o más Años , Anestésicos Locales/administración & dosificación , Humanos , Lidocaína/administración & dosificación , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Factores de Tiempo
16.
J Biol Chem ; 292(16): 6810-6820, 2017 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-28235803

RESUMEN

Matrix metalloproteinase 9 (MMP9) is a member of a large family of proteases that are secreted as inactive zymogens. It is a key regulator of the extracellular matrix, involved in the degradation of various extracellular matrix proteins. MMP9 plays a pathological role in a variety of inflammatory and oncology disorders and has long been considered an attractive therapeutic target. GS-5745, a potent, highly selective humanized monoclonal antibody inhibitor of MMP9, has shown promise in treating ulcerative colitis and gastric cancer. Here we describe the crystal structure of GS-5745·MMP9 complex and biochemical studies to elucidate the mechanism of inhibition of MMP9 by GS-5745. GS-5745 binds MMP9 distal to the active site, near the junction between the prodomain and catalytic domain, and inhibits MMP9 by two mechanisms. Binding to pro-MMP9 prevents MMP9 activation, whereas binding to active MMP9 allosterically inhibits activity.


Asunto(s)
Anticuerpos Monoclonales Humanizados/química , Colitis Ulcerosa/tratamiento farmacológico , Metaloproteinasa 9 de la Matriz/química , Inhibidores de la Metaloproteinasa de la Matriz/química , Neoplasias Gástricas/tratamiento farmacológico , Sitio Alostérico , Anticuerpos/química , Dominio Catalítico , Cristalografía por Rayos X , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Gelatina/química , Eliminación de Gen , Células HEK293 , Humanos , Concentración 50 Inhibidora , Unión Proteica , Proteínas Recombinantes/química , Resonancia por Plasmón de Superficie
17.
Am J Med ; 130(6): e241-e244, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28161348

RESUMEN

BACKGROUND: Overuse of laboratory investigations is widely prevalent in hospitalized patients, leads to discomfort, and increases direct and indirect costs. OBJECTIVE: We implemented a simple, inexpensive, mindfulness strategy on our inpatient medical clinical teaching unit to reduce unnecessary laboratory orders through education, a forcing function, and daily structured laboratory "time outs." METHODS: On a 26-bed unit in an academic hospital center, the per-period laboratory costs per patient were compared pre- and postintervention using segmented regression analysis of an interrupted time series. RESULTS: The average cost per admitted patient decreased from $117 to $66, with an estimated savings of $50,657 over 985 admissions. After adjusting for fiscal period and the presence of our intervention, there was a significant reduction in the per-patient number of total tests, complete blood counts, and electrolyte panels performed (P <.001 for all level and time trend changes). CONCLUSION: This trainee-designed and -led intervention, centered around structured, mindfulness-based laboratory test ordering, was successful at decreasing the overuse of common daily blood work in hospitalized patients.


Asunto(s)
Técnicas de Laboratorio Clínico/economía , Hospitalización/economía , Laboratorios de Hospital/economía , Atención Plena , Procedimientos Innecesarios/economía , Canadá , Ahorro de Costo , Hospitales de Enseñanza/economía , Humanos
18.
Pediatr Allergy Immunol Pulmonol ; 30(3): 148-154, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35923008

RESUMEN

Children born preterm are at risk of hospital admission for respiratory infection in the first years of life. Vitamin D deficiency has been associated with increased risk of developing lower respiratory tract infection (LRTI). We assessed vitamin D levels in children born preterm admitted to the hospital ward or pediatric intensive care unit (PICU) with viral LRTI. A prospective observational cohort study was conducted over 3 years that enrolled 87 children <3 years of age, born <37 weeks of gestation. Children were enrolled in the ward and PICU if they had a diagnosis of LRTI with confirmed viral testing. Children seen in the outpatient clinic for well-child care were enrolled as study controls. Vitamin D and cathelicidin levels were measured and associations between vitamin D, cathelicidin, and admission sites were tested. Vitamin D levels were lower in children admitted to the PICU when compared to controls (28 ng/mL versus 36 ng/mL; P < 0.03) but were not different between children admitted to the ward or PICU. Overall, vitamin D levels were lower in children born late preterm (≥34 weeks, LPT) when compared to those born early preterm (<34 weeks, EPT), (28 ng/mL versus 34 ng/mL; P = 0.016), and EPT children were more likely to receive multivitamin supplementation before admission. Vitamin D levels in children born prematurely, admitted to the PICU, were lower than in controls. Overall levels were lower in LPT infants and this group did not receive multivitamin supplementation as much as those considered EPT. Prior research has shown associations between low vitamin D levels and respiratory disease. To our knowledge, this is the first study showing an association between low vitamin D levels and severity of respiratory disease, specifically in preterm children. Further, we found that late preterm children have lower levels of vitamin D and less frequent multivitamin supplementation.

19.
J Diet Suppl ; 14(3): 334-345, 2017 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-27653386

RESUMEN

Resistant starch (RS) has been well characterized for its glycemic control properties; however, there is little consensus regarding the influence of RS on blood lipid concentrations and lipoprotein distribution and size. Therefore, this study aimed to characterize the effect of daily RS supplementation in a controlled capsule delivery on biomarkers of cardiovascular (blood lipids, lipoproteins) and diabetes (glucose, insulin) risk in a pig model. Twelve 8-week-old male Yorkshire pigs were placed on a synthetic Western diet and randomly divided into two groups (n = 6/group) for 30 days: (1) a placebo group supplemented with capsules containing unmodified pre-gelatinized potato starch (0 g/RS/day); and (2) an RS group supplemented with capsules containing resistant potato starch (10 g/RS/day). Serum lipids including total-cholesterol (C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides did not differ (p > 0.05) between the RS and placebo groups. Although the total numbers of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles were similar (p > 0.05) between the two groups, total high-density lipoprotein (HDL) particles were higher (+28%, p < 0.05) in the RS group compared with placebo, resulting from an increase (p < 0.05) in the small HDL subclass particles (+32%). Compared with the placebo group, RS supplementation lowered (p < 0.05) fasting serum glucose (-20%) and improved (p < 0.05) insulin resistance as estimated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) without a change in insulin. Additionally, total serum glucagon-like-peptide 1 (GLP-1) was higher (+141%, p < 0.05) following RS supplementation compared with placebo. This data suggests that in addition to the more well-characterized effect of RS intake in lowering blood glucose and improving insulin sensitivity, the consumption of RS may be beneficial in lipid management strategies by enhancing total HDL particle number.


Asunto(s)
Dieta Occidental , Suplementos Dietéticos , Lipoproteínas HDL/sangre , Almidón/administración & dosificación , Animales , Biomarcadores/sangre , Glucemia/análisis , Ayuno/sangre , Péptido 1 Similar al Glucagón/sangre , Insulina/sangre , Resistencia a la Insulina , Lípidos/sangre , Lipoproteínas LDL/sangre , Masculino , Distribución Aleatoria , Porcinos , Triglicéridos/sangre
20.
Urology ; 99: 186-191, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27771424

RESUMEN

OBJECTIVE: To compare the frequency of postoperative encounters in the 30-day and 90-day postoperative periods for various bladder outlet obstruction surgical therapies. MATERIALS AND METHODS: All patients who underwent transurethral resection of the prostate (TURP), GreenLight laser photovaporization of the prostate (GL-PVP) (American Medical Systems Inc.), and holmium laser enucleation of the prostate (HoLEP) from January 1, 2012 to December 31, 2014 were followed for 6 months postoperatively. All postoperative encounters such as patient calls or questions, catheter exchanges or removals, and hospital-based readmissions or emergency department visits were recorded in the electronic medical record. RESULTS: Two hundred and ninety-one consecutive patients underwent outlet procedures during the study period: TURP (N = 199; mean age, 71 years; mean body mass index [BMI], 28.5), HoLEP (N = 60; mean age, 68 years; mean BMI, 28.1), or GL-PVP (N = 32; mean age, 72 years; mean BMI, 29.3). No statistically significant difference was observed for age, BMI, preoperative American Urological Association symptom score, or preoperative maximum flow velocity between the 3 groups. Thirty-day postoperative encounters differed significantly between the 3 surgery types (P < .001). Specifically, there were fewer encounters within 30 days of surgery for TURP compared to both HoLEP (≥1 encounter: TURP = 48.7%, HoLEP = 66.7%; P = .006) and GL-PVP (≥1 encounter: TURP = 48.7%, GL-PVP = 93.7%; P < .001). The number of encounters within 90 days postoperatively was also significantly lower for TURP patients (P < .001). CONCLUSION: TURP results in fewer postoperative encounters in both the 30-day and 90-day postoperative periods compared to HoLEP and GL-PVP. Laser prostate therapies may place increased burden on clinic staff during the 30-day and 90-day postoperative periods.


Asunto(s)
Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Visita a Consultorio Médico/tendencias , Complicaciones Posoperatorias/epidemiología , Hiperplasia Prostática/cirugía , Medición de Riesgo/métodos , Resección Transuretral de la Próstata/efectos adversos , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Incidencia , Terapia por Láser/efectos adversos , Terapia por Láser/métodos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Pronóstico , Hiperplasia Prostática/complicaciones , Estudios Retrospectivos , Factores de Tiempo , Resección Transuretral de la Próstata/métodos , Resultado del Tratamiento , Estados Unidos/epidemiología , Obstrucción del Cuello de la Vejiga Urinaria/cirugía
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