SHOX gene is expressed in vertebral body growth plates in idiopathic and congenital scoliosis : implications for the etiology of scoliosis in Turner Syndrome

Reduced SHOX gene expression has been demonstrated to be associated with all skeletal abnormalities in Turner syndrome, other than scoliosis (and kyphosis). There is evidence to suggest that Turner syndrome scoliosis is clinically and radiologically similar to idiopathic scoliosis, although the phenotypes are dissimilar. This pilot gene expression study used relative quantitative real-time PCR (qRT-PCR) of the SHOX (short stature on X) gene to determine whether it is expressed in vertebral body growth plates in idiopathic and congenital scoliosis. After vertebral growth plate dissection, tissue was examined histologically and RNA was extracted and its integrity was assessed using a Bio-Spec Mini, NanoDrop ND-1000 spectrophotometer and standard denaturing gel electrophoresis. Following cDNA synthesis, gene-specific optimization in a Corbett RotorGene 6000 real-time cycler was followed by qRT-PCR of vertebral tissue. Histological examination of vertebral samples confirmed that only growth plate was analyzed for gene expression. Cycling and melt curves were resolved in triplicate for all samples. SHOX abundance was demonstrated in congenital and idiopathic scoliosis vertebral body growth plates. SHOX expression was 11-fold greater in idiopathic compared to congenital (n = 3) scoliosis (p = 0.027). This study confirmed that SHOX was expressed in vertebral body growth plates, which implies that its expression may also be associated with the scoliosis (and kyphosis) of Turner syndrome. SHOX expression is reduced in Turner syndrome (short stature). In this study, increased SHOX expression was demonstrated in idiopathic scoliosis (tall stature) and congenital scoliosis.

The increased risks of death and extra lengths of hospital and ICU stay from hospital-acquired bloodstream infections : a case-control study

Objectives Hospital-acquired bloodstream infections are known to increase the risk of death and prolong hospital stay, but precise estimates of these two important outcomes from well-designed studies are rare, particularly for non-intensive care unit (ICU) patients. We aimed to calculate accurate estimates, which are vital for estimating the economic costs of hospital-acquired bloodstream infections.

Mastery Motivation in Children with Down Syndrome : Promoting and Sustaining Interest in Learning

Motivation is central to children’s learning. Without persistent effort, especially in the face of failure, and an eagerness to engage in challenging tasks, individuals are unlikely to learn as effectively as they might. Because of their cognitive impairments, children with Down syndrome will almost certainly have difficulties with learning. These difficulties will be ameliorated somewhat by strong engagement with learning activities whereas problems with motivation are likely to further jeopardise their academic progress as well as potentially limiting achievements in other areas of life. In this chapter we begin with a general overview of motivation. Using the framework of mastery motivation, we review the relatively small amount of research about children with Down syndrome. We identify the individual characteristics and features of children’s environments that are likely to be related to lower or higher levels of mastery motivation. In the final section, we consider implications for educators and then draw together the findings to provide a set of recommendations for future research.

Acute poststreptococcal glomerulonephritis : public health implications of recent clusters in New South Wales and epidemiology of hospital admissions

Acute poststreptococcal glomerulonephritis (APSGN) is an inflammatory kidney condition that can complicate Group A streptococcal infections. Two clusters of APSGN occurred recently in New South Wales (NSW), Australia; one in a rural town in December 1999 and the other in a Sydney suburb in January 2000. We interviewed carers of the affected children but found no common exposures except three of the Sydney cases were cousins in frequent contact. To assess the probability of these clusters occurring, we analysed hospital admissions for acute glomerulonephritis, as a proxy for APSGN in younger patients. The incidence of acute glomerulonephritis in NSW during 1989/90-1997/8 in residents aged under 20 years was 2(.)2/100000/year (95% CI 2(.)0-2(.)5). Incidence was highest in children aged 5-9 years, boys and Aboriginal children. We found no evidence for other clusters during that period. The recent clusters highlight the continued potential for unexpected future outbreaks of APSGN.

Chemotherapy induced reversible posterior leukoencephalopathy syndrome

The reversible posterior leukoencephalopathy syndrome (RPLES) is a condition characterised by reversible neurological and radiological findings that has been associated with use of immunosuppressive, chemotherapeutic and more recently novel targeted therapies. We describe the case of a 50-year-old woman with advanced non-small cell lung cancer who developed status epilepticus shortly after receiving cisplatin and gemcitabine chemotherapy. The clinical, radiological and EEG findings during and post event are presented and are in keeping with a diagnosis of RPLES. Early recognition of this rare syndrome, supportive management and withdrawal of the offending agent appear to result in a reversal of the manifestations described. © 2007 Elsevier Ireland Ltd. All rights reserved.

The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease

Recent studies have demonstrated that angiogenesis and suppressed cell- mediated immunity (CMI) play a central role in the pathogenesis of malignant disease facilitating tumour growth, invasion and metastasis. In the majority of tumours, the malignant process is preceded by a pathological condition or exposure to an irritant which itself is associated with the induction of angiogenesis and/or suppressed CMI. These include: cigarette smoking, chronic bronchitis and lung cancer; chronic oesophagitis and oesophageal cancer; chronic viral infections such as human papilloma virus and ano-genital cancers, chronic hepatitis B and C and hepatocellular carcinoma, and Epstein- Barr virus (EBV) and lymphomas; chronic inflammatory conditions such as Crohn's disease and ulcerative colitis and colorectal cancer; asbestos exposure and mesothelioma and excessive sunlight exposure/sunburn and malignant melanoma. Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. The increased blood supply would facilitate the development and proliferation of an abnormal clone or clones of cells arising as the result of: (a) an inherited genetic abnormality; and/or (b) acquired somatic mutations, the latter due to local production and/or enhanced delivery of carcinogens and mutagenic growth factors. With progressive detrimental mutations and growth-induced tumour hypoxia, the transformed cell, to a lesser or greater extent, may amplify the angiogenic process and CMI suppression, thereby facilitating further tumour growth and metastasis. There is accumulating evidence that long-term treatment with cyclo-oxygenase inhibitors (aspirin and indomethacin), cytokines such as interferon-α, anti-oestrogens (tamoxifen and raloxifene) and captopril significantly reduces the incidence of solid tumours such as breast and colorectal cancer. These agents are anti-angiogenic and, in the case of aspirin, indomethacin and interferon-α have proven immunomodulatory effects. Collectively these observations indicate that angiogenesis and suppressed CMI play a central role in the development and progression of malignant disease. (C) 2000 Elsevier Science Ltd.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

The effects of the indoor environment of residential care homes on dementia suffers in Hong Kong : a critical incident technique approach

Dementia is an irreversible and incurable syndrome that leads to progressive impairment of cognitive functions and behavioural and psychological symptoms such as agitation, depression and psychosis. Appropriate environmental conditions can help delay its onset and progression, and indoor environmental (IE) factors have a major impact. However, there is no firm understanding of the full range of relevant IE factors and their impact levels. This paper describes a preliminary study to investigate the effects of IE on Hong Kong residential care homes (RCH) dementia residents. This involved six purposively selected focus groups, each comprising the main stakeholders of the dementia residents’ caregivers, RCH staff and/or registered nurses, and architects. Using the Critical Incident Technique, the main context and experiences of behavioural problems of dementia residents caused by IE were explored and the key causal RCH IE quality factors identified, together with the associated responses and stress levels involved. The findings indicate that the acoustic environment, lighting and thermal environment are the most important influencing factors. Many of the remedies provided by the focus groups are quite simple to carry out and are summarised in the form of recommendations to current RCHs providers and users. The knowledge acquired in this initial study will help enrich the knowledge of IE design for dementiaspecific residential facilities. It also provides some preliminary insights for healthcare policymakers and practitioners in the building design/facilities management and dementia-care sectors into the IE factors contributing to a more comfortable, healthy and sustainable RCH living environment in Hong Kong.

Development of a new signal processing diagnostic tool for vibration signals acquired in transient conditions

The diagnostics of mechanical components operating in transient conditions is still an open issue, in both research and industrial field. Indeed, the signal processing techniques developed to analyse stationary data are not applicable or are affected by a loss of effectiveness when applied to signal acquired in transient conditions. In this paper, a suitable and original signal processing tool (named EEMED), which can be used for mechanical component diagnostics in whatever operating condition and noise level, is developed exploiting some data-adaptive techniques such as Empirical Mode Decomposition (EMD), Minimum Entropy Deconvolution (MED) and the analytical approach of the Hilbert transform. The proposed tool is able to supply diagnostic information on the basis of experimental vibrations measured in transient conditions. The tool has been originally developed in order to detect localized faults on bearings installed in high speed train traction equipments and it is more effective to detect a fault in non-stationary conditions than signal processing tools based on spectral kurtosis or envelope analysis, which represent until now the landmark for bearings diagnostics.

A preliminary study of the effects of Tai Chi and Qigong medical exercise on indicators of metabolic syndrome, glycaemic control, health-related quality of life, and psychological health in adults with elevated blood glucose

Objectives To evaluate the feasibility, acceptability and effects of a Tai Chi and Qigong exercise programme in adults with elevated blood glucose. Design, Setting, and Participants A single group pre–post feasibility trial with 11 participants (3 male and 8 female; aged 42–65 years) with elevated blood glucose. Intervention Participants attended Tai Chi and Qigong exercise training for 1 to 1.5 h, 3 times per week for 12 weeks, and were encouraged to practise the exercises at home. Main Outcome Measures Indicators of metabolic syndrome (body mass index (BMI), waist circumference, blood pressure, fasting blood glucose, triglycerides, HDL-cholesterol); glucose control (HbA1c, fasting insulin and insulin resistance (HOMA)); health-related quality of life; stress and depressive symptoms. Results There was good adherence and high acceptability. There were significant improvements in four of the seven indicators of metabolic syndrome including BMI (mean difference −1.05, p<0.001), waist circumference (−2.80 cm, p<0.05), and systolic (−11.64 mm Hg, p<0.01) and diastolic blood pressure (−9.73 mm Hg, p<0.001), as well as in HbA1c (−0.32%, p<0.01), insulin resistance (−0.53, p<0.05), stress (−2.27, p<0.05), depressive symptoms (−3.60, p<0.05), and the SF-36 mental health summary score (5.13, p<0.05) and subscales for general health (19.00, p<0.01), mental health (10.55, p<0.01) and vitality (23.18, p<0.05). Conclusions The programme was feasible and acceptable and participants showed improvements in metabolic and psychological variables. A larger controlled trial is now needed to confirm these promising preliminary results.

Plasmodium vivax malaria incidence over time and its association with temperature and rainfall in four counties of Yunnan Province, China

Background Transmission of Plasmodium vivax malaria is dependent on vector availability, biting rates and parasite development. In turn, each of these is influenced by climatic conditions. Correlations have previously been detected between seasonal rainfall, temperature and malaria incidence patterns in various settings. An understanding of seasonal patterns of malaria, and their weather drivers, can provide vital information for control and elimination activities. This research aimed to describe temporal patterns in malaria, rainfall and temperature, and to examine the relationships between these variables within four counties of Yunnan Province, China. Methods Plasmodium vivax malaria surveillance data (1991–2006), and average monthly temperature and rainfall were acquired. Seasonal trend decomposition was used to examine secular trends and seasonal patterns in malaria. Distributed lag non-linear models were used to estimate the weather drivers of malaria seasonality, including the lag periods between weather conditions and malaria incidence. Results There was a declining trend in malaria incidence in all four counties. Increasing temperature resulted in increased malaria risk in all four areas and increasing rainfall resulted in increased malaria risk in one area and decreased malaria risk in one area. The lag times for these associations varied between areas. Conclusions The differences detected between the four counties highlight the need for local understanding of seasonal patterns of malaria and its climatic drivers.

Imported Dengue cases, weather variation and autochthonous Dengue incidence in Cairns, Australia

BACKGROUND Dengue fever (DF) outbreaks often arise from imported DF cases in Cairns, Australia. Few studies have incorporated imported DF cases in the estimation of the relationship between weather variability and incidence of autochthonous DF. The study aimed to examine the impact of weather variability on autochthonous DF infection after accounting for imported DF cases and then to explore the possibility of developing an empirical forecast system. METHODOLOGY/PRINCIPAL FINDS Data on weather variables, notified DF cases (including those acquired locally and overseas), and population size in Cairns were supplied by the Australian Bureau of Meteorology, Queensland Health, and Australian Bureau of Statistics. A time-series negative-binomial hurdle model was used to assess the effects of imported DF cases and weather variability on autochthonous DF incidence. Our results showed that monthly autochthonous DF incidences were significantly associated with monthly imported DF cases (Relative Risk (RR):1.52; 95% confidence interval (CI): 1.01-2.28), monthly minimum temperature ((o)C) (RR: 2.28; 95% CI: 1.77-2.93), monthly relative humidity (%) (RR: 1.21; 95% CI: 1.06-1.37), monthly rainfall (mm) (RR: 0.50; 95% CI: 0.31-0.81) and monthly standard deviation of daily relative humidity (%) (RR: 1.27; 95% CI: 1.08-1.50). In the zero hurdle component, the occurrence of monthly autochthonous DF cases was significantly associated with monthly minimum temperature (Odds Ratio (OR): 1.64; 95% CI: 1.01-2.67). CONCLUSIONS/SIGNIFICANCE Our research suggested that incidences of monthly autochthonous DF were strongly positively associated with monthly imported DF cases, local minimum temperature and inter-month relative humidity variability in Cairns. Moreover, DF outbreak in Cairns was driven by imported DF cases only under favourable seasons and weather conditions in the study.

The epidemiology of microbial keratitis with silicone hydrogel contact lenses

It was widely anticipated that after the introduction of silicone hydrogel lenses, the risk of microbial keratitis would be lower than with hydrogel lenses because of the reduction in hypoxic effects on the corneal epithelium. Large-scale epidemiological studies have confirmed that the absolute and relative risk of microbial keratitis is unchanged with overnight use of silicone hydrogel materials. The key findings include the following: (1) The risk of infection with 30 nights of silicone hydrogel use is equivalent to 6 nights of hydrogel extended wear; (2) Occasional overnight lens use is associated with a greater risk than daily lens use; (3) The rate of vision loss due to corneal infection with silicone hydrogel contact lenses is similar to that seen in hydrogel lenses; (4) The spectrum of causative organisms is similar to that seen in hydrogel lenses, and the material type does not impact the corneal location of presumed microbial keratitis; and (5) Modifiable risk factors for infection include overnight lens use, the degree of exposure, failing to wash hands before lens handling, and storage case hygiene practice. The lack of change in the absolute risk of disease would suggest that exposure to large number of pathogenic organisms can overcome any advantages obtained from eliminating the hypoxic effects of contact lenses. Epidemiological studies remain important in the assessment of new materials and modalities. Consideration of an early adopter effect with studies involving new materials and modalities and further investigation of the impact of second-generation silicone hydrogel materials is warranted.

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism.