How does the developing brain respond to recent experience? Repetition suppression (RS) is a robust and well-characterized response of to recent experience found, predominantly, in the perceptual ...cortices of the adult brain. We use functional near-infrared spectroscopy (fNIRS) to investigate how perceptual (temporal and occipital) and frontal cortices in the infant brain respond to auditory and visual stimulus repetitions (spoken words and faces). In Experiment 1, we find strong evidence of repetition suppression in the frontal cortex but only for auditory stimuli. In perceptual cortices, we find only suggestive evidence of auditory RS in the temporal cortex and no evidence of visual RS in any ROI. In Experiments 2 and 3, we replicate and extend these findings. Overall, we provide the first evidence that infant and adult brains respond differently to stimulus repetition. We suggest that the frontal lobe may support the development of RS in perceptual cortices.
Pulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary ...angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post-PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA-89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6-minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)-quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: ΔPVR (-27.9 ± 20.2% vs. -13.9 ± 23.9%,
< 0.05) and ΔmPAP (-17.1 ± 14.4% vs. -8.5 ± 18.0%,
< 0.05). There was a negative correlation between pre-BPA PVR and TTTL (
= -0.47,
< 0.05) which persisted post-BPA. PVR, mPAP, WHO FC and 6MWD were not improved significantly post-BPA in PP patients. BPA response was not related to TTTL terciles or CTPA-quantified residual disease burden. Patients PP experienced inferior response to BPA, despite similar baseline and procedural characteristics to IC. BPA does not abolish the relationship between TTTL and postsurgical PVR in PP patients, suggesting that BPA is less effective in treating residual PH after surgery in an experienced surgical center.
Ammopiptanthus mongolicus (Maxim. Ex Kom.) Cheng f., an endangered ancient legume species, endemic to the Gobi desert in north-western China. As the only evergreen broadleaf shrub in this area, A. ...mongolicus plays an important role in the region's ecological-environmental stability. Despite the strong potential of A. mongolicus in providing new insights on drought tolerance, sequence information on the species in public databases remains scarce. To both learn about the role of gene expression in drought stress tolerance in A. mongolicus and to expand genomic resources for the species, transcriptome sequencing of stress-treated A. mongolicus plants was performed.
Using 454 pyrosequencing technology, 8,480 and 7,474 contigs were generated after de novo assembly of RNA sequences from leaves of untreated and drought-treated plants, respectively. After clustering using TGICL and CAP3 programs, a combined assembly of all reads produced a total of 11,357 putative unique transcripts (PUTs). Functional annotation and classification of the transcripts were conducted by aligning the 11,357 PUTs against the public protein databases and nucleotide database (Nt). Between control and drought-treated plants, 1,620 differentially expressed genes (DEGs) were identified, of which 1,106 were up-regulated and 514 were down-regulated. The differential expression of twenty candidate genes in metabolic pathways and transcription factors families related to stress-response were confirmed by quantitative real-time PCR. Representatives of several large gene families, such as WRKY and P5CS, were identified and verified in A. mongolicus for the first time.
The additional transcriptome resources, gene expression profiles, functional annotations, and candidate genes provide a more comprehensive understanding of the stress response pathways in xeric-adapted plant species such as A. mongolicus.
Several patient-reported outcome measures have been developed to assess health status in pulmonary arterial hypertension. The required change in instrument scores needed, to be seen as meaningful to ...the individual, however remain unknown. We sought to identify minimal clinically important differences in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and to validate these against objective markers of functional capacity. Minimal clinically important differences were established from a discovery cohort (n = 129) of consecutive incident cases of idiopathic pulmonary arterial hypertension with CAMPHOR scores recorded at treatment-naïve baseline and 4–12 months following pulmonary arterial hypertension therapy. An independent validation cohort (n = 87) was used to verify minimal clinically important differences. Concurrent measures of functional capacity relative to CAMPHOR scores were collected. Minimal clinically important differences were derived using anchor- and distributional-based approaches. In the discovery cohort, mean (SD) was 54.4 (16.4) years and 64% were female. Most patients (63%) were treated with sequential pulmonary arterial hypertension therapy. Baseline CAMPHOR scores were: Symptoms, 12 (7); Activity, 12 (7) and quality of life, 10 (7). Pulmonary arterial hypertension treatment resulted in significant improvements in CAMPHOR scores (p < 0.05). CAMPHOR minimal clinically important differences averaged across methods for health status improvement were: Symptoms, –4 points; Activity, –4 points and quality of life –3 points. CAMPHOR Activity score change ≥minimal clinically important difference was associated with significantly greater improvement in six-minute walk distance, in both discovery and validation populations. In conclusion, CAMPHOR scores are responsive to pulmonary arterial hypertension treatment. Minimal clinically important differences in pulmonary hypertension-specific scales may provide useful insights into treatment response in future clinical trials.
Abstract Background Among pre-adolescents, the importance of different sources of cytomegalovirus (CMV) infection is unclear. Objective To assess the importance of several CMV sources among ...pre-adolescent children. Study design We used data from a United States population-based sample conducted from 1988 to 1994: 4–10-year-old participants ( n = 3386) of the Third National Health and Nutrition Examination Survey. We tested available sera for CMV-specific-IgG and assessed CMV prevalence differences by surrogates for exposure to childhood CMV sources (maternal CMV serostatus, breast-feeding, older sibling CMV serostatus, and child care center attendance). Results CMV infection was more prevalent (70%) among Mexican American children with foreign-born householders than among children with native-born householders (31% non-Hispanic White, 39% non-Hispanic Black, and 37% Mexican American children). Child's serostatus was associated with their mother's (prevalence difference range (PDR) = 33–40%) and older sibling's serostatus (PDR = 39–50%). Breast-feeding was associated with CMV in some racial/ethnic and householder groups (PDR = −5.1% to 22.7%). There was little difference in CMV seroprevalence by child care center attendance (PDR = −6.5% to −0.4%). Conclusions This study expands understanding of CMV by identifying the importance of householder nativity and demonstrating the importance of family transmission among the general population of pre-adolescents.
Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (PH). Despite excellent outcomes following PEA, a small proportion of ...patients have residual proximal disease or present with recurrent chronic thromboembolic PH and may benefit from further surgery. The aim of this study was to analyse outcomes following reoperative PEA at a high-volume national tertiary referral centre for the management of chronic thromboembolic PH.
This retrospective analysis was performed using our prospectively maintained PH database to identify all patients who underwent reoperative PEA surgery between the commencement of the programme in 1997 and January 2017, and the patients' data were collected for analysis.
Twelve patients underwent reoperative PEA during the period of study. The mean interval between primary procedure and reoperative procedure was 6.3 years. Significant improvements were observed in pulmonary haemodynamics following reoperative PEA. Mean pulmonary arterial pressure decreased from 46.8 to 29.8 mmHg (P < 0.0001) and pulmonary vascular resistance decreased from 662 to 362 dyne·s·cm-5 (P = 0.0007). A significant functional improvement in the 6-min walking test distance was also observed, increasing from 327 to 460 m at 6 months postoperatively (P = 0.0018). Median length of hospital stay was 12 days. In-hospital mortality was 8.3% with 1-year survival of 83.3%.
Reoperative PEA is technically possible and relatively safe, achieving good functional and physiological outcomes. Patients must be carefully selected by a multidisciplinary team, and surgery should be performed in experienced centres.
Background: Sexual and nonsexual transmission of cytomegalovirus (CMV) occurs, but the frequency of sexual transmission in the general population of the United States is unknown. Methods: Using data ...from 15- to 44-year-old (n = 7883) participants of the Third National Health and Nutrition Examination Survey (19881994), we examined the association between CMV seroprevalence and sexual activity markers. Using logistic regression, we calculated standardized prevalence differences (PDs)—the weighted average CMV prevalence among higher sexual risk groups minus CMV prevalence among the lowest sexual risk group—for each of several sexual activity markers (ever had sex, number of sex partners lifetime and past year, age at first intercourse, potential years of sexual activity, ever use oral contraceptives, herpes simplex virus type 2 antibody, and a calculated composite marker). Results: Even after controlling for covariates, we found associations between CMV seroprevalence and sexual activity among nonHispanic black all PDs for sexual activity markers were positive and composite PD = 8.5%, 95% confidence interval (CI) = 4.0%-13.1% and non-Hispanic white women (15 of 18 PDs for sexual activity markers were positive and composite PD = 10.8%, 95% CI = 3.1%-18.5%). We found a borderline significant association among Mexican American women (13 of 18 PDs for sexual activity markers were positive and composite PD = 3.5%, 95% CI = -0.7% to 7.6%). We found little or no association within each racial/ethnic group of men. Conclusions: Sexual activity measurably influences CMV seroprevalence among women of childbearing age, indicating that congenital CMV prevention messages should include strategies to reduce sexual transmission of CMV among pregnant women.
Riociguat for pulmonary hypertension Cannon, John E; Pepke-Zaba, Joanna
Expert review of clinical pharmacology,
05/2014, Letnik:
7, Številka:
3
Journal Article
Recenzirano
Pulmonary hypertension, an elevation of the mean pulmonary artery pressure ≥25 mmHg, ultimately leads to premature death due to right ventricular dysfunction. Ten treatments from three classes of ...drugs are licensed for the management of pulmonary arterial hypertension. These treatments have improved exercise capacity but median survival is still poor. Additionally there are no licensed therapies for the other groups of pulmonary hypertension. Riociguat is a novel drug that stimulates soluble guanylate cyclase independently of nitric oxide and in synergy with nitric oxide. This review summarises the available evidence for riociguat in the treatment across all groups of pulmonary hypertension with a focus on pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.