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1.
Public Health ; 216: 58-65, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36801593

RESUMO

OBJECTIVES: In addition to being home to more than seven million HIV-infected individuals, South Africa also has a high burden of COVID-19 and related comorbidities worldwide. We aimed to identify the most influential "beliefs" and "attitudes" on vaccine decision-making behavior. STUDY DESIGN: This study used panel data from cross-sectional surveys. METHODS: We used the data from Black South Africans who participated in the "COVID-19 Vaccine Surveys" (November 2021 and February/March 2022) in South Africa. Besides standard risk factor analysis, such as multivariable logistic regression models, we also used the modified version of population attributable risk percent and estimated the population-level impacts of beliefs and attitudes on vaccine decision-making behavior using the methodology in multifactorial setting. RESULTS: A total of 1399 people (57% men and 43% women) who participated in both surveys were analyzed. Of these, 336 (24%) reported being vaccinated in survey 2. Overall low perceived risk, concerns around efficacy, and safety were identified as the most influential factors and associated with 52%-72% (<40 years) and 34%-55% (40+ years) of the unvaccinated individuals. CONCLUSION: Our findings highlighted the most influential beliefs and attitudes on vaccine decision-making and their population-level impacts, which are likely to have significant public health implications exclusively for this population.


Assuntos
COVID-19 , Vacinas , Masculino , Humanos , Feminino , Vacinas contra COVID-19 , África do Sul/epidemiologia , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Vacinação
2.
BMC Public Health ; 22(1): 822, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468743

RESUMO

BACKGROUND: In Australia in 2017, 89% of 15-year-old females and 86% of 15-year-old males had received at least one dose of the HPV vaccine. However, considerable variation in HPV vaccination initiation (dose one) across schools remains. It is important to understand the school-level characteristics most strongly associated with low initiation and their contribution to the overall between-school variation. METHODS: A population-based ecological analysis was conducted using school-level data for 2016 on all adolescent students eligible for HPV vaccination in three Australian jurisdictions. We conducted logistic regression to determine school-level factors associated with lower HPV vaccination initiation (< 75% dose 1 uptake) and estimated the population attributable risk (PAR) and the proportion of schools with the factor (school-level prevalence). RESULTS: The factors most strongly associated with lower initiation, and their prevalence were; small schools (OR = 9.3, 95%CI = 6.1-14.1; 33% of schools), special education schools (OR = 5.6,95%CI = 3.7-8.5; 8% of schools), higher Indigenous enrolments (OR = 2.7,95% CI:1.9-3.7; 31% of schools), lower attendance rates (OR = 2.6,95%CI = 1.7-3.7; 35% of schools), remote location (OR = 2.6,95%CI = 1.6-4.3; 6% of schools,) and lower socioeconomic area (OR = 1.8,95% CI = 1.3-2.5; 33% of schools). The highest PARs were small schools (PAR = 79%, 95%CI:76-82), higher Indigenous enrolments (PAR = 38%, 95%CI: 31-44) and lower attendance rate (PAR = 37%, 95%CI: 29-46). CONCLUSION: This analysis suggests that initiatives to support schools that are smaller, with a higher proportion of Indigenous adolescents and lower attendance rates may contribute most to reducing the variation of HPV vaccination uptake observed at a school-level in these jurisdictions. Estimating population-level coverage at the school-level is useful to guide policy and prioritise resourcing to support school-based vaccination programs.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Austrália/epidemiologia , Feminino , Humanos , Masculino , Infecções por Papillomavirus/prevenção & controle , Instituições Acadêmicas , Vacinação
3.
Ann Oncol ; 31(5): 590-598, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32245699

RESUMO

BACKGROUND: Little is known about mechanisms of resistance to poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinum chemotherapy in patients with metastatic breast cancer and BRCA1/2 mutations. Further investigation of resistance in clinical cohorts may point to strategies to prevent or overcome treatment failure. PATIENTS AND METHODS: We obtained tumor biopsies from metastatic breast cancer patients with BRCA1/2 deficiency before and after acquired resistance to PARPi or platinum chemotherapy. Whole exome sequencing was carried out on each tumor, germline DNA, and circulating tumor DNA. Tumors underwent RNA sequencing, and immunohistochemical staining for RAD51 foci on tumor sections was carried out for functional assessment of intact homologous recombination (HR). RESULTS: Pre- and post-resistance tumor samples were sequenced from eight patients (four with BRCA1 and four with BRCA2 mutation; four treated with PARPi and four with platinum). Following disease progression on DNA-damaging therapy, four patients (50%) acquired at least one somatic reversion alteration likely to result in functional BRCA1/2 protein detected by tumor or circulating tumor DNA sequencing. Two patients with germline BRCA1 deficiency acquired genomic alterations anticipated to restore HR through increased DNA end resection: loss of TP53BP1 in one patient and amplification of MRE11A in another. RAD51 foci were acquired post-resistance in all patients with genomic reversion, consistent with reconstitution of HR. All patients whose tumors demonstrated RAD51 foci post-resistance were intrinsically resistant to subsequent lines of DNA-damaging therapy. CONCLUSIONS: Genomic reversion in BRCA1/2 was the most commonly observed mechanism of resistance, occurring in four of eight patients. Novel sequence alterations leading to increased DNA end resection were seen in two patients, and may be targetable for therapeutic benefit. The presence of RAD51 foci by immunohistochemistry was consistent with BRCA1/2 protein functional status from genomic data and predicted response to later DNA-damaging therapy, supporting RAD51 focus formation as a clinically useful biomarker.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Platina/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
4.
J Appl Microbiol ; 128(1): 116-123, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31559683

RESUMO

AIMS: This study investigated the efficacy of hydrogen peroxide vapour (HPV) at inactivating hazard group 3 bacteria that have been presented dried from their growth medium to present a realistic challenge. METHODS AND RESULTS: Hydrogen peroxide vapour technology (Bioquell) was used to decontaminate a class III microbiological safety cabinet containing biological indicators (BIs) made by drying standard working suspensions of the following agents: Bacillus anthracis (Ames) spores, Brucella abortus (strain S99), Burkholderia pseudomallei (NCTC 12939), Escherichia coli O157 ST11 (NCTC 12079), Mycobacterium tuberculosis (strain H37Rv) and Yersinia pestis (strain CO92) on stainless steel coupons. Extended cycles were used to expose the agents for 90 min. The HPV cycle completely inactivated B. anthracis spores, B. abortus, B. pseudomallei, E. coli O157 and Y. pestis when BIs were processed using quantitative and qualitative methods. Whilst M. tuberculosis was not completely inactivated, it was reduced by 4 log10 from a starting concentration of 106 colony-forming units. CONCLUSIONS: This study demonstrates that HPV is able to inactivate a range of HG3 agents at high concentrations with associated organic matter, but M. tuberculosis showed increased resistance to the process. SIGNIFICANCE AND IMPACT OF THE STUDY: This publication demonstrates that HPV can inactivate HG3 agents that have an organic load associated with them. It also shows that M. tuberculosis has higher resistance to HPV than other agents. This shows that an appropriate BI to represent the agent of interest should be chosen to demonstrate a decontamination is successful.


Assuntos
Contenção de Riscos Biológicos/métodos , Descontaminação/métodos , Desinfetantes/farmacologia , Gases/farmacologia , Peróxido de Hidrogênio/farmacologia , Bactérias/efeitos dos fármacos , Contenção de Riscos Biológicos/instrumentação , Farmacorresistência Bacteriana , Biomarcadores Ambientais/efeitos dos fármacos , Aço Inoxidável
5.
Health Educ Res ; 34(2): 188-199, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30601982

RESUMO

Faith-based health promotion programs have been effective in increasing healthy eating (HE) and physical activity (PA). Very few reports exist regarding church leaders' anticipated and experienced barriers and facilitators to program implementation. Pastors (n = 38, 70%) and program coordinators (n = 54, 100%) from churches (N = 54) who attended a program training answered open-ended questions about anticipated barriers and facilitators to implementing the HE and PA parts of the Faith, Activity, and Nutrition (FAN) program. Twelve months later, pastors (n = 49, 92%) and coordinators (n = 53, 98%) answered analogous questions about their experienced barriers and facilitators to implementing the HE and PA parts of the FAN program. Responses were coded using thematic analysis. Similar themes appeared at baseline and follow-up for anticipated and experienced barriers and facilitators. The most common barriers were no anticipated barriers, resistance to change, church characteristics, and lack of participation/motivation. The most common facilitators were internal support, leadership, and communication. Few differences were found between anticipated and experienced barriers and facilitators. Understanding these perspectives, particularly overcoming resistance to change and church characteristics through strong leadership and internal support from church leaders, will improve future program development, resources, and technical assistance in faith-based and non-faith-based communities alike.


Assuntos
Dieta Saudável/métodos , Exercício Físico/fisiologia , Organizações Religiosas/organização & administração , Promoção da Saúde/organização & administração , Clero , Comunicação , Humanos , Liderança , Motivação , Estado Nutricional , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa
7.
Clin Rehabil ; 28(10): 1025-38, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25082956

RESUMO

OBJECTIVE: To examine whether using a knee-ankle-foot orthosis helps maintain ankle-foot dorsiflexion range of motion over time. DESIGN: A multicentre randomized controlled trial. SETTING: Two hospitals and one rehabilitation centre in the Netherlands and the USA. SUBJECTS: Children (4-16 years old) with spastic cerebral palsy who were able to walk. INTERVENTION: Use of a knee-ankle-foot orthosis, equipped with an Ultraflex ankle power unit, for at least 6 hours every other night for one year. PRIMARY OUTCOME MEASURE: ankle-foot dorsiflexion range of motion. SECONDARY OUTCOME MEASURES: ankle-foot and knee angle in gait and gross motor function. Wearing time was also measured. Measurements were taken at baseline and at 3, 6, 9 and 12 months. RESULTS: 28 children (experimental group: n=15, control group: n=13) participated in the study. 11 participants (experimental: n=4, control: n=7) did not complete all five measurements, as they needed additional treatment. No significant difference was found in the decrease of ankle-foot dorsiflexion range of motion between the experimental and control groups (difference: -1.05°, 95% confidence interval: -4.71° - 2.61°). In addition, secondary outcome measures did not show differences between groups. Despite good motivation, knee-ankle-foot orthosis wearing time was limited to a mean±SD of 3.2±1.9 hours per prescribed night due to discomfort. CONCLUSIONS: Knee-ankle-foot orthosis with dynamic ankle and fixed knee are poorly tolerated and are not beneficial in preventing a reduction in ankle-foot dorsiflexion range of motion in children with spastic cerebral palsy, at least with limited use.


Assuntos
Paralisia Cerebral/reabilitação , Pé Equino/prevenção & controle , Transtornos Neurológicos da Marcha/reabilitação , Extremidade Inferior/fisiopatologia , Aparelhos Ortopédicos/estatística & dados numéricos , Amplitude de Movimento Articular/fisiologia , Paralisia Cerebral/complicações , Criança , Pé Equino/etiologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Extremidade Inferior/fisiologia , Masculino , Análise Multinível , Países Baixos , Aparelhos Ortopédicos/efeitos adversos , Fatores de Tempo , Estados Unidos/etnologia
8.
Perspect Public Health ; 144(3): 162-173, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38509693

RESUMO

AIM: This study aims to establish whether digital surveillance methods for notifiable diseases in Australia collect and report data in relation to marginalised populations. METHODS: The literature was systematically reviewed to identify primary research studies published between January 2005 and July 2023. Studies were included if they described an Australian digital surveillance system for notifiable conditions. The results were synthesised with a focus on evaluating the collection and reporting of data in relation to marginalised populations. RESULTS: A total of 13 articles reporting on seven surveillance systems were identified. Influenza and adverse events following immunisation were the two most common notifiable conditions monitored. A total of six surveillance systems encompassing 16 articles reported information on sub-populations. Of these, three surveillance systems (nine articles) included data on marginalised populations. CONCLUSION: The data collected or reported in relation to sub-groups that characterise diversity in terms of health care needs, access, and marginalised populations are minimal. It is recommended that a set of equity and reporting principles is established for the future creation and use of any digital surveillance system.


Assuntos
Vigilância da População , Humanos , Austrália/epidemiologia , Notificação de Doenças/métodos , Vigilância da População/métodos
9.
Epidemiol Infect ; 141(4): 687-96, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22687530

RESUMO

This study investigated the relationships between Legionnaires' disease (LD) incidence and weather in Glasgow, UK, by using advanced statistical methods. Using daily meteorological data and 78 LD cases with known exact date of onset, we fitted a series of Poisson log-linear regression models with explanatory variables for air temperature, relative humidity, wind speed and year, and sine-cosine terms for within-year seasonal variation. Our initial model showed an association between LD incidence and 2-day lagged humidity (positive, P = 0·0236) and wind speed (negative, P = 0·033). However, after adjusting for year-by-year and seasonal variation in cases there were no significant associations with weather. We also used normal linear models to assess the importance of short-term, unseasonable weather values. The most significant association was between LD incidence and air temperature residual lagged by 1 day prior to onset (P = 0·0014). The contextual role of unseasonably high air temperatures is worthy of further investigation. Our methods and results have further advanced understanding of the role which weather plays in risk of LD infection.


Assuntos
Doença dos Legionários/epidemiologia , Modelos Lineares , Tempo (Meteorologia) , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Umidade , Incidência , Masculino , Pessoa de Meia-Idade , Escócia/epidemiologia , Estações do Ano , Temperatura , Vento
11.
Eur J Hybrid Imaging ; 6(1): 29, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36517647

RESUMO

BACKGROUND: The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending 18F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using 18F-FDG uptake as a surrogate marker. METHODS: A retrospective audit was conducted of the brain 18F-FDG uptake in 52 patients who underwent PET scans for possible cardiac sarcoidosis or suspected intracardiac infection, following a ketogenic diet and prolonged fasting. SUVbw for whole brain and separate brain regions was compared with serum glucose and serum ketone body (beta-hydroxybutyrate) levels. RESULTS: The expected negative association between serum glucose levels and whole brain 18F-FDG uptake was confirmed. A reduction in SUVbw due to increasing serum ketones levels was also observed that was independent of and in addition to the effects of glucose. The magnitude of the reduction in SUVbw related to serum glucose level and serum ketone level was found to be greater in the precuneus than in the cerebellum or whole brain. CONCLUSION: In a real-world clinical PET setting, cerebral 18F-FDG uptake appears to be affected by glycaemia and ketonaemia. This means when assessing the brain, both serum glucose and ketone levels need to be considered when SUVs are used to distinguish between pathologic and physiologic states. The magnitude of this effect appears to vary between different brain regions. This regional difference should be taken into consideration when selecting the appropriate brain region for SUV normalisation, particularly when undertaking database comparison in the assessment of dementia.

12.
Curr Probl Cancer ; 46(2): 100793, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34565601

RESUMO

For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. This study aims to investigate the efficacy and safety of TAS-102 in a real-world population from Victoria, Australia. A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to those enrolled in the registration study (RECOURSE). Across 13 sites, 107 patients were treated with TAS-102. The median age was 60 years (range: 31-83), compared to 63 for RECOURSE. Comparing registry TAS-102-treated and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 36% vs 49% were RAS wild-type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median progression-free survival (PFS) was 3.3 months compared to 2 months in RECOURSE, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths, where TAS-102 dose at treatment initiation was at clinician discretion.TRACC registry patients treated with TAS-102 were younger than those from the RECOURSE trial, with similar overall survival observed. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Austrália , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Pirrolidinas , Estudos Retrospectivos , Timina/uso terapêutico , Trifluridina/uso terapêutico , Uracila/uso terapêutico
13.
Integr Org Biol ; 3(1): obab019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34355122

RESUMO

Synopsis Siphonophores are free-living predatory colonial hydrozoan cnidarians found in every region of the ocean. Siphonophore tentilla (tentacle side branches) are unique biological structures for prey capture, composed of a complex arrangement of cnidocytes (stinging cells) bearing different types of nematocysts (stinging capsules) and auxiliary structures. Tentilla present an extensive morphological and functional diversity across species. While associations between tentillum form and diet have been reported, the evolutionary history giving rise to this morphological diversity is largely unexplored. Here we examine the evolutionary gains and losses of novel tentillum substructures and nematocyst types on the most recent siphonophore phylogeny. Tentilla have a precisely coordinated high-speed strike mechanism of synchronous unwinding and nematocyst discharge. Here we characterize the kinematic diversity of this prey capture reaction using high-speed video and find relationships with morphological characters. Since tentillum discharge occurs in synchrony across a broad morphological diversity, we evaluate how phenotypic integration is maintaining character correlations across evolutionary time. We found that the tentillum morphospace has low dimensionality, identified instances of heterochrony and morphological convergence, and generated hypotheses on the diets of understudied siphonophore species. Our findings indicate that siphonophore tentilla are phenotypically integrated structures with a complex evolutionary history leading to a phylogenetically-structured diversity of forms that are predictive of kinematic performance and feeding habits.


Los sifonóforos son cnidarios hidrozoos coloniales depredadores que habitan todas las regiones pelágicas del océano. Las téntilas (ramificaciones laterales de los tentáculos) de los sifonóforos son estructuras biológicas dedicadas a la captura de presas. Las téntilas se componen de una matriz compleja de cnidocitos (células urticantes) portadores de diferentes tipos de nematocistes (cápsulas urticantes) y estructuras auxiliares. Las téntilas presenta una extensa diversidad morfológica y funcional en las diferentes especies de sifonóforo. Las relaciones entre la forma de las téntilas y las dietas de los sifonóforos has sido estudiadas previamente, sin embargo, la historia evolutiva que dio lugar a esta diversidad morfológica no ha sido explorada apenas. En este estudio examinamos las adquisiciones y pérdidas evolutivas de las subestructuras de la téntila y los tipos de nematocisto utilizando la filogenia molecular más reciente de los sifonóforos. Las téntilas presentan un mecanismo de disparo a alta velocidad, sincronizando las diferentes subestructuras con gran precisión, durante el cual se la téntila de desenrolla mientras los nematocistes se disparan sobre la presa. En este estudio caracterizamos la diversidad cinemática de estas reacciones para la captura de presas utilizando video de alta velocidad, y describimos su relación con los caracteres morfológicos. Dado que la descarga de las téntilas ocurre en sincronía en toda su diversidad morfológica, hemos evaluado cómo la evolución con integración fenotípica mantiene las correlaciones entre los caracteres morfológicos a través del tiempo. Hallamos que el morfo-espacio de las téntilas tiene baja dimensionalidad, encontramos casos de heterocronía y convergencia morfológica, y generamos hipótesis sobre las dietas de especies de sifonóforo poco estudiadas. Nuestros hallazgos indican que las téntilas de los sifonóforos son estructuras con fenotipos integrados y con una historia evolutiva compleja que ha dado lugar a una diversidad filogenéticamente estructurada de formas asociadas a diferentes rendimientos cinemáticos y hábitos alimenticios.

14.
Vaccine ; 39(41): 6117-6126, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34493408

RESUMO

BACKGROUND: Schools are the primary setting for the delivery of adolescent HPV vaccination in Australia. Although this strategy has achieved generally high vaccination coverage, gaps persist for reasons that are mostly unknown. This study sought to identify school-level correlates of low vaccination course initiation and completion in New South Wales, Tasmania, and Western Australia to inform initiatives to increase uptake. METHODS: Initiation was defined as the number of first doses given in a school in 2016 divided by vaccine-eligible student enrolments. Completion was the number of third doses given in a school in 2015-2016 divided by the number of first doses. Low initiation and completion were defined as coverage ≤ 25thpercentile of all reporting schools. We investigated correlations between covariates using Spearman's rank correlation coefficients. Due to multicollinearity, we used univariable logistic regression to investigate associations between school characteristics and low coverage. RESULTS: Median initiation was 84.7% (IQR: 75.0%-90.4%) across 1,286 schools and median completion was 93.8% (IQR: 86.0%-97.3%) across 1,295 schools. There were strong correlations between a number of school characteristics, particularly higher Indigenous student enrolments and lower attendance, increasing remoteness, higher postcode socioeconomic disadvantage, and smaller school size. Characteristics most strongly associated with low initiation in univariate analyses were small school size, location in Tasmania, and schools catering for special educational needs. Low completion was most strongly associated with schools in Tasmania and Western Australia, remote location, small size, high proportion of Indigenous student enrolments, and low attendance rates. CONCLUSION: This study provides indicative evidence that characteristics of schools and school populations are associated with the likelihood of low initiation and completion of the HPV vaccination course. The findings will guide further research and help target initiatives to improve vaccination uptake in schools with profiles associated with lower coverage.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Austrália , Humanos , Programas de Imunização , Infecções por Papillomavirus/prevenção & controle , Instituições Acadêmicas , Vacinação
15.
Eur J Pharm Biopharm ; 153: 226-240, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32585351

RESUMO

The oral administration of solid dosage forms is the commonest method to achieve systemic therapy and relies on the drug's solubility in human intestinal fluid (HIF), a key factor that influences bioavailability and biopharmaceutical classification. However, HIF is difficult to obtain and is known to be variable, which has led to the development of a range of simulated intestinal fluid (SIF) systems to determine drug solubility in vitro. In this study we have applied a novel multidimensional approach to analyse and characterise HIF composition using a published data set in both fasted and fed states with a view to refining the existing SIF approaches. The data set provided 152 and 172 measurements of five variables (total bile salt, phospholipid, total free fatty acid, cholesterol and pH) in time-dependent HIF samples from 20 volunteers in the fasted and fed state, respectively. The variable data sets for both fasted state and fed state are complex, do not follow normal distributions but the amphiphilic variable concentrations are correlated. When plotted 2-dimensionally a generally ellipsoid shaped data cloud with a positive slope is revealed with boundaries that enclose published fasted or fed HIF compositions. The data cloud also encloses the majority of fasted state and fed state SIF recipes and illustrates that the structured nature of design of experiment (DoE) approaches does not optimally cover the variable space and may examine media compositions that are not biorelevant. A principal component analysis in either fasted or fed state in combination with fitting an ellipsoid shape to enclose the data results in 8 points that capture over 95% of the compositional variability of HIF. The variable's average rate of concentration change in both fasted state and fed state over a short time scale (10 min) is zero and a Euclidean analysis highlights differences between the fasted and fed states and among individual volunteers. The results indicate that a 9-point DoE (8 + 1 central point) could be applied to investigate drug solubility in vitro and provide statistical solubility limits. In addition, a single point could provide a worst-case solubility measurement to define the lowest biopharmaceutical classification boundary or for use during drug development. This study has provided a novel description of HIF composition. The approach could be expanded in multiple ways by incorporation of further data sets to improve the statistical coverage or to cover specific patient groups (e.g., paediatric). Further development might also be possible to analyse information on the time dependent behaviour of HIF and to guide HIF sampling and analysis protocols.


Assuntos
Líquidos Corporais/química , Secreções Intestinais/química , Intestinos/química , Administração Oral , Jejum/fisiologia , Humanos , Absorção Intestinal/fisiologia , Preparações Farmacêuticas/química , Fosfolipídeos/química , Solubilidade
16.
Hernia ; 24(2): 353-358, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32052297

RESUMO

PURPOSE: Lateral abdominal wall hernias are rare defects but, due to their location, repair is difficult, and recurrence is common. Few studies exist to support a standard protocol for repair of these lateral hernias. We hypothesized that anchoring our repair to fixed bony structures would reduce recurrence rates. METHODS: A retrospective review of all patients who underwent lateral hernia repair at our institution was performed. RESULTS: Eight cases (seven flank and one thoracoabdominal) were reviewed. The median defect size was 105 cm2 (range 36-625 cm2). The median operative time was 185 min (range 133-282 min). There were no major complications. One patient who was repaired without mesh attachment to bony landmarks developed a recurrence at ten months and subsequently underwent reoperation. Patients with mesh secured to bony landmarks were recurrence free at a median follow-up of 171 days. CONCLUSIONS: Lateral hernias present a greater challenge due to their anatomic location. An open technique with mesh fixation to bony structures is a promising solution to this complex problem.


Assuntos
Hérnia Abdominal/cirurgia , Herniorrafia/métodos , Telas Cirúrgicas , Músculos Abdominais/cirurgia , Parede Abdominal/cirurgia , Adulto , Idoso , Procedimentos Cirúrgicos Eletivos , Feminino , Hérnia Abdominal/classificação , Herniorrafia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Recidiva , Reoperação , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , Parede Torácica/cirurgia
17.
Science ; 183(4123): 422-4, 1974 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-4358074

RESUMO

When inhibitors of protein synthesis are added to BALB/c mouse cells in culture, induction of naturally integrated C-type RNA virus occurs in a high percentage of cells. The action of protein synthesis inhibitors differs from that of halogenated pyrimidines, another class of virus inducers, in their effects on biologically distinguishable viruses. The use of such inhibitors to study integrated virus expression provides a means for studying gene regulation in mammalian cells.


Assuntos
Antibacterianos/farmacologia , Biossíntese de Proteínas , Retroviridae/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Compostos de Benzil/farmacologia , Bromodesoxiuridina/farmacologia , Linhagem Celular , Cicloeximida/farmacologia , Citarabina/farmacologia , Dactinomicina/farmacologia , Depressão Química , Idoxuridina/farmacologia , Rim , Camundongos , Camundongos Endogâmicos BALB C , Puromicina/farmacologia , Pirrolidinas/farmacologia , Ratos , Retroviridae/crescimento & desenvolvimento , Ribonucleosídeos/farmacologia , Fatores de Tempo , Ensaio de Placa Viral
18.
Science ; 223(4633): 286-9, 1984 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-6322296

RESUMO

The retroviral long terminal repeat (LTR) contains transcriptional control elements that affect viral gene expression. By deletion mutagenesis of the genome of the cloned Abelson murine leukemia virus, regulatory signals could be mapped to at least three domains within the LTR. A defective 5' LTR that did not sustain transforming gene function was complemented by an intact LTR positioned at the 3' end of the genome. This versatility of the retroviral genome with respect to its transcriptional control elements appears to provide a strong selective advantage for viral gene expression.


Assuntos
Vírus da Leucemia Murina de Abelson/genética , Regulação da Expressão Gênica , Genes Virais , Vírus da Leucemia Murina/genética , Sequências Repetitivas de Ácido Nucleico , Transcrição Gênica , Animais , Linhagem Celular , Transformação Celular Viral , Clonagem Molecular , Camundongos , Mutação , Transfecção
19.
Science ; 252(5006): 704-6, 1991 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-1673802

RESUMO

Genetic factors contribute to heart disease. In this study, linkage analyses have been performed in a family that is predisposed to sudden death from cardiac arrhythmias, the long QT syndrome (LQT). A DNA marker at the Harvey ras-1 locus (H-ras-1) was linked to LQT with a logarithm of the likelihood ratio for linkage (lod score) of 16.44 at theta = 0, which confirms the genetic basis of this trait and localizes this gene to the short arm of chromosome 11. As no recombination was observed between LQT and H-ras-1, and there is a physiological rationale for its involvement in this disease, ras becomes a candidate for the disease locus.


Assuntos
Genes ras , Escore Lod , Síndrome do QT Longo/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 11 , Eletrocardiografia , Humanos , Síndrome do QT Longo/fisiopatologia , Mutação , Linhagem , Polimorfismo de Fragmento de Restrição
20.
Science ; 242(4885): 1541-4, 1988 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-3201242

RESUMO

Three variations to the structure of the nicotinamide adenine dinucleotide (NAD)-dependent L-lactate dehydrogenase from Bacillus stearothermophilus were made to try to change the substrate specificity from lactate to malate: Asp197----Asn, Thr246----Gly, and Gln102----Arg). Each modification shifts the specificity from lactate to malate, although only the last (Gln102----Arg) provides an effective and highly specific catalyst for the new substrate. This synthetic enzyme has a ratio of catalytic rate (kcat) to Michaelis constant (Km) for oxaloacetate of 4.2 x 10(6)M-1 s-1, equal to that of native lactate dehydrogenase for its natural substrate, pyruvate, and a maximum velocity (250 s-1), which is double that reported for a natural malate dehydrogenase from B. stearothermophilus.


Assuntos
Geobacillus stearothermophilus/enzimologia , L-Lactato Desidrogenase/genética , Malato Desidrogenase/metabolismo , Sítios de Ligação , Geobacillus stearothermophilus/genética , Cinética , L-Lactato Desidrogenase/metabolismo , Modelos Moleculares , Conformação Proteica , Especificidade por Substrato
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