Increased tube formation and up-regulation of FGFR3 mRNA expression in microvascular endothelial cell by exosomes derived from SW480-7.

INTRODUCTION: Extracellular vesicles (exosome-like vesicles) are small membrane vesicles ranging from 20-200nm in size that are released by various cells into the extracellular space. These extracellular vesicles play a major role in cell-to-cell communication and contain materials, such as proteins, mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The effect of exosomes derived from an invasive colon cancer cell line on angiogenesis is unclear. Hence, the aim of this study is to investigate the effect of exosomes derived from an invasive colon cancer cell line on angiogenesis of endothelial cells. MATERIALS AND METHODS: In the present study, the exosomes from the cell culture supernatants of an invasive colon cancer cell line SW480-7 were characterised. The effect on tube formation and expression of angiogenic genes in a microvascular endothelial cell, telomerase-immortalised microvascular endothelial cell (TIME) was examined after co-cultured with exosomes secreted from SW480-7. RESULTS: Zetasizer result showed average diameter of exosomes derived from SW480-7 was 246.2 nm and morphological analysis showed the size of majority of exosomes were less than 200 nm. Results showed that exosomes derived from SW480-7 increased tube formation and up-regulated FGFR3 mRNA expression in TIME. CONCLUSION: Our findings suggest that exosomes derived from SW480-7 increased tube formation and up-regulated expression of FGFR3 mRNA in TIME.

Comparison of United Kingdom and United States screening criteria for detecting retinopathy of prematurity in Hong Kong.

INTRODUCTION: We examined whether the United Kingdom (UK) or the United States (US) screening criteria are more appropriate for retinopathy of prematurity (ROP) screening in Hong Kong, in terms of sensitivity for detecting type 1 ROP and the number of infants requiring screening. METHODS: In this retrospective cohort study, we reviewed the medical records of all infants who underwent ROP screening from 2009 to 2018 at a tertiary hospital in Hong Kong. During this period, all infants born at gestational age (GA) ≤31 weeks and 6 days or birth weight (BW) <1501 g (ie, the UK screening criteria) underwent ROP screening. We determined the number of infants requiring screening and the number of type 1 ROP cases that would have been missed if the US screening criteria (GA ≤30 weeks & 0 days or BW ≤1500 g) had been used. RESULTS: Overall, 796 infants were screened using the UK screening criteria. If the US screening criteria had been used, the number of infants requiring screening would have decreased by 21.1%; all type 1 ROP cases would have been detected (38/38, 100% sensitivity). Of the 168 infants who would not have been screened using the US screening criteria, only four of them (2.4%) had developed ROP (all maximum stage 1 only). CONCLUSION: In our population, the use of the US screening criteria could reduce the number of infants screened without compromising sensitivity for the detection of type 1 ROP requiring treatment. We suggest narrowing the GA criterion for consistency with the US screening criteria during ROP screening in Hong Kong.

Thermal Disorder in Finite-Length Carbon Nanowire.

Enhancement in chemisorption is one of the active research areas in carbon materials. To remedy the thermally degraded chemisorption occurring at high temperatures, we report a comprehensive study of kink structures in free-standing monoatomic carbon nanowires upon heating. Our Monte Carlo simulation considers multi-monoatomic carbon chains laterally interacting by van der Waals forces. Our study reveals that carbon nanowires maintain their linearity regardless of chain length at low temperatures, but this is not the case at high temperatures. Disordered kink structure is observed in short carbon chains, especially above the Peierls transition temperature. A severe kink structure may increase the possibility of attaching negatively charged atoms, thereby contributing to the development of next-generation materials for chemisorption at high temperatures. We have also provided an important indication that any physical property of the finite-length carbon chain predicted by ab initio calculation should reconsider the atomic rearrangement due to thermal instability at high temperatures.

Paediatric glaucoma in Hong Kong: a multicentre retrospective analysis of epidemiology, presentation, clinical interventions, and outcomes.

PURPOSE: To document the epidemiology, presentation, clinical interventions, and outcomes of paediatric glaucoma in Hong Kong. METHODS: This multicentre territory-wide retrospective study was performed by reviewing charts of patients with paediatric glaucoma in six clusters of the Hong Kong Hospital Authority and The Chinese University of Hong Kong from 2006 to 2015. RESULTS: This study included 150 eyes of 98 patients with paediatric glaucoma (presenting age: 5.2±5.7 years). Of them, 35 eyes (23.3%) had primary congenital glaucoma, 22 eyes (14.7%) had juvenile open-angle glaucoma, and 93 eyes (62.0%) had secondary glaucoma. The most prevalent types of secondary glaucoma were lens-related after cataract extraction (18.0%), Axenfeld-Rieger anomaly (5.3%), uveitis (5.3%), Sturge-Weber syndrome (4.7%), and traumatic (3.3%). The most common clinical presentations were parental concerns (20.7%) including cloudy cornea (12.7%) and tearing/photophobia (8.0%), followed by poor visual acuity (18.0%), high intraocular pressure (13.3%), and strabismus (6.0%). The follow-up duration was 8.46±6.51 years. Furthermore, 63.2% of eyes with primary glaucoma and 45.2% of eyes with secondary glaucoma were treated surgically. The final visual acuity was 0.90±0.98 LogMAR; intraocular pressure was 18.4±6.6 mm Hg; and number of glaucoma medications was 2.22±1.61. CONCLUSION: Primary congenital glaucoma was most prevalent, followed by juvenile open-angle glaucoma and aphakic glaucoma. Most eyes with primary glaucoma required surgical treatment. Parental concerns were important clinical presentations. Basic assessments by healthcare providers to identify glaucoma signs (eg, poor visual acuity, high intraocular pressure, and strabismus) warranted prompt referral to an ophthalmologist.

Impact of Recurrence Score on type and duration of chemotherapy in breast cancer.

Background: The use of Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) testing has been shown to change treatment decisions in approximately 30% of breast cancer (bca) cases, but research on how Recurrence Score testing has affected the type of chemotherapy offered is limited. We sought to determine if the availability of Oncotype dx testing resulted in a change to the type and duration of chemotherapy regimens used in the treatment of early-stage hormone receptor-positive bca. Methods: In a population-based cohort study, patients treated in the 2 years before the availability of Oncotype dx testing were compared with patients treated in the 2 years after testing availability. Charts were audited and divided into 2 groups: pre-Oncotype dx and post-Oncotype dx. The groups were compared for differences in duration of chemotherapy (12 weeks vs. >12 weeks), types of agents used (anthracycline vs. non-anthracycline), and myelosuppressive potential of the chosen regimen. Results: Of 834 patients who fulfilled the enrolment criteria, 360 fell into the pre-Oncotype dx era, and 474, into the post-Oncotype dx era. An increase of 11.2 percentage points, to 69.5% from 58.3%, was observed in the proportion of patients receiving short-course compared with long-course chemotherapy (p = 0.068). The proportion of patients prescribed anthracycline-containing regimens declined in the post-Oncotype dx era (47.7% pre vs. 32.2% post, p = 0.016). The selection of more-myelosuppressive chemotherapy protocols increased in the post-Oncotype dx era (67.4% pre vs. 78.8% post, p = 0.044). Conclusions: In the present study, the availability of Oncotype dx testing was observed to influence the choice of chemotherapy type in the setting of early-stage bca.

Analog modulation by the flexoelectric effect in liquid crystals.

We have solved the long-standing problems of stability and hysteresis, and we are able to obtain the homogeneous uniform lying helix structure in polymer-free cholesteric liquid crystals. This is instrumental for the present work to demonstrate the analog modulation at high speed and high precision. The device is configured for the transverse field switching wherein the substrate surface is flat. In addition to the response time of 10 ms at room temperature, we have obtained the R-squared and the adjusted R-squared as a measure of true sine wave for the sinusoidal responding transmissions from 1 Hz to 100 kHz that are all greater than 0.9993. In a Michelson interferometer, the phase shift at wavelength 633 nm after two passes has been measured to be equal to about $\pi /{9}$π/9 at 4.6 V/µm for the chiral-doped nematic mixtures E7.

Control of the ductile and brittle behavior of titanium alloys in diamond cutting by applying a magnetic field.

As a result of extensive investigations into deformation mechanisms of titanium alloys, it has been found that ductile and brittle behavior occurs during diamond cutting of the alloys. Other than implementing ductile regime machining for improving machining performances, in this study, an application of magnetic field in diamond cutting is proposed to enhance the machining performances in both ductile and brittle deformations in diamond cutting of titanium alloys. Results from the experiments showed that under the influence of a magnetic field, the cutting heat at the tool/titanium interface decreased, and surface damages induced from the brittle deformation were remarkably suppressed. The surface quality of both ductile and brittle deformation areas was enhanced in a presence of the magnetic field, which the surface profiles were less distortive with fewer cracks and defects in brittle deformation regions, and the cutting forces at the transition point became less fluctuant and much smoother. This study contributes enhancements of machining performances in ductile and brittle machining in diamond cutting of titanium alloys, increasing the precise level of machined components made with titanium alloys.

Update on the Hong Kong Reference Framework for Hypertension Care for Adults in Primary Care Settings-review of evidence on the definition of high blood pressure and goal of therapy.

The Hong Kong Reference Framework for Hypertension Care for Adults in Primary Care Settings is updated regularly to ensure it reflects the latest medical development and best practice. In 2017, guidelines from the United States included a major change, adopting the lower blood pressure values of 130/80 mm Hg in defining hypertension, in contrast to the prevailing international consensus of 140/90 mm Hg. After thorough review of the literature and international guidelines, the Advisory Group on Hong Kong Reference Framework for Care of Diabetes and Hypertension in Primary Care Settings (Advisory Group) recommends that the definition of hypertension adopted in the Reference Framework should remain unchanged as a blood pressure of ≥140/90 mm Hg, as there is currently inadequate evidence and lack of general consensus to support such change in Hong Kong. The Advisory Group agrees on individualised treatment goals, and recommends that the initial blood pressure goal for individuals with uncomplicated hypertension should be <140/90 mm Hg; for those who can tolerate it, the goal should be ≤130/80 mm Hg. A lower blood pressure is advisable for young or overweight/obese patients, smokers, and patients with other cardiovascular risk factors.

Ductile and brittle transition behavior of titanium alloys in ultra-precision machining.

Titanium alloys are extensively applied in biomedical industries due to their excellent material properties. However, they are recognized as difficult to cut materials due to their low thermal conductivity, which induces a complexity to their deformation mechanisms and restricts precise productions. This paper presents a new observation about the removal regime of titanium alloys. The experimental results, including the chip formation, thrust force signal and surface profile, showed that there was a critical cutting distance to achieve better surface integrity of machined surface. The machined areas with better surface roughness were located before the clear transition point, defining as the ductile to brittle transition. The machined area at the brittle region displayed the fracture deformation which showed cracks on the surface edge. The relationship between depth of cut and the ductile to brittle transaction behavior of titanium alloys in ultra-precision machining(UPM) was also revealed in this study, it showed that the ductile to brittle transaction behavior of titanium alloys occurred mainly at relatively small depth of cut. The study firstly defines the ductile to brittle transition behavior of titanium alloys in UPM, contributing the information of ductile machining as an optimal machining condition for precise productions of titanium alloys.

The body composition profile is associated with response to anti-TNF therapy in Crohn's disease and may offer an alternative dosing paradigm.

BACKGROUND: Anti-tumour necrosis factor (TNF)s form a major part of therapy in Crohn's disease and have a primary nonresponse rate of 10%-30% and a secondary loss of response rate of 5% per year. Myopenia is prevalent in Crohn's disease and is measured using body composition analysis tools. AIM: To test the hypothesis that body composition can predict outcomes of anti-TNF primary nonresponse and secondary loss of response. METHODS: Between January 2007 and June 2012, 106 anti-TNF naïve patients underwent anti-TNF therapy for Crohn's disease with body composition parameters analysed using CT scans to estimate body fat-free mass. The outcome measures were primary nonresponse and secondary loss of response. COX-regression analysis was used with 3 year follow-up data. RESULTS: A total of 106 patients were included for analysis with 26 (24.5%) primary nonresponders and 29 (27.4%) with secondary loss of response to anti-TNF therapy. Sex-specific cut-offs for muscle and fat were ascertained by stratification analysis. On univariate analysis, primary nonresponse was associated with low albumin (OR 0.94; 0.88-0.99, P = .04) and presence of myopenia (OR 4.69; 1.83-12.01, P = .001) when taking into account patient's medical therapy, severity of disease and body composition. On multivariate analysis, presence of myopenia was associated with primary nonresponse (OR 2.93; 1.28-6.71, P = .01). Immunomodulator therapy was associated with decreased secondary loss of response (OR 0.48; 0.23-0.98, P = .04). BMI was poorly correlated with lean body mass (r2 = 0.15, P = .54). CONCLUSIONS: In this cohort study, body composition profiles did not correlate well with BMI. Myopenia was associated with primary nonresponse with potential implications for dosing and serves as an explanation for pharmacokinetic failure.

Factors associated with impaired color vision without retinopathy amongst people with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) may develop color vision impairment. This study aimed to determine the prevalence and factors associated with impaired color vision in patients with T2DM but without diabetic retinopathy. METHODS: Enrolment criteria included multi-ethnic Asian participants, age 21 to 80 years, with known T2DM for a minimum of 2 years. Their diagnoses were affirmed from oral glucose tolerance test results and they were screened for impaired color vision using the Farnsworth D-15 instrument. Demographic characteristics were described and clinical data for the preceding 2 years were analyzed using logistic regression. RESULTS: Twenty-two percent of 849 eligible participants had impaired color vision with higher involvement of the right eye. Impaired blue-yellow color-vision(Tritanomaly) was the commonest impaired color vision. Participants with impaired color vision were significantly associated with age and lower education; longer duration of T2DM (median 6 years vs 4 years); higher HbA1c level and HDL-Cholesterol in 2nd year; lower mean total cholesterol, mean LDL-Cholesterol and mean triglyceride in 2nd year. They also have poorer vision beyond 6/12 in the affected eye. Logistic regression showed that impaired color vision was associated with older patients (OR=1.04), increased duration of T2DM (OR=1.07); prescription of Tolbutamide (OR=3.79) and lower mean systolic blood pressure (OR=0.98). CONCLUSION: Almost one in four participants with T2DM had impaired color vision, largely with tritanomaly. Color vision screening may be considered for participants who develop T2DM for 6 years or longer, but this requires further cost-effectiveness evaluation.

Box C/D sRNA stem ends act as stabilizing anchors for box C/D di-sRNPs.

Ribosomal RNA (rRNA) modifications are essential for ribosome function in all cellular organisms. Box C/D small (nucleolar) ribonucleoproteins [s(no)RNPs] catalyze 2'-O-methylation, one rRNA modification type in Eukarya and Archaea. Negatively stained electron microscopy (EM) models of archaeal box C/D sRNPs have demonstrated the dimeric sRNP (di-sRNP) architecture, which has been corroborated by nuclear magnetic resonance (NMR) studies. Due to limitations of the structural techniques, the orientation of the box C/D sRNAs has remained unclear. Here, we have used cryo-EM to elucidate the sRNA orientation in a M. jannaschii box C/D di-sRNP. The cryo-EM reconstruction suggests a parallel orientation of the two sRNAs. Biochemical and structural analyses of sRNPs assembled with mutant sRNAs indicate a potential interaction between the sRNA stem ends. Our results suggest that the parallel arrangement of the sRNAs juxtaposes their stem ends into close proximity to allow for a stabilizing interaction that helps maintain the di-sRNP architecture.

Gene expression profile alone is inadequate in predicting complete response in multiple myeloma.

With advent of several treatment options in multiple myeloma (MM), a selection of effective regimen has become an important issue. Use of gene expression profile (GEP) is considered an important tool in predicting outcome; however, it is unclear whether such genomic analysis alone can adequately predict therapeutic response. We evaluated the ability of GEP to predict complete response (CR) in MM. GEP from pretreatment MM cells from 136 uniformly treated MM patients with response data on an IFM, France led study were analyzed. To evaluate variability in predictive power due to microarray platform or treatment types, additional data sets from three different studies (n=511) were analyzed using same methods. We used several machine learning methods to derive a prediction model using training and test subsets of the original four data sets. Among all methods employed for GEP-based CR predictive capability, we got accuracy range of 56-78% in test data sets and no significant difference with regard to GEP platforms, treatment regimens or in newly diagnosed or relapsed patients. Importantly, permuted P-value showed no statistically significant CR predictive information in GEP data. This analysis suggests that GEP-based signature has limited power to predict CR in MM, highlighting the need to develop comprehensive predictive model using integrated genomics approach.

Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis.

BACKGROUND: Between 75 000 and 125 000 U.S. infants are hospitalized for respiratory syncytial virus (RSV) bronchiolitis every year. Up to half will be diagnosed with asthma in later childhood. Vitamin D deficiency has been associated with susceptibility to asthma and respiratory infections. Measured vitamin D is largely bound to vitamin D-binding protein (VDBP); VDBP levels are influenced by its gene (GC) haplotype. OBJECTIVE: We assessed the relationship between polymorphisms rs7041 and rs4588, which define haplotypes GC1s, GC1f, and GC2, and RSV bronchiolitis susceptibility and subsequent asthma. METHODS: We retrospectively recruited 198 otherwise healthy children (93% White) hospitalized for severe RSV bronchiolitis in Boston and 333 parents into a follow-up study to assess asthma diagnosis. Data were analysed using family-based genetic association tests. We independently validated our results in 465 White children hospitalized with RSV bronchiolitis and 930 White population controls from the Netherlands. RESULTS: The rs7041_C allele (denoting haplotype GC1s) was overtransmitted (P = 0.02, additive model) in the entire Boston cohort, in Whites (P = 0.03), and especially in children subsequently diagnosed with asthma (P = 0.006). The GC1f haplotype was undertransmitted in the asthma subgroups (all races and White, both P < 0.05). The rs7041_C allele was also more frequent in the RSV bronchiolitis group compared with controls (OR 1.12, 95% CI 1.02, 1.4, P = 0.03) in the Netherlands, especially in mechanically ventilated patients (P = 0.009). CONCLUSION AND CLINICAL RELEVANCE: GC1s haplotype carriage may increase the risk of RSV bronchiolitis in infancy and subsequent asthma development. The GC1s haplotype is associated with higher VDBP levels, resulting in less freely available vitamin D. KEY MESSAGES: Vitamin D-binding protein (VDBP) haplotypes influence free vitamin D levels. We report an association between a VDBP haplotype and hospitalization for RSV bronchiolitis in infancy in two independent cohorts.