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1.
Soc Psychiatry Psychiatr Epidemiol ; 56(10): 1903-1911, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33606048

RESUMO

PURPOSE: Evidence suggests that the distinctive relational qualities of peer support-compared to clinical-patient relationships-can be eroded in regulated healthcare environments. Measurement of fidelity in trials of peer support is lacking. This paper reports the development and testing of a fidelity index for one-to-one peer support in mental health services, designed to assess fidelity to principles that characterise the distinctiveness of peer support. METHODS: A draft index was developed using expert panels of service user researchers and people doing peer support, informed by an evidence-based, peer support principles framework. Two rounds of testing took place in 24 mental health services providing peer support in a range of settings. Fidelity was assessed through interviews with peer workers, their supervisors and people receiving peer support. Responses were tested for spread and internal consistency, independently double rated for inter-rater reliability, with feedback from interviewees and service user researchers used to refine the index. RESULTS: A fidelity index for one-to-one peer support in mental health services was produced with good psychometric properties. Fidelity is assessed in four principle-based domains; building trusting relationships based on shared lived experience; reciprocity and mutuality; leadership, choice and control; building strengths and making connections to community. CONCLUSIONS: The index offers potential to improve the evidence base for peer support in mental health services, enabling future trials to assess fidelity of interventions to peer support principles, and service providers a means of ensuring that peer support retains its distinctive qualities as it is introduced into mental health services.


Assuntos
Transtornos Mentais , Serviços de Saúde Mental , Aconselhamento , Humanos , Transtornos Mentais/terapia , Grupo Associado , Psicometria , Reprodutibilidade dos Testes
2.
Neurobiol Learn Mem ; 174: 107273, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659349

RESUMO

Sleep and memory processing impairments range from mild to severe in the psychosis spectrum. Relationships between memory processing and sleep characteristics have been described for schizophrenia, including unaffected first-degree relatives, but they are less clear across other high-risk groups within the psychosis spectrum. In this study, we investigated high-risk individuals with accumulated risk-factors for psychosis and subthreshold symptoms. Out of 1898 screened individuals, 44 age- and sex-matched participants were sub-grouped into those with substantial environmental risk factors for psychosis and subthreshold psychotic symptoms (high-risk group) and those without these phenotypes (low-risk controls). Four groups (high/low risk, morning/evening training) were trained and tested in the laboratory for sustained attention, motor skill memory (finger-tapping task) and declarative memory (word-pair learning task) immediately after training, again after a night of EEG-recorded sleep at home or a period of daytime wakefulness, and again after 24 h from training. No differences in sustained attention or in memory consolidation of declarative and motor skill memory were found between groups for any time period tested. However, a group difference was found for rapid-eye movement (REM) sleep in relation to motor skill memory: the longer the total sleep time, particularly longer REM sleep, the greater the performance gain, which occurred only in high-risk individuals. In conclusion, our results suggest a gain in motor skill performance with sufficient sleep opportunity for longer REM sleep in high-risk individuals with subthreshold psychotic symptoms. Declarative memory did not benefit from sleep consolidation above or beyond that of the control group.


Assuntos
Consolidação da Memória , Transtornos Psicóticos/psicologia , Sono , Adolescente , Adulto , Atenção , Eletroencefalografia , Feminino , Humanos , Masculino , Destreza Motora , Fenótipo , Polissonografia , Desempenho Psicomotor , Transtornos Psicóticos/fisiopatologia , Adulto Jovem
3.
Colorectal Dis ; 21(8): 869-878, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30932326

RESUMO

AIM: The best treatment for tailgut cysts has not been firmly established. We report a systematic review of the cases in the available literature in order to provide an evidence base for treatment. METHOD: A systematic search of articles wholly or partly in English was made of PubMed, Embase and Google Scholar; additional studies were discovered by searching reference lists and contacting authors directly. Search terms 'tailgut cyst', 'tail gut cyst', 'retrorectal hamartoma' and 'retrorectal tumour' were used for case reports or case series; no publication date restrictions were imposed. Only studies with histological confirmation of diagnosis and reporting the age and gender of patients were included. Papers were excluded by consensus between the first two authors. RESULTS: A total of 196 individual cases were analysed in detail including 51 cases of neoplasia. The overall rate of neoplastic transformation was 26.6%. Although the male:female cyst incidence ratio was 1:4, men over 18 had a significantly greater relative risk of neoplasm at 1.94 (P = 0.0055). Radiological evidence of nodular thickening of the cyst wall significantly increased the relative risk of the presence of cancer (P = 0.0023). CONCLUSIONS: Current orthodoxy that these are not dangerous embryological remnants is unfounded and may be false. The available data suggest the risk of malignant transformation is high and will apply to any residual tissue after excision. The same rationale behind total mesorectal excision in rectal cancer applies to tailgut cysts. Consequently they should be resected with similar oncological margins.


Assuntos
Cistos/complicações , Hamartoma/complicações , Doenças Retais/complicações , Neoplasias Retais/epidemiologia , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/etiologia
4.
J Dairy Sci ; 102(9): 8400-8404, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279548

RESUMO

The objective of this study was to determine the herd-level variables that are associated with overmilking in 64 Michigan dairy herds with a mean herd size of 451 cows (range: 59-2,771 cows). Participating producers completed surveys to indicate their mastitis management practices and attitudes. Additionally, milking protocols were observed and milk flow dynamics for 3,824 cows were estimated using digital vacuum recorders. The median duration of overmilking was 47 s (95% confidence interval, CI: 38.6 to 55.9 s), with a mean of 55% (95% CI: 49.5 to 61.1%) of cows within each herd overmilked by at least 30 s. Median milking time for all herds was 324 s (95% CI: 302 to 346 s) and was found to be positively correlated with median duration of overmilking (r = 0.670). Backward multivariate analysis was used to determine which of 45 herd-level milking and management variables were associated with median duration of overmilking. Median duration of overmilking was negatively associated with the duration of time needed to complete 1 milking for the entire herd (adjusted R2 = 0.13). Herds that operate milking facilities below maximum daily capacity may be prone to overmilking. Given the low coefficient of determination, variables unaccounted for in this study, such as equipment function or manual detachment by milking operators, are likely the most important risk factors for overmilking.


Assuntos
Indústria de Laticínios , Mastite Bovina , Leite , Animais , Bovinos , Indústria de Laticínios/métodos , Feminino , Humanos , Michigan , Análise Multivariada , Fatores de Risco , Inquéritos e Questionários
5.
J Dairy Sci ; 102(3): 2544-2550, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30639006

RESUMO

The objective of this study was to determine the herd-level variables that were associated with total stimulation time during the premilking routine in 64 Michigan dairy herds. The mean herd size was 452 cows (range = 59 to 2,771 cows). For each herd, surveys were administered to producers to gather mastitis management practices and attitudes. Additionally, milking protocols were observed and milk flow dynamics were measured by use of digital vacuum recorders. Backward multivariate regression analysis was used to determine which of 47 herd-level milking and management variables were associated with mean total stimulation time. Mean total stimulation time was 14.2 s (range = 2.4-40.8 s) and was positively associated with increasing latency period (time interval between first stimulation and cluster attachment). Total stimulation time was negatively associated with greater herd size and number of visits to each cow in the premilking routine. In summary, increased stimulation time is more likely in herds that foster a lower sense of urgency of cow throughput during milking, as evidenced by a positive association with longer latency periods and fewer preparation visits per cow. Tactile stimulation is critical for efficient milk ejection; if inadequate, cows are at greater risk of delayed milk ejection and bimodal milk flow, which in turn has been associated with teat congestion and reduced milk flow. This study offers insight as to some of the herd factors that may be limiting adequate tactile stimulation.


Assuntos
Criação de Animais Domésticos , Bovinos/fisiologia , Glândulas Mamárias Animais/fisiologia , Ejeção Láctea/fisiologia , Animais , Feminino , Michigan , Análise Multivariada
6.
J Dairy Sci ; 102(1): 696-705, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30343911

RESUMO

The objective of this study was to determine which herd-level variables were associated with delayed milk ejection (bimodal milk let-down) in 64 Michigan dairy herds. Median herd size was 294 cows (range 59 to 2,771 cows). For each herd, milking protocols were observed and milk flow dynamics were estimated by use of digital vacuum recorders. Surveys were also administered to the producers to measure mastitis management practices and attitudes. Milk flow dynamics were recorded for a total of 3,824 cow milkings, with a mean of 60 milkings per herd (range of 11 to 154). Backward multivariable analysis was used to determine which of the 47 herd-level milking and management variables were associated with delayed milk ejection (cows with milk let-down periods between milking cluster attachment and the incline phase of milk flow of >30 s). Delayed milk ejection occurred in an average of 25% of the cows in each herd (range 0 to 75%). A multivariable model found that the proportion of cows in a herd with delayed milk ejection was negatively associated with mean total time of tactile stimulation during premilking routines and positively associated with herd size.


Assuntos
Bovinos/fisiologia , Indústria de Laticínios/métodos , Lactação/fisiologia , Ejeção Láctea/fisiologia , Animais , Feminino , Michigan , Leite
7.
Ann Oncol ; 29(2): 341-346, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29140422

RESUMO

Background: To report our experience utilizing a multidisciplinary clinic (MDC) at Indiana University (IU) since the publication of the International Germ Cell Cancer Collaborative Group (IGCCCG), and to compare our overall survival (OS) to that of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program. Patients and methods: We conducted a retrospective analysis of all patients with metastatic germ-cell tumor (GCT) seen at IU from 1998 to 2014. A total of 1611 consecutive patients were identified, of whom 704 patients received an initial evaluation by our MDC (including medical oncology, pathology, urology and thoracic surgery) and started first-line chemotherapy at IU. These 704 patients were eligible for analysis. All patients in this cohort were treated with cisplatin-etoposide-based combination chemotherapy. We compared the progression-free survival (PFS) and OS of patients treated at IU with that of the published IGCCCG cohort. OS of the IU testis cancer primary cohort (n = 622) was further compared with the SEER data of 1283 patients labeled with 'distant' disease. The Kaplan-Meier method was used to estimate PFS and OS. Results: With a median follow-up of 4.4 years, patients with good, intermediate, and poor risk disease by IGCCCG criteria treated at IU had 5-year PFS of 90%, 84%, and 54% and 5-year OS of 97%, 92%, and 73%, respectively. The 5-year PFS for all patients in the IU cohort was 79% [95% confidence interval (CI) 76% to 82%]. The 5-year OS for the IU cohort was 90% (95% CI 87% to 92%). IU testis cohort had 5-year OS 94% (95% CI 91% to 96%) versus 75% (95% CI 73% to 78%) for the SEER 'distant' cohort between 2000 and 2014, P-value <0.0001. Conclusion: The MDC approach to GCT at high-volume cancer center associated with improved OS outcomes in this contemporary dataset. OS is significantly higher in the IU cohort compared with the IGCCCG and SEER 'distant' cohort.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oncologia/métodos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/mortalidade , Adolescente , Adulto , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Intervalo Livre de Progressão , Estudos Retrospectivos , Adulto Jovem
8.
Reprod Domest Anim ; 53(3): 718-724, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29537110

RESUMO

Emerging research suggests that the nitric oxide system may play a role in persistent breeding-induced endometritis (PBIE) in the mare. Differences in uterine nitric oxide (NO) levels between mares susceptible or resistant to PBIE and a dose-dependent inhibitory effect of NO on uterine contractility have been demonstrated. The objectives of this study were to investigate the difference in total nitric oxide synthase (NOS) activity of the endometrium between susceptible and resistant mares and the effect of a specific inducible nitric oxide synthase (iNOS) inhibitor on the endometrial NOS activity in vitro. Six susceptible and six resistant mares were selected based on preset criteria and the results of an intrauterine challenge with killed spermatozoa during oestrus. Endometrial biopsy samples were collected 24 hr post-challenge and cultured at 37°C for 24 hr in L-arginine supplemented minimum essential medium with or without a specific iNOS inhibitor (1,400 W dihydrochloride, 1 mM). The medium and the cultured endometrial tissue were collected after 24 hr of culture and assayed for NO and total protein, respectively. Total NO content of the medium, normalized to endometrial tissue wet weight or total protein, was used as a measure of endometrial NOS activity. Non-parametric tests were applied for statistical analysis. Susceptible mares had significantly greater endometrial NOS activity than resistant mares. The iNOS inhibitor treatment significantly reduced NOS activity in endometrial samples derived from susceptible and resistant mares. These findings provide a basis for in vivo testing of specific iNOS inhibitors as preventative or therapeutic options for PBIE in mares.


Assuntos
Suscetibilidade a Doenças/veterinária , Endometrite/veterinária , Doenças dos Cavalos/enzimologia , Óxido Nítrico Sintase/metabolismo , Animais , Endometrite/enzimologia , Endométrio/enzimologia , Inibidores Enzimáticos/farmacologia , Feminino , Cavalos , Masculino , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Espermatozoides
9.
Reprod Domest Anim ; 53(3): 822-825, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29575379

RESUMO

A 1-year-old, previously spayed phenotypic female Poodle/Soft-coated Wheaten Terrier (Whoodle) cross was presented for a suspected ovarian remnant. Serum luteinizing hormone (LH) concentration was below the detection limit (<1 ng/ml Witness® LH), and serum progesterone concentration was elevated in the chemiluminescence immunoassay (CLIA; 20 ng/ml), consistent with dioestrus and presence of ovarian tissue. Transabdominal ultrasound revealed a retroperitoneal soft tissue structure suspected to be a gonad. On exploratory laparotomy, a gonad was removed from the cranial retroperitoneum, cranial to the right kidney, after ligation of its primary blood supply. Histological examination proved the gonad to be an ovotestis. Subsequent cytogenetics revealed a 78 XX karyotype, thus confirming the diagnosis of ectopic ovotestis in a XX ovotesticular, SRY-negative, disorder of sexual development in a dog.


Assuntos
Cães/anormalidades , Transtornos Ovotesticulares do Desenvolvimento Sexual/veterinária , Animais , Feminino , Cariótipo , Hormônio Luteinizante/sangue , Transtornos Ovotesticulares do Desenvolvimento Sexual/genética , Transtornos Ovotesticulares do Desenvolvimento Sexual/cirurgia , Progesterona/sangue
10.
J Allergy Clin Immunol ; 140(6): 1587-1591.e1, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28577971

RESUMO

BACKGROUND: Food allergy prevalence is reported to be increasing, but epidemiological data using patients' electronic health records (EHRs) remain sparse. OBJECTIVE: We sought to determine the prevalence of food allergy and intolerance documented in the EHR allergy module. METHODS: Using allergy data from a large health care organization's EHR between 2000 and 2013, we determined the prevalence of food allergy and intolerance by sex, racial/ethnic group, and allergen group. We examined the prevalence of reactions that were potentially IgE-mediated and anaphylactic. Data were validated using radioallergosorbent test and ImmunoCAP results, when available, for patients with reported peanut allergy. RESULTS: Among 2.7 million patients, we identified 97,482 patients (3.6%) with 1 or more food allergies or intolerances (mean, 1.4 ± 0.1). The prevalence of food allergy and intolerance was higher in females (4.2% vs 2.9%; P < .001) and Asians (4.3% vs 3.6%; P < .001). The most common food allergen groups were shellfish (0.9%), fruit or vegetable (0.7%), dairy (0.5%), and peanut (0.5%). Of the 103,659 identified reactions to foods, 48.1% were potentially IgE-mediated (affecting 50.8% of food allergy or intolerance patients) and 15.9% were anaphylactic. About 20% of patients with reported peanut allergy had a radioallergosorbent test/ImmunoCAP performed, of which 57.3% had an IgE level of grade 3 or higher. CONCLUSIONS: Our findings are consistent with previously validated methods for studying food allergy, suggesting that the EHR's allergy module has the potential to be used for clinical and epidemiological research. The spectrum of severity observed with food allergy highlights the critical need for more allergy evaluations.


Assuntos
Anafilaxia/epidemiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Etnicidade , Hipersensibilidade Alimentar/epidemiologia , Fatores Sexuais , Alérgenos/imunologia , Feminino , Humanos , Imunoglobulina E/metabolismo , Masculino , Prevalência , Teste de Radioalergoadsorção , Risco , Frutos do Mar , Estados Unidos/epidemiologia
11.
HIV Med ; 17(8): 623-30, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27019207

RESUMO

OBJECTIVES: We established a subcohort of HIV-positive individuals from 10 sexual health clinics within the Australian HIV Observational Database (AHOD). The aim of this study was to assess demographic and other factors that might be associated with an incident sexually transmitted infection (STI). METHODS: The cohort follow-up was from March 2010 to March 2013, and included patients screened at least once for an STI. We used survival methods to determine time to first new and confirmed incident STI infection (chlamydia, gonorrhoea, syphilis or genital warts). Factors evaluated included sex, age, mode of HIV exposure, year of AHOD enrolment, hepatitis B or C coinfection, time-updated CD4 cell count, time-updated HIV RNA viral load, and prior STI diagnosis. RESULTS: There were 110 first incident STI diagnoses observed over 1015 person-years of follow-up, a crude rate of 10.8 [95% confidence interval (CI) 9.0-13.0] per 100 person-years. Factors independently associated with increased risk of incident STI included younger age [≥ 50 vs. 30-39 years old, adjusted hazards ratio (aHR) 0.4; 95% CI 0.2-0.8; P < 0.0001]; prior STI infection (aHR 2.5; 95% CI 1.6-3.8; P < 0.001), and heterosexual vs. men who have sex with men (MSM) as the likely route of exposure (aHR 0.2; 95% CI 0.1-0.6; P < 0.001). CONCLUSIONS: In this cohort of individualsbeing treated with antiretroviral drugs, those who were MSM, who were 30-39 years old, and who had a prior history of STI, were at highest risk of a further STI diagnosis.


Assuntos
Condiloma Acuminado/epidemiologia , Infecções por HIV/complicações , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Seguimentos , Infecções por HIV/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
12.
Vet Pathol ; 53(3): 545-58, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26459517

RESUMO

The receptor tyrosine kinase (RTK) KIT is a major focus of current research into canine mast cell tumors (MCTs). Little is known about the role of other RTKs, such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs). These RTKs are dysregulated in many human and animal cancers and are key regulators of tumor angiogenesis. The aims of this study were to assess the expression and activation (phosphorylation) status of KIT, VEGFR2, and PDGFR (α and ß) in canine MCTs and to examine associations with various clinical outcomes. c-KITmutational status and KIT cellular localization pattern were also evaluated for these tumors. Twenty-seven MCTs, consisting of 5 subcutaneous and 22 cutaneous tumors, from 25 dogs were evaluated. MCT biopsies, cultured mast cells, and skin from the surgical margin were analyzed through Western blotting. MCT biopsies were also used for KIT immunohistochemical labeling and polymerase chain reaction for c-KITmutational analysis. MCT had heterogeneous expression profiles for all 3 RTKs, which varied in intensity and activation status. Statistical analyses showed phosphorylated KIT, VEGFR2, and KIT cellular localization to be predictive of decreased survival time, disease-free interval, and increased metastatic rate. Expression of VEGFR2 and KIT diffuse cytoplasmic labeling were also significantly associated with increased rate of local recurrence. The results of the study show that phosphorylated KIT, KIT, VEGFR2, and PDGFRß, in addition to KIT localization, may be valuable prognostic determinants in MCTs and should be further studied to improve diagnostic and therapeutic modalities.


Assuntos
Biomarcadores Tumorais/metabolismo , Doenças do Cão/diagnóstico , Mastócitos , Receptores Proteína Tirosina Quinases/metabolismo , Neoplasias Cutâneas/veterinária , Animais , Doenças do Cão/enzimologia , Doenças do Cão/patologia , Cães , Feminino , Masculino , Mastócitos/enzimologia , Mastócitos/patologia , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptores Proteína Tirosina Quinases/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Proc Biol Sci ; 282(1817): 20151453, 2015 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-26468242

RESUMO

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research.


Assuntos
Ecossistema , Abastecimento de Alimentos , Periodicidade , Estações do Ano , Agricultura , Animais , Biodiversidade , Mudança Climática , Humanos , Plantas
14.
J Biomed Inform ; 55: 188-95, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25917057

RESUMO

Accurate electronic health records are important for clinical care and research as well as ensuring patient safety. It is crucial for misspelled words to be corrected in order to ensure that medical records are interpreted correctly. This paper describes the development of a spelling correction system for medical text. Our spell checker is based on Shannon's noisy channel model, and uses an extensive dictionary compiled from many sources. We also use named entity recognition, so that names are not wrongly corrected as misspellings. We apply our spell checker to three different types of free-text data: clinical notes, allergy entries, and medication orders; and evaluate its performance on both misspelling detection and correction. Our spell checker achieves detection performance of up to 94.4% and correction accuracy of up to 88.2%. We show that high-performance spelling correction is possible on a variety of clinical documents.


Assuntos
Confiabilidade dos Dados , Registros Eletrônicos de Saúde/organização & administração , Processamento de Linguagem Natural , Garantia da Qualidade dos Cuidados de Saúde/métodos , Vocabulário Controlado , Processamento de Texto/métodos , Aprendizado de Máquina , Uso Significativo/organização & administração , Processamento de Texto/normas
15.
J Vet Pharmacol Ther ; 37(5): 500-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24611596

RESUMO

Tulathromycin, a long acting macrolide antibiotic, has demonstrated efficacy against respiratory pathogens including Mycoplasma bovis and M. hyopneumoniae. A pharmacokinetic study was performed to evaluate the clinical applicability of tulathromycin in desert tortoises following a single intramuscular dose of 5 mg/kg. A single blood sample was collected from 110 different desert tortoises at 0.25, 0.5, 1, 4, 8, 24, 48, 72, 120, and 240 h following drug administration. Plasma concentrations of the parent form of tulathromycin were measured using liquid chromatography/mass spectrometry. As each tortoise was only bled once, pharmacokinetic parameters were initially estimated using a naïve pooled data approach. Given the variability in the data, population-based compartmental modeling was also performed. Using nonparametric population compartmental modeling, a two-compartment model with first-order absorption and elimination best fit the data. An observed Cmax of 36.2 ± 29.7 µg/mL was detected at 0.25 h (observed Tmax ). The elimination half-life (T½el ) was long (77.1 h) resulting in detectable plasma concentrations 240 h postadministration. This study represents a preliminary step in evaluating the utility of tulathromycin in chelonian species and demonstrates that population data modeling offers advantages for estimating pharmacokinetic parameters where sparse data sampling occurs and there is substantial variability in the data.


Assuntos
Antibacterianos/farmacocinética , Dissacarídeos/farmacocinética , Compostos Heterocíclicos/farmacocinética , Tartarugas/metabolismo , Animais , Antibacterianos/administração & dosagem , Dissacarídeos/administração & dosagem , Compostos Heterocíclicos/administração & dosagem , Injeções Intramusculares , Tartarugas/sangue
16.
Ann R Coll Surg Engl ; 106(4): 359-363, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37642083

RESUMO

INTRODUCTION: There has been an almost 100% increase in referrals to breast cancer diagnostic clinics in the past decade. Breaching of the two-week cancer referral target is now commonplace, potentially delaying diagnoses of breast malignancy in many women. Almost one in five of these referrals are women with mastalgia, not a symptom linked to breast cancer. The objective of the study was the safe introduction of an advanced nurse practitioner-led telephone service for women with mastalgia to improve the service for women and create capacity for those with "red flag" breast symptoms. METHODS: Referrals to clinic were triaged, women with mastalgia only were directed to a telephone-based assessment clinic and symptoms evaluated using a multidisciplinary created proforma. RESULTS: Within 23 months, 1,427 women were assessed in the breast pain telephone assessment clinic: 863 (61%) were aged over 40 and 564 (39%) aged under 40. A total of 1,238 underwent telephone assessment. Reassurance and discharge only was needed for 365 (26%). The aetiology of pain was identified as musculoskeletal in 1,104/1,238 (89%) of patients, with only 39/1,238 (3.2%) identified as having true breast pain. Additional symptoms were mentioned by 264 women (18%) during the consultation; all immediately redirected back to a diagnostic clinic. Mammography was undertaken in 609 women (43%). Seven women (0.6%) were diagnosed with a breast malignancy. Patient survey indicated that 93% of patients were satisfied with the care received and 97% said they would recommend the service to a family member or friend. CONCLUSIONS: Although face-to-face assessments for breast pain remain the standard practice in many breast units, data indicating the safety of a telephone assessment clinic, along with high levels of patient satisfaction, question whether services can be delivered differently.


Assuntos
Neoplasias da Mama , Mastodinia , Profissionais de Enfermagem , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Mastodinia/diagnóstico , Mastodinia/etiologia , Mastodinia/terapia , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Encaminhamento e Consulta , Telefone
17.
Environ Microbiol ; 15(5): 1441-51, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22857133

RESUMO

Phaeocystis globosa is an ecologically important bloom-forming phytoplankton, which sequesters substantial amounts of inorganic carbon and can form carbon-enriched chitinous star-like structures. Viruses infecting P. globosa (PgVs) play a significant regulatory role in population dynamics of the host species. However, the extent to which viruses alter host physiology and its carbon assimilation on single cell level is still largely unknown. This study demonstrates for the first time the impact of viral infection on carbon assimilation and cell morphology of individual axenic P. globosa cells using two single cell techniques: high resolution nanometre-scale Secondary-Ion Mass Spectrometry (nanoSIMS) approach and atomic force microscopy (AFM). Up until viral lysis (19 h post infection), the bulk carbon assimilation by infected P. globosa cultures was identical to the assimilation by the non-infected cultures (33 µmol C l(-1)). However, single cell analysis showed that viral infection of P. globosa impedes the release of star-like structures. Non-infected cells transfer up to 44.5 µmol C l(-1) (36%) of cellular biomass in the form of star-like structures, suggesting a vital role in the survival of P. globosa cells. We hypothesize that impediment of star-like structures in infected P. globosa cells may inactivate viral infectivity by forming flocculants after cell lysis. Moreover, we show that substantial amounts of newly produced viruses (≈ 68%) were attached to P. globosa cells prior to cell lysis. Further, we speculate that infected cells become more susceptible for grazing which provides potential reasons for the sudden disappearance of PgVs in the environment. The scenarios of enhanced grazing is at odds to the current perspective that viral infections facilitates microbial mediated processes by diverting host material away from the higher trophic levels.


Assuntos
Quitina/metabolismo , Haptófitas/virologia , Vírus/metabolismo , Biomassa , Carbono/metabolismo , Haptófitas/citologia , Fitoplâncton/citologia , Fitoplâncton/virologia , Análise de Célula Única , Microbiologia da Água
19.
Nat Genet ; 10(2): 161-6, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7545056

RESUMO

The epidermis is readily accessible for genetic manipulation and is easily monitored. Using pig skin because it is very similar to human skin morphologically, we have developed a method to transiently express biologically active factors in epidermis. Following direct injection of naked plasmid DNA into skin, DNA is taken up and transiently expressed at high levels by epidermal keratinocytes. Injection of interleukin-8 plasmid DNA into skin results in the appropriate biological response of neutrophil recruitment, demonstrating functional utility. In addition to this model's therapeutic uses, the biological effects of structural gene products on the epidermis could also be studied in vivo.


Assuntos
Epiderme/metabolismo , Técnicas de Transferência de Genes , Interleucina-8/genética , Plasmídeos/genética , Animais , Sequência de Bases , Transporte Biológico , Quimiotaxia de Leucócito , Células Epidérmicas , Epiderme/imunologia , Expressão Gênica , Humanos , Interleucina-8/biossíntese , Queratinócitos/imunologia , Queratinócitos/metabolismo , Contagem de Leucócitos , Dados de Sequência Molecular , Ativação de Neutrófilo , Plasmídeos/metabolismo , Plasmídeos/farmacocinética , RNA/análise , Suínos , beta-Galactosidase/biossíntese , beta-Galactosidase/genética
20.
SAR QSAR Environ Res ; 34(12): 983-1001, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38047445

RESUMO

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating. The DGM/NIHS provided a curated training dataset of approximately 12,000 chemicals and a trial dataset of approximately 1,600 chemicals, and each participating team predicted the Ames mutagenicity of each trial chemical using various Ames/QSAR models. The DGM/NIHS then provided the Ames test results for trial chemicals to assist in model improvement. Although overall model performance on the Second Project was not superior to that on the First, models from the eight teams participating in both projects achieved higher sensitivity than models from teams participating in only the Second Project. Thus, these evaluations have facilitated the development of QSAR models.


Assuntos
Mutagênicos , Relação Quantitativa Estrutura-Atividade , Mutagênicos/toxicidade , Mutagênicos/química , Testes de Mutagenicidade , Mutagênese , Japão
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