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BACKGROUND: In social prescribing, link workers support individuals whose persistent health problems are exacerbated by loneliness by connecting them to community-based social activities. This approach is well established in the UK and is gaining attention in Australia. However, a major limitation of research to date has been a lack of theoretically informed and rigorous evaluations of social prescribing. We will address these points in this study, applying a social identity framework to examine the effects of group-based social prescribing (SP) activity compared to primary care treatment as usual (TAU). METHODS: Ninety participants experiencing loneliness recruited from primary care services and community centres across five sites in Southeast Queensland will be assigned to one of two conditions (SP, TAU) and assessed at two timepoints (baseline, + 8 weeks). Individuals will be aged 18 years and over, have sufficient English language skills to provide consent, and at the time of recruitment they will not be experiencing acute symptoms or social issues that require urgent intervention. Primary outcomes are loneliness, mental well-being, and health service use (total number of GP, hospital, and allied health visits in the past 3 months). Secondary outcomes will assess social group processes, including number of important social groups, new group identification, multiple identity compatibility, and group-based support and emotion regulation. DISCUSSION: This study will provide comprehensive data about the extent to which, and how, social prescribing to community-based group activities may help people to feel less lonely, more socially integrated, and healthy over the first 8 weeks. If effective, this social identity-informed model of social prescribing can be disseminated in communities across Australia. TRIAL REGISTRATION: ANZCTR, Registered 8 June 2022 - Retrospectively registered, https://www.anzctr.org.au/ACTRN12622000801718.aspx.
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Solidão , Saúde Mental , Adolescente , Adulto , Nível de Saúde , Humanos , Solidão/psicologia , Queensland , Projetos de PesquisaRESUMO
Development and health during calfhood are paramount for the success of dairy operations because they are associated with longevity and productivity later in life. Thus, provision of nutritional supplements has been explored as an alternative to improve growth of preweaned calves. Holstein calves (female = 472, male = 46) from 2 dairies located in the San Joaquin Valley were assigned randomly to receive 25 g/d of Gammulin (APC Inc.) from 2 to 24 d of age (GAM = 263) or to receive no supplementation (control = 255). Calves were fed a mixture of waste milk and milk replacer (3.79 L/d), and study personnel added the supplement to the bottles of calves in the GAM treatment daily. Study personnel monitored calves 6 d/wk and recorded starter intake, fecal score (1 = firm, 4 = watery), and attitude score (1 = alert and responsive, 4 = recumbent). Blood samples were collected (4, 7, 14, 26, 44, 56, and 68 d of age) to determine concentrations of total protein, glucose (n = 64), nonesterified fatty acids (n = 64), ß-hydroxybutyrate (n = 171), and hematocrit (n = 518). Calves (n = 64) were treated with 0.5 mg of ovalbumin at 3, 21, and 42 d of age, and concentration of anti-ovalbumin IgG was measured. The percentage of polymorphonuclear leukocytes positive for phagocytosis and oxidative burst after the ex vivo exposure to an enteropathogenic Escherichia coli was evaluated (n = 64). We followed the female calves through the end of the first lactation or until they left the herd to evaluate the effect of treatment on first-lactation performance. Treatment did not affect metabolic and immune responses. During the supplementation (1 to 24 d of age), starter intake did not differ between treatments, but the GAM treatment reduced starter intake (638.5 ± 1.1 vs. 696.6 ± 1.1 g/d; mean ± standard error of the mean) from 25 to 60 d of age and average daily gain (798.8 ± 15.4 and 749.5 ± 15.2) from 23 to 60 d of age, resulting in reduced body weight at 60 d of age (68.4 ± 0.4 vs. 69.8 ± 0.5 kg). From 1 to 24 d of age, GAM treatment reduced the number of days calves had fecal score = 4 (ratio of number of days = 0.92; 95% confidence interval = 0.84-1.00) and it reduced the number of electrolyte treatments calves received (ratio of number of treatments = 0.92; 95% confidence interval = 0.85-0.99). Treatment did not affect the hazard of first calving and first-lactation 305-d milk yield, but the adjusted hazard ratio (0.82; 95% confidence interval = 0.65, 1.04) of pregnancy in the first lactation tended to be reduced for the GAM treatment. In the conditions of this experiment, supplementation with 25 g/d of GAM to the liquid feed from 2 to 24 d of age did not improve calfhood health and performance.
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Ração Animal , Dieta , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Dieta/veterinária , Suplementos Nutricionais , Feminino , Lactação , Masculino , Leite , Gravidez , DesmameRESUMO
BACKGROUND: Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS, OMIA 001595-9940 ) is a previously reported recessively inherited disorder in Australian Poll Merino/Merino sheep. Affected lambs are stillborn with various congenital defects as reflected in the name of the disease, as well as short stature, a short and broad cranium, a small thoracic cavity, thin ribs and brachysternum. The BCRHS phenotype shows similarity to certain human short stature syndromes, in particular the human 3M syndrome-2. Here we report the identification of a likely disease-causing variant and propose an ovine model for human 3M syndrome-2. RESULTS: Eight positional candidate genes were identified among the 39 genes in the approximately 1 Mb interval to which the disease was mapped previously. Obscurin like cytoskeletal adaptor 1 (OBSL1) was selected as a strong positional candidate gene based on gene function and the resulting phenotypes observed in humans with mutations in this gene. Whole genome sequencing of an affected lamb (BCRHS3) identified a likely causal variant ENSOARG00000020239:g.220472248delC within OBSL1. Sanger sequencing of seven affected, six obligate carrier, two phenotypically unaffected animals from the original flock and one unrelated control animal validated the variant. A genotyping assay was developed to genotype 583 animals from the original flock, giving an estimated allele frequency of 5%. CONCLUSIONS: The identification of a likely disease-causing variant resulting in a frameshift (p.(Val573Trpfs*119)) in the OBSL1 protein has enabled improved breeding management of the implicated flock. The opportunity for an ovine model for human 3M syndrome and ensuing therapeutic research is promising given the availability of carrier ram semen for BCRHS.
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Modelos Animais de Doenças , Nanismo/genética , Mutação da Fase de Leitura , Hipotonia Muscular/genética , Carneiro Doméstico/genética , Sequência de Aminoácidos , Animais , Austrália , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA/veterinária , Feminino , Frequência do Gene , Humanos , Masculino , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Genoma/veterináriaRESUMO
Previous research has shown that the medial temporal lobes (MTL) are more strongly engaged when individuals think about the future than about the present, leading to the suggestion that future projection drives MTL engagement. However, future thinking tasks often involve scene processing, leaving open the alternative possibility that scene-construction demands, rather than future projection, are responsible for the MTL differences observed in prior work. This study explores this alternative account. Using functional magnetic resonance imaging, we directly contrasted MTL activity in 1) high scene-construction and low scene-construction imagination conditions matched in future thinking demands and 2) future-oriented and present-oriented imagination conditions matched in scene-construction demands. Consistent with the alternative account, the MTL was more active for the high versus low scene-construction condition. By contrast, MTL differences were not observed when comparing the future versus present conditions. Moreover, the magnitude of MTL activation was associated with the extent to which participants imagined a scene but was not associated with the extent to which participants thought about the future. These findings help disambiguate which component processes of imagination specifically involve the MTL.
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Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiologia , Pensamento/fisiologia , Adolescente , Feminino , Previsões , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Distribuição Aleatória , Adulto JovemRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the upper airways, often associated with the formation of nasal polyps (CRSwNP). It is well established that macroscopically normal (non-polypoidal) sinonasal mucosa in CRSwNP patients can undergo polypoidal change over time, turning into frank polyps. However, little is known about what drives this process. This study aimed to investigate potential drivers of nasal polyp formation or growth through comparison of the immunological profiles of nasal polyps with contiguous non-polypoidal sinonasal mucosa, from the same patients. METHODS: The immune profiles of three types of tissue were compared; nasal polyps and adjacent non-polypoidal sinonasal mucosa from 10 CRSwNP patients, and sinonasal mucosa from 10 control patients undergoing trans-sphenoidal pituitary surgery. Nasal polyp and control samples were also stimulated with Staphylococcus aureus enterotoxin B (SEB) using a nasal explant model, prior to cytokine analysis. Real time quantitative polymerase chain reaction (IL-5, T-bet, IL-17A, FoxP3, TLR-4, IL-8, IL-1beta and IL-6) and Luminex (IFNgamma, IL-5 and IL-17A) were used to quantify pro-inflammatory responses. RESULTS: Nasal polyps and contiguous non-polypoidal sinonasal mucosa from CRSwNP patients displayed a very similar pro-inflammatory profile. When stimulated with SEB, nasal polyps displayed a Th2/Th17 mediated response when compared to controls. CONCLUSIONS: In CRSwNP, nasal polyps and non-polypoidal sinonasal mucosa from the same patient displayed a similar pro-inflammatory profile skewed towards the Th2/Th17 pathway in nasal polyps following SEB stimulation, with evidence of disordered bacterial clearance. These factors may contribute to enhanced survival of bacteria and development of a chronic inflammatory milieu, potentially driving new polyp formation and recurrence following surgical removal.
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Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Citocinas/metabolismo , Humanos , Mucosa , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologiaRESUMO
PURPOSE: The Exercise for Health trials were randomised, controlled trials designed to evaluate an 8-month pragmatic exercise intervention, commencing 6 weeks post-surgery for women with newly diagnosed breast cancer residing in urban or rural/regional Australia. For these exploratory analyses, the primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. METHODS: Consenting urban- (n = 194) and rural/regional-residing women (n = 143) were randomised to exercise (intervention delivered face-to-face or by telephone) or usual care. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for survival outcomes (exercise group, n = 207, 65% urban women; usual care group, n = 130, 46% urban women). RESULTS: After a median follow-up of 8.3 years, there were 11 (5.3%) deaths in the exercise group compared with 15 (11.5%) deaths in the usual care group (OS HR for the exercise group: 0.45, 95% CI 0.20-0.96; p = 0.04). DFS events for the exercise versus usual care group were 25 (12.1%) and 23 (17.7%), respectively (HR: 0.66, 95% CI 0.38-1.17; p = 0.16). HRs for OS favoured exercise irrespective of age, body mass index, stage of disease, intervention compliance, and physical activity levels at 12 months post-diagnosis, although were stronger (p < 0.05) for younger women, women with stage II + disease, women with 1 + comorbidity at time of diagnosis, higher intervention compliance and for those who met national physical activity guidelines at 12 months post-diagnosis. CONCLUSION: An exercise intervention delivered during and beyond treatment for breast cancer, and that was designed to cater for all women irrespective of place of residence and access to health services, has clear potential to benefit survival. Trial numbers: ACT RN: 012606000233527; ACT RN: 12609000809235.
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Neoplasias da Mama/terapia , Terapia por Exercício , Exercício Físico/fisiologia , Adulto , Austrália/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/fisiopatologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Qualidade de VidaRESUMO
In the original publication of the article, under the heading Discussion, 1st paragraph, the sentence that reads as, "Nonetheless, our observed improvements of over 50% for OS and over 30% for DFS (HRs: 0.45 and 0.66, respectively) are consistent with results from other available studies" should read as "Nonetheless, our observed improvements of over 50% for OS and DFS (HRs: 0.45 and 0.66, respectively) are consistent with results from other available studies." Under the heading Discussion, 3rd paragraph, the sentence that reads as "We cannot discount the possibility such as education, income and access to care [1, 7]" should read as "We cannot discount the possibility such as education, income and access to care, which ultimately have on survival outcomes [1, 7]."
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Conventional detection of viruses and virus-like diseases of plants is accomplished using a combination of molecular, serological, and biological indexing. These are the primary tools used by plant virologists to monitor and ensure trees are free of known viral pathogens. The biological indexing assay, or bioassay, is considered to be the "gold standard" as it is the only method of the three that can detect new, uncharacterized, or poorly characterized viral disease agents. Unfortunately, this method is also the most labor intensive and can take up to three years to complete. Next generation sequencing (NGS) is a technology with rapidly expanding possibilities including potential applications for the detection of plant viruses. In this study, comparisons are made between tree fruit testing by conventional and NGS methods, to demonstrate the efficacy of NGS. A comparison of 178 infected trees, many infected with several viral pathogens, demonstrated that conventional and NGS were equally capable of detecting known viruses and viroids. Comparable results were obtained for 170 of 178 of the specimens. Of the remaining eight specimens, some discrepancies were observed between viruses detected by the two methods, representing less than 5% of the specimens. NGS was further demonstrated to be equal or superior for the detection of new or poorly characterized viruses when compared with a conventional bioassay. These results validated both the effectiveness of conventional virus testing methods and the use of NGS as an additional or alternative method for plant virus detection.
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Patologia Vegetal , Vírus de Plantas , Viroides , Frutas/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Vírus de Plantas/genética , Viroides/genéticaRESUMO
Most studies evaluating lymphedema treatment effect focus on objective reductions in limb volume, with little attention given to subjective treatment outcomes. The objective of this work was to describe the range of lymphedema symptoms experienced by patients and the importance of symptom improvement following treatment. The second aim was to explore lymphedema treatment use and the effect of individual treatments on symptoms, from the patient's perspective. Australian adults with lymphedema (n = 421) completed a self-administered questionnaire. Information was collected about patients' symptoms, the importance of symptom improvement following treatment, as well as treatment types used and perceived effectiveness of each treatment. In addition to swelling, the vast majority of participants experienced heaviness and tightness in the affected region. Overall, symptoms of lymphedema varied between individuals but the majority considered subjective symptom improvement to be an important outcome of treatment. The most commonly used treatments were compression garments, self- massage, prescribed exercises, and manual lymph drainage, and the majority (95%) of participants had used multiple treatments to manage their lymphedema. The impact of treatments on subjective symptoms varies widely between treatments. Consequently, in addition to objective measures of swelling, it is important to include patient-reported outcomes in future prospective lymphedema treatment studies.
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Linfedema/complicações , Linfedema/terapia , Adulto , Austrália , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVES: Occupational vaccination of health care workers is strongly recommended to prevent health care associated transmission but coverage in general remains suboptimal. The aim of this survey was to: 1. Estimate levels vaccination coverage for annual flu and MMR vaccines among hospital-based health care workers; 2. Explore the reasons behind low vaccination rates; and 3. Identify potential practical and policy solutions. STUDY DESIGN: A cross-sectional study. METHODS: An opportunistic survey was used to estimate MMR and flu vaccination coverage, and review attitudes and explore solutions. Staff from eight randomly selected wards, stratified by ward-level patient susceptibility, were invited to participate. RESULTS: In total 133 staff responded, an approximate response rate of 68%. Seventy one percent had ever received an MMR and 42% had received the most recent flu vaccination. Actively declining vaccination was more common for flu than MMR (29% and 7% respectively). Side-effects, insufficient knowledge and vaccine ineffectiveness were popular justifications for declining flu vaccination but not MMR. Not seeing vaccination as a professional responsibility was associated with declining flu vaccination (P < 0.001). Improving vaccination coverage with booster vaccines for new staff and immunity testing received strong support from staff working with vulnerable groups (82% and 74% respectively); 70% of this staff group also supported compulsory vaccination. CONCLUSIONS: Improving staff education may increase coverage. Clarification of the benefits of vaccination in specific staff groups may also improve uptake. Routine booster vaccinations and immunity testing were generally acceptable and compulsory vaccination of certain staff groups warrants further investigation.
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Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Influenza/administração & dosagem , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Corpo Clínico Hospitalar/psicologia , Vacinação/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Corpo Clínico Hospitalar/estatística & dados numéricos , Pessoa de Meia-Idade , Medição de RiscoRESUMO
The use of compression garments during exercise is recommended for women with breast cancer-related lymphedema, but the evidence behind this clinical recommendation is unclear. The aim of this randomized, cross-over trial was to compare the acute effects of wearing versus not wearing compression during a single bout of moderate-load resistance exercise on lymphedema status and its associated symptoms in women with breast cancer-related lymphedema (BCRL). Twenty-five women with clinically diagnosed, stable unilateral breast cancer-related lymphedema completed two resistance exercise sessions, one with compression and one without, in a randomized order separated by a minimum 6 day wash-out period. The resistance exercise session consisted of six upper-body exercises, with each exercise performed for three sets at a moderate-load (10-12 repetition maximum). Primary outcome was lymphedema, assessed using bioimpedance spectroscopy (L-Dex score). Secondary outcomes were lymphedema as assessed by arm circumferences (percent inter-limb difference and sum-of-circumferences), and symptom severity for pain, heaviness and tightness, measured using visual analogue scales. Measurements were taken pre-, immediately post- and 24 hours post-exercise. There was no difference in lymphedema status (i.e., L-Dex scores) pre- and post-exercise sessions or between the compression and non-compression condition [Mean (SD) for compression pre-, immediately post- and 24 hours post-exercise: 17.7 (21.5), 12.7 (16.2) and 14.1 (16.7), respectively; no compression: 15.3 (18.3), 15.3 (17.8), and 13.4 (16.1), respectively]. Circumference values and symptom severity were stable across time and treatment condition. An acute bout of moderate-load, upper-body resistance exercise performed in the absence of compression does not exacerbate lymphedema in women with BCRL.
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Neoplasias da Mama/terapia , Bandagens Compressivas , Linfedema/terapia , Treinamento Resistido , Extremidade Superior/fisiopatologia , Idoso , Austrália , Fenômenos Biomecânicos , Terapia Combinada , Estudos Cross-Over , Espectroscopia Dielétrica , Impedância Elétrica , Feminino , Humanos , Linfedema/diagnóstico , Linfedema/etiologia , Linfedema/fisiopatologia , Pessoa de Meia-Idade , Medição da Dor , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Extremidade Superior/patologiaRESUMO
Interest has increased in CDX2 gene expression in oesophageal non-goblet-cell columnar metaplasia as recent investigations indicate such metaplasia possesses neoplastic potential. This study aims to assess expression of the transcription factor CDX2 specifically in non-goblet-cell cardia and fundic oesophageal metaplastic tissue, and to compare the location of CDX2 expression in non-goblet-cell specimens to that in goblet-cell specimens. A total of 43 patient specimens (20 fundic-type metaplasia, 42 cardia-type metaplasia and 18 intestinal metaplasia goblet cell-positive) were examined in this study. These were selected over six months from a patient database using the systematised nomenclature of human and veterinary medicine coding system (SNOMED). CDX2 was detected in patient specimens with an anti-CDX2 mouse monoclonal antibody. The types of mucosa in each specimen were confirmed by haematoxylin and eosin (H&E) staining. Fundic specimens were consistently CDX2-negative (0%). CDX2 expression was distinct in 55% of cardia and 100% of intestinal cases. Nearly all cardia-positive cases displayed focal expression (95.5%) and all intestinal cases displayed diffuse distribution of expression. Almost all cardia- and intestinal-positive specimens demonstrated epithelial expression (95.5% and 100%, respectively). The percentage of cardia-positive specimens with deep tissue expression was lower than in intestinal specimens (31.8% vs. 94.4%, respectively). This study confirms CDX2 as an early marker for Barrett's oesophagus in the absence of goblet cells as expression was noted in cardia metaplasia. CDX2 appears to induce the transformation of the normal oesophageal mucosa to cardia type, which then differentiates to an intestinal type under the influence of gastro-oesophageal reflux disease.
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Esôfago de Barrett/metabolismo , Proteínas de Homeodomínio/metabolismo , Esôfago de Barrett/patologia , Biomarcadores/metabolismo , Fator de Transcrição CDX2 , Cárdia/metabolismo , Cárdia/patologia , Diferenciação Celular , Humanos , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Microscopia de Polarização , Proteínas Supressoras de Tumor/metabolismoRESUMO
An indirect-drive inertial fusion experiment on the National Ignition Facility was driven using 2.05 MJ of laser light at a wavelength of 351 nm and produced 3.1±0.16 MJ of total fusion yield, producing a target gain G=1.5±0.1 exceeding unity for the first time in a laboratory experiment [Phys. Rev. E 109, 025204 (2024)10.1103/PhysRevE.109.025204]. Herein we describe the experimental evidence for the increased drive on the capsule using additional laser energy and control over known degradation mechanisms, which are critical to achieving high performance. Improved fuel compression relative to previous megajoule-yield experiments is observed. Novel signatures of the ignition and burn propagation to high yield can now be studied in the laboratory for the first time.
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Canine nonangiogenic, nonlymphogenic, gastrointestinal sarcomas have been previously diagnosed as gastrointestinal stromal tumors (GIST), leiomyosarcomas, or nonspecified spindle cell sarcomas, but diagnostic criteria for each entity are poorly defined. We propose a classification for canine nonangiogenic, nonlymphogenic, gastrointestinal sarcomas based on microscopic, immunohistochemical, and molecular characteristics. Applying the classification to 40 canine nonangiogenic, nonlymphogenic, gastrointestinal sarcomas documented its diagnostic and prognostic value. Eighteen (45%) sarcomas were classified as GIST based on positive KIT immunoreactivity. All GISTs were positive for vimentin, 14 (78%) were positive for S-100, and 6 (33%) were positive for smooth muscle actin (SMA). In contrast to their human counterparts, canine GISTs occurred mainly in the small intestine (67%) but commonly metastasized (5/18) to liver, lymph nodes, and omentum. Six GISTs had an activated KIT mutation in exon 11 of c-Kit, but no mutations were detected in exons 8, 9, 13, and 17. Twelve (30%) sarcomas were classified as leiomyosarcomas based on positive labeling for SMA and negative labeling for KIT. Four of these neoplasms were well differentiated leiomyosarcomas characterized by weak to no labeling for vimentin, and 8 were poorly differentiated leiomyosarcomas characterized by strong labeling for vimentin. None of the leiomyosarcomas metastasized, but poorly differentiated leiomyosarcomas had a higher risk of local invasion. Ten (25%) sarcomas were classified as non-GIST/nonleiomyosarcomas that were negative for KIT and SMA but positive for vimentin and either S-100 and/or PGP 9.5. These neoplasms most likely represent sarcomas of neurogenic differentiation resembling Schwann cells or perineurial or endoneurial fibroblasts, respectively.
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Doenças do Cão/classificação , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Neoplasias Gastrointestinais/veterinária , Sarcoma/veterinária , Actinas/metabolismo , Animais , Cães , Neoplasias Gastrointestinais/classificação , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia , Imuno-Histoquímica/veterinária , Mutação/genética , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/imunologia , Sarcoma/classificação , Sarcoma/diagnóstico , Sarcoma/patologia , Vimentina/metabolismoRESUMO
Ischemic stroke affects millions of individuals worldwide and a high prevalence of survivors experience cognitive deficits. At present, the underlying mechanisms that drive post-stroke cognitive decline are not well understood. Microglia play a critical role in the post-stroke inflammatory response, but experimental studies show that an accumulation of chronically activated microglia can be harmful and associates with cognitive impairment. This study assessed the effect of acute post-stroke minocycline treatment on chronic microglia and astrocyte expression within the infarct and remote white matter regions, as well as its effect on various domains of cognitive function post-stroke. Nine-month-old male rats received an injection of endothelin-1 into the right dorsal striatum to induce transient focal ischemia, and then were treated with minocycline or saline for 4 days post-stroke. Rats were tested using a series of lever-pressing tasks and the Morris water maze to assess striatal-based learning, cognitive flexibility, and spatial learning and reference memory. We found that minocycline-treated rats had smaller stroke-induced infarcts and less microglia activation in the infarct area and remote white matter regions compared to saline-treated rats at 28 days post-stroke. The behavioural testing results differed according to the cognitive domain; whereas minocycline-treated rats trended towards improved striatal-based learning in a lever-pressing task, but cognitive flexibility was unaffected during the subsequent set-shifting task. Furthermore, minocycline treatment unexpectedly impaired spatial learning, yet it did not alter reference memory. Collectively, we show that post-stroke minocycline treatment can reduce chronic microglia activation even in remote brain regions, with domain-specific effects on cognitive function.
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BACKGROUND: Tissue factor (TF), which has a role in normal tissue haemostasis, was reported to be aberrantly expressed, associated with higher microvascular density and a poor prognosis in intestinal-type gastric adenocarcinoma in the Japanese population. This is the first study to look at the relationship of TF and the metaplasia-adenoma-carcinoma sequence (MACS) of gastric cancer in a European population. METHODS: The expression of TF was examined immunohistochemically in 191 gastric tissue samples: (13: normal; 18: intestinal metaplasia; 160: gastric adenocarcinoma) from the European population. RESULTS: TF was not expressed in normal gastric mucosal cells. A strong intensity of staining was found in intestinal metaplasia cells but in 2 of 18 samples. TF expression increased with advancing stage of gastric cancer (P<0.0001, Jonckheere's test for ordered medians). Stage 3-4 gastric cancers preferentially expressed TF (34%, P=0.04). In comparison with the Japanese study, TF was not expressed at a higher level in intestinal vs diffuse-type gastric cancers and expression had 'no prognostic' significance. CONCLUSION: TF may be involved in tumour progression along the MACS of gastric cancer in the European population and is shown to start in precancerous lesions. However, clinical features may differ due to differences in biological features in the two populations, as reflected by differences in TF expression profile.
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Adenoma/metabolismo , Carcinoma/metabolismo , Neoplasias Gástricas/metabolismo , Estômago/patologia , Tromboplastina/biossíntese , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenoma/genética , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/genética , Carcinoma/patologia , Progressão da Doença , Feminino , Mucosa Gástrica/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Metaplasia/genética , Metaplasia/metabolismo , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Tromboplastina/genética , Tromboplastina/metabolismo , População BrancaRESUMO
BACKGROUND: The transcription factor FOXM1 is an important regulator of the cell cycle through controlling periodic gene expression during the G2 and M phases. One key target for FOXM1 is the gene encoding the protein kinase PLK1 and PLK1 itself acts in a positive feedback loop to phosphorylate and activate FOXM1. Both FOXM1 and PLK1 have been shown to be overexpressed in a variety of different tumour types. METHODS: We have used a combination of RT-PCR, western blotting, tissue microarrays and metadata analysis of microarray data to study whether the FOXM1-PLK1 regulatory axis is upregulated and operational in oesophageal adenocarcinoma. RESULTS: FOXM1 and PLK1 are expressed in oesophageal adenocarcinoma-derived cell lines and demonstrate cross-regulatory interactions. Importantly, we also demonstrate the concomitant overexpression of FOXM1 and PLK1 in a large proportion of oesophageal adenocarcinoma samples. This co-association was extended to the additional FOXM1 target genes CCNB1, AURKB and CKS1. In a cohort of patients who subsequently underwent surgery, the expression of several FOXM1 target genes was prognostic for overall survival. CONCLUSIONS: FOXM1 and its target gene PLK1 are commonly overexpressed in oesophageal adenocarcinomas and this association can be extended to other FOXM1 target genes, providing potentially important biomarkers for predicting post-surgery disease survival.
Assuntos
Adenocarcinoma/genética , Proteínas de Ciclo Celular/genética , Neoplasias Esofágicas/genética , Fatores de Transcrição Forkhead/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Adenocarcinoma/metabolismo , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Estudos de Coortes , Neoplasias Esofágicas/metabolismo , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/metabolismo , Regulação para Cima , Quinase 1 Polo-LikeRESUMO
The current study examined healthy weight control practices among a sample of college women enrolled at an urban university (N=715; age=19.87±1.16; 77.2% Caucasian; 13.4% African American, 7.2% Asian, 2.2% other races). Participants completed measures as part of an on-line study about health habits, behaviors, and attitudes. Items from the Three Factor Eating Questionnaire were selected and evaluated with exploratory factor analysis to create a healthy weight control practices scale. Results revealed that college women, regardless of weight status, used a comparable number (four of eight) of practices. Examination of racial differences between Caucasian and African American women revealed that normal weight African American women used significantly fewer strategies than Caucasian women. Of note, greater use of healthy weight control practices was associated with higher cognitive restraint, drive for thinness, minutes of physical activity, and more frequent use of compensatory strategies. Higher scores on measures of binge and disinhibited eating, body dissatisfaction, negative affect, and depressive symptoms were associated with greater use of healthy weight control practices by underweight/normal weight but not by overweight/obese college women. Results suggest that among a sample of college females, a combination of healthy and potentially unhealthy weight control practices occurs. Implications of the findings suggest the need for effective weight management and eating disorder prevention programs for this critical developmental life stage. Such programs should be designed to help students learn how to appropriately use healthy weight control practices, as motivations for use may vary by weight status.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Sobrepeso/epidemiologia , Magreza/epidemiologia , Programas de Redução de Peso/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Índice de Massa Corporal , Exercício Físico , Comportamento Alimentar , Feminino , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Humanos , Inquéritos e Questionários , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
Although cancer survivors are recommended to exercise, they may lack confidence (self-efficacy) to be active. This research aimed to measure exercise barriers and related selfefficacy in individuals with cancer-related lymphedema as well as examine relationships between self-efficacy and participant characteristics. A cross-sectional survey was undertaken in individuals with cancer-related lymphedema using a validated 14-item Likert scale assessing self-efficacy to overcome general and lymphedema-specific exercise barriers (0%=not at all confident, 100%=extremely confident). Demographic, medical and lymphedema data were also collected. Of 109 participants (52% response), 79% (n=86) had breast cancer-related lymphedema. Participants were found to be moderately confident to exercise when facing general (48% [95% CI: 44, 52]) and lymphedema- specific exercise barriers (51% [95% CI: 47, 55]). Participants who were female, sedentary (p<0.05), had lymphedema for ≥2 years, and reported greater symptom burden (p<0.05) recorded lower general exercise barriers selfefficacy. Lower lymphedema-specific exercise barriers self-efficacy was reported by individuals who were sedentary, had cancers other than breast, and higher symptom burden. These findings suggest general and lymphedema- specific barriers challenge exercise confidence in those with cancer-related lymphedema, and strategies tailored to improve confidence in overcoming exercise barriers are warranted. Supporting individuals to be sufficiently active during and following cancer treatment should consider behavior change strategies tailored to the unique needs faced by individuals with lymphedema.
Assuntos
Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Linfedema , Linfedema Relacionado a Câncer de Mama/diagnóstico , Linfedema Relacionado a Câncer de Mama/etiologia , Linfedema Relacionado a Câncer de Mama/terapia , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Estudos Transversais , Exercício Físico , Feminino , Humanos , Linfedema/diagnóstico , Linfedema/etiologia , Linfedema/terapia , Masculino , AutoeficáciaRESUMO
There is little information about how weight change in horses impacts bone turnover and the metabolism of minerals associated with bone. This study evaluated weight change in mature horses as a factor that could alter bone turnover and fecal P output. Fifteen horses (555 ± 8 kg) were assigned to three treatments: weight loss (LO; n = 5), weight maintenance (MA; n = 5), and weight gain (GA; n = 5). Diets contained 75%, 100%, and 145% of maintenance digestible energy requirements for the three treatments, respectively, but contained similar amounts of protein and minerals. At the end of the weight change period (27 ± 6 d), blood samples were analyzed for bone biomarkers and a 5-day total fecal collection was conducted to measure fecal mineral output. Horses fed the MA diet had an average daily weight change that was not different from either the GA or LO treatments, while weight change was different between the GA group and the LO group (0.49 kg/d vs. -1.16 kg/d; P = .017). Weight change was negatively correlated with cross-linking C-terminal telopeptides of type-I collagen, a biomarker of bone resorption (r = -0.62; P = .014) and tended to be positively correlated with bone alkaline phosphatase, a biomarker of bone formation (r = 0.48; P = .068). Also, fecal P output tended to be lower in GA than in LO horses (P = .085), while MA was intermediate and not different, suggesting that weight loss was increasing bone resorption, resulting in a tendency for higher P loss from the body. Weight change in horses can influence bone metabolism as well as mineral excretion.