Surge of Sympathetic Activity during Hyperventilation at the End of Apnea for Patients with Obstructive Sleep Apnea.

Background and Objectives: The mechanisms connecting obstructive sleep apnea (OSA) and cardiovascular disease are multifactorial, involving intermittent hypoxia, hypercapnia, and sympathetic activation. The aim of this study was to explore the oscillations of sympathetic activity during the sleep apnea episodes throughout the entire night in patients with OSA. Materials and Methods: The participants received whole-night polysomnography (PSG), and electrocardiogram (EKG) data from the PSG were collected for heart rate variability (HRV) analysis. HRV measurements were conducted in the time and frequency domains. The root mean square of successive differences between normal heartbeats (RMSSD), which reflects parasympathetic activity, and the ratio of the absolute power of the low-frequency band (0.04-0.15 Hz) to the absolute power of the high-frequency band (0.015-0.4 Hz) (LF/HF ratio), which indicates sympathetic activity, were computed. Results: A total of 43 participants (35 men and 8 women) were included in the analysis. The mean age of the participants was 44.1 ± 11.3 years old, and the mean BMI was 28.6 ± 5.4 kg/m2. The sleep apnea episodes throughout the entire night in patients with OSA were selected randomly and occurred most frequently during the non-REM stages (39, 90.7%). The selected sleep apnea episodes typically exhibited multiple apneas, often interrupted by snoring respiration and followed by hyperventilation at the end of the episode (HE). Our findings indicate that the centers of the 5 min HRV window for the lowest and highest LF/HF ratios, at 111.8 ± 88.2 and 117.4 ± 88.6 min after sleep onset, respectively, showed a statistically significant difference (p < 0.001). Similarly, the ratios of the lowest and highest LF/HF, at 0.82 ± 0.56 and 3.53 ± 2.94, respectively, exhibited a statistically significant difference (p < 0.001). Conclusions: In the current study, the selected sleep apnea episodes throughout the entire night in patients with OSA occurred primarily during the non-REM stages. Additionally, we observed that sympathetic activity reached its peak in the window that includes hyperventilation at the end stage of apnea, potentially posing a cardiovascular risk. However, additional studies are needed to validate these results.

Association of Heart Rate Variability with Obstructive Sleep Apnea in Adults.

Background and Objectives: Heart rate variability (HRV) analysis is a noninvasive method used to examine autonomic system function, and the clinical applications of HRV analysis have been well documented. The aim of this study is to investigate the association between HRV and the apnea-hypopnea index (AHI) in patients referred for polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis. Materials and Methods: Patients underwent whole-night PSG. Data on nocturnal HRV and AHI were analyzed. We determined the correlation of time- and frequency-domain parameters of HRV with the AHI. Results: A total of 62 participants (50 men and 12 women) were enrolled. The mean age, body mass index (BMI), neck circumference, and AHI score of the patients were 44.4 ± 11.5 years, 28.7 ± 5.2, 40.2 ± 4.8 cm, and 32.1 ± 27.0, respectively. The log root mean square of successive differences between normal heartbeats (RMSSD) were negatively correlated with BMI (p = 0.034) and neck circumference (p = 0.003). The log absolute power of the low-frequency band over high-frequency band (LF/HF) ratio was positively correlated with the AHI (p = 0.006). A higher log LF/HF power ratio (ß = 5.01, p = 0.029) and BMI (ß = 2.20, p < 0.001) were associated with a higher AHI value in multiple linear regression analysis. Conclusions: A higher log LF/HF power ratio and BMI were positively and significantly associated with the AHI during whole-night PSG in adult patients.

Validation of snoring detection using a smartphone app.

PURPOSE: Snoring is closely related to obstructive sleep apnea in adults. The increasing abundance and availability of smartphone technology has facilitated the examination and monitoring of snoring at home through snoring apps. However, the accuracy of snoring detection by snoring apps is unclear. This study explored the snoring detection accuracy of Snore Clock-a paid snoring detection app for smartphones. METHODS: Snoring rates were detected by smartphones that had been installed with the paid app Snore Clock. The app provides information on the following variables: sleep duration, snoring duration, snoring loudness (in dB), maximum snoring loudness (in dB), and snoring duration rate (%). In brief, we first reviewed the snoring rates detected by Snore Clock; thereafter, an ear, nose, and throat specialist reviewed the actual snoring rates by using the playback of the app recordings. RESULTS: In total, the 201 snoring records of 11 patients were analyzed. Snoring rates measured by Snore Clock and those measured manually were closely correlated (r = 0.907). The mean snoring detection accuracy rate of Snore Clock was 95%, with a positive predictive value, negative predictive value, sensitivity, and specificity of 65% ± 35%, 97% ± 4%, 78% ± 25%, and 97% ± 4%, respectively. However, the higher the snoring rates, the higher were the false-negative rates for the app. CONCLUSION: Snore Clock is compatible with various brands of smartphones and has a high predictive value for snoring. Based on the strong correlation between Snore Clock and manual approaches for snoring detection, these findings have validated that Snore Clock has the capacity for at-home snoring detection.

Plate osteosynthesis of single metacarpal fracture: WALANT technique is a cost-effective approach to reduce postoperative pain and discomfort in contrast to general anesthesia and wrist block.

BACKGROUND: The WALANT (wide-awake local anesthesia with no tourniquet) technique was based on local infiltration of lidocaine and epinephrine. This technique has rapidly gained popularity in recent years and can perform most hand operations. This study aimed to investigate the time spent on anesthesia and operation and perform an economic analysis among general anesthesia, wrist block with a tourniquet, and the WALANT technique for the internal fixation of metacarpal fractures. METHODS: We retrospectively reviewed all the single metacarpal fractures managed with the same procedure, open reduction, and internal fixation with the plate between January 2015 and December 2019. They were divided into three groups according to the method of anesthesia: (1) general anesthesia (GA group), (2) wrist block with a tourniquet (WB group), and (3) WALANT technique (WALANT group). We collected and analyzed patient demographic data, perioperative or postoperative complications, number of hospital days, and postoperative functional recovery assessment. RESULTS: A total of 63 patients met the inclusion criteria, including 24 in the GA group, 28 in the wrist block group using a tourniquet, and 11 in the WALANT group. There were no complications during the operation and follow-up in each group. The GA group had an average of 32.8 min of anesthesia time, significantly longer than the other two groups. However, there is no significant difference regarding surgical time among the presenting three groups. The discomfort of vomiting and nausea after surgery occurred in 20 patients in the GA group (38.1%). Nevertheless, there was no postoperative vomiting and nausea present in both the WB and WALANT groups. Most patients achieved full recovery of pre-injury interphalangeal and metacarpophalangeal motion at the final assessment of functional recovery. CONCLUSIONS: The patients undergoing metacarpal fixation surgery under WALANT or WB had significantly less anesthesia time and postoperative vomiting and nausea. Moreover, there was no difference in surgical time and intraoperative complications. The time-related reduction improved the utilization of the operation room for additional cases. The reduction of the preoperative examination, anesthesia fee, postoperative recovery room observation, and hospitalization can effectively reduce medical costs. Furthermore, the WALANT group is more acceptable because of no tourniquet, which commonly causes discomfort.

Metabolomics profiling of haloperidol and validation of thromboxane-related signaling in the early development of zebrafish.

Haloperidol is a common butyrophenone-derivative antipsychotic drug that is used clinically to treat schizophrenia and to control Tourette disorder. Haloperidol has been shown to be an embryonic toxicant and to cause a variety of adverse effects that affect human embryonic development. However, the pathway impaired by haloperidol during the developmental stages remains unclear. To elucidate the innate toxicological pathway of haloperidol, we investigated the lethality of haloperidol during the embryonic development of zebrafish. We observed that haloperidol caused serious morphological changes, with an LD50 of 9.7 x 10-6 ± 2.4 x 10-6 µg/L. Next, we established a systematic approach to perform metabolite profiling in embryonic zebrafish with various concentrations of haloperidol and analyzed the metabolites using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). A total of 304 metabolites were identified and 86 metabolites were chosen to predict potential pathways. Among the metabolites, we found through prediction that numerous metabolomics-biological pathways are associated with haloperidol, including peroxisome-proliferator-activated receptor (ppar), thromboxane, and mTOR signaling. Quantitative real time-qPCR was then used to validate the gene expression potentially associated with the thromboxane, which is a metabolic product of arachidonic acid and considered to be important for cell proliferation and the inflammatory response. To sum up, analysis of metabolites in the zebrafish model provides a system for mining biomarkers that reflect biological significance and highlight the therapeutic potency in humans. In addition, it may show potential for application to other pharmaceuticals to identify their various activities and clarify functional mechanisms in the future.

Fucoidan⁻Fucoxanthin Ameliorated Cardiac Function via IRS1/GRB2/ SOS1, GSK3ß/CREB Pathways and Metabolic Pathways in Senescent Mice.

The effects of low molecular weight fucoidan (LMWF) in combination with high-stability fucoxanthin (HSFUCO) on cardiac function and the metabolic pathways of aging mice (Mus musculus) were investigated. We demonstrated that LMWF and HSFUCO could improve cardiac function in aging mice. Aging mice were treated with LMWF and HSFUCO, either on their own or in combination, on 28 consecutive days. Electrocardiography and whole-cell patch-clamp were used to measure QT interval and action potential duration (APD) of the subjects. Cardiac tissue morphology, reactive oxygen species, and Western blot were also applied. Ultra-high-performance liquid chromatography⁻quadrupole time-of-flight (UPLC-QTOF) mass spectrometry was used for investigating metabolic alterations. The use of LMWF and HSFUCO resulted in improvements in both ventricular rhythms (QT and APD). Treatment with fucoidan and fucoxanthin reduced the expression levels of SOS1 and GRB2 while increasing GSK3ß, CREB and IRS1 proteins expression in the aging process. Three main metabolic pathways, namely the TCA cycle, glycolysis, and steroid hormone biosynthesis, were highly enriched in the pathway enrichment analysis. When taken together, the LMWF and HSFUCO treatment improved both the ventricular rhythm and the muscular function of aging subjects by interfering with the metabolism and gene function.

Arsenic induces cardiac rhythm dysfunction and acylcarnitines metabolism perturbation in rats.

BACKGROUND: Arsenic has been shown to cause various diseases (such as blackfoot disease, cardiovascular diseases, bladder cancer and skin cancer) in many areas of the world. However, the effects of arsenic on cardiac rhythm functions still lack investigation. METHODS: In this study, different concentrations of arsenic were orally applied to Sprague Dawley rats in order to examine the relationship between arsenic and cardiovascular rhythm (i.e. long QT) via electrocardiography measurement. In addition, QT correction formulas were used to correct the QT interval. Linear regression analysis was used to examine the correlation between the QT interval and cardiac cycle length, corrected QT and heart rate. A metabolomic approach was applied to study carnitine-derived metabolites under arsenic exposure by using an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) system. RESULTS: The present findings showed that exposure to arsenic causes QT and corrected (QTc) prolongation and heart rate declines. However, the linear correlation analysis showed that there is no significant correlation between cardiac cycle length and the QT interval in both the uncorrected QT and corrected QT. The expression of acylcarnitine metabolites can be used to discriminate the control and arsenic-treated groups. CONCLUSIONS: This study provides information concerning the effect of arsenic at different concentrations on cardiac rhythm (such as QT, QTc, and heart rate) but not on cardiac cycle length. The metabolism of acylcarnitine metabolites can be a potential pathway for arsenic-induced cardiac rhythm dysfunction in rats.

Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling.

Heterogeneous nuclear ribonucleoprotein K (hnRNP K) binds to the promoter region of mu-opioid receptor (MOR) to regulate its transcriptional activity. How hnRNP K contributes to the analgesic effects of morphine, however, is largely unknown. We provide evidence that morphine increases hnRNP K protein expression via MOR activation in rat primary cortical neurons and HEK-293 cells expressing MORs, without increasing mRNA levels. Using the bicistronic reporter assay, we examined whether morphine-mediated accumulation of hnRNP K resulted from translational control. We identified potential internal ribosome entry site elements located in the 5' untranslated regions of hnRNP K transcripts that were regulated by morphine. This finding suggests that internal translation contributes to the morphine-induced accumulation of hnRNP K protein in regions of the central nervous system correlated with nociceptive and antinociceptive modulatory systems in mice. Finally, we found that down-regulation of hnRNP K mediated by siRNA attenuated morphine-induced hyperpolarization of membrane potential in AtT20 cells. Silencing hnRNP K expression in the spinal cord increased nociceptive sensitivity in wild-type mice, but not in MOR-knockout mice. Thus, our findings identify the role of translational control of hnRNP K in morphine-induced analgesia through activation of MOR.

Toxicological Evaluation of Low Molecular Weight Fucoidan in Vitro and in Vivo.

For a long time, fucoidan has been well known for its pharmacological activities, and recently low molecular weight fucoidan (LMF) has been used in food supplements and pharmaceutical products. In the present study, LMF was extracted from Laminaria japonica by enzyme hydrolysis. The toxicity of LMF in mouse and rat models was determined by many methods, such as total arsenic content, bacterial reverse mutation assay, chromosome aberration assay, and in vivo micronucleus assay. The present findings showed that LMF at 5000 µg/mL exhibited no mutagenicity. It also produced no formatting disruption of red blood cells in vivo. At 2000 mg/kg BW/day there were no toxicological indications. LMF is expected to be used as a safe food supplement.

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor.

Leptin has been proposed to modulate cardiac electrical properties via ß-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 µg/kg) decreased resting heart rate; at high doses (150-300 µg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 µg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of ß-adrenergic receptor stimulation. During inhibition of ß-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias.

PP2 prevents isoproterenol stimulation of cardiac pacemaker activity.

Increasing evidence has demonstrated the potential risks of cardiac arrhythmias (such as prolonged QT interval) using tyrosine kinase inhibitors for cancer therapy. We report here that a widely used selective inhibitor of Src tyrosine kinases, PP2, can inhibit and prevent isoproterenol stimulation of cardiac pacemaker activity. In dissected rat sinus node, PP2 inhibited and prevented isoproterenol stimulation of spontaneous beating rate. In isolated sinus node myocytes, PP2 suppressed the hyperpolarization-activated "funny" current (If) by negatively shifting the activation curve and decelerating activation kinetics, associated with decreased cell surface expression and reduced tyrosine phosphorylation of hyperpolarization-activated cyclic nucleotide-modulated channel 4 (HCN4) channel proteins. In human embryonic kidney 293 cells overexpressing recombinant human HCN4 channels, PP2 reversed isoproterenol stimulation of HCN4 and inhibited HCN4-573x, a cAMP-insensitive human HCN4 mutant. Isoprotenrenol had little effects on HCN4-573x. These results demonstrated that inhibition of presumably tyrosine Src kinase activity in heart by PP2 decreased and prevented the potential ß-adrenergic stimulation of cardiac pacemaker activity. These effects are mediated, at least partially, by a cAMP-independent attenuation of channel activity and cell surface expression of HCN4, the key channel protein that controls the heart rate.

Cardiovascular effects in rats after intratracheal instillation of metal welding particles.

Studies have indicated that pulmonary exposure to welding fumes can induce a series of adverse effects in the respiratory system, including infection, bronchitis, siderosis and decreased pulmonary function. Recent clinical and epidemiological studies have found that pulmonary exposure to welding fumes is also associated with a higher incidence of cardiovascular events. However, there is insufficient evidence to confirm a direct effect of welding fumes on the cardiovascular system. The present study investigated the effects of pulmonary exposure to welding fumes on the heart and the vascular system in rats. Two chemically distinct welding fumes generated from manual metal arc-hard surfacing (MMA-HS) and gas metal arc-mild steel (GMA-MS) welding were tested. Three groups of rats were instilled intratracheally with MMA-HS (2 mg/rat), GMA-MS (2 mg/rat) or saline as control once a week for seven weeks. On days 1 and 7 after the last treatment, basal cardiovascular function and the cardiovascular response to increasing doses of adrenoreceptor agonists were assessed. MMA-HS treatment reduced the basal levels of left ventricle end-systolic pressure and dP/dt(max) at 1 day post-treatment, and decreased dP/dt(min) in response to isoproterenol (ISO) at 7 days post-treatment. Unlike MMA-HS, GMA-MS only affected left ventricular end-diastolic pressure in response to ISO at 7 days post-treatment. Treatment with MMA-HS or GMA-MS did not alter heart rate and blood pressure. Our findings suggest that exposure to different welding fumes can induce different adverse effects on the cardiovascular system, and that cardiac contractility may be a sensitive indicator of cardiovascular dysfunction.

PP2 prevents ß-adrenergic stimulation of cardiac pacemaker activity.

One of the main strategies for cancer therapy is to use tyrosine kinase inhibitors for inhibiting tumor proliferation. Increasing evidence has demonstrated the potential risks of cardiac arrhythmias (such as prolonged QT interval) of these drugs. We report here that a widely used selective inhibitor of Src tyrosine kinases, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), can inhibit and prevent ß-adrenergic stimulation of cardiac pacemaker activity. First, in dissected rat sinus node, PP2 inhibited and prevented the isoproterenol-induced increase of spontaneous beating rate. Second, in isolated rat sinus node myocytes, PP2 suppressed the hyperpolarization-activated "funny" current (traditionally called cardiac pacemaker current, I(f)) by negatively shifting the activation curve and decelerating activation kinetics. Third, in isolated rat sinus node myocytes, PP2 decreased the Src kinase activity, the cell surface expression, and tyrosine phosphorylation of hyperpolarization-activated, cyclic nucleotide-modulated channel 4 (HCN4) channel proteins. Finally, in human embryonic kidney 293 cells overexpressing recombinant human HCN4 channels, PP2 reversed the enhancement of HCN4 channels by isoproterenol and inhibited 573x, a cyclic adenosine momophosphate-insensitive human HCN4 mutant. These results demonstrated that inhibition of Src kinase activity in heart by PP2 decreased and prevented ß-adrenergic stimulation of cardiac pacemaker activity. These effects are mediated, at least partially, by a cAMP-independent attenuation of channel activity and cell surface expression of HCN4, the main channel protein that controls the heart rate.

High yield production of pigeon circovirus capsid protein in the E. coli by evaluating the key parameters needed for protein expression.

BACKGROUND: Pigeon circovirus (PiCV) is considered to be a viral agent central to the development of young pigeon disease syndrome (YPDS). The Cap protein, a structural protein encoded by the cap (or C1) gene of PiCV, has been shown to be responsible for not only capsid assembly, but also has been used as antigen for detecting antibody when the host is infected with PiCV. The antigenic characteristics of the Cap protein potentially may allow the development of a detection kit that could be applied to control PiCV infection. However, poor expression and poor protein solubility have hampered the production of recombinant Cap protein in the bacteria. This study was undertaken to develop the optimal expression of recombinant full-length Cap protein of PiCV using an E. coli expression system. RESULTS: The PiCV cap gene was cloned and fused with different fusion partners including a His-tag, a GST-tag (glutathioine-S-transferase tag) and a Trx-His-tag (thioredoxin-His tag). The resulting constructs were then expressed after transformation into a number of different E. coli strains; these then had their protein expression evaluated. The expression of the recombinant Cap protein in E. coli was significantly increased when Cap protein was fused with either a GST-tag or a Trx-His tag rather than a His-tag. After various rare amino acid codons presented in the Cap protein were optimized to give the sequence rCapopt, the expression level of the GST-rCapopt in E. coli BL21(DE3) was further increased to a significant degree. The highest protein expression level of GST-rCapopt obtained was 394.27 ± 26.1 mg/L per liter using the E. coli strain BL21(DE3)-pLysS. Moreover, approximately 74.5% of the expressed GST-rCapopt was in soluble form, which is higher than the soluble Trx-His-rCapopt expressed using the BL21(DE3)-pLysS strain. After purification using a GST affinity column combined with ion-exchange chromatography, the purified recombinant GST-rCapopt protein was found to have good antigenic activity when tested against PiCV-infected pigeon sera. CONCLUSIONS: These findings shows that the E. coli-expressed full-length PiCV Cap protein has great potential in terms of large-scaled production and this should allow in the future the development of a serodiagnostic kit that is able to clinically detect PiCV infection in pigeons.

Influences of Ipomoea batatas Anti-Cancer Peptide on Tomato Defense Genes.

AIMS: This study investigates the impact of IbACP (Ipomoea batatas anti-cancer peptide) on defense-related gene expression in tomato leaves, focusing on its role in plant defense mechanisms. BACKGROUND: Previously, IbACP was isolated from sweet potato leaves, and it was identified as a peptide capable of inducing an alkalinization response in tomato suspension culture media. Additionally, IbACP was found to regulate the proliferation of human pancreatic adenocarcinoma cells. OBJECTIVE: Elucidate IbACP's molecular influence on defense-related gene expression in tomato leaves using next-generation sequencing analysis. METHOD: To assess the impact of IbACP on defense-related gene expression, transcriptome data were analyzed, encompassing various functional categories such as photosynthesis, metabolic processes, and plant defense. Semi-quantitative reverse-transcription polymerase chain reaction analysis was employed to verify transcription levels of defense-related genes in tomato leaves treated with IbACP for durations ranging from 0 h (control) to 24 h. RESULTS: IbACP induced jasmonic acid-related genes (LoxD and AOS) at 2 h, with a significant up-regulation of salicylic acid-dependent gene NPR1 at 24 h. This suggested a temporal antagonistic effect between jasmonic acid and salicylic acid during the early hours of IbACP treatment. Downstream ethylene-responsive regulator genes (ACO1, ETR4, and ERF1) were consistently down-regulated by IbACP at all times. Additionally, IbACP significantly up-regulated the gene expressions of suberization-associated anionic peroxidases (TMP1 and TAP2) at all time points, indicating enhanced suberization of the plant cell wall to prevent pathogen invasion. CONCLUSION: IbACP enhances the synthesis of defense hormones and up-regulates downstream defense genes, improving the plant's resistance to biotic stresses.

Oscillation of Sympathetic Activity in Patients with Obstructive Sleep Apnea during the First Hour of Sleep.

(1) Background: Snoring is a cardinal symptom of obstructive sleep apnea (OSA) and has been suggested to potentially increase sympathetic activity. On the other hand, sleep itself usually leads to a decrease in sympathetic activity. Heart rate variability (HRV) analysis is a non-invasive technique used to assess autonomic nervous system function. However, there is limited research on the combined impact of sleep and snoring on sympathetic activity in individuals with OSA, particularly during the first hour of sleep (non-rapid eye movement sleep). The current study aims to investigate the net effect of sleep and snoring on sympathetic activity and explore factors that might contribute to increased sympathetic activity in individuals with OSA during the first hour of sleep. (2) Methods: The participants were referred from the outpatient department for OSA diagnosis and underwent whole-night polysomnography (PSG). Electrocardiogram (EKG) data from the PSG were downloaded for HRV analysis. HRV measurements were conducted in both the time and frequency domain, including the root mean square of successive differences between normal heartbeats (RMSSD) and the ratio of the absolute power of the low-frequency (LF) band (0.04-0.15 Hz) to the absolute power of the high-frequency (HF) band (0.15-0.4 Hz) (LF/HF ratio), respectively. (3) Results: A total of 45 participants (38 men and 7 women) were included in the analysis. The RMSSD gradually increased from 0-5 min to 50-60 min (p = 0.024), while the LF/HF ratio decreased (p < 0.001) during the first hour of sleep (non-rapid eye movement sleep). The LF/HF ratios of the "S" (snoring) episodes were compared with those of the pre-S episodes. An elevated LF/HF ratio during the S episode was associated with the first snoring episode occurring more than 20 min after lying down to sleep (Odds ratio, OR = 10.9, p = 0.004) and with patients diagnosed with severe OSA (OR = 5.01, p = 0.045), as determined by logistic regression. (4) Conclusions: The study observed an increase in the value of RMSSD and a decrease in the value of the LF/HF ratio during the first hour of sleep for patients with OSA. Higher LF/HF ratios were associated with the first occurrence of snoring while lying down for more than 20 min and with patients with severe OSA.

Defective calcium inactivation causes long QT in obese insulin-resistant rat.

The majority of diabetic patients who are overweight or obese die of heart disease. We suspect that the obesity-induced insulin resistance may lead to abnormal cardiac electrophysiology. We tested this hypothesis by studying an obese insulin-resistant rat model, the obese Zucker rat (OZR). Compared with the age-matched control, lean Zucker rat (LZR), OZR of 16-17 wk old exhibited an increase in QTc interval, action potential duration, and cell capacitance. Furthermore, the L-type calcium current (I(CaL)) in OZR exhibited defective inactivation and lost the complete inactivation back to the closed state, leading to increased Ca(2+) influx. The current density of I(CaL) was reduced in OZR, whereas the threshold activation and the current-voltage relationship of I(CaL) were not significantly altered. L-type Ba(2+) current (I(BaL)) in OZR also exhibited defective inactivation, and steady-state inactivation was not significantly altered. However, the current-voltage relationship and activation threshold of I(BaL) in OZR exhibited a depolarized shift compared with LZR. The total and membrane protein expression levels of Cav1.2 [pore-forming subunit of L-type calcium channels (LTCC)], but not the insulin receptors, were decreased in OZR. The insulin receptor was found to be associated with the Cav1.2, which was weakened in OZR. The total protein expression of calmodulin was reduced, but that of Cavß2 subunit was not altered in OZR. Together, these results suggested that the 16- to 17-wk-old OZR has 1) developed cardiac hypertrophy, 2) exhibited altered electrophysiology manifested by the prolonged QTc interval, 3) increased duration of action potential in isolated ventricular myocytes, 4) defective inactivation of I(CaL) and I(BaL), 5) weakened the association of LTCC with the insulin receptor, and 6) decreased protein expression of Cav1.2 and calmodulin. These results also provided mechanistic insights into a remodeled cardiac electrophysiology under the condition of insulin resistance, enhancing our understanding of long QT associated with obese type 2 diabetic patients.

Long-term benefits of a new oral appliance on adult snoring: a trend analysis.

Background: Snoring constitutes a worldwide public health concern that may be associated with daytime fatigue, endothelial dysfunction, vascular injury, stroke, cardiovascular diseases, and diabetes among female patients. This study explored the effects of the so-called Lin Oral Appliance (LOA) on Taiwanese adults' snoring rates. Methods: A time series analysis was conducted to examine the associations between LOAs' tongue compressors of different lengths, and snoring rates were calculated using the SnoreClock app. The LOA comprises 2 components: custom- made dental braces and tongue compressors of adjustable lengths; different versions had different-length compressors. Results: Our multiple linear regression time-series model revealed the effects of the LOA on snoring rates. The results indicated the following: i) LOA tongue compressor lengths of 1 and 2.5 cm (LOA-1 and LOA-2.5, respectively) were associated with reduced snoring rates; ii) sleep durations of 5.5-7.5 h and daytime sleepiness were associated with increased snoring rates; and iii) among participants with snoring rates above 10%, the snoring rates observed 1-7 days before a given day constituted a significant factor influencing snoring rates on the given day. Conclusions: We discovered that the LOA could reduce snoring rates and that the 2.5-cm compressor length in the LOA produced the best results.

Correlation between snoring sounds and obstructive sleep apnea in adults: a meta-regression analysis.

Objective: Snoring is a dominant clinical symptom in patients with obstructive sleep apnea (OSA), and analyzing snoring sounds might be a potential alternative to polysomnography (PSG) for the assessment of OSA. This study aimed to systematically examine the correlation between the snoring sounds and the apnea-hypopnea index (AHI) as the measures of OSA severity. Material and Methods: A comprehensive literature review using the MEDLINE, Embase, Cochrane Library, Scopus, and PubMed databases identified the published studies reporting the correlations between and severity of snoring and the AHI values by meta-regression analysis. Results: In total, 13 studies involving 3,153 adult patients were included in this study. The pooled correlation coefficient for snoring sounds and AHI values was 0.71 (95%CI: 0.49, 0.85) from the random-effects meta-analysis with the Knapp and Hartung adjustment. The I 2 and chi-square Q test demonstrated significant heterogeneity (97.6% and p<0.001). After adjusting for the effects of the other covariates, the mean value of the Fisher's r-to-z transformed correlation coefficient would have 0.80 less by the snoring rate (95%CI = -1.02, -0.57), 1.46 less by the snoring index (95%CI = -1.85, -1.07), and 0.21 less in the mean body mass index (95%CI = -0.31, -0.11), but 0.15 more in the mean age (95%CI = 0.10, 0.20). It fitted the data very well (R 2=0.9641). Conclusion: A high correlation between the severity of snoring and the AHI was found in the studies with PSG. As compared to the snoring rate and the snoring index, the snoring intensity, the snoring frequency, and the snoring time interval index were more sensitive measures for the severity of snoring.

Snoring Index and Neck Circumference as Predictors of Adult Obstructive Sleep Apnea.

Background. Snoring is the cardinal symptom of obstructive sleep apnea (OSA). The acoustic features of snoring sounds include intra-snore (including snoring index [SI]) and inter-snore features. However, the correlation between snoring sounds and the severity of OSA according to the apnea−hypopnea index (AHI) is still unclear. We aimed to use the snoring index (SI) and the Epworth Sleepiness Scale (ESS) to predict OSA and its severity according to the AHI among middle-aged participants referred for polysomnography (PSG). Methods. In total, 50 participants (mean age, 47.5 ± 12.6 years; BMI: 29.2 ± 5.6 kg/m2) who reported snoring and were referred for a diagnosis of OSA and who underwent a whole night of PSG were recruited. Results. The mean AHI was 30.2 ± 27.2, and the mean SI was 87.9 ± 56.3 events/hour. Overall, 11 participants had daytime sleepiness (ESS > 10). The correlation between SI and AHI (r = 0.33, p = 0.021) was significant. Univariate linear regression analysis showed that male gender, body mass index, neck circumference, ESS, and SI were associated with AHI. SI (ß = 0.18, p = 0.004) and neck circumference (ß = 2.40, p < 0.001) remained significantly associated with AHI by the multivariate linear regression model. Conclusion. The total number of snores per hour of sleep and neck circumference were positively associated with OSA among adults referred for PSG.