Intracellular Alkalinization Induces Cytosolic Ca2+ Increases by Inhibiting Sarco/Endoplasmic Reticulum Ca2+-ATPase (SERCA)

Intracellular pH (pHi) and Ca2+ regulate essentially all aspects of cellular activities. Their inter-relationship has not been mechanistically explored. In this study, we used bases and acetic acid to manipulate the pHi. We found that transient pHi rise induced by both organic and inorganic bases, but not acidification induced by acid, produced elevation of cytosolic Ca2+. The sources of the Ca2+ increase are from the endoplasmic reticulum (ER) Ca2+ pools as well as from Ca2+ influx. The store-mobilization component of the Ca2+ increase induced by the pHi rise was not sensitive to antagonists for either IP3-receptors or ryanodine receptors, but was due to inhibition of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), leading to depletion of the ER Ca2+ store. We further showed that the physiological consequence of depletion of the ER Ca2+ store by pHi rise is the activation of store-operated channels (SOCs) of Orai1 and Stim1, leading to increased Ca2+ influx. Taken together, our results indicate that intracellular alkalinization inhibits SERCA activity, similar to thapsigargin, thereby resulting in Ca2+ leak from ER pools followed by Ca2+ influx via SOCs

Evaluation of Commercially Available Machine Interpretation Applications for Simple Clinical Communication.

BACKGROUND: Accessing professional medical interpreters for brief, low risk exchanges can be challenging. Machine translation (MT) for verbal communication has the potential to be a useful clinical tool, but few evaluations exist. OBJECTIVE: We evaluated the quality of three MT applications for English-Spanish and English-Mandarin two-way interpretation of low complexity brief clinical communication compared with human interpretation. DESIGN: Audio-taped phrases were interpreted via human and 3 MT applications. Bilingual assessors evaluated the quality of MT interpretation on four assessment categories (accuracy, fluency, meaning, and clinical risk) using 5-point Likert scales. We used a non-inferiority design with 15% inferiority margin to evaluate the quality of three MT applications with professional medical interpreters serving as gold standards. MAIN MEASURES: Proportion of interpretation exchanges deemed acceptable, defined as a composite score of 16 or greater out of 20 based on the four assessment categories. KEY RESULTS: For English to Spanish, the proportion of MT-interpreted phrases scored as acceptable ranged from 0.68 to 0.84, while for English to Mandarin, the range was from 0.62 to 0.76. Both Spanish/Mandarin to English MT interpretation had low acceptable scores (range 0.36 to 0.41). No MT interpretation met the non-inferiority threshold. CONCLUSION: While MT interpretation was better for English to Spanish or Mandarin than the reverse, the overall quality of MT interpretation was poor for two-way clinical communication. Clinicians should advocate for easier access to professional interpretation in all clinical spaces and defer use of MT until these applications improve

Pathway and kinetics of cyhalothrin biodegradation by Bacillus thuringiensis strain ZS-19

10.1038/srep08784Scientific Reports

Frequency and spatial characteristics of highfrequency neuromagnetic signals in childhood epilepsy

Purpose. Invasive intracranial recordings have suggested that high-frequency oscillation is involved in epileptogenesis and is highly localized to epileptogenic zones. The aim of the present study is to characterize the frequency and spatial patterns of high-frequency brain signals in childhood epilepsy using a non-invasive technology. Methods. Thirty children with clinically diagnosed epilepsy were studied using a whole head magnetoencephalography (MEG) system. MEG data were digitized at 4 000 Hz. The frequency and spatial characteristics of high-frequency neuromagnetic signals were analyzed using continuous wavelet transform and beamformer. Threedimensional magnetic resonance imaging (MRI) was obtained for each patient to localize magnetic sources. Results. Twenty-six patients showed highfrequency (100-1 000 Hz) components (26/30, 86%). Nineteen patients showed more than one high-frequency component (19/30, 63%). The frequency range of high-frequency components varied across patients. The highest frequency band was identified around 910 Hz. The loci of high-frequency epileptic activities were concordant with the lesions identified by magnetic resonance imaging for 21 patients (21/30, 70%). The MEG source localizations of high-frequency components were found to be concordant with intracranial recordings for nine of the eleven patients who underwent epilepsy surgery (9/11, 82%). Conclusion. The results have demonstrated that childhood epilepsy was associated with high-frequency epileptic activity in a wide frequency range. The concordance of MEG source localization, MRI and intracranial recordings suggests that measurement of high-frequency neuromagnetic signals might provide a novel approach for clinical management of childhood epilepsy

Frequency and spatial characteristics of highfrequency neuromagnetic signals in childhood epilepsy

Purpose. Invasive intracranial recordings have suggested that high-frequency oscillation is involved in epileptogenesis and is highly localized to epileptogenic zones. The aim of the present study is to characterize the frequency and spatial patterns of high-frequency brain signals in childhood epilepsy using a non-invasive technology. Methods. Thirty children with clinically diagnosed epilepsy were studied using a whole head magnetoencephalography (MEG) system. MEG data were digitized at 4 000 Hz. The frequency and spatial characteristics of high-frequency neuromagnetic signals were analyzed using continuous wavelet transform and beamformer. Threedimensional magnetic resonance imaging (MRI) was obtained for each patient to localize magnetic sources. Results. Twenty-six patients showed highfrequency (100-1 000 Hz) components (26/30, 86%). Nineteen patients showed more than one high-frequency component (19/30, 63%). The frequency range of high-frequency components varied across patients. The highest frequency band was identified around 910 Hz. The loci of high-frequency epileptic activities were concordant with the lesions identified by magnetic resonance imaging for 21 patients (21/30, 70%). The MEG source localizations of high-frequency components were found to be concordant with intracranial recordings for nine of the eleven patients who underwent epilepsy surgery (9/11, 82%). Conclusion. The results have demonstrated that childhood epilepsy was associated with high-frequency epileptic activity in a wide frequency range. The concordance of MEG source localization, MRI and intracranial recordings suggests that measurement of high-frequency neuromagnetic signals might provide a novel approach for clinical management of childhood epilepsy

Serological responses to koi herpesvirus (KHV) in a non-cyprinid reservoir host

Koi herpesvirus (KHV) is a highly contagious virus that causes KHV disease (KHVD) inducing high mortality in carp and koi (Cyprinus carpio L.). In the late stage, latency occurs with very low, often non-detectable virus concentrations, which represents a challenge for virus detection. After validation according to OIE recommendations, an antibody ELISA was established to recognize antibodies of C. carpio against KHV infection. In this study, the ELISA was modified to detect anti-KHV antibodies from a non-cyprinid fish. Experimentally infected rainbow trout (Oncorhynchus mykiss) were able to transmit KHV to naïve carp at two different temperatures, demonstrating their potential as a reservoir host. At 20°C, KHVD was induced in carp but not at 15°C. Unexpectedly, rainbow trout developed humoral response against KHV at both temperatures. In contrast to carp, at 15°C trout produced neutralizing antibodies but not at 20°C. While antibodies obtained from infected carp sera reacted in a similar way against all KHV, antibodies from rainbow trout sera reacted differently to the same isolates by ELISA. The data show that even when non-cyprinid fish species are infected with KHV, they can produce antibodies that differ from those observed in carp