Evaluation of a group-based sensorimotor intervention programme to improve Chinese handwriting of primary school students.

Objective: Sensorimotor performance is influential in Chinese handwriting, but few studies have examined the efficacy of sensorimotor-based interventions on Chinese handwriting among primary school students with poor handwriting performance. The study aims to evaluate a sensorimotor-based intervention to improve handwriting in the mainstream primary schools. Methods: This study adopted a two-group pretest-posttest design. An 8-session group-based sensorimotor intervention was delivered to school-aged children (mean age = 8.1, 68% male). Group A had 2 sessions every week, while Group B had 4 sessions every week. Analysis of variance with repeated measures was used to test the effects. Results: The intervention had a significant time effect (p < .05) in terms of improving handwriting process (d = 0.33-1.10), manual dexterity (d = 0.57), visual memory (d = 0.70), visual-spatial perception (d = 0.37), and motor and postural skills (d = 0.73). The effect sizes ranged from medium to large. For the handwriting process, time per character had a significant group × time interaction, with post hoc analysis showing that Group A had a significantly large effect (d = 1.89, p < .001) while Group B did not. Conclusions: The group-based sensorimotor intervention programme appeared to show improvements in students with fair skills in writing Chinese characters. It appears that the effect is better if the training sessions are spaced out in one month rather than intensively conducted within two weeks. It might be related to more involvement from parents, and students need more time for practice after the training sessions.

Assessing frailty in the acute medical admission of elderly patients.

BACKGROUND: Managing acute admission of frail older patients is a challenge in hospitals. Length of inpatient stay, inpatient mortality and the 90-day readmission rate are significant in this group of patients. The Comprehensive Geriatric Assessment (CGA), a multidisciplinary diagnostic and treatment process, is the best approach for identifying medical conditions, mental health, functional capacity and social circumstances in acute geriatric care. METHODS: A review of the records of older patients aged 75 and over, acutely admitted to a district general hospital in England from 15 March 2012 to 16 April 2012 was conducted. We developed a frailty assessment tool and applied it to these patients, in order to determine who would be classified as frail. We then established if the patients meeting this criteria were then correctly assessed using the CGA. All patient data were processed and analysed using a statistical package for data analysis. RESULTS: A total of 232 patients with a mean age of 84.25 ± 5.8 years were included. Out of these, 129 patients (55.6%) fulfilled the frailty criteria as determined with our frailty-assessment tool; 80.6% presented with lack of mobility over 24 hours, 69.8% were admitted with falls, 47.3% had known dementia or delirium and 45% were admitted from care homes. Patients aged over 85 years were more likely to have frailty compared with patients aged 75-85 years old (odds ratio [OR]: 4.78, 95% confidence interval [CI]: 2.6-8.6, p value >0.001). Patients assessed by a front door geriatric team were more likely to be reviewed with the CGA than those not seen by this team (adjusted OR 2.8, 95% CI: 1-7.6, p value=0.04). CONCLUSION: The prevalence of frailty is high in acute admissions of older patients and it is important that they are properly identified and assessed with a CGA in order to ensure effective multidisciplinary care.

Abrogated expression of DEC1 during oesophageal squamous cell carcinoma progression is age- and family history-related and significantly associated with lymph node metastasis.

BACKGROUND: Oesophageal squamous cell carcinoma (SCC) causes the highest number of cancer deaths in some regions of Northern China. Previously, we narrowed down a critical region at 9q33-34, identified to be associated with tumour-suppressive function of deleted in oesophageal cancer 1 (DEC1) in oesophageal SCC. METHODS: We generated DEC1 antibody and constructed tissue microarrays (TMAs) utilising tissue specimens from Henan, a high-risk region for oesophageal SCC, to investigate the importance of DEC1 expression in this cancer. RESULTS: Tissue microarray immunohistochemical staining reveals significant loss of DEC1 from hyperplasia, to tumour, and to lymph node metastasis. In addition, the loss of DEC1 in tumour is age-dependent. Interestingly, there is significant abrogation of DEC1 expression in patients with a family history of oesophageal SCC. Deleted in oesophageal cancer 1 localises to both the cytoplasm and nucleus. The vesicular pattern of DEC1 in the cytoplasm appears to localise at the Golgi and Golgi-endoplasmic reticulum intermediate compartment. CONCLUSION: This is the first TMA study to suggest a clinical association of DEC1 in lymph node metastatic oesophageal SCC, early onset oesophageal SCC and familial oesophageal SCC development. Subcellular localisation of DEC1 and its expression in oesophageal SCC tissues provide important insight for further deciphering the molecular mechanism of DEC1 in oesophageal SCC development.

Prostate cancer cells modulate osteoblast mineralisation and osteoclast differentiation through Id-1.

BACKGROUND: Id-1 is overexpressed in and correlated with metastatic potential of prostate cancer. The role of Id-1 in this metastatic process was further analysed. METHODS: Conditioned media from prostate cancer cells, expressing various levels of Id-1, were used to stimulate pre-osteoclast differentiation and osteoblast mineralisation. Downstream effectors of Id-1 were identified. Expressions of Id-1 and its downstream effectors in prostate cancers were studied using immunohistochemistry in a prostate cancer patient cohort (N=110). RESULTS: We found that conditioned media from LNCaP prostate cancer cells overexpressing Id-1 had a higher ability to drive osteoclast differentiation and a lower ability to stimulate osteoblast mineralisation than control, whereas conditioned media from PC3 prostate cancer cells with Id-1 knockdown were less able to stimulate osteoclast differentiation. Id-1 was found to negatively regulate TNF-beta and this correlation was confirmed in human prostate cancer specimens (P=0.03). Furthermore, addition of recombinant TNF-beta to LNCaP Id-1 cell-derived media blocked the effect of Id-1 overexpression on osteoblast mineralisation. CONCLUSION: In prostate cancer cells, the ability of Id-1 to modulate bone cell differentiation favouring metastatic bone disease is partially mediated by TNF-beta, and Id-1 could be a potential therapeutic target for prostate cancer to bone metastasis.

Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma.

Id protein family consists of four members namely Id-1 to Id-4. Different from other basic helix-loop-helix transcription factors, they lack the DNA binding domain. Id proteins have been shown to be dysregulated in many different cancer types and their prognostic value has also been demonstrated. Recently, Id-1 has been shown to be upregulated in oesophageal squamous cell carcinoma (ESCC). However, the prognostic implications of Id proteins in ESCC have not been reported. We examined the expression of the Id proteins in ESCC cell lines and clinical ESCC specimens and found that Id protein expressions were dysregulated in both the ESCC cell lines and specimens. By correlating the expression levels of Id proteins and the clinicopathological data of our patient cohort, we found that M1 stage tumours had significantly higher nuclear Id-1 expression (P=0.012) while high nuclear Id-1 expression could predict development of distant metastasis within 1 year of oesophagectomy (P=0.005). In addition, high levels of Id-2 expression in both cytoplasmic and nuclear regions predicted longer patient survival (P=0.041). Multivariate analysis showed that high-level expression of Id-2 in both cytoplasmic and nuclear regions and lower level of nuclear Id-1 expression were independent favourable predictors of survival in our ESCC patients. Our results suggest that Id-1 may promote distant metastasis in ESCC, and both Id-1 and Id-2 may be used for prognostication for ESCC patients.

Review on Medusa:a polymer-based sustained release technology for protein and peptide drugs.

The polymer-based Medusa system (Flamel Technologies) has been designed for slow release of therapeutic proteins and peptides. The Medusa II consists of a poly L-glutamate backbone grafted with hydrophobic alpha-tocopherol molecules, creating a colloidal suspension of nanoparticles (10 - 50 nm) in water. The sustained drug release is based on reversible drug interactions with hydrophobic nanodomains within the nanoparticles. In vivo, it is suggested that the therapeutic protein is displaced by endogenous proteins present in physiological fluids, leading to a slow drug release. The peak concentration is dramatically decreased and the protein release substantially extended. The Medusa technology has been applied to subcutaneous injection for several therapeutic proteins, such as IL-2 and IFN-alpha(2b), in animal models (rats, dogs, monkeys) and clinical trials in renal cancer (IL-2) and hepatitis C (IFN-alpha(2b)) patients.

Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer.

AIM: Development of metastasis is one of the main causes of prostatic cancer-related death. We have previously found that up-regulation of TWIST, a highly conserved basic helix-loop-helix transcription factor, in prostatic cancer cells can promote epithelial to mesenchymal transition through down-regulation of E-cadherin. The present study aimed to investigate the prognostic significance of TWIST and to correlate TWIST and E-cadherin expression in prostatic cancer specimens. METHODS AND RESULTS: TWIST and E-cadherin expression was studied in 115 prostatic cancer specimens, eight cases of prostatic intraepithelial neoplasia and 37 cases of benign prostatic hyperplasia by immunohistochemistry. Increased cytoplasmic expression of TWIST was associated with malignant transformation of prostatic epithelium and histological progression of prostatic cancer, while nuclear TWIST expression was significant in predicting the metastatic potential of the primary prostatic cancer. In addition, high levels of TWIST expression were also significantly associated with aberrant E-cadherin expression. CONCLUSIONS: These results suggest that TWIST may serve as a prognostic marker for high-grade prostatic cancer. In addition, up-regulation of TWIST in combination with aberrant E-cadherin expression in primary prostatic cancer specimens may predict development of distal metastatic disease.

The significance of LMO2 expression in the progression of prostate cancer.

LIM domain only 2 (LMO2) proteins are important regulators in determining cell fate and controlling cell growth and differentiation. This study has investigated LMO2 expression in human prostatic tissue specimens, prostate cancer cell lines, and xenografts; and has assessed the possible role and mechanism of LMO2 in prostate carcinogenesis. Immunohistochemical analysis on a tissue microarray consisting of 91 human prostate specimens, including normal, prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, and invasive carcinoma, revealed that overexpression of LMO2 was significantly associated with advanced tumour stage, as measured by Gleason score (p = 0.012), as well as with the development of distant metastasis (p = 0.018). These data were supported by quantitative real-time PCR experiments, where LMO2 mRNA levels were found to be significantly higher in prostate tumour specimen than in normal epithelium (p = 0.037). The expression of LMO2 in cell lines and xenografts representing androgen-dependent (AD) and androgen-independent (AI) prostate cancer stages was further studied. Consistent with the in vivo data, LMO2 mRNA and protein were found to be overexpressed in the more aggressive AI cells (PC3, DU145, and AI CWR22 xenografts) compared with less aggressive AD cells (LNCaP and AD CWR22 xenografts). Furthermore, stable introduction of LMO2 into LNCaP cells conferred enhanced cell motility and invasiveness in vitro, accompanied by down-regulation of E-cadherin expression. Taken together, these findings provide the first evidence to support the hypothesis that LMO2 may play an important role in prostate cancer progression, possibly via repression of E-cadherin expression.

Mapping of domains responsible for nucleocapsid protein-phosphoprotein interaction of Henipaviruses.

Hendra virus (HeV) and Nipah virus (NiV) are members of a new genus, Henipavirus, in the family paramyxoviridae. Each virus encodes a phosphoprotein (P) that is significantly larger than its counterparts in other known paramyxoviruses. The interaction of this unusually large P with its nucleocapsid protein (N) was investigated in this study by using recombinant full-length and truncated proteins expressed in bacteria and a modified protein-blotting protein-overlay assay. Results from our group demonstrated that the N and P of both viruses were able to form not only homologous, but also heterologous, N-P complexes, i.e. HeV N was able to interact with NiV P and vice versa. Deletion analysis of the N and P revealed that there were at least two independent N-binding sites on P and they resided at the N and C termini, respectively. Similarly, more than one P-binding site was present on N and one of these was mapped to a 29 amino acid (aa) C-terminal region, which on its own was sufficient to interact with the extreme C-terminal 165 aa region of P.

Complete nucleotide sequences of Nipah virus isolates from Malaysia.

We have completely sequenced the genomes of two Nipah virus (NiV) isolates, one from the throat secretion and the other from the cerebrospinal fluid (CSF) of the sole surviving encephalitic patient with positive CSF virus isolation in Malaysia. The two genomes have 18246 nucleotides each and differ by only 4 nucleotides. The NiV genome is 12 nucleotides longer than the Hendra virus (HeV) genome and both genomes have identical leader and trailer sequence lengths and hexamer-phasing positions for all their genes. Both NiV and HeV are also very closely related with respect to their genomic end sequences, gene start and stop signals, P gene-editing signals and deduced amino acid sequences of nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, glycoprotein and RNA polymerase. The existing evidence demonstrates a clear need for the creation of a new genus within the subfamily Paramyxovirinae to accommodate the close similarities between NiV and HeV and their significant differences from other members of the subfamily.

Acute confusion secondary to pneumocephalus in an elderly patient.

PRESENTATION: an 83-year-old man was admitted to hospital with acute confusion 3 days after a direct flight from Australia. OUTCOME: computed tomography (CT) brain scan and magnetic resonance imaging head scan revealed the cause to be pneumocephalus, apparently the result of barotrauma caused by Valsalva manoeuvres when he attempted to unblock his nose during the flight. After 5 days of nursing in the vertical position the patient's Abbreviated Mental Score returned to normal. A CT brain scan 6 weeks later showed complete resolution of the pneumocephalus.

A PC-based surgical simulator for laparoscopic surgery.

Surgical simulators for minimally invasive surgery have been developing in the 1990s. Most of them use high-end UNIX workstations for real-time simulation of complex human organ models. Only few of them have input devices with force feedback. Recently, personal computer technologies have made real-time display of relatively complex models feasible. We are developing an Intel-based laparoscopic surgical simulator that provides near real-time intuitive interaction between the trainee and simulated models of human organs. The surgical simulator has a prototypical scenario of cholecystectomic surgery. It can interactively simulate the deformation and cutting of cystic duct and vein. In addition, a set of input devices with force feedback has been designed and tested to imitate the manipulation of surgical instruments. The input device has five degrees of freedom and three of them are driven by DC motors to produce force feedback.

Quantitation of homoharringtonine in plasma by high-performance liquid chromatography with amperometric detection.

A high-performance liquid chromatographic procedure was developed for the quantitation of homoharringtonine in plasma. Harringtonine was used as an internal standard, and 1 ml of sample was required. The single-step extraction with dichloromethane resulted in almost 100% recovery for homoharringtonine and harringtonine. Analysis was performed on a reversed-phase CN column with amperometric detection. Chromatography was completed in 12 min. At an oxidation potential of +1.0 V, the detection limit was 1 ng/ml at a signal-to-noise ratio of 2. The mean analytical recovery for homoharringtonine was 99.5%. The within-run precision and between-run precision were both less than 11%. The method is equally applicable for plasma or serum, and it has been demonstrated to be applicable for study of the pharmacokinetics of homoharringtonine in patients suffering from acute non-lymphocytic leukaemia.

Pre-operative parenteral nutrition in patients with oesophageal cancer: a prospective, randomised clinical trial.

A prospective randomised clinical trial was conducted to examine the efficacy of 2 weeks pre-operative parenteral nutrition (PPN) for the prevention of complications following surgery for oesophageal cancer. Forty patients were studied, the diet of twenty being supplemented by pre-operative parenteral nutrition. There were no significant differences in age, nutritional status, tumour staging and histology between the two groups of patients. The use of PPN resulted in a significant gain in body weight and nitrogen but failed to produce an overall reduction in post-operative morbidity and mortality rates. However patients receiving PPN exhibited two types of changes in serum albumin levels. Those with a fall in serum albumin levels associated with an increase in body weight (indicating an expansion of extracellular volume) had a significantly higher incidence of post-operative pulmonary complications than the group exhibiting a rise in serum albumin levels concomitant with increase in body weight. These data suggested that two weeks PPN might not be adequate in certain patients and a longer period of PPN is required. They also show no clinical benefit from the routine use of pre-operative parenteral nutrition in all patients, but do not exclude benefit in selected groups.

Simultaneous quantitation of catecholamines and O-methylated metabolites in urine by isocratic ion-pairing high-performance liquid chromatography with amperometric detection.

A simple high-performance liquid chromatographic procedure was developed for the simultaneous determination of catecholamines and metanephrines in urine. One-step sample preparation was achieved with Bio-Rex 70 ion-exchange resin. The extract was assayed on a C18 reversed-phase column. Dihydroxybenzylamine was used as an internal standard. The eluent was monitored by an electrochemical detector with an oxidation potential of +0.85 V. The use of 1-heptanesulphonic acid in the mobile phase permitted the separation of norepinephrine, epinephrine, dopamine, normetanephrine and metanephrine in a single chromatogram. The corresponding detection limits were 5, 9, 14, 10 and 30 nmol/l, respectively. For the between-day precision, the coefficients of variation at physiological and pathological concentrations were less than 11%. Compounds with similar chemical structures and drugs commonly prescribed for the treatment of hypertension were assayed and found not to cause interferences in the chromatogram. The assay is reliable and is suitable for the analysis of clinical specimens. Reference values were established for normotensive Chinese patients with no neurological or endocrine disorders and also for patients suffering from essential hypertension.

Single-dose pharmacokinetics of ceftriaxone in healthy Chinese adults.

The pharmacokinetics of ceftriaxone were investigated in six healthy mainland Chinese adults (four males and two females). A single 1.0-g dose was administered intravenously or intramuscularly in a two-way crossover design. Plasma and saliva samples were collected on 11 occasions between 0 and 36 h after dosing. Ceftriaxone was not detected in any saliva samples. The mean volume of distribution and mean elimination half-life of ceftriaxone in plasma were 8.5 liters and 8.1 h, respectively. The mean total body clearance after intravenous administration was 0.68 liter/h. The mean Tmax and Cmax after intramuscular injection were 1.4 h and 131 micrograms/ml, respectively. The area under the plasma concentration-time curves after intravenous and intramuscular administrations were 1,507 and 1,493 micrograms X h/ml, respectively. The bioavailability for a 1.0-g intramuscular dose of ceftriaxone was calculated to be 100%. These pharmacokinetic parameters for ceftriaxone in healthy Chinese adults were very similar to those previously reported in the literature. Thus, ceftriaxone may be administered to treat Chinese patients without any major modification in the standard dosing regimen.

Methylphenidate hydrochloride given with or before breakfast: II. Effects on plasma concentration of methylphenidate and ritalinic acid.

Methylphenidate HCl (Ritalin) is often prescribed for the treatment of hyperactivity and is usually administered orally 30 minutes to 1 hour before meals, based on an assumption that meals may interfere with the absorption or metabolism of the drug. Seven boys who were taking methylphenidate regularly for the treatment of hyperactivity were hospitalized and given their established dose of the drug intravenously or orally, either with breakfast or in a fasted state. Blood samples were taken to determine the pharmacokinetics of the drug in each condition. Few differences between the "fed" and "fasted" states were noted, but the statistically significant differences indicated that meals accelerate rather than impede the absorption of methylphenidate.

Liquid-chromatographic analysis for methylphenidate (Ritalin) in serum.

We describe a "high performance" liquid chromatographic method for quantitating methylphenidate in serum. The internal standard, 4,5-diphenylimidazole, and serum or plasma sample are extracted in chloroform, evaporated, and redissolved in 20 mmol/L potassium phosphate (pH 3.5)/high-purity acetonitrile, 80/20 by vol. A centrifuged aliquot is chromatographed on mu-Bondapak C-18 with the phosphate/acetonitrile solvent as mobile phase, a flow rate of 1.6 mL/min, and a column temperature of 40 degrees C. Absorbances are read at 192 nm. This method reliably measures concentrations greater than 20 micrograms/L and has analytical recoveries of 74%.