Development of Microfluidic Cell Culture Models of the Blood-Retinal Barriers

Tohoku University梶弘和課

Clinical significance of time to positivity for yeast in candidemia

PurposeCandidemia is an important issue of nosocomial bloodstream infections, and is associated with a high mortality rate. However, little information is available before final species identification, which takes days after the episode of candidemia. This study tried to determine whether time to positivity (TTP) for yeast helps in predicting the species of candidemia.MethodsA retrospective cohort study was conducted in Taiwan, which included 434 episodes of nonduplicated candidemia during the period between 2006 and 2009. The demographic features, clinical characteristics, TTP for yeast, and acute illness scores were included for analysis.ResultsThe mean age of patients with candidemia was 70.4 ± 15.2 years, and the 30-day crude mortality rate was 48.2%. Forty-five percent of patients suffered from shock status with a mean Acute Physiological and Chronic Health Evaluation II score of 27.0 ± 8.7 and a mean Sequential Organ Failure Assessment score of 9.7 ± 4.5, whereas 50% were admitted to the intensive care units. Candida albicans was still the most commonly identified pathogen (58.1%), followed by C. tropicalis (14.7%), C. parapsilosis (13.1%), and C. glabrata (8.3%). Results of multivariate logistic regression showed that TTP for yeast within 48 hours would more favor C. tropicalis (p = 0.044), and less favor C. glabrata (p = 0.025) and C. parapsilosis (p < 0.001). Patients with parenteral nutrition usage were more frequently associated with a TTP for yeast within 48 hours, whereas those with previous exposure to an antifungal agent had a longer TTP for yeast.ConclusionThe TTP for yeast might provide a hint of the responsible Candida species before final identification among critical patients with candidemia. The association between antifungal agents and TTP would need more evidence for elucidation

Mechanical punctate pain threshold is associated with headache frequency and phase in patients with migraine

Objective: Previous studies regarding the quantitative sensory testing are inconsistent in migraine. We hypothesized that the quantitative sensory testing results were influenced by headache frequency or migraine phase. Methods: This study recruited chronic and episodic migraine patients as well as healthy controls. Participants underwent quantitative sensory testing, including heat, cold, and mechanical punctate pain thresholds at the supraorbital area (V1 dermatome) and the forearm (T1 dermatome). Prospective headache diaries were used for headache frequency and migraine phase when quantitative sensory testing was performed. Results: Twenty-eight chronic migraine, 64 episodic migraine and 32 healthy controls completed the study. Significant higher mechanical punctate pain thresholds were found in episodic migraine but not chronic migraine when compared with healthy controls. The mechanical punctate pain thresholds decreased as headache frequency increased then nadired. In episodic migraine, mechanical punctate pain thresholds were highest (p<0.05) in those in the interictal phase and declined when approaching the ictal phase in both V1 and T1 dermatomes. Linear regression analyses showed that in those with episodic migraine, headache frequency and phase were independently associated with mechanical punctate pain thresholds and accounted for 29.7% and 38.9% of the variance in V1 (p¼0.003) and T1 (p<0.001) respectively. Of note, unlike mechanical punctate pain thresholds, our study did not demonstrate similar findings for heat pain thresholds and cold pain thresholds in migraine. Conclusion: Our study provides new insights into the dynamic changes of quantitative sensory testing, especially mechanical punctate pain thresholds in patients with migraine. Mechanical punctate pain thresholds vary depending on headache frequency and migraine phase, providing an explanation for the inconsistency across studies

Pain sensitivities predict prophylactic treatment outcomes of flunarizine in chronic migraine patients: A prospective study

Abstract Background We aimed to assess the differences in quantitative sensory testing between chronic migraine and healthy controls and to explore the association between pain sensitivities and outcomes in chronic migraine following preventive treatment. Methods In this prospective open-label study, preventive-naïve chronic migraine and healthy controls were recruited, and cold, heat, mechanical punctate, and pressure pain thresholds over the dermatomes of first branch of trigeminal nerve and first thoracic nerve were measured by quantitative sensory testing at baseline. Chronic migraines were treated with flunarizine and treatment response was defined as ≥50% reduction in the number of monthly headache days over the 12-week treatment period. Results Eighty-four chronic migraines and fifty age-and-sex-matched healthy controls were included in the analysis. The chronic migraine had higher cold pain thresholds over the dermatomes of the first branch of trigeminal nerve and the first thoracic nerve (p  158 g (p = 0.020) or heat pain threshold over the dermatome of the first branch of the trigeminal nerve > 44.9°C (p = 0.002) were more likely to be responders. Conclusions Chronic migraine were generally more sensitive compared to healthy controls. Preventive treatment with flunarizine should be recommended particularly for chronic migraine who have relatively normal sensitivity to mechanical punctate or heat pain. Trial registration: This study was registered on ClinicalTrials.gov (Identifier: NCT02747940)

Non-prompt surgery for patients with acute type A aortic dissection without pre-operative shock and malperfusion

BackgroundAcute type A aortic dissection (ATAAD) requires urgent surgical treatment. However, during daily practice, there were some patients with ATAAD sought for medical attention several days after symptoms occurred and some other patients hesitated to receive aortic surgery after the diagnosis of ATAAD was made. This study aims to investigate the surgical outcomes of non-prompt aortic surgery (delayed diagnosis caused by the patient or delayed surgery despite immediate diagnosis) for ATAAD patients.MethodsFrom November 2004 to June 2020, of more than 200 patients with ATAAD patients who underwent aortic surgery at our hospital, there were 30 patients without pre-operative shock and malperfusion who sought for medical attention with symptoms for several days or delayed aortic surgery several days later despite ATAAD was diagnosed. Of the 30 patients (median age 60.9, range 33.4~82.5 years) in the study group, there were 18 patients undergoing surgery when they arrived at our hospital (delayed diagnosis by the patient) and 12 patients receiving surgery days later (delayed surgery despite immediate diagnosis). Patients with prompt surgery after symptom onset (control group) were matched from our database by propensity score matching. The surgical mortality rate and post-operative morbidities were compared between the study group and control group.ResultsThe in-hospital mortality was 3.3% for the study group and 6.7% for the control group (p = non-significant). The incidence of post-operative cerebral permanent neurological defect was 0% for the study group and 13.3% for the control group (p = 0.112). There were three patients receiving aortic re-intervention or re-do aortic surgery during follow-up for the study group and two patients for the control group.ConclusionPrompt surgery for ATAAD is usually a good choice if everything is well prepared. Besides, urgent but non-prompt aortic surgery could also provide acceptable surgical results for ATAAD patients without pre-operative shock and malperfusion who did not seek medical attention or who could not make their minds to undergo surgery immediately after symptom onset. Hospitalization with intensive care is very important for pre-operative preparation and monitoring for the patients who decline prompt aortic surgery

Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis

<p>Abstract</p> <p>Background</p> <p>Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos.</p> <p>Results</p> <p>We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes.</p> <p>Conclusion</p> <p>The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through polymerase chain reaction experiments. SpecificDB provides comprehensive information and a user-friendly interface.</p

Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis

<p>Abstract</p> <p>Background</p> <p>Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos.</p> <p>Results</p> <p>We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes.</p> <p>Conclusion</p> <p>The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through polymerase chain reaction experiments. SpecificDB provides comprehensive information and a user-friendly interface.</p

Acute Q Fever and Scrub Typhus, Southern Taiwan

Acute Q fever and scrub typhus are zoonoses endemic to southern Taiwan. Among the 137 patients with acute Q fever (89, 65.0%) or scrub typhus (43, 31.4%), we identified 5 patients (3.6%) who were co-infected with Coxiella burnetii and Orientia tsutsugamushi