HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion

This article has been made available through the Brunel Open Access Publishing Fund.PTK6/Brk is a non-receptor tyrosine kinase overexpressed in cancer. Here we demonstrate that cytosolic PTK6 is rapidly and robustly induced in response to hypoxic conditions in a HIF-1-independent manner. Furthermore, a proportion of hypoxic PTK6 subsequently re-localized to the cell membrane. We observed that the rapid stabilization of PTK6 is associated with a decrease in PTK6 ubiquitylation and we have identified c-Cbl as a putative PTK6 E3 ligase in normoxia. The consequences of hypoxia-induced PTK6 stabilization and subcellular re-localization to the plasma membrane include increased cell motility and invasion, suggesting PTK6 targeting as a therapeutic approach to reduce hypoxia-regulated metastatic potential. This could have particular significance for breast cancer patients with triple negative disease.A Breast Cancer Campaign pilot grant awarded to E.M.H. supported this study. I.M.P. is supported by University of Hull HEFCE funding, and Royal Society and Breast Cancer Campaign pilot grants. S.A.E. is supported by ICR HEFCE funding and Cancer Research UK program grant C309/A11566. A.H. is supported by Brunel University HEFCE funding. E.M.H. is supported by a Cancer Research UK grant

Would Older Adults with Mild Cognitive Impairment Adhere to and Benefit from a Structured Lifestyle Activity Intervention to Enhance Cognition?: A Cluster Randomized Controlled Trial

Background Epidemiologic evidence suggests that cognitive and physical activities are associated with better cognition in late life. The present study was conducted to examine the possible benefits of four structured lifestyle activity interventions and compare their effectiveness in optimizing cognition for older adults with mild cognitive impairment (MCI). Method and Findings This was a 12-month cluster randomized controlled trial. 555 community-dwelling Chinese older adults with MCI (295 with multiple-domain deficits (mdMCI), 260 with single-domain deficit (sdMCI)) were recruited. Participants were randomized into physical exercise (P), cognitive activity (C), integrated cognitive and physical exercise (CP), and social activity (S, active control) groups. Interventions comprised of one-hour structured activities three times per week. Primary outcome was Clinical Dementia Rating sum of boxes (CDR-SOB) scores. Secondary outcomes included Chinese versions of Alzheimer's Disease Assessment Scale Cognitive subscale (ADAS-Cog), delayed recall, Mini-Mental State Examination, Category Verbal Fluency Test (CVFT) and Disability Assessment for Dementia - Instrumental Activities of Daily Living (DAD-IADL). Percentage adherence to programs and factors affecting adherence were also examined. At 12th month, 423 (76.2%) completed final assessment. There was no change in CDR-SOB and DAD-IADL scores across time and intervention groups. Multilevel normal model and linear link function showed improvement in ADAS-Cog, delayed recall and CVFT with time (p<0.05). Post-hoc subgroup analyses showed that the CP group, compared with other intervention groups, had more significant improvements of ADAS-Cog, delayed recall and CVFT performance with sdMCI participants (p<0.05). Overall adherence rate was 73.3%. Improvements in ADAS-Cog and delayed recall scores were associated with adherence after controlling for age, education, and intervention groups (univariate analyses). Conclusions Structured lifestyle activity interventions were not associated with changes in everyday functioning, albeit with some improvements in cognitive scores across time. Higher adherence was associated with greater improvement in cognitive scores. Factors to enhance adherence should be specially considered in the design of psychosocial interventions for older adults with cognitive decline.published_or_final_versio

Age, Education, and Cognitive Decline: a prospective study of cognitive function in community-dwelling Chinese older adults in Hong Kong

Conference Theme: Mental Health for AllFree Paper 3.1 – Neuroscience and Mental HealthBackground: This study aimed to investigate the changes in cognitive profiles and the effect of age and education on such changes in an older community cohort over a 5-year period. Methods: A random sample of 787 non-demented Chinese elders in Hong Kong was assessed with a comprehensive neuropsychological battery at baseline, in the 2nd and 5th year. Results: A total of 454 subjects were assessed at the 5th year. For subjects with normal cognitive function at baseline, 186 (56.9%) remained cognitively normal, 115 (35.2%) had mild cognitive impairment (MCI), and 26 (7.9%) became demented. For subjects with MCI at baseline, 28 (22%) reverted to normal, 59 (46.5%) remained as MCI, 40 (31.5%) became demented. The decline in scores of Cantonese Mini-Mental State Examination was significant over the years, with the rate of decline being greater after the 2nd year. Using logistic regression, age and education had significant predictive effects on the progression to dementia, but the protective effect of education was lost if the subjects were already suffering from MCI at the baseline. Age was a significant factor affecting the cognitive function over time, while the effect of education was lost in the baseline MCI subjects. Conclusions: A decline in cognitive profile took place before the clinical diagnosis of dementia. The protective effect of education on cognitive function appeared to have lost when the person started to have MCI

Cognitive predictors for five-year conversion to dementia in community-dwelling Chinese older adults

BACKGROUND: This study evaluates which cognitive measure is best for predicting incident dementia in a population-based random sample of Chinese older adults without dementia over a five-year period. METHODS: A total of 787 community-dwelling Chinese older adults without dementia in Hong Kong were assessed at baseline (T0), at two years (T1), and at five years (T2). RESULTS: The annual conversion rate to dementia was 1.6% and 6.3% for baseline normal participants and baseline mild cognitive impairment (MCI) participants, respectively. The Cantonese version of Mini-mental State Examination (CMMSE) scores declined significantly over time. In participants who progressed to dementia, Category Verbal Fluency Test (CVFT) scores dropped significantly from T0 to T1. A 1-SD drop of either CMMSE or CVFT in two years predicted dementia at five years with 91.5% sensitivity and 62.0% specificity. A stable CMMSE and CVFT at two years predicted a 91% chance of not progressing to clinical dementia at five years. CONCLUSION: In this community sample of Chinese older adults, a decline in cognitive screening tests in short term (two years) offered useful information in predicting dementia conversion over a longer period.published_or_final_versio

Can the Hospital Anxiety and Depression (HAD) Scale be used on Chinese elderly in general practice?

A study was carried out in a general practice in Hong Kong to find out if the Hospital Anxiety and Depression (HAD) Scale could be used to detect psychological problems in Chinese elderly. The HAD Scale was translated into Cantonese and administered by an interviewer to 298 Chinese aged 60 or above before their doctor consultations. The acceptance rate of the Scale was 96% and each interview took only 5-10 min to complete. All 298 elderly understood and completed the HAD Scale. Validation of the results of the HAD Scale by the Clinical Interview Schedule (CIS) was done on a random sample of 100 elderly. Relative operating characteristic (ROC) analysis showed that the optimal cut-off points of the HAD Scale was a depression score of 6 and an anxiety score of 3. The sensitivity was 80%, specificity was 90%, OMR (overall misclassification rate) was 12%, positive predictive value was 67% and negative predictive value was 95%. Thirty-six per cent of the,elderly had scores above these cut-off points. More females than males had high anxiety scores. Nearly half of those with positive HAD scores were not known to have any psychological illness. The HAD Scale has great potential to be used as a screening instrument for psychological illnesses in Cantonese-speaking Chinese elderly all over the world.postprin

Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arhtritis Models of the Mouse

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Prevalence and Antibiotic Resistance Patterns of Escherichia coli among Hospitalised Patients at Thika District Hospital

Background: Emerging resistance to antimicrobial drugs increases  morbidity and mortality by hampering the provision of effective  chemotherapy, and makes treatment more costly. The emergence of resistance to antimicrobial agents is a global public health problem, especially in pathogens causing nosocomial infections.Objectives: To determine the carriage of E. coli from wounds and urine in catheterised inpatients at Thika District Hospital (TDH) and to determine antimicrobial resistance patterns to β-lactams, aminoglycosides and (fluoro) quinolones.Design: A cross-sectional study.Setting: Thika District Hospital among hospitalised patients.Subjects: A total of 450 specimens were collected and forty two (42) Escherichia coli isolated. Pus swabs were collected from wounds and urine was collected aseptically from the inpatients with catheters. Escherichia coli were identified by culture methods and biochemical tests. Antimicrobial susceptibility testing was performed by Kirby-Bauer disc diffusion method and interpreted according to Clinical Laboratory Standards Institute recommendations.Results: Susceptibility results in aminoglycosides were, resistance for amikacin, gentamicin and kanamycin was 20%, 39% and 51% respectively. Resistance in penicillin was ampicillin 85% and piperacillin 83%. Resistance for sulfamethoxazole was 83%, tetracycline 66 %, nalidixic acid 44 % and chloramphenicol 39%. In amoxicillin/clavulanic acid, resistance was 68%. Cephalosporins’ resistance was ceftazidime 22 %, cefotaxime 56 %. Resistance for imipenem and tazobactam was 7% and 12 % respectively.Conclusion: Due to observations on resistance to antimicrobial agents commonly used in Thika District Hospital, this shows that there is need to revise antimicrobial policy in this region in the treatment of E. coli infections

Phylogenetics in plant biotechnology: principles, obstacles and opportunities for the resource poor

Phylogenetic inference has become routine for most studies of genetic variation among plant taxa. However, inferring phylogenies can be confounded by both biological and computational or statisticalcomplexities, resulting in misleading evolutionary hypotheses. This is particularly critical because the “true tree” can only truly be known in exceptional circumstances. Moreover, selecting appropriatemarker(s), characters, sample sizes and the appropriate reconstruction methods offers a challenge to most evolutionary geneticists. Textbooks are generic (and sometimes outdated), and in resource poor labs, they may altogether be inaccessible. In this review, we take the worker through the low-down on reconstructing a phylogeny, review the enigmatic biological and computational problems, and examine cases where cheaper markers and extremely small sample sizes can recover a reliable phylogeny

Localizing genes using linkage disequilibrium in plants: integrating lessons from the medical genetics

Finding genes controlling quantitative traits will aid molecular breeding for crops and livestock with superior yields, growth rates, and evolutionary potential. Such genes can be located using thecandidate gene approach, genome wide scans, or by within family mapping. Linkage disequilibrium (LD) or association mapping, is a candidate gene approach that relies on detecting a statisticalassociation between the desired quantitative trait and a molecular marker allele. This approach is emerging as a leading tool for precise estimation of QTL positions, because it offers several advantages over family-based mapping: LD mapping detects associations with greater resolution, the associations detected are relevant population wide, and in plants, the use of natural populations would circumvent the need to raise large controlled crosses. However, LD approach is facing obstacles, with well over 60% of studies reporting associations in the medical genetics disapproved in subsequent tests. A large proportion of these false associations (or lack of it) result from population stratification, while the rest may be caused by other demographic and evolutionary processes that create a statistical association between a marker allele and the trait, such as bottlenecks, natural selection, hybridization and genetic drift. The problem is expected to escalate in plants, owing to the complex population structures. Regardless of the many recent methods that purport to take into account populationstratification during association tests, we discuss the reasons why in plants, a priori knowledge of population structures is essential in any robust association analysis

Comparative performance of Anigen © FMD NSP Ab ELISA (Korea), NSP Priocheck® kit, liquid phase blocking ELISA kits and virus neutralisation tests in the detection of foot and mouth disease virus antibodies in animals sera from Kilifi county, Kenya

Background: Foot and mouth disease (FMD) is a highly contagious viral infection of hoof cloven animals. Performance of serological tests used for FMD is faced with challenges like low test sensitivity, low tests agreement levels, in concise test cut-offs, cost of the tests and numerous FMD serotypes which may lead to misdiagnosis.Objective: To determine the sensitivity of assays Anigen © FMD NSP Ab ELISA –Korea, NSP Priocheck® kits with Liquid Phase Blocking Enzyme Linked Immunosorbent Assay compared with Virus neutralisation test ( the gold standard).Design: A cross-sectional study design.Setting: Kilifi County.Subjects: Four hundred and twenty one cattle.Results: The results showed that both Anigen © FMD NSP Ab ELISA (Korea), NSP Priocheck® Netherlands assays had low sensitivity but high specificity. Liquid Phase Blocking ELI SA had the highest sensitivity 100%. LPBE had a Positive Predictive Value (PPV) =100%, Anigen © FMD NSP Ab ELISA–Korea 94.44% and NSP Priocheck® Netherlands had the lowest 44.74% compared with the VNT 100%. The Cohen's kappa coefficient showed a perfect agreement level of 90%, 93%, 100 and 100% respectively.Conclusion: This study showed no significant difference in sensitivity and both structural and non-structural proteins tests should always be used concurrently