Αρχειοθήκη ιστολογίου

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Κυριακή 17 Δεκεμβρίου 2017

The alternatively spliced exon of COL5A1 is mutated in autosomal recessive classical Ehlers-Danlos syndrome

Thumbnail image of graphical abstract

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Nalmefene attenuates malignant potential in colorectal cancer cell via inhibition of opioid receptor

Abstract
Morphine is postulated a risk factor in promoting tumor growth and metastasis during the preoperative period, and high glycolysis of tumor cells is proved to accelerate tumor progression. In this study, we investigated whether nalmefene, an opioid receptor inhibitor, could inhibit CT26 colon cancer cell growth through influencing cell glycolysis. CCK8 and transwell migration assays showed that nalmefene inhibited CT26 cells viability and migration in a concentration-dependent manner. Extracellular acidification rate and oxygen consumption rate showed that nalmefene inhibited glycolysis of CT26 cells. Moreover, western blot analysis and quantitative real-time PCR revealed that nalmefene decreased the expressions of enzymes related to glycolysis. Flow cytometry results revealed that intracellular calcium (Ca2+) level was changed by nalmefene, western blot analysis showed that nalmefene decreased calmodulin expression and calcium/calmodulin dependent protein kinases II (CaMK II) phosphorylation, thus inhibiting the serine/threonine kinase (AKT)-glycogen synthase kinase-3β (GSK-3β) pathway. Furthermore, the effects of KN93, an inhibitor of CaMK II, were similar to the effects of nalmefene, and the anti-tumor effect of nalmefene could be counteracted by morphine. In conclusion, the anti-tumor effect of nalmefene may be achieved by inhibiting opioid receptor and down-regulating calmodulin expression and CaMK II phosphorylation, thus inhibiting AKT-GSK-3β pathway and the glycolysis of CT26 cells.

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A special issue on TGF-β signaling: regulation, crosstalk, and biology



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Dai-Huang-Fu-Zi-Tang Alleviates Intestinal Injury Associated with Severe Acute Pancreatitis by Regulating Mitochondrial Permeability Transition Pore of Intestinal Mucosa Epithelial Cells

Objective. The aim of the present study was to examine whether Dai-Huang-Fu-Zi-Tang (DHFZT) could regulate mitochondrial permeability transition pore (MPTP) of intestinal mucosa epithelial cells for alleviating intestinal injury associated with severe acute pancreatitis (SAP). Methods. A total of 72 Sprague-Dawley rats were randomly divided into 3 groups (sham group, SAP group, and DHFZT group, per group). The rats in each group were divided into 4 subgroups ( per subgroup) accordingly at 1, 3, 6, and 12 h after the operation. The contents of serum amylase, D-lactic acid, diamine oxidase activity, and degree of MPTP were measured by dry chemical method and enzyme-linked immunosorbent assay. The change of mitochondria of intestinal epithelial cells was observed by transmission electron microscopy. Results. The present study showed that DHFZT inhibited the openness of MPTP at 3, 6, and 12 h after the operation. Meanwhile, it reduced the contents of serum D-lactic acid and activity of diamine oxidase activity and also drastically relieved histopathological manifestations and epithelial cells injury of intestine. Conclusion. DHFZT alleviates intestinal injury associated SAP via reducing the openness of MPTP. In addition, DHFZT could also decrease the content of serum diamine oxidase activity and D-lactic acid after SAP.

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Surface Electromyography Analysis of the Lower Extremities of Subjects Participating in Baduanjin Exercises

Purpose. The purpose of this study was to assess the effects of practicing Baduanjin exercises on the lower extremities of subjects using electromyography analysis. Subjects. 110 healthy adults were randomly assigned as subjects to two groups: SG group who received sixteen weeks of Baduanjin training and CG group who received no training. Methods. The methods used in this study included the use of a sixteen-channel sEMG system to record and measure activity changes in vastus medialis and vastus lateralis. Results. After 16 weeks of Baduanjin training, the results of this study showed that the SG group had significant increases in RMS (root mean square) (in vastus lateralis, > 0.05; in vastus medialis, 0.05; in vastus medialis, 0.05; in vastus medialis,

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Correction to: Dissociating the capture of attention from saccade activation by subliminal abrupt onsets

Abstract

Attentional capture and effects on saccade metrics by subliminal abrupt onset cues have been studied with peripheral cues at one out of several (two to four) display locations, swiftly followed by additional onsets at the other display locations. The lead time of the cue was too short to be seen. Here, we were interested in whether such subliminal onset cues influenced saccades primarily by way of attention or by way of direct saccade activation. In separate blocks, participants made speeded pro-saccades towards a black target or anti-saccades away from the target. Prior to the targets, an abrupt onset cue was presented either at the same side as the target (valid condition) or at the opposite side (invalid condition). If cues influenced performance by way of attentional capture, we expected facilitation of target processing in valid compared to invalid conditions (cueing effect) in the pro- as well as in the anti-saccade task. If the cues activated saccades in their direction, we expected the cueing effect to drop in the anti-saccade task compared to the pro-saccade task because in the anti-saccade task the invalid cue would activate the finally required response, whereas the valid cue would activate the alternative response, leading to interference. Results were in line with the former of these possibilities suggesting that subliminal abrupt onsets influenced saccades by way of attention with no or little direct activation of saccades.



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The effect of proprioceptive acuity variability on motor adaptation in older adults

Abstract

Motor adaptation requires efficient integration of sensory information with predicted sensory consequences of one's own action. However, the effect of reduced sensory acuity on motor adaptation in humans remains to be further investigated. Here, we examined the variability of proprioceptive acuity during an arm-position matching task and the pattern of visuomotor adaptation in older and young adults, and determined the relationship between the two variables. The older adults, a known example of impaired proprioceptive acuity, exhibited greater trial-to-trial variability during the arm-position matching task as compared with the young adults. Furthermore, the older adults showed a slower rate of adaptation to a 30° visuomotor rotation during targeted reaching movements, as well as larger movement errors in the later phase of adaptation, than the young adults. Our correlation analyses indicated a negative association between the variability in proprioceptive acuity and the rate of visuomotor adaptation in the older adults; and no association was observed in the young adults. These findings point to a possibility that an increase in the variability of proprioceptive acuity due to aging may weaken the integration of predicted and actual sensory feedback, which in turn may result in poor visuomotor adaptation in older adults.



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The Canadian Medical Association should support a medical access stream for cannabis [Letters]



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Medical schools addressing student anxiety, burnout and depression [News]



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Probiotic capsules and xylitol chewing gum to manage symptoms of pharyngitis: a randomized controlled factorial trial [Research]

BACKGROUND:

Reducing the use of antibiotics for upper respiratory tract infections is needed to limit the global threat of antibiotic resistance. We estimated the effectiveness of probiotics and xylitol for the management of pharyngitis.

METHODS:

In this parallel-group factorial randomized controlled trial, participants in primary care (aged 3 years or older) with pharyngitis underwent randomization by nurses who provided sequential intervention packs. Pack contents for 3 kinds of material and advice were previously determined by computer-generated random numbers: no chewing gum, xylitol-based chewing gum (15% xylitol; 5 pieces daily) and sorbitol gum (5 pieces daily). Half of each group were also randomly assigned to receive either probiotic capsules (containing 24 x 109 colony-forming units of lactobacilli and bifidobacteria) or placebo. The primary outcome was mean self-reported severity of sore throat and difficulty swallowing (scale 0–6) in the first 3 days. We used multiple imputation to avoid the assumption that data were missing completely at random.

RESULTS:

A total of 1009 individuals consented, 934 completed the baseline assessment, and 689 provided complete data for the primary outcome. Probiotics were not effective in reducing the severity of symptoms: mean severity scores 2.75 with no probiotic and 2.78 with probiotic (adjusted difference –0.001, 95% confidence interval [CI] –0.24 to 0.24). Chewing gum was also ineffective: mean severity scores 2.73 without gum, 2.72 with sorbitol gum (adjusted difference 0.07, 95% CI –0.23 to 0.37) and 2.73 with xylitol gum (adjusted difference 0.01, 95% CI –0.29 to 0.30). None of the secondary outcomes differed significantly between groups, and no harms were reported.

INTERPRETATION:

Neither probiotics nor advice to chew xylitol-based chewing gum was effective for managing pharyngitis. Trial registration: ISRCTN, no. ISRCTN51472596



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Viral misinformation threatens public health [News]



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Newborn screening for severe combined immunodeficiency: a primer for clinicians [Review]



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We need to mandate drug cost transparency on electronic medical records [Commentary]



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Risks of novel therapeutics: gonococcemia in an immune-suppressed patient receiving eculizumab [Practice]



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Updating our language around substance use disorders [Letters]



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Calcific tendinitis of the gluteus maximus of a 53-year-old woman [Practice]



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An outpatient "evolution" in orthopedic surgery [News]



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Medical sensations: experience doctoring [Humanities]



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Beyond health care: the other determinants of health [Coda]



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Most impactful factors on the health-related quality of life of a geriatric population with cancer

BACKGROUND

As the population of older adults with cancer continues to grow, the most important factors contributing to their health-related quality of life (HRQOL) remain unclear.

METHODS

A total of 1457 older adults (aged ≥65 years) with cancer participated in a telephone survey. Outcomes were measured using the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the 12-Item Short Form Survey (SF-12) from the Medical Outcomes Study (version 2). Statistical techniques used to identify factors in 4 domains (physical, psychological, social, and spiritual) most strongly associated with HRQOL included linear models, recursive partitioning, and random forests. Models were developed in a training data set (920 respondents) and performance was assessed in a validation data set (537 respondents).

RESULTS

Respondents were a median of 19 months from diagnosis, and 28.1% were receiving active treatment. The most relevant factors found to be associated with PCS were symptom severity, comorbidity scores, leisure-time physical activity, and having physical support needs. The most relevant factors for MCS were having emotional support needs, symptom severity score, and the number of financial hardship events. Results were consistent across modeling techniques. Symptoms found to be strongly associated with PCS included fatigue (adjusted proportion of summary score's variance [R2] = 0.34), pain (adjusted R2 = 0.32), disturbed sleep (adjusted R2 = 0.16), and drowsiness (adjusted R2 = 0.16). Symptoms found to be strongly associated with MCS included fatigue (adjusted R2 = 0.23), problems remembering things (adjusted R2 = 0.17), disturbed sleep (adjusted R2 = 0.16), and lack of appetite (adjusted R2 = 0.16).

CONCLUSIONS

The findings of the current study support the importance of addressing persistent symptoms, managing comorbidities, promoting leisure-time physical activity, and addressing financial challenges. A long-term comprehensive approach is needed to ensure the well-being of older adults with cancer. Cancer 2017. © 2017 American Cancer Society.



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Injectable simvastatin gel for minimally invasive periosteal distraction: In vitro and in vivo studies in rat

Abstract

Objectives

To evaluate whether the subperiosteal injection of simvastatin (SIM) with a novel in situ gel-forming system, SrHA/Alg (strontium hydroxyapatite/alginate), can stimulate vertical bone augmentation in a rat calvarial model.

Material and methods

The SrHA/Alg solution was synthesized and combined with different doses of SIM (0.01, 0.02, 0.1, and 0.2 mg) to form the following groups: (1) SrHA/Alg only, (2) SrHA/Alg/0.01, (3) SrHA/Alg/0.02, (4) SrHA/Alg/0.1, and (5) SrHA/Alg/0.2. The SIM release pattern was analyzed, and rat primary periosteum-derived cell (PDC) responses were investigated. Twenty male Wistar rats were enrolled in the calvarial subperiosteal injection experiment with each animal receiving a 200-μl single subperiosteal injection of SrHA/Alg with different amounts of SIM (0, 0.01, 0.02, and 0.1 mg) incorporated (n = 5). The 0.2 mg dose group was not tested in vivo due to the severe toxicity found in vitro. The new bone formation was assessed histologically and radiologically at 8 weeks.

Results

The slow release of SIM was confirmed, and PDC viability decreased in the SrHA/Alg/0.2 group. Alkaline phosphatase positive areas and mineralization areas were significantly greater in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups (p < .05). The mRNA expression level of Runx2 significantly increased in the SrHA/Alg/SIM-0.02 group by day 7 (p < .05) and significantly higher levels of VEGF were found in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups at different time points (p < .05). In vivo, no prominent clinical sign of inflammation was observed, and the most significant bone gain was shown in the SrHA/Alg/0.02 group (p < .05). The osteoclast formation within the newly formed bone area was reduced in the SrHA/Alg/0.1 group (p < .05).

Conclusions

When combined with SrHA/Alg system, the 0.02 mg SIM seemed to be the optimal dose to stimulate subperiosteal bone formation without inducing inflammation. This combination may hold potential therapeutic benefits for clinical bone augmentation in a minimally invasive manner.



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Acid-induced experimental knee pain and hyperalgesia in healthy humans

Abstract

Inflammation and the related acidity in peri-articular structures may be involved in pain generation and hyperalgesia in knee osteoarthritis. This study investigated pain and associated hyperalgesia provoked by infusion of acidic saline into the infrapatellar fat pad. Twenty-eight subjects participated in two sessions in which acidic saline (AS, pH 5) or neutral saline (NS, pH 7.4) were infused into the infrapatellar fat pad for 15 min. Pain intensity, pain area, mechanical and thermal sensitivity, and maximal voluntary knee extension force were recorded. Repeated infusions were performed in 14 subjects. Infusion of AS caused significantly higher pain intensity, larger pain areas, induced hyperalgesia around the infused knee, and reduced extension force. No significant pain facilitation or spreading of hyperalgesia was found after repeated infusions as compared with single infusions. Acidic saline infused into the infrapatellar fat pad provoked pain and localized mechanical hyperalgesia. Thus, this acid-induced pain model may mimic the early-stage responses to tissue injury of knee osteoarthritis.



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Chronic Exposure to Water of Lake Qaroun Induced Metal-Related Testicular Damage and Endocrine Disruption in Male Fish

Abstract

The uncontrolled releasing of hazardous wastes into Lake Qaroun was adversely impacting the aquatic environment and its biota. Therefore, this approach was designed to investigate the impact of these discharges on the reproductive and testicular function of Oreochromis niloticus. Several biomarkers were applied on the testicular tissues as metal bioaccumulation levels, histological examination with recording the ovotestis appearance and antioxidant status after 45 days of exposure to 0, 10, 20, & 30% of Lake Qaroun water (LQW). The bioaccumulated Cu, Mn, Fe, Pb, and Cd were unequally distributed in the testes but all these metals showed a significant concentration-dependent elevation among the studied groups. The exposure to LQW significantly increased the histological alterations in the testicular tissues as vacuolar degeneration, loss of tubular organization, and degeneration of Leydig cell. Based on the frequent appearance of histopathological abnormalities and ovotestis recording, the most deformed testicular tissues were observed in the 30% LQW-exposed groups. The ovotestis severity index (OSI) was significantly raised in LQW-exposed groups compared to the control group. The activities of superoxide dismutase, catalase as well as glutathione-reduced levels were significantly (p < 0.05) decreased in testes after chronic exposure to LQW. On the other pole, the activities of glutathione peroxidase enzyme and malondialdehyde formation were sharply increased. In view of the above, the exposure to LQW induced metal-related oxidative damage to the testicular tissues and impaired the male reproductive health. This study showed strong correlations between the anthropogenic activities around Lake Qaroun and the reproductive dysfunction in fish.



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Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study

Objectives

To evaluate the efficacy, safety, and tolerability of perampanel, a selective, non-competitive, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as an adjunctive treatment for patients with refractory partial-onset seizures (POS) from Asia-Pacific.

Materials & methods

This multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT01618695) involved patients aged ≥12 years with refractory POS (receiving 1-3 antiepileptic drugs). Patients were randomized (1:1:1:1) to receive once-daily placebo or perampanel 4, 8, or 12 mg over a 6-week titration and 13-week maintenance double-blind period. Enzyme-inducing antiepileptic drugs were equally stratified between groups. The primary efficacy endpoint was percent change in POS frequency per 28 days (double-blind phase vs baseline). Other efficacy endpoints included ≥50% responder rate and seizure freedom. Treatment-emergent adverse events (TEAEs) were also monitored.

Results

Of 710 randomized patients, seizure frequency data were available for 704 patients. Median percent changes in POS frequency per 28 days indicated dose-proportional reductions in seizure frequency: −10.8% with placebo and −17.3% (= .2330), −29.0% (= .0003), and −38.0% (< .0001) with perampanel 4, 8, and 12 mg, respectively. In total, 108 (15.3%) patients discontinued treatment; 44 (6.2%) due to TEAEs. TEAEs occurring in ≥5% of patients, and reported at least twice as frequently with perampanel vs placebo, included dizziness and irritability.

Conclusions

Adjunctive perampanel (8 and 12 mg/d) significantly improved seizure control in patients with refractory POS. Safety and tolerability were acceptable at daily doses of perampanel 4-12 mg.



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Early tapering of immunosuppressive agents after HLA-matched donor transplantation can improve the survival of patients with advanced acute myeloid leukemia

Abstract

Disease recurrence is the most important obstacle to achieve long-term survival for patients with advanced acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to reduce the relapse risk and improve the survival, the strategy of early tapering of immunosuppressive agents was prospectively evaluated. Thirty-one patients with advanced AML received early tapering of immunosuppressive drugs, while 32 patients with AML in complete remission (CR) were given the routine tapering of immunosuppressive agents after HLA-matched donor transplantation. All advanced AML patients achieved CR after allo-HSCT. At 24 months after transplantation, relapse incidences were 22% in advanced group and 16% in CR group (P = 0.553); disease-free survival (DFS) and overall survival (OS) were 57.7 and 57.8% in advanced group, while in CR group were 66.6% (P = 0.388) and 66.2% (P = 0.423); immunosuppressive agent-free DFS (IDFS) were similar between two groups (P = 0.407). Acute graft-versus-host disease (aGvHD) incidences were similar between two groups (P = 0.311). Chronic GvHD (cGvHD) incidence was much higher in advanced group than in CR group (70.4 vs 38.7%, P = 0.02), but severe cGvHD had no difference. In multivariate analysis, cGvHD was an independent prognostic factor for lower risk of relapse and better DFS and OS; early tapering of immunosuppressive agents was an independent prognostic factor for cGvHD. The study suggested that advanced AML patients could be directly treated with allo-HSCT and its survival could be improved through the strategy of early tapering of immunosuppressive agents without significant adverse effects (Clinicaltrials.org NCT03150134).



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Reinterpreting recent thymic emigrant function: defective or adaptive?

Cody A Cunningham | Eric Y Helm | Pamela J Fink

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Cucurbitacin-B attenuates CCl4-induced hepatic fibrosis in mice through inhibition of STAT-3

Abstract

Liver fibrosis is a major health concern worldwide. Inhibitors of Signal Transducer and Activator of Transcription 3 (STAT3) have been reported to attenuate experimental liver fibrosis. Therefore, the aim of current study was to investigate the potential ameliorative effect of cucurbitacin-B (Cucu-B) against CCl4-induced liver fibrosis in mice. Treatment with Cucu-B (5 mg/kg) preserved hepatocellular membrane integrity and amended the metabolic function as indicated by preventing the rise of serum liver function markers. This was confirmed histologically. CCl4-induced oxidative stress was improved by Cucu-B treatment (1 & 5 mg/kg). Further, Cucu-B treatment ameliorated the fibrotic state as evidenced by inhibiting the rise of hydroxyproline liver content and mitigating the overexpressions of collagen-1α, α-smooth muscle actin (α-SMA) and transforming growth factor beta (TGF-β) as well as the downexpression of matrix metalloproteinase-2 (MMP-2) mRNA. Importantly, STAT3 activity was inhibited by Cucu-B as confirmed by decreased phosphorylation of STAT3 without changing total STAT3 expression. This was substantiated by the reduced Bcl-2 together with increased Bax mRNA expressions with subsequent elevation of Bax/Bcl-2 ratio. In conclusion, Cucu-B hampers CCl4-induced liver fibrosis in mice. This can be attributed – at least partly – to inhibition of oxidative stress, inflammation and STAT3 signaling.

This article is protected by copyright. All rights reserved.

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Cucurbitacin-B protected against CCl4-induced liver injury and fibrosis in mice. This was confirmed histologically and biochemically. Fibrosis-related markers were also improved by cucurbitacin-B treatment. These actions can be attributed, at least partly, to inhibition of oxidative stress, inflammation and STAT3 signaling.



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ALLO: a tool to discriminate and prioritize allosteric pockets

Abstract

Allosteric proteins make up a substantial proportion of human drug targets. Thus, rational design of small molecule binders that target these proteins requires the identification of putative allosteric pockets and an understanding of their potential activity. Here, we characterized allosteric pockets using a set of physicochemical descriptors and compared them to pockets that are found on the surface of a protein. Further, we trained predictive models capable of discriminating allosteric pockets from orthosteric pockets and models capable of prioritizing allosteric pockets in a set of pockets found on a given protein. Such models might be useful for identifying novel allosteric sites and in turn, potentially new allosteric drug targets. Datasets along with a Python program encapsulating the predictive models are available at github. com/fibonaccirabbits/allo.

This article is protected by copyright. All rights reserved.

Thumbnail image of graphical abstract

In this work, we characterized allosteric pockets using a set of physicochemical descriptors and compared them to pockets that are found on the surface of a protein. Further, we trained predictive models capable of discriminating allosteric pockets from orthosteric pockets and models capable of prioritizing allosteric pockets in a set of pockets found on a given protein.



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Tripterygium wilfordii Glycosides Upregulate the New Anti-Inflammatory Cytokine IL-37 through ERK1/2 and p38 MAPK Signal Pathways

As a Chinese traditional patent medicine, Tripterygium wilfordii glycosides (TWG) have been approved by the China State Food and Drug Administration (Z32021007) for autoimmune and inflammatory diseases. Application of TWG leads to significant decrease of the inflammatory cytokines, such as IL-6, IL-1β, and TNF-α. However, little is known whether TWG could regulate the anti-inflammatory cytokines and what the mechanism is. Here, we found that TWG could induce the upregulation of IL-37 which is a new anti-inflammatory cytokine. Furthermore, the inhibitors of ERK1/2 and/or p38 MAPK pathways suppressed IL-37 expression induced by TWG, indicating that the two pathways took part in this process. In conclusion, TWG could upregulate the anti-inflammatory cytokine IL-37 and ERK1/2 and p38 MAPK signal pathways were involved in the upregulation of IL-37 induced by TWG. The results showed that TWG had a potent activity on promoting the expression of IL-37, a new anti-inflammatory cytokine, which help further understanding the anti-inflammatory mechanism for the clinical application of TWG in therapy of diseases.

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Crystalloid Coload Reduced the Incidence of Hypotension in Spinal Anesthesia for Cesarean Delivery, When Compared to Crystalloid Preload: A Meta-Analysis

Objective. To determine whether crystalloid infusion just after intrathecal injection (coload) would be better than infusion before anesthesia (preload) for hypotension prophylaxis in spinal anesthesia for cesarean delivery. Methods. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and other databases for randomized controlled trials comparing coload of crystalloid with preload in parturients receiving spinal anesthesia for cesarean delivery. Primary outcome was intraoperative incidence of hypotension. Other outcomes were intraoperative need for vasopressors, hemodynamic variables, neonatal outcomes (umbilical artery pH and Apgar scores), and the incidence of maternal nausea and vomiting. We used RevMan 5.2 and STATA 12.0 for the data analyses. Results. Ten studies with 824 cases were included. The incidence of hypotension was significantly higher in the preload group compared with the coload group (57.8% versus 47.1%, odds ratio [OR] = 1.62, 95% confidence interval [CI] = 1.11–2.37, and ). More patients needed intraoperative vasopressors (OR = 1.71, 95% CI = 1.07–2.04, and ) when receiving crystalloid preload. In addition, the incidence of nausea and vomiting was higher in the preload group (OR = 3.40, 95% CI = 1.88–6.16, and ). There were no differences in neonatal outcomes between the groups. Conclusions. For parturients receiving crystalloid loading in spinal anesthesia for cesarean delivery, coload strategy is superior to preload for the prevention of maternal hypotension.

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Methodology for Sputum Induction and Laboratory Processing

Here we describe the technique of sputum induction. This protocol also explains the sputum processing to perform a differential cell count and to collect sputum supernatant and cells for further analysis.

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In Vitro Growth of Mouse Preantral Follicles Under Simulated Microgravity

55641fig1.jpg

A highly promising technique to generate tissue constructs without using matrix is to culture cells in a simulated microgravity condition. Using a rotary culture system, we examined ovarian follicle growth and oocyte maturation in terms of follicle survival, morphology, growth, and oocyte function under the simulated microgravity condition.

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Optimization, Purification, and Starch Stain Wash Application of Two New α-Amylases Extracted from Leaves and Stems of Pergularia tomentosa

A continuous research is attempted to fulfil the highest industrial demands of natural amylases presenting special properties. New α-amylases extracted from stems and leaves of Pergularia tomentosa, which is widespread and growing spontaneously in Tunisia, were studied by the means of their activities optimization and purification. Some similarities were recorded for the two identified enzymes: (i) the highest amylase activity showed a promoted thermal stability at 50°C; (ii) the starch substrate at 1% enhanced the enzyme activity; (iii) the two α-amylases seem to be calcium-independent; (iv) Zn2+, Cu2+, and Ag2+ were considered as important inhibitors of the enzyme activity. Following the increased gradient of elution on Mono Q-Sepharose column, an increase in the specific activity of 11.82-fold and 10.92-fold was recorded, respectively, for leaves and stems with the presence of different peaks on the purification profiles. Pergularia amylases activities were stable and compatible with the tested commercial detergents. The combination of plant amylase and detergent allowed us to enhance the wash performance with an increase of 35.24 and 42.56%, respectively, for stems and leaves amylases. Characterized amylases were reported to have a promoted potential for their implication notably in detergent industry as well as biotechnological sector.

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Quantitative Analysis and Biological Efficacies regarding the Neuroprotective and Antineuroinflammatory Actions of the Herbal Formula Jodeungsan in HT22 Hippocampal Cells and BV-2 Microglia

Jodeungsan (JDS) is a traditional herbal formula that comprises seven medicinal herbs and is broadly utilized to treat hypertension, dementia, and headache. However, the effects of JDS and its herbal components on neurodegenerative diseases have not been reported. We examined the inhibitory effects of JDS and its seven components on neuronal cell death and inflammation using HT22 hippocampal cells and BV-2 microglia, respectively. Among its seven herbal components, Uncaria sinensis (US), Chrysanthemum morifolium (CM), Zingiber officinale (ZO), Pinellia ternata (PT), Citrus unshiu (CU), and Poria cocos (PC) exhibited significant neuroprotective effects in HT22 cells. In BV-2 cells, JDS significantly suppressed the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), indicating the antineuroinflammatory activity of JDS. In addition, the herbal extracts from ZO, Panax ginseng (PG), PT, CU, and PC exhibited inhibitory effects on the inflammatory response in microglia. These data imply that the JDS effect on neurodegeneration occurs via coordination among its seven components. To establish a quality control for JDS, a simultaneous analysis using five standard compounds identified hesperidin ( mg/g) as the most abundant phytochemical of JDS. Further investigation of the combinatorial activities of two or more standard compounds will be necessary to verify their antineurodegenerative regulatory mechanisms.

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Effect of Airborne Particle Abrasion on Microtensile Bond Strength of Total-Etch Adhesives to Human Dentin

Aim of this study was to investigate a specific airborne particle abrasion pretreatment on dentin and its effects on microtensile bond strengths of four commercial total-etch adhesives. Midcoronal occlusal dentin of extracted human molars was used. Teeth were randomly assigned to 4 groups according to the adhesive system used: OptiBond FL (FL), OptiBond Solo Plus (SO), Prime & Bond (PB), and Riva Bond LC (RB). Specimens from each group were further divided into two subgroups: control specimens were treated with adhesive procedures; abraded specimens were pretreated with airborne particle abrasion using 50 μm Al2O3 before adhesion. After bonding procedures, composite crowns were incrementally built up. Specimens were sectioned perpendicular to adhesive interface to produce multiple beams, which were tested under tension until failure. Data were statistically analysed. Failure mode analysis was performed. Overall comparison showed significant increase in bond strength () between abraded and no-abraded specimens, independently of brand. Intrabrand comparison showed statistical increase when abraded specimens were tested compared to no-abraded ones, with the exception of PB that did not show such difference. Distribution of failure mode was relatively uniform among all subgroups. Surface treatment by airborne particle abrasion with Al2O3 particles can increase the bond strength of total-etch adhesives.

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Foveal Avascular Zone in Normal Tension Glaucoma Measured by Optical Coherence Tomography Angiography

Aim. To measure diameter of foveal avascular zone (FAZ), FAZ area, and vessel density using Optical Coherence Tomography Angiography (OCT-A) in patients with normal tension glaucoma (NTG) and to establish the possible role of OCT-A in diagnosis and follow-up of patients with NTG. Methods. Twenty-one eyes of 21 patients with NTG and 30 eyes of 30 healthy subjects underwent complete ophthalmic examination as well as OCT-A on ZEISS AngioPlex. macula scans were used to measure vertical, horizontal, and maximum diameter of FAZ by two graders. Mean values and interobserver variability were analyzed. Image J was used for analysis of FAZ area and vessel density. Results. Mean vertical diameter (, ), horizontal diameter (, ), maximum diameter (, ), and FAZ area (, ) were statistically significantly enlarged in the NTG group compared to those in the control group. Vessel density (, ) was statistically significantly decreased in the NTG group compared to that in the control group. Conclusion. OCT-A could have an important role in the future in diagnosis of patients with NTG. In patients with NTG, there is larger FAZ area, while the vessel density is reduced in comparison to the control group.

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Regulating the Balance of Th17/Treg via Electroacupuncture and Moxibustion: An Ulcerative Colitis Mice Model Based Study

Aim. To investigate the relationship between the effects of electroacupuncture/moxibustion and the balance of Th17/Treg in treating ulcerative colitis (UC) and to preliminary compare the effects of the above two methods. Methods. DSS-induced UC mice were treated by electroacupuncture and moxibustion. Disease activity index (DAI) was scored; intestinal pathological structure and ultrastructure were observed. The levels of IL-2, IL-6, IL-10, IL-17A, IL-17F, and TGF-β in plasma were measured by ELISA. The percentages of Treg and Th17 in spleen lymphocytes were analyzed by flow cytometry. Also, the expressions of TLR2, TLR4, RORγt, and FOXP3 in the distal colon were detected by immunohistochemistry or western blot. Results. Both electroacupuncture and moxibustion can relieve UC. These effects are further supported by ELISA results. In addition, the ratio of Treg and Th17 in spleen lymphocytes and the expression of TLR2 and TLR4 are significantly improved. Also, the expression of RORγt and FOXP3 in distal colon were improved. Besides, the effect of moxibustion is better than that of electroacupuncture on TLR2, TLR4, and FOXP3 expression (). Conclusion. Both electroacupuncture and moxibustion may ameliorate UC by regulating the balance of Th17/Treg. Whether moxibustion has better efficacy than electroacupuncture needs further study.

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Curcuma longa Is Able to Induce Apoptotic Cell Death of Pterygium-Derived Human Keratinocytes

Pterygium is a relatively common eye disease that can display an aggressive clinical behaviour. To evaluate the in vitro effects of Curcuma longa on human pterygium-derived keratinocytes, specimens of pterygium from 20 patients undergoing pterygium surgical excision were collected. Pterygium explants were put into culture and derived keratinocytes were treated with an alcoholic extract of 1.3% Curcuma longa in 0.001% Benzalkonium Chloride for 3, 6, and 24 h. Cultured cells were examined for CAM5.2 (anti-cytokeratin antibody) and CD140 (anti-fibroblast transmembrane glycoprotein antibody) expression between 3th and 16th passage to assess cell homogeneity. TUNEL technique and Annexin-V/PI staining in flow cytometry were used to detect keratinocyte apoptosis. We showed that Curcuma longa exerts a proapoptotic effect on pterygium-derived keratinocytes already after 3 h treatment. Moreover, after 24 h treatment, Curcuma longa induces a significant increase in TUNEL as well as Annexin-V/PI positive cells in comparison to untreated samples. Our study confirms previous observations highlighting the expression, in pterygium keratinocytes, of nuclear VEGF and gives evidence for the first time to the expression of nuclear and cytoplasmic VEGF-R1. All in all, these findings suggest that Curcuma longa could have some therapeutic potential in the treatment and prevention of human pterygium.

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Chiari 1 Malformation in a Child with Febrile Seizures, Parasomnias, and Sleep Apnea Syndrome

Introduction. The type I is the most common Chiari malformation in children. In this condition, the lower part of the cerebellum, but not the brain stem, extends into the foramen magnum at the base of the skull leading to disturbances in cerebrospinal fluid circulation and to direct compression of nervous tissue. Case report. We describe a 4-year-old Caucasian female child with febrile seizures, headache, parasomnias, and a delay of speech. The child underwent a magnetic resonance imaging to investigate these neurological signs, disclosing a Chiari malformation type 1. The polysomnography showed a mild-moderate sleep-disordered breathing, increased number of central sleep apneas, and generalized spike waves at sleep onset. Conclusions. Seizures have been seldom described in CM1 patients. The main reasons for performing MRI in this case were frequent seizures, a delay of speech, and headache, leading to an unexpected diagnosis of CM1. Polysomnography detected a discrete SDB.

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Epidemiology of Respiratory Pathogens among Elderly Nursing Home Residents with Acute Respiratory Infections in Corsica, France, 2013–2017

Background. The current study aims to describe the demographical and clinical characteristics of elderly nursing home (NH) residents with acute respiratory infections (ARIs) during four winter seasons (2013/2014–2016/2017), as well as the microbiological etiology of these infections. Methods. Seventeen NHs with at least one ARI resident in Corsica, France, were included. An ARI resident was defined as a resident developing a sudden onset of any constitutional symptoms in addition to any respiratory signs. Nasopharyngeal swabs from ARI residents were screened for the presence of 21 respiratory agents, including seasonal influenza viruses. Results. Of the 107 ARI residents enrolled from NHs, 61 (57%) were positive for at least one of the 21 respiratory pathogens. Forty-one (38.3%) of the 107 ARI residents had influenza: 38 (92%) were positive for influenza A (100% A(H3N2)) and three (8%) for influenza B/Victoria. Axillary fever (≥38°C) was significantly more common among patients infected with influenza A(H3N2). Conclusion. The circulation of seasonal respiratory viruses other than influenza A(H3N2) seems to be sporadic among elderly NH residents. Investigating the circulation of respiratory viruses in nonwinter seasons seems to be important in order to understand better the dynamic of their year-round circulation in NHs.

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miRNAs in Prediction of Prognosis in Clear Cell Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of urinary malignancy. Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, accounting for 70–80% of RCC. In recent years, miRNAs have been found to be closely associated with the outcome of the patients with ccRCC. In this review, we summarize recent advances in research exploring the role of miRNAs in predicting prognosis in patients with ccRCC.

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A Fatty Acids Mixture Reduces Anxiety-Like Behaviors in Infant Rats Mediated by GABAA Receptors

Fatty acids (C6–C18) found in human amniotic fluid, colostrum, and maternal milk reduce behavioral indicators of experimental anxiety in adult Wistar rats. Unknown, however, is whether the anxiolytic-like effects of fatty acids provide a natural mechanism against anxiety in young offspring. The present study assessed the anxiolytic-like effect of a mixture of lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, elaidic acid, and linoleic acid in Wistar rats on postnatal day 28. Infant rats were subjected to the elevated plus maze, defensive burying test, and locomotor activity test. Diazepam was used as a reference anxiolytic drug. A group that was pretreated with picrotoxin was used to explore the participation of -aminobutyric acid-A (GABAA) receptors in the anxiolytic-like effects. Similar to diazepam, the fatty acid mixture significantly increased the frequency of entries into and time spent on the open arms of the elevated plus maze and decreased burying behavior in the defensive burying test, without producing significant changes in spontaneous locomotor activity. These anxiolytic-like effects were blocked by picrotoxin. Results suggest that these fatty acids that are contained in maternal fluid may reduce anxiety-like behavior by modulating GABAergic neurotransmission in infant 28-day-old rats.

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Emergence of Lassa Fever Disease in Northern Togo: Report of Two Cases in Oti District in 2016

Background. Lassa fever belongs to the group of potentially fatal hemorrhagic fevers, never reported in Togo. The aim of this paper is to report the first two cases of Lassa fever infection in Togo. Case Presentation. The two first Lassa fever cases occurred in two expatriate's health professionals working in Togo for more than two years. The symptoms appeared among two health professionals of a clinic located in Oti district in the north of the country. The absence of clinical improvement after antimalarial treatment and the worsening of clinical symptoms led to the medical evacuation. The delayed diagnosis of the first case led to a fatal outcome. The second case recovered under ribavirin treatment. Conclusion. The emergence of this hemorrhagic fever confirms the existence of Lassa fever virus in Togo. After a period of intensive Ebola virus transmission from 2013 to 2015, this is an additional call for the establishment and enhancement of infection prevention and control measures in the health care setting in West Africa.

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Corpuls CPR Generates Higher Mean Arterial Pressure Than LUCAS II in a Pig Model of Cardiac Arrest

According to the European Resuscitation Council guidelines, the use of mechanical chest compression devices is a reasonable alternative in situations where manual chest compression is impractical or compromises provider safety. The aim of this study is to compare the performance of a recently developed chest compression device (Corpuls CPR) with an established system (LUCAS II) in a pig model. Methods. Pigs ( = 5/group) in provoked ventricular fibrillation were left untreated for 5 minutes, after which 15 min of cardiopulmonary resuscitation was performed with chest compressions. After 15 min, defibrillation was performed every 2 min if necessary, and up to 3 doses of adrenaline were given. If there was no return of spontaneous circulation after 25 min, the experiment was terminated. Coronary perfusion pressure, carotid blood flow, end-expiratory CO2, regional oxygen saturation by near infrared spectroscopy, blood gas, and local organ perfusion with fluorescent labelled microspheres were measured at baseline and during resuscitation. Results. Animals treated with Corpuls CPR had significantly higher mean arterial pressures during resuscitation, along with a detectable trend of greater carotid blood flow and organ perfusion. Conclusion. Chest compressions with the Corpuls CPR device generated significantly higher mean arterial pressures than compressions performed with the LUCAS II device.

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