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BACKGROUND AND PURPOSE: Cardiovascular disease (CVD) encompasses a range of disorders that affect health and functioning in older adults. While cognitive declines have been linked to both cardiovascular and cerebral blood perfusion, protective neurovascular mechanisms raise the question whether cerebrovascular perfusion differs as a function of cardiovascular health status. The present study examined whether cerebrovascular perfusion significantly differs between healthy older adults with and without diagnosed CVD. The study also examined whether previously documented sex differences in cerebral perfusion would be replicated. METHODS: Twenty CVD patients without significant heart failure and 39 healthy controls were recruited to undergo a comprehensive assessment including an interview, echocardiogram, and magnetic resonance imaging (MRI). Arterial spin labeling (ASL) was used to quantify cerebral blood perfusion. RESULTS: Both groups exhibited mean left ventricular ejection fractions that fell within normal limits. In line with previous research, women exhibited significantly higher cerebral perfusion than men. There were no significant group differences in whole brain cerebrovascular perfusion, regional perfusion, or white matter perfusion by patient status after accounting for sex and age. CONCLUSIONS: These findings suggest that the effects of mild CVD on cerebrovascular perfusion are minimal. Future studies are needed to investigate the mechanisms involved in maintaining cerebrovascular perfusion in the context of altered peripheral perfusion determine and to determine whether this finding extends to more acute or severe CVD.

The Cretaceous sandstone reservoir in the Kuche Depression, Tarim Basin, western China, was investigated with reference to its reservoir property evolution during diagenesis. Six general diagenetic stages were recognised through petrographic, mineralogical and geochemical analyses. Fluid–rock interaction experiments were conducted under these six continuous diagenetic conditions, that is, with a simulation sequence of compaction → early diagenesis → organic acid incursion I → elevated temperature/pressure → organic acid incursion II → late diagenesis. Corresponding to these six experimental stages, a total of six models were constructed. Finally, an extended model of fluid–rock interaction during diagenesis at a geological timescale (from 30 Ma to present) was constructed after various parameters had been validated. Results demonstrate the diagenetic stages from both the experimental and numerical simulations generally matched findings obtained from the petrographic and geochemical analyses: (i) With compaction becoming weakened, cementation by various minerals was gradually increased. (ii) Quartz overgrowth occurred because the contemporaneous sedimentary water was alkaline. (iii) Most minerals (for example, calcite and feldspar minerals) displayed dissolution owing to the first organic acid incursion, resulting in the visual porosity to increase to 29.26%. (iv) Increases of temperature and pressure caused a minor fluctuation of the porosity change. (v) The cement that formed during earlier stages largely dissolved with the second organic acid incursion. (vi) During the last stage, the reservoir fluid was diluted by sedimentary alkaline water and most minerals precipitated under an alkalic environment. The present porosity simulated is about 11.4%, comparable with the actually measured data. This study demonstrates that the combination of petrographic observations, laboratory experiments and numerical simulations can not only reconstruct the diagenetic process, but also provide a quantitative evaluation and prediction of reservoir petrophysical properties. This article is protected by copyright. All rights reserved.

Objective In-person lifestyle interventions for obesity treatment yield significant improvements in depression. These improvements may be attributed to the excellent weight losses produced by in-person interventions. In contrast, Internet programs yield more modest weight losses, and their effect on depression is unknown. This study is the first to examine whether Internet-delivered obesity treatment impacts depressive symptoms. Methods Participants (N = 136) were randomized to either a community campaign plus Internet behavioral weight loss (IBWL) or community campaign alone (Control). IBWL did not include online social support components. A measure of depressive symptoms was administered, and weight was objectively assessed. Results Of the total sample, 24% met the clinical cutoff for elevated depression risk at baseline. IBWL participants lost more weight during treatment (P = 0.005) and experienced significantly greater improvements in depressive symptoms (P = 0.02). Among participants who met the clinical cutoff for elevated risk for depression at baseline, those assigned to IBWL had greater improvements in depressive symptoms during treatment compared to Control (P = 0.033). Consequently, at post-treatment, a smaller percentage of IBWL participants were at elevated risk for depression. Conclusions This study is the first to show that Internet-delivered obesity treatment improves depression risk and depressive symptoms in individuals with overweight or obesity.

Hydrogen sulphide (H2 S) is generated endogenously from L-cysteine (L-Cys) by the enzymes cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). In addition, L-Cys is commonly used as a precursor in the food and pharmaceutical industries. The aim of the present study is to determine whether L-Cys regulates intestinal nutrient transport. To that end, the presence of CBS and CSE in the jejunum epithelium was assessed by immunohistochemistry, Western blotting and the methylene blue assay. In addition, in vivo L-Cys (100 mg/kg, administered immediately after the glucose load) significantly increased blood glucose levels 30 min after the oral administration of glucose to mice. This effect of L-Cys was completely blocked by amino-oxyacetic acid (AOA; 50 mg/kg; administered at the same time as L-Cys) an inhibitor of CBS. Measurements of the short-circuit current (Isc) in the rat jejunum epithelium revealed that L-Cys (1 mmol/L; 6 min before the administration of L-alanine) enhances Na(+)-coupled L-alanine or glucose transport, and that this effect is inhibited by AOA (1 mmol/L;10 min before the administration of L-Cys), but not D,L-propargylglycine (PAG;1 mmol/L; 10 min before the administration of L-Cys), a CSE inhibitor. Notably, L-Cys-evoked enhancement of nutrient transport was alleviated by glibenclamide (Gli;0.1 mmol/L; 10 min before the administration of L-Cys), a K(+) channel blocker. Together, the data indicate that L-Cys enhances jejunal nutrient transport, suggesting a new approach to future treatment of nutrition-related maladies, including a range of serious health consequences linked to undernutrition.

Objectives This study aimed to test the safety and efficiency of a novel stent retriever, RECO, in a swine model. Background The stent retrievers show great benefit for patients with acute ischemic stroke. Methods The framework of the stent was optimized. The proximal stent was closed; mechanical connection replaced the electrolysis connection and the push wire located on the longitudinal axis. After tests in vitro, the safety and thrombectomy efficiency of RECO device were evaluated by angiography and histological analysis in a swine model with placement of experimental soft or hard thrombi. Results No device-related thrombi were observed on the perioperative term or 1 month later. The endothelial cells were intact and the smooth muscle cells did not migrate or proliferate. Device-related vasospasm was detected in 9% vessels undergoing the procedure and was alleviated after delivery of a dose of nitroglycerin. The RECO device demonstrated a high recanalization rate in the target vessels with a mean of 1.3 runs. No residual thrombi were observed under the DSA or microscope. Conclusions Our data indicated that RECO device was a novel, safe and effective stent based clot retriever. A phase IIa clinical trial, RESTORE, is undergoing (NCT01983644). © 2015 Wiley Periodicals, Inc.

Objective To examine whether overweight social network members and normative influence for obesity are associated with weight loss outcomes during obesity treatment.

Objective To examine whether adding either small, variable financial incentives or optional group sessions improves weight losses in a community-based, Internet behavioral program. Methods Participants (N = 268) from Shape Up Rhode Island 2012, a 3-month Web-based community wellness initiative, were randomized to: Shape Up+Internet behavioral program (SI), Shape Up+Internet program+incentives (SII), or Shape Up+Internet program+group sessions (SIG). Results At the end of the 3-month program, SII achieved significantly greater weight losses than SI (SII: 6.4% [5.1-7.7]; SI: 4.2% [3.0-5.6]; P = 0.03); weight losses in SIG were not significantly different from the other two conditions (SIG: 5.8% [4.5-7.1], P's ≥ 0.10). However, at the 12-month no-treatment follow-up visit, both SII and SIG had greater weight losses than SI (SII: 3.1% [1.8-4.4]; SIG: 4.5% [3.2-5.8]; SI: 1.2% [−0.1-2.6]; P's ≤ 0.05). SII was the most cost-effective approach at both 3 (SII: $34/kg; SI: $34/kg; SIG: $87/kg) and 12 months (SII: $64/kg; SI: $140/kg; SIG: $113/kg). Conclusions Modest financial incentives enhance weight losses during a community campaign, and both incentives and optional group meetings improved overall weight loss outcomes during the follow-up period. However, the use of the financial incentives is the most cost-effective approach.

Background and Purpose H2S induces vasodilatation by opening KATP channels but it may also affect other ion channels. The aim of this study was to investigate the effect of H2S on intestinal motility in rats and its underlying mechanism. Experimental Approach The tension of intestinal muscle strips, afferent firing of intestinal mesenteric nerves, length of duodenal smooth muscle cells and whole-cell membrane potential of dorsal root ganglion (DRG) neurons were monitored. H2S-producing enzymes were located by immunofluorescence staining. Key results NaHS exerted early transient excitation and late long-lasting inhibition on the intestinal contraction. The excitation was attenuated by TRPV1 antagonists capsazepine, A784168, SB-366791 and NK1 receptor antagonist L703606, while the inhibition was attenuated by glibenclamide. NaHS increased duodenal afferent nerve firing and depolarized DRG neurons. These effects were reduced by capsazepine and A784168. NaHS relaxed isolated duodenal smooth muscle cells. The KATP channels were expressed in smooth muscle cells. Cystathionine β-synthase and cystathionine γ-lyase were expressed in rat duodenal myenteric neurons. L-cysteine and S-adenosyl-L-methionine increased the contraction of duodenal muscle strips, an effect attenuated by capsazepine and L703606. Conclusions and Implications NaHS induces biphasic effects on intestinal motility in rats while endogenous H2S only exerts an excitatory effect. This transient excitatory effect might be mediated by activation of TRPV1 channels in sensory nerve terminals with the consequent release of substance P. The long-lasting inhibitory effect might be mediated by activation of KATP channels in the smooth muscle cells. These findings reveal a novel mechanism for the excitatory effect of H2S on gastrointestinal motility.

Controversies and risks continue to be reported about exogenous mesenchymal stem cell-based therapies. In contrast with employing exogenous stem cells, making use of lung resident mesenchymal stem cells (LR-MSCs) could be advantageous. Our study sought to isolate the LR-MSCs and explore their potential to differentiate into alveolar epithelial type II cells (ATII cells). Total lung cells were first precultured, from which the Sca-1(+) CD45(-) CD31(-) population was purified using fluorescence activated cell sorting (FACS). By these methods, it would seem that the Sca-1(+) CD45(-) CD31(-) cells were LR-MSCs. Similar to bone marrow derived mesenchymal stem cells (BM-MSCs), these cells express Sca-1, CD29, CD90, CD44 and CD106, but not CD31 or CD45. They share the same gene expression file with the BM-MSCs and have a similar DNA content during long-term culturing. Furthermore, they could be serially passaged with all these properties being sustained. Above all, LR-MSCs could differentiate into ATII cells when co-cultured with ATII cells in a trans-well system. These findings demonstrated that the Sca-1(+) CD45(-) CD31(-) cells appear to be LR-MSCs that can differentiate into ATII cells. This approach may hold promise for their use in the treatment of lung disease.

Background and objective While commercial liquid culture techniques have emerged over 20 years ago, Ziehl–Neelsen (ZN) smear microscopy remains the primary method for diagnosis of tuberculosis (TB) in China because of cost considerations. The microscopic observation drug susceptibility (MODS) assay has been evaluated in different parts of the world to determine whether it can give comparable result to commercial liquid techniques. However, most reports detail evaluation of sputum specimens. This study evaluated the performance of MODS assay for detection of Mycobacterium tuberculosis in extrapulmonary specimens in a Chinese population. Methods A total of 173 samples, including pleural fluid (n = 112) and cerebrospinal fluid (CSF, n = 61) samples, were collected from patients suspected to have extrapulmonary TB and tested by ZN smear microscopy, Lowenstein–Jensen (LJ) culture and the MODS assay. Discordant results among MODS assay and the other two methods were resolved by 90-day follow-up evaluation for all suspected patients. Results The sensitivity of the MODS assay on pleural fluid and CSF samples was 20.5% and 37.5%, respectively, while the specificity of MODS assay on both types of samples approximated 100%. The median time to culture results for the MODS and LJ methods was 14 days, 32 days for pleural fluid, and 9 days and 31 days for CSF samples, respectively. Conclusions MODS assay is useful to diagnose extrapulmonary TB and may be an effective and affordable method in resource-limited countries.

We sought to explore the treatment effects and the repair mechanisms of bone marrow derived mesenchymal stem cells (MSCs) during HCl-induced acute lung injury (ALI). MSCs were delivered through the tail veins of rats 24 h after intranasal instillation of HCl. The results showed that MSCs did not ameliorate the histopathologic changes of ALI and pulmonary fibrosis. We found that the activated Wnt/β-catenin signaling may regulate the differentiation of MSCs and is associated with lung fibroblasts activation, pulmonary fibrosis and tissue repair process in ALI rats. Immunofluorescence and histology analysis indicated that activated canonical Wnt/β-catenin signaling induced most MSCs to differentiate into myofibroblasts or fibroblasts in vivo. However, inhibition of Wnt/β-catenin signaling by Dickkopf-1 (DKK1) promotes epithelial differentiation of MSCs induced by native alveolar epithelial cells which are beneficial to repair the injured lung epithelium. Inhibition of Wnt/β-catenin signaling after MSCs transplantation ameliorated pulmonary fibrosis and improved pulmonary function which attenuated the lung injury. In vitro study, activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblasts markers, which was attenuated by DKK1. Furthermore, Wnt3α activated Wnt/β-catenin signaling in lung fibroblasts to enhance the expression of collagen I, vimentin and α-smooth muscle actin, but DKK1 attenuated these proteins expression. These findings demonstrated that canonical Wnt/β-catenin signaling plays a key role in regulating differentiation of MSCs in vivo or in vitro and the pathogenesis of fibrotic diseases. Our study suggested that inhibition of abnormal activated Wnt/β-catenin signaling would promote MSCs epithelial differentiation to repair lung injury and reduce pulmonary fibrosis.

Background It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL). Materials and methods 52 older adults underwent neuroimaging and were administered the Mini Mental State Examination (MMSE), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and measures of attention/executive function. ASL and T1-weighted MRI were used to quantify total brain perfusion, total brain volume (TBV), and cortical thickness. Results Regression analyses showed reduced total brain perfusion was associated with poorer performance on the MMSE, RBANS total index, immediate and delayed memory composites, and Trail Making Test B. Reduced frontal lobe perfusion was associated with worse executive and memory function. A similar pattern emerged between temporal lobe perfusion and immediate memory. Regression analyses revealed that decreased total brain perfusion was associated with smaller TBV and mean cortical thickness. Regional effects of reduced total cerebral perfusion were found on temporal and parietal lobe volumes and frontal and temporal cortical thickness. Discussion Reduced cerebral perfusion is independently associated with poorer cognition, smaller TBV, and reduced cortical thickness in older adults. Conclusion Prospective studies are needed to clarify patterns of cognitive decline and brain atrophy associated with cerebral hypoperfusion.

Background The effect of hydrogen sulfide (H2 S) on visceral nociception is elusive. The conflicting evidence of its pro- and antinociceptive effects raises a series of questions with respect to the effect of H2 S on colonic afferent activity and the underlying mechanism, which was further elucidated in this study. Methods Colonic mesenteric afferent nerve spikes of normal male C57BL/6J mice, Cbs+/- mice, and Wistar rats were recorded in vitro. The abdominal withdrawal reflex (AWR) induced by colorectal distension (CRD) was evaluated in Cbs+/- mice and WT littermates. Key results Sodium hydrosulfide (NaHS) significantly decreased colonic afferent spontaneous discharge, chemosensitivity to bradykinin, mechanosensitivity to ramp distention, and intraluminal pressure in mice. Reducing the relaxant action of NaHS on intestinal smooth muscle using the nonspecific K+ channel blocker TEA (10 mmol/L) did not block the inhibition of NaHS on afferent nerve activity. The inhibitory effects of NaHS (0.5 mmol/L) on colonic afferent sensitivity were largely eliminated by the pretreatment with nonspecific NOS inhibitor NG -Methyl-l-arginine acetate salt (1 mmol/L), the specific nNOS inhibitor NPLA (1 μmol/L), or N-type Ca2+ channel blocker ω-conotoxin GVIA (1 μmol/L). Compared with WT mice, Cbs+/- mice showed increased mesenteric afferent sensitivity to colonic distention and enhanced hyperalgesic response to CRD. Intraperitoneal administration of NaHS (60 μmol/kg) alleviated the nociception response to CRD in both Cbs+/- and WT mice. Conclusions and inferences H2 S downregulates colonic mesenteric afferent sensitivity by a nNOS-dependent mechanism in mice. Our findings may demonstrate a new mechanism for the antinociceptive effect of H2 S in colon.

Gene delivery into MSCs (mesenchymal stem cells) has great promise for gene therapy, and lentiviral transduction has recently been shown to be a highly efficient method for gene delivery. Our previous studies indicated that the umbilical cord is a new source of MSCs; however, it was unclear whether the UC-MSCs (umbilical-cord-derived MSCs) would retain their characteristics after LV (lentivirus)-mediated gene transduction. The aim of the present study is to investigate the feasibility of transducing UC-MSCs with lentiviral vectors and to determine whether these transduced stem cells would retain their ability to differentiate into different lineages. Herein, we demonstrate that the percentage of EGFP (enhanced green fluorescent protein)-positive cells increased with the MOI (multiplicity of infection) and the number of transduction cycles. In addition, we observed that the transduced MSCs were capable of differentiating into adipogenic and osteogenic lineages expressing lineage-specific genes while maintaining high EGFP expression levels. In their undifferentiated state, the UC-MSCs continued to express both the transgene [EGFP or TNF (tumour necrosis factor)-Tumstatin] and stem cell markers such as Oct-4, Nanog, BMI-1 and nucleostemin. The presence of exogenous antitumour molecule-coding gene integration was verified by PCR and RT-PCR (reverse transcription-PCR) and also by immunohistochemistry. It was also shown that TNF-Tumstatin that can be secreted by MSCs has a cytotoxic effect on prostate cancer cells in vitro. These findings suggest that lentiviral transduction may be used to deliver therapeutic genes to human UC-MSCs and this may have a wide range of applications in gene therapy.

Controversies and risks continue to be reported about exogenous mesenchymal stem cell-based therapies. In contrast with employing exogenous stem cells, making use of lung resident mesenchymal stem cells (LR-MSCs) could be advantageous. Our study sought to isolate the LR-MSCs and explore their potential to differentiate into alveolar epithelial type II cells (ATII cells). Total lung cells were first precultured, from which the Sca-1(+) CD45(-) CD31(-) population was purified using fluorescence activated cell sorting (FACS). By these methods, it would seem that the Sca-1(+) CD45(-) CD31(-) cells were LR-MSCs. Similar to bone marrow derived mesenchymal stem cells (BM-MSCs), these cells express Sca-1, CD29, CD90, CD44 and CD106, but not CD31 or CD45. They share the same gene expression file with the BM-MSCs and have a similar DNA content during long-term culturing. Furthermore, they could be serially passaged with all these properties being sustained. Above all, LR-MSCs could differentiate into ATII cells when co-cultured with ATII cells in a trans-well system. These findings demonstrated that the Sca-1(+) CD45(-) CD31(-) cells appear to be LR-MSCs that can differentiate into ATII cells. This approach may hold promise for their use in the treatment of lung disease.