[Effects of temperature and relative humidity on the number of outpatients with chronic obstructive pulmonary disease and their interaction effect in Lanzhou, China].

OBJECTIVE: To understand the relationships of daily average temperature and relative humidity with outpatient visit frequency of patients with chronic obstructive pulmonary disease, and whether temperature and relative humidity have a lag effect. METHODS: The effects of daily average temperature, relative humidity, and their interaction in Lanzhou between January 2013 and December 2017 on the outpatient visit frequency of chronic obstructive pulmonary disease patients were analyzed using Poisson generalized linear regression model combined with distributed lag non-linear model. RESULTS: There was a non-linear relationship between the daily average temperature and the outpatient visit frequency of chronic obstructive pulmonary disease patients. Between -12 °C and -8 °C, the outpatient visit frequency increased gradually with the decrease of the daily average temperature, and the outpatient visit frequency of chronic obstructive pulmonary disease patients increased by 11.60% per 1 °C of temperature drop. The daily average relative humidity also presented a non-linear effect on the outpatient visit frequency chronic obstructive pulmonary disease patients. When the daily average relative humidity was in the range of 15%-28%, the outpatient visit frequency increased gradually with the decrease of relative humidity, and the outpatient visit frequency of COPD patients increased by 37.05% for every 1% decrease of relative humidity. A synergistic effect was found between air temperature and relative humidity on chronic obstructive pulmonary disease, that is, under different relative humidity, the effect of air temperature was different. When the daily average relative humidity ≤ 50% and the daily average temperature≤11 °C, the effect of air temperature was the most obvious. For every 1 °C drop in temperature, the daily out-patient visit frequency of the whole population increased by 12.68% (5.62% in males and 7.56% in females; 5.24% in population < 65 years and 14.74% in population ≥ 65 years). When the daily average relative humidity > 50% and the daily average temperature ≤ 11 °C, the daily outpatient visit frequency of the whole population increased by 9.00% for every 1 °C drop in temperature (< 65 years, 7.11%; ≥65 years, 10.93%). When the daily average temperature > 11 °C, the temperature had no effect on the daily outpatient visit frequency of chronic obstructive pulmonary disease patients under different relative humidity. CONCLUSION: The presence of a certain extent of interaction is observed between daily average temperature and relative humidity. Low-temperature and dry environment (relative humidity ≤50%, temperature ≤11 °C) as well as low-temperature and high-humidity environment (relative humidity > 50%, temperature ≤11 °C) can both increase the risk of outpatient visit in chronic obstructive pulmonary disease patients.

Longitudinal dental maturation of children with complete unilateral cleft lip and palate: A case-control cohort study.

OBJECTIVES: Many reports suggest that children with cleft lip and palate (CLP) have delayed dental development and asymmetrical timing of tooth-pair formation. We aimed to investigate the dental maturation of permanent teeth in children with complete unilateral CLP (UCLP) and compare the findings with non-CLP children. SETTING AND SAMPLE POPULATION: This case-control study used 115 radiographs of children with complete UCLP and controls (non-CLP children matched on age, gender and ethnicity) from a hospital-based dental clinic in Singapore. MATERIAL AND METHODS: Orthopantomographs of 60 children with complete UCLP (5-9 years old) and 55 children (9-13 years old) from the same cohort were investigated using the Demirjian's method and compared with controls to determine if there were any differences in dental maturation with age. RESULTS: Delayed dental maturation was found in the 5- to 9-year-old children with UCLP compared to controls by 0.55 years (standard deviation: 0.75) (P<.001). There was no significant difference between the dental maturation of children with UCLP and controls in the 9- to 13-year-old group (P=.744). The group with UCLP had higher risk of asymmetrically developing tooth pairs than the control group for both age groups (P<.001). CONCLUSION: No difference in dental maturation between UCLP and controls in the 9- to 13-year-old group was found. However, there was diametrical difference in dental maturation in the 5- to 9-year-old group, which attenuated as they grew older. There was a consistently higher risk of asymmetrical tooth formation in children with UCLP than in controls.

A case of successfully managed pregnancy in a patient with complex cyanotic congenital heart disease.

Medical advances have increased survival of patients with congenital heart disease. However, cardiac disease in pregnancy carries significant maternal and fetal risks, posing enormous challenges to obstetricians. Cyanotic congenital heart disease is associated with maternal complications such as arrhythmias, thromboembolic events and death. Fetal complications include small for gestational age, miscarriage and prematurity. Cyanotic congenital heart disease patients who continue their pregnancies require holistic multidisciplinary team care with early and coordinated planning for delivery. Management of such patients include early counseling regarding pregnancy-associated risks, close monitoring of their cardiac function and regular scanning for fetal assessment. Choice of anesthesia for these patients requires meticulous planning to achieve a favorable balance between systemic and pulmonary vascular resistance, ensuring minimal change in right-to-left shunting. We report a case of a successfully managed pregnancy in a patient with complex congenital heart disease and a single ventricle of left ventricle morphology.

Repeated failed non-invasive prenatal testing in a woman with immune thrombocytopenia and antiphospholipid syndrome: lessons learnt.

We present a case of a 37-year-old Chinese woman (gravida 4 para 0) with a history of immune thrombocytopenia and type IIb antiphospholipid syndrome. She was started on 100 mg of aspirin, 20 mg of prednisolone and 20 mg of subcutaneous low-molecular-weight heparin daily for her fourth pregnancy. She opted for non-invasive prenatal testing for aneuploidy screening but had failed results three times consecutively from insufficient fetal cfDNA initially or high variance in cfDNA counts on redraws. She declined invasive karyotyping. Her pregnancy was complicated by severe pre-eclampsia and fetal growth restriction at 19+6 weeks of gestation and was terminated. Subsequent fetal karyotyping revealed a normal karyotype of 46XY with no apparent abnormalities.

Elucidating the roles of miR-372 in cell proliferation and apoptosis of nasopharyngeal carcinoma TW01 cells.

AIM: Deregulation of microRNA has been associated with cancer progression and the modification of cancer phenotypes could be achieved by targeting microRNA expression. This study aimed to determine the effects of miR-372 on cell progression and gene expression in nasopharyngeal carcinoma cell line, TW01. MATERIALS AND METHODS: NPC TW01 cells were transfected with the miR-372 precursor molecules. Gene expression studies were conducted using RT-PCR assays for nine cancer related genes. The effects of miR-372 on cell proliferation, cell cycle arrest and apoptosis were also investigated. RESULTS: Expression of -miR-372 caused cell cycle arrest at the S phase that was accompanied by an overall decrease of cells entering the G2/M phase. miR-372 did not have any significant effect on apoptosis. Of the nine genes studied, four were up-regulated, namely CDKN1A, INCA1, LATS2 and BIRC5. The other five genes - CDK2, CCNA1, TP53, BAX and BCL2 were down-regulated by miR-372. CONCLUSION: This preliminary study indicated the tumor suppressing roles of miR-372 in cell cycle progression of TW01 cells, possibly via the down-regulation of CDK2 and CCNA1 as well as the up-regulation of CDKN1A and INCA1.Key Words: apoptosis, microRNA, nasopharyngeal carcinoma, miR-372, CDK2, CCNA1.

Magnetoelastic vibrational biomaterials for real-time monitoring and modulation of the host response.

Magnetoelastic (ME) biomaterials are ferromagnetic materials that physically deform when exposed to a magnetic field. This work describes the real-time control and monitoring capabilities of ME biomaterials in wound healing. Studies were conducted to demonstrate the capacity of the materials to monitor changes in protein adsorption and matrix stiffness. In vitro experiments demonstrated that ME biomaterials can monitor cell adhesion and growth in real-time, and a long-term in vivo study demonstrated their ability to monitor the host response (wound healing) to an implant and control local cell density and collagen matrix production at the soft tissue-implant interface. This approach represents a potentially self-aware and post-deployment activated biomaterial coating as a means to monitor an implant surface and provide an adjuvant therapy for implant fibrosis.

Effects of IL-6, IL-10 and TGF-ß on the expression of survivin and apoptosis in nasopharyngeal carcinoma TW01 cells.

UNLABELLED: The aim of this study is to investigate whether IL-6, IL-10 and TGF-ß are able to confer resistance to apoptosis in nasopharyngeal carcinoma cells by upregulating the expression of survivin. METHODS: The human nasopharyngeal carcinoma cell line TW01 (WHO NPC Type I) was cultured in DMEM-F12 Ham medium containing 10% FBS in a humidified atmosphere of 5% CO(2) and 37°C and treated with different concentrations of IL-6, IL-10 and TGF-ß. Survivin mRNA expression was measured by real-time quantitative PCR and Western blot. Apoptosis was determined based on the assay for caspase-3 activity. RESULTS: Of all the cytokines tested, only TGF-ß (10 pg/mL) induced the over-expression of survivin at a significant level and this correlated with resistance to apoptosis (p ≤ 0.05). To confirm if survivin is responsible for resistance to apoptosis, YM155 which is a survivin inhibitor was used and the results showed that YM155 abrogated the protective effect of TGF-ß. Interestingly, IL-10 did not significantly alter the expression of survivin. CONCLUSIONS: We conclude that TGF-ß up-regulates the expression of survivin leading to the resistance to apoptosis in NPC TW01 cells.

Novel multiplex oligonucleotide-conjugated bead suspension array for rapid identification of enterovirus 71 subgenogroups.

A high-throughput multiplex bead suspension array was developed for the rapid subgenogrouping of EV71 strains, based on single nucleotide polymorphisms observed within the VP1 region with a high sensitivity as low as 1 PFU. Of 33 viral isolates and 55 clinical samples, all EV71 strains were successfully detected and correctly subgenogrouped.

Over-investigated and under-treated: children with febrile convulsion in a Malaysian district hospital.

INTRODUCTION: We conducted a retrospective audit on the inpatient assessment and care of children admitted with febrile convulsion to Hospital Batu Pahat, a district hospital in Malaysia, using the Malaysian national clinical practice guidelines and the American Academy of Paediatrics practice parameters on febrile convulsion as the reference standards. METHODS: The case notes of 100 consecutive children admitted in 2004 were analysed. The documentation of major clinical features, selection of investigations, the timeliness of antipyresis and frequency of parental education were evaluated. RESULTS: In general, the major clinical features that were relevant to the presenting problem were adequately documented, although fever was not mentioned as a presenting complaint in one quarter of the cases. On an average, about five investigations were ordered for every patient on admission. There was no major difference in the number of investigations conducted between children who were more severely ill and the rest of the patients. The majority of the investigations did not yield any useful diagnostic information. Only 38 percent of the children received antipyretics and 53 percent were tepid-sponged during fever, with 23 percent having received tepid-sponging without concurrently receiving antipyretics. No parental education on febrile convulsion was recorded in half of the cases. CONCLUSION: Excessive unjustified investigations, deficient antipyresis when required and inadequate communication with the family of children with febrile convulsion were observed. Awareness of such deficiencies from this audit should lead to regular staff education, monitoring and future audits in order to improve the quality of our clinical care.

The largest outbreak of hand; foot and mouth disease in Singapore in 2008: the role of enterovirus 71 and coxsackievirus A strains.

BACKGROUND: During 2008, Singapore experienced its largest ever outbreak of hand, foot and mouth disease (HFMD), resulting in 29686 cases, including four cases of encephalitis and one fatality. METHODS: A total of 51 clinical specimens from 43 patients with suspected HFMD at the National University Hospital, Singapore were collected for virus isolation and identification by reverse transcription polymerase chain reaction (RT-PCR) and sequencing. RESULTS: Enteroviruses were identified in 34 samples (66.7%), with 11 samples (21.6%) being positive for enterovirus 71 (EV71). Other non-EV71 enteroviruses (including coxsackievirus A4, A6, A10, and A16) were identified in 23 samples (45.1%). The most prevalent virus serotypes were CA6, CA10, and EV71. CA6 and CA10 accounted for 35.3% of all HFMD cases, which may explain the high transmissibility and low fatality that characterized this unprecedented epidemic associated with relatively mild disease. Phylogenetic analyses of 10 circulating EV71 strains indicated that they belonged to two subgenogroups, i.e., B5 (80%) and C2 (20%). The VP1 sequences of the 2008 EV71 strains also exhibited continuous mutations during the outbreak, reflecting the relatively high mutation rate of the EV71 capsid protein, which may have implications for future vaccine development. CONCLUSIONS: A safe and effective vaccine against EV71 is certainly warranted in view of its potential neurovirulence and its role in HFMD epidemics of recurring frequency with resultant fatalities in Asia, as well as other parts of the world.

In vitro modulation of naturally occurring flavonoids on cytochrome P450 2A6 (CYP2A6) activity.

1. The effect of flavonoids on coumarin 7-hydroxylation, an activity marker of an important human liver cytochrome P450 isoform, cytochrome P450 2A6 (CYP2A6), was investigated in this study. 2. Coumarin 7-hydroxylase activity was measured fluorometrically in reaction mixtures containing cDNA-expressed CYP2A6, nicotinamide adenine dinucleotide phosphate generating system and 10 uM coumarin, at various concentrations of flavonoids. 3. Among the 23 compounds tested, most of the active members were from flavonol group of hydroxylated flavonoids, with myricetin being the most potent inhibitor followed by quercetin, galangin, and kaempferol. 4. Further exploration of the inhibition mechanism of these compounds revealed that myricetin, galangin, and kaempferol exhibited mixed-type of inhibition pattern while quercetin was observed to exhibit competitive mode of inhibition. 5. Structure-function analyses revealed that degree of inhibition was closely related to the number and location of hydroxyl groups, glycosylation of the free hydroxyl groups, degree of saturation of the flavane nucleus as well as the presence of the alkoxylated function.

Biological properties of TW01 cells expressing latent membrane protein-1 gene of EBV-derived from nasopharyngeal carcinoma cells at different stages of malignancy.

BACKGROUND AND AIM: Epstein-Barr virus (EBV), a human gammaherpesvirus is intimately associated with nasopharyngeal carcinoma (NPC), with the incidence of the virus detected in malignant tissues being close to 100% in NPC endemic areas. The viral latent gene, latent membrane protein 1 (LMP1), has all the typical characteristics of an oncogene and extensive studies have shown beyond doubt its abilities in cellular transformation giving rise to malignant phenotypes. The present study compares the gene sequence and biological properties of LMP1 gene derived from two patients with different stages of NPC--one presented with dysplastic, pre-malignant lesion and the other with malignant lesion. METHODS: The sequences of the LMP1 genes derived from pre-malignant (NORLMP1) and malignant (NPCLMP1) tissues were compared. NORLMP1 and NPCLMP1 were expressed in TW01 cells and their biological properties conferred were assessed in terms of in vitro invasion capability, ability to resist apoptosis and regulation of E-cadherin (CDH1) expression. RESULTS: NORLMP1 and NPCLMP1, possessed numerous amino acid changes with respect to the wild-type B95.8 LMP1. Both LMP1 variants demonstrated distinct biological properties when expressed in TW01 cells. NORLMP1-expressing TW01 cells exhibited more aggressive phenotypes than the NPCLMP1-expressing counterpart in terms of invasive ability, resistance to stimuli-induces apoptosis and regulation of CDH1 expression. CONCLUSION: It could be inferred from the present study that LMP1 genes derived from two patients with different stages of NPC differed in their gene sequences that manifested in distinct biological properties.

Human leukocyte class I antigen alleles A2 and A11 are not associated with nasopharyngeal carcinoma in West Malaysia.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is the second most common cancer among Malaysian Chinese males. We determined the frequencies of 17 human leukocyte antigens (HLA), HLA-A and HLA-B, alleles in 88 Malaysian Chinese with NPC. METHODS: Using polymerase chain reaction sequence-specific primers, the frequencies of 17 HLA-A and HLA-B alleles were analysed. They were A1, A2, A11, A31, A32, A33, B8, B13, B27, B38, B39, B44, B46, B55, B58, B61 and B71. RESULTS: Three of the 17 alleles were detected in NPC patients. They were A1 (0.6 percent), A2 (56.3 percent) and A11 (43.2 percent). Three of the 17 alleles were detected in age- and sex-matched healthy individuals. They were A2 (50.0 percent), A11 (50.0 percent) and B27 (4.7 percent). The A2 and A11 alleles were evenly distributed in both groups, while A1 was only found in one NPC patient and B27 exclusively in healthy individuals. CONCLUSION: We conclude that A1 is very rare, and A2, A11, A31, A32, A33, B8, B13, B38, B39, B44, B46, B55, B58, B61 and B71 alleles have no associations with the occurrence of NPC in Malaysia, while allele B27 is negatively associated.

Information sources used by New South Wales cancer clinicians: a qualitative study.

BACKGROUND: This study identified (i) information sources used by cancer clinicians to guide pharmacological treatments, (ii) utilization of, and opinions about, online information sources and (iii) clinicians' ability to access a specific cancer treatment protocol (escalated bleomycin, etiposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) for Hodgkin's Lymphoma). The work was carried out before activation of the Cancer Institute New South Wales Standard Cancer Treatment (CI-SCaT) programme. METHODS: We conducted semistructured interviews with a purposeful sample of senior and junior doctors, nurses and pharmacists treating adult cancer patients (n = 32) in eight New South Wales public hospitals. RESULTS: Information seeking processes are context specific and vary from clinician to clinician and ward to ward. Clinicians use human, electronic and printed information sources at, or close to, the point of patient care; however, experienced colleagues are preferred where information is needed quickly or in unfamiliar clinical situations. Barriers to using online cancer information are environmental (hardware, connection speeds, time), personal (poor computer literacy and lack of awareness of appropriate sites) and economic (costs of journal subscriptions). Just over half of participants were able to locate a specific cancer protocol and none of these protocols was fully consistent with CI-SCaT recommendations. CONCLUSION: There is no standardized approach to the pharmacological treatment of cancer patients in this sample of New South Wales clinicians. CI-SCaT will fill a gap with respect to standardizing oncology treatment. However, to ensure maximal CI-SCaT uptake, implementation plans should harness positive behavioural influences and attempt to modify the negative forces that act on hospital clinicians in their day-to-day work.

Evaluation of plasma Epstein-Barr virus DNA load as a prognostic marker for nasopharyngeal carcinoma.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is an important cancer in Malaysia and is one of the major causes of cancer mortality in this country. This study evaluates the diagnostic and prognostic values in the quantitative relationship between the cell-free Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) load and the tumour burden. METHODS: Blood plasma from 18 untreated NPC patients, 20 NPC patients who had been treated with radiotherapy, and 12 healthy individuals were evaluated. EBV copy number was determined following DNA extraction using real-time quantitative polymerase chain reaction. RESULTS: The cell-free EBV DNA load was shown to be proportionately related to the presence of malignant disease. While the EBV copy number in untreated NPC patients had a median of 2,043 copies/ml, viral load in plasma of healthy controls was significantly lower (median of 0 copy/ml). A significant decrease in EBV load was observed in patients who had undergone radiotherapy while a high viral load indicated in one patient correlated to tumour relapse and presence of distant metastasis upon clinical investigation. CONCLUSION: The blood plasma EBV DNA load was shown to be proportionately related to the presence of malignant disease. This preliminary study underscores the prognostic value of cell-free EBV DNA quantification.

Mammography and screening for breast cancer.

Mammography has been in general use as a breast imaging procedure for many years. More recently, it has taken on another important role, as a screening procedure for breast cancer. This article reviews its effectiveness in reducing morbidity and mortality resulting from the disease.

Use of magnetic resonance imaging in the evaluation of nasopharyngeal cancer.

Computerised tomographic (CT) scanning is an established modality in the diagnosis and evaluation of tumours of the nasopharynx. Magnetic resonance (MR) imaging is a newer tool which has rapidly gained acceptance in the same regard due to its innate ability to better characterise and detail soft tissue structures, and its multiplanar scanning ability. This study reviews our experience, in a series of 30 cases, with the use of MR imaging in lesions of the nasopharynx, in particular nasopharyngeal carcinoma. Most of our patients showed involvement of the pharyngeal mucosal and parapharyngeal spaces, as expected. A large number also had intracranial extension. Our sample was probably biased as patients with neurological involvement are more likely to be assessed by MR than CT. Soft tissue infiltration, particularly intracranial extension, was very clearly delineated, especially when intravenous contrast (gadolinium DTPA) was administered. Bone erosion was not well demonstrated. In current clinical practice where radiotherapy is the most common form of treatment for nasopharyngeal carcinoma however, there does not in general, appear to be any clear advantage of MR over CT in the imaging of this particular disease, although there are some exceptions.

Transforming growth factor-alpha (TGF-alpha) in a semisolid dosage form: preservative and vehicle selection.

The selection of an ideal semisolid vehicle for growth factors presents a challenge. Some antimicrobial agents are known to delay wound healing. The objective of this investigation was to identify appropriate preservatives and vehicles for TGF-alpha. Criteria for acceptance are noninterference with the mitogenic activity of TGF-alpha as well as adequate product preservation. Vehicles considered were o/w creams, ointments, and a gel. Combinations of six preservatives were tested. Selection was determined using both microbial preservative challenge and TGF-alpha mitogenic assay. In the former, 10 species of microorganisms were inoculated into formulation samples. At selected time intervals, it was determined whether colonies decreased, increased, or remained constant. In the mitogenic assay, samples of either preservatives or formulation prototypes were introduced to TGF-alpha-stimulated fibroblast cell cultures. Mitogenesis was determined by measuring 3H-dThd uptake into newly synthesized DNA. As preservatives, sorbic acid and quaternium-15 appear to satisfy both selection criteria. A thermosetting gel appears most promising as vehicle.