Functional outcome after selective dorsal rhizotomy: a retrospective case control study.

PURPOSE: This study examines long-term benefit on functional outcomes and quality of life after selective dorsal rhizotomy (SDR) in children with spastic diplegia in Hong Kong. METHOD: This is a case control study. Individuals with spastic diplegia who were at 6 to 12 years post-SDR were recruited. Age, gender, cognition, and Gross Motor Function Classification System level-matched individuals with spastic diplegia who had not undergone SDR were recruited as controls. Outcome measures included physical level, functional level, physiological level, and quality of life. All data were compared by independent t-test. RESULTS: Individuals post-SDR (n = 15) demonstrated a significantly better range of ankle dorsiflexion in knee extension by - 5.7 ± 10.9° than the control group (n = 12). No other significant differences were observed. CONCLUSION: SDR is a safe, one-off procedure and provides long-term reduction in spasticity with no major complications. With the heterogeneity, we did not demonstrate between-group differences in long-term functional outcomes.

Design and Synthesis of 56 Shape-Diverse 3D Fragments.

Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under-represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis). A key, and unique, underpinning design feature of this fragment collection is that assessment of fragment shape and conformational diversity (by considering conformations up to 1.5 kcal mol-1 above the energy of the global minimum energy conformer) is carried out prior to synthesis and is also used to select targets for synthesis. The 3D fragments were designed to contain suitable synthetic handles for future fragment elaboration. Finally, by comparing our 3D fragments with six commercial libraries, it is clear that our collection has high three-dimensionality and shape diversity.

Carbide and nitride phase characterization in a transition metal carbo-nitride using x-ray spectroscopy and atom probe tomography.

A multi-phase hafnium carbo-nitride was investigated by various analytical methods. Incomplete homogenization between mixed HfC-HfN starting powders subjected to hot isostatic pressing resulted in both carbon-rich and nitrogen-rich phases. The compositions of these two phases were quantified in detail by wavelength dispersive spectroscopy and atom probe tomography, with the atom probe tips having either a small or a large shank angle geometry. For each of the two phases, an agreement of the compositions obtained by wavelength dispersive spectroscopy and atom probe tomography was found. However, the quality of the mass spectrum and hit multiplicity (single hits) were generally higher for the carbon-rich as compared to the nitrogen-rich carbo-nitride. Though the atom probe tip geometry does not appear to influence the composition, the mass resolving power did improve with the larger shank angle geometry while the hit multiplicity deteriorated slightly. Finally, our results demonstrate that hafnium carbide requires less thermal assistance to field evaporate than hafnium nitride.

Complex evaporation behavior of a transition metal carbo-nitride (Hf(C,N)) studied by atom probe tomography.

The use of pulsed lasers in atom probe tomography has enabled the analysis of lower conductivity materials such as hafnium carbo-nitrides. The variability of experimental parameters can have a profound effect on field evaporation behavior, data quality and compositional accuracy. This is especially challenging for materials such as hafnium carbo-nitride, where a mixture of covalent, ionic and metallic bonding types is present. Here we study the influence of laser pulse energy on how the field evaporation evolves in a hafnium carbo-nitride and how that impacts data quality and compositional accuracy. Changing the laser pulse energy, while keeping other parameters constant, alters the resulting composition. A gain in Hf concentration is observed for higher laser pulse energies while at the same time the N concentration decreases. At lower laser pulse energies, the obtained composition is in good agreement with the reference bulk composition of the material. Furthermore, our results demonstrate that assessing the quality of an APT experiment or dataset merely based on commonly used metrics such as quality of mass spectrum, hit distribution on the detector, hit multiplicity and mass resolving power, can be misleading and is not enough to ensure the most accurate compositional data. Moreover, it is shown that the complex evaporation behavior of transition metal carbo-nitrides and potential ion loss mechanisms are not well enough understood yet and further work is required to fully comprehend these complex behaviors in these types of ceramics.

Sonographic evaluation of diaphragmatic function during breathing control.

OBJECTIVE: To investigate the effect of "breathing control" on sonographic diaphragmatic excursion. METHOD: A prospective, randomized, assessor-blinded study design involving 20 physiotherapy students; ten with knowledge of the breathing control technique (Group BC) and ten without (Group CON). All participants were asked to perform a Chester step test. Group BC performed BC, while Group CON adopted their own breathing pattern during recovery after the step test. Respiratory rate and sonographic parameters of the diaphragm including diaphragmatic excursion, speed of diaphragmatic contraction (slope of contraction), and inspiratory time were recorded before and after the step test. RESULTS: All baseline data were similar for both groups except age. Respiratory rate at 1 min post-step test was higher in Group CON (24.6±4.9 bpm) compared to Group BC (15.6 ± 3.8 bpm) (p < 0.001). Post-step test sonographic evaluation demonstrated an increase in diaphragmatic excursion with a significant time and group interaction (F(4,72) = 5.499, p = 0.005). Post hoc analysis revealed that the diaphragmatic excursion was significantly higher in Group BC compared to Group CON at first, second and third minute post-step test. Time and group interactions were not significant in inspiration time (F(4,72) = 2.459, p = 0.082) nor the slope of contraction (F(4,72) = 0.655, p = 0.582)]. CONCLUSION: Post-exercise diaphragmatic excursion was higher in participants applying BC. Non-invasive ultrasonography is able to promote objective evaluation of the relationship between breathing techniques and diaphragmatic function.

Completeness of Neisseria meningitidis reporting in New York City, 1989-2010.

Invasive meningococcal disease (IMD) completeness of reporting has never been assessed in New York City (NYC). We conducted a capture-recapture study to assess completeness of reporting, comparing IMD reports made to the NYC Department of Health and Mental Hygiene (DOHMH) and records identified in the New York State hospital discharge database [Statewide Planning and Research Cooperative System (SPARCS)] by ICD-9 codes from 1989 to 2010. Reporting completeness estimates were calculated for the entire study period, and stratified by year, age group, clinical syndrome, and reporting system. A chart review of hospital medical records from 2008 to 2010 was conducted to validate hospital coding and to adjust completeness estimates. Overall, 2194 unique patients were identified from DOHMH (n = 1300) and SPARCS (n = 1525); 631 (29%) were present in both. Completeness of IMD reporting was 41% [95% confidence interval (CI) 40-43]. Differences in completeness were found by age, clinical syndrome, and reporting system. The chart review found 33% of hospital records from 2008 to 2010 had no documentation of IMD. Removal of those records improved completeness of reporting to 51% (95% CI 49-53). Our data showed a low concordance between what is reported to DOHMH and what is coded by hospitals as IMD. Additional guidance to clinicians on IMD reporting criteria may improve completeness of IMD reporting.

Effects of footwear on running economy in distance runners: A meta-analytical review.

OBJECTIVES: Previous studies reported inconsistent findings about the effects of footwear on running economy, which is a surrogate measure of running performance. This meta-analytical review compared the running economy between running in barefoot, minimalists, and standard running shoes. DESIGN: Meta-analysis. METHODS: Electronic searches on MEDLINE, CINAHL, SPORTDiscus, and Cochrane Library databases were performed and the reference lists of the screened articles were also scrutinized. Two reviewers screened clinical trials that measured the oxygen cost of runners in different footwear conditions. RESULTS: Thirteen studies were selected in this meta-analysis with a total of 168 runners included. Barefoot running was shown to be more economic than shod running (p<0.01; standardized mean difference=-0.43; 95% Confidence Interval=-0.21 to -0.64; Z=3.96). Similar pattern was found when comparing minimalist and shoe (p<0.01; standardized mean difference=-0.49; 95% Confidence Interval=-0.29 to -0.70; Z=4.64). The observed changes were of small effect. Conversely, no significant difference in the metabolic cost was found between running in minimalists and barefoot running (p=0.45). CONCLUSIONS: Barefoot running or running in minimalist may require lower utilization of oxygen than shod running. Theoretically, the lower oxygen cost may improve long distance running performance. However, more than half of the runners in the included studies had previous barefoot experience and the findings may not apply to those habitual shod runners who are undergoing the transition. In addition, high risk of bias was reported in the included studies and quality study in the future is still warranted.

The ribosomal protein S26 regulates p53 activity in response to DNA damage.

Ribosomal proteins have emerged as novel regulators of the Mdm2-p53 feedback loop, especially in the context of ribosomal stress. RPS26 is a recently identified Diamond-Blackfan Anemia-related ribosomal protein and its role in p53 activation has not been previously explored. In this study we found knockdown of RPS26 induced p53 stabilization and activation via a RPL11-dependent mechanism, resulting in p53-dependent cell growth inhibition. Moreover, RPS26 has the ability to interact with Mdm2 and inhibits Mdm2-mediated p53 ubiquitination that leads to p53 stabilization upon overexpression. Importantly, we discovered that RPS26 knockdown impaired p53's ability to transcriptionally activate its target genes in response to DNA damage, without affecting its stability. Accordingly, the cells lost the ability to induce G2/M cell cycle arrest. We further found that upon RPS26 knockdown, the DNA damage induced recruitment of p53 to the promoters of its target genes and p53 acetylation were both greatly reduced. In addition, RPS26 can interact with p53 independent of Mdm2 and coexist in a complex with p53 and p300. These data establish a role of RPS26 in DNA damage response by directly influencing p53 transcriptional activity, and suggest that RPS26 acts distinctively in different scenarios of p53 activation. Our finding also implicates p53 transcriptional activity control as an important mechanism of p53 regulation by ribosomal proteins.

Development and evaluation of a positive youth development course for university students in Hong Kong.

With higher education, university graduates are important elements of the labor force in knowledge-based economies. With reference to the mental health and developmental problems in university students, there is a need to review university's role in nurturing holistic development of students. Based on the positive youth development approach, it is argued that promoting intrapersonal competencies is an important strategy to facilitate holistic development of young people in Hong Kong. In The Hong Kong Polytechnic University, a course entitled Tomorrow's Leader focusing on positive youth development constructs to promote student well-being will be offered on a compulsory basis starting from 2012/13 academic year under the new undergraduate curriculum structure. The proposed course was piloted in 2010/11 school year. Different evaluation strategies, including objective outcome evaluation, subjective outcome evaluation, process evaluation, and qualitative evaluation, are being carried out to evaluate the developed course. Preliminary evaluation findings based on the piloting experience in 2010/11 academic year are presented in this paper.

T-cell response to human papillomavirus type 58 L1, E6, And E7 peptides in women with cleared infection, cervical intraepithelial neoplasia, or invasive cancer.

Human papillomavirus type 58 (HPV-58) exists in a relatively high prevalence in certain parts of the world, including East Asia. This study examined the T-cell response to HPV-58 L1, E6, and E7 peptides among women with cleared infection, cervical intraepithelial neoplasia grade 2 (CIN2) or CIN3, or invasive cervical cancer (ICC). Peptides found to be reactive in the in vitro peptide binding assay or mouse-stimulating study were tested with a gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay to detect peptide-specific responses from the peripheral blood mononuclear cells (PBMC) collected from 91 HPV-58-infected women (32 with cleared infection, 16 CIN2, 15 CIN3, and 28 ICC). Four HLA-A11-restricted HPV-58 L1 peptides, located at amino acid positions 296 to 304, 327 to 335, 101 to 109, and 469 to 477, showed positive IFN-gamma ELISPOT results and were mainly from women with cleared infection. Two HLA-A11-restricted E6 peptides (amino acid positions 64 to 72 and 94 to 102) and three HLA-A11-restricted E7 peptides (amino acid positions 78 to 86, 74 to 82, and 88 to 96) showed a positive response. A response to E6 and E7 peptides was mainly observed from subjects with CIN2 or above. One HLA-A2-restricted E6 peptide, located at amino acid position 99 to 107, elicited a positive response in two CIN2 subjects. One HLA-A24-restricted L1 peptide, located at amino acid position 468 to 476, also elicited a positive response in two CIN2 subjects. In summary, this study has identified a few immunogenic epitopes for HPV-58 E6 and E7 proteins. It is worthwhile to further investigate whether responses to these epitopes have a role in clearing an established cervical lesion.

Identification of hemopexin in tear film.

Human tear fluid is a complex mixture of aqueous lipids, proteins, enzymes, and other biochemical and cellular elements. By conventional comparative proteomic approaches, we investigated the proteome in human tear fluid and compared the tear protein profile of normal control subjects with that of patients suffering from the ocular inflammatory disease vernal keratoconjunctivitis (VKC). Collected tear samples were directed to two-dimensional polyacrylamide gel electrophoresis protein separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry peptide identification. Six differentially expressed proteins-interleukin 4, phospholipase A2, albumin, lactoferrin, hemopexin, and lipocalin-were displayed. Hemopexin had not been reported previously in tear film. Enzyme-linked immunosorbent assay confirmed that hemopexin concentrations were significantly higher in VKC tear samples and increased with disease stages. The results implied clinical interest of hemopexin in the tear proteome and eye diseases.

Novel hypoglycemic effects of Ganoderma lucidum water-extract in obese/diabetic (+db/+db) mice.

In this study, we evaluated the pharmacological effects of Ganoderma lucidum (G. lucidum) (water-extract) (0.003, 0.03 and 0.3g/kg, 4-week oral gavage) consumption using the lean (+db/+m) and the obese/diabetic (+db/+db) mice. Different physiological parameters (plasma glucose and insulin levels, lipoproteins-cholesterol levels, phosphoenolpyruvate carboxykinase (PEPCK), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) and isolated aorta relaxation of both species were measured and compared. G. lucidum (0.03 and 0.3g/kg) lowered the serum glucose level in +db/+db mice after the first week of treatment whereas a reduction was observed in +db/+m mice only fed with 0.3g/kg of G. lucidum at the fourth week. A higher hepatic PEPCK gene expression was found in +db/+db mice. G. lucidum (0.03 and 0.3g/kg) markedly reduced the PEPCK expression in +db/+db mice whereas the expression of PEPCK was attenuated in +db/+m mice (0.3g/kg G. lucidum). HMG CoA reductase protein expression (in both hepatic and extra-hepatic organs) and the serum insulin level were not altered by G. lucidum. These data demonstrate that G. lucidum consumption can provide beneficial effects in treating type 2 diabetes mellitus (T2DM) by lowering the serum glucose levels through the suppression of the hepatic PEPCK gene expression.

Hyperintensity of the precentral gyral subcortical white matter and hypointensity of the precentral gyrus on fluid-attenuated inversion recovery: variation with age and implications for the diagnosis of amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Hyperintensity of the subcortical white matter (SWM) of the precentral gyrus and hypointensity of the precentral gyrus gray matter (PGGM) on fluid-attenuated inversion recovery (FLAIR) are described as potentially useful diagnostic findings in amyotrophic lateral sclerosis (ALS). A detailed study of the prevalence of these findings in various age groups has not been described. METHODS: One hundred twenty-two patients underwent axial FLAIR brain examinations as part of either hearing loss or tinnitus evaluation. Examinations were randomly selected to reflect an even spread through the decades from ages 15 to 78 years and were reviewed by 2 readers, blinded to patient's age and sex, for the presence/absence of the above 2 signs. If SWM hyperintensity was present, it was graded as intense as caudate nucleus (grade 1) or insula (grade 2). RESULTS: We identified 32 cases of grade 1 and 5 cases of grade 2 SWM hyperintensity, and 28 cases of PGGM hypointensity. Both signs showed significant Spearman correlation with increasing age (r = 0.55, P < .001 for grade 1, r = 0.45, P < .001 for grade 2 SWM hyperintensity, r = 0.45, P < .001 for PGGM hypointensity). Analysis of variance showed there was a significant difference between the different age groups (P < .001) for both signs. Grading of the SWM and PGGM signals were highly reproducible with very good interobserver agreement (r = 0.88, P < .001, and r = 0.97, P < .001, respectively). CONCLUSION: This study suggests a statistically significant relationship between increasing age and the frequency of precentral gyrus SWM hyperintensity and PGGM hypointensity on FLAIR, and reinforces previous reports that these signs can be seen in patients who do not have ALS.

Hyperintensity of the middle cerebellar peduncles on fluid-attenuated inversion recovery imaging: variation with age and implications for the diagnosis of multiple system atrophy.

BACKGROUND AND PURPOSE: T2 hyperintensity of the middle cerebellar peduncle (MCP) is described in a number of diseases, including multiple system atrophy (MSA). We hypothesize that mild MCP hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging can be a normal finding. To our knowledge, a detailed study of the prevalence of this finding in various age groups with the FLAIR sequence has not been described. METHODS: One hundred twenty-two patients underwent an axial FLAIR examination of the brain as part of either a hearing loss or tinnitus work-up (ie, to exclude an acoustic neuroma or a retrocochlear cause). Subjects aged 15-78 years were included to reflect an even spread through the decades and were divided into 6 age groups. A radiologist and an MR imaging fellow graded the examinations subjectively, blinded to age: 0 for normal or 1 for the presence of MCP hyperintensity if the increased signal intensity was greater than that of adjacent pons and cerebellar white matter. Spearman rank correlation test of MCP hyperintensity with age and analysis of variance (ANOVA) were performed. RESULTS: Of 122 patients, we identified 17 with MCP FLAIR hyperintensity. None of these patients had a clinical condition that could cause MCP hyperintensity. MCP hyperintensity did not show a statistically significant correlation with age (r = 0.05, P = .62). Patients were divided into 6 age groups, and ANOVA showed no statistically significant difference in the incidence of MCP hyperintensity between different age groups (P = .95). However, results were highly reproducible with excellent interobserver correlation (r = 0.97, P < .001). CONCLUSIONS: Mild MCP FLAIR hyperintensity can occur normally, and this finding shows no relationship with age.

The solitary enhancing cerebral lesion: can FLAIR aid the differentiation between glioma and metastasis?

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the diagnostic utility of fluid-attenuated inversion recovery (FLAIR) in differentiating between glioma and metastasis by assessing for nonenhancing adjacent cortical signal intensity abnormality in patients who present with a solitary enhancing cerebral lesion. METHODS: After approval from the institutional ethics committee was obtained, the MR imaging studies of 70 patients with a solitary enhancing lesion, without previous surgery or treatment, were reviewed. The axial FLAIR studies were initially reviewed for cortical involvement. If cortex involvement was detected, comparison with the axial T1, with and without gadolinium enhancement, was made to determine whether the cortex involvement was in an area without enhancement. If this was the case, the study was considered positive for glioma. Statistical analysis consisted of binary logistic regression and a 2 x 2 contingency table. RESULTS: Involvement of the adjacent cortex with FLAIR signal intensity abnormality but without enhancement was seen in 19 of 70 patients; 16 were gliomas and 3 were solitary metastasis. The sensitivity and specificity of this finding were 44% and 91%, respectively. The positive predictive value for glioma was 84%. CONCLUSION: FLAIR, when interpreted in concert with pre- and postgadolinium T1-weighted images, may be useful in differentiating glioma from metastasis when a solitary enhancing cerebral lesion is present. The presence of nonenhancing adjacent cortical involvement in a solitary enhancing lesion is a frequent and relatively specific sign.

Right internal carotid pseudoaneurysm mimicking a retropharyngeal abscess in a child.

A 7-year-old girl with tonsillar infection with antibiotics. Two weeks later, there was a right sided neck lump. Computed tomography scans demonstrated a predominantly hypodense right retropharyngeal area with peripheral enhancement and mass effect. There was intense enhancement within the postero-superior aspect of the lesion which was continuous with the right internal carotid artery. Ultrasound demonstrated tapering of the right internal carotid artery. Magnetic resonance imaging and magnetic resonance arteriography showed a right internal carotid artery pseudoaneurysm. Surgical exploration confirmed the finding. This case highlights an unusual presentation of an internal carotid pseudoaneurysm and how imaging provided the diagnosis.

A randomized, double blind, placebo-controlled study to investigate the use of conscious sedation in conjunction with paracervical block for reducing pain in termination of first trimester pregnancy by suction evacuation.

BACKGROUND: This study evaluated the role of conscious sedation in pain relief during termination of first trimester pregnancy by suction evacuation (SE) under local anaesthesia. METHODS: A hundred women undergoing SE before 12 weeks gestation were randomized by computer using the sealed envelope method to receive placebo (saline) or conscious sedation (2 mg midazolam and 25 microg fentanyl) i.v. 5 min before cervical dilatation. Paracervical block was given to all patients, 2 min later. Pain scores during and after SE, post-operative side-effects and satisfaction level were compared. RESULTS: No statistically significant differences in pain scores were found between the two groups. Post-operative side-effects such as dizziness (P = 0.015) and drowsiness (P < 0.001) were significantly more severe in the conscious sedation group. However, patients in the conscious sedation group reported better satisfaction levels than the control group (P = 0.003). CONCLUSION: The use of conscious sedation significantly improved patient satisfaction during termination of first trimester pregnancy by SE under local anaesthesia, despite a lack of improvement in pain relief and the presence of increased severe dizziness/drowsiness in the post-operative period.

Characterization of the biologically important interaction between troponin C and the N-terminal region of troponin I.

The N-terminal regulatory region of Troponin I, residues 1-40 (TnI 1-40, regulatory peptide) has been shown to have a biologically important function in the interactions of troponin I and troponin C. Truncated analogs corresponding to shorter versions of the N-terminal region (1-30, 1-28, 1-26) were synthesized by solid-phase methodology. Our results indicate that residues 1-30 of TnI comprises the minimum sequence to retain full biological activity as measured in the acto-S1-TM ATPase assay. Binding of the TnI N-terminal regulatory peptides (TnI 1-30 and the N-terminal regulatory peptide (residues 1-40) labeled with the photoprobe benzoylbenzoyl group, BBRp) were studied by gel electrophoresis and photochemical cross-linking experiments under various conditions. Fluorescence titrations of TnI 1-30 were carried out with TnC mutants that carry a single tryptophan fluorescence probe in either the N- or C-domain (F105W, F105W/C domain (88-162), F29W and F29W/N domain (1-90)) (Fig. 1). Low Kd values (Kd < 10(-7) M) were obtained for the interaction of F105W and F105W/C domain (88-162) with TnI 1-30. However, there was no observable change in fluorescence when the fluorescence probe was located at the N-domain of the TnC mutant (F29W and F29W/N domain (1-90)). These results show that the regulatory peptide binds strongly to the C-terminal domain of TnC.