Inflammation alters trafficking of extrasynaptic AMPA receptors in tonically firing lamina II neurons of the rat spinal dorsal horn

Peripheral inflammation alters AMPA receptor (AMPAR) subunit trafficking and increases AMPAR Ca²⁺ permeability at synapses of spinal dorsal horn neurons. However, it is unclear whether AMPAR trafficking at extrasynaptic sites of these neurons also changes under persistent inflammatory pain conditions. Using patch-clamp recording combined with Ca²⁺ imaging and cobalt staining, we found that, under normal conditions, an extrasynaptic pool of AMPARs in rat substantia gelatinosa (SG) neurons of spinal dorsal horn predominantly consists of GluR2-containing Ca²⁺-impermeable receptors. Maintenance of complete Freund’s adjuvant (CFA)-induced inflammation was associated with a marked enhancement of AMPA-induced currents and [Ca²⁺]_i transients in SG neurons, while, as we previously showed, the amplitude of synaptically evoked AMPAR-mediated currents was not changed 24 h after CFA. These findings indicate that extrasynaptic AMPARs are upregulated and their Ca²⁺ permeability increases dramatically. This increase occurred in SG neurons characterized by intrinsic tonic firing properties, but not in those exhibited strong adaptation. This increase was also accompanied by an inward rectification of AMPA-induced currents and enhancement of sensitivity to a highly selective Ca²⁺-permeable AMPAR blocker, IEM-1460. Electron microcopy and biochemical assays additionally showed an increase in the amount of GluR1 at extrasynaptic membranes in dorsal horn neurons 24 h post-CFA. Taken together, our findings indicate that CFA-induced inflammation increases functional expression and proportion of extrasynaptic GluR1-containing Ca²⁺-permeable AMPARs in tonically firing excitatory dorsal horn neurons, suggesting that the altered extrasynaptic AMPAR trafficking might participate in the maintenance of persistent inflammatory pain.     

Problem solving strategies integrated into nursing process to promote clinical problem solving abilities of RN-BSN students

A set of problem solving strategies integrated into nursing process in nursing core courses (PSNP) was developed for students enrolled in a post-RN baccalaureate nursing program (RN-BSN) in a university in Taiwan. The purpose of this study, therefore, was to evaluate the effectiveness of PSNP on students' clinical problem solving abilities. The one-group post-test design with repeated measures was used. In total 114 nursing students with 47 full-time students and 67 part-time students participated in this study. The nursing core courses were undertaken separately in three semesters. After each semester's learning, students would start their clinical practice, and were asked to submit three written nursing process recordings during each clinic. Assignments from the three practices were named post-test I, II, and III sequentially, and provided the data for this study. The overall score of problem solving indicated that score on the post-test III was significantly better than that on post-test I and II, meaning both full-time and part-time students' clinical problem solving abilities improved at the last semester. In conclusion, problem-solving strategies integrated into nursing process designed for future RN-BSN students are recommendable.     

Anticancer peptide Q7 suppresses the growth and migration of human endometrial cancer by inhibiting DHCR24 expression and modulating the AKT-mediated pathway

Endometrial cancer is one of the most common malignancy affecting women in developed countries. Resection uterus or lesion area is usually the first option for a simple and efficient therapy. Therefore, it is necessary to find a new therapeutic drug to reduce surgery areas to preserve fertility. Anticancer peptides (ACP) are bioactive amino acids with lower toxicity and higher specificity than chemical drugs. This study is to address an ACP, herein named Q7, which could downregulate 24-Dehydrocholesterol Reductase (DHCR24) to disrupt lipid rafts formation, and sequentially affect the AKT signal pathway of HEC-1-A cells to suppress their tumorigenicity such as proliferation and migration. Moreover, lipo-PEI-PEG-complex (LPPC) was used to enhance Q7 anticancer activity in vitro and efficiently show its effects on HEC-1-A cells. Furthermore, LPPC-Q7 exhibited a synergistic effect in combination with doxorubicin or paclitaxel. To summarize, Q7 was firstly proved to exhibit an anticancer effect on endometrial cancer cells and combined with LPPC efficiently improved the cytotoxicity of Q7.     

Early Life Low-Calorie Sweetener Consumption Impacts Energy Balance during Adulthood

Children frequently consume beverages that are either sweetened with sugars (sugar-sweetened beverages; SSB) or low-calorie sweeteners (LCS). Here, we evaluated the effects of habitual early life consumption of either SSB or LCS on energy balance later during adulthood. Male and female rats were provided with chow, water, and a solution containing either SSB (sucrose), LCS (acesulfame potassium (ACE-K) or stevia), or control (no solution) during the juvenile and adolescent periods (postnatal days 26–70). SSB or LCS consumption was voluntary and restricted within the recommended federal daily limits. When subsequently maintained on a cafeteria-style junk food diet (CAF; various high-fat, high-sugar foods) during adulthood, ACE-K-exposed rats demonstrated reduced caloric consumption vs. the controls, which contributed to lower body weights in female, but not male, ACE-K rats. These discrepant intakes and body weight effects in male ACE-K rats are likely to be based on reduced gene expression of thermogenic indicators (UCP1, BMP8B) in brown adipose tissue. Female stevia-exposed rats did not differ from the controls in terms of caloric intake or body weight, yet they consumed more SSB during CAF exposure in adulthood. None of the SSB-exposed rats, neither male nor female, differed from the controls in terms of total adult caloric consumption or body weight measures. The collective results reveal that early life LCS consumption alters sugar preference, body weight, and gene expression for markers of thermogenesis during adulthood, with both sex- and sweetener-dependent effects.     

Antifungal susceptibility testing and the correlation with clinical outcome in neonatal candidemia.

The objective of this article is to assess the distribution of minimal inhibition concentrations (MIC) for candidal isolates from bloodstreams in neonates and to assess the correlation of clinical outcome with antifungal susceptibility testing. Of the 62 episodes of neonatal candidemia in a Children's Hospital between January 1994 and July 1998, 38 stocked isolates from 38 infants' bloodstreams were available and underwent antifungal susceptibility test according to National Committee for Clinical Laboratory Standards M27-A document. Correlation of clinical response with in vitro results was assessed in 37 patient-episode-isolate events. No less than 90% of these isolates tested were susceptible to amphotericin B, flucytosin, and fluconazole. The ranges of amphotericin B MICs and flucytosin MICs were narrow, ranging from 0.25 to 2 microg/mL, respectively. The range of fluconazole MICs was broad, ranging from 0.25 to >64 microg/mL. Successful therapy was achieved in 18 (62%) of 29 amphotericin B-treated patient-episode-susceptible isolate (MIC < or =1 microg/mL) events and 9 (64%) of 14 fluconazole-treated patient-episode-susceptible isolate events, respectively. Most isolates from the bloodstreams of neonates with candidemia were susceptible to antifungal agents tested but a low MIC of the antifungal agent did not predict successful therapy in this study. Correlating MICs with clinical outcome in neonatal candidemia requires complex evaluation of other factors.     

Immunogenicity and fecal poliovirus excretion in sequential use of inactivated and oral poliovirus vaccines.

BACKGROUND AND PURPOSE: Though inoculation with inactivated poliovirus vaccine (IPV) is advocated, sequential use of IPV and live oral poliovirus vaccines (OPV) has many advantages. This study aimed to define the immunogenicities of IPV and OPV in Taiwanese children after the use of a sequential schedule of IPV-OPV and also to determine whether prior IPV inoculation hampers the fecal passage of OPV. METHODS: Fifty-nine infants were recruited to receive IPV-OPV sequential vaccinations consisting of IPV given at the ages of 2 and 4 months and OPV given at the ages of 6 and 18 months. Blood samples were taken at ages 2, 6, 18, and 19 months for antibody determination, and stool samples were collected to isolate vaccine strains of poliovirus after the second dose of OPV, at the age of 18 months. RESULTS: None of the children had severe systemic or local reactions. Protective antibodies were detected in all infants at the age of 6 months, 2 months after the second IPV dose. The antibody titers were augmented at the age of 19 months, 1 month after the booster dose of OPV. Stool samples collected 7 days after the second dose of OPV yielded at least one type of poliovirus in 9 of 18 children. Analysis of stool samples revealed that poliovirus was excreted by the 28th day in only two of the children. CONCLUSIONS: Our study showed that both IPV and OPV exhibit immunogenicity in Taiwanese children. Side effects of an IPV-OPV sequential schedule were mild and infrequent. Viral shedding in stools after OPV vaccination was preserved in a substantial proportion of subjects. These findings suggest that this sequential vaccination schedule can maintain herd immunity.     

Stable carbon isotopic characterization of rice vinegar protein as an intrinsic reference for discriminating the authenticity of brewed rice vinegar

Rice vinegar plays an important role in daily life. However, some unscrupulous manufacturers may deliberately add synthetic acetic acid in vinegar products to reduce fermentation time and save production costs. To protect the rights and health of consumers, vinegar authenticity must be controlled. The rice vinegar protein was used as an intrinsic reference and its stable carbon isotope ratio (δ¹³C_protein) was analyzed by elemental analyzer-isotope ratio mass spectrometry. The stable carbon isotope ratio difference between the acetic acid and the rice vinegar protein (Δδ¹³C_{acetic acid-protein}) was calculated to evaluate vinegar authenticity. Sixteen rice vinegar samples were analyzed and a stable carbon isotopic pattern of rice vinegar was established by the 95% confidence interval for Δδ¹³C_{acetic acid-protein} (0.27‰–2.10‰). An acetic acid adulteration curve of Δδ¹³C_{acetic acid-protein} was also assumed according to the data from rice vinegar samples, and its validity was confirmed by rice vinegar deliberately blended with acetic acid at different ratios (25, 50, and 75%). The Δδ¹³C_{acetic acid-protein} values of the adulterated vinegars decreased with increasing amounts blended acetic acid, but the δ¹³C_protein values did not, showing that rice vinegar protein could be used as an intrinsic reference for identifying the adulterated rice vinegar. The rice vinegar adulterated with acetic acid at higher than approximately 10% could be detected.     

Predictive Factors for a Successful Treatment Outcome in Patients with Different Voiding Dysfunction Subtypes Who Received Urethral Sphincter Botulinum Injection

Voiding dysfunction is a common but bothersome problem in both men and women. Urethral sphincter botulinum toxin A (BoNT-A) injections could serve as an option in refractory cases. This study analyzed the efficacy and outcome predictors of the injections in patients with functional, non-neurogenic voiding dysfunction. Patients who received urethral sphincter BoNT-A injection for refractory voiding dysfunction due to detrusor underactivity (DU) or urethral sphincter dysfunction were retrospectively reviewed. A successful outcome was defined as a marked improvement as reported in the global response assessment. The study evaluated the therapeutic efficacy of urethral sphincter BoNT-A injections and measured the changes in urodynamic parameters after the procedure in the patients. A total of 181 patients including 138 women and 43 men were included. The overall success rate was 64%. A lower success rate was noted in patients with DU compared to those with urethral sphincter dysfunction in both genders. In the multivariable analysis, recurrent urinary tract infection (UTI) and bladder voiding efficiency (BVE) were positive predictors for a successful outcome, while DU was a negative predictor. Urethral sphincter BoNT-A injection is an effective treatment for refractory non-neurogenic voiding dysfunction. Baseline BVE and history of recurrent UTI positively predict a successful outcome. DU is a negative outcome predictor.     

Heart rate as an early predictor of severe cardiomyopathy and increased mortality in peripartum cardiomyopathy

BackgroundDelays in diagnosis of peripartum cardiomyopathy (PPCM) are common and are associated with worse outcomes; however, few studies have addressed methods for improving early detection.HypothesisWe hypothesized that easily accessible data (heart rate [HR] and electrocardiograms [ECGs]) could identify women with more severe PPCM and at increased risk of adverse outcomes.MethodsClinical data, including HR and ECG, from patients diagnosed with PPCM between January 1998 and July 2016 at our institution were collected and analyzed. Linear and logistic regression were used to analyze the relationship between HR at diagnosis and the left ventricular ejection fraction (LVEF) at diagnosis. Outcomes included overall mortality, recovery status, and major adverse cardiac events.ResultsAmong 82 patients meeting inclusion criteria, the overall mean LVEF at diagnosis was 26 ± 11.1%. Sinus tachycardia (HR > 100) was present in a total of 50 patients (60.9%) at the time of diagnosis. In linear regression, HR significantly predicted lower LVEF (F = 30.00, p < .0001). With age‐adjusted logistic regression, elevated HR at diagnosis was associated with a fivefold higher risk of overall mortality when initial HR was >110 beats per minute (adjusted odds ratio 5.35, confidence interval 1.23–23.28), p = .025).ConclusionIn this study, sinus tachycardia in women with PPCM was associated with lower LVEF at the time of diagnosis. Tachycardia in the peripartum period should raise concern for cardiomyopathy and may be an early indicator of adverse prognosis.     

Transient-evoked otoacoustic emission signals predicting outcomes of acute sensorineural hearing loss in patients with Ménière’s disease

Abstract

Background: Fluctuating hearing loss is characteristic of Ménière’s disease (MD) during acute episodes. However, no reliable audiometric hallmarks are available for counselling the hearing recovery possibility.

Aims/objectives: To find parameters for predicting MD hearing outcomes.

Material and methods: We applied machine learning techniques to analyse transient-evoked otoacoustic emission (TEOAE) signals recorded from patients with MD. Thirty unilateral MD patients were recruited prospectively after onset of acute cochleo-vestibular symptoms. Serial TEOAE and pure-tone audiogram (PTA) data were recorded longitudinally. Denoised TEOAE signals were projected onto the three most prominent principal directions through a linear transformation. Binary classification was performed using a support vector machine (SVM). TEOAE signal parameters, including signal energy and group delay, were compared between improved (PTA improvement: ≥15?dB) and nonimproved groups using Welch’s t-test.

Results: Signal energy did not differ (p?=?.64) but a significant difference in 1-kHz (p?=?.045) group delay was recorded between improved and nonimproved groups. The SVM achieved a cross-validated accuracy of >80% in predicting hearing outcomes.

Conclusions and significance: This study revealed that baseline TEOAE parameters obtained during acute MD episodes, when processed through machine learning technology, may provide information on outer hair cell function to predict hearing recovery.