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INTRODUCTION: Smoking among New Zealand (NZ) adolescents has declined since 2000, but ethnic disparities remain pronounced. To inform prevention efforts, we investigated exposure to and relative importance of known predictors of adolescent smoking and how these have changed over time, for Maori (NZ's indigenous population) and adolescents overall. METHODS: We used repeat cross-sectional data, 2003-2015, from a national survey of 14- to 15-year olds (N = 20 443-31 696 per year). For the overall sample and for Maori and non-Maori, we calculated adjusted odds ratios (aORs) to assess the association between regular smoking and risk factors each year: one or more parents smoke, best friend smokes, older sibling(s) smoke, and past week exposure to smoking in the home. We calculated population attributable risk (PAR) for risk factors in 2003 and 2015. RESULTS: Between 2003 and 2015, aORs for exposure to smoking in the home increased from 1.7 (95% CI 1.6% to 1.8%) to 2.6 (2.1% to 3.1%) overall and from 1.8 (1.6% to 2.1%) to 3.4 (2.5% to 4.5%) for Maori; aORs for "best friend smokes" also increased, while aORs for sibling smoking and parental smoking did not change meaningfully. PAR for exposure to smoking in the home increased from 17% to 31% overall and from 28% to 57% for Maori, while PARs for other risk factors decreased. CONCLUSIONS: Exposure to smoking in the home has become more strongly associated with adolescent smoking over time and is an increasingly important risk factor at the population level (independent of parental smoking), particularly for Maori. IMPLICATIONS: Our findings have implications for reducing smoking uptake and ethnic disparities in NZ, and potentially elsewhere, given the similarity in risk factors and trends for adolescent smoking internationally. Our findings suggest that reducing second-hand smoke exposure in homes will likely reduce uptake of smoking. Because Maori children are both more exposed and appear to be more strongly influenced by exposure to smoking in the home, interventions to reduce indoor smoking could have differentially positive effects for Maori. Greater research and policy attention to reducing smoking in homes is warranted.
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Comportamento do Adolescente/etnologia , Comportamento do Adolescente/psicologia , Etnicidade/psicologia , Poluição por Fumaça de Tabaco/efeitos adversos , Fumar Tabaco/etnologia , Fumar Tabaco/psicologia , Adolescente , Criança , Estudos Transversais , Feminino , Amigos/psicologia , Humanos , Masculino , Nova Zelândia/epidemiologia , Pais/psicologia , Fatores de Risco , Fumar Tabaco/efeitos adversosRESUMO
BACKGROUND: Significant health inequities exist around maternal and infant health for Maori, the indigenous people of Aotearoa New Zealand - and in particular around a premature (preterm) delivery. Maori babies are more likely to be born preterm (8.1%, compared to an overall rate of 7.4%) and they are more likely to have a preterm death. An essential part of redressing these disparities is to examine the clinical care pathway and outcomes associated with preterm deliveries. This paper describes a protocol utilising national and local health collections to enable such a study. DESIGN: This is a retrospective cohort study comprising 5 years data pertaining to preterm deliveries from 2010 to 2014. These data are generated from linked national administrative and local health information collections to explore a range of neonatal outcomes and infant mortality in relation to the antenatal care pathway and known risk factors for preterm delivery. This study is being conducted within a Kaupapa Maori paradigm that dismisses victim blaming and seeks to intervene at structural levels to improve the health and wellbeing of Maori whanau (family). SIGNIFICANCE OF THE STUDY: Our data-linkage methodology optimises the utility of New Zealand health collections to address a significant health issue. Our findings will fill the information gaps around the burden of preterm delivery by quantifying the incidence of preterm delivery and adverse neonatal and infant outcomes in Aotearoa New Zealand. It will explore access to evidenced based care including use of steroids before birth, and appropriate place of delivery. The results from this study will inform maternity care services to improve management of preterm deliveries - both locally and internationally. This in turn will improve the preterm sequela by reducing the long-term health burden and health inequities.
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Procedimentos Clínicos , Recém-Nascido Prematuro , Havaiano Nativo ou Outro Ilhéu do Pacífico , Nascimento Prematuro/etnologia , Displasia Broncopulmonar/etnologia , Feminino , Humanos , Incidência , Lactente , Mortalidade Infantil/etnologia , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Nova Zelândia/epidemiologia , Cuidado Pré-Natal , Estudos Retrospectivos , Fatores de RiscoRESUMO
Neutropenic infections are life-threatening and require empiric antibiotic treatment. We examined 1139 blood culture isolates from our institution over a 36-year period from neutropenic patients to examine temporal trends and disease associations. Positive associations were found between viridans streptococci and acute myeloid leukaemia, coagulase negative staphylococci and acute lymphoblastic leukaemia and Pseudomonas aeruginosa and indolent B-cell malignancies.
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Bacteriemia/sangue , Hemocultura/estatística & dados numéricos , Neutropenia/sangue , Antibacterianos/uso terapêutico , Antineoplásicos/efeitos adversos , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Neutropenia/etiologiaRESUMO
BACKGROUND/OBJECTIVES: Mitochondrial dysfunction occurs in vital organs in experimental acute pancreatitis (AP) and may play an important role in determining severity of AP. However, obtaining vital organ biopsies to measure mitochondrial function (MtF) in patients with AP poses considerable risk of harm. Being able to measure MtF from peripheral blood will bypass this problem. Furthermore, whether mitochondrial dysfunction is detectable in peripheral blood in mild AP is unknown. Therefore, the objective was to evaluate peripheral blood MtF in experimental and clinical AP. METHOD: Mitochondrial respiration was measured using high resolution oxygraphy in an experimental study in caerulein induced AP and in a separate study, in patients with mild AP. Superoxide, cytochrome c, mitochondrial membrane potential (ΔΨ) and adenine triphosphate (ATP) were also measured as other markers of MtF. RESULTS: Even though some states of mitochondrial respiration were increased in both experimental and clinical AP, this did not lead to an increase in net ATP in patients with AP. The increased leak respiration in both studies was further proof of dyscoupled mitochondria. In the clinical study there were also features of mitochondrial dysfunction with increased leak flux control ratio, superoxide, ΔΨ and decreased cytochrome c. CONCLUSION: There is evidence of mitochondrial dysfunction with dyscoupled mitochondria, increased superoxide and decreased cytochrome c in patients with mild acute pancreatitis. Further studies should now determine whether mitochondrial function alters with severity in AP and whether mitochondrial dysfunction responds to treatments.
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Doenças Mitocondriais/metabolismo , Monócitos/metabolismo , Pancreatite/metabolismo , Doença Aguda , Trifosfato de Adenosina/metabolismo , Adulto , Idoso , Animais , Ceruletídeo , Citocromos c/metabolismo , Feminino , Humanos , Masculino , Potencial da Membrana Mitocondrial , Pessoa de Meia-Idade , Estresse Oxidativo , Consumo de Oxigênio , Pancreatite/induzido quimicamente , Ratos , Ratos Wistar , Superóxidos/metabolismoRESUMO
An important aspect of synaptic plasticity in the brain is axonal transport of essential components such as mitochondria from the soma to the synapse. For uninterrupted transport of cellular cargo down the axon, functional microtubules are required. Altered microtubule dynamics induced by changes in expression of microtubule-associated tau protein affects normal microtubule function and interferes with axonal transport. Here we investigate the effects of the nontaxoid-binding-site microtubule-stabilizing agents peloruside A (PelA) and laulimalide, compared with the taxoid-site-binding agents paclitaxel (Ptx) and ixabepilone, on axonal transport of mitochondria in 1-day-old rat pup cerebral cortical neuron cultures. The differences in effects of these two types of compound on mitochondrial trafficking were specifically compared under conditions of excess tau expression. PelA and laulimalide had no adverse effects on their own on mitochondrial transport compared with Ptx and ixabepilone, which inhibited mitochondrial run length at higher concentrations. PelA, like Ptx, was able to partially reverse the blocked mitochondrial transport seen in ECFP-htau40-overexpressing neurons, although at higher concentrations of microtubule-stabilizing agent, the PelA response was improved over the Ptx response. These results support a neuroprotective effect of microtubule stabilization in maintaining axonal transport in neurons overexpressing tau protein and may be beneficial in reducing the severity of neurodegenerative diseases such as Alzheimer's disease.
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Transporte Axonal/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Mitocôndrias/fisiologia , Neurônios/efeitos dos fármacos , Moduladores de Tubulina/farmacologia , Animais , Animais Recém-Nascidos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Células Cultivadas , Córtex Cerebral/citologia , Epotilonas/farmacologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Lactonas/farmacologia , Macrolídeos/farmacologia , Proteínas de Membrana/genética , Microtúbulos/efeitos dos fármacos , Neurônios/ultraestrutura , Paclitaxel/farmacologia , Ratos , Ratos Sprague-Dawley , TransfecçãoRESUMO
Synergies between invasive species and climate change are widely considered to be a major biodiversity threat. However, invasive species are also hypothesized to be susceptible to population collapse, as we demonstrate for a globally important invasive species in New Zealand. We observed Argentine ant populations to have collapsed in 40 per cent of surveyed sites. Populations had a mean survival time of 14.1 years (95% CI = 12.9-15.3 years). Resident ant communities had recovered or partly recovered after their collapse. Our models suggest that climate change will delay colony collapse, as increasing temperature and decreasing rainfall significantly increased their longevity, but only by a few years. Economic and environmental costs of invasive species may be small if populations collapse on their own accord.
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Formigas/fisiologia , Mudança Climática , Espécies Introduzidas , Animais , Biota , Modelos Biológicos , Nova Zelândia , Dinâmica Populacional , Chuva , TemperaturaRESUMO
Glioblastoma is the most common and most aggressive primary brain cancer in adults. Standard treatment of glioblastoma consisting of maximal safe resection, adjuvant radiotherapy and chemotherapy with temozolomide, results in an overall median survival of 14.6 months. The aggressive nature of glioblastoma has been attributed to the presence of glioblastoma stem cells which express components of the renin-angiotensin system (RAS). This phase I clinical trial investigated the tolerability and efficacy of a treatment targeting the RAS and its converging pathways in patients with glioblastoma. Patients who had relapsed following standard treatment of glioblastoma who met the trial criteria were commenced on dose-escalated oral RAS modulators (propranolol, aliskiren, cilazapril, celecoxib, curcumin with piperine, aspirin, and metformin). Of the 17 patients who were enrolled, ten completed full dose-escalation of the treatment. The overall median survival was 19.9 (95% CI:14.1-25.7) months. Serial FET-PET/CTs showed a reduction in both tumor volume and uptake in one patient, an increase in tumor uptake in nine patients with decreased (n = 1), unchanged (n = 1) and increased (n = 7) tumor volume, in the ten patients who had completed full dose-escalation of the treatment. Two patients experienced mild side effects and all patients had preservation of quality of life and performance status during the treatment. There is a trend towards increased survival by 5.3 months although it was not statistically significant. These encouraging results warrant further clinical trials on this potential novel, well-tolerated and cost-effective therapeutic option for patients with glioblastoma.
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Neoplasias Encefálicas , Glioblastoma , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Humanos , Qualidade de Vida , Sistema Renina-Angiotensina , Temozolomida/uso terapêuticoRESUMO
Cannabis is the most popular illicit drug used by adolescents. Yet, there are only a few studies that have examined the effects of cannabis use on learning and memory during this sensitive and important neurodevelopmental stage. Male adolescent Sprague-Dawley rats were treated with Δ(9)-tetrahydrocannabinol (THC, 6 mg/kg) daily for 27 days and concurrently trained in a spatial learning and memory task. The chronic effects of cannabis use were specifically examined by assessing animal behaviour during the 'postacute' period (17 h after drug exposure), when minimal acute drug burden is expected to be present. The postacute period is a good model for cannabis use patterns in human adolescents. In addition, we investigated whether the hierarchical organization of working memory (chunking) was impaired by THC-treatment. We show that THC exposure impairs adolescent learning when tested in the postacute period, and that THC impairs the ability of animals to use a chunking strategy.
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Comportamento Animal/efeitos dos fármacos , Dronabinol/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Comportamento Espacial/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Research indicates that radiation therapists (RTs) are at risk of burnout and that there is a lack of evidence on effective coping strategies for managing work-related stressors within this workforce. Peer group supervision (PGS) is a useful tool in assisting staff to manage stress in the clinical setting, improve reflective practice and provide support. The aim of this research was to investigate New Zealand (NZ) RTs' perceptions of participating in PGS. METHODS: In-service training on PGS was offered to all RT centres in NZ, and five of the nine centres agreed to partake in PGS. Participants anonymously completed the same online questionnaire, six months apart. The questionnaire consisted of the Clinical Supervision Evaluation Questionnaire (CSEQ), an open-ended question and demographics. The CSEQ asks participants to indicate their agreement with 14 statements related to Purpose, Process and Impact of PGS. RESULTS: Overall, 71 and 48 participants completed the first and second surveys, respectively. In contrast to previous studies, this study found that confidence in practice, team support and group safety were valued by participants. This was supported by the qualitative data that revealed four themes: supportive groups, time out to reflect, organisational barriers and group process issues. RTs with one to five years' experience were more likely to structure their meetings, understand the purpose of the meetings and had clearer expectations of the group process. CONCLUSIONS: PGS may address burnout for RTs with one to five years' experience. This group of RTs feel patient-related matters can be discussed openly during PGS, and PGS appears to be helping to improve their practice and reduce stress. More experienced RTs appear to be using the groups as a 'professional support group', rather than 'peer supervision', as a strategy for managing organisational stressors associated with burnout.
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Atitude do Pessoal de Saúde , Esgotamento Profissional/prevenção & controle , Grupo Associado , Percepção , Radioterapia , Adulto , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Grupos de Autoajuda , Adulto JovemRESUMO
STUDY OBJECTIVES: The aims were (1) to investigate differences by ethnicity and socioeconomic status (SES) in objective measures of sleep in children aged 7-9 years and (2) determine whether measures of sleep predict child achievement in reading or mathematics after controlling for ethnicity and SES. METHODS: Four groups of parent-child dyads were recruited: Maori, low-SES schools (n = 18); Maori, high-SES schools (n = 17); New Zealand European, low-SES schools (n = 18); New Zealand European, high-SES schools (n = 17). Child sleep was measured by actigraphy. Parents and teachers reported child daytime sleepiness and behavior, and children completed a self-report of anxiety symptoms. Teachers also reported on child achievement in reading and mathematics. RESULTS: Children from low-SES schools went to bed later on school nights (F[1,68] = 12.150, P = .001) and woke later (F[1,68] = 15.978, P < .001) than children from high-SES schools but had similar sleep duration. There were no differences related to ethnicity. Children from low-SES schools were almost 3 times more likely to be below national standards for mathematics. Children not meeting academic standards in mathematics had a later sleep start time, lower sleep period efficiency, and a decreased total sleep time. However, when SES and sleep period efficiency were modeled together neither were found to significantly influence achievement in mathematics. CONCLUSIONS: In this study, SES influenced sleep timing but not the quality and quantity of sleep in 7- to 9-year-old children, and a significant independent effect of sleep efficiency on learning could not be demonstrated.
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Etnicidade , Leitura , Criança , Humanos , Matemática , Nova Zelândia , Instituições Acadêmicas , Sono , Classe SocialRESUMO
Despite its critical role in clinical suicidology, empirical evidence on the nature of countertransference (CT) to patients at risk for suicide (PRS) is lacking. This study aimed to provide a systematic description of CT phenomena to PRS. Psychiatrists, psychologists, and psychotherapists completed the Therapist Response Questionnaire (TRQ) online, with reference to a PRS. Factor analysis (n = 267) yielded a 7-factor structure, including 1) entrapped/rejecting, 2) fulfilled/engaging, 3) aroused/reacting, 4) informal/boundary crossing, 5) protective/overinvolvement, 6) ambivalent/inconsistent, and 7) mistreated/controlling. On average, clinicians reported that CT dimensions tended to not apply to them, except for the positively connoted factor. Our findings suggest that patients at risk for suicide elicit specific dimensions of CT. We offer two alternative interpretations of clinicians' CT endorsement patterns.
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Contratransferência , Psiquiatria , Psicologia , Psicoterapeutas , Suicídio , Atitude do Pessoal de Saúde , Análise Fatorial , Feminino , Humanos , Masculino , Nova Zelândia , Relações Profissional-Paciente , Psicometria , Inquéritos e QuestionáriosRESUMO
Background: To investigate the hypothesis that increased uptake of long-acting reversible contraception (LARC) by women played a role in the declining abortion rates observed in New Zealand between 2008 and 2014. Materials and Methods: This quantitative ecological study analyzed routinely collected national data pertaining to abortion numbers, contraceptive prescriptions, and census population estimates for the period 2004-2014. Annual prescription and prevalence rates (per 1000 women) were calculated for short- and long-acting methods to investigate changes over time. Poisson's regression was used to (1) test whether the abortion rate changed by year; (2) whether 2010 (when the contraceptive implant became subsidized) was a significant point of change; and (3) test the relationship between declining abortions and patterns of contraceptive use. Results: Estimated LARC prevalence increased from 2009 to 2014, with a corresponding decrease observed in prescription of short-acting methods. The declining abortion rate accelerated each year from 2008 to 2014 (with a faster decline from 2010 to 2014), but 2010 was not a significant point of change. Three factors had statistically significant associations with declining abortion rates (p < 0.01): year (acting as a surrogate for all social changes), women's use of the levonorgestrel (LNG)-implant, and the combined model: use of the LNG-implant and copper intrauterine device (CuIUD) had the best fit (using Akaike's Information Criterion), indicating that this variable explained more of the year-to-year variability in abortion rates. Conclusions: The shift toward women's increased use of the two publically funded LARC methods (LNG-implants and CuIUD) was significantly associated with the declining abortion rates in New Zealand.
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Aborto Induzido/estatística & dados numéricos , Anticoncepcionais Femininos/uso terapêutico , Contracepção Reversível de Longo Prazo/estatística & dados numéricos , Anticoncepção/métodos , Comportamento Contraceptivo/estatística & dados numéricos , Feminino , Humanos , Dispositivos Intrauterinos de Cobre/estatística & dados numéricos , Levanogestrel/uso terapêutico , Nova Zelândia/epidemiologiaRESUMO
BACKGROUND: Binge-drinking prevalence among New Zealand adolescents has declined sharply since 2001, as it has in many other high-income countries. Other adolescent risk behaviours (e.g. smoking, cannabis use and precocious sexual activity) have also declined, raising the possibility of common underlying drivers. This study investigates potential contributing factors - both factors that predict risk behaviours in general, and alcohol-specific factors - and the extent to which they account for the decline in binge drinking. METHODS: The study used nationally representative survey data collected in 2001 (Nâ¯=â¯6513), 2007 (Nâ¯=â¯5934) and 2012 (Nâ¯=â¯5489). The outcome measure was prevalence of past month binge drinking (5+ drinks/session). Predictor variables included factors that predict risk behaviours in general (parental monitoring, family attachment, school attachment, having a part-time job, time spent hanging out with friends); alcohol-specific factors (parental alcohol use, adolescent attitude toward alcohol use); and attitude toward and current use of tobacco and cannabis. Likelihood of binge drinking was modelled for each survey year (ref=2001), adjusting for demographic factors. Predictors were added to this base model, with the degree of attenuation of the odds ratio for year indicating the extent to which the included predictor(s) accounted for the trend. RESULTS: Compared with 2001 the odds of binge-drinking in 2012 were 0.33. The strongest independent contributor to the decline was adolescent attitude toward alcohol use, followed by current cannabis use, then current tobacco use. Collectively, general factors in home, school and leisure settings did not significantly contribute to the downward trend in binge drinking. CONCLUSION: Decreasing acceptability of alcohol use among adolescents was the most important identified contributor to adolescent binge-drinking decline. Drinking, smoking and cannabis use trends were empirically linked, yet the decline in binge drinking was not significantly explained by the included predictors common to risk behaviours in general.
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Comportamento do Adolescente , Consumo Excessivo de Bebidas Alcoólicas , Consumo de Álcool por Menores , Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Humanos , Nova Zelândia/epidemiologiaRESUMO
BACKGROUND: There is accumulating evidence of the presence of embryonic stem cell (ESC)-like cells in benign tumors. AIM: This study aimed to identify ESC-like cells in Schwannoma using the induced-pluripotent stem cell (iPSC) markers OCT4, SOX2, NANOG, KLF4 and c-MYC. METHODS: Immunohistochemical (IHC) staining (n = 20) and RT-qPCR (n = 6) were performed on Schwannoma tissue samples (STS) to investigate protein and mRNA expression of these iPSC markers, respectively. Immunofluorescence (IF) staining was performed to investigate co-localization of the iPSC markers with CD34, α-SMA and CD133. RESULTS: IHC staining and RT-qPCR demonstrated protein and mRNA expression of all five iPSC markers, respectively. IF staining showed expression of SOX2, KLF4 and c-MYC on the tumor cells and the endothelium of the tumor microvessels which also expressed OCT4, while NANOG was exclusively expressed on the endothelium of the tumor microvessels. The OCT4+/CD34+ endothelium expressed CD133. CONCLUSION: We have identified a putative OCT4+/SOX2+/NANOG+/KLF4+/c-MYC+/CD133+ ESC-like subpopulation on the endothelium of tumor microvessels and an OCT4-/SOX2+/NANOG-/KLF4+/c-MYC+/CD133+ ESC-like subpopulation, within Schwannoma.
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Neoplasias Encefálicas/metabolismo , Células-Tronco Embrionárias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neurilemoma/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Fator 4 Semelhante a KruppelRESUMO
Cancer stem cells (CSCs) have been identified in many cancer types including primary head and neck cutaneous squamous cell carcinoma (HNcSCC). This study aimed to identify and characterize CSCs in metastatic HNcSCC (mHNcSCC). Immunohistochemical staining performed on mHNcSCC samples from 15 patients demonstrated expression of the induced pluripotent stem cell (iPSC) markers OCT4, SOX2, NANOG, KLF4, and c-MYC in all 15 samples. In situ hybridization and RT-qPCR performed on four of these mHNcSCC tissue samples confirmed transcript expression of all five iPSC markers. Immunofluorescence staining performed on three of these mHNcSCC samples demonstrated expression of c-MYC on cells within the tumor nests (TNs) and the peri-tumoral stroma (PTS) that also expressed KLF4. OCT4 was expressed on the SOX2+/NANOG+/KLF4+ cells within the TNs, and the SOX2+/NANOG+/KLF4+ cells within the PTS. RT-qPCR demonstrated transcript expression of all five iPSC markers in all three mHNcSCC-derived primary cell lines, except for SOX2 in one cell line. Western blotting showed the presence of SOX2, KLF4, and c-MYC but not OCT4 and NANOG in the three mHNcSCC-derived primary cell lines. All three cell lines formed tumorspheres, at the first passage. We demonstrated an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ CSC subpopulation and an OCT4+/NANOG-/SOX2+/KLF4+/c-MYC+ subpopulation within the TNs, and an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ subpopulation within the PTS of mHNcSCC.
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OBJECTIVE: Because clozapine and risperidone have been shown to reduce neuroinflammation in humans and mice, the Clozapine and Risperidone in Progressive Multiple Sclerosis (CRISP) trial was conducted to determine whether clozapine and risperidone are suitable for progressive multiple sclerosis (pMS). METHODS: The CRISP trial (ACTRN12616000178448) was a blinded, randomised, placebo-controlled trial with three parallel arms (n=12/arm). Participants with pMS were randomised to clozapine (100-150 mg/day), risperidone (2.0-3.5 mg/day) or placebo for 6 months. The primary outcome measures were safety (adverse events (AEs)/serious adverse events (SAE)) and acceptability (Treatment Satisfaction Questionnaire for Medication-9). RESULTS: An interim analysis (n=9) revealed significant differences in the time-on-trial between treatment groups and placebo (p=0.030 and 0.025, clozapine and risperidone, respectively) with all participants receiving clozapine being withdrawn during the titration period (mean dose=35±15 mg/day). Participants receiving clozapine or risperidone reported a significantly higher rate of AEs than placebo (p=0.00001) but not SAEs. Specifically, low doses of clozapine appeared to cause an acute and dose-related intoxicant effect in patients with pMS who had fairly severe chronic spastic ataxic gait and worsening over all mobility, which resolved on drug cessation. INTERPRETATION: The CRISP trial results suggest that patients with pMS may experience increased sensitivity to clozapine and risperidone and indicate that the dose and/or titration schedule developed for schizophrenia may not be suitable for pMS. While these findings do not negate the potential of these drugs to reduce multiple sclerosis-associated neuroinflammation, they highlight the need for further research to understand the pharmacodynamic profile and effect of clozapine and risperidone in patients with pMS. TRIAL REGISTRATION NUMBER: ACTRN12616000178448.
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Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM tissue samples demonstrated expression of iPSC markers OCT4, SOX2, KLF4, and c-MYC in all samples, while NANOG was expressed at low levels in two samples. Immunofluorescence (IF) staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the tumor nests (TNs) and another within the peritumoral stroma (PTS) of HNmMM tissues. IF also showed expression of NANOG by some OCT4+/SOX2+/KLF4+/c-MYC+ cells within the TNs in an HNmMM tissue sample that expressed NANOG on IHC staining. In situ hybridization (n = 6) and reverse-transcription quantitative polymerase chain reaction (n = 5) on the HNmMM samples confirmed expression of all five iPSC markers. Western blotting of primary cell lines derived from four of the 20 HNmMM tissue samples showed expression of SOX2, KLF4, and c-MYC but not OCT4 and NANOG, and three of these cell lines formed tumorspheres in vitro. We demonstrate the presence of two putative CSC subpopulations within HNmMM, which may be a novel therapeutic target in the treatment of this aggressive cancer.
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Neoplasias de Cabeça e Pescoço/patologia , Melanoma/patologia , Células-Tronco Neoplásicas/patologia , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator 4 Semelhante a Kruppel , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
BACKGROUND AND AIM: Eosinophilic esophagitis (EoE) is an immune-mediated inflammatory condition of the esophagus. Recent literature has shown an increasing incidence of the disease. However, no epidemiological data exist regarding New Zealand rates of EoE. The disease is associated with atopy, and New Zealand's high rate of atopic disease means the disease may be important in our population. We carried out a retrospective study to describe the incidence of EoE in the Wellington region of New Zealand, as well as key histological and clinical factors associated with the disease. METHOD: A search was made of laboratory and endoscopic databases in the Wellington region to identify all diagnosed cases in the five years between January 1, 2011, and December 31, 2015. Case notes were examined to determine the key demographic and clinical parameters in the cases. Incidence rates were calculated for each year, and the effects of age group and sex on the incidence rates were analyzed. RESULT: We found 152 cases of EoE in the Wellington region with an annual incidence of 6.95 per 100,000 person/years. We found no evidence of a significant difference in incidence rates by year in our study population. There was a significantly lower incidence rate in those aged <16 compared to those aged ≥16 (RR=0.26). Males had a higher incidence rate than females with an estimated rate ratio of 2.45 (p<0.05). CONCLUSION: Our results are in contrast to previous reports of increasing incidence rates and may reflect a leveling off of incidence. Further research is needed to determine whether the low incidence in our pediatric age group is due to ascertainment bias or due to a real difference in the epidemiology of EoE in NZ compared to other countries.
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OBJECTIVES: To determine the level of agreement among patients with rheumatoid arthritis (RA) with the principles and recommendations of the treat-to-target (T2T) initiative in New Zealand (NZ) and to further explore specific patient opinions via online iterative surveys. METHODS: Participants with RA were recruited from rheumatology clinics in NZ and invited to receive and reply to surveys administered via the Patient Opinion Real-Time Anonymous Liaison (PORTAL) system. An enrolment survey recorded demographics, disease duration and treatment and then RA T2T surveys were administered weekly. A Likert scale 1-5 measured agreement with the principles and recommendations and further surveys explored responses of interest identified by investigators from each prior survey. RESULTS: One hundred and ninety patients consented to participate in PORTAL and 132 in the RA T2T surveys. Level of agreement with RA T2T principles was: 93.3% to 99.3% and to the recommendations: 77.3%-100%. The lowest level of agreement 77.3% was with recommendation 8, 3 monthly treatment adjustment, and the highest was 100% agreement with recommendation 10, shared decision-making. Patients agreed less with low disease activity as the target compared with remission (91.4% and 98%). Despite high-level agreement for the use of a disease activity score (95.7%), 23% did not feel the individual components reflected their disease control. Patients rated difficulty coping, erosions on imaging, health-related quality of life and pain all significantly higher than C-reactive protein as indicators of worsening arthritis. CONCLUSIONS: Despite a high level of patient agreement with RA T2T this study highlights the importance of patient engagement in the RA T2T process to individualize therapy adjustments, make shared decisions and decide on targets that accurately reflect disease control according to patients.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Avaliação de Processos e Resultados em Cuidados de Saúde , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Guias de Prática Clínica como Assunto , Adaptação Psicológica , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/psicologia , Efeitos Psicossociais da Doença , Progressão da Doença , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Percepção da Dor , Participação do Paciente , Qualidade de Vida , Indução de Remissão , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: Cannabis use declined in New Zealand adolescents between 2001 and 2012. We investigated i) whether changes in adolescent cannabis use occurred across all demographic groups, and ii) whether declining cannabis use was accompanied by increasing use of other psychoactive drugs. METHOD: We conducted secondary analysis of repeat cross-sectional data from nationally representative surveys of secondary school students (2001, 2007, 2012) to determine trends in never-use of cannabis and other psychoactive drugs by age, sex, ethnicity, deprivation, school decile and urban/rural locale. Logistic regression was used to test whether changes in cannabis non-use over time varied between demographic groups. RESULTS: Never-use of cannabis and of other psychoactive substances increased between 2001 and 2012 in all included age, ethnic, sex and socioeconomic groups. Maori, younger students and those in low decile schools demonstrated the greatest reductions in cannabis use over the study period. CONCLUSION: The decline in adolescent cannabis use between 2001 and 2012 occurred across all main demographic groups and was not accompanied by a rise in the use of other psychoactive drugs. Ethnic and socioeconomic inequities in adolescent cannabis use decreased over the study period.