Shrinking microbubbles with microfluidics: mathematical modelling to control microbubble sizes.

Microbubbles have applications in industry and life-sciences. In medicine, small encapsulated bubbles (<10 µm) are desirable because of their utility in drug/oxygen delivery, sonoporation, and ultrasound diagnostics. While there are various techniques for generating microbubbles, microfluidic methods are distinguished due to their precise control and ease-of-fabrication. Nevertheless, sub-10 µm diameter bubble generation using microfluidics remains challenging, and typically requires expensive equipment and cumbersome setups. Recently, our group reported a microfluidic platform that shrinks microbubbles to sub-10 µm diameters. The microfluidic platform utilizes a simple microbubble-generating flow-focusing geometry, integrated with a vacuum shrinkage system, to achieve microbubble sizes that are desirable in medicine, and pave the way to eventual clinical uptake of microfluidically generated microbubbles. A theoretical framework is now needed to relate the size of the microbubbles produced and the system's input parameters. In this manuscript, we characterize microbubbles made with various lipid concentrations flowing in solutions that have different interfacial tensions, and monitor the changes in bubble size along the microfluidic channel under various vacuum pressures. We use the physics governing the shrinkage mechanism to develop a mathematical model that predicts the resulting bubble sizes and elucidates the dominant parameters controlling bubble sizes. The model shows a good agreement with the experimental data, predicting the resulting microbubble sizes under different experimental input conditions. We anticipate that the model will find utility in enabling users of the microfluidic platform to engineer bubbles of specific sizes.

Dripping and jetting in microfluidic multiphase flows applied to particle and fiber synthesis.

Dripping and jetting regimes in microfluidic multiphase flows have been investigated extensively, and this review summarizes the main observations and physical understandings in this field to date for three common device geometries: coaxial, flow-focusing and T-junction. The format of the presentation allows for simple and direct comparison of the different conditions for drop and jet formation, as well as the relative ease and utility of forming either drops or jets among the three geometries. The emphasis is on the use of drops and jets as templates for microparticle and microfiber syntheses, and a description is given of the more common methods of solidification and strategies for achieving complex multicomponent microparticles and microfibers.

Risk factors for extra-pulmonary tuberculosis compared to pulmonary tuberculosis.

BACKGROUND: Tuberculosis (TB) continues to be a major global health problem. Extra-pulmonary TB (EPTB) manifests with protean symptoms, and establishing a diagnosis is more difficult than pulmonary TB (PTB). SETTING: A university-affiliated hospital in southern Taiwan. OBJECTIVE: To analyse the risk factors for EPTB compared with PTB. DESIGN: This retrospective study compared patients with EPTB and PTB in southern Taiwan by analysing their demographic data and clinical underlying diseases. Risk factors for EPTB were further analysed. RESULTS: A total of 766 TB patients were enrolled in this study, with 102 (13.3%) EPTB and 664 (86.7%) PTB cases. Of the 766 patients, 3% of PTB patients had EPTB, while 19.6% of EPTB patients also had PTB. The most frequently involved EPTB site was the bone and joints (24.5%). The incidence of EPTB vs. PTB decreased significantly for each decade increase in patient age. Multivariate logistic regression analysis showed that being female, not being diabetic, having end-stage renal disease and not smoking were independent risk factors for EPTB. CONCLUSION: This study defines the risk factors for EPTB compared with PTB. Awareness of these factors is essential for physicians to have a high index of suspicion for accurate and timely diagnosis.

Liver transplantation for biliary atresia in Taiwan: a national study.

A national database for orthotopic liver transplantation (OLT) among biliary atresia (BA) cases in Taiwan has not been reported. Using the National Health Insurance (NHI) database to investigate the prognostic features of patients with BA receiving OLT, we studied the prognosis of this procedure for BA. The NHI in Taiwan covers most of the population (>99%). From 1996-2004, 106 BA patients underwent transplantation. A linear time trend analysis was performed to estimate the annual slope for BA patients to receive OLT. The rate of increase per year of 2.6 cases was significant (R(2) = .649; P = .029). The 5-year overall survival after OLT was 97.1% +/- 1.6%, which was not different between those who had or had not previously undergone portoenterostomy (94.9% vs 97.8%; P = .160). It was not different among patients undergoing transplantation during the various seasons (P = .505). Our data confirmed the effectiveness of OLT for the treatment of BA in children with or without KP in Taiwan.

In situ hybridization and RT-PCR detection of Macrobrachium rosenbergii nodavirus in giant freshwater prawn, Macrobrachium rosenbergii (de Man), in Taiwan.

Between January and March 2006, suspected outbreaks of white tail disease were observed in post-larvae and juveniles of Macrobrachium rosenbergii in hatcheries and nursery ponds at Kaohsiung and Pingtung Counties in southern Taiwan. Pathognomonic lesions showed the presence of large oval and/or irregular basophilic, cytoplasmic inclusion bodies in the infected muscles and hepatopancreas. Reverse transcriptase polymerase chain reaction (RT-PCR) assay and in situ hybridization (ISH) revealed evidence of M. rosenbergii nodavirus (MrNV) infection but did not detect extra small virus. Phylogenetic analysis indicated that there were very high identities between nucleotide sequences among six strains obtained in this study (99.5-100%), moderate identities with Caribbean and Indian strains (98.2-98.6%), but slightly lower identity with a Chinese strain (95.2%). This is the first confirmation of MrNV in giant freshwater prawns, using an RT-PCR and ISH, in Taiwan.

Unusual pox lesions found in Chinese jungle mynahs (Acridotheres cristatellus).

Pox lesions involving feathered and unfeathered skin, the oral cavity and the uropygial gland were found in Chinese jungle mynahs. Characteristic intracytoplasmic inclusions were detected in the proliferative cells of all lesions. Ultrastructurally, the virus particles consisted of a convoluted outer membrane enclosing lateral bodies and a biconcave central core, typical for poxvirus. The nucleotide sequences of the amplicon obtained with a set of primers for the 4b core protein of fowl poxvirus revealed that the mynah poxvirus was phylogenetically related to wood pigeon poxvirus. This is the first report of poxvirus infection affecting the uropygial gland.

Relationship between magnesium levels in drinking water and sudden infant death syndrome.

The possible association between the risk of death from sudden infant death syndrome (SIDS) and the levels of magnesium in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Characteristics for all SIDS deaths (501 cases) among Taiwan residents from 1988 through 1997 were compared with those of people who died from other causes (501 controls). The levels of magnesium in the drinking water of these residents were determined from data obtained from the Taiwan Water Supply Corporation (TWSC). The controls were pair-matched to the SIDS cases by sex, month and year of birth. The results of our study show that there is a significant trend towards a decreased risk of SIDS with increasing magnesium levels in drinking water.

Adverse pregnancy outcome in a petrochemical polluted area in Taiwan.

The petrochemical industry is the main source of industrial air pollution in Taiwan. Reported here are the results from an ongoing study of outdoor air pollution and the health of individuals living in a community in close proximity to petrochemical industrial complexes. The prevalences of term low birth weight (LBW) in the petrochemical municipality and control municipality were 3.22%, and 1.84%, respectively. After controlling for several possible confounders (including maternal age, season, marital status, maternal education, and infant sex), the adjusted odds ratio was 1.767 (1.002-3.116) for term LBW in the petrochemical municipality. Data provide further support for the hypothesis that air pollution can affect the outcome of pregnancy.

Molecular characterization of Newcastle disease viruses isolated from recent outbreaks in Taiwan.

A reverse transcription-polymerase chain reaction (RT-PCR) was described which amplified a portion of the F and HN genes of Newcastle disease virus (NDV) isolated from recent outbreaks in Taiwan. The F protein plays an important role in determining the virulence of NDV strains. Sequencing of a region specifying the F protein cleavage site was therefore undertaken and this verified the correlation between deduced amino sequences and pathogenicity. Analysis of the deduced amino acid sequences of the F protein cleavage site showed that all recent Taiwanese isolates in 1999 were velogenic viruses. All the virulent viruses have the amino acid sequence 112RRQKR116 for the C-terminus of the F2 protein and phenylanine (F) at the N-terminus of the F1 protein, residue 117. A phylogenetic tree based on the nucleotide sequences of the F gene revealed that recent Taiwanese NDV isolates responsible for recent outbreaks were classified into two distant genotypes (VI and VII). Genotype VI virus is the first finding in Taiwan and has a highly genetic similarity to European isolates, suggesting that they might have originated from a common ancestor.

Adverse health effects among household waste collectors in Taiwan.

Household waste collectors (HWCs) are potentially exposed to a variety of bioaerosols and toxic materials. Collection of household waste is also a job which requires repeated heavy physical activity such as lifting, carrying, pulling, and pushing. The object of this study was to assess whether there is an excess of adverse health outcomes among HWCs. The subjects were all current employees of the Household Waste Collection Department in the County of Kaohsiung, Taiwan. The survey questionnaire was completed by 533 HWCs and 320 office workers. Our data indicate that household waste collection presents a risk for the development of chronic respiratory symptoms (cough, phlegm, wheezing, and chronic bronchitis), musculoskeletal symptoms (low back pain and elbow/wrist pain), and injuries caused by sharp objects.

Increased risk of preterm delivery in areas with air pollution from a petroleum refinery plant in Taiwan.

The petrochemical and petroleum industries are among the main sources of industrial air pollution in Taiwan. Data in this study concern outdoor air pollution and the health of individuals living in communities in close proximity to a petroleum refinery plant. The prevalence of delivery of preterm birth infants was significantly higher in mothers living in a petroleum refinery area compared to controls in Taiwan. After controlling for several possible confounders (including maternal age, season, marital status, maternal education, and infant sex), the adjusted odds ratio was 1.41 (95% CI = 1.08-1.82) for delivery of preterm infants in the polluted region. Data support the view that air pollution can affect the outcome of pregnancy.

Association between chlorination of drinking water and adverse pregnancy outcome in Taiwan.

Chlorination has been the major means of disinfecting drinking water in Taiwan. The use of chlorinated water has been hypothesized to lead to several adverse birth outcomes, including low birth weight and preterm delivery. We performed a study to examine the relationship between the use of chlorinated water and adverse birth outcomes in Taiwan. The study areas included 14 chlorinating municipalities (CHMs), which were defined as municipalities in which > 90% of the municipal population was served by chlorinated water, and 14 matched nonchlorinating municipalities (NCHMs), defined as municipalities in which < 5% of the municipal population is served by chlorinated water. The CHMs and NCHMs were similar to one another in terms of level of urbanization and sociodemographic characteristics. The study population comprised 18,025 women residing in the 28 municipalities who had a first parity singleton birth between 1 January 1994 and 31 December 1996 and for which complete information on maternal age, education, gestational age, birth weight, and sex of the baby were available. The results of our study suggest that there was no association between consumption of chlorinated drinking water and the risk of low birth weight.

Calcium and magnesium in drinking water and risk of death from prostate cancer.

The possible association between the increased risk of prostate cancer and the levels of calcium and magnesium in drinking water from municipal supplies was investigated in a matched cancer case-control study in Taiwan. All eligible prostate-cancer deaths (682 cases) of Taiwan residents from 1987 through 1993 were compared with deaths from other causes (682 controls). The levels of calcium and magnesium in the drinking water of these residents were also determined. Data on calcium and magnesium levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes, and the controls were pair-matched to the cases by year of birth and death. The adjusted odds ratios for prostate cancer death for those with higher magnesium levels in their drinking water, as compared to the lowest tertile, were 0.73 (95% CI = 0.51-1.03) and 0.64 (95% CI = 0.43-0.96), respectively. The adjusted odd ratios for the relationship between calcium levels in drinking water and prostate cancer were not statistically significant. The results of the present study show that there may be a significant protective effect of magnesium intake from drinking water and other dietary sources against the risk of prostate cancer development.

Female lung cancer mortality and sex ratios at birth near a petroleum refinery plant.

This study was conducted to assess whether female mortality from lung cancer is associated with residence in communities adjacent to a petroleum refinery plant and whether petroleum air pollution could affect the sex ratios of births. The Kaohsiung Refinery of the Chinese Petroleum Corp. is the oldest oil refinery in Taiwan and is located between the Tso-Ying and the Nan-Tzu municipalities. Standardized mortality ratios (SMRs) for female lung cancer and sex ratios of births were calculated for each municipality for the years 1971-1996. Cumulative-sum techniques were used to detect the occurrence of changes in the SMRs. The study results show that mortality from female lung cancer rose gradually about 30 to 37 years after the operation of a petroleum refinery plant began. However, the association between exposure to the petroleum air pollution and abnormal sex ratios at birth was not significant.

CP-101,606, an NR2B subunit selective NMDA receptor antagonist, inhibits NMDA and injury induced c-fos expression and cortical spreading depression in rodents.

(1S, 2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606) is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors containing the NR2B subunit. This compound was used to investigate the role of NR2B containing receptors in three responses to NMDA receptor activation in vivo. In mouse, CP-101,606 completely inhibited increases in fos-like immunoreactivity in dentate gyrus caused by a subconvulsant intraperitoneal dose of NMDA. In rat, the compound completely blocked cortical c-fos mRNA induction following focal injury in parietal cortex and the initiation and propagation of electrically induced cortical spreading depression. Inhibition of these responses by CP-101,606 indicates that c-fos induction and cortical spreading depression are dependent on activation of NMDA receptors containing the NR2B subunit. Since NMDA receptor dependent c-fos induction and cortical spreading depression may contribute to neuron loss after focal CNS injury, inhibition of these responses by CP-101,606 may contribute to the neuroprotective efficacy of the compound.

Antiparkinsonian actions of CP-101,606, an antagonist of NR2B subunit-containing N-methyl-d-aspartate receptors.

In the setting of nigrostriatal dopamine depletion, glutamatergic pathways to the striatum and basal ganglia output nuclei become overactive. Systemically administered glutamate receptor antagonists may have direct antiparkinsonian actions in rodents, but there is little evidence for this in primates. Glutamate antagonists may also potentiate conventional dopaminergic therapies; however, there is concern that broad spectrum, nonselective antagonists may have unwanted side-effects. Because subunit-selective antagonists may avoid these liabilities, we have examined the antiparkinsonian effects of a selective antagonist of the NR2B subunit of the NMDA receptor. In rats, CP-101,606 decreased haloperidol-induced catalepsy with an ED(50) of about 0.5 mg/kg. In MPTP-treated monkeys, CP-101,606 (1 mg/kg) reduced parkinsonian motor symptoms by 20%. At a dose of 0.05 mg/kg, CP-101,606 markedly potentiated the effect of a submaximal dose of levodopa, reducing motor symptoms by about 50% compared to vehicle and by about 30% compared to levodopa alone. No side-effects were apparent at any dose of CP-101,606. We conclude that CP-101,606 has direct antiparkinsonian actions in both rodents and monkeys and it synergistically potentiates levodopa in MPTP-treated monkeys. Clinical evaluation of selective NR2B antagonists may be warranted in Parkinson's disease.

Fluoride in drinking water and cancer mortality in Taiwan.

The possibility that cancer risk is associated with naturally fluoridated water in Taiwan is examined. The 1982-1991 age-adjusted mortality rates for cancer for 10 municipalities whose water supplies contained the highest naturally occurring fluoride concentrations in Taiwan were compared to those rates for 10 matched municipalities with unfluoridated water. The two groups had similar urbanization levels and sociodemographic characteristics. Our study does not support the suggestion that fluoridation of water supplies is associated with an increase in cancer mortality in Taiwan.

Chlorination of drinking water and sex ratio at birth in Taiwan.

Chlorination has been the major strategy for disinfecting drinking water in Taiwan. The objective of the present study was to determine whether the chlorination of drinking water was associated with abnormal sex ratios, an indicator of exposure to pollutants. A "chlorinating municipality" (CHM) was defined as one in which more than 90% of the municipality population was served with chlorinated water. A "nonchlorinating municipality" (NCHM) was one in which less than 5% of the municipality population was served with chlorinated water. The results of this study found no association between the use of chlorinated drinking water and abnormal sex ratios at birth in Taiwan. The imbibing of chlorinated water may not reflect contaminant exposure using sex ratio as a biomonitor.

Esophageal cancer mortality and total hardness levels in Taiwan's drinking water.

The possible association between the risk of esophageal cancer and hardness levels in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible esophageal cancer deaths (2084 cases) of Taiwan residents from 1987 through 1996 were compared with deaths from other causes (2084 controls), and the hardness levels of the drinking water used by these residents were determined. Data on water hardness throughout Taiwan have been collected from the Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes and the controls were pair-matched to the cases by sex, year of birth, and year of death. The results show that there is a 42% excess risk of mortality from esophageal cancer in relation to the use of soft water (adjusted odds ratio and 95% confidence intervals was 1.42 (1.22-1.66). This is an important finding for the Taiwan water industry and human health.