[Incidence and related factors of antiviral drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019].

Objective: To analyze the incidence and related factors of drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019. Methods: From April 2017 to April 2019, face-to-face questionnaires and blood sample testing were conducted in all health care institutions providing maternal and perinatal care and midwifery-assisted services in 7 prevention of mother-to-child transmissi project areas in Xinjiang, Yunnan and Guangxi provinces/autonomous regions. Information was collected during the perinatal period and viral load, CD4+T lymphocytes and drug resistance genes were detected at the same time. The multivariate logistic regression model was used to analyze the relationship between different factors and drug resistance in HIV-infected pregnant and postpartum women. Results: A total of 655 HIV-infected pregnant and postpartum women were included in this study. The incidence of drug resistance was 3.4% (22/655), all of whom were cross-drug resistant. The rate of low, moderate and high drug resistance was 2.1% (14/655), 1.2% (8/655) and 0.8% (5/655), respectively. The drug resistance rate in the people who had previously used antiviral drugs was 1.9% (8/418), and the drug resistance rate in the people who had not used drugs was 5.9% (14/237). The NNRTI drug resistance accounted for 2.8% (18/655) and the NRTI drug resistance rate was 2.5% (16/655). The multivariate logistic regression model showed that the risk of HIV resistance was lower in pregnant women who had previously used antiviral drugs (OR=0.32, 95%CI: 0.11-0.76). Conclusion: Strengthening the management of antiviral drug use and focusing on pregnant and postpartum women who have not previously used antiviral drugs can help reduce the occurrence of drug-resistant mutations. Personalized antiviral therapy should be considered to achieve viral inhibition effects in clinical practice.

[Analysis of the catastrophic health expenditure of HIV-positive maternal households in high AIDS endemic areas in Liangshan prefecture].

Objective: To analysis the income and expenditure of HIV-positive pregnant women and the catastrophic health expenditure of their households in high AIDS endemic areas in Liangshan prefecture. Methods: From December 2018 to January 2019, a total of 250 pregnant women were recruited from 2 of 17 counties in Liangshan Prefecture, including 133 HIV-positive pregnant women and 117 HIV-negative pregnant women. The data, including basic information of pregnant women, basic information of the family, annual family income in 2017, annual family health expenditure in 2017, and maternal and child-related expenditure in 2017, were collected for analyzing the incidence of catastrophic health expenditure in the family. Results: The average annual income and average annual health expenditure of HIV-positive pregnant women households were 7 000 CNY and 2 000 CNY, while those of HIV-negative pregnant women households were 10 000 CNY and 3 000 CNY, respectively. Based on the criteria of 15%, 25% and 40%, the incidence of catastrophic health expenditure of HIV-positive pregnant households was 39.10%, 33.83% and 27.82%, with average differences of 34.84%, 31.17% and 26.65%, respectively, while that of HIV-negative pregnant women households was 38.46%, 33.33% and 23.93%, with average differences of 31.68%, 28.35% and 24.22%, respectively. Conclusion: The incidence of catastrophic health expenditure of pregnant households in high AIDS endemic areas in Liangshan prefecture is high. The incidence of HIV-positive families is slightly higher than that of HIV-negative families. We suggest that medical insurance compensation in Liangshan prefecture should be improved to reduce the impact of catastrophic health expenditure.

[Status on maternal testing and detection of HIV infection among pregnant women in Liangshan Yi Autonomous Prefecture, Sichuan province, 2008-2016].

Objective: To understand the status of maternal testing, detection and trends of HIV infection among pregnant women in Liangshan Yi Autonomous Prefecture (Liangshan) of Sichuan province during 2008-2016. Methods: Data were collected from the monthly work report on maternal HIV testings and the case-reporting records of HIV-positive pregnant women, from the National Management Information System of China's Prevention of Mother-to-child transmission of HIV, syphilis, and HBV Program. Descriptive method was applied to show both the maternal HIV and predelivery HIV testing rates and maternal HIV positive rates as well as the distribution in different counties, between 2008 and 2016. Results: During 2008-2016, both maternal HIV test rates and predelivery maternal HIV testing increased from 40.7% (8 191/20 125) and 8.0% (1 607/20 125) to 95.7% (88 000/91 946) and 70.1% (64 421/91 946), respectively (trend χ(2)=94 497.28, P<0.001; trend χ(2)=90 655.03, P<0.001). A total of 3 271 HIV-positives were detected from 436 519 pregnant women, with the HIV positive rate as 0.75% (95%CI: 0.72%-0.77%). Among 3 271 HIV-positive pregnant women, 1 527 (46.7%) of them were tested at labor. The maternal HIV-positive rates at labor increased yearly (trend χ(2)=9.21, P=0.002). In 2016, the maternal HIV-positive rate at labor was 1.32% (95%CI: 1.18%-1.47%), which was higher than that (0.67%, 95%CI: 0.61%-0.73%) in the pregnant women who received HIV test predelivery (χ(2)=88.23, P<0.001). The maternal HIV- positive rates in Butuo, Zhaojue, Jinyang, Meigu, and Yuexi counties all appeared ≥1%, in 2016,respectively. Conclusions: The maternal HIV test rates increased in Liangshan during 2008-2016, but the maternal HIV test rates at labor were relatively high. The HIV prevalence among pregnant women in Liangshan was severe and late for pregnant women to receive testing.

[Epidemic trend of COVID-19 in Chinese mainland].

Objective: In order to understand the epidemic trend of COVID-19 and evaluate the effect of prevention and control, this study aims to evaluate the epidemic dynamics of COVID-19 in Chinese mainland from January 16 to February 14, 2020. Methods: The daily number of new confirmed COVID-19 cases detected by nucleic acid was collected from the National Health Commission from January 16, 2020 to February 14, 2020. The analysis included the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in Chinese mainland was 50 031, including 37 930 in Hubei Province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei Province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion: The epidemic prevention and control measures taken by the state and governments at all levels have effectively curbed the spread of the COVID-19 epidemic in Chinese mainland.

Suppression of αvß6 downregulates P-glycoprotein and sensitizes multidrug-resistant breast cancer cells to anticancer drugs.

Multidrug resistance (MDR) in breast cancer treatment is the major cause leading to the failure of chemotherapy. P-glycoprotein (P-gp), the product of the human MDR1 gene, plays a key role in resistance to chemotherapy and confers cross-resistance to many structurally unrelated anticancer drugs. We have previously reported that integrin αvß6 plays a critical role in breast cancer invasion and metastasis. However, whether and how αvß6 is associated with P-gp and regulated by potential genetic mechanisms in breast cancer remains unclear. In the present study, we further investigated the reversal effect and underlying mechanisms of MDR in breast cancer. Two small interfering RNA constructs (pSUPER-ß6shRNAs) targeting two different regions of the ß6 gene have been designed to inhibit αvß6 expression by transfecting them into adriamycin-resistant MCF-7/ADR cell lines. Suppression of αvß6 dramatically downregulated the levels of MDR1 gene mRNA and P-gp. In particular, ß6shRNA-mediated silencing of αvß6 gene increased significantly the cellular accumulation of Rhodamine 123 and markedly decreased drug efflux ability, suggesting that ß6shRNAs indeed inhibit P-gp mediated drug efflux and effectively overcome drug resistance. In addition, inhibition of integrin αvß6 suppressed the expression of ERK1/2. Interestingly, our data demonstrate that suppression of integrin αvß6 caused significant downregulation of Bcl-2, Bcl-xL and upregulation of caspase 3, Bad, accompanied by increasing activity of cytochrome C. A possible connection between αvß6 and P-gp in drug resistance biology is suggested. Taken together, ß6shRNA could efficiently inhibit αvß6 and MDR1 expression in vitro and these findings may offer specifically useful means to reverse MDR in breast cancer therapy.

MicroRNA-646 inhibits proliferation and cell cycle progression of nasopharyngeal carcinoma cells by targeting mTOR.

OBJECTIVE: To clarify whether microRNA-646 could regulate the proliferative potential and cell cycle progression of nasopharyngeal carcinoma cells through targeting mammalian target of rapamycin (mTOR). It, therefore, could influence the occurrence and progression of nasopharyngeal carcinoma. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect expression of the levels of microRNA-646 and mTOR in tumor tissues and paracancerous tissues of patients with nasopharyngeal carcinoma. Besides, their expressions in nasopharyngeal carcinoma cell lines were determined by qRT-PCR. Survival analysis was conducted to evaluate the sensitivity and specificity of microRNA-646 in diagnosing nasopharyngeal carcinoma. The overall survival of patients with nasopharyngeal carcinoma was calculated based on their expression levels of microRNA-646. The regulatory effects of microRNA-646 and mTOR on proliferative potential and cell cycle progression were explored by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Dual-luciferase reporter gene assay was conducted to verify the relationship between microRNA-646 and mTOR, which was further confirmed by Pearson correlation analysis. Finally, gain-of-function experiments were carried out to determine whether microRNA-646 could regulate the proliferative potential and cell cycle progression of nasopharyngeal carcinoma cells by targeting mTOR. RESULTS: MicroRNA-646 was lowly expressed in nasopharyngeal carcinoma tissues and cell lines. Survival analysis confirmed the diagnostic value of microRNA-646 in nasopharyngeal carcinoma. Besides, the nasopharyngeal carcinoma patients with high level of microRNA-646 were expected to have a longer 5-year survival time compared with those with low level. Overexpression of microRNA-646 inhibited the proliferative potential and cell cycle progression of HONE1 and SUNE1 nasopharyngeal carcinoma cells. Dual-luciferase reporter gene assay detected the binding of microRNA-646 to mTOR. Moreover, mTOR was highly expressed in nasopharyngeal carcinoma tissues and cell lines. A negative correlation was found between microRNA-646 and mTOR. That is, the overexpression of mTOR could reverse the inhibitory effects of microRNA-646 on the proliferative potential and cell cycle progression of HONE1 and SUNE1 cells. CONCLUSIONS: MicroRNA-646 remains a low level in nasopharyngeal carcinoma. It inhibits the proliferative potential and cell cycle progression of nasopharyngeal carcinoma cells by targeting mTOR. It can, therefore, inhibit the development of nasopharyngeal carcinoma.

[HIV early infant diagnosis test in HIV-exposed children in China, 2015-2017].

Objective: To understand the early infant diagnosis (EID) test rate and associated factors in HIV-exposed children in China during 2015-2017. Methods: The follow-up information cards of 12 096 HIV-exposed children for 18 months after birth during 2015-2017 were collected from the Management Information System of China's Prevention of Mother-to-Child Transmission of HIV for a retrospective analysis. The EID test characteristics of HIV exposed children and associated factors were analyzed. Results: From 2015 to 2017, the EID test rate in HIV exposed children increased from 65.6% to 83.4% in China (trend χ(2) P<0.001). The EID test rate within 8 weeks after birth increased from 61.1% to 76.8% (trend χ(2) P<0.001), but the EID positive rate decreased from 8.7% to 3.4% (trend χ(2) P<0.001). The EID positive rate in fatal HIV-exposed children was 47.7%, 36.9% and 36.3% during 2015-2017, respectively, the differences were not significant. EID test rate was associated with ethnic group, living area, survival status and the year reaching 18-month-old of the children. Conclusions: The performance of EID test has been standardized step by step in China. The positive rate of EID test decreased gradually with year. However, the EID test rates in children who were from minority ethnic groups, lived in areas with lower prevalence of HIV infection and died within 18 months after birth were relatively low.

Laser Cooling of Radium Ions.

The unstable radium nucleus is appealing for probing new physics due to its high mass, octupole deformation, and energy level structure. Ion traps, with long hold times and low particle numbers, are excellent for work with radioactive species, such as radium and radium-based molecular ions, where low activity, and hence low total numbers, is desirable. We address the challenges associated with the lack of stable isotopes in a tabletop experiment with a low-activity (∼10 µCi) source where we laser-cool trapped radium ions. With a laser-cooled radium ion we measured the 7p^{2}P_{1/2}^{o} state's branching fractions to the ground state, 7s^{2}S_{1/2}, and a metastable excited state, 6d^{2}D_{3/2}, to be p=0.9104(7) and 0.0896(7), respectively. With a nearby tellurium reference line we measured the 7s^{2}S_{1/2}→7p^{2}P_{1/2}^{o} transition frequency, 640.096 63(6) THz.

[Serologic surveillance indicators analysis among syphilis-infected pregnant women in East China].

Objective: To analyze serologic surveillance indicators during pregnancy among syphilis-infected women who delivered in 2013 in East China. Methods: Data were from national 'Information System of Prevention of Mother-to-child Transmission of HIV, syphilis and HBV Management' and in total 5 206 syphilis-infected pregnant women who delivered in 2013 and in East China were involved in the analysis. Information on demographic characters, laboratory tests, and treatment regimens were collected. The maternal non-treponemal testing surveillance and titer distribution were described and compare the proportions between pregnant women receiving standard testing and non-standard testing, taking baseline testing and testing before delivery or at the third trimester. Multivariate logistic regression model was analyzed using maternal titer control as dependent variable, using prior history of syphilis infection, syphilis stages, titer, gestational weeks of treatment initiation and treatment regimens as independent variables in 3 940 pregnant women with both baseline testing results and testing results before delivery or at the third trimester. Results: The ages of the 5 206 syphilis infected pregnant women were (28.1±5.8) years old. The numbers of women received penicillin treatment, other treatment regimens and no treatment were 2 967 (57.0%), 281 (5.4%), and 1 958 (37.6%), respectively. The number of women with maternal seroconversion, 4-fold or greater titer decline, or titer increase were 349 (6.7%), 251 (4.8%) and 28 (0.5%). Multivariate analysis results showed that compared with pregnant women with prior history of syphilis, the OR(95%CI) for maternal titer control was 1.49 (1.18-1.88) among those with syphilis-infection history. Compared with pregnant women initiated treatment at 28 gestational weeks or before, the OR (95%CI) for maternal titer control was 4.09 (3.19-5.24) among those who initiated treatment after 28 gestational weeks. Compared with pregnant women initiated treatment at 28 gestational weeks or before, the OR (95%CI) for maternal titer control was 4.09 (3.19-5.24) among those who initiated treatment after 28 gestational weeks or received no treatment. Compared with pregnant women received penicillin treatment, the OR (95%CI) for maternal titer control among those received non-penicillin treatment and those received no treatment were 2.35 (1.46-3.76) and 1.55 (1.13-2.12), respectively. Conclusion: In East China, the proportion of women achieved seroconversion or 4-fold or greater titer decline during pregnancy was very low. Pregnant women with no prior history of syphilis infection, early maternal initiation of treatment, and penicillin treatment were more likely to reach maternal titer control.

[Comprehensive review of factors and preventions of mother to child transmission of hepatitis B virus].

Mother-to-child transmission of hepatitis B virus (HBV) is one of major public health issues. Difference is found on effect of preventions of mother to child transmission of HBV such as Hepatitis B vaccine, Hepatitis B immunoglobulin and antiretroviral drugs. Based on the risks of hepatitis B virus on children, influencing factors and interventions of HBV mother-to-child transmission were explored to improve prevention mother-to-child transmission of hepatitis B and to search appropriate strategies reducing mother-to-child transmission of HBV.

Association between killer cell immunoglobulin-like receptor 2DS5 gene with essential hypertension in the Chinese Han patients.

Hypertension has been suggested to be mediated by immunity and inflammation. As immune system genes, killer cell immunoglobulin-like receptors (KIRs) genes play an important role in the pathogenesis of autoimmune diseases. We conducted a community population-based case-control study to analyse associations between KIR genes and hypertension. KIR genes were genotyped using sequence-specific primer polymerase chain reaction in 380 unrelated essential hypertensives and 527 normotensives. The frequencies of KIR2DS5 gene were significantly decreased in participants with high high-sensitivity C-reactive protein (hsCRP) compared with participants with low hsCRP (17.02% vs 34.08%, p = .016). The presence of KIR2DS5 gene was independently associated with decreased risk of hypertension (odds ratio = 0.62; 95% confidence interval: 0.43-0.89), after adjusted for conventional risk factors, hsCRP and other KIR genes. We found that participants with KIR2DS5 gene had a decreased risk of hypertension compared with participants without KIR2DS5 gene. Our findings suggested that KIR2DS5 gene may be protective against hypertension.

Ineffectiveness of the Tobacco Hazards Prevention Act in patients with severe and persistent mental illness.

OBJECTIVES: The effect of the Tobacco Hazards Prevention Act (THPA) on the reduction of tobacco use in the general population in Taiwan is understood. However, there has been little research on how these policies affect people with severe and persistent mental illness (SPMI). Hence, the influence of the THPA on daily cigarette use by patients with SPMI was investigated in a 3-year follow-up. The risk and protective factors in smoking behavior and cessation were investigated. STUDY DESIGN: This is an observational study. METHODS: A total of 144 participants (78 of whom had smoked >100 cigarettes throughout their lifetime) were randomly selected from a healthcare network. Then, 100 of 144 patients with SPMI, included 50 smokers and 50 non-smokers, have agreed with 1st year follow-up. Eighty-two patients with SPMI, consisted of 44 smokers and 38 non-smokers, have agreed with 2nd year follow-up. RESULTS: Although women were less likely to smoke than men, those who did smoke reduced the number of cigarettes less than men over the 3-year period. Less-educated patients were more likely to smoke than those who were more educated but reduced the number of daily cigarettes more after implementation of the THPA. Maternal overprotection was a risk factor and paternal care a protective factor for smoking. Addiction, a perception of pleasure, interpersonal relationships, and self-destructive behavior increased cigarette smoking. Patients perceived that smoking alleviated their depressive symptoms. CONCLUSIONS: The THPA was ineffective for patients with SPMI. Some factors had different effects on the development of smoking behavior and the cessation process. Understanding the etiology of smoking can help policymakers establish more effective programs for smoking prevention and cessation.

Intensified nitrate and phosphorus removal in an electrolysis -integrated horizontal subsurface-flow constructed wetland.

A novel electrolysis-integrated horizontal subsurface-flow constructed wetland system (E-HFCWs) was developed for intensified removal of nitrogen and phosphorus contaminated water. The dynamics of nitrogen and phosphorus removal and that of main water qualities of inflow and outflow were also evaluated. The hydraulic retention time (HRT) greatly enhanced nitrate removal when the electrolysis current intensity was stabilized at 0.07 mA/cm2. When the HRT ranged from 2 h to 12 h, the removal rate of nitrate increased from 20% to 84%. Phosphorus (P) removal was also greatly enhanced-exceeding 90% when the HRT was longer than 4 h in the electrolysis-integrated HFCWs. This improved P removal is due to the in-situ formation of ferric ions by anodizing of sacrificial iron anodes, causing chemical precipitation, physical adsorption and flocculation of phosphorus. Thus, electrolysis plays an important role in nitrate and phosphorus removal. The diversity and communities of bacteria in the biofilm of substrate was established by the analysis of 16S rDNA gene sequences, and the biofilm was abundant with Comamonadaceae and Xanthomonadaceae bacteria in E-HFCWs. Test results illustrated that the electrolysis integrated with horizontal subsurface-flow constructed wetland is a feasible and effective technology for intensified nitrogen and phosphorus removal.

[Mode of delivery among HIV-positive pregnant women in areas with high prevalence of HIV in China, 2007-2013].

OBJECTIVE: To describe the changing demographic profile over time of pregnant women diagnosed with HIV infection, and trends in mode of delivery and pregnancy outcome. METHODS: An observational investigation was conducted based on a population of 1 128 HIV-positive pregnant women at eight sites in China in provinces with high prevalence of HIV among pregnant women and children between 2007 and 2013. The study area included Shangcai and Weishi counties in Henan province; Ruili and Longchuan counties and Linxiang prefecture in Yunnan province; Yining County in Xinjiang; and Lingshan county and Babu district in Guangxi province. Main outcome measures were maternal characteristics, mode of delivery, and related trends over time by Cochram-Mantel-Haenszel(CMH) χ(2)-test. RESULTS: A total hospital delivery rate of 96.4% was reported. For each year during the period 2007-2013, hospital delivery rates were 95.1% (253/266), 94.8% (188/198), 93.7% (164/175), 98.8% (159/161), 98.6% (141/143), 97.4% (114/117), and 100.0% (68/68), respectively (χ(2)CMH=7.68, P=0.006). The neonatal survival rate increased by 0.7% incrementally from 2007 to 2013, with 98.5% (262/266), 99.0% (196/198), 99.4% (174/175), 99.4% (160/161), 100.0% (143/143), 100.0% (117/117), and 100.0% (68/68), respectively (χ(2)CMH=4.58, P=0.030). The proportions of vaginal deliveries in those years were 62.2% (166/266), 54.8% (109/198), 59.9% (105/175), 61.7% (100/161), 66.7% (96/143), 58.8% (69/117), and 66.7% (46/68), respectively (χ(2)CMH=1.19, P= 0.276). The average rate for midwives skilled in procedures such as artificial rupture of membranes and episiotomy was 37.8% (261/691), with proportions decreasing during the study period at 39.2% (65/166), 47.4% (52/109), 35.9% (38/105), 46.0% (46/100), 25.5% (25/96), 31.2% (22/69), and 28.3% (13/46), respectively (χ(2CMH)=6.76, P=0.009). CONCLUSION: The annual rate of reported hospital delivery increased between 2007 and 2013, with a declining rate of skilled midwifery over the same period. Survival of neonates born to HIV-infected mothers in China has increased to nearly equivalent levels as those of developed countries.

Association between matrix metalloproteinase-9 rs3918242 polymorphism and development of coronary artery disease in a Chinese population.

We conducted a case-control study to investigate the role of one single nucleotide polymorphism of MMP-9 rs3918242 in the development of coronary artery disease. The rs3918242 was amplified with 435-bp DNA fragments using polymerase chain reaction coupled with restriction fragment length polymorphism. When compared with control subjects, patients with coronary artery disease had higher systolic and diastolic blood pressure, as well as higher triglycerides (P < 0.05), were more likely to suffer from diabetes mellitus, and had lower total cholesterol and high-density lipopolysaccharides. Using unconditional logistic analysis, we found that individuals with CT and TT genotypes were associated with increased risk of coronary artery disease in a co-dominant model, and the ORs (95%CI) were 1.50 (1.02-2.20) and 6.89 (2.51-23.41) for CT and TT, respectively. We observed that the T allele of rs3918242 was correlated with increased risk of coronary artery disease (OR = 1.88, 95%CI = 1.39-2.55). In conclusion, we suggest that the TT and CT genotypes and T allele of MMP-9 rs3918242 polymorphism is correlated with an increased risk of coronary artery disease in a Chinese population.

Configurable NOR gate arrays from Belousov-Zhabotinsky micro-droplets.

We investigate the Belousov-Zhabotinsky (BZ) reaction in an attempt to establish a basis for computation using chemical oscillators coupled via inhibition. The system consists of BZ droplets suspended in oil. Interdrop coupling is governed by the non-polar communicator of inhibition, Br2. We consider a linear arrangement of three droplets to be a NOR gate, where the center droplet is the output and the other two are inputs. Oxidation spikes in the inputs, which we define to be TRUE, cause a delay in the next spike of the output, which we read to be FALSE. Conversely, when the inputs do not spike (FALSE) there is no delay in the output (TRUE), thus producing the behavior of a NOR gate. We are able to reliably produce NOR gates with this behavior in microfluidic experiment.

Association between a functional single nucleotide polymorphism in the brain-derived neurotrophic factor gene and risk of child asthma.

Brain-derived neurotrophic factor (BDNF) promotes synaptic remodeling and modulates the function of other neurotransmitters. Allergic inflammation triggers neuronal dysfunction and structural changes in the airways. Genetic polymorphisms in functional regions of the BDNF gene have a plausible role in modulating the risk of child asthma (CA). This study examined the potential association between CA and three single nucleotide polymorphisms (SNPs) in BDNF (rs2030323, rs6265, and rs16917204 in the promoter, exon 4, and 3'-untranslated regions, respectively). The study was conducted in 350 children with asthma and 356 healthy controls. The genotype and allele frequencies and difference between groups were analyzed using HaploView 4.0 and SPSS 20.0 software platforms. The analysis revealed a strong association between the rs6265 genotype distribution and CA. The frequency of the G allele was significantly higher in CA patients than in healthy controls (P = 0.0007, odds ratio = 1.323, 95% confidence interval = 1.073-1.632). Strong linkage disequilibrium was observed between rs16917204 and rs6265. A significantly higher number of G-G haplotypes were observed in CA patients than in controls (P = 0.024 after Bonferroni correction), while the G-A haplotypes were more significant in controls (P = 0.013 after Bonferroni correction). This suggested that BDNF gene polymorphisms confer susceptibility to CA, and also support the notion that BDNF dysfunction is involved in the pathophysiological process of CA.

Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

UNLABELLED: Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. CONCLUSIONS: (a) These results confirm the importance of DA release in the NAc for reward-related states, with DA increasing in the core, but not shell subregion. (b) They provide first evidence that during the withholding of expected reward, DA decreases in the NAc core, but not shell region. (c) This decrease in DA appears only after a delay between delivery of reward and extinction likely due to it being masked by persisting DA release. We hypothesize the decrease in extinction-induced release of DA in the NAc core to be a marker for the despair/depression that is known to accompany the failure to obtain expected rewards/reinforcers.

Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence.

Injectable extended-release naltrexone (XRNTX) presents an effective therapeutic strategy for opioid addiction, however its utility could be hampered by poor adherence. To gain a better insight into this phenomenon, we utilized blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) in conjunction with a validated cue-induced craving procedure to examine neural correlates of XRNTX adherence. We operationalized treatment adherence as the number of monthly XRNTX injections (range: 0-3) administered to a group of fully detoxified heroin-dependent subjects (n=32). Additional outcomes included urine toxicology screening and self-reported tobacco use. The presented heroin-related visual cues reliably elicited heroin craving in all tested subjects. Nine, five, three and 15 of the participants, respectively, received zero, one, two and three XRNTX injections, predicted by the individual baseline fMRI signal change in response to the cues in the medial prefrontal cortex, a brain region involved in inhibitory self-control and emotional appraisal. The incidence of opioid-positive urines during the XRNTX therapy was low and remained about half the pre-treatment rate after the XRNTX ended. During the treatment, cigarette smoking behaviors followed patterns of opioid use, while cocaine consumption was increased with reductions in opioid use. The present data support the hypothesis that medial prefrontal cortex functions are involved in adherence to opioid antagonist therapy. A potential role of concurrent non-opioid addictive substances consumption during the XRNTX pharmacotherapy warrants further investigation. Our findings set the stage for further bio-behavioral investigations of the mechanisms of relapse prevention in opioid dependence.