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.

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.

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.

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.

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.

Manganese exposure to PC-12 cells alters triacylglycerol metabolism and promotes neurite outgrowth.

Exposure of PC-12 cells to MnCl2 (10-100 microM for 1 to 3 days) resulted in both morphological and metabolic changes as indicated by promotion of neurite outgrowth and an increased incorporation of labeled fatty acids (14:0, 18:1 and 20:4) into triacylglycerols (TG). Cells prelabeled with [14C]arachidonic acid (AA) showed a time-dependent decrease in labeled TG, and the rate of decline was inhibited by Mn (100 microM). In the pulse-chase type of study, the decrease in the proportion of labeled TG as well as labeled phosphatidylcholine (PC) was marked by an increase in labeled phosphatidylinositol and phosphatidylethanolamine. These results support previous notion that TG plays an important role in channeling the fatty acid nutrients for biosynthesis of membrane phospholipids. Thus, the Mn-induced inhibition of the ability to transfer TG fatty acids to other lipids in PC-12 cells may be an underlying cause for the observed morphological changes.

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.

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.

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.

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.

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

The possible association between the risk of pancreatic cancer mortality and hardness levels in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible pancreatic cancer deaths (883 cases) of Taiwan residents from 1990 through 1994 were compared with deaths from other causes (883 controls), and the hardness levels of the drinking water used by these residents were determined. Data on water hardness throughout Taiwan was collected from Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes and were pair matched to the cancer cases by sex, year of birth, and year of death. The results show that there is a 39 % excess risk of mortality from pancreatic cancer in relation to the use of soft water. Trend analyses showed an increasing odds ratio for pancreatic cancer with decreasing levels of hardness in drinking water. This is an important finding for the Taiwan water industry and human health.

Effects of indoor environmental factors on risk for acute otitis media in a subtropical area.

The objective of this study was to examine the relationship between indoor environmental factors and acute otitis media in a subtropical area. A case-control study was performed using participants from a prevalence survey that included 219 school children with acute otitis media and 219 age- and gender-matched controls. The study was confined to 4164 primary school children aged 6-12 yr attending 8 primary schools in Kaohsiung rural municipalities who participated in a prevalence study of the health effects of an indoor environment. An acute otitis media case was defined as a child with acute symptoms (presenting with earache, fever, irritability, and/or discharge from the ear) diagnosed by a physician in the previous year. Controls selected from the same school did not have chronic or acute respiratory illness or an ear-related illness during the same period. Information regarding the home environment was obtained using a structured written questionnaire, completed by the parents of the children. Of the many indoor environmental factors included in this study, only living in a home with indications of dampness (mold, flooding, home dampness) showed an association with acute otitis media. It was concluded that dampness in the home is a new public health issue in subtropical areas.

Epidemiology of swine toxoplasmosis in Taiwan.

From July 1987 to June 1988, serum samples from 3,880 pigs from eight geographic locations in Taiwan were examined for Toxoplasma gondii antibodies using the latex agglutination test (LA test) and IgM-enzyme-linked immunosorbent assay (IgM-ELISA). A total of 1,073 samples (27.65%) were positive by the LA test. The percentage of positive reactions varied by location as follows: Taoyuan 44.44% (128/288), Taichung 27.60% (183/663), Tainan 22.28% (119/534), Kaohsiung 19.60% (98/500), Pingtung 17.92% (86/480), Hualien 33.95% (163/480), Ilan 31.66% (152/480), Taitung 31.64% (144/455). In the IgM-ELISA 1,828 of 3,880 samples (47.11%) were positive and the distribution of positive reactions were: Taoyuan 59.02% (170/288), Taichung 53.69% (356/663), Tainan 52.24% (279/534), Kaohsiung 54.60% (273/500), Pingtung 18.95% (91/480), Ilan 47.50% (228/480), Hualien 42.70% (205/480), Taitung 49.67% (226/455). On one farm, 20 of 120 sows experienced abortion and stillbirths due to Toxoplasma gondii. Lesions and T. gondii were found in lungs, liver, kidneys, heart, and placenta of one of the aborted fetuses.

Female lung cancer and petrochemical air pollution in Taiwan.

To investigate the relationship between petrochemical air pollution and female lung cancer, we conducted a matched case-control study among women who had died in Taiwan from 1990 through 1994. Data about all eligible female lung cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group included women who died from nonneoplasms and diseases that were not associated with respiratory problems. We pair-matched the controls to the cases by sex, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. We used the proportion of a municipality's total population employed in the petrochemical manufacturing industry as an indicator of a resident's exposure to air emissions from the petrochemical manufacturing industry. The subjects were divided into tertiles according to the above indicator. Women who lived in the 2 groups of municipalities characterized by higher levels of petrochemical pollution had a statistically significant higher risk of developing lung cancer than the group that lived in municipalities with the lowest petrochemical air pollution levels (after controlling for possible confounders). The linear trend was also statistically significant (p < .05). The results of this study shed important light on the relationship between the Taiwan petrochemical industry and the resulting risk to human health.

Magnesium in drinking water and the risk of death from diabetes mellitus.

This report examines whether magnesium in drinking water is protective against the probability of dying from diabetes mellitus. All eligible deaths from diabetes (6781 cases) of Taiwan residents from 1990 through 1994 were compared with deaths from other causes (6781 controls), and the levels of magnesium in the drinking water of these residents was determined. Data on magnesium levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation (TWSC). Controls were pair matched to the cases by sex, year of birth, and year of death. The results of the present study show that there seems to be a significant protective effect of magnesium intake from drinking water on the risk of dying from diabetes mellitus. This is an important finding for the Taiwan water industry and human health.

Histopathological survey of protozoa, helminths and acarids of imported and local psittacine and passerine birds in Japan.

A total of 534 psittacine and passerine birds consisting of 241 imported and 293 local birds were examined histologically. As a result, the following parasites were found: Giardia (86 cases), Knemido-coptes (26 cases), coccidia (10 cases), Ascaridia (6 cases), Cryptosporidium (5 cases), Sarcocystis (5 cases), tapeworm (4 cases), microfilaria (2 cases), Hexamita (1 case), and Spiroptera (1 case). High incidences of giardiasis and knemido-coptic infestation were detected in the local birds, but rarely in the imported birds. Giardial trophozoites were observed mainly in the duodenum of budgerigars (Melopsittacus undulatus). Knemidocoptic mites burrowed into the epidermis producing proliferative dermatitis in 25 budgerigars and 1 African Grey Parrot (Psittacus erithacus erithacus). This ectoparasite often infested the skin around the cloaca. Coccidiosis was seen only in the small intestines of the finch (Poephila gouldiae gouldiae), African Grey Parrot, Rainbow lory (Trichoglossus haematodus), Indian Ring-necked parakeet (Psittacula krameri manillensis) and peach-faced lovebird (Agapornis roseicollis). Two parrots (Amazona aestiva aestiva and Psittacus erithacus erithacus) and two budgerigars had intestinal cryptosporidiosis. Conjunctivitis associated with cryptosporidial infection was seen in a lovebird. Sarcocystis cysts containing crescent-shaped bradyzoites were found not only in the thigh and breast but also in the heart and cloacal muscles. Other organisms such as Ascaridia, tapeworm, microfilaria, Hexamita, and Spiroptera were clinically less significant. However, infections such as Giardia and Cryptosporidim might have zoonotic implications.

Catarrhal proventriculitis associated with a filamentous organism in pet birds.

Catarrhal proventriculitis due to infection by an unidentified organism was diagnosed in 79 of 534 pet birds examined histologically. It was more prevalent in domestic birds (70 cases) than in imported ones (9 cases). A high incidence of the disease was encountered in budgerigars (Melopsittacus undulatus) and it was occasionally found in finches (Poephila gouldiae gouldiae), parakeets (Psittacula Krameri manillensis), Amazona parrots (Amazona aestiva aestiva) and cockatiels (Nymphicus hollandicus). The agent was a large filamentous rod, and was stained positively with Gram, GMS and PAS methods. Histologically, it induced a mild to moderate exudative or proliferative inflammation in the proventriculus. All the cases had an erosion in the gizzard. Ultrastructurally, the organism had a eukaryotic nucleus and three cell-wall layers. Concurrent infections were very common, including adenoviruses (37 cases), giardiasis (31 cases), candidiasis (13 cases), papovaviruses (11 cases) and knemidocoptic mites (11 cases).