Effect of the Blood Pressure and Antihypertensive Drugs on Cerebral Small Vessel Disease: A Mendelian Randomization Study.

BACKGROUND: Previous studies yielded conflicting results about the influence of blood pressure (BP) and antihypertensive treatment on cerebral small vessel disease. Here, we conducted a Mendelian randomization study to investigate the effect of BP and antihypertensive drugs on cerebral small vessel disease. METHODS: We extracted single-nucleotide polymorphisms for systolic BP and diastolic BP from a genome-wide association study (N=757 601) and screened single-nucleotide polymorphisms associated with calcium channel blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers from public resources as instrumental variables. Then, we chose the genome-wide association study of white matter hyperintensity (WMH; N=18 381), cerebral microbleed (3556 cases, 22 306 controls), white matter perivascular space (9317 cases, 29 281 controls), basal ganglia perivascular space (BGPVS; 8950 cases, 29 953 controls), hippocampal perivascular space (HIPPVS; 9163 cases, 29 708 controls), and lacunar stroke (6030 cases, 248 929 controls) as outcome data sets. Subsequently, we conducted a 2-sample Mendelian randomization analysis. RESULTS: We found that elevated systolic BP significantly increases the risk of BGPVS (odds ratio [OR], 1.05 [95% CI, 1.04-1.07]; P=1.72×10-12), HIPPVS (OR, 1.04 [95% CI, 1.02-1.05]; P=2.71×10-7), and lacunar stroke (OR, 1.41 [95% CI, 1.30-1.54]; P=4.97×10-15). There was suggestive evidence indicating that elevated systolic BP is associated with higher WMH volume (ß=0.061 [95% CI, 0.018-0.105]; P=5.58×10-3) and leads to an increased risk of cerebral microbleed (OR, 1.16 [95% CI, 1.04-1.29]; P=7.17×10-3). Elevated diastolic BP was significantly associated with higher WMH volume (ß=0.087 [95% CI, 0.049-0.124]; P=5.23×10-6) and significantly increased the risk of BGPVS (OR, 1.05 [95% CI, 1.04-1.06]; P=1.20×10-16), HIPPVS (OR, 1.03 [95% CI, 1.02-1.04]; P=2.96×10-6), and lacunar stroke (OR, 1.31 [95% CI, 1.21-1.41]; P=2.67×10-12). The use of calcium channel blocker to lower BP was significantly associated with lower WMH volume (ß=-0.287 [95% CI, -0.408 to -0.165]; P=4.05×10-6) and significantly reduced the risk of BGPVS (OR, 0.85 [95% CI, 0.81-0.89]; P=8.41×10-19) and HIPPVS (OR, 0.88 [95% CI, 0.85-0.92]; P=6.72×10-9). CONCLUSIONS: Our findings contribute to a better understanding of the pathogenesis of cerebral small vessel disease. Additionally, the utilization of calcium channel blockers to decrease BP can effectively reduce the likelihood of WMH, BGPVS, and HIPPVS. These findings offer valuable insights for the management and prevention of cerebral small vessel disease.

An evolutionary game and system dynamics approach for the production and consumption of carbon-labeled products-based on a media monitoring perspective.

Carbon label is acknowledged as an effective way to combat the problem of global warming. As a powerful way to encourage individuals to adjust their consumption patterns and to promote the development of green consumption, carbon-labeled products are widely developed in China. To reveal the production and consumption process of carbon-labeled products, the present study constructs a tripartite game model consisting of the government, carbon-labeled products manufacturers and consumers based on a media monitoring perspective. The evolutionary stability strategy (ESS) is firstly determined by solving the replication dynamic equations and stability analysis of the equilibrium point, followed by the strategy analysis and sensitivity analysis through numerical simulation. The results show that media supervision can effectively complement and constrain government supervision. In addition, it can promote enterprises to standardize production and enhance consumers' trust and willingness to buy carbon-labeled products. The introduction of media supervision can well realize the ideal equilibrium of "effective government supervision, enterprise compliance and consumer support for purchase".

The fatty acid imbalance of cystic fibrosis exists at birth independent of feeding in pig and ferret models.

Persons with cystic fibrosis (CF) exhibit a unique alteration of fatty acid composition, marked especially among polyunsaturates by relative deficiency of linoleic acid and excess of Mead acid. Relative deficiency of docosahexaenoic acid is variably found. However, the initial development of these abnormalities is not understood. We examined fatty acid composition in young CF ferrets and pigs, finding abnormalities from the day of birth onward including relative deficiency of linoleic acid in both species. Fatty acid composition abnormalities were present in both liver and serum phospholipids of newborn CF piglets even prior to feeding, including reduced linoleic acid and increased Mead acid. Serum fatty acid composition evolved over the first weeks of life in both non-CF and CF ferrets, though differences between CF and non-CF persisted. Although red blood cell phospholipid fatty acid composition was normal in newborn animals, it became perturbed in juvenile CF ferrets including relative deficiencies of linoleic and docosahexaenoic acids and excess of Mead acid. In summary, fatty acid composition abnormalities in CF pigs and ferrets exist from a young age including at birth independent of feeding and overlap extensively with the abnormalities found in humans with CF. That the abnormalities exist prior to feeding implies that dietary measures alone will not address the mechanisms of imbalance.

Oxidative stress and impaired insulin secretion in cystic fibrosis pig pancreas.

Cystic fibrosis-related diabetes (CFRD) is one the most common comorbidities in cystic fibrosis (CF). Pancreatic oxidative stress has been postulated in the pathogenesis of CFRD, but no studies have been done to show an association. The main obstacle is the lack of suitable animal models and no immediate availability of pancreas tissue in humans. In the CF porcine model, we found increased pancreatic total glutathione (GSH), glutathione disulfide (GSSG), 3-nitrotyrosine- and 4-hydroxynonenal-modified proteins, and decreased copper zinc superoxide dismutase (CuZnSOD) activity, all indicative of oxidative stress. CF pig pancreas demonstrated increased DHE oxidation (as a surrogate marker of superoxide) in situ compared to non-CF and this was inhibited by a SOD-mimetic (GC4401). Catalase and glutathione peroxidase activities were not different between CF and non-CF pancreas. Isolated CF pig islets had significantly increased DHE oxidation, peroxide production, reduced insulin secretion in response to high glucose and diminished secretory index compared to non-CF islets. Acute treatment with apocynin or an SOD mimetic failed to restore insulin secretion. These results are consistent with the hypothesis that CF pig pancreas is under significant oxidative stress as a result of increased O2 ●- and peroxides combined with reduced antioxidant defenses against reactive oxygen species (ROS). We speculate that insulin secretory defects in CF may be due to oxidative stress.

Telomere length and multiple sclerosis: a Mendelian randomization study.

PURPOSE OF THE STUDY: Previous studies have established that telomere length is associated with multiple sclerosis (MS). However, confounding factors and reverse causality bias can impair observational research. Here, we conducted a two-sample MR study to see if telomere length is causally linked to MS using publically available GWAS summary statistics. MATERIALS AND METHODS: We screened 13 independent single-nucleotide polymorphisms (SNPs) related to leukocyte telomere length in a recent genome-wide association meta-analysis, which was available for 78,592 samples of European ancestry. The summary statistics for MS were from the latest meta-analyses conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC), which included 115,803 European participants (47,429 MS, 68,374 controls). RESULTS: We found that leukocyte telomere length and MS are correlated (IVW estimate of odds ratio (OR): 2.13 per 1-SD increase in genetically determined telomere length, 95% confidence interval (CI): 1.55-2.92, p = 3.18 × 10-6). CONCLUSION: Our MR study supported that leukocyte telomere length and MS have a positive causal relationship. Further researches are warranted to elucidate the physiological mechanism.

The negative affectivity dimension of Type D personality associated with increased risk for acute ischemic stroke and white matter hyperintensity.

OBJECTIVE: This study was conducted to examine the relationship among type D personality, acute ischemic stroke (AIS), and white matter hyperintensity (WMH). METHODS: In a cross-sectional study conducted between September 2020 and June 2021, 235 patients aged 50-85 years with first-ever ischemic cerebrovascular disease, including 146 males and 89 females, were enrolled. All participants underwent the Type D Scale-14 test containing negative affectivity (NA) and social inhibition (SI) subscales. Clinical and laboratory data were also collected for analysis. The patients were divided into the AIS group (n = 148) and the transient ischemic attack (TIA) group (n = 87) according to whether there was an acute lesion. RESULTS: Patients with type D personality had a higher frequency of AIS and LAA and a higher level of WMH. Multiple logistic regression showed that the NA score was related to a 1.11-fold increase in the odds of AIS (95% CI: 1.03-1.19). Neither NA nor SI showed a clear association with a higher frequency of LAA. Higher scores of NA (OR = 1.07, 95% CI: 1.01-1.15), SI (OR = 1.11, 95% CI: 1.03-1.19), and the interaction between the two dimensions (OR = 1.03, 95% CI: 1.01-1.05) were independently associated with an increased load of WMH. CONCLUSION: Type D personality was related to AIS and WMH. In particular, it was NA, not SI, affected the occurrence of AIS. Our findings may provide new insights regarding behavioral vulnerability for the development of cerebrovascular disorders.

Correlation between neutrophil-to-lymphocyte ratio and stability of carotid plaques.

OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) has been proved to be a strong predictor of carotid atherosclerotic plaque, but the correlation between NLR and the stability of carotid plaque is not clear. Thus we conducted a study to evaluate the correlation between NLR and the stability of carotid atherosclerotic plaque, and to develop a new evaluation scale for rapid clinical evaluation of carotid plaque stability. METHODS: We recruited 528 patients with acute anterior circulation ischemic stroke who were in accordance with extracranial and intracranial large artery atherosclerosis of Chinese ischemic stroke subtype. Blood routine examination and carotid ultrasound examination were performed on admission. According to the ultrasonic characteristics, the patients were divided into plaque stabilization group and plaque instability group. RESULTS: There was significant difference in NLR between plaque stability and instability groups (P < 0.001). The risk of plaque instability increased with the increase of NLR (odds ratio (OR), 4.737; 95% confidence interval (CI), 3.404-6.592; P < 0.001). Receiver operating characteristic (ROC) curve showed that the critical point of NLR is 2.55 and the area under the curve (AUC) was 0.782 (95%CI, 0.740-0.823; P < 0.001). The best cut-off value of the evaluation scale was ≥ 4 points (sensitivity, 0.77; specificity, 0.75; accuracy, 0.76). CONCLUSION: There is a correlation between NLR and carotid plaque instability. NLR may be useful as a potential inflammation biomarker indicating the risk of unstable carotid plaques. The new scoring scale is a reliable index to predict the stability of carotid plaque.

Daytime sleepiness and risk of stroke: A Mendelian randomization analysis.

OBJECTIVE: Daytime sleepiness is known to be related to stroke, but whether daytime sleepiness is a risk factor for stroke remains unclear. We conducted a two-sample Mendelian randomization study to assess the relationship between daytime sleepiness and stroke, ischemic stroke (IS) and IS subtypes. METHODS: Thirty-six single-nucleotide polymorphisms (SNPs) associated with daytime sleepiness were selected as instrumental variables, which were identified from a recent genome-wide association study(N = 452,071). Summary statistics of the SNPs on stroke, IS and IS subtypes were derived from the MEGASTROKE consortium with 40,585 stroke cases and 406,111 controls. RESULTS: We found that daytime sleepiness was associated with large artery stroke (OR, 6.75; 95%CI, 1.49-30.57; p = 0.013), but not with all stroke (OR, 1.29; 95%CI, 0.81-2.05; p = 0.282), all ischemic stroke(OR, 1.46; 95%CI, 0.90-2.39; p = 0.136), cardioembolic stroke(OR, 1.0; 95%CI, 0.39-2.64; p = 0.984), or small artery stroke(OR, 1.52; 95%CI, 0.46-5.05; p = 0.485). CONCLUSION: Our findings indicated that daytime sleepiness is causally associated with an increased risk of large artery stroke. Further studies are necessary to verify our results and explain the physiological mechanisms.

Educational attainment protects against epilepsy independent of cognitive function: A Mendelian randomization study.

OBJECTIVE: Observational studies have suggested that increased levels of education and cognition are associated with a reduced risk of epilepsy. However, such associations are easily influenced by confounding or reverse causality. Hence, we conducted a two-sample univariable and multivariable Mendelian randomization (MR) to estimate the total and independent causal effects of educational attainment and cognition on epilepsy risk. METHODS: We performed MR estimates on International League Against Epilepsy (ILAE) Consortium genome-wide association study (GWAS) data (15 212 epilepsy cases and 29 677 controls). We then validated the results in FinnGen (3424 epilepsy cases and 110 963 controls) and applied meta-analysis to all the results. RESULTS: In the meta-analysis of the ILAE and FinnGen results, genetically determined increased educational attainment was associated with a reduced risk of epilepsy (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.80-0.88; P < .001). Similarly, genetically determined increased cognitive function was associated with a reduced risk of epilepsy (OR 0.94, 95% CI 0.88-1.00, P = .043). When educational attainment and cognitive function were included in the same multivariable MR, only educational attainment was still associated with a reduced risk of epilepsy (OR 0.88, 95% CI 0.81-0.95, P = .002). SIGNIFICANCE: This MR study provides evidence to support that increased educational attainment can reduce the risk of developing epilepsy independent of cognitive function.

Autoimmunity to urothelial antigen causes bladder inflammation, pelvic pain, and voiding dysfunction: a novel animal model for Hunner-type interstitial cystitis.

Recent evidence revealed that Hunner-type interstitial cystitis (HIC) is a robust inflammatory disease potentially associated with enhanced immune responses and histologically characterized by epithelial denudation and lymphoplasmacytic infiltration with frequent clonal expansion of infiltrating B cells. To date, few animal models that reproduce the histological and clinical correlates of HIC have yet been established. In the present study, we aimed to develop a novel animal model for HIC via autoimmunity to the bladder urothelium using the transgenic mouse model (URO-OVA) that expresses the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the bladder urothelium. OVA-specific lymphocytes (splenocytes) were generated by immunization of C57BL/6 mice with OVA protein and injected intravenously into URO-OVA mice. The splenocytes from OVA-immunized C57BL/6 mice showed increased interferon (IFN)-γ production in response to OVA stimulation in vitro. URO-OVA mice adoptively transferred with OVA-primed splenocytes developed cystitis exhibiting histological chronic inflammatory changes such as remarkable mononuclear cell infiltration predominantly composed of T and B lymphocytes, increased vascularity, and mucosal hyperemia in the bladder at days 7-28 with a peak at day 21 tested. No systemic inflammation was found in cystitis-induced URO-OVA mice, nor was any inflammation found in wild-type C57BL/6 mice adoptively transferred with OVA-primed splenocytes. Along with bladder inflammation, URO-OVA mice demonstrated significantly increased pelvic nociceptive responses, voiding dysfunction, and upregulated mRNA expression levels for IFN-γ, tumor necrosis factor-α (TNF-α), and substance P precursor in the bladder. This model reproduces the histological and clinical features of human HIC, providing a novel model for HIC research.

Individualized intervention to improve rates of exclusive breastfeeding: A randomised controlled trial.

BACKGROUND: Despite breastfeeding is significant benefits for maternal and infant, the discontinuation of breastfeeding is high. Some of studies showed that the effect of intervention in improving the rate of exclusively breastfeeding is unclear. The aim of this study is to investigate the effectiveness of individualized intervention compared with routine care in improving rates of exclusive breast feeding. METHODS: Women were divided into two groups. We provided individual antenatal breastfeeding education and postnatal lactation support to intervention group. Control group received routine care. Significance was set at P < .05. RESULTS: We recruited 352 women of whom 176 were randomized to intervention group, 176 to control group. In total, 293 (83.2%) completed 4 months of follow-up. At discharge from hospital, 43.2% of women randomized to intervention group were exclusively breastfeeding compared with 30.0% of women in control group (relative risk 1.78; 95% confidence interval [CI] 1.12-2.82). At 4 months, 70.9% of women in the intervention group were exclusively breastfeeding compared with 46.2% of the women in the control group (2.84; 1.76-4.60). At discharge from hospital, 95.1% of women in the intervention group were breastfeeding on demand compared with 68.1% of women receiving routine care (9.00; 4.09-19.74). At 4 months, 94.6% of women in intervention group were breastfeeding on demand compared with 75.9% of women in the control group (5.57; 2.48-12.49). CONCLUSION: The regular ongoing individualized antenatal education and postnatal support can effective increase the rates of exclusive breastfeeding from delivery to postpartum 4 months and change the breastfeeding behavior.

Fetal hyperglycemia acutely induces persistent insulin resistance in skeletal muscle.

Offspring exposed in utero to maternal diabetes exhibit long-lasting insulin resistance, though the initiating mechanisms have received minimal experimental attention. Herein, we show that rat fetuses develop insulin resistance after only 2-day continuous exposure to isolated hyperglycemia starting on gestational day 18. Hyperglycemia-induced reductions in insulin-induced AKT phosphorylation localized primarily to fetal skeletal muscle. The skeletal muscle of hyperglycemia-exposed fetuses also exhibited impaired in vivo glucose uptake. To address longer term impacts of this short hyperglycemic exposure, neonates were cross-fostered and examined at 21 days postnatal age. Offspring formerly exposed to 2 days late gestation hyperglycemia exhibited mild glucose intolerance with insulin signaling defects localized only to skeletal muscle. Fetal hyperglycemic exposure has downstream consequences which include hyperinsulinemia and relative uteroplacental insufficiency. To determine whether these accounted for induction of insulin resistance, we examined fetuses exposed to late gestational isolated hyperinsulinemia or uterine artery ligation. Importantly, 2 days of fetal hyperinsulinemia did not impair insulin signaling in murine fetal tissues and 21-day-old offspring exposed to fetal hyperinsulinemia had normal glucose tolerance. Similarly, fetal exposure to 2-day uteroplacental insufficiency did not perturb insulin-stimulated AKT phosphorylation in fetal rats. We conclude that fetal exposure to hyperglycemia acutely produces insulin resistance. As hyperinsulinemia and placental insufficiency have no such impact, this occurs likely via direct tissue effects of hyperglycemia. Furthermore, these findings show that skeletal muscle is uniquely susceptible to immediate and persistent insulin resistance induced by hyperglycemia.

A randomized interventional study to promote milk secretion during mother-baby separation based on the health belief model: A consort compliant.

BACKGROUND: Breast milk is the most important nutrition for premature babies, but mothers of premature infants have difficulty in initiating and sustaining lactation. Breastfeeding infants who are separated with mothers have decreased morbidity. Nevertheless, such decrease is limited due to insufficient milk supply resulting from mother-baby separation during lac. OBJECTIVE: To evaluate the effect of intervention methods based on the health belief model on promoting the secretion of milk among mothers who were separated with their babies. METHODS: In this prospective, randomized controlled clinical trial, we enrolled 260 separation mothers between September 26, 2016 and March 7, 2017, in a 3rd-grade women and children hospital of Chengdu. The mothers all had cesarean delivery and were randomized into 2 groups: the intervention group (educated by investigators based on the health belief) and the control group (routinely educated by obstetric nurses). Data on the onset of lactation and the milk volume during 3 days postpartum were collected. The breast swelling rate within 3 days postpartum and the exclusive breastfeeding rate at 42 days postpartum were compared. The psychologic scores of separation maternal in both groups were assessed with State-Trait Anxiety Inventory at the 3rd day postpartum. RESULTS: Compared with the control group, the intervention group had significantly earlier lactation time (P < .01), significantly larger milk volume (P < .01) during 24, 24 to 48, and 48 to 72 hours, and significantly lower psychologic scores (P < .01) at the 3rd-day postpartum.The onset of lactation among mothers who initiated milk expression within 1 hour after childbirth were earlier than those who initiated milk expression between 1 and 6 hours (P < .01); the milk volume within 24-hour postpartum did not differ significantly between the 2 groups (P > .05). However, the milk volume of the early-expression group (<1 hour) was significantly higher than that of the late-expression group (1-6 hours) during 24 to 48 and 48 to72 hours (P < .05).The breast swelling rate of separation mothers within 3 days postpartum in the intervention group was lower than that in the control group (P < .05). The exclusive breastfeeding rate of mothers in the intervention group was significantly higher than that in the control group (59% vs 35%; P < .01) at 42 days postpartum. CONCLUSION: Nursing intervention based on the health belief model can stimulate milk secretion in mothers who were separated with their babies.

[A preliminary study of the difference in composition of intestinal bifidobacteria between healthy infants and infants with allergic diseases].

OBJECTIVE: To investigate the association between intestinal bifidobacteria and allergic diseases in infants by comparing the composition of intestinal bifidobacteria between healthy infants and infants with allergic diseases. METHODS: A total of 48 infants were enrolled, and fecal samples were collected on days 0, 2, 7, and 15 and at months 1, 6, and 12 after birth. Among these infants, 22 who experienced allergic diseases before the age of 1 year were enrolled as allergic group and 26 healthy infants were enrolled as healthy group. Quantitative real-time PCR was used for the qualitative and quantitative analyses of Bifidobacterium and 8 species of bifidobacteria in fecal samples. RESULTS: There was a difference in the composition of intestinal bifidobacteria between the two groups within 1 month after birth: the healthy group showed a reduction in bifidobacteria on day 2, while this feature was not observed in the allergic group. Compared with the healthy group, the allergic group had a significantly lower detection count of Bifidobacterium at month 1 (P<0.05) and a significantly lower detection rate of B.breve on day 15 (P<0.05), with delayed colonization of B.infantis. CONCLUSIONS: Intestinal bifidobacteria and their composition within 1 month after birth may be associated with the development of allergic diseases, and this period of time may be a critical period for the prevention and treatment of allergic diseases in infants.

Risk factors for episiotomy during vaginal childbirth: A retrospective cohort study in Western China.

OBJECTIVE: To assess the incidence rates and risk factors for episiotomy during vaginal childbirth in a Western China context. METHODS: A retrospective hospital-based cohort study was conducted using computerized data of 3721 singleton vaginal deliveries after 28 weeks of gestation. Women who underwent episiotomy were compared with those who did not. RESULTS: The overall prevalence of episiotomy was 44.0% (1636/3721); 52.9% (1458/2756) among primiparas and 18.4% (178/965) among multiparas (P < 0.001). Adjusted risk factors significantly associated with episiotomy included primiparity, prolonged second stage of labor, and labor-management personnel. Risk factors specific to primiparas were increasing maternal age (per year) (OR = 1.04, 95% CI 1.01 to 1.07, P = 0.035), increasing biparietal diameter (per centimeter) (OR = 1.40, 95% CI 1.06 to 1.84, P = 0.017), first stage of labor beyond 10-hour (OR = 1.36, 95% CI 1.10 to 1.68, P = 0.005), and birth weight (per 100 g) (OR = 1.06, 95% CI 1.03 to 1.09, P < 0.001). Birth weight resulted in an adjusted risk increase of 6.1% among primiparas for every 100 additional grams of birth weight. For the analysis stratified by labor-management personnel, moderately experienced midwifery was a risk factor of episiotomy (OR = 1.76, 95% CI 1.21 to 2.56, P = 0.003); midwives with bachelor's degree (OR = 1.47, 95% CI 1.15 to 1.88, P = 0.002), and obstetricians with doctor's degree (OR = 2.00, 95% CI 1.18 to 3.39, P = 0.010) were most likely to perform episiotomy. CONCLUSION: Episiotomy is still commonly performed in Western China. A survey of maternity care professionals' knowledge of and attitudes towards episiotomy is urgently required to explore the complex reasons for conducting episiotomy.

Development of a polarized pancreatic ductular cell epithelium for physiological studies.

Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate ([Formula: see text]) secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at the air-liquid interface developed typical epithelial cell morphology and stable transepithelial resistance and expressed epithelial cell markers (zona occludens-1 and ß-catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers. Polarized cells were studied in Ussing chambers bathed in Krebs-Ringer [Formula: see text] solution at 37°C gassed with 5% CO2 to measure short-circuit currents ( Isc). Ratiometric measurement of extracellular pH was performed with fluorescent SNARF-conjugated dextran at 5% CO2. Cells demonstrated a baseline Isc (12.2 ± 3.2 µA/cm2) that increased significantly in response to apical forskolin-IBMX (∆ Isc: 35.4 ± 3.8 µA/cm2, P < 0.001) or basolateral secretin (∆ Isc: 31.4 ± 2.5 µA/cm2, P < 0.001), both of which increase cellular levels of cAMP. Subsequent addition of apical GlyH-101, a CFTR inhibitor, decreased the current (∆ Isc: 20.4 ± 3.8 µA/cm2, P < 0.01). Extracellular pH and [Formula: see text] concentration increased significantly after forskolin-IBMX (pH: 7.18 ± 0.23 vs. 7.53 ± 0.19; [Formula: see text] concentration, 14.5 ± 5.9 vs. 31.8 ± 13.4 mM; P < 0.05 for both). We demonstrate the development of a polarized pancreatic ductular epithelial cell epithelium with CFTR-dependent [Formula: see text] secretion in response to secretin and cAMP. This model is highly relevant, as porcine pancreas physiology is very similar to humans and pancreatic damage in the cystic fibrosis pig model recapitulates that of humans. NEW & NOTEWORTHY Pancreas ductular epithelial cells control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate secretion. Their function is critical because when CFTR is deficient in cystic fibrosis bicarbonate secretion is lost and the pancreas is damaged. Mechanisms that control pancreatic bicarbonate secretion are incompletely understood. We generated well-differentiated and polarized porcine pancreatic ductular epithelial cells and demonstrated feasibility of bicarbonate secretion. This novel method will advance our understanding of pancreas physiology and mechanisms of bicarbonate secretion.

Polyunsaturated fatty acid composition and childhood adversity: Independent correlates of depressive symptom persistence.

Childhood experiences, personality, and polyunsaturated essential fatty acid (PUFA) composition have all been shown to affect the likelihood of depressive symptoms. Few studies have addressed relationships between these factors in their influence on the occurrence or course of depressive symptoms. The following analysis was designed to do so. Subjects, 15-20 years old, had either begun antidepressant treatment within the preceding month (n = 88), or had never taken psychiatric medications (n = 92). Baseline assessments included a structured diagnostic interview, the self-completed Multiphasic Personality Questionnaire, and a determination of plasma PUFA phospholipid composition. Depressive symptom levels were assessed at baseline and again at 4, 8 and 12 months. Omega-3 composition and general childhood trauma scores were unrelated to each other but both correlated, in predicted directions, with negative emotionality. Low omega-3 composition and history of childhood trauma were associated with persistence of depressive symptoms during follow-up, largely through their effects on negative emotionality. Negative emotionality appears to comprise a final common pathway to depressive disorder through which the diverse risk factors of childhood adversity and low omega-3 composition are expressed.

[A preliminary analysis of changes in composition of intestinal microbiota during infancy using polymerase chain reaction-denaturing gradient gel electrophoresis].

OBJECTIVE: To investigate the composition of bacteria in the stools of infants and the colonization of intestinal microbiota during infancy. METHODS: Fresh stools were collected from 15 healthy infants at 0, 2, 4, 7, 10, 14, and 28 days and 3, 6, and 12 months after birth. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) was used to analyze the composition of intestinal microbiota, perform sequencing of dominant bacteria, and to analyze the changes in the composition of intestinal microbiota during infancy. RESULTS: DGGE fingerprint showed that the composition of intestinal microbiota during infancy changed significantly over time after birth. The cloning and sequencing results indicated that Proteobacteria colonized the earliest, mainly the obligate aerobes Enterobacter and Pseudomonas, followed by the obligate anaerobes (Clostridium hathewayi and Veillonella parvula) and the facultative anaerobe Clostridium ramosum in Firmicutes, and Verrucomicrobia. Actinobacteria colonized the latest, mainly Bifidobacterium, and gradually became dominant bacteria. CONCLUSIONS: During infancy, obligate aerobes colonize the intestinal tract the earliest, followed by obligate anaerobes and facultative anaerobes. Proteobacteria colonizes the earliest, followed by Firmicutes and Verrucomicrobia, and Actinobacteria, mainly Bifidobacterium, colonizes the latest.

[Analyzing Colonization of Bifidobacteria in Infants with Real-time Fluorescent Quantitative PCR].

OBJECTIVES: In order to know how intestinal Bifidobacteria community could be built in the infants and whether the environmental factors could affect them, the present study was conducted to characterizethe species composition and trace the quantitative changes of intestinal Bifidobacteria of the infants in their early stages with non-culture dependent molecular method. The possible association of Bifidobacteria community of the infants with their health was also discussed. METHODS: Total 16 of full-term newborn infants born between March and April 2013 were recruited for the present study. Fecal samples were collected from them at 1 day, 2 days, 4 days, 7 days, 10 days, 14 days, 28 days, 3 months, 6 months and 1 year after birth. Real-time fluorescent quantitative PCR with genus and species specific premiers was used to detect Bifidobacteria and 8 predominate species in human intestine qualitatively and quantitatively present in these collected fecal samples. RESULTS: Total 136 fecal sample were collected and Bifidobacteria were detected from 93.4% (127/136) of them with the concentration of 1.0×10 5 to 1.0×10 11 CFU/g. Bifidobacteria were found in 83.3% of the fecal samples collected from the first day after birth with more than about 10 5 CFU/g. However, Bifidobacteria were detected relative low until 14 days and were taxonomically belonged only to one or two species. Bifidobacteria were found in almost 100% of the fecal samples collected after birth 28 days with more than 108 CFU/g, and the detected species of Bifidobacteria was increased to 3 species after 28 days to 6 months. All of the fecal samples collected from one year had more than 3 species of Bifidobacteria with high cell counts. Among the detected Bifidobacteria were B.breve 92.1%, B.infantis 66.1%, B. catenulatum 59.8%, B. bifidum 25.2%, B. longum 24.4%, B.dentium 13.4%, B.angulatum 5.5% and B.adolescentis 1.6%, respectively. CONCLUSIONS: The detected Bifidobacteria greatly varied qualitatively and quantitatively after birth to one year which could be considered as the important and sensitive period for Bifidobacteria to colonize and built its communityin the infants. Different from previous studies, the colonization of Bifidobacteria in the tested infants was found delayed and the composition and diversity of Bifidobacteria species was different from other studies. These might result from different deliveryway, feeding pattern and other environmental factors related to the tested infants.

Depression, Social Support, and Coping Styles among Pregnant Women after the Lushan Earthquake in Ya'an, China.

AIM: The aim of this study is to assess the depression of pregnant women in the aftermath of an earthquake, and to identify the social support that they obtained, their coping styles and socio-demographic factors associated with depression. METHODS: A total of 128 pregnant women from three hospitals in the epicenter area were recruited immediately after the Ya'an earthquake. Their depression was investigated using the Edinburgh Postnatal Depression Scale (EPDS) with a cutoff score of 14; the social support that they obtained was measured using the Social Support Questionnaire; and their coping styles were assessed using the Coping Styles Questionnaire. RESULTS: Immediately after the earthquake, the incidence rate of depression in pregnant women was 35.2%, higher than that of the general pregnant population (7%-14%). The EPDS scores were significantly correlated with gestation age at the time of the earthquake, objective support, subjective support, use of support, negative coping style, and positive coping style. The regression analysis indicated that risk factors of prenatal depression include the number of children, relatives wounded, subjective support, and coping styles. A further analysis of the interaction between social support and two types of coping styles with depression showed that there was interaction effect between subjective social support and positive coping styles in relation to EPDS scores. There was an inverse relationship between low EPDS scores and positive coping styles and high social support, and vice versa. CONCLUSION: The timing of the occurrence of the earthquake may not necessarily affect the progress of the illness and recovery from depression, and psychological intervention could be conducted in the immediate aftermath after the earthquake. The impact of coping styles on prenatal depression appeared to be linked with social support. Helping pregnant women to adopt positive coping styles with good social support after a recent major earthquake, which is a stressor, may reduce their chances of developing prenatal depression.