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1.
Genetica ; 152(1): 11-29, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38099985

RESUMEN

The African grass or Nile rat (NR) (Arvicanthis niloticus) is a herbivorous diurnal rodent which is used as a biological model for research on type 2 diabetes mellitus (T2DM) and the circadian rhythm. Similar to humans, male NRs develop T2DM with high-carbohydrate diets. The NR thus provides a unique opportunity to identify the nutritional and underlying genetic factors that characterise human T2DM, as well as the effects of potential anti-diabetic phytochemicals such as Water-Soluble Palm Fruit Extract. Whole genome sequencing (WGS) could help identify possible genetic causes why NRs spontaneously develop T2DM in captivity. In this study, we performed WGS on a hepatic deoxyribonucleic acid (DNA) sample isolated from a male NR using PacBio high-fidelity long-read sequencing. The WGS data obtained were then de novo assembled and annotated using PacBio HiFi isoform sequencing (Iso-Seq) data as well as previous Illumina RNA sequencing (RNA-Seq) data. Genes related to insulin and circadian rhythm pathways were present in the NR genome, similar to orthologues in the rat, mouse and human genomes. T2DM development in the NR is thus most likely not attributable to structural differences in these genes when compared to other biological models. Further studies are warranted to gain additional insights on the genetic-environmental factors which underlie the genetic permissiveness of NRs to develop T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insulina , Humanos , Ratones , Animales , Masculino , Murinae/genética , Diabetes Mellitus Tipo 2/genética , Ritmo Circadiano/genética
2.
Public Health ; 232: 146-152, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38781781

RESUMEN

OBJECTIVES: Modern slavery is a public health challenge. The objective of this research was to build and refine a public health approach to addressing it. STUDY DESIGN: This was a participatory qualitative study with a proof-of-concept exercise. METHODS: Nine deliberative workshops with 65 people working across the antislavery sector. Thematic analysis of qualitative data. Of the nine workshops, two were proof of concept. These explored and tested the public health framework devised. RESULTS: Participants contributed to the development of a public health framework to modern slavery that included multiple elements across national, local, and service levels. There were six 'C's to national components: policy that was coherent, co-ordinated, consistent, comprehensive, co-operative and compliant with international law. Local components centred on effective local multiagency partnerships and service design and delivery focussed on trauma-informed, flexible, person-centred care. CONCLUSIONS: A public health approach to modern slavery is a promising development in the antislavery field in the United Kingdom and globally. It was well supported by workshop participants and appeared to be operable. Barriers to its implementation exist, however, including the challenge of intersectoral working and an incongruent policy environment.


Asunto(s)
Esclavización , Salud Pública , Investigación Cualitativa , Humanos , Reino Unido , Política de Salud
3.
Pediatr Surg Int ; 39(1): 236, 2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37468717

RESUMEN

INTRODUCTION: During "bowel management week," abdominal radiographs are used to monitor the amount and location of stool. A radiologist familiar with the treatment plan can provide an improved interpretation. The goal of this paper is to standardize the radiological reports during a bowel management week. METHODS: We saw 744 patients during bowel management week from May 2016 until March 2023. Diagnosis included: anorectal malformation (397), idiopathic constipation (180), Hirschsprung disease (89), and spina bifida (78). Laxatives were the treatment for 51% of patients, and 49% received enemas. Characteristic radiographs were selected for each treatment group for a proposed reading standardization. RESULTS: When the stool is visualized, it is crucial to report its location. Having a contrast enema helps with the correct interpretation of the colonic anatomy. It is also essential to always compare the amount of stool with the radiograph from the previous day to determine if there is an increase or decrease in stool. Examples of radiographs are shown to guide the use of the preferred proposed terminology. CONCLUSION: Providing information regarding which treatment modality the patient is receiving and stating that a patient is on a bowel management week treatment is crucial for the radiologist to provide adequate interpretation. The radiologist must be familiar with the treatment goals and purpose of the daily radiograph.


Asunto(s)
Incontinencia Fecal , Enfermedad de Hirschsprung , Humanos , Estreñimiento/terapia , Laxativos , Intestinos , Enema , Enfermedad de Hirschsprung/terapia , Enfermedad de Hirschsprung/tratamiento farmacológico , Incontinencia Fecal/terapia
4.
Breast Cancer Res Treat ; 191(2): 409-422, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34739658

RESUMEN

PURPOSE: It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I-III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. METHODS: Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher's exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes RESULTS: In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p = .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p = .05) and diabetes (p = .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p = .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. CONCLUSION: Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.


Asunto(s)
Neoplasias de la Mama , Antraciclinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Medición de Resultados Informados por el Paciente
5.
Osteoporos Int ; 32(7): 1413-1420, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33415374

RESUMEN

Most adherence studies only consider treatment following a first prescription. Using an extended follow-up, we found that 60% of seniors starting oral bisphosphonate therapy were exposed for ≥ 3 years (48% for ≥ 5 years). Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years. INTRODUCTION: The purpose of this study was to identify and describe patterns of long-term oral bisphosphonate use among seniors using a novel methodological approach that considers extended follow-up. METHODS: Among Ontarians aged 66 years or older, we identified subjects with a first dispensing of alendronate or risedronate between November 2000 and December 2016. We followed them until death or December 2019 to identify patients with ≥ 3 years of bisphosphonate use, defined as a proportion of days covered ≥ 80%, using 3-year rolling windows. We calculated the proportion of patients with long-term therapy (≥ 3 years of use) using Kaplan-Meier estimates. We described patterns of long-term use and compared patient characteristics between patients with and without long-term therapy. RESULTS: We identified 260,784 eligible seniors initiating bisphosphonate therapy. Of these, 60% continued therapy ≥ 3 years (77% women), and 48% continued ≥ 5 years. Characteristics did not meaningfully differ between patients with or without long-term therapy. The median length of long-term therapy was 7.0 (IQR 5.1) years for women and 6.1 (IQR 4.3) years for men. Only 20% experienced a treatment gap before long-term therapy, yet 50% experienced a treatment gap of ≥ 120 days after a median 5.3 years of therapy. Eighty-one percent who returned to therapy following a treatment gap re-initiated an oral bisphosphonate, with 18% switching to denosumab. CONCLUSIONS: Among seniors initiating oral bisphosphonates, we found that 60% receive at least 3 years of therapy when using an extended follow-up. Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.


Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis , Alendronato/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Osteoporosis/tratamiento farmacológico
6.
Public Health Nurs ; 38(3): 412-418, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33201523

RESUMEN

More clinical sites are essential to meeting the learning needs of nursing students who will care for patients with chronic disease after graduation. Partnerships between schools of nursing and academic practices can increase clinical training capacity, allow future nurse practitioners (NPs) to apply knowledge and skills in the context of care delivery, and potentially improve patient outcomes with little associated risk. This article describes the experiences of primary care NP students (n = 37), NP faculty (n = 2), and clinic providers (n = 2) in an academic practice partnership performing home visits with complex pediatric asthma and adult heart failure (HF) patients. A 14-item postexperience survey was used to obtain student feedback. Over 75% (n = 28) of student participants responded. Most respondents, 80% assigned to pediatric asthma patients and 90% assigned to adult HF patients, reported the home visit experience prepared them to care for patients with chronic diseases. Clinic providers indicated the extra attention to both patient groups reduced barriers to care and improved care continuity. This partnership offers a model for developing clinical skills in advanced practice nursing students and enhancing scarce clinical placement resources. Findings were used to refine the program and expand to include all 150 students in the subsequent academic year.


Asunto(s)
Bachillerato en Enfermería , Educación en Enfermería , Estudiantes de Enfermería , Adulto , Niño , Enfermedad Crónica , Manejo de la Enfermedad , Humanos
7.
Aust Crit Care ; 34(3): 217-225, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33039302

RESUMEN

BACKGROUND: Patients on extracorporeal membrane oxygenation (ECMO) often require prolonged periods of bed rest owing to their severity of illness along with the care required to maintain the position and integrity of the ECMO cannula. Many patients on ECMO receive passive exercises, and rehabilitation is often delayed owing to medical instability, with a high proportion of patients demonstrating severe muscle weakness. The physiological effects of an intensive rehabilitation program started early after ECMO commencement remain unknown. OBJECTIVES: The primary objective of this study was to describe the respiratory and haemodynamic effects of early intensive rehabilitation compared with standard care physiotherapy over a 7-d period in patients requiring ECMO. METHODS: This was a physiological substudy of a multicentre randomised controlled trial conducted in one tertiary referral hospital. Consecutive adult patients undergoing ECMO were recruited. Respiratory and haemodynamic parameters, along with ECMO settings, were recorded 30 min before and after each session and continuously during the session. In addition, the minimum and maximum values for these parameters were recorded outside of the rehabilitation or standard care sessions for each 24-h period over the 7 d. The number of minutes of exercise per session was recorded. RESULTS: Fifteen patients (mean age = 51.5 ± standard deviation of 14.3 y, 80% men) received ECMO. There was no difference between the groups for any of the respiratory, haemodynamic, or ECMO parameters. The minimum and maximum values for each parameter were recorded outside of the rehabilitation or standard care sessions. The intensive rehabilitation group (n = 7) spent more time exercising per session than the standard care group (n = 8) (mean = 28.7 versus 4.2 min, p < 0.0001). Three patients (43%) in the intensive rehabilitation group versus none in the standard care group mobilised out of bed during ECMO. CONCLUSIONS: In summary, early intensive rehabilitation of patients on ECMO had minimal effect on physiological parameters.


Asunto(s)
COVID-19 , Oxigenación por Membrana Extracorpórea , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modalidades de Fisioterapia , Proyectos Piloto , Estudios Retrospectivos , Resultado del Tratamiento
8.
Emerg Infect Dis ; 26(7): 1542-1547, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32315281

RESUMEN

We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. Its genome is closest to that of severe acute respiratory syndrome-related coronaviruses from horseshoe bats, and its receptor-binding domain is closest to that of pangolin viruses. Its origin and direct ancestral viruses have not been identified.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Quirópteros/virología , Animales , Betacoronavirus/clasificación , Betacoronavirus/genética , Filogenia , Recombinación Genética , SARS-CoV-2
9.
Emerg Infect Dis ; 26(12): 2961-2965, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32730733

RESUMEN

Severe acute respiratory syndrome coronavirus 2 did not replicate efficiently in 13 bat cell lines, whereas severe acute respiratory syndrome coronavirus replicated efficiently in kidney cells of its ancestral host, the Rhinolophus sinicus bat, suggesting different evolutionary origins. Structural modeling showed that RBD/RsACE2 binding may contribute to the differential cellular tropism.


Asunto(s)
SARS-CoV-2/fisiología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Tropismo Viral/genética , Animales , COVID-19 , Quirópteros/virología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Pandemias , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , SARS-CoV-2/genética , Replicación Viral
10.
FASEB J ; 33(9): 10327-10338, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31264891

RESUMEN

Controversy remains about how diet affects the vascular endothelial dysfunction associated with disordered insulin-glucose homeostasis. It is postulated that the type and level of certain macronutrients contribute to endothelial dysfunction in vascular diabetes complications. However, it is not well understood how specific macronutrients affect the molecular inflammatory response under conditions of hyperglycemia. Here, we examined retinal microvascular endothelial injury in streptozotocin (STZ)-diabetic rats fed a laboratory Western diet (WD). WD, characterized by its high content of saturated fat, cholesterol, and sugar, significantly increased retinal leukocyte accumulation and endothelial injury in the STZ-diabetic rats. Suppression of endothelial NF-κB signaling in the STZ model reduced the WD-induced increase in leukocyte accumulation. To isolate the effect of dietary fat, we generated high-fat diets with varying fatty acid balance and type. These diets contained moderate amounts of carbohydrates but no sugar. We found that neither high levels of saturated or unsaturated fats per se increased retinal leukocyte accumulation and endothelial injury in the STZ-diabetic rat model but that the combination of high levels of dietary cholesterol with specific saturated fatty acids that are abundant in WD exacerbated leukocyte accumulation and endothelial injury in the retinas of STZ-diabetic rats.-Barakat, A., Nakao, S., Zandi, S., Sun, D., Schmidt-Ullrich, R., Hayes, K. C., Hafezi-Moghadam, A. In contrast to Western diet, a plant-based, high-fat, low-sugar diet does not exacerbate retinal endothelial injury in streptozotocin-induced diabetes.


Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Retinopatía Diabética/patología , Dieta Baja en Carbohidratos/efectos adversos , Dieta Alta en Grasa/efectos adversos , Dieta Vegetariana/efectos adversos , Dieta Occidental/efectos adversos , Modelos Animales de Enfermedad , Retina/efectos de los fármacos , Animales , Diabetes Mellitus Experimental/dietoterapia , Retinopatía Diabética/etiología , Retinopatía Diabética/metabolismo , Azúcares de la Dieta/efectos adversos , Células Endoteliales/efectos de los fármacos , Incidencia , Masculino , Ratas , Ratas Long-Evans , Retina/lesiones
11.
Mol Biol Rep ; 47(12): 9409-9427, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33222119

RESUMEN

The Nile rat (Arvicanthis niloticus) is a novel diurnal carbohydrate-sensitive rodent useful for studies on type 2 diabetes mellitus (T2DM) and the metabolic syndrome. Hepatic responses to T2DM and any interventions thereof can be evaluated via transcriptomic gene expression analysis. However, the study of gene expression via real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) requires identification of stably expressed reference genes for accurate normalisation. This study describes the evaluation and identification of stable reference genes in the livers from Control Nile rats as well as those supplemented with Water-Soluble Palm Fruit Extract, which has been previously shown to attenuate T2DM in this animal model. Seven genes identified as having stable expression in RNA-Sequencing transcriptome analysis were chosen for verification using real-time RT-qPCR. Six commonly used reference genes from previous literature and two genes from a previous microarray gene expression study in Nile rats were also evaluated. The expression data of these 15 candidate reference genes were analysed using the RefFinder software which incorporated analyses performed by various algorithms. The Hpd, Pnpla6 and Vpp2 genes were identified as the most stable across the 36 samples tested. Their applicability was demonstrated through the normalisation of the gene expression profiles of two target genes, Cela1 and Lepr. In conclusion, three novel reference genes which can be used for robust normalisation of real-time RT-qPCR data were identified, thereby facilitating future hepatic gene expression studies in the Nile rat.


Asunto(s)
Alimentación Animal , Frutas/química , Expresión Génica/efectos de los fármacos , Murinae/genética , Phoeniceae/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Agua/química , Administración Oral , Algoritmos , Animales , Suplementos Dietéticos , Perfilación de la Expresión Génica , Genes Esenciales , Hígado/metabolismo , Masculino , Programas Informáticos , Solubilidad , Transcriptoma/efectos de los fármacos
12.
Breast Cancer Res Treat ; 173(1): 245, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30306432

RESUMEN

In the original publication, the sixth author name was published incorrectly as A. Wood. The correct author name should read as W. A. Wood.

13.
Osteoarthritis Cartilage ; 27(6): 885-894, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30825608

RESUMEN

OBJECTIVE: Examine associations of hip abductor strength with (1) cartilage damage worsening in the tibiofemoral and patellofemoral compartments 2 years later, and (2) poor function and disability outcomes 5 years later. METHODS: Participants had knee osteoarthritis (K/L ≥ 2) in at least one knee. Hip abductor strength was measured using Biodex Dynamometry. Participants underwent 3.0T MRI of both knees at baseline and 2 years later. Baseline-to-2-year cartilage damage progression, defined as any worsening of WORMS cartilage damage score, was assessed at each tibiofemoral and patellofemoral surface. LLFDI (Late-Life Function and Disability Instrument) and Chair-Stand-Rate were recorded at baseline and 5-year follow-up; outcomes analyzed using quintiles. Poor outcomes were defined as remaining in the same low-function quintiles or being in a worse quintile at 5-year follow-up. We analyzed associations of baseline hip abductor strength with cartilage damage worsening and function and disability outcomes using multivariable log-binomial models. RESULTS: 275 knees from 164 persons [age = 63.7 (SD = 9.8) years, 79.3% women] comprised the structural outcome sample, and 187 persons [age = 64.2 (9.7), 78.6% women] the function and disability outcomes sample. Greater baseline hip abductor strength was associated with reduced risks of baseline-to-2-year medial patellofemoral and lateral tibiofemoral cartilage damage worsening [adjusted relative risks (RRs) range: 0.80-0.83) and with reduced risks of baseline-to-5-year poor outcomes for Chair-Stand-Rate and LLFDI Basic Lower-Extremity Function and Disability Limitation (adjusted RRs range: 0.91-0.94). CONCLUSION: Findings support a beneficial role of hip abductor strength for disease modification and for function and disability outcomes, and as a potential therapeutic target in managing knee osteoarthritis.


Asunto(s)
Actividades Cotidianas , Cartílago Articular/diagnóstico por imagen , Fuerza Muscular , Osteoartritis de la Rodilla/fisiopatología , Rendimiento Físico Funcional , Músculo Cuádriceps , Anciano , Nalgas , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético , Osteoartritis de la Rodilla/diagnóstico por imagen , Factores Protectores , Muslo
14.
Osteoporos Int ; 30(11): 2311-2319, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31317249

RESUMEN

Characteristics of patients starting oral bisphosphonate therapy changed over time, reflecting trends in osteoporosis management (e.g., new drugs to market), and general healthcare delivery (e.g., benzodiazepine use declined, statin use increased). When designing studies that examine osteoporosis drug effects, potential time-related biases must be considered. INTRODUCTION: To describe the type of oral bisphosphonate initiated and characteristics of patients starting oral bisphosphonate therapy over time. METHODS: We identified community-dwelling older adults (ages ≥ 66 years) initiating oral bisphosphonate therapy from April 1996 to March 2016 (1996 to 2015 fiscal years) using healthcare administrative data in Ontario. Patients with conditions other than osteoporosis that may impact bisphosphonate prescribing were excluded. The bisphosphonate initiated and patient characteristics were summarized by fiscal year and stratified by sex. RESULTS: We identified 560,817 eligible patients (81% women). Most patients initiated cyclical etidronate from 1996 until 2005, and then weekly regimens became dominant. In 2008, risedronate became the main oral bisphosphonate (46% risedronate, 43% alendronate, 11% etidronate); with its use increasing after availability of monthly and delayed-release risedronate formulations. In 2015, 71% of patients started risedronate, 28% started alendronate, and less than 2% started etidronate. Characteristics of patients changed over time, reflecting changes in osteoporosis management and general healthcare delivery. Over time, a larger proportion of men (9% to 28%) and patients with diabetes (women 10% to 17%, men 14% to 22%) initiated therapy; benzodiazepine (women 22% to 13%, men 20% to 10%) and estrogen-based hormone replacement therapy (12% to 15% of women 1996-2002 to 3% since 2008) decreased, while statin use increased (women 15% to 39%, men 14% to 52%). CONCLUSIONS: The characteristics of patients starting oral bisphosphonate therapy have changed over time. Consideration must be given to these time trends when designing studies that examine osteoporosis drug effects.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiología , Administración Oral , Anciano , Anciano de 80 o más Años , Alendronato/uso terapéutico , Esquema de Medicación , Ácido Etidrónico/uso terapéutico , Femenino , Humanos , Masculino , Ontario/epidemiología , Farmacoepidemiología/tendencias , Ácido Risedrónico/uso terapéutico , Factores Sexuales , Factores de Tiempo
15.
J Appl Microbiol ; 127(5): 1381-1390, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31342602

RESUMEN

AIMS: This study investigated the potential synergy between erythromycin and nisin against clinical Group B Streptococcus (GBS) strains. METHODS AND RESULTS: The combination of erythromycin and nisin was examined for synergistic activity using checkerboard and time-kill assays against invasive and colonizing GBS strains. Additionally, the immunological effect of the antibiotic combination was investigated in vitro using human U937 cells and ELISA analysis. Checkerboard assays confirmed an additive effect when the antimicrobials were combined, while time-kill assays demonstrated a synergistic effect when antimicrobials were combined for invasive GBS isolates. Furthermore, a significantly lower TNF-alpha response (P < 0·05) was observed in U937 cells challenged with GBS when erythromycin and nisin were used in combination. CONCLUSIONS: The results suggest that erythromycin and nisin can act synergistically to inhibit the growth of GBS. SIGNIFICANCE AND IMPACT OF THE STUDY: Group B Streptococcus is the leading cause of invasive neonatal disease worldwide and is becoming increasingly more prevalent in adults. Resistance to some conventionally used antibiotics, such as erythromycin and clindamycin, continue to rise among GBS, indicating a need for alternative treatments. This study demonstrates the potential of an erythromycin-nisin combination for treatment of GBS infections and encourages further investigation of this treatment option.


Asunto(s)
Antibacterianos/farmacología , Eritromicina/farmacología , Nisina/farmacología , Streptococcus agalactiae/efectos de los fármacos , Clindamicina/farmacología , Sinergismo Farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/crecimiento & desarrollo , Streptococcus agalactiae/aislamiento & purificación , Células U937
16.
J Infect Dis ; 218(2): 197-207, 2018 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-29346682

RESUMEN

Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4.


Asunto(s)
Betacoronavirus/fisiología , Quirópteros , Dipeptidil Peptidasa 4/metabolismo , Evolución Molecular , Receptores Virales/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Internalización del Virus , Animales , Betacoronavirus/clasificación , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Células HEK293 , Humanos , Filogenia , Unión Proteica , Análisis de Secuencia de ADN , Glicoproteína de la Espiga del Coronavirus/genética
17.
Breast Cancer Res Treat ; 168(1): 43-55, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29124455

RESUMEN

PURPOSE: Ensuring and measuring adherence to prescribed exercise regimens are fundamental challenges in intervention studies to promote exercise in adults with cancer. This study reports exercise adherence in women who were asked to walk 150 min/week throughout chemotherapy treatment for early breast cancer. Participants were asked to wear a FitbitTM throughout their waking hours, and Fitbit steps were uploaded directly into study computers. METHODS: Descriptive statistics are reported, and both unadjusted and multivariable linear regression models were used to assess associations between participant characteristics, breast cancer diagnosis, treatment, chemotherapy toxicities, and patient-reported symptoms with average Fitbit steps/week. RESULTS: Of 127 women consented to the study, 100 had analyzable Fitbit data (79%); mean age was 48 and 31% were non-white. Mean walking steps were 3956 per day. Nineteen percent were fully adherent with the target of 6686 steps/day and an additional 24% were moderately adherent. In unadjusted analysis, baseline variables associated with fewer Fitbit steps were: non-white race (p = 0.012), high school education or less (p = 0.0005), higher body mass index (p = 0.0024), and never/almost never drinking alcohol (p = 0.0048). Physical activity variables associated with greater Fitbit steps were: pre-chemotherapy history of vigorous physical activity (p = 0.0091) and higher self-reported walking minutes/week (p < 0.001), and higher outcome expectations from exercise (p = 0.014). Higher baseline anxiety (p = 0.03) and higher number of chemotherapy-related symptoms rates "severe/very severe" (p = 0.012) were associated with fewer steps. In multivariable analysis, white race was associated with 12,146 greater Fitbit steps per week (p = 0.004), as was self-reported walking minutes prior to start of chemotherapy (p < 0.0001). CONCLUSIONS: Inexpensive commercial-grade activity trackers, with data uploaded directly into research computers, enable objective monitoring of home-based exercise interventions in adults diagnosed with cancer. Analysis of the association of walking steps with participant characteristics at baseline and toxicities during chemotherapy can identify reasons for low/non-adherence with prescribed exercise regimens.


Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias de la Mama/rehabilitación , Terapia por Ejercicio/estadística & datos numéricos , Monitoreo Fisiológico/instrumentación , Cooperación del Paciente/estadística & datos numéricos , Caminata/estadística & datos numéricos , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Terapia por Ejercicio/métodos , Femenino , Monitores de Ejercicio , Humanos , Mastectomía , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/estadística & datos numéricos , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Medición de Resultados Informados por el Paciente , Estudios Prospectivos
18.
Int J Obes (Lond) ; 41(1): 46-53, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27671034

RESUMEN

BACKGROUND: The gold standard for categorisation of weight status is clinically measured body mass index (BMI), but this is often not practical in large epidemiological studies. OBJECTIVES: To determine if a child's weight perception or a mother's perception of a child's weight status is a viable alternative to measured height and weight in determining BMI classification. Secondary outcomes are to determine the influence of a mother's BMI on her ability to categorise the child's BMI and a child's ability to recognise his/her own BMI. METHODS: Cross-sectional analysis of the growing up in Ireland cohort study, a nationally representative cohort of 8568 9-year-old children. The variables considered for this analysis are the child's gender, BMI (International Obesity Taskforce grade derived from measured height and weight) and self-perceived weight status, and the mother's weight perception of the child, BMI (derived from measured height and weight) and self-perceived weight status. Cohen's weighted-kappa was used to evaluate the strength of the agreement between pairwise combinations of the BMI variables. Cumulative and adjacent categories logistic regression were used to predict how likely a person rates themselves as under, normal or overweight, based on explanatory variables. RESULTS: Mothers are more accurate at correctly classifying their child's BMI (κ=0.5; confidence intervals (CI) 0.38-0.51) than the children themselves (κ=0.25; CI 0.23-0.26). Overweight mothers are better raters of their child's BMI (κ=0.51; CI 0.49-0.54), compared with normal (κ=0.44; CI 0.41-0.47) or underweight mothers (κ=0.4; CI 0.22-0.58), regardless of whether the mother's BMI is derived from measured height and weight or self-perceived. The mother's perception of the child's weight status is not an influencing factor on the child's ability to correctly classify him/herself, but the child's self-perceived weight status influences the mother's ability to correctly classify the child. CONCLUSIONS: A mother's BMI classification of her child is a viable alternative to BMI measurement in large epidemiological studies.


Asunto(s)
Índice de Masa Corporal , Madres/psicología , Obesidad Infantil/psicología , Autoinforme , Adulto , Peso Corporal , Niño , Estudios Transversales , Femenino , Conocimientos, Actitudes y Práctica en Salud , Encuestas Epidemiológicas , Humanos , Irlanda/epidemiología , Modelos Logísticos , Estudios Longitudinales , Masculino , Obesidad Infantil/epidemiología , Factores Socioeconómicos
19.
Osteoarthritis Cartilage ; 25(2): 242-248, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27729289

RESUMEN

OBJECTIVE: Knee sagittal dynamic joint stiffness (DJS) describes the biomechanical interaction between change in external knee flexion moment and flexion angular excursion during gait. In theory, greater DJS may particularly stress the patellofemoral (PF) compartment and thereby contribute to PF osteoarthritis (OA) worsening. We hypothesized that greater baseline knee sagittal DJS is associated with PF cartilage damage worsening 2 years later. METHODS: Participants all had OA in at least one knee. Knee kinematics and kinetics during gait were recorded using motion capture systems and force plates. Knee sagittal DJS was computed as the slope of the linear regression line for knee flexion moments vs angles during the loading response phase. Knee magnetic resonance imaging (MRI) scans were obtained at baseline and 2 years later. We assessed the association between baseline DJS and baseline-to-2-year PF cartilage damage worsening using logistic regression with generalized estimating equations (GEE). RESULTS: Our sample had 391 knees (204 persons): mean age 64.2 years (SD 10.0); body mass index (BMI) 28.4 kg/m2 (5.7); 76.5% women. Baseline knee sagittal DJS was associated with baseline-to-2-year cartilage damage worsening in the lateral (OR = 5.35, 95% CI: 2.37-12.05) and any PF (OR = 2.99, 95% CI: 1.27-7.04) compartment. Individual components of baseline DJS (i.e., change in knee moment or angle) were not associated with subsequent PF disease worsening. CONCLUSION: Capturing the concomitant effect of knee kinetics and kinematics during gait, knee sagittal DJS is a potentially modifiable risk factor for PF disease worsening.


Asunto(s)
Cartílago Articular/patología , Osteoartritis de la Rodilla/patología , Articulación Patelofemoral/patología , Cartílago Articular/fisiopatología , Progresión de la Enfermedad , Femenino , Marcha/fisiología , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Articulación de la Rodilla/fisiopatología , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Articulación Patelofemoral/diagnóstico por imagen , Articulación Patelofemoral/fisiopatología , Estudios Prospectivos
20.
Respir Res ; 18(1): 16, 2017 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-28088206

RESUMEN

BACKGROUND: There are challenges for researchers and clinicians to select the most appropriate physical activity tool, and a balance between precision and feasibility is needed. Currently it is unclear which physical activity tool should be used to assess physical activity in Bronchiectasis. The aim of this research is to compare assessment methods (pedometer and IPAQ) to our criterion method (ActiGraph) for the measurement of physical activity dimensions in Bronchiectasis (BE), and to assess their feasibility and acceptability. METHODS: Patients in this analysis were enrolled in a cross-sectional study. The ActiGraph and pedometer were worn for seven consecutive days and the IPAQ was completed for the same period. Statistical analyses were performed using SPSS 20 (IBM). Descriptive statistics were used; the percentage agreement between ActiGraph and the other measures were calculated using limits of agreement. Feedback about the feasibility of the activity monitors and the IPAQ was obtained. RESULTS: There were 55 (22 male) data sets available. For step count there was no significant difference between the ActiGraph and Pedometer, however, total physical activity time (mins) as recorded by the ActiGraph was significantly higher than the pedometer (mean ± SD, 232 (75) vs. 63 (32)). Levels of agreement between the two devices was very good for step count (97% agreement); and variation in the levels of agreement were within accepted limits of ±2 standard deviations from the mean value. IPAQ reported more bouted- moderate - vigorous physical activity (MVPA) [mean, SD; 167(170) vs 6(9) mins/day], and significantly less sedentary time than ActiGraph [mean, SD; 362(115) vs 634(76) vmins/day]. There were low levels of agreement between the two tools (57% sedentary behaviour; 0% MVPA10+), with IPAQ under-reporting sedentary behaviour and over-reporting MVPA10+ compared to ActiGraph. The monitors were found to be feasible and acceptable by participants and researchers; while the IPAQ was accepta ble to use, most patients required assistance to complete it. CONCLUSIONS: Accurate measurement of physical activity is feasible in BE and will be valuable for future trials of therapeutic interventions. ActiGraph or pedometer could be used to measure simple daily step counts, but ActiGraph was superior as it measured intensity of physical activity and was a more precise measure of time spent walking. The IPAQ does not appear to represent an accurate measure of physical activity in this population. TRIAL REGISTRATION: Clinical Trials Registration Number NCT01569009 : Physical Activity in Bronchiectasis.


Asunto(s)
Acelerometría/instrumentación , Actigrafía/instrumentación , Bronquiectasia/diagnóstico , Bronquiectasia/fisiopatología , Ejercicio Físico , Encuestas y Cuestionarios , Acelerometría/métodos , Actigrafía/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio/instrumentación , Monitoreo Ambulatorio/métodos , Irlanda del Norte , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
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