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Restenosis and destructive vascular remodeling are the main reasons for treatment failure in patients undergoing percutaneous coronary intervention (PCI). In this study, we explored the efficacy of magnolol (a traditional Chinese medicine) in the treatment of restenosis. The results of this study showed that the activities of thrombin and PAR-1 (protease-activated receptor 1) were significantly decreased by the treatment of magnolol. Based on protein docking analysis, magnolol exhibits its potential to bind to the PAR-1 active site. In addition, thrombin-induced connective tissue growth factor (CTGF) expression and the upstream of CTGF such as JNK-1 (but not JNK-2), c-Jun, and AP-1 were distinctly inhibited by magnolol (50 μM) in vascular smooth muscle cells (VSMC). For the functional assay, magnolol (50 μM) significantly inhibited the migration of VSMC, and rats treated with magnolol (13 mg/kg/day) after balloon angioplasty has observed a significant reduction in the formation of common arterial neointima. In conclusion, we identified a novel mechanism by which magnolol acts as the thrombin activity inhibitor and may be the PAR-1 antagonist. In accordance with these functions, magnolol could decrease thrombin-induced CTGF expression in VSMCs via PAR-1/JNK-1/AP-1 signaling.

The dentate gyrus (DG) receives substantial input from the homologous brain area of the contralateral hemisphere. This input is by and large excitatory. Viral-tracing experiments provided anatomical evidence for the existence of GABAergic connectivity between the two DGs, but the function of these projections has remained elusive. Combining electrophysiological and optogenetic approaches, we demonstrate that somatostatin-expressing contralateral DG (SOM

Android's fragmented ecosystem makes the delivery of security updates and OS upgrades cumbersome and complex. While Google initiated various projects such as Android One, Project Treble, and Project Mainline to address this problem, and other involved entities (e.g., chipset vendors, manufacturers, carriers) continuously strive to improve their processes, it is still unclear how effective these efforts are on the delivery of updates to supported end-user devices. In this paper, we perform an extensive quantitative study (Aug. 2015 to Dec. 2019) to measure the Android security updates and OS upgrades rollout process. Our study leverages multiple data sources: the Android Open Source Project (AOSP), device manufacturers, and the top four U.S. carriers (AT&T, Verizon, T-Mobile, and Sprint). Furthermore, we analyze an end-user dataset captured in 2019 (152M anonymized HTTP requests associated with 9.1M unique user identifiers) from a U.S.-based social network. Our findings include unique measurements that, due to the fragmented and inconsistent ecosystem, were previously challenging to perform. For example, manufacturers and carriers introduce a median latency of 24 days before rolling out security updates, with an additional median delay of 11 days before end devices update. We show that these values alter per carrier-manufacturer relationship, yet do not alter greatly based on a model's age. Our results also delve into the effectiveness of current Android projects. For instance, security updates for Treble devices are available on average 7 days faster than for non-Treble devices. While this constitutes an improvement, the security update delay for Treble devices still averages 19 days.

Early metabolic bone disease (MBD) detection is important in preterm infants to decrease long-term consequence. We aim to explore the early MBD biochemical marker in extremely low-birth-weight (ELBW) infants.Retrospective cohort study of 95 preterm infants born in a tertiary care-level neonatal intensive care unit between January 2015 and June 2018, with birth weight1000 g. Thirty-five infants were "nothing by mouth" for14 days and categorized as the high-risk group; the remaining 60 were categorized as the control group. Mineral intake in the first 14 days and the trend of serum calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were compared in both groups.The Ca and P supplementation in the first 2 weeks of life were inadequate in both groups. Compared with the control group, significantly lower serum P (mg/dL) levels were noted in the high-risk group on weeks 2 (3.65 ± 1.2 vs 4.67 ± 1.45; P.001), 4 (3.21 ± 0.95 vs 5.83 ± 1.18; P.0001), and 6 (3.94 ± 1.1 vs 6.22 ± 0.78; P.0001). There was no significant difference in the serum Ca level, and significantly higher ALP (U/L) levels were found up until 2 months of life in the high-risk group (458.36 ± 189.02 vs 335.7 ± 111.51; P.014).Hypophosphatemia developed as early as 2 weeks old in high-risk preterm infants because of inadequate supplementation. Neither the serum Ca or ALP levels were affected. Thus, the routine monitoring of serum P level should be started 2 weeks after birth for early MBD detection in extremely ELBW infants.

This manuscript introduces a 1D analytical model to predict the Bulk Acoustic Wave (BAW) resonator aging when it is due to package stress relaxation. Classical micro-acoustic resonator aging models rely on a logarithmic function to estimate the 10-year instability. However, this function is fitted through experiments and does not take into account the physical stress phenomenon. Instead, our proposed analytical model computes the frequency drift by relating the thermally-induced stress in BAW to the creep response of attached epoxy. To validate the model, we design an experiment in which a type of BAW resonator known as DBAR is attached to a single epoxy layer and subjected to different baking conditions.

This paper introduces TI's mirror-encapsulated bulk acoustic wave (BAW) resonator technology and two novel system applications. Similar to other BAW resonators, the dual-Bragg acoustic resonator (DBAR) utilizes piezoelectric aluminum nitride (AIN) thin film between two metal electrodes. However, the DBAR operation requires no cavity on either side of the resonant body. This unique micro-acoustic resonator technology enables cost-effective system integration in mass production. The first system application is a novel network synchronizer based on an integrated ultra-low noise voltage-controlled BAW oscillator (VCBO). When operating as a jitter cleaner, the synthesized output clock rms jitter can be reduced to less than 60 fs (12 kHz–20 MHz). The second application uses this 2.5 GHz DBAR-oscillator as a high-frequency reference clock, achieving a ±30 ppm Bluetooth Low Energy (BLE) compliant crystal-less radio.

Objective To study the trends of arrhythmia hospitalizations with comorbid alcohol use disorders (AUDs) in terms of demographic characteristics and inpatient outcomes. Methods We used the Nationwide Inpatient Sample (NIS) data from 2010 to 2014 and included 570,556 arrhythmia inpatients (age, 15-54 years), and 55,730 inpatients had comorbid AUD. We used the linear-by-linear association test for measuring the differences in demographics, comorbidities, and hospital outcomes over the study period of 2010 to 2014, and the analysis of variance (ANOVA) for measuring the changes seen in the length of stay (LOS) and total charges. Results Arrhythmia inpatients with AUD were majorly males (85.9%), and older-age adults (45 to 54 years, 68%). Hypertension (52.2%), tobacco abuse (42.3%), and elevated cholesterol and lipids (22.6%) were the most prevalent comorbidities in the study population. There was a statistically significant increasing trend in arrhythmia inpatients with AUD with comorbid diabetes, hypertension, and obesity over the five-year period. In-hospital mortality had a variable trend from 1.1% in 2010 to 1.3% in 2014, but there was a statistically non-significant difference in the trend (P = 0.418). Mean LOS was three days with statistically no significant change during the study period (P = 0.080), whereas total charges have been increasing significantly (P

Septal parvalbumin-expressing (PV+) and calbindin-expressing (CB+) projections inhibit low-threshold and fast-spiking interneurons, respectively, in the medial entorhinal cortex (MEC). We investigate how the two inputs control neuronal activity in the MEC in freely moving mice. Stimulation of PV+ and CB+ terminals causes disinhibition of spatially tuned MEC neurons, but exerts differential effects on temporal coding and burst firing. Thus, recruitment of PV+ projections disrupts theta-rhythmic firing of MEC neurons, while stimulation of CB+ projections increases burst firing of grid cells and enhances phase precession in a cell-type-specific manner. Inactivation of septal PV+ or CB+ neurons differentially affects context, reference, and working memory. Together, our results reveal how specific connectivity of septal GABAergic projections with MEC interneurons translates into differential modulation of MEC neuronal coding.

Objectives We used the Nationwide Inpatient Sample (NIS) to identify the demographic predictors and study the impact of chronic comorbidities on the risk of in-hospital mortality in Alzheimer's disease (AD). Methods We included 132,405 AD patients from the NIS (2012-2014). We used descriptive statistics to discern the differences in demographics and comorbidities by in-hospital mortality. Logistic regression analysis was used to evaluate the predictors and impact of comorbidities that increase the risk of association with in-hospital mortality. Results The in-hospital mortality in AD inpatients is 1.69%, and a greater proportion were female (58.4%) and white (81.5%). Male and hispanic had a higher mortality risk than their counterparts. Hypertension (72%) is the most prevalent comorbidity. Congestive cardiac failure (CCF) and renal failure were significantly associated with a higher risk of in-hospital mortality in AD inpatients by 1.4 and 1.5 times, respectively. Psychiatric comorbidities (depression 20.4%, and psychosis 21.4%) were prevalent in AD inpatients but were negatively associated with mortality. Comorbid tumors without metastasis (1.2%) and metastatic cancer (0.3%) were least prevalent but significantly increased the risk of in-hospital mortality by 1.6 times and 2.2 times, respectively. Conclusion CCF and renal failure were significantly associated with a higher risk of in-hospital mortality in AD patients. Less prevalent comorbidities, tumors with/without metastasis increased in-hospital mortality by 59% to 117%. An integrated care model is required to manage comorbidities in AD patients to improve health-related quality of life and reduce morbidity and mortality.

BackgroundAdjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial.ObjectiveTo determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes.MethodsA multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis.Results405 patients were included with the median age of 67 years (range 27–92, IQR 59–73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, pConclusionAdjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.

Background/purpose(s): This study aimed to investigate clinical features and antimicrobial susceptibility of inpatient children with nontyphoidal salmonellosis from 2010 to 2018. Methods: We retrospectively collected pediatric patients with nontyphoidal Salmonella infection confirmed by positive cultures in a tertiary medical center in Taiwan from 2010 to 2018. Patients' characteristics, clinical manifestations, and laboratory data were collected. Serogroup category and antimicrobial susceptibility were also analyzed. Results: Of total 569 isolates, ampicillin resistant rate was 53% in average, third-generation cephalosporin resistant rate was 6.7%, ciprofloxacin resistant rate was 9% and trimethoprim–sulfamethoxazole resistant rate was 30%. Compared to the resistant rates in 2010, the resistance rate of third generation cephalosporin was significantly higher (3.4% vs. 11%, p = 0.003) but that of ciprofloxacin was significantly lower (20% vs. 11%, p

Introduction: Xeroderma pigmentosum complementation group C (XPC) protein is an important DNA damage recognition factor involved in nucleotide excision repair and regulation of non-small-cell lung cancer (NSCLC) cell proliferation and viability. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) blocks ATP binding to heat shock protein 90 (Hsp90), resulting in destabilization of Hsp90-client protein complexes. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor expressed by many types of tumors. Bevacizumab (Avastin) is a humanized monoclonal antibody against human VEGF used as an antiangiogenesis agent in the therapy of many cancers, proving successful in increasing objective tumor response rate and prolonging overall survival in NSCLC patients. Methods: After the bevacizumab and/or 17-AAG treatment, the expressions of XPC mRNA were determined by quantitative real-time PCR analysis. Protein levels of XPC and phospho-AKT were determined by Western blot analysis. We used specific XPC small interfering RNA and PI3K inhibitor (LY294002) to examine the role of the AKT-XPC signal in regulating the chemosensitivity of bevacizumab and 17-AAG. Cell viability was assessed by the MTS assay and trypan blue exclusion assay. Results: In this study, bevacizumab decreased XPC expression in human lung squamous cell carcinoma H520 and H1703 cells via AKT inactivation. Enhancement of AKT activity by transfection with constitutively active AKT vectors increased XPC expression and cell survival after treatment with bevacizumab. In addition, 17-AAG synergistically enhanced bevacizumab-induced cytotoxicity and cell growth inhibition in H520 and H1703 cells, associated with downregulation of XPC expression and inactivation of AKT. Discussion/Conclusion: Together, these results may provide a rationale to combine bevacizumab with Hsp90 inhibitors in future to enhance therapeutic effects for lung cancer.

Wireless sensor nodes with low power and small form factor are desirable for emerging IoT applications. These nodes usually consist of a processor, memory, radio, sensors, battery, and two quartz crystals: one at 32kHz to synchronize data transmission and the other in the MHz range to synthesize RF signals. SoC integration of the memory, processor, and radio is common; however the MHz crystal remains external, which makes up a significant portion of the entire wireless node size.

Background Enterovirus D68 (EV-D68) was discovered in 1962 and has unique characteristics compared to the characteristics of other enteroviruses. There were few documented cases before the epidemic in the United States in 2014. The Taiwan Centers for Diseases Control also confirmed that EV-D68 has been endemic, and some cases of acute flaccid myelitis were reported in Taiwan. To understand the current EV-D68 serostatus, we performed an EV-D68 seroepidemiology study in Taiwan in 2017. Methods After informed consent was obtained, we enrolled preschool children, 6- to 15-year-old students and 16- to 49-year-old people. The participants underwent a questionnaire investigation and blood sampling to measure the EV-D68 neutralization antibody. Results In total, 920 subjects were enrolled from the northern, central, southern and eastern parts of Taiwan with a male-to-female ratio of 1.03. The EV-D68 seropositive rate was 32% (26/82) in infants, 18% (27/153) in 1-year-old children, 43% (36/83) in 2-year-old children, 60% (94/156) in 3- to 5-year-old children, 89% (108/122) in 6- to 11-year-old primary school students, 98% (118/121) in 12- to 15-year-old high school students, 100% (122/122) in 16- to 49-year-old women and 100% (81/81) in 16- to 49-year-old males in 2017. Among preschool children, EV-D68 seropositivity was related to age (p for trend

A 16-channel closed-loop neuromodulation system-on-chip (SoC) for human epileptic seizure control is proposed and designed. In the proposed SoC, a 16-channel neural-signal acquisition unit (NSAU), a biosignal processor (BSP), a 16-channel high-voltage-tolerant stimulator (HVTS), and wireless power and bidirectional data telemetry are designed. In the NSAU, the input protection circuit is used to prevent MOSFET from overstressing by the high-voltage stimulations. Hence, NSAUs can share electrodes with stimulators. The auto-reset chopper-stabilized capacitive-coupled instrumentation amplifiers (AR-CSCCIAs) are designed with the chopper-stabilized technique with a new offset reduction loop. The measured input-referred noise is 2.09 $\mu \textrm {V}_{\mathrm {rms}}$ and the noise-efficiency factor (NEF) is 3.78. The entropy-and-spectrum seizure detection algorithm is implemented in the BSP with 0.76-s seizure detection latency and 97.8% detection accuracy. When the seizure onset is detected by the BSP, the HVTS with adaptive supply control delivers 0.5–3-mA biphasic current stimulation to suppress the seizure onset. The proposed SoC is powered wirelessly, and the bidirectional data telemetry is realized through the same pair of coils in 13.56 MHz. The downlink data rate is 211 Kb/s with the binary phase-shift keying (BPSK) modulation and a new BPSK demodulator. The uplink data rate is 106 Kb/s with the load-shift keying (LSK) modulation. The proposed SoC is fabricated in a 0.18- $\mu \text{m}$ CMOS technology and occupies 25 mm2. Electrical tests have been performed to characterize the SoC performance. In vivo animal experiments using mini-pigs have been performed to successfully verify the closed-loop neuromodulation functions on epileptic seizure suppression.

The study investigated the exposure of spray painters to organic solvents, toxic metals, and hexavalent chromium over 21 working days in 2017. The results found these concentrations of 12 VOCs to be below the short-term exposure limit (STEL) established by the US Occupational Safety and Health Administration (OSHA). The mass concentration of total particulate matter (PM) exposure to workers was 20.01 ± 10.78 mg/m3, which exceeds OSHA’s permissible exposure level of 15 mg/m3. The mean concentration of the total metals for all particle sizes was 109.1 ± 12.0 μg/m3, and those for lead (496,017.0 ng/m3) and iron (252,123.8 ng/m3) were the highest of metal elements. Significantly, the mean concentrations of Pb and As exceeded OSHA’s permissible exposure limits (PELs) of 0.05 and 0.01 mg/m3, respectively. The total hexavalent chromium concentration was 1163.01 ng/m3, and the individual particle sizes (PM1−2.5, PM1, and PM0.25) were strongly and positively correlated with the Cr(VI) concentrations for PM2.5. The study determined that approximately 56.14% of the hexavalent chromium inhaled during the spray-painting process was deposited in the upper respiratory system of the head airway region, followed by the alveolar and tracheobronchial regions, with fractions of 11.93 and 0.05%, respectively. Although the mean ratio of hexavalent chromium to total chromium was only 3.6% for all particle sizes, the cancer risk of the total particles in Cr(VI) (1.6 × 10−3) exceeded the acceptable risk value (10−6). The cancer risks of As and Cr(VI) associated with quasi-ultrafine particles, PM0.5–1, PM1–2.5, and PM> 2.5, also exceeded 10−6. Comparison of the carcinogenicity risk of VOCs and metals suggests that the adverse health effect of inhaled particles on spray-painting workers is more serious than that from VOC exposure.

Hepatitis B virus (HBV) is an aetiological factor for liver cirrhosis and hepatocellular carcinoma (HCC). Despite current antiviral therapies that successfully reduce the viral load in patients with chronic hepatitis B, persistent hepatitis B surface antigen (HBsAg) remains a risk factor for HCC. To explore whether intrahepatic viral antigens contribute directly to hepatocarcinogenesis, we monitored the mitotic progression of HBV-positive cells. Cytokinesis failure was increased in HBV-positive HepG2.2.15 and 1.3ES2 cells, as well as in HuH-7 cells transfected with a wild-type or X-deficient HBV construct, but not in cells transfected with an HBsAg-deficient construct. We show that expression of viral large surface antigen (LHBS) was sufficient to induce cytokinesis failure of immortalized hepatocytes. Premitotic defects with DNA damage and G2 /M checkpoint attenuation preceded cytokinesis in LHBS-positive cells, and ultimately resulted in hyperploidy. Inhibition of polo-like kinase-1 (Plk1) not only restored the G2 /M checkpoint in these cells, but also suppressed LHBS-mediated in vivo tumourigenesis. Finally, a positive correlation between intrahepatic LHBS expression and hepatocyte hyperploidy was detected in >70% of patients with chronic hepatitis B. We conclude that HBV LHBS provokes hyperploidy by inducing DNA damage and upregulation of Plk1; the former results in atypical chromatin structures, and the latter attenuates the function of the G2 /M DNA damage checkpoint. Our data uncover a mechanism by which genomic integrity of hepatocytes is disrupted by viral LHBS. These findings highlight the role of intrahepatic surface antigen as an oncogenic risk factor in the development of HCC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The first deep geothermal energy development project in Taiwan was launched at the Ilan Plain in northeastern Taiwan, where metamorphic rock is covered by sediments and detailed subsurface structures were poorly known. An eastward plunging anticline containing a fault system was effectively imaged in our seismic sections. However, since some rock fragments recovered from the exploration wells were still questioned, two fault structure models were proposed. One is an extensional strike-slip fault system, and the other is an active normal fault system, which depends on whether the rock fragments were affiliated with the Hsuehshan Range or with the Backbone Range.

Cancer-related hypercalcemia (CRH) is a critical paraneoplastic disorder in advanced cancer patients. In clinical practice, patients with CRH have a poor prognosis. The medical records of 3198 oral cancer patients with CRH diagnosed at Taichung Veterans General Hospital from 1 January 2003 to 31 December 2015 were reviewed. The criteria for patient enrolment were a diagnosis of hypercalcemia or the use of antihypercalcemia medication. Patients who met any of the following criteria were excluded: use of total parenteral nutrition, incomplete serum calcium data, and unknown date of death. The total incidence of CRH was 6.95‰ per year. A total of 91 patients were enrolled; their median survival time was 28 days. The patients were divided into two groups by survival time, with a cut-off point of 30 days. Reduced serum albumin, leucocytosis, and clodronate use had a statistically significant effect on survival in the univariate analysis (all P

Clinical presentation is heterogeneous for autosomal dominant nonsyndromic hearing loss (ADNSHL). Variants of KCNQ4 gene is a common genetic factor of ADNSHL. Few studies have investigated the association between hearing impairment and the variant c.546C>G of KCNQ4. Here, we investigated the phenotype and clinical manifestations of the KCNQ4 variant. Study subjects were selected from the participants of the Taiwan Precision Medicine Initiative. In total, we enrolled 12 individuals with KCNQ4 c.546C>G carriers and 107 non-carriers, and performed pure tone audiometry (PTA) test and phenome-wide association (PheWAS) analysis for the patients. We found that c.546C>G variant was related to an increased risk of hearing loss. All patients with c.546C>G variant were aged >65 years and had sensorineural and high frequency hearing loss. Of these patients, a third (66.7%) showed moderate and progressive hearing loss, 41.7% complained of tinnitus and 16.7% complained of vertigo. Additionally, we found a significant association between KCNQ4 c.546C>G variant, aortic aneurysm, fracture of lower limb and polyneuropathy in diabetes. KCNQ4 c.546C>G is likely a potentially pathogenic variant of ADNSHL in the elderly population. Genetic counseling, annual audiogram and early assistive listening device intervention are highly recommended to prevent profound hearing impairment in this patient group.

Background: Nasopharyngeal carcinoma (NPC) is a common cancer in eastern Asia. Chemoradiotherapy is the main treatment modality for NPC. Dysphagia and aspiration is not uncommon in post-irradiated NPC patients. The purpose of this study was to investigate the risk factors for recurrent pneumonia and the prognosis. Methods: A retrospective chart review was conducted from January 2004 to December 2014. NPC patients who had been hospitalized for pneumonia in the study hospital were enrolled. The diagnosis of pneumonia was based on radiological evidence of chest inflammation and clinical symptoms. Patients' characteristics including demographic data, the hospital course, and the outcome of pneumonia were collected and analyzed. Results: A total of 113 NPC patients were enrolled in this study. Among them, 96 NPC patients had pneumonia after radiotherapy: 43 had pneumonia twice, and 18 had multiple episodes of pneumonia. Forty-nine patients had tube feeding. The 30-day mortality rate was 51%. The mortality rate was significantly associated with metastatic nasopharyngeal carcinoma (r = 0.328, p

Membrane excitability in the axonal growth cones of embryonic neurons influences axon growth. Voltage-gated K+(Kv) channels are key factors in controlling membrane excitability, but whether they regulate axon growth remains unclear. Here, we report that Kv3.4 is expressed in the axonal growth cones of embryonic spinal commissural neurons, motoneurons, dorsal root ganglion neurons, retinal ganglion cells, and callosal projection neurons during axon growth. Ourin vitro(cultured dorsal spinal neurons of chick embryos) andin vivo(developing chick spinal commissural axons and rat callosal axons) findings demonstrate that knockdown of Kv3.4 by a specific shRNA impedes axon initiation, elongation, pathfinding, and fasciculation. In cultured dorsal spinal neurons, blockade of Kv3.4 by blood depressing substance II suppresses axon growth via an increase in the amplitude and frequency of Ca2+influx through T-type and L-type Ca2+channels. Electrophysiological results show that Kv3.4, the major Kv channel in the axonal growth cones of embryonic dorsal spinal neurons, is activated at more hyperpolarized potentials and inactivated more slowly than it is in postnatal and adult neurons. The opening of Kv3.4 channels effectively reduces growth cone membrane excitability, thereby limiting excessive Ca2+influx at subthreshold potentials or during Ca2+-dependent action potentials. Furthermore, excessive Ca2+influx induced by an optogenetic approach also inhibits axon growth. Our findings suggest that Kv3.4 reduces growth cone membrane excitability and maintains [Ca2+]iat an optimal concentration for normal axon growth.SIGNIFICANCE STATEMENTAccumulating evidence supports the idea that impairments in axon growth contribute to many clinical disorders, such as autism spectrum disorders, corpus callosum agenesis, Joubert syndrome, Kallmann syndrome, and horizontal gaze palsy with progressive scoliosis. Membrane excitability in the growth cone, which is mainly controlled by voltage-gated Ca2+(Cav) and K+(Kv) channels, modulates axon growth. The role of Cav channels during axon growth is well understood, but it is unclear whether Kv channels control axon outgrowth by regulating Ca2+influx. This report shows that Kv3.4, which is transiently expressed in the axonal growth cones of many types of embryonic neurons, acts to reduce excessive Ca2+influx through Cav channels and thus permits normal axon outgrowth.

A regulated cross-couple charge pump with new charging current smoothing technique is proposed and verified in a 0.18- $\mu \text {m}~1.8$ -V/3.3-V CMOS process. The transient behaviors of 3-stage cross-couple charge pump and the expressions for the charging current are described in detail. The experiment results show that the charging current ripples are reduced by a factor of three through using the proposed new clocking scheme. The voltage ripples in the power supply line, which is connected with the charge pump input, are also smoothed greatly as the filter circuit does. The proposed scheme is used to decrease the smoothing capacitance in the power line of charge pump for reducing the size of implantable devices in biomedical application. In addition, the power efficiency is improved. The proposed cross-couple charge pump can provide 10.5-V output voltage with 3.5-mA output current, and the power efficiency of the charge pump can be up to 69%.

Enterovirus 71 (EV71) is one of the major pathogens that cause severe enteroviral infections. Our aim was to study the behavioral and household risk factors for its serious complications.Between May 2011 and November 2012, we enrolled children who had symptoms of EV71 infection from six hospitals in Taiwan. The caregivers of each patient were interviewed to determine their hand hygiene habits in relation to EV71 infection. The severity of EV71 infection was classified as follows: Stage 1, hand-foot-mouth disease or herpangina; Stage 2, meningitis or myoclonic jerk; Stage 3A, encephalitis; Stage 3B, cardiopulmonary failure. Stages 2 to 3B were defined as severe EV71 infection. Children with Stages 3A and 3B infection were designated as the critical group.A total of 399 patients had laboratory-confirmed EV71 infection. Three risks factors were associated with the different degrees of severity in EV71 infection. Children2 years old had much greater risks for severe EV71 infection [odds ratio (OR) 1.8; 95% confidence interval (CI), 1.2-2.8], delayed medical evaluation for critical infection (OR 9.4; 95% CI, 3.6-24.1), and developmental retardation for cardiopulmonary failure (OR 8.3; 95% CI, 2.0-33.7). Among all the habits and household factors, caregivers in the critical group had a significantly lower rate in terms of cleaning the faucet after washing their hands (OR 2.63; 95% CI, 1.14-6.08).Children2 years old, developmental retardation, and delayed medical intervention were associated with severe EV71 infection. Cleaning water faucets after hand washing was a protective habit that reduced the risk of complications.

This protocol describes the process forthe neutralizing antibody test of EV-D68.

Objectives Lymphovascular space invasion (LVSI) is an independent risk factor for recurrence and poor survival in early-stage endometrioid endometrial cancer (EEC), but optimal adjuvant treatment is unknown. We aimed to compare the survival of women with early-stage EEC with LVSI treated postoperatively with observation (OBS), radiation (RAD, external beam and/or vaginal brachytherapy), or chemotherapy (CHEMO)+/−RAD. Methods This was a multi-institutional, retrospective cohort study of women with stage I or II EEC with LVSI who underwent hysterectomy+/−lymphadenectomy from 2005 to 2015 and received OBS, RAD, or CHEMO+/−RAD postoperatively. Progression-free survival and overall survival were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. Results In total, 478 women were included; median age was 64 years, median follow-up was 50.3 months. After surgery, 143 (30%) underwent OBS, 232 (48.5%) received RAD, and 103(21.5%) received CHEMO+/−RAD (95% of whom received RAD). Demographics were similar among groups, but those undergoing OBS had lower stage and grade. A total of 101 (21%) women recurred. Progression-free survival (PFS) was improved in both CHEMO+/−RAD (HR = 0.18, 95% CI: 0.09–0.39) and RAD (HR = 0.31, 95% CI: 0.18–0.54) groups compared to OBS, though neither adjuvant therapy was superior to the other. However, in grade 3 tumors, the CHEMO+/−RAD group had superior PFS compared to both RAD (HR 0.25; 95% CI: 0.12–0.52) and OBS cohorts (HR = 0.10, 95% CI: 0.03–0.32). Overall survival did not differ by treatment. Conclusions In early-stage EEC with LVSI, adjuvant therapy improved PFS compared to observation alone. In those with grade 3 EEC, adjuvant chemotherapy with or without radiation improved PFS compared to observation or radiation alone.

Objective The study purpose was to report the outcomes of patients undergoing endometrial cancer surgical staging with laparoscopic abdominal access entry using a left upper quadrant (LUQ) access technique. Methods This was a retrospective cohort study conducted from 1 January 2013 to 1 January 2018. The setting was an academic, single institution gynecologic oncology service with a high volume of minimally invasive surgery (MIS). The patient cohort included obese (defined as BMI > 30 kg/m2) or morbidly obese (BMI > 40 kg/m2) women undergoing MIS for endometrial cancer staging. All patients underwent laparoscopic abdominal access via a 5-mm or 10-mm optical trocar system using a LUQ technique. Results In total, 317 patients were included with a median age of 54 years (range, 24–79) and median BMI 42.5 kg/m2 (range, 32–70); 60 % morbidly obese. Successful LUQ access was achieved in 98.1 %. Of those with a failed LUQ approach, two had undergone previous LUQ surgery and 4 had ≥1 previous midline vertical incisions. There was one LUQ trocar-related visceral injury (0.3 %) and no vascular injuries during the study period. Conclusion A LUQ abdominal technique is a safe and reliable method of laparoscopic access in morbidly obese women undergoing MIS for endometrial cancer staging. This may be the preferred method of laparoscopic access for women with a panniculus or central adiposity, given the caudal displacement of the umbilicus and poor correlation with intraperitoneal anatomic landmarks in this setting.

Background Gold nanoparticles (Au-NPs) have extensive applications in electronics and biomedicine, resulting in increased exposure and prompting safety concerns for human health. After absorption, nanoparticles enter circulation and effect endothelial cells. We previously showed that exposure to Au-NPs (40–50 nm) collapsed endothelial tight junctions and increased their paracellular permeability. Inhaled nanoparticles have gained significant attention due to their biodistribution in the brain; however, little is known regarding their role in cerebral edema. The present study investigated the expression of aquaporin 1 (AQP1) in the cerebral endothelial cell line, bEnd.3, stimulated by Au-NPs. Results We found that treatment with Au-NPs induced AQP1 expression and increased endothelial permeability to water. Au-NP exposure rapidly boosted the phosphorylation levels of focal adhesion kinase (FAK) and AKT, increased the accumulation of caveolin 1 (Cav1), and reduced the activity of extracellular regulated protein kinases (ERK). The inhibition of AKT (GDC-0068) or FAK (PF-573228) not only rescued ERK activity but also prevented AQP1 induction, whereas Au-NP-mediated Cav1 accumulation remained unaltered. Neither these signaling molecules nor AQP1 expression responded to Au-NPs while Cav1 was silenced. Inhibition of ERK activity (U0126) remarkably enhanced Cav1 and AQP1 expression in bEnd.3 cells. These data demonstrate that Au-NP-mediated AQP1 induction is Cav1 dependent, but requires the repression on ERK activity. Mice receiving intranasally administered Au-NPs displayed cerebral edema, significantly augmented AQP1 protein levels; furthermore, mild focal lesions were observed in the cerebral parenchyma. Conclusions These data suggest that the subacute exposure of nanoparticles might induce cerebral edema, involving the Cav1 dependent accumulation on endothelial AQP1.

This work introduces an integrated reference clock system using a 2.5 GHz mirror-encapsulated BAW (bulk acoustic wave) resonator as the frequency source. With acoustic mirrors also placed on top of the resonator, this symmetrical DBAR (dual-Bragg acoustic resonator) structure offers extra design freedoms to alter the resonator’s acoustic properties. A DBAR requires no cavity on either side of the resonator yet still immune to mass loading effect from contamination and assembly. This advantage enables cost-effective system integration by directly marrying a DBAR and a CMOS die in a plastic package. System chips utilizing DBAR as the high-frequency reference clocks are demonstrated here. With compensation algorithm and careful design of the package, these DBAR-based clocking systems can achieve ±25 ppm stability over the entire operation temperature range (including aging, solder shift, etc.), resulting industry’s first crystal-less BLE (Bluetooth Low Energy) radio chip.

This protocol describes the process for the neutralizing antibody test of EV71.

Background During recent 20 years, enterovirus 71 (EV71) has emerged as a major concern among children, particularly in the Asia-Pacific region. To understand current EV71 serostatus, to find risk factors associated with EV71 infection and to establish future EV71 vaccine policy, we performed a seroepidemiology study in Taiwan in 2017. Methods After informed consent was obtained, we enrolled preschool children, 6–15-year-old students, 16–50-year-old people. They received a questionnaire and a blood sample was collected to measure the EV71 neutralization antibody. Results Altogether, 920 subjects were enrolled with a male-to-female ratio of 1.03. The EV71 seropositive rate was 10% (8/82) in infants, 4% (6/153) in 1-year-old children, 8% (7/83) in 2-year-old children, 8% (13/156) in 3–5-year-old children, 31% (38/122) in 6–11-year-old primary school students, 45% (54/121) in 12–15-year-old high school students and 75% (152/203) in 16-50-year-old people. Risk factors associated with EV71 seropositivity in preschool children were female gender, having siblings, more siblings, and contact with herpangina or hand-foot-and-mouth disease. The risk factor with EV71 seropositivity in 16–50-year-old people was having children in their families in addition to older age (p

In this paper, we propose a consortium blockchainbased system sharing malicious IP to prevent further attacks happening among other hosts. In our scheme, every security operation center (SOC) serving as a blockchain-node uploads some suspicious IPs to find the potential attackers' IPs. A smart contract is responsible for comparing the loaded IPs and the existing ones without human interference. If IPs in different lists are matched with certain degree, this system will respond by giving the whole list of malicious IP. By means of these steps, shares of IP lists are achieved and attacks are prevented in advance. Besides, when uploading and sharing, we utilize elliptic curve cryptography to ensure data confidentiality and integrity.

Objective: To develop and verify a CMOS bone-guided cochlear implant (BGCI) microsystem with electrodes placed on the bone surface of the cochlea and the outside of round window for treating high-frequency hearing loss. Methods: The BGCI microsystem consists of an external unit and an implanted unit. The external system-on-chip is designed to process acoustic signals through an acquisition circuit and an acoustic DSP processor to generate stimulation patterns and commands that are transmitted to the implanted unit through a 13.56 MHz wireless power and bidirectional data telemetry. In the wireless power telemetry, a voltage doubler/tripler (2X/3X) active rectifier is used to enhance the power conversion efficiency and generate 2 and 3 V output voltages. In the wireless data telemetry, phase-locked loop based binary phase-shift keying and load-shift keying modulators/demodulators are adopted for the downlink and uplink data through high- Q coils, respectively. The implanted chip with four-channel high-voltage-tolerant stimulator generates biphasic stimulation currents up to 800 μ A. Results: Electrical tests on the fabricated BGCI microsystem have been performed to verify the chip functions. The in vivo animal tests in guinea pigs have shown the evoked third wave of electrically evoked auditory brainstem response waveforms. It is verified that auditory nerves can be successfully stimulated and acoustic hearing can be partially preserved. Conclusion and Significance: Different from traditional cochlear implants, the proposed BGCI microsystem is less invasive, preserves partially acoustic hearing, and provides an effective alternative for treating high-frequency hearing loss.

OBJECTIVE: Hypertension-associated parenchymal arteriole (PA) dysfunction reduces cerebral perfusion and impairs cognition. This is associated with impaired TRPV4-mediated PA dilation; therefore, we tested the hypothesis that TRPV4 channels are important regulators of cerebral perfusion, PA structure and dilation, and cognition. METHODS: 10–12-month-old male TRPV4 knockout (WKY-Trpv4(em4Mcwi)) and age-matched control WKY rats were studied. Cerebral perfusion was measured by MRI with arterial spin labeling. PA structure and function were assessed using pressure myography and cognitive function using the novel object recognition test. RESULTS: Cerebral perfusion was reduced in the WKY-Trpv4(em4Mcwi) rats. This was not a result PA remodeling because TRPV4 deletion did not change PA structure. TRPV4 deletion did not change PA myogenic tone development, but PAs from the WKY-Trpv4(em4Mcwi) rats had severely blunted endothelium-dependent dilation. The WKY-Trpv4(em4Mcwi) rats had impaired cognitive function and exhibited depressive-like behavior. The WKY-Trpv4(em4Mcwi) rats also had increased microglia activation, and increased mRNA expression of GFAP and tumor necrosis factor alpha suggesting increased inflammation. CONCLUSION: Our data indicate that TRPV4 channels play a critical role in cerebral perfusion, PA dilation, cognition and inflammation. Impaired TRPV4 function in diseases such as hypertension may increase the risk for the development of vascular dementia.

This study designs a tunnel type wind mill to increase the capability of wind energy capture. The main design works including the wind collection duct which can rotate along with the wind direction. This makes the wind enter the duct in best condition. After the wind enter the duct, both the direction of the duct is changed to vertical direction which makes the wind direction changes to downward. In the meantime, the diameter of the duct is also changed. The change of the diameter of the duct increases the speed of wind flow. A wind turbine with a nose is used to collect the wind energy. The nose makes the speed of the air flow increase more. In addition to the increasing the speed, the other advantage is to make the air flow flows to the outer part of the turbine blades. It is well known that the outer part of the turbine blade can get more energy than the inner part of the blade. This design can more wind energy than regular wind turbine.

Additional file 1: Table S1. Characteristics of gold particles. Table S2. Effects of Au-NPs and Au-MPs on bEnd.3 cell viability. Table S3. Primer sets for qPCR. Figure S1. Changes in mRNA level of AQP1 and Cav1 in Au-NP-treated bEnd.3 cells. Figure S2. Au-NPs did not induce AQP1 expression in cells with hypo-expression level of Cav1. Figure S3. Au-NP treatment rapidly changed the phosphorylating status of FAK, AKT and ERK in concentration-dependent manner. Figure S4. The ERKs functioned as the negative controller on Cav1 and AQP1 expression in bEnd.3 cells. Figure S5. Proposed signaling pathway responsible for Au-NP-mediated AQP1 expression in bEnd.3 endothelial cells.

Capsaicin, an ingredient of green and red bell peppers, shows anticancer activity in several malignant cell lines. Thymidylate synthase (TS) is a well-validated anticancer drug target in non-small cell lung cancer (NSCLC) cells. However, whether capsaicin and 5-fluorouracil (5-FU) induce synergistic cytotoxicity in NSCLC cells by regulating TS expression is unclear. This study investigated the cytotoxicity of capsaicin and 5-FU co-treatment on two hoursuman lung adenocarcinoma cell lines, H520 and H1703, and the underlying mechanisms. Capsaicin decreased TS expression in a p38 mitogen-activated protein kinase (MAPK) inactivation–dependent manner in H520 and H1703 cells. Enhancement of p38 MAPK activity by transfection with constitutive active mitogen-activated protein kinase kinase six vectors increased TS expression and cell survival. In addition, capsaicin and 5-FU co-treatment enhanced synergistic cytotoxicity and inhibited cell growth associated with TS downregulation and p38 MAPK inactivation in H520 and H1703 cells. Capsaicin and 5-FU co-treatment did not affect the cellular content of capsaicin. These results show that capsaicin may be combined with 5-FU to treat NSCLC.

Head and neck cancers (HNCs) usually present a poor prognosis and cause high morbidity rates. Recent surveys have demonstrated that HNC incidence rates are still on the increase in many countries. Our study objective was to assess the end-of-life care for patients with HNCs in Taiwan. Data was retrieved from Taiwan’s National Health Insurance Research Database, where we identified patients who had been diagnosed with HNCs from January 1997 to December 2010. Each patient’s annual trend of opioid use and hospice care needs, along with the distribution of place of death in the study cohort, were all analyzed. A total of 98,211 HNC patients diagnosed between 1997 and 2010 were eligible for this study. The majority of HNC patients died in hospital. Patients who were male, lived in capital area, had a higher income, had received palliative hospice care, and had been prescribed opioids tended to choose to die at home or in hospice wards. Both opioid prescription and hospice care have increased during the past 10 years; however, the rate of palliative hospice care remained below 50%. Our results demonstrate that greater efforts are needed to implement palliative care for HNC patients in Taiwan.

Background/Purpose The aim of this study was to investigate clinical presentation, serotype distribution and genetic correlation of group B streptococcus (GBS) diseases. Since serotype VI prevalence far exceeded that reported in prior studies, genetic relationship of isolates was further analyzed. Methods GBS isolates obtaining from patients with invasive diseases and pregnant women with colonization between June 2007 and December 2010 were analyzed. All isolates were tested for serotypes by multiplex PCR assay and pulsed-field gel electrophoresis (PFGE). Serotype VI isolates were further analyzed by multilocus sequence typing (MLST). Results A total of 134 GBS isolates were recovered from blood of 126 patients with invasive disease (94.0%) and anogenital swabs of 8 pregnant women (6.0%). Most common serotype was Ib (21.6%), followed by V (20.1%), VI (18.7%), III (15.7%), II (11.9 %), Ia (11.2%), and IX (0.7%). Serotype VI was also the leading type in infants with early onset disease (EOD; 3/8, 37.5%) and colonizing pregnant women (3/8, 37.5%). PFGE distinguished 33 pulsotypes, reflecting genetic diversity among GBS isolates. Among 25 serotype VI isolates tested, 14 were ST-1, seven were ST-679, three were ST-678, one was ST-681, and distributed into four PFGE pulsotypes. ST-678, ST-679, and ST-681 were novel sequence types; ST-678 and ST-679 are single-locus variants of ST-1 that belongs to clonal complex (CC) 1. Conclusion CC1 dissemination of serotype VI GBS thus emerges as an important invasive pathogen in infants and nonpregnant adults in central Taiwan. Serotype prevalence of GBS must be continuously monitored geographically to guide prevention strategy of GBS vaccines.

Stroke pathogenesis involves complex oxidative stress-related pathways. The nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) pathways have been considered molecular targets in pharmacologic intervention for ischemic diseases. Andrographolide, a labdane diterpene, has received increasing attention in recent years because of its various pharmacologic activities. We determined that andrographolide modulates the mitogen-activated protein kinase (MAPK)-Nrf2-HO-1 signaling cascade in primary cerebral endothelial cells (CECs) to provide positive protection against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in rats. In the present study, andrographolide (10 μM) increased HO-1 protein and messenger RNA expressions, Nrf2 phosphorylation, and nuclear translocation in CECs, and these activities were disrupted by a p38 MAPK inhibitor, SB203580, but not by the extracellular signal-regulated kinase inhibitor PD98059 or c-Jun amino-terminal kinase inhibitor SP600125. Similar results were observed in confocal microscopy analysis. Moreover, andrographolide-induced Nrf2 and HO-1 protein expressions were significantly inhibited by Nrf2 small interfering RNA. Moreover, HO-1 knockdown attenuated the protective effect of andrographolide against oxygen-glucose deprivation-induced CEC death. Andrographolide (0.1 mg/kg) significantly suppressed free radical formation, blood-brain barrier disruption, and brain infarction in MCAO-insulted rats, and these effects were reversed by the HO-1 inhibitor zinc protoporphyrin IX. The mechanism is attributable to HO-1 activation, as directly evidenced by andrographolide-induced pronounced HO-1 expression in brain tissues, which was highly localized in the cerebral capillary. In conclusion, andrographolide increased Nrf2-HO-1 expression through p38 MAPK regulation, confirming that it provides protection against MCAO-induced brain injury. These findings provide strong evidence that andrographolide could be a therapeutic agent for treating ischemic stroke or neurodegenerative diseases.

// Tim Ting-Chung Yen 1 , Anderson Yang 1 , Wen-Tai Chiu 2, 3 , Tian-Neng Li 1 , Lyu-Han Wang 1 , Yi-Hsuan Wu 1 , Hui-Chen Wang 4 , Linyi Chen 5, 6 , Wen-Ching Wang 1 , Wenya Huang 7 , Chien-Wen Chang 8 , Margaret Dah-Tsyr Chang 1, 6 , Meng-Ru Shen 3, 9 , Ih-Jen Su 3, 10, 11 , Lily Hui-Ching Wang 1, 6 1 Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 300, Taiwan 2 Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan 3 Center of Infectious Diseases and Signal Transduction, National Cheng Kung University, Tainan 701, Taiwan 4 Institute of Pharmaceutics, Development Center for Biotechnology, Taipei 22180, Taiwan 5 Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300, Taiwan 6 Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan 7 Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan 8 Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan 9 Department of Pharmacology, National Cheng Kung University, Tainan 701, Taiwan 10 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 704, Taiwan 11 Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan Correspondence to: Lily Hui-Ching Wang, e-mail: lilywang@life.nthu.edu.tw Ih-Jen Su, e-mail: suihjen0704@stust.edu.tw Keywords: SOCE, ER stress, hepatitis B virus, ground-glass hepatocytes, aneuploidy Received: August 21, 2015 Accepted: February 28, 2016 Published: March 16, 2016 ABSTRACT Hepatitis B virus (HBV) is a driver of hepatocellular carcinoma, and two viral products, X and large surface antigen (LHBS), are viral oncoproteins. During chronic viral infection, immune-escape mutants on the preS2 region of LHBS (preS2-LHBS) are gain-of-function mutations that are linked to preneoplastic ground glass hepatocytes (GGHs) and early disease onset of hepatocellular carcinoma. Here, we show that preS2-LHBS provoked calcium release from the endoplasmic reticulum (ER) and triggered stored-operated calcium entry (SOCE). The activation of SOCE increased ER and plasma membrane (PM) connections, which was linked by ER- resident stromal interaction molecule-1 (STIM1) protein and PM-resident calcium release- activated calcium modulator 1 (Orai1). Persistent activation of SOCE induced centrosome overduplication, aberrant multipolar division, chromosome aneuploidy, anchorage-independent growth, and xenograft tumorigenesis in hepatocytes expressing preS2- LHBS. Chemical inhibitions of SOCE machinery and silencing of STIM1 significantly reduced centrosome numbers, multipolar division, and xenograft tumorigenesis induced by preS2-LHBS. These results provide the first mechanistic link between calcium homeostasis and chromosome instability in hepatocytes carrying preS2-LHBS. Therefore, persistent activation of SOCE represents a novel pathological mechanism in HBV-mediated hepatocarcinogenesis.

Sudden sensorineural hearing loss (SSNHL) in pregnancy is rare. It usually occurs in the third trimester. SSNHL in pregnancy does not increase risks during delivery or subsequent stroke.This study aimed to investigate the incidence and to determine the factors associated with SSNHL in pregnancy.Data were retrieved from Taiwan's National Health Insurance Database (NHIRD), covering the years 2000-2009. Patients admitted for SSNHL during pregnancy were enrolled. An age-matched controlled cohort was randomly selected from pregnant women without SSNHL in the NHIRD. The clinical characteristics of both cohorts were collected for further analyses.Thirty-three patients with SSNHL in pregnancy were enrolled. The estimated incidence of SSNHL in pregnancy in Taiwan was 2.71 per 100,000 pregnancies. The incidence of SSNHL in pregnancy was lower than that of the general female population. The incidence of SSNHL in the third trimester was higher compared to the other two. The incidence of SSNHL occurring in the 30-39 years old age group was higher than other groups. Women with better socioeconomic status had a higher incidence of SSNHL. There were no identified systemic diseases before SSNHL. Two patients had pre-eclampsia and one patient had premature delivery. Nevertheless, SSNHL in pregnancy did not increase the risk for stroke.