Diagnosis of atrial fibrillation based on AI-detected anomalies of ECG segments.

Early detection of atrial fibrillation (AF) is crucial for its effective management and prevention. Various methods for detecting AF using deep learning (DL) based on supervised learning with a large labeled dataset have a remarkable performance. However, supervised learning has several problems, as it is time-consuming for labeling and has a data dependency problem. Moreover, most of the DL methods do not provide any clinical evidence to physicians regarding the analysis of electrocardiography (ECG) for classification or detection of AF. To address these limitations, in this study, we proposed a novel AF diagnosis system using unsupervised learning for anomaly detection with three segments, PreQ, QRS, and PostS, based on the normal ECG. Two independent datasets, PTB-XL and China, were used in three experiments. We used a long short-term memory (LSTM)-based autoencoder to train the segments of the normal ECG. Based on the threshold of anomaly scores using mean squared error (MSE), it distinguished between normal and AF segments. In Experiment A, the best score was that of PreQ, which detected AF with an AUROC score of 0.96. In Experiment B and C for cross validation of each dataset, the best scores were also of PreQ, with AUROC scores of 0.9 and 0.95, respectively. To verify the significance of the anomaly score in distinguishing between AF and normal segments, we utilized an XG-Boosted model after generating anomaly scores in the three segments. The XG-Boosted model achieved an AUROC score of 0.98 and an F1 score of 0.94. AF detection using DL has been controversial among many physicians. However, our study differentiates itself from previous studies in that we can demonstrate evidence that distinguishes AF from normal segments based on the anomaly score.

Tele-monitoring system for intensive care ventilators in isolation rooms.

The COVID-19 pandemic and discovery of new mutant strains have a devastating impact worldwide. Patients with severe COVID-19 require various equipment, such as ventilators, infusion pumps, and patient monitors, and a dedicated medical team to operate and monitor the equipment in isolated intensive care units (ICUs). Medical staff must wear personal protective equipment to reduce the risk of infection. This study proposes a tele-monitoring system for isolation ICUs to assist in the monitoring of COVID-19 patients. The tele-monitoring system consists of three parts: medical-device panel image processing, transmission, and tele-monitoring. This system can monitor the ventilator screen with obstacles, receive and store data, and provide real-time monitoring and data analysis. The proposed tele-monitoring system is compared with previous studies, and the image combination algorithm for reconstruction is evaluated using structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR). The system achieves an SSIM score of 0.948 in the left side and a PSNR of 23.414 dB in the right side with no obstacles. It also reduces blind spots, with an SSIM score of 0.901 and a PSNR score of 18.13 dB. The proposed tele-monitoring system is compatible with both wired and wireless communication, making it accessible in various situations. It uses camera and performs live data monitoring, and the two monitoring systems complement each other. The system also includes a comprehensive database and an analysis tool, allowing medical staff to collect and analyze data on ventilator use, providing them a quick, at-a-glance view of the patient's condition. With the implementation of this system, patient outcomes may be improved and the burden on medical professionals may be reduced during the COVID-19 pandemic-like situations.

Isradipine, an L-type calcium channel inhibitor, attenuates cue-associated methamphetamine-seeking in mice.

Methamphetamine (meth) is an addictive psychostimulant and there are no FDA-approved treatment options for patients suffering from meth use disorders. In addition to being addictive, meth is also neurotoxic and chronic administration results in degeneration of substantia nigra pars compacta (SNc) dopamine and locus coeruleus (LC) norepinephrine neurons in mice. Optimal treatment strategies for meth use disorders would attenuate maladaptive meth-seeking behavior as well as provide neuroprotection. The L-type calcium channel inhibitor isradipine and the monoamine oxidase (MAO) inhibitor rasagiline both prevent chronic meth-induced SNc and LC degeneration but effects on meth-seeking are unknown. To test whether these clinically available compounds can mitigate meth-seeking, mice were implanted with chronic indwelling jugular vein catheters and allowed to self-administer meth (0.1 mg/kg/infusion) for 10 consecutive days (2-hrs/day) on a fixed ratio (FR) 1 schedule of reinforcement with meth infusions paired to a cue light. One day after the last self-administration session mice were tested for cue-associated meth-seeking behavior wherein the meth-associated cue light was contingently presented but meth reinforcement withheld. Isradipine (3 mg/kg) attenuated cue-associated meth-seeking in both male and female mice. In contrast, rasagiline (1 mg/kg) had no effect on seeking in either sex. These results suggest that isradipine may have the potential to serve as a dual-purpose pharmacotherapy for meth use disorders by attenuating seeking behavior and providing neuroprotection.

Differential vulnerability of locus coeruleus and dorsal raphe neurons to chronic methamphetamine-induced degeneration.

Methamphetamine (meth) increases monoamine oxidase (MAO)-dependent mitochondrial stress in axons of substantia nigra pars compacta (SNc), and ventral tegmental area (VTA) dopamine neurons. Chronic administration of meth results in SNc degeneration and MAO inhibition is neuroprotective, whereas, the VTA is resistant to degeneration. This differential vulnerability is attributed, at least in part, to the presence of L-type Ca2+ channel-dependent mitochondrial stress in SNc but not VTA dopamine neurons. MAO is also expressed in other monoaminergic neurons such as noradrenergic locus coeruleus (LC) and serotonergic dorsal raphe (DR) neurons. The impact of meth on mitochondrial stress in LC and DR neurons is unknown. In the current study we used a genetically encoded redox biosensor to investigate meth-induced MAO-dependent mitochondrial stress in LC and DR neurons. Similar to SNc and VTA neurons, meth increased MAO-dependent mitochondrial stress in axonal but not somatic compartments of LC norepinephrine and DR serotonin neurons. Chronic meth administration (5 mg/kg; 28-day) resulted in degeneration of LC neurons and MAO inhibition was neuroprotective whereas DR neurons were resistant to degeneration. Activating L-type Ca2+ channels increased mitochondrial stress in LC but not DR axons and inhibiting L-type Ca2+ channels in vivo with isradipine prevented meth-induced LC degeneration. These data suggest that similar to recent findings in SNc and VTA dopamine neurons, the differential vulnerability between LC and DR neurons can be attributed to the presence of L-type Ca2+ channel-dependent mitochondrial stress. Taken together, the present study demonstrates that both meth-induced MAO- and L-type Ca2+ channel-dependent mitochondrial stress are necessary for chronic meth-induced neurodegeneration.

Acute and protracted abstinence from methamphetamine bidirectionally changes intrinsic excitability of indirect pathway spiny projection neurons in the dorsomedial striatum.

Methamphetamine (meth) is an addictive psychostimulant and illicit use presents significant personal and socioeconomic harm. Behavioral studies support the involvement of the dorsal striatum in drug-seeking but stimulant induced dysfunction in this region is understudied. The dorsal striatum can be subdivided into the dorsomedial (DMS) and dorsolateral (DLS) striatum with the DMS implicated in goal-directed and DLS in habitual behaviors; both regions are primarily composed of GABAergic direct (dSPNs) and indirect pathway (iSPNs) spiny projection neurons. To examine the effect of repeated meth on SPNs, mice were administered meth (2 mg/kg) for ten consecutive days and intrinsic excitability, dendritic excitability, and spine density were examined. DMS iSPN intrinsic excitability was increased at 1 day but decreased at 21 days of abstinence. In contrast, DMS dSPN intrinsic excitability was unchanged at either timepoint. Dendritic excitability and spine densities were unaltered in DMS iSPNs and dSPNs at 1 and 21 days of abstinence. The effect of repeated meth on iSPN excitability was specific to the DMS; DLS iSPN intrinsic excitability, dendritic excitability, and spine density were unchanged at 1 and 21 days of abstinence. These findings point toward DMS iSPN dysfunction in meth use disorders with differential dysfunction dependent on abstinence duration.

The application of a deep learning system developed to reduce the time for RT-PCR in COVID-19 detection.

Reducing the time to diagnose COVID-19 helps to manage insufficient isolation-bed resources and adequately accommodate critically ill patients. There is currently no alternative method to real-time reverse transcriptase polymerase chain reaction (RT-PCR), which requires 40 cycles to diagnose COVID-19. We propose a deep learning (DL) model to improve the speed of COVID-19 RT-PCR diagnosis. We developed and tested a DL model using the long short-term memory method with a dataset of fluorescence values measured in each cycle of 5810 RT-PCR tests. Among the DL models developed here, the diagnostic performance of the 21st model showed an area under the receiver operating characteristic (AUROC), sensitivity, and specificity of 84.55%, 93.33%, and 75.72%, respectively. The diagnostic performance of the 24th model showed an AUROC, sensitivity, and specificity of 91.27%, 90.00%, and 92.54%, respectively.

Evaluation of transdermal delivery of nanoemulsions in ex vivo porcine skin using two-photon microscopy and confocal laser-scanning microscopy.

This study experimentally evaluates the self-targeting ability of asiaticoside-loaded nanoemulsions compared with nontargeted nanoemulsions in ex vivo experiments with porcine skin samples. Homebuilt two-photon and confocal laser-scanning microscopes were employed to noninvasively examine the transdermal delivery of two distinct nanoemulsions. Prior to the application of nanoemulsions, we noninvasively observed the morphology of porcine skin using two-photon microscopy. We have successfully visualized the distributions of the targeted and nontargeted nanoemulsions absorbed into the porcine skin samples. Asiaticoside-loaded nanoemulsions showed an improved ex vivo transdermal delivery through the stratum corneum compared with nonloaded nanoemulsions. As a secondary measure, nanoemulsions-applied samples were sliced in the depth direction with a surgical knife in order to obtain the complete depth-direction distribution profile of Nile red fluorescence. XZ images demonstrated that asiaticoside-loaded nanoemulsion penetrated deeper into the skin compared with nontargeted nanoemulsions. The basal layer boundary is clearly visible in the case of the asiaticoside-loaded skin sample. These results reaffirm the feasibility of using self-targeting ligands to improve permeation through the skin barrier for cosmetics and topical drug applications.

Effects of Prunella vulgaris labiatae extract on specific and non-specific immune responses in tilapia (Oreochromis niloticus).

We examined the effects of Prunella vulgaris Labiatae (P. vulgaris L.) on specific and non-specific immune responses of Nile tilapia, Oreochromis niloticus. The optimal concentration without toxicity of P. vulgaris was determined to 30-40 µg/ml in vitro and 120 µg/100 g of fish in vivo. P. vulgaris significantly elicited an antibody titer compared to FCA or ß-glucan. ß-glucan plus P. vulgaris group synergistically enhanced antibody production. No significant difference in antibody production was observed between P. vulgaris and P. vulgaris plus ß-glucan group. A respiratory burst activity of head kidney (HK) leucocytes of tilapia administered with 300 or 500 µg P. vulgaris was significantly (p < 0.05) enhanced compared with the PBS-injected control group and FCA-treated group. Maximum increase in the NBT reduction value was observed in 500 µg P. vulgaris group but no significant difference was found between 300 and 500 µg P. vulgaris group. The level of serum lysozyme activity was significantly (p < 0.05) higher in the 300 and 500 µg P. vulgaris than 100 µg P. vulgaris and FCA group. The phagocytic activities of HK leucocytes from tilapia administered with 300 and 500 µg P. vulgaris were significantly (p < 0.05) higher than 100 µg P. vulgaris and the control group. P. vulgaris was revealed with a good immunoadjuvant evoking the specific and non-specific immune responses of tilapia.

Genetic distances and variations of three clupeid species determined by PCR technique.

In this study, seven oligonucleotides primers were shown to generate the shared loci, specific loci, unique shared loci to each species and shared loci by the three species which could be obviously calculated. Euclidean genetic distances within- and between-species were also calculated by complete linkage method with the sustenance of the hierarchical dendevrepogram program Systat version 13. The genomic DNA isolated from herring (Clupea pallasii), Korean anchovy (Coilia nasus) and large-eyed herring (Harengula zunashi), respectively, in the Yellow Sea, were amplified several times by PCR reaction. The hierarchical dendevrepogram shows three chief branches: cluster 1 (PALLASII 01, 02, 03, 04, 06 and 07), cluster 2 (NASUS 08, 09, 10, 11, 12, 13 and 14), and cluster 3 (ZUNASHI 15, 16, 17, 18, 19, 20, 21 and PALLASII 05). In three clupeid species, the shortest genetic distance displaying significant molecular difference was between individual PALLASII no. 03 and PALLASII no. 02 (0.018). Individual no. 06 of PALLASII was most distantly related to NASUS no. 11 (genetic distance = 0.318). Individuals from herring (C. pallasii) species (0.920) exhibited higher bandsharing values than did individuals from Korean anchovy (C. nasus) species (0.872) (P<0.05). As a result, this PCR analysis generated on the genetic data displayed that the herring (C. pallasii) species was widely separated from Korean anchovy (C. nasus) species. Reversely, individuals of Korean anchovy (C. nasus) species were a little closely related to those of large-eyed herring (H. zunashi) species.

The effect of mistletoe, Viscum album coloratum, extract on innate immune response of Nile tilapia (Oreochromis niloticus).

The purpose of the present study was to evaluate the effect of dietary mistletoe extracts on non-specific immune response and disease resistance of Nile tilapia (Oreochromis niloticus) against Aeromonas hydrophila infection. Tilapia fingerlings were fed with a diet containing 0 mg as a control, 10 mg, 50 mg, and 200 mg mistletoe powder kg(-1) dry diet for 80 days. The immunological parameters, respiratory burst activity, lysozyme activity, alternative complement haemolysis activity (ACH(50)), and phagocytic activity of fish were investigated following 20, 40 and 80 days of feeding. Fish were challenged with A. hydrophila on 80 days after feeding and mortalities were checked over 10 days post-infection. The results show that fish fed with mistletoe extract exhibited an increase in activity in all immunological parameters (P < 0.05) compared to the control group depending on feeding periods and doses of mistletoe. Following challenge with A. hydrophila, 42% less survivability was observed in the control group than in other experimental diet groups. The highest survival rate (83%) was shown in the group fed with a 50 mg mistletoe kg(-1) diet. The results suggest that mistletoe enables tilapia to promote immunity and be more resistant to A. hydrophila infection.

Essential Oil Prepared from Cymbopogon citrates Exerted an Antimicrobial Activity Against Plant Pathogenic and Medical Microorganisms.

Essential oils are mixtures of volatile, lipophilic compounds originating from plants. Some essential oils have useful biological activities including antimicrobial, spasmolytic, antiplasmodial, and insect-repelling activities. In this study, we tested the antimicrobial activity of essential oil prepared from the aromatic plant, Cymbopogon citrates, against three important plant pathogenic and medical microorganisms, Pectobacterium carotovorum, Colletotrichum gloeosporioides, and Aspergillus niger. It effectively inhibited the growth of the bacterium, Pectobacterium carotovorum, in a dose-dependent fashion, and 0.5% of the oil inhibited the growth of bacteria completely. Similarly, the essential oil inhibited the growth of plant pathogenic fungus, Colletotrichum gloeosporioides, and the addition of 1% of essential oil completely inhibited the growth of fungus even after 5 days of culture. Finally, it effectively inhibited the growth of the medically and industrially important fungal species, Aspergillus spp. These results suggest that the essential oil from Cymbopogon citrates may be an environmentally safe alternative to inhibit antimicrobial agents for various uses.

TUNABLE RING LASER BASED ON A SEMICONDUCTOR OPTICAL AMPLIFIER AT 1300 NM USING A SIMPLE WAVELENGTH SELECTION FILTER.

A simple, compact, and low cost tunable ring laser with a commercial semiconductor optical amplifier (SOA) was demonstrated. The tunable ring laser is based on an external wavelength filter cavity that is analogous with the Littman configuration with a diffraction grating, a mirror, and a simple slit. The unique structural advantage of this new system is that the slit is displaced to select a desired wavelength instead of tilting the mirror as in the Littman configuration. This allows easy control over the selected wavelength by the translating action of the slit. The full width half maximum (FWHM) wavelength turning range is 45 nm, and the wavelength resolution is about 2 pm. The demonstrated tunable ring laser has 2 mW output power. The side mode suppression ratios is 70-73 dB.

Dietary Korean mistletoe enhances cellular non-specific immune responses and survival of Japanese eel (Anguilla japonica).

The present study was performed to investigate the immunostimulatory effects of Korean mistletoe extract (KM-110; Viscum album Coloratum) on the non-specific immune response and protection against Aeromonas hydrophila infection in Japanese eel (Anguilla japonica). Eels were fed under 4 regimes, 0%, 0.1%, 0.5% and 1.0% KM-110 mixed diet. On day 14 after feeding, 15 fish from each group were injected i.p. with live A. hydrophila (3 x 10(6)CFU) and the remaining unchallenged fish from each group were used to study the innate immune response. On 14 days post-infection, the total survival rates were 26.6% in control, and 33.3%, 66.6% and 80% in 0.1%, 0.5% and 1% KM-110-treated groups, respectively. The maximum lysozyme activity was observed in the 1% KM-110-treated group. There was no significant difference of lysozyme activity between 0.1% and 0.5% KM-110 group. Superoxide anion (O(2)(-)) production was significantly (p<0.05) augmented in the 0.5% and 1% KM-110 groups compared to the control and 0.1% KM-110 group. No significant difference of (O(2)(-) production was found between 0.5% and 1% KM-110 group. Likewise, there was a significant increase in phagocytic activity in the 0.5% KM-110 group compared with the 0.1% group (p<0.05), but no significant difference between the 0.5% and the 1% KM-110 group indicating that 0.5% KM-110 concentration is suitable for stimulating maximum phagocytic activity resulting in a high amount of ROI production. Considering the present results, KM-110 could be utilized as a promising immunostimulating substance for a diet in aquaculture.

Cloning and expression of partial Japanese flounder (Paralichthys olivaceus) IgD.

The cDNA sequence of the Japanese flounder (Paralychthys olivaceus) IgD has been previously reported (GenBank accession no. AB052658) and this was followed by the detection of IgD mRNA expression in some flounder organ tissues. However, it has not been determined whether the flounder IgD gene is virtually expressed into IgD protein. To characterize the flounder immunoglobulins utilized in elucidating the mechanism, evolution and diversity of the flounder immune system, antibodies specific to IgD and IgM were necessary. In the present study, partial flounder recombinant IgD (rIgD), IgM (rIgM) and the conserved regions of IgD and IgM (rCIg) were produced by cloning the cDNA sequence using isotype specific primers which were designed to produce unique fragments of IgD and IgM specific amino acid sequences. The production of recombinant Igs was ascertained by SDS-gel electrophoresis and immunoblot analysis using anti-T7 d Taq antibody. The produced recombinant Igs were purified using affinity columns, and used as immunogens. Antibodies specific to the isotype of flounder Igs were generated by immunizing rabbits with rfIgs and the antibodies produced were identified by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Specificities of the generated antibodies were evaluated by testing cross-reactivity between recombinant IgM and IgD. By ELISA, rabbit antibodies against the rfIgD fragment (anti-rfIgD) failed to recognize any kind of flounder serum Igs, whereas respective antibodies against rfCIg (anti-rfCIg) and rfIgM fragments (anti-rfIgM) reacted with serum Igs. Likewise, in immunoblot assays, though anti-rfIgD did not, both anti-rfCIg and anti-rfIgM bound with the ~85 kd flounder IgM heavy chain. By flow cytometry analysis, anti-rfCIg, anti-rfIgD and anti-rfIgM reacted with 6%, 3% and 6.5% of cells, respectively, suggesting that flounder IgD is not secreted in serum but expressed on flounder B-like cell surfaces as in mammals. Antibodies produced against recombinant flounder Igs could be used to develop sandwich assay systems for detecting flounder Igs and for further investigating the flounder immune system.

Characterization of monoclonal antibodies against heavy and light chains of flounder (Paralichthys olivaceus) immunoglobulin.

Flounder (Paralichthys olivaceus) Immunoglobulins (Igs) were purified from the serum of mouse IgG-immunized flounder by using affinity chromatography. Under denaturing conditions in SDS-PAGE, the flounder Igs appeared to be composed of 2 heavy (H) chains (72 and 77 kDa) and two light (L) chains (26 and 28 kDa). Monoclonal antibodies (MAbs) were produced by the fusion of myeloma cells (SP2/0) with Balb/c mouse spleen cells that were previously sensitized against affinity-purified flounder Igs. In a Western blot analysis, the produced MAbs, FIM511, FIM519, and FIM562 recognized both the 72 and 77 kDa H chains, 26 kDa, and 28 kDa L chain, respectively. Mouse antiserum against flounder Igs reacted more strongly with the L chain of 28 kDa than with 26 kDa, suggesting that the 28 kDa molecule is more immunogenic than the 26 kDa L chain molecule. In a FACS analysis, the ratios of the Ig+ cell population in the flounder head kidney and spleen cells were 49% and 24%, respectively. Unexpectedly, however, the ratios of the Ig+ B-like cell population in the flounder were not significantly augmented, even after the immunization of an immunogenic antigen. This suggests that the humoral immune response in fish could be considerably different from that in mammals. The produced MAbs in this study would be useful in characterizing flounder Ig+ B-like cells and in developing flounder Ig detecting an immunoassay system.