Association of genetic variants in the Sirt1 and Nrf2 genes with the risk of metabolic syndrome in a Chinese Han population.

BACKGROUND: Metabolic syndrome (MetS) is a complex of interrelated risk factors, including central adiposity, increased blood pressure, hyperglycemia, elevated triglyceride levels and low high-density lipoprotein. Few studies have reported the genetic variants in the Sirt1 and Nrf2 genes (Sirt1 rs7895833 A > G, Sirt1 rs2273773 C > T and Nrf2 rs6721961 C > A) that increase the risk of type 2 diabetes mellitus and are correlated with some glycemic and metabolic traits in the Chinese Han population. METHODS: Our study recruited 141 individuals with MetS and 549 individuals without MetS to investigate the associations between three single nucleotide polymorphisms (SNPs) of Sirt1 and Nrf2 and the risk of MetS in a Chinese Han population using the PCR-CTPP method. RESULTS: This research showed that the risk of MetS was 2.41 times higher for the AA genotype (P = 0.038) and 1.94 times higher for the AG genotype (P = 0.016) compared with carriers of the GG genotype. The serum levels of low-density lipoprotein cholesterol and HOMA-IR were significantly higher (P < 0.05) in carriers of the AA genotype of Sirt1 rs7895833 than in carriers of the AG and GG genotypes in the general population. The serum level of total cholesterol in the AA genotype was lower (P = 0.033) than that in the other two genotypes. However, the genotype frequencies of Sirt1 rs2273773 and Nrf2 rs6721961 in the MetS group were not significantly different from those in the control subjects, and those two genetic variants were not correlated with metabolic traits. CONCLUSIONS: These results underscore the contributions of SNPs of Sirt1 rs7895833 to MetS susceptibility as well as glycemic and metabolic traits in a Chinese population.

[PTX3 promotes proliferation, invasion and drug resistance of neuroblastoma cells in children by regulating TLR4/NF-κB signaling pathway].

Objective: To investigate the effect of pentraxin 3 (PTX3) on the proliferation, invasion and drug resistance of pediatric neuroblastoma cells and its mechanism. Methods: si-RNA (si-RNA group), si-PTX3 (si-PTX3 group), siRNA+ pcDNA3.1 (siRNA+ pcDNA3.1 group), si-PTX3+ pcDNA3.1 (si-PTX3+ pcDNA3.1 group), siRNA+ pcDNA3.1-Toll-like receptor 4 (siRNA+ pcDNA3.1-TLR4 group) and si-PTX3+ pcDNA3.1-TLR4 (si-PTX3+ pcDNA3.1-TLR4 group) were transfected into SH-SY5Y cells. Collected 32 cases of tumor tissue and cancerous tissue in children with childhood neuromaternal cells who were treated at Zhumadian center hospital from July 2016 to August 2019. Real-time fluorescent quantitative polymerase chain (RT-qPCR) reaction and immunohistochemistry experiments were used to detect the protein expressions of PTX3 in neuroblastoma tissues and normal tissues. 5-Ethynyl-2'-deoxyuridine (EdU) was used to detect the proliferation effect of PTX3 on neuroblastoma cell SH-SY5Y. Western blot experiment was used to detect the protein expression levels of vascular endothelial growth factor (VEGF), resistance-related proteins including P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), and invasion-related protein matrix metalloproteinase-1 (MMP-1). Results: PTX3 mRNA expressions in neuroblastoma tissues were 0.87±0.07, higher than 0.13±0.06 of normal tissues, and the differences were statistically significant (P<0.05), The expression of the immunohistochemistry test PTX3 protein was consistent with the qRT-PCR results. Compared with the si-RNA group (0.95±0.08; 1.02±0.10), the mRNA and protein expressions of PTX3 in the si-PTX3 group (0.25±0.05; 0.45±0.66) decreased, the differences were statistically significant (all P<0.05). The number of EdU positive cells, invasion rate, VEGF, MMP-1, P-gp and MRP-1 protein expressions in si-RNA group were (31.86±1.86)%, (28.12±2.96)%, (0.58±0.07), (0.44±0.06), (0.46±0.08) and (0.51±0.05), respectively, higher than (19.73±1.22)%, (8.45±1.06)%, (0.25±0.05), (0.19±0.03), (0.19±0.06) and (0.16±0.07) in si-PTX3 group, and the differences were statistically significant (all P<0.05). The Number of EdU positive cells [(19.49±1.68)%], invasion rate [(8.48±1.36)%], VEGF protein expression (0.10±0.15), P-gp (0.18±0.07) , TLR4 (0.45±0.06), p-p65 (0.25±0.05) protein expressions in si-PTX3+ pcDNA3.1 group were relatively lower compared with siRNA+ pcDNA3.1 group [(38.21±2.67)%, (26.39±2.14)%, 0.49±0.05, 0.52±0.06, 0.93±0.14 and 0.82±0.06] (all P<0.05). The number of EdU-positive cells [(62.73±5.18)%], invasion rate [(50.45±3.25)%], VEGF protein expression (2.17±0.17), P-gp (2.15±0.16), TLR4 (2.68±0.16), p-p65 (2.48±0.13) protein expressions in the siRNA+ pcDNA3.1-TLR4 group increased compared with siRNA+ pcDNA3.1 group (all P<0.05). Conclusions: Inhibition of PTX3 can inhibit the proliferation and invasion of neuroblastoma cells SH-SY5Y, and reduce drug resistance. Its mechanism may be achieved by regulating the TLR4/NF-κB signaling pathway. This result can provide a new perspective for pediatric neuroblasts tumor diagnosis and clinical treatment.

[Clinical features and pathological analysis of lacrimal gland occupying lesions in 91 cases].

Objective: To analyze the pathogenesis, histopathological classification and clinical features of lacrimal gland occupying lesions. Methods: This was a retrospective case series study. Clinical data of 91 patients (102 eyes) with lacrimal gland area occupying diseases who received ophthalmic surgery in the Second People's Hospital of Yunnan Province from January 2014 to November 2018 were retrospectively analyzed, including patients' age, reasons for treatment, gender, imageological examination data and pathological diagnosis results. All patients had more than one medical imaging examination results and histopathological diagnosis results. Results: Among 91 cases, 46 patients (50.5%) were male and 45 (49.5%) were female. The age distribution ranged from 1.1 years to 72 years old, with an average age of 43 years. All of benign tumors added up to 58 cases (63.7%). Pleomorphic adenoma (43 cases, 47.3%), dermoid cyst (6 cases, 6.6%), and inflammatory pseudotumor (6 cases, 6.6%) were the most common cases in the benign lacrimal gland occupying tumors. There were 33 cases (36.3%) of malignant tumors. Adenoid cystic carcinoma (15 cases, 16.5%), adenocarcinoma (6 cases, 6.6%) and lymphoma (5 cases, 5.5%) had the highest incidence among the malignant lacrimal gland occupying tumors. The most common reason for seeking medical treatment was exophthalmos (50 cases, 54.9%; 30 cases were pleomorphic adenoma). Brow arch mass (22 cases, 24.2%) and pain in and around the eye (9 cases, 9.9%; 5 cases were adenoid cystic carcinoma) were also major reasons. Conclusions: The most common benign lacrimal gland area occupying lesion in surgery patients of Yunnan is pleomorphic adenoma, which more occurred in patients with exophthalmos as the main symptoms. The most common malignant tumor in the lacrimal gland area is adenoid cystic carcinoma and the most common reason to seek medical advice was pain in and around the eye. (Chin J Ophthalmol, 2019, 55:842-846).

Applying the zero-inflated Poisson model with random effects to detect abnormal rises in school absenteeism indicating infectious diseases outbreak.

Records of absenteeism from primary schools are valuable data for infectious diseases surveillance. However, the analysis of the absenteeism is complicated by the data features of clustering at zero, non-independence and overdispersion. This study aimed to generate an appropriate model to handle the absenteeism data collected in a European Commission granted project for infectious disease surveillance in rural China and to evaluate the validity and timeliness of the resulting model for early warnings of infectious disease outbreak. Four steps were taken: (1) building a 'well-fitting' model by the zero-inflated Poisson model with random effects (ZIP-RE) using the absenteeism data from the first implementation year; (2) applying the resulting model to predict the 'expected' number of absenteeism events in the second implementation year; (3) computing the differences between the observations and the expected values (O-E values) to generate an alternative series of data; (4) evaluating the early warning validity and timeliness of the observational data and model-based O-E values via the EARS-3C algorithms with regard to the detection of real cluster events. The results indicate that ZIP-RE and its corresponding O-E values could improve the detection of aberrations, reduce the false-positive signals and are applicable to the zero-inflated data.

[Anti-CD(25) monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease in 80 patients receiving allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the efficacy of anti-CD(25) monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 80 patients with SR-aGVHD from January 1st 2012 to December 31st 20l6 were enrolled in this study. Acute GVHD were classified as classic aGVHD (n=72) and late-onset aGVHD (n=8). Anti-CD(25) monoclonal antibodys (mAb) were administrated on days 1, 4, 8, 15, and 22. The efficacy of anti-CD(25) mAb was evaluated at day 28 after the initial treatment. The associated factors of clinical outcome were analyzed. Results: The overall response (OR) rate of anti-CD(25) mAb was 75% (60/80), with complete response (CR) rate, partial response (PR) rate and no response(NR) rate 52.5% (42/80), 22.5% (18/80), and 25% (20/80), respectively. GVHD-relapse was not observed with a median follow-up time of 394.5 days (range, 12-1 761 days). The 6-month overall survival (OS) rate was 68.4%(95%CI 63.2%-73.6%). The 1-year OS rate was 63.1% (95%CI 57.6%-68.6%), and 2-years OS rate was 50.7% (95%CI 44.3%-57.1%). Non-relapse mortality (NRM) rate of 1 and 3 years was 32.6% (95%CI 27.2%-38%) and 41.7% (95%CI 35.3%-48.1%), respectively. The 1 and 2 years cumulative incidence of chronic graft versus host disease (cGVHD) was 32.9% (95%CI 26.4%-39.4%) and 38.9% (95%CI 31.8%-46.0%). By univariate and multivariate analysis, liver involvement was an independent poor risk factor of SR-aGVHD (OR=4.66, 95%CI 1.145-18.962, P=0.032). Conclusion: Anti-CD(25) mAb serves as an alternative and effective salvage therapy for SR-aGVHD at present. Liver involvement is a predictive factor of poor response in patients with SR-aGVHD.

High-free androgen index is associated with increased risk of non-alcoholic fatty liver disease in women with polycystic ovary syndrome, independent of obesity and insulin resistance.

BACKGROUND/OBJECTIVE: Central obesity and insulin resistance (IR) are common conditions in women with polycystic ovary syndrome (PCOS) and in subjects with non-alcoholic fatty liver disease (NAFLD). However, few studies have addressed the association between hyperandrogenism (HA) and NAFLD. We aimed to determine whether variations in the free androgen index (FAI) might be associated with NAFLD prevalence. SUBJECTS/METHODS: A cross-sectional study was performed including 400 Chinese women with PCOS and 100 age, and body mass index (BMI)-matched women. The anthropometric and serum biochemical parameters related to sex steroids, glucose and lipid profiles were examined. Liver fat content (LFC) was measured by quantitative ultrasound. RESULTS: The prevalence of NAFLD was 56.23% in PCOS patients and 38% in controls (P=0.001), and this prevalence increased with FAI quartile independently of obesity and homeostasis model assessment of insulin resistance (HOMA-IR). The FAI level increased from non-NAFLD group to NAFLD group. The FAI was positively associated with the metabolic parameters LFC, BMI, waist circumference, alanine aminotransferases, aspartate, triglyceride, total cholesterol and low-density lipoprotein cholesterol, and was negatively associated with high-density lipoprotein. Moreover, in multivariate logistic regression analysis BMI, high-sensitivity C-reactive protein (hsCRP), FAI, LFC and HOMA-IR were significantly associated with NAFLD. The cut-off values of FAI, LFC, BMI and hsCRP to predict NAFLD were 9.86%, 17.19%, 24.38% and 0.72%, respectively. The area under the curve for predicting NAFLD in PCOS patients showed comparable sensitivity and specificity between BMI and a new index combining FAI with hsCRP. CONCLUSIONS: A higher FAI level is associated with increased LFC and NAFLD prevalence independent of obesity and IR.

Age and gender differences in self-control and its intergenerational transmission.

BACKGROUND: Few studies have been conducted in people of Asian descent that have reported to demonstrate the distinct developmental trends in good self-control and poor control. To fill this gap, we conducted a national cross-sectional survey among adolescents and young adults in China to further clarify the age and gender differences in self-control from a dual-systems perspective. METHODS: A total of 2910 adolescents (female, n = 1698) and their parents from five different provinces in China were surveyed using the Dual-Modes of Self-Control Scale (DMSC-S) and the Parents' Perceived Self-Control Scale. The mean age of the adolescent sample was 17.47 years (ranging from 12.50 to 25.42 years). RESULTS: Boys exhibited greater good self-control than girls. Poor control increased between 12 and 17 years of age and declined thereafter; however, good self-control increased over the entire study period. Both good self-control and poor control in student participants were significantly associated with parents' perceived self-control; moreover, the association between good self-control and parental self-control was mediated by SES. CONCLUSION: The roles of age, gender, parental self-control and SES varied in a dual-systems model of self-control: good self-control and poor control. Implications of these results are discussed.

[Effects of repetitive transcranial magnetic stimulation on upper limb motor function in patients with stroke: a meta analysis].

Objective: To perform a meta analysis of studies that investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on upper limb motor function in patients with stroke. Methods: We searched for related articles published before October 2015 in MEDLINE(Pubmed) (January 1966 to October 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (October 2015), EMBASE(SCOPUS) (January 1974 to October 2015), Chinese Biomedical Database (CBMDisc) (January 1978 to October 2015), China National Knowledge Infrastructure (CNKI) (January 1979 to October 2015) and Wanfang database(January 1989 to October 2015). Results: A total of nine studies with 289 patients were included in this analysis.The results showed that rTMS had a significant effect for ischemic stroke patients with upper limb motor disorder with SMD 0.43, 95%CI 0.19-0.67, P=0.000 4. Further subgroup analyses about high or low frequency rTMS demonstrated low frequency rTMS showed prominent effects for the stroke patients with SMD 0.50, 95%CI 0.14-0.85, P=0.007.Only 3 patients from the 9 studies included in this analysis reported adverse effects from rTMS. Conclusions: The meta analysis suggests that rTMS has a positive effect on motor recovery in patients with stroke, especially the low frequency rTMS may be more beneficial.The clinical application of rTMS in patients with stroke is relatively safe.Intermittent theta-burst stimulation might be a useful intervention.

[Clinical-based study of ovarian cancer patients with and without BRCA1/2 genes mutation: clinical features and pedigree analysis].

Objective: To compare the clinical and histological features and prognosis of patients with ovarian cancer from different genetic background, and to make further understanding of the genetic model of BRCA genes used pedigree analysis. Methods: There were 71 patients from 67 independent families enrolled in our study from Apr. 2000 to Jun. 2009 in Peking Union Medical College Hospital. All exons of BRCA1/2 genes were analyzed using denaturing high-performance liquid chromatography(DHPLC) followed by direct sequencing, and clinical features of patients were compared by statistical analysis. Pedigree analysis of two families with BRCA genes mutation were performed. Results: The mutation rate of BRCA genes was 28% (20/71). The frequency of BRCA1 and BRCA2 gene mutation was 23% (16/71) and 6% (4/71), respectively (P=0.004). Histology types of patients with and without BRCA genes mutation were different. The onset age between patients with and without BRCA genes mutation was similar (52.6 versus 54.6 years old, P=0.393), and tend to be early-onset breast or ovarian cancer in high-risk group. There was no significant difference of platinum-resistant rate, disease free survival and overall survival rate between patients with and without BRCA genes mutation (all P>0.05). According to the pedigree analysis, up to 100% of female offspring inherited pathogenic mutations, and male offspring could be a mutation carrier. Conclusions: The genetic screening and clinical intervention should be performed as early as possible for the members from families at risk of hereditary ovarian cancer. Genetic consulting is important for patients with high-grade papillary serous adenocarcinoma of ovary. It is still unknown that whether the patients with BRCA gene mutations have better prognosis than sporadic ones, and further perspective, randomized controlled trial is still needed.

[Current status of job burnout in clinical nurses in a grade A tertiary hospital and related influencing factors].

Objective: To investigate the current status of job burnout in clinical nurses in a grade A tertiary hospitalin Shaoxing,China and related influencing factors. Methods: In October 2016, the Nursing Burnout Scale (NBS)was used for the investigation of 304 clinical nurses in a grade A tertiary hospital.The contents of the investigation included general data(including age,education background,working years,marital status, frequency of night shifts,professional title, and way of employment), characteristics of working environment,burnout, personality characteristics,coping strategy,and psychosomatic symptoms.SPSS 18.0 was used to conduct Pearson correlation analysis of the scores of each dimension of NBS. A multivariate regression analysis was performed with the demographic features of clinical nurses as the independent variable and the scores of each dimension of NBS as the dependent variable. Results: Among the clinical nurses in this grade A tertiary hospital, the incidence rate of severe burnout was 74%.The Pearson correlation analysis showed that burnout,pessimistic personality,negative coping,and psychosomatic symptoms were positively correlated with working environment(r=0.530,0.316,0.116,and 0.502); pessimistic personality and psychosomatic symptoms were positively correlated with burnout(r=0.618 and 0.675); psychosomatic symptoms were positively correlated withpessimistic personality(r=0.540); negative coping was negatively correlated with pessimistic personality(r=-0.145).The multivariate linear regression analysis showed that department(Department of Internal Medicine or Department of Surgery,B=-0.364 and -0.428)and frequency of night shifts(<6 times/month and 6-10 times/month,B=0.199 and 0.256)were influencing factors for the score of working environment; department(Department of Internal Medicine or Department of Surgery, B=-0.350 and -0.360)was an influencing factor for the score of burnout; 1-3 working years(B=-0.238)was an influencing factor for the score of pessimistic personality; married state,1-3 working years,and department (Department of Internal Medicine or Department of Surgery)were influencing factors for the score of psychosomatic symptoms(B=0.263,-0.301,-0.322,and -0.391). Conclusion: There is a high incidence rate of job burnout among clinical nurses in this grade A tertiary hospital,which is associated with burnout,working environment, pessimistic personality,and psychosomatic symptoms.Marital status,working years,department,and frequency of night shifts are major influencing factors for job burnout.

DNMT3A -448A>G polymorphism and cancer risk: a meta-analysis.

Cancer is a major public health problem worldwide that involves complex processes and factors. For instance, methylation is important in tumorigenesis. DNA (cytosine-5)-methyltransferase 3A (DNMT3A) is the main de novo methyltransferase implicated in this process. In DNMT3A, the -448A>G polymorphism is associated with cancer; however, the results of various studies have been conflicting. To clarify the role of DNMT3A polymorphisms in cancer, we conducted a meta-analysis of 2014 cases and 3089 control subjects. Odds ratios with 95% confidence intervals were estimated to evaluate the association between the DNMT3A -448A>G polymorphism and cancer risk. The results showed that DNMT3A may be a protective factor against all cancer types and colorectal cancer groups. Further studies should be conducted including different ethnicities and large population sizes to generate a comprehensive conclusion.

The expression of 11ß-HSDs, GR, and H6PDH in subcutaneous adipose tissue from polycystic ovary syndrome subjects.

The aim of the work was to investigate the expression of 11ß-hydroxysteroid dehydrogenase (11ß-HSD) type 1 and 2, hexose-6-phosphate dehydrogenase (H6PDH), and glucocorticoids receptor (GR) mRNA in subcutaneous adipose tissue (SAT) from obese women with or without polycystic ovary syndrome (PCOS), and the association between their expression and the adipocytokines' concentration. Sixteen women with PCOS (group P) and 18 age- and BMI-matched control women (group C) were enrolled for the study. Subcutaneous adipose tissue was collected from the abdomen. The genes' expression was detected by real-time PCR, and the adipocytokines' concentration was measured by ELISA. Peripheral insulin sensitivity was assessed by homeostatic assessment model of insulin resistance (HOMA-IR). ß-cell function was assessed by homeostasis model assessment of ß-cell function (HOMA-IS). The expression of 11ß-HSD1 mRNA was significantly higher in PCOS subjects (p<0.05) than controls; there was no difference for the expression of 11ß-HSD2, GR, and H6PDH mRNA between the 2 groups. The stepwise multiple linear regression analysis showed that the mRNA level of 11ß-HSD1 was positively correlated to the concentration of the serum tumor necrosis factor-alpha (TNF-α). Expression of 11ß-HSD1 mRNA was increased in the SAT from the women with PCOS, which may contribute to the increased local active glucocorticoids (cortisol), and subsequently affects the secretion of the local adipose tissue.

Trichosanthes kirilowii: A New Host of Cucurbit mild mosaic virus in China.

Chinese cucumber (Trichosanthes kirilowii Maxim.) is a type of perennial liana plant of the Cucurbitaceae family that is mainly distributed in East Asia and northern Australia. It is an important medicinal plant and commonly used in Chinese herbalism, where it is considered to be one of the 50 fundamental herbs (2). During the summer and autumn of 2012, T. kirilowii plants showing symptoms of mild mosaic on the upper leaves and bright yellow color on the lower leaves were observed in the Haidian district of Beijing, China. Recently similar symptoms induced by Cucurbit mild mosaic virus (CuMMV) on squash have been reported. CuMMV is a new member of the genus Fabavirus in the Comovirinae subfamily, discovered in China in 2006 (1). Total RNA was extracted from five leaf samples of independent plants and used for reverse transcription with an oligo (dT)18 primer, followed by PCR with a pair of CuMMV virus-specific primers FaR13012F (5'-CGAGTGCGAGTTAGAAATTGGGATG-3') and FaR15783R (5'-TCACTTTGAGGTGATAAAACAATCC-3') to amplify a 2,772-bp fragment including RNA-dependent RNA polymerase (RdRp) coding region. The expected target fragment was obtained in all symptomatic plant samples but not from an asymptomatic plant. Nucleotide sequence comparison analysis showed that the virus isolated from T. kirilowii (GenBank Accession No. KC959843) had 95.33% nucleotide identity and 99.15% amino acid identity in the RdRp sequence with a CuMMV isolate from squash (GenBank Accession No. FJ194941) (1). In addition, symptomatic samples tested positive for CuMMV by Western blot using CuMMV small coat protein (SCP) specific polyclonal antibody (1). To our knowledge, this is the first report of T. kirilowii as natural host of CuMMV in China. The impact of CuMMV on T. kirilowii production remains to be determined; however, the extended host range for this virus suggests a potential threat of CuMMV to cucurbit crops in China. References: (1) S. W. Dong et al. Arch. Virol.157:597, 2012. (2) J. H. Hong et al. China Pharmacist 7:561, 2004.

[Association of temperament type and mother's emotional state with acute respiratory infection in children].

OBJECTIVE: To explore the correlation of temperament type and mother's emotional state with acute respiratory tract infections in children so as to provide evidence for comprehensive treatment of the infections. METHODS: A total of 200 children aged between 3 and 6 were enrolled in this study from two kindergartens of Guangzhou and Hengyang. The mothers were invited to complete a questionnaire of the children's general information followed by assessment using children's temperament scale and the Depression-Anxiety-Stress Scale. RESULTS: The total incidence of acute respiratory infection was significantly higher in children with a hard- to-raise temperament than the easy- to-raise children (P < 0.05); the incidences of acute rhinitis, acute pharyngitis, acute laryngitis and acute bronchitis were all significantly higher in the hard-to-raise children (P < 0.05). A significant positive correlation was identified between the total number of episodes of acute respiratory tract infection in children and their mothers' stress and anxiety levels (P < 0.01). Acute rhinitis and acute tracheitis in the children were both positively correlated with the mothers' stress scores (P < 0.05), while acute pharyngitis and acute laryngitis were positively correlated with the mothers' anxiety scores (P < 0.05), while acute bronchitis was positively correlated with the mothers' stress and anxiety scores (P < 0.05). Multiple linear regression analysis with the factors influencing the types of acute respiratory tract infections in children as the independent variables suggested that the easy-to-raise type of temperament was a protective factor against acute rhinitis in children (P < 0.05), while mothers' anxiety was a risk factor of acute laryngitis in children (P < 0.05); the mothers' stress was a risk factor for acute bronchitis in children (P < 0.05). CONCLUSION: Acute respiratory tract infection in children is closely related to the temperament type of the children and the emotional state of the mothers, which are important therapeutic targets in comprehensive interventions of acute respiratory tract infection in children.

A model of cellular cardiac-neural coupling that captures the sympathetic control of sinoatrial node excitability in normotensive and hypertensive rats.

Hypertension is associated with sympathetic hyperactivity. To represent this neural-myocyte coupling, and to elucidate the mechanisms underlying sympathetic control of the cardiac pacemaker, we developed a new (to our knowledge) cellular mathematical model that incorporates signaling information from cell-to-cell communications between the sympathetic varicosity and sinoatrial node (SAN) in both normotensive (WKY) and hypertensive (SHR) rats. Features of the model include 1), a description of pacemaker activity with specific ion-channel functions and Ca(2+) handling elements; 2), dynamic ß-adrenergic modulation of the excitation of the SAN; 3), representation of ionic activity of sympathetic varicosity with NE release dynamics; and 4), coupling of the varicosity model to the SAN model to simulate presynaptic transmitter release driving postsynaptic excitability. This framework captures neural-myocyte coupling and the modulation of pacemaking by nitric oxide and cyclic GMP. It also reproduces the chronotropic response to brief sympathetic stimulations. Finally, the SHR model quantitatively suggests that the impairment of cyclic GMP regulation at both sides of the sympathetic cleft is crucial for development of the autonomic phenotype observed in hypertension.

The etomidate requirement is decreased in patients with obstructive jaundice.

BACKGROUND: Patients with obstructive jaundice have increased sensitivity to inhaled anesthetics. In rodent brain, bilirubin can enhance γ-aminobutyric acid A/glycinergic synaptic transmission. Etomidate is a nonbarbiturate hypnotic that induces sedation through γ-aminobutyric acid A receptors in the central nervous system. We tested the hypothesis that patients with obstructive jaundice have an altered sensitivity to etomidate. METHODS: The study design was a comparison of etomidate requirements to reach a Bispectral Index of 50 in patients with obstructive jaundice versus patients with chronic cholelithiasis and normal bilirubin levels. Etomidate was infused at 30 µg/kg/min until this end point was reached. RESULTS: The etomidate requirement in the obstructive jaundice group was lower than that in the control group (150±46 µg/kg vs 206±74 µg/kg, P=0.007). The average decrease in etomidate requirement was 56 µg/kg (95% confidence interval: 16-96 µg/kg). In addition, we found a significant negative correlation between serum total bilirubin and etomidate requirement with Pearson r of -0.545, and 95% confidence interval for r value (-0.791 to -0.148). All subjects were hemodynamically stable during the study. CONCLUSIONS: Etomidate requirements to reach a level of anesthesia defined by a Bispectral Index of 50 are reduced in patients with obstructive jaundice.

Critical Analysis of Apixaban Dose Adjustment Criteria.

Apixaban is indicated for the prevention of ischemic stroke in non-valvular atrial fibrillation (NVAF), as well as for the prevention and treatment of venous thromboembolism (VTE). Dose adjustment is based on age, weight, and serum creatinine in NVAF, while there are no recommended adjustment criteria for VTE. Such adjustment is unconventional compared to other commonly used medications. The objective of this manuscript is to critically analyze each apixaban dosing adjustment criterion and its associated outcomes. PubMed articles from March 2013 to March 2020 were selected with search terms "apixaban," and "dose adjustment," "adjustment," or "adjustment criteria." Pharmacokinetic studies demonstrated increased apixaban exposure in patients >65 years of age, those with extreme body weights, and those with advanced renal impairment, though post-hemodialysis dosing may off-set the elevated apixaban exposure. However, clinical data show that among patients >75 years, <60 kg, and with estimated glomerular filtration rate <50 mL/min, including those on dialysis, there is no reduction in apixaban safety or efficacy. Published literature describes variable dosing strategies utilized in clinical practice. Overall, apixaban dose adjustment criteria may need to be re-evaluated.

Dissecting the Role of VicK Phosphatase in Aggregation and Biofilm Formation of Streptococcus mutans.

VicRK (WalRK or YycFG) is a conserved 2-component regulatory system (TCS) that regulates cell division, cell wall biosynthesis, and homeostasis in low-GC Gram-positive bacteria. VicRK is also associated with biofilm formation of Streptococcus mutans on the tooth surface as it directly regulates the extracellular polysaccharide (EPS) synthesis. Of the 2 components, VicK possesses both autokinase and phosphatase activities, which regulate the phosphorylation and dephosphorylation of the regulator VicR in response to environmental cues. However, the dual mechanism of VicK as the autokinase/phosphatase in regulating S. mutans' responses is not well elucidated. Previously, it has been shown that the phosphatase activity depends on the PAS domain and residues in the DHp domain of VicK in S. mutans. Specifically, mutating proline at 222 in the PAS domain inhibits VicK phosphatase activity. We generated a VicKP222A mutant to determine the level of VicR-P in the cytoplasm by Phos-tag sodium dodecyl sulfate polyacrylamide gel electrophoresis. We show that in VicKP222A phosphatase, attenuation increased phosphorylated VicR (VicR-P) that downregulated glucosyltransferases, gtfBC, thereby reducing the synthesis of water-insoluble polysaccharides (WIS-EPS) in the biofilm. In addition, VicKP222A presented as long-rod cells, reduced growth, and displayed asymmetrical division. A major adhesin of S. mutans, SpaP was downregulated in VicKP222A, making it unable to agglutinate in saliva. In summary, we have confirmed that VicK phosphatase activity is critical to maintain optimal phosphorylation status of VicR in S. mutans, which is important for cell growth, cell division, EPS synthesis, and bacterial agglutination in saliva. Hence, VicK phosphatase activity may represent a promising target to modulate S. mutans' pathogenicity.

Curriculum Design and Scholarship for New Educators: A Professional Development Workshop for Medical Students.

Introduction: Medical students' professional development includes their role as educators. Despite greater opportunities to join medical education curriculum development, medical students' engagement in these activities remains limited. A recent national study on student leadership in curricular change revealed a formal lack of leadership and training in medical education as significant barriers. Medical students' unawareness of how to disseminate curricula as educational scholarship and its value to their careers also restricts the fullness of their formation as educators. Methods: We designed a 3-hour, interactive, project-focused conference workshop for medical students without prior knowledge in curriculum development. Of participants, 64 worked in 10 groups creating medical curricula using Kern's six-step approach in student-facilitated breakout sessions. Completed group projects were presented, including brief action plans for transforming their work into scholarship. The workshop was evaluated using a mixed-methods approach. Results: Of survey respondents, 44 mostly medical students, faculty, and administrators from different institutions rated the workshop as a very positive experience, and the pacing of the breakout groups as effective. A notable increase in self-reported mastery, as measured by learning objectives aligned with Kern's six-step model, was recorded from student respondents as compared to faculty. A sense of readiness to participate in curricular decisions either at the home institution or in individual career paths was evident from narrative comments. Discussion: Our workshop provided medical students with a foundation in curriculum development and educational scholarship. Session design provided flexibility in the pace of breakout sessions and allowed in-depth discussion of educational topics.

A randomized controlled trial to evaluate the effectiveness of a distance asthma learning program for pediatricians.

OBJECTIVES: To assess provider acceptability of a distance learning program for pediatric asthma and pilot test its effects on physician knowledge, attitudes and treatment practices. DESIGN: Randomized controlled trial. SETTING: Louisville and the surrounding central Kentucky region. PARTICIPANTS: Twenty-four pediatricians in clinical practice. Interventions. A distance learning program for pediatric asthma consisting of Web- or CD-ROM-based multimedia learning modules and two teleconference calls. OUTCOME MEASURES: Learner satisfaction and change in physician asthma knowledge, attitudes, and treatment behavior at 1 to 4 months (short term) and 6 to 8 months (long term). RESULTS: Pediatricians had graduated from medical school a mean of 11.6 years before baseline (SD +/-8.9); 56% were female. On all learner satisfaction items, the average score was a 4.0 or greater on a 5-point scale, indicating a favorable response from the participants. Participants in the education group reported increased familiarity with asthma guideline for prescribing daily-inhaled corticosteroids compared to control physicians (p = .03) at short-term follow-up. Participants also expressed increased confidence in selecting a medicine for patients requiring a low-dose inhaled steroid (p = .03). However, these differences were not seen at long-term follow-up. Compared to the control group, there was no significant increase in the proportion of patients receiving inhaled steroids for persistent asthma at short- or long-term follow-up. CONCLUSIONS: Pediatricians utilizing an asthma distance learning program expressed a high degree of learner satisfaction. The program was associated with a temporary increase in familiarity and confidence in implementing components of the asthma guidelines.