Methods for preventing middle ear barotrauma in computer-controlled pressurization of monoplace hyperbaric chambers.

Middle ear barotrauma (MEB), one of the side effects of hyperbaric oxygen (HBO2) therapy, sometimes cannot be directly diagnosed during the therapy itself. Instead, its incidence and degree are judged based on subjective statements made by patients when in conversation with medical staff regarding how they feel. To prevent MEB in practice, it is proposed that the tympanic membrane evaluation system and automatic control chamber developed in a previous study be applied as part of a prevention algorithm [16]. The proposed algorithm, which determines and equalizes the unbalanced pressure of a subject based on their tympanic admittance, was evaluated in conjunction with conventional HBO2 therapy in an experiment involving 100 subjects. Among the 50 subjects in the control group who received HBO2 therapy 16 subjects experienced MEB. In contrast, the experimental group of 50 subjects were treated with a hyperbaric chamber protocol incorporating the automatic control system and proposed algorithm. At the conclusion of the treatment, no subjects exhibited middle ear barotrauma. In the case of the control group, while the target pressure was achieved, middle ear barotrauma still occurred. However, in the case of the experimental group, the pressure inside the chamber was adjusted as per the algorithm, which allowed the target pressure for every subject to be achieved without experiencing MEB. When a particular subject was unable to perform any pressure equalization method such as swallowing or the Valsalva maneuver, the chamber was not pressurized based on the tympanic admittance and thus no MEB occurred.

An anti-barotrauma system for preventing barotrauma during hyperbaric oxygen therapy.

In the present study, a tympanometry-based anti-barotrauma (ABT) device was designed using eardrum admittance measurements to develop an objective method of preventing barotrauma that occurs during hyperbaric oxygen (HBO2) therapy. The middle ear space requires active equalization, and barotrauma of these tissues during HBO2therapy constitutes the most common treatment-associated injury. Decongestant nasal sprays and nasal steroids are used, but their efficacy is questionable to prevent middle ear barotrauma (MEB) during HBO2 treatment. Accordingly, a tympanometry-based ABT device was designed using eardrum admittance measurements to develop an objective method for preventing MEB, which causes pain and injury, and represents one of the principal reasons for patients to stop treatment. This study was conducted to test a novel technology that can be used to measure transmembrane pressures, and provide chamber attendants with real-time feedback regarding the patient's equalization status prior to the onset of pain or injury. Eardrum admittance values were measured according to pressure changes inside a hyperbaric oxygen chamber while the system was fitted to the subject. When the pressure increased to above 200 daPa, eardrum admittance decreased to 16.255% of prepressurization levels. After pressure equalization was achieved, eardrum admittance recovered to 95.595% of prepressurization levels. A one-way repeated measures analysis of variance contrast test was performed on eardrum admittance before pressurization versus during pressurization, and before pressurization versus after pressure equalization. The analysis revealed significant differences at all points during pressurization (P⟨0.001), but no significant difference after pressure equalization was achieved. This ABT device can provide objective feedback reflecting eardrum condition to the patient and the chamber operator during HBO2 therapy.

Association analysis of PDE4B polymorphisms with schizophrenia and smooth pursuit eye movement abnormality in a Korean population.

Schizophrenia is a debilitating mental disorder with a high heritability rate. Located on chromosome 1p31.3, the human cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B) gene has been considered as an important candidate gene for the risk of schizophrenia. Several genetic association studies reported the association between PDE4B polymorphisms and the risk of schizophrenia in Caucasian, African American, Indian, and Japanese populations. The aim of this study is to examine the association of PDE4B variations with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. A case-control association analysis was carried out by comparing the genotype distribution of eight PDE4B polymorphisms between 457 schizophrenia patients and 386 normal healthy subjects. Differences in the frequency distribution of PDE4B single nucleotide polymorphisms (SNPs) and haplotypes were analyzed by logistic regression analyses controlling for age as a covariate. Statistical analyses revealed nominal significant associations of rs1040716, rs472952, rs1321177, and rs2144719 with the risk of schizophrenia (p = 0.02~0.05). The rs11208756 polymorphism showed a nominal significant association with SPEM abnormality (p = 0.05). In a meta-analysis with Japanese and Korean populations, three SNPs (rs472952, rs1040716, and rs2180335) revealed significant associations with schizophrenia (meta-p value = 0.0038~0.019). Our results support previously reported association of PDE4B variations with schizophrenia in other populations. The findings in this study add a new evidence for the involvement of PDE4B gene in schizophrenia etiology.

Lack of association of the RTN4R genetic variations with risk of schizophrenia and SPEM abnormality in a Korean population.

This study examined the association of the reticulon 4 receptor (RTN4R) gene with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Although we failed to provide convincing evidence that RTN4R is associated with schizophrenia development and SPEM impairment, our findings may be useful for further genetic studies.

Association of RANBP1 haplotype with smooth pursuit eye movement abnormality.

Schizophrenia is a multifactorial disorder and smooth pursuit eye movement (SPEM) disturbance is proposed as one of the most consistent neurophysiological endophenotype in schizophrenia. The aim of this study was to examine the genetic association of RANBP1 polymorphisms with the risk of schizophrenia and with the risk of SPEM abnormality in schizophrenia patients in a Korean population. Two SNPs of RANBP1 were genotyped by TaqMan assay. Their genetic effect of single/haplotype polymorphisms on the risk of schizophrenia and SPEM abnormality from 354 patients and 396 controls were performed using χ² and multiple regression analyses. Although no RANBP1 polymorphisms were associated with the risk of schizophrenia, a common haplotype, RANBP1-ht2 (rs2238798G-rs175162T), showed significant association with the risk of SPEM abnormality among schizophrenia patients after multiple correction (P(corr) = 0.002-0.0003). The results of present study provide the evidence that RANBP1 on 22q11.21 locus might be causally related to the SPEM abnormality rather than the development of schizophrenia.

Association of ZDHHC8 polymorphisms with smooth pursuit eye movement abnormality.

The zinc finger DHHC domain-containing protein 8 (ZDHHC8) is located in the 22q11 microdeletion region and may contribute to the behavioral deficit associated with 22q11 deletion syndrome. Although polymorphisms of ZDHHC8 have been reported to be associated with the risk of schizophrenia, those associations are still controversial. This study was performed to validate the genetic association of ZDHHC8 polymorphisms with the risk of schizophrenia, and also to scrutinize the association with smooth pursuit eye movement (SPEM) abnormality in a Korean population. Five SNPs of ZDHHC8 were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using allele-based chi(2) analyses. Association of ZDHHC8 polymorphisms with SPEM abnormality among 166 schizophrenic patients were analyzed using multiple regressions. No ZDHHC8 polymorphisms were found to be associated with the risk of schizophrenia. However, four SNPs and one haplotype (ht4) were strongly associated with the risk of SPEM abnormality even after multiple correction (P = 0.00005-0.0007, P(corr) = 0.0001-0.002). The results of the present study provide the first evidence that ZDHHC8 on the 22q11 locus might have influence on SPEM function of schizophrenia patients in a Korean population and may provide a new clue for understanding differential effects of candidate genes in schizophrenia.

Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality.

Schizophrenia is a multifactorial disorder characterized by the contribution of multiple susceptibility genes that may act in conjunction with epigenetic processes and environmental factors. The catechol-O-methyltransferase (COMT) gene, which is located in the 22q11 microdeletion, has been considered as a candidate gene for schizophrenia because of its ability to degrade catecholamines, including dopamine. In a genetic analysis, neurophysiological endophenotype in schizophrenia, such as smooth pursuit eye movement (SPEM) disturbance, is considered to be a good trait marker, because it may be under more direct genetic control. This study was performed to examine the genetic association of COMT polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population. Six single-nucleotide polymorphisms of COMT were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using chi(2) analyses. Among the schizophrenic patients, 166 subjects were selected for association analyses of COMT polymorphisms with SPEM abnormality. From the six COMT polymorphisms, rs6267 showed an association with the reduced risk of schizophrenia after correction (P(corr) = 0.02). In analysis of SPEM abnormality, no significant associations were detected with COMT polymorphisms. The results of the present study provide the evidence that in a Korean population, COMT on the 22q11 locus is likely involved in the development of schizophrenia, but not in the SPEM function abnormality.

Investigating the potential genetic association between RANBP9 polymorphisms and the risk of schizophrenia.

Schizophrenia is a serious mental disorder that is affected by genetic and environmental factors. As the disease has a high heritability rate, genetic studies identifying candidate genes for schizophrenia have been conducted in various populations. The gene for human Ran­binding protein 9 (RANBP9) is a newly discovered candidate gene for schizophrenia. As RANBP9 is a small guanosine­5'­triphosphate­binding protein that interacts with the disrupted in schizophrenia 1 protein, it is considered to be an important molecule in the pathogenesis of schizophrenia. However, to date, no study has examined the possible association between the genetic variations of RANBP9 and the risk of schizophrenia. In the present study, it was hypothesized that RANBP9 variations may influence the risk of schizophrenia. In order to investigate the association between RANBP9 polymorphisms and the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, a case­control association analysis was performed. Using a TaqMan assay, five single­nucleotide polymorphisms and an insertion/deletion variation within the start codon region of RANBP9 were genotyped. Five major haplotypes were identified in 449 patients with schizophrenia and 393 unrelated healthy individuals as controls (total, n=842). However, the association analyses revealed no associations between all genetic variants and schizophrenia and SPEM abnormality. To the best of our knowledge, this is the first study to investigate an association between RANBP9 polymorphisms and schizophrenia and SPEM abnormality. The findings of allele frequencies and association results in this study may aid in further genetic etiological studies in schizophrenia in various populations.

Development and evaluation of a multi-frequency bioelectrical impedance analysis analyzer for estimating acupoint composition.

The purpose of this study was to suggest a new method of estimating acupoint compositions by using a multi-frequency bioelectrical impedance analysis (MF-BIA) method at 5 kHz, 50 kHz and 200 kHz within 2 cm of acupoints divided into local segments. To verify the system developed, we confirmed the stable occurrence of a constant current at every frequency, regardless of the impedance connected to the electrodes. Moreover, we found left and right distal bicep brachii aponeurosis to be identical by using ultrasound imaging, and we analyzed the repeatability of the findings by making 10 consecutive sets of measurements (p > 0.05). To evaluate the practical use of the acupoint composition, we used the MF-BIA analyzer to measure the left and right LU3, LU4, and LU9 at the lung meridian. We confirmed that the potentials generated were equal to the changes in the cell membrane function, which were caused by the applied frequency (p < 0.01). We also verified that the MF-BIA analyzer measurements corresponded to the acupoint components by comparing the left and right potentials generated (p > 0.05). Hence, we conclude that the MF-BIA analyzer can be used to estimate the acupoint composition based on the acupoint state.

Use of pupil size to determine the effect of electromagnetic acupuncture on activation level of the autonomic nervous system.

Magnetic fields are widely considered as a method of treatment to increase the therapeutic effect when applied to acupoints. Hence, this study proposes a new method which creates significant stimulation of acupoints by using weak magnetic fields. We conducted this experiment in order to confirm the effect on the activation level of the autonomic nervous system by measuring pupil sizes in cases of stimulation by using manual acupuncture and electromagnetic acupuncture (EMA) at BL15. We selected 30 Hz of biphasic wave form with 570.1 Gauss. To confirm the biopotential by the magnetic flux density occurring in EMA that affected the activation of the autonomic nervous system, we observed the biopotential induced at the upper and the mid left and right trapezius. We observed a significant decrease in pupil size only in the EMA group (p < 0.05), thus confirming that EMA decreased the pupil size through activation of the parasympathetic nerve in the autonomic nervous system. Moreover, we confirmed that the amplitude of the biopotential which was caused by 570.1 Gauss was higher than ±20 µA. Thus, we can conclude that EMA treatment successfully activates the parasympathetic nerve in the autonomic nervous system by inducing a biotransformation by the induced biopotential.

Genetic association analysis of CNR1 and CNR2 polymorphisms with schizophrenia in a Korean population.

Located on 6q15 and 1p36.11, cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) genes are considered to be a positional and functional candidate gene for the development of mental disorders such as schizophrenia because CNR1 is known as a regulator of dopamine signaling in the hippocampus and the cerebral cortex. However, few genetic studies have been carried out to investigate an association of CNR1 and CNR2 polymorphisms and the risk of schizophrenia. In this study, although the result indicates that CNR1 and CNR2 variations are unlikely to influence schizophrenia susceptibility in a Korean population, the findings would provide meaningful information for further genetic studies.

Development and evaluation of a bio-ion measurement system on acupoints for meridian diagnosis.

The aim of this study was to develop a new method of measuring the meridian energy potential (MEP) at an acupoint with bioelectrical impedance in order to establish an objective meridian diagnosis. To confirm the reflection of the changes in body composition at acupoints, the changes in the MEP on the bladder meridian before, during and after cupping were observed. Additionally, to evaluate the usefulness of diagnosis, the MEP on the stomach meridian before and after a meal was measured. Significant increases were found at every acupoint during cupping and after eating a meal. It was confirmed that the MEP data reflected changes in body composition at every acupoint and that these changes were associated with functioning of the associated internal organs. In conclusion, we propose the usefulness of this method, which can indicate the state of acupoints.

Lack of association between DISC1 polymorphisms and risk of schizophrenia in a Korean population.

The DISC1 gene is considered to be a strong candidate gene for the development of schizophrenia. This study examines the association of DISC1 polymorphisms with schizophrenia in a Korean population. Although we fail to discover convincing evidence that DISC1 affects schizophrenia development, our findings may be useful for further genetic studies.

Lack of associations of neuregulin 1 variations with schizophrenia and smooth pursuit eye movement abnormality in a Korean population.

Schizophrenia is a serious and disabling mental disorder with a high heritability rate. The human neuregulin 1 (NRG1) on 8p12 has been implicated as a candidate gene for schizophrenia. However, controversial results of the associations of NRG1 polymorphisms with schizophrenia and related phenotypes have been reported. In this study, four NRG1 single nucleotide polymorphisms, three in the promoter region, and one nonsynonymous in coding region, were genotyped in a total of 825 subject including 435 schizophrenia cases and 390 normal controls of Korean ethnicity. Although logistic association analysis of NRG1 polymorphisms and haplotypes with schizophrenia showed a nominal association in rs4623364G > C (P = 0.04), the significance disappeared after corrections for multiple testing (corrected P > 0.05). Additional case/control and multiple regression analyses in schizophrenia patients using a method that measures the smooth pursuit eye movement (SPEM) function globally based on natural logarithmic values of the signal/noise ratio also showed no association between NRG1 variants and SPEM abnormality among patients with schizophrenia (P > 0.05). Despite the need for further replications in other cohorts, our findings provide additional supporting information that four variants in NRG1 investigated in this study may not be associated with schizophrenia and its related SPEM function in a Korean population.

Genetic association analysis of ERBB4 polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population.

The human receptor tyrosine-protein kinase erbB-4 (ERBB4) gene mediates neuregulin 1 (NRG1) signaling, and is involved in neuronal migration and differentiation. Despite the potential significance of ERBB4 in the development of schizophrenia, relatively few genetic studies for the association of ERBB4 with schizophrenia were performed in the populations including Ashkenazi Jews, Americans including Caucasians and African Americans, and Han Chinese. In this study, differences in ERBB4 variations were investigated to determine association with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Seven polymorphisms in ERBB4 gene were genotyped in 435 schizophrenia cases and 390 unrelated healthy controls. In order to investigate the relationship between ERBB4 and the risk of schizophrenia and SPEM abnormality, differences in SNP and haplotype distribution were analyzed using logistic and multiple regression analyses. However, we failed to replicate the associations reported by previous studies in other populations. Although statistically not significant, the tendency towards associations between ERBB4 polymorphisms and the risk of schizophrenia and SPEM abnormality in this study from a Korean population would be helpful for further genetic etiology studies in schizophrenia.