Microdroplet-Enabled Co-Cultivation and Characterization of Microbial Communities.

The majority of existing microbial species, in particular bacteria living in synergistic communities, have not been cultured in the laboratory. One important reason behind this unculturability" is that conventional laboratory cultivation is aimed at pure cultures of individual species. The objective of this dissertation is to develop micro uidic co-cultivation platforms to expand the repertoire of cultivable species from natural microbial communities and to characterize co-cultivated communities. We first aimed to make use of highly parallel micro-droplets to co-cultivate symbiotic microbial communities. We fabricated a micro uidic device that could readily encapsulate and co-cultivate subsets of a community, using aqueous droplets dispersed in a continuous oil phase. To demonstrate the effectiveness of this approach in discovering synergistic interactions among microbes, we tested it with a synthetic model system consisting of cross-feeding E. coli mutants. This technology is being extended and applied to the investigation of drug-producing natural microbiota isolated from tunicates. We next combined droplet co-cultivation with oxygen gradient generation to provide both the optimal oxygen concentration and the environment for microbial interx actions. Our device was composed of two glass layers with uid channels separated by a 50-m-thick PDMS membrane. A linear oxygen gradient established in the gas channel was successfully transferred to droplets in the liquid channel. A murine fecal microbial sample, of which the bacteria lived with limited oxygen concentration in their native environment, was cultivated and different species were enriched in chambers featuring different oxygen conditions. To further parallelize and automate the droplet-enabled co-cultivation technology, we have also developed a simple and robust method for incubation of millions of droplets using a microcentrifuge tube, and have combined it with a micro uidic device for automated droplet sorting. Automated sorting is performed hydrodynamically based on analysis of uorescent droplet images representing cell density after cultivation. This dissertation demonstrates that droplet-enabled co-cultivation can effectively decompose complex microbial communities into subsets of symbiotic members and thus facilitate the elucidation of underlying microbial interactions. In addition, automated droplet sorting can be exploited for engineering purposes such as ultrahighthroughput screening of microbial strain libraries.Ph.D.Chemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91564/1/pjhyang_1.pd

Relationships between 24-Hour Blood Pressures, Subcortical Ischemic Lesions, and Cognitive Impairment

Background and Purpose The most important treatment for subcortical vascular dementia (SVaD) is controlling the blood pressure (BP). However, the few studies that have investigated the relationships between diurnal BP rhythm and subcortical ischemic vascular cognitive impairment have produced inconclusive results. In the study presented here, the 24-hour BP values of three groups of subjects-patients with subcortical vascular mild cognitive impairment (SvMCI), patients with SVaD, and normal controls-were compared using working criteria and 24-hour ambulatory BP (ABP) monitoring. Methods The subjects (42 patients with SVaD, 37 patients with SvMCI, and 30 controls) were selected according to the Study`s inclusion/exclusion criteria. All subjects underwent brain magnetic resonance (MR) imaging and MR angiography, detailed neuropsychological testing, and 24-hour ABP monitoring. Results The prevalence of nondippers differed markedly between the control group and both the SVaD and SvMCI groups. Loss of nocturnal dipping was significantly associated with SVaD [odds ratio (OR), 4.827; 95% confidence interval (CI), 1.07-12.05]. Conclusions It was found that SVaD is associated with loss of nocturnal BP dipping combined with increased pulse pressure and systolic BP (SBP) variability. Correction of these factors could therefore be important in the prevention of SVaD, independent of measures used to reduce BP. J Clin Neurol 2009;5:139-145Ohmine T, 2008, HYPERTENS RES, V31, P75van Boxtel MPJ, 2006, J HUM HYPERTENS, V20, P5, DOI 10.1038/sj.jhh.1001934van der Flier WM, 2005, STROKE, V36, P2116Birns J, 2005, STROKE, V36, P1308, DOI 10.1161/01.STR.0000165901.38039.5fYamamoto Y, 2005, CEREBROVASC DIS, V19, P302, DOI 10.1159/000084498BOWLER JV, 2005, J NEUROL NEUROSUR S5, V76, P35KU HM, 2004, J KOREAN NEUROPSYCHI, V43, P189O`Brien E, 2003, J HYPERTENS, V21, P821, DOI 10.1097/01.hjh.0000059016.82022.caKANG Y, 2003, INCHEON HUMAN BRAINOhkubo T, 2002, J HYPERTENS, V20, P2183de Leeuw FE, 2002, BRAIN, V125, P765O`Brien JT, 2002, ANN NY ACAD SCI, V977, P436Kario K, 2001, HYPERTENSION, V38, P852Wahlund LO, 2001, STROKE, V32, P1318Dufouil C, 2001, NEUROLOGY, V56, P921Puisieux F, 2001, EUR NEUROL, V46, P115Staessen JA, 1999, JAMA-J AM MED ASSOC, V282, P539Swan GE, 1998, NEUROLOGY, V51, P986Blacher J, 1998, HYPERTENSION, V32, P570Cummings JL, 1998, J PSYCHOSOM RES, V44, P627Kilander L, 1998, HYPERTENSION, V31, P780Guo ZC, 1997, AM J EPIDEMIOL, V145, P1106Liao DP, 1996, STROKE, V27, P2262LAUNER LJ, 1995, JAMA-J AM MED ASSOC, V274, P1846YAMAMOTO Y, 1995, STROKE, V26, P829VERDECCHIA P, 1994, HYPERTENSION, V24, P793KUUSISTO J, 1993, HYPERTENSION, V22, P771SHIMADA K, 1992, J HYPERTENS, V10, P875SCHERR PA, 1991, AM J EPIDEMIOL, V134, P1303TOHGI H, 1991, STROKE, V22, P603OBRIEN E, 1988, LANCET, V2, P397PARATI G, 1987, J HYPERTENS, V5, P93HACHINSKI VC, 1975, ARCH NEUROL-CHICAGO, V32, P632

Combined Effects of Surface Morphology and Mechanical Straining Magnitudes on the Differentiation of Mesenchymal Stem Cells without Using Biochemical Reagents

Existing studies examining the control of mesenchymal stem cell (MSC) differentiation into desired cell types have used a variety of biochemical reagents such as growth factors despite possible side effects. Recently, the roles of biomimetic microphysical environments have drawn much attention in this field. We studied MSC differentiation and changes in gene expression in relation to osteoblast-like cell and smooth muscle-like cell type resulting from various microphysical environments, including differing magnitudes of tensile strain and substrate geometries for 8 days. In addition, we also investigated the residual effects of those selected microphysical environment factors on the differentiation by ceasing those factors for 3 days. The results of this study showed the effects of the strain magnitudes and surface geometries. However, the genes which are related to the same cell type showed different responses depending on the changes in strain magnitude and surface geometry. Also, different responses were observed three days after the straining was stopped. These data confirm that controlling microenvironments so that they mimic those in vivo contributes to the differentiation of MSCs into specific cell types. And duration of straining engagement was also found to play important roles along with surface geometry

A Case of Nephrogenic Diabetes Insipidus with a Rare X-linked Recessive Mutation in an Infant with Developmental and Growth Retardation Tracked by the Korean National Health Screening Program

Nephrogenic diabetes insipidus (DI) is a rare disease in which the patient cannot concentrate urine despite appropriate or high secretion of antidiuretic hormone. Congenital nephrogenic DI is caused by the arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2) gene mutation; the AVPR2 genetic mutation accounts for 90% of the cases. National health screening for infants and children was launched in 2007 in order to prevent accidents and promote public health in infants and children in Korea. The program has been widely used as a primary clinical service in Korea. We treated an infant with faltering growth and delayed development detected by the National health screening program, and diagnosed the problem as nephrogenic DI caused by a rare missense mutation of c.490T>C on the AVPR2 gene. This case can be a good educational nephrogenic DI with a rare AVPR2 mutation, which was well screened and traced by the national health screening program for infants and children in Korea

Liquid crystal display using combined fringe and in-plane electric fields

A high performance liquid crystal display using combined fringe and in-plane horizontal electric fields is proposed. The strong electric fields cause more liquid crystals to reorient almost in plane above and between the pixel electrodes. As a result, the operation voltage is lower and transmittance is higher than those of fringe field switching and in-plane switching modes, while preserving a wide viewing angle. Such a high performance device is particularly attractive for large panel liquid crystal displays

Obsessive-Compulsive Behavior Disappearing after Left Capsular Genu Infarction

This case report describes a 74-year-old woman with obsessive-compulsive behaviors that disappeared following a left capsular genu infarction. The patient's capsular genu infarction likely resulted in thalamocortical disconnection in the cortico-basal ganglia-thalamocortical loop, which may have caused the disappearance of her obsessive-compulsive symptoms. The fact that anterior capsulotomy has been demonstrated to be effective for treating refractory obsessive-compulsive disorder further supports this hypothesis

Regional outbreak of staphylococcal scalded skin syndrome in healthy children

Purpose : Staphylococcal scalded skin syndrome (SSSS) is a relatively uncommon superficial blistering skin disease that is due to Staphylococcus aureus. We had experienced a regional outbreak of SSSS over 3 years in healthy children. Methods : We retrospectively reviewed the medical records of those patients diagnosed as SSSS. Most of neonatal cases were nosocomial infections and excluded from the analysis. The clinical features, laboratory findings, the isolation and antibiotic resistance of S. aureus, the antibiotic management and other supportive treatments were analyzed. Results : Fifty-five patients with SSSS were admitted to our hospital from October 2001 to September 2004. The median age of patients was 3.0 years. Of the 55 patients, 9 were the generalized type, 13 were the intermediate type and 33 were the scarletiniform rash. All the patients were living in neighborhood of the Jinju area. S. aureus were isolated from 9 of the patients and all of the isolated S. aureus were methicillin resistant. All the patients except two were treated with intravenous flocloxacillin or nafcillin and/or cefotaxime. All the patients recovered during the follow-up period of 2 to 3 weeks. Conclusion : We experienced a regional outbreak of SSSS in previous healthy children. Further study for finding the carriers of S. aureus caused SSSS and preventing the spread of this disease is needed. Additionally, guidelines for treating SSSS due to methicillin resistant S. aureus should be established

Signal change in hippocampus and current source of spikes in Panayiotopoulos syndrome

A 4-year-old girl with Panayiotopoulos syndrome presented with a history of 4 prolonged autonomic seizures. The clinical features of her seizures included, in order of occurrence, blank staring, pallor, vomiting, hemi-clonic movement on the right side, and unresponsiveness. A brain magnetic resonance imaging (MRI) showed a slightly high T2 signal in the left hippocampus. Interictal electoencephalogram revealed spikes in the occipital area of the left hemisphere. We analyzed the current-source distribution of the spikes to examine the relationship between the current source and the high T2 signal. The current source of the occipital spikes was not only distributed in the occipital area of both cerebral hemispheres, but also extended to the posterior temporal area of the left hemisphere. These findings suggest that the left temporal lobe may be one of the hyperexcitable areas and form part of the epileptogenic area in this patient. We hypothesized that the high T2 signal in the left hippocampus of our patient may not have been an incidental lesion, but instead may be related to the underlying electroclinical diagnosis of Panayiotopoulos syndrome, and particularly seizure. This notion is important because an abnormal T2 signal in the hippocampus may represent an acute stage of hippocampal injury, although there is no previous report of hippocampal pathology in Panayiotopoulos syndrome. Therefore, long-term observation and serial follow-up MRIs may be needed to confirm the clinical significance of the T2 signal change in the hippocampus of this patient

Factors associated with mumps meningitis and the possible impact of vaccination

PurposeMumps meningitis is a common complication of mumps infection; however, information on mumps meningitis in the postvaccine era is limited. The purpose of the present study was to determine factors associated with mumps meningitis and to discuss the effect of vaccination on this disease.MethodsWe retrospectively reviewed patients younger than 19 years with mumps, diagnosed at a university hospital in Korea between 2003 and 2013. Patients were divided into groups with and without meningitis, and the clinical features of the 2 groups were compared.ResultsThe study enrolled 119 patients: 19 patients with meningitis and 100 patients without. Univariate analysis showed that older age (median: 15 years vs. 9.5 years, respectively), a longer interval from last vaccination (median: 10.2 years vs. 4.8 years, respectively), and febrile presentation (94.7% vs. 31.0%, respectively) were significantly associated with mumps meningitis. Sex, number of vaccination doses, bilateral parotitis, and the presence of complications other than meningitis did not differ between the 2 groups. In multivariate logistic regression analysis, age (odds ratio, 1.38; 95% confidence interval, 1.01–1.89; P=0.04) and fever (odds ratio, 30.46; 95% confidence interval, 3.27–283.61; P<0.01) remained independent factors for mumps meningitis.ConclusionClinicians in the postvaccine era should be aware of the possibility of mumps meningitis in febrile cases of mumps in adolescents, regardless of the number of vaccination doses. To establish the role of vaccination in mumps meningitis, further studies will be necessary

Successful treatment by exchange transfusion of a young infant with sodium nitroprusside poisoning

Although sodium nitroprusside (SNP) is often used in pediatric intensive care units, cyanide toxicity can occur after SNP treatment. To treat SNP-induced cyanide poisoning, antidotes such as amyl nitrite, sodium nitrite, sodium thiosulfate, and hydroxycobalamin should be administered immediately after diagnosis. Here, we report the first case of a very young infant whose SNP-induced cyanide poisoning was successfully treated by exchange transfusion. The success of this alternative method may be related to the fact that exchange transfusion not only removes the cyanide from the blood but also activates detoxification systems by supplying sulfur-rich plasma. Moreover, exchange transfusion replaces cyanide-contaminated erythrocytes with fresh erythrocytes, thereby improving the blood's oxygen carrying capacity more rapidly than antidote therapy. Therefore, we believe that exchange transfusion might be an effective therapeutic modality for critical cases of cyanide poisoning