Multidimensional analysis for the correlation of physico-chemical attributes to osteoblastogenesis in TiNbZrSnTa alloys.

Data-enabled approaches that complement experimental testing offer new capabilities to investigate the interplay between chemical, physical and mechanical attributes of alloys and elucidate their effect on biological behaviours. Reported here, instead of physical causation, statistical correlations were used to study the factors responsible for the adhesion, proliferation and maturation of pre-osteoblasts MC3T3-E1 cultured on Titanium alloys. Eight alloys with varying wt% of Niobium, Zirconium, Tin and Tantalum (Ti- (2-22 wt%)Nb- (5-20 wt%)Zr- (0-18 wt%)Sn- (0-14 wt%)Ta) were designed to achieve exemplars of allotropes (incl., metastable-ß, ß + α', α″). Following confirmation of their compositions (ICP, EDX) and their crystal structure (XRD, SEM), their compressive bulk properties were measured and their surface features characterised (XPS, SFE). Because these alloys are intended for the manufacture of implantable orthopaedic devices, the correlation focuses on the effect of surface properties on cellular behaviour. Physico-chemical attributes were paired to biological performance, and these highlight the positive interdependencies between oxide composition and proliferation (esp. Ti4+), and maturation (esp. Zr4+). The correlation reveals the negative effect of oxide thickness, esp. TiOx and TaOx on osteoblastogenesis. This study also shows that the characterisation of the chemical state and elemental electronic structure of the alloys' surface is more predictive than physical properties, namely SFE and roughness.

FEV3, FEV6 and their derivatives for detecting airflow obstruction in adult Chinese.

BACKGROUND: Forced expiratory volume in 3 seconds (FEV(3)) and 6 seconds (FEV(6)) could complement FEV(1) and forced vital capacity (FVC) for detecting airflow obstruction. OBJECTIVE: To compare FEV(1)/ FEV(6) and FEV(3)/FVC with FEV(1)/FVC in the detection of airflow obstruction. METHOD: Previous lung function data were re-analysed to establish reference values for FEV(3) and FEV(6). Data from a separate cohort of male smokers were used as test set. FEV(1), FEV(3), FEV(6), FVC, FEV(1)/FVC, FEV(1)/ FEV(6) and FEV(3)/FVC were regressed against age, standing height, weight and body mass index, and the mean and 95% confidence intervals for the lower limit of normal (LLN) values for these parameters were determined. RESULTS: The percentage of smokers with airflow obstruction in the test population using FEV(1)/FVC < LLN was 15.0%, while using FEV(1)/ FEV(6) < LLN and FEV(3)/FVC < LLN they were respectively 18.5% and 18.1%. Using FEV(1)/FVC < LLN as reference, the sensitivity and specificity of FEV(1)/ FEV(6) < LLN in identifying airflow obstruction were 82.3% and 92.8%, while those for FEV(3)/FVC < LLN were 78.5% and 92.6%; the positive and negative predictive values were 67% and 96.7% for FEV(1)/ FEV(6) < LLN and 65.3% and 96% for FEV(3)/FVC < LLN. CONCLUSION: FEV(3)/FVC < LLN and FEV(1)/ FEV(6) < LLN are comparable to FEV(1)/FVC < LLN for detecting airflow obstruction. FEV(3)/FVC < LLN could be useful in screening for airflow obstruction, while FEV(1)/ FEV(6) < LLN is useful in detecting airflow limitation in the elderly or in subjects with severe airflow obstruction.

Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study.

OBJECTIVES: To investigate the possible benefits and adverse effects of the addition of lopinavir/ritonavir to a standard treatment protocol for the treatment of severe acute respiratory syndrome. DESIGN: Retrospective matched cohort study. SETTING: Four acute regional hospitals in Hong Kong. PATIENTS AND METHODS: Seventy-five patients with severe acute respiratory syndrome treated with lopinavir/ritonavir in addition to a standard treatment protocol adopted by the Hospital Authority were matched with controls retrieved from the Hospital Authority severe acute respiratory syndrome central database. Matching was done with respect to age, sex, the presence of co-morbidities, lactate dehydrogenase level and the use of pulse steroid therapy. The 75 patients treated with lopinavir/ritonavir were divided into two subgroups for analysis: lopinavir/ritonavir as initial treatment, and lopinavir/ritonavir as rescue therapy. These groups were compared with matched cohorts of 634 and 343 patients, respectively. Outcomes including overall death rate, oxygen desaturation, intubation rate, and use of pulse methylprednisolone were reviewed. RESULTS: The addition of lopinavir/ritonavir as initial treatment was associated with a reduction in the overall death rate (2.3%) and intubation rate (0%), when compared with a matched cohort who received standard treatment (15.6% and 11.0% respectively, P<0.05) and a lower rate of use of methylprednisolone at a lower mean dose. The subgroup who had received lopinavir/ritonavir as rescue therapy, showed no difference in overall death rate and rates of oxygen desaturation and intubation compared with the matched cohort, and received a higher mean dose of methylprednisolone. CONCLUSION: The addition of lopinavir/ritonavir to a standard treatment protocol as an initial treatment for severe acute respiratory syndrome appeared to be associated with improved clinical outcome. A randomised double-blind placebo-controlled trial is recommended during future epidemics to further evaluate this treatment.

Methylation of p15 and p16 genes in adult acute leukemia: lack of prognostic significance.

BACKGROUND: Gene-promoter methylation is an epigenetic mechanism of transcription inactivation. In this study, the authors investigated the frequency and prognostic significance of p15 and p16 gene methylation in adult acute leukemia. METHOD: The methylation-specific polymerase chain reaction (MS-PCR) was used to analyze p15 and p16 gene methylation in 49 cases of acute lymphoblastic leukemia (ALL) and 29 cases of acute myelogenous leukemia (AML). RESULTS: At presentation, 93 % of cases of AML (8 of 8 M1, 10 of 11 M2, 2 of 2 M4, 5 of 6 M5, and 2 of 2 M6; French-American-British classification system) showed p15 methylation, but none showed p16 methylation. In ALL, 57% (5 of 8 T-ALL, 16 of 30 common-ALL, 6 of 7 pre-B ALL, and 1 of 4 early B-precursor ALL) showed p15 methylation. Only 6% showed p16 methylation, all of whom had concomitant p15 methylation. One patient acquired p16 methylation during relapse. In 23 ALL karyotyped cases, p15 methylation was found in 6 of 9 cases with normal karyotype, 3 of 7 cases with the Philadelphia chromosome, 3 of 5 cases with complex, 1 with hyperdiploidy, and 1 with trisomy 21. Three more cases with unsuccessful karyotyping but bcr/abl fusion showed p15 methylation as well. Five ALL patients were tested serially for minimal residual disease (MRD) with MS-PCR that has a sensitivity of 10(-4) to 10(-5). All showed continuous positive MS-PCR that heralded hematologic relapse. The prognostic significance of p15 methylation was tested in ALL patients, showing no impact on complete remission, 5-year overall survival, or 5-year disease-free survival. CONCLUSION: Gene methylation of p15, but not p16, is frequent in adult acute leukemias. Methylation of p15 at diagnosis was of no prognostic significance in ALL but may be useful for monitoring MRD.

Methylation of p15 and p16 genes in acute promyelocytic leukemia: potential diagnostic and prognostic significance.

PURPOSE: To investigate the frequency of p15 and p16 gene promoter methylation in acute promyelocytic leukemia (APL), and to define its value in the detection of minimal residual disease (MRD) and treatment prognostication. PATIENTS AND METHODS: Bone marrow DNA obtained from 26 patients with APL at diagnosis and during follow-up was studied with the methylation-specific polymerase chain reaction (MS-PCR). Serial marrow DNA was studied by MS-PCR for MRD, and disease-free and overall survival were correlated with p15 methylation status at diagnosis. RESULTS: MS-PCR for p16 and p15 gene methylation has a maximum sensitivity of 10(-4) and 10(-5). At diagnosis, 19 patients (73.1%) exhibited p15 methylation, whereas only three patients (11.5%) exhibited p16 methylation, all of whom had concomitant p15 methylation. During follow-up, p16 methylation was acquired in two patients, one during the third hematologic relapse, and the other during transformation into therapy-related myelodysplastic syndrome. Six patients were evaluated serially with MS-PCR for p15 methylation at diagnosis and at follow-up examinations. Persistent p15 methylation preceded subsequent hematologic relapses in two patients, and conversion to negative MS-PCR for p15 methylation correlated with prolonged survival in another four patients. The 5-year disease-free survival of patients with p15 methylation was significantly inferior to that of patients without p15 methylation (15% v 62.5%; P =.02), and this remained significant in multivariate analysis. CONCLUSION: In APL, p15 but not p16 gene methylation is frequent. It is possible that p16 methylation is acquired during clonal evolution. p15 methylation is a potential marker of MRD and might be of prognostic significance.

Design and performance of a fibrous bed bioreactor for odor treatment.

Biological processes have become popular for odor treatment. In this study, a novel fibrous bed bioreactor was applied for treatment of odorous gas. The column reactor was packed with spirally wound fibrous sheet material on which a consortium of microorganisms selected from activated sludge was immobilized. The first stage of this work comprised a preliminary study that aimed at investigating the feasibility of the fibrous bed bioreactor for treatment of odorous volatile fatty acids (VFAs). In this stage, the performance of a fibrous bed bioreactor at increasing mass loadings ranging from 9.7 to 104.2 g/(m3.h) was studied. VFA removal efficiencies above 90% were achieved at mass loadings up to 50.3 g/(m3.h). At a mass loading of 104.2 g/(m3.h), removal efficiency was found to be 87.7%. In the second stage of the work, the process was scaled up with design and operational considerations, namely, packing medium, process condition, and configuration selections. A trickling biofilter with synthetic fibrous packing medium was selected. It was operated under countercurrent flow of gas and liquid streams. The effects of inlet concentration and empty bed retention time on bioreactor performance were studied. The bioreactor was effective in treating odorous VFAs at mass loadings up to 32 g/(m3.h), at which VFAs started to accumulate in the recirculation liquid, indicating that the biofilm was unable to degrade all the VFAs introduced. Although VFAs accumulated in the liquid phase, the removal efficiency remained above 99%, implying that the biochemical reaction rate, rather than gas-to-liquid mass transfer rate, was the limiting factor of this process. The bioreactor was stable for long-term operation; no clogging and degeneration of the packing medium was observed during the 4-mo operation.

Performance of fibrous bed bioreactor for treating odorous gas. Scientific note.

A fibrous bed bioreactor was used for treatment of odorous volatile fatty acid (VFA). The effect of gaseous VFA (acetic, propionic, and butyric acids) mass loading on the bioreactor performance was investigated. The VFA degrading microbial culture was selected from activated sludge by the three VFAs using a shake-flask culture. The selected microorganisms were then immobilized in a biofilter using cotton fabric as packing material. In the biofiltration experiment, the inlet gas flow rates ranged from 1 to 4 L/min, the total VFA concentrations ranged from 0.10 to 0.43 g/m3, and the resulting total mass loadings of VFA studied ranged from 9.7 to 104.3 g/m3/h. At total mass loading of 104.3 g/m3/h, the VFA removal efficiency was 87.7%. Higher removal efficiencies (>90%) were achieved at mass loadings below 50.3 g/m3/h.

Kartagener's syndrome: a re-visit with Chinese perspectives.

The objective of this study was to evaluate the clinical, radiological investigation profiles, and ciliary function and ultrastructure in Chinese patients with Kartagener's syndrome (presence of dextrocardia, sinusitis and bronchiectasis). All patients with dextrocardia were assessed for the presence of sinusitis and bronchiectasis in our hospital network. Patients identified with Kartagener's were assessed when they were at steady state for their bronchiectasis. Seven cases (4 males; mean age 34.9 years) were identified and systematically reviewed. The mean 24 h sputum volume was 26.6 +/- 32.77 mL/day and the patients suffered from a mean of 2.9 exacerbations/year. Nasal symptoms (anosmia in one, obstruction in six and persistent discharge in three patients) were common. Only two cases (1 M) were married and both had normal fertility. Lung function assessment showed a mean FEV1/FVC of 83.3 +/- 38.78/86.5 +/- 36.72 (% predicted) with little reversibility. High resolution computerized tomography (HRCT) revealed bronchiectactic involvement of the lower lobes in seven and middle lobe/lingula in four cases. Assessment of alpha-1-anti-trypsin, aspergillus precipitins, auto-antibodies and serology for Pseudomonas pseudomallei was normal. Sputum culture yielded Pseudomonas aeruginosa in three, Haemophilus influenzae in three and commensals in one case. Phase contrast microscopy assessment of respiratory cilia, obtained by brushing the inferior turbinate, revealed that most of the mucosa was unciliated. The mean ciliary beat frequency was 5.2 +/- 6.76 Hz (range 0-13.7; normal range 12-18 Hz). Four patients had immotile cilia whilst the rest had normal ciliary movement. Transmission electron microscopy showed the absence of dynein arms in four patients. The results of this study show that patients with Kartagener's syndrome may have normal ciliary ultrastructure and the absence of dynein arms is not necessarily associated with ciliary immotility. The presence of ciliary immotility might have prognostic value as these patients appear to have more active bronchiectasis. Our experience on this series should help clinicians in the investigation and management of these patients.

Symptomatology and quality of life in patients with rate-responsive pacemakers: a double-blind, randomized, crossover study.

Although the hemodynamic advantages of rate-responsive (RR) pacing are well established, the symptomatic benefits remain controversial and the effects on the quality of life have not been assessed. Sixteen patients with RR pacemakers and a mean age of 56 (range 22-77) years were involved in a double-blind crossover study to assess their exercise capacity (treadmill testing), symptomatology, and quality of life (structured questionnaires). Pacemakers were implanted because of symptomatic heart block or sick sinus syndrome. Ventricular demand pacemakers were randomly programmed into the constant rate (VVI) or RR pacing modes for four-week study periods. All patients exercised longer in the RR mode than in the VVI mode (570 +/- 29 vs. 437 +/- 17 s, p less than 0.001). Statistically significant improvements in "shortness of breath" and "energy during daily activities" as measured by a 10-point scale were reported in the RR pacing mode by the patients and were also observed by their close relatives. Symptoms such as "chest pain" and "palpitations" were not worsened during RR pacing. Nondisease-specific "quality of life" was studied in 11 patients using the Nottingham Health Profile which showed a trend for an improved quality of life in five of the six dimensions of perceived health, although none of the changes were statistically significant. This study suggests that RR pacing should be recommended in selected patients on symptomatic grounds.