Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 108
Filter
1.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38912910

ABSTRACT

Foam targets have gained considerable importance over the last decade in laser-matter interaction. They find widespread applications such as in inertial confinement fusion and secondary sources for particles and radiation. At the same time, the advent of high repetition-rate laser systems, be they short-pulse in the tens of femtosecond regime or in the kilo-Joule nanosecond regime, calls for equally high repetition rate targetry systems. A well-established repetition-rate targetry system is the tape target. In this article, we present the successful marriage of a tape target delivery system with 3D-printed foam targets produced by two photon polymerization.

2.
J Visc Surg ; 159(2): 108-113, 2022 04.
Article in English | MEDLINE | ID: mdl-34446363

ABSTRACT

OBJECTIVE: Leiomyoma is the most common benign tumor of the esophagus. Extra mucosal enucleation is the standard treatment. Herein we evaluated the feasibility and the outcomes of Minimally Invasive Surgery (MIS) using video-assisted thoracoscopic (VATS) or laparoscopic surgery (VALS) for esophageal leiomyoma enucleation. SUBJECTS AND METHODS: Retrospective study of patients who were treated via VATS or VALS for esophageal leiomyoma enucleation in "Hanoi Viet Duc Hospital" from 2010 to 2017 by the same operator. The operative approach, tumor size, complications and outcomes after surgery were recorded. RESULTS: Seventy-five patients were included. Mean age was 41.9 (range 20-68) years. The male/female sex ratio was 2.1:1. Fifty-five patients had clinical symptoms (73.3%). Tumors were identified in the upper third (12%), middle third (51%), and lower third (37%) of the esophagus. Mean tumor size was 3.7 (range 2-11) cm. VALS enucleation was performed in 23 patients who had leiomyoma located near the cardia (gastroesophageal junction or abdominal esophagus). The remaining 52 patients underwent right (n=42) or left VATS (n=10). Five patients (6.7%) sustained esophageal mucosa injury during dissection, repaired by MIS without late morbidity. A mini-incision (2 mini-laparotomies and 1 thoracotomy) was required in three patients (4%) due to large tumor size or mucosal injury. The mean operative time was 105min in VATS and 174min in VALS. No major perioperative surgical or medical complications were reported. The mean duration of hospital stay was 7.2 (range 5-12) days. CONCLUSIONS: MIS enucleation of esophageal leiomyoma is technically safe and associated with a high therapeutic success rate with low medico-surgical morbidity. VATS could be applied for almost all esophageal leiomyoma tumors; however, the VALS approach was preferred for tumors located near the gastroesophageal junction in order to create an anti-reflux valve after enucleation.


Subject(s)
Esophageal Neoplasms , Laparoscopy , Leiomyoma , Adult , Aged , Esophageal Neoplasms/complications , Female , Humans , Leiomyoma/surgery , Male , Middle Aged , Retrospective Studies , Thoracoscopy , Valsartan , Young Adult
3.
Int J Stroke ; 16(8): 972-980, 2021 10.
Article in English | MEDLINE | ID: mdl-33435860

ABSTRACT

BACKGROUND: The composition of the thrombus influences its retrievability by mechanical thrombectomy. PURPOSE: Our study aimed to report on thrombi resistant to aspiration, regarding susceptibility vessel sign and histologic composition. METHODS: This observational study was based on a prospective database of acute anterior circulation ischemic strokes treated by mechanical thrombectomy. Endovascular first-line strategy was aspiration and in case of failure, combined therapy-rescue was performed. The positivity of susceptibility vessel sign (SVS+) or its negativity (SVS-) was assessed on T2* sequences. The thrombus composition was analyzed with hematoxylin eosin staining. RESULTS: Histological analysis was performed on 102 clots. Thrombi with SVS- were significantly richer in fibrin/platelets, p = 0.04. Out of 210 mechanical thrombectomy, aspiration first pass strategy was performed in 131/210 (62%) patients. Combined therapy-rescue was needed in 37% of aspiration first pass strategy cases (n = 131). Clots retrieved combined therapy-rescue were richer in fibrin/platelets 63.9% versus 50.8% for aspiration first pass strategy, p = 0.03. Logistic regression analysis showed that fibrin/platelet-poor clots (<60%) were significantly more likely to be recanalized by aspiration first pass strategy compared to fibrin/platelet-rich clots (>60%) that were more likely recanalized by combined therapy-rescue after aspiration first pass strategy failure (OR = 3.5; 95% CI = 1.2-10.8; p = 0.0054). CONCLUSIONS: Our results confirm that SVS- clots are rich in fibrin/platelets and suggest that these "white clots" are less likely to be retrieved by aspiration alone and more often require the use of combined therapy.


Subject(s)
Stroke , Thrombosis , Blood Platelets , Fibrin , Humans , Stroke/therapy , Thrombectomy , Thrombosis/therapy , Treatment Outcome
4.
Int J Epidemiol ; 50(2): 633-643, 2021 05 17.
Article in English | MEDLINE | ID: mdl-33232447

ABSTRACT

BACKGROUND: The Pooled Uranium Miners Analysis (PUMA) study draws together information from cohorts of uranium miners from Canada, the Czech Republic, France, Germany and the USA. METHODS: Vital status and cause of death were ascertained and compared with expectations based upon national mortality rates by computing standardized mortality ratios (SMRs) overall and by categories of time since first hire, calendar period of first employment and duration of employment as a miner. RESULTS: There were 51 787 deaths observed among 118 329 male miners [SMR = 1.05; 95% confidence interval (CI): 1.04, 1.06]. The SMR was elevated for all cancers (n = 16 633, SMR = 1.23; 95% CI: 1.21, 1.25), due primarily to excess mortality from cancers of the lung (n = 7756, SMR = 1.90; 95% CI: 1.86, 1.94), liver and gallbladder (n = 549, SMR = 1.15; 95% CI: 1.06, 1.25), larynx (n = 229, SMR = 1.10; 95% CI: 0.97, 1.26), stomach (n = 1058, SMR = 1.08; 95% CI: 1.02, 1.15) and pleura (n = 39, SMR = 1.06; 95% CI: 0.75, 1.44). Lung-cancer SMRs increased with duration of employment, decreased with calendar period and persisted with time since first hire. Among non-malignant causes, the SMR was elevated for external causes (n = 3362, SMR = 1.41; 95% CI: 1.36, 1.46) and respiratory diseases (n = 4508, SMR = 1.32; 95% CI: 1.28, 1.36), most notably silicosis (n = 814, SMR = 13.56; 95% CI: 12.64, 14.52), but not chronic obstructive pulmonary disease (n = 1729, SMR = 0.98; 95% CI: 0.93, 1.02). CONCLUSIONS: Whereas there are important obstacles to the ability to detect adverse effects of occupational exposures via SMR analyses, PUMA provides evidence of excess mortality among uranium miners due to a range of categories of cause of death. The persistent elevation of SMRs with time since first hire as a uranium miner underscores the importance of long-term follow-up of these workers.


Subject(s)
Lung Neoplasms , Occupational Diseases , Occupational Exposure , Radon , Uranium , Canada/epidemiology , Cohort Studies , Europe/epidemiology , France , Germany , Humans , Male , North America/epidemiology , Occupational Exposure/adverse effects
5.
Sci Rep ; 10(1): 7310, 2020 Apr 30.
Article in English | MEDLINE | ID: mdl-32355206

ABSTRACT

Origins of polarization fatigue in ferroelectric capacitors under electric field cycling still remain unclear. Here, we experimentally identify origins of polarization fatigue in ferroelectric PbZr0.52Ti0.48O3 (PZT) thin-film capacitors by investigating their fatigue behaviours and interface structures. The PZT layers are epitaxially grown on SrRuO3-buffered SrTiO3 substrates by a pulsed laser deposition (PLD), and the capacitor top-electrodes are various, including SrRuO3 (SRO) made by in-situ PLD, Pt by in-situ PLD (Pt-inPLD) and ex-situ sputtering (Pt-sputtered). We found that fatigue behaviour of the capacitor is directly related to the top-electrode/PZT interface structure. The Pt-sputtered/PZT/SRO capacitor has a thin defective layer at the top interface and shows early fatigue while the Pt-inPLD/PZT/SRO and SRO/PZT/SRO capacitor have clean top-interfaces and show much more fatigue resistance. The defective dielectric layer at the Pt-sputtered/PZT interface mainly contains carbon contaminants, which form during the capacitor ex-situ fabrication. Removal of this dielectric layer significantly delays the fatigue onset. Our results clearly indicate that dielectric layer at ferroelectric capacitor interfaces is the main origin of polarization fatigue, as previously proposed in the charge injection model.

6.
Ther Apher Dial ; 24(5): 554-560, 2020 Oct.
Article in English | MEDLINE | ID: mdl-31856402

ABSTRACT

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine produced during acute inflammation. Few studies have evaluated the association between serum TNF-α and its receptors and their clinical outcomes in hemodialysis patients. However, a study assessing patients using a low-flux dialyzer reuse has not been conducted yet. The serum TNF-α concentrations of 319 prevalent hemodialysis patients (mean age, 45 ± 15 years; median duration of hemodialysis, 48 [interquartile range, 26-79] months; 185 males and 134 females) was examined to predict their 3-year mortality. The patients were divided into tertiles according to their serum TNF-α concentrations: T1 (n = 106; serum TNF-α concentration, <41.22 pg/mL), T2 (n = 106; serum TNF-α level, from 41.22 to 67.28 pg/mL), and T3 (n = 107; serum TNF-α concentration, ≥ 67.29 pg/mL). During the 36-month follow-up period, a total of 50 (15.7%) patients died from all causes. The Kaplan-Meier analysis revealed that the all-cause mortality in T3 was significantly higher compared to that in T1 and T2 (log-rank test, P < .001). The serum TNF-α level was a significant predictor for all-cause mortality (area under the curve = 0.887, P < .001, cutoff value, 89.812 pg/mL, sensitivity = 76%, specificity = 96.3%). The serum TNF-α level was a better predictor of mortality than the duration of hemodialysis and serum albumin, serum high-sensitivity C-reactive protein, and serum beta-2 microglobulin concentrations. The serum TNF-α concentration was a good predictor of the 3-year mortality in low-flux hemodialysis patients.


Subject(s)
Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Renal Dialysis/mortality , Tumor Necrosis Factor-alpha/blood , Adult , Biomarkers/blood , Female , Humans , Kaplan-Meier Estimate , Kidney Failure, Chronic/blood , Male , Middle Aged , Proportional Hazards Models , Renal Dialysis/methods , Renal Dialysis/statistics & numerical data , Survival Analysis , Vietnam/epidemiology
7.
Pharmacol Rep ; 71(6): 1190-1200, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31669883

ABSTRACT

BACKGROUND: Increased mortality due to type 2 diabetes mellitus (T2DM) has been associated with renal and/or cardiovascular dysfunction. Dipeptidyl dipeptidase-4 inhibitors (iDPP-4s) may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms. In this study, the pharmacological profile of a new iDPP-4 (LASSBio-2124) was investigated in rats with cardiac and renal dysfunction induced by T2DM. METHODS: T2DM was induced in rats by 2 weeks of a high-fat diet followed by intravenous injection of streptozotocin. Metabolic disturbance and cardiac, vascular, and renal dysfunction were analyzed in the experimental groups. RESULTS: Sitagliptin and LASSBio-2124 administration after T2DM induction reduced elevated glucose levels to 319.8 ±â€¯13.2 and 279.7 ±â€¯17.8 mg/dL, respectively (p < 0.05). LASSBio-2124 also lowered the cholesterol and triglyceride levels from 76.8 ±â€¯8.0 to 42.7 ±â€¯3.2 mg/dL and from 229.7 ±â€¯25.4 to 100.7 ±â€¯17.1 mg/dL, in diabetic rats. Sitagliptin and LASSBio-2124 reversed the reduction of the plasma insulin level. LASSBio-2124 recovered the increased urinary flow in diabetic animals and reduced 24-h proteinuria from 23.7 ±â€¯1.5 to 13.3 ±â€¯2.8 mg (p < 0.05). It also reduced systolic and diastolic left-ventricular dysfunction in hearts from diabetic rats. CONCLUSION: The effects of LASSBio-2124 were superior to those of sitagliptin in the cardiovascular systems of T2DM rats. This new prototype showed promise for the avoidance of comorbidities in a T2DM experimental model, and thus may constitute an innovative therapeutic agent for the treatment of these conditions in the clinical field in future.


Subject(s)
Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Heart/drug effects , Kidney Diseases/drug therapy , Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Glucagon-Like Peptide 1/metabolism , Kidney Diseases/metabolism , Male , Rats , Rats, Wistar , Sitagliptin Phosphate/pharmacology , Streptozocin/pharmacology , Ventricular Dysfunction, Left/drug therapy , Ventricular Dysfunction, Left/metabolism
8.
Hum Mov Sci ; 64: 101-107, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30710860

ABSTRACT

Three-dimensional gait analysis is the gold standard for gait-assessment in patients with stroke. This technique is commonly used to assess the effect of treatment on gait parameters. In clinical practice, three gait analyses are usually carried out (baseline, after treatment and follow-up), the objectives were to define the reproducibility and the Minimum Detectable Change (MDC) for gait parameters in stance and swing measured using 3D-gait analysis, and to assess changes in MDC across three repeated 3D-gait analyses. Three gait analyses (V1, V2 and V3) were performed at 7-day intervals in twenty-six patients with chronic stroke. Kinematic data (in the sagittal plane, during swing and stance) and spatiotemporal data were evaluated for the paretic limb. Reliability was tested using repeated measures ANOVA with a Tukey post hoc test, and the MDC values were calculated for each parameter. Only the range of hip motion during swing changed significantly between V1 and V2, but no other kinematic parameters changed. No significant differences were observed for the spatiotemporal parameters. MDC values were always higher during the V1vsV2 comparison for both kinematic and spatiotemporal parameters. This is the first study to evaluate the MDC for kinematic and spatiotemporal parameters during stance and swing. Reliability of kinematic and spatiotemporal data across sessions was very good over the three sessions. MDC values were the lowest between V2 and V3 for most parameters. Use of the MDC will allow clinicians to more accurately determine the effect of treatments.


Subject(s)
Gait/physiology , Stroke/physiopathology , Analysis of Variance , Ankle Joint/physiology , Biomechanical Phenomena/physiology , Chronic Disease , Female , Gait Analysis/methods , Hip Joint/physiology , Humans , Knee Joint/physiology , Male , Middle Aged , Paresis/physiopathology , Reproducibility of Results
9.
Front Pharmacol ; 9: 1395, 2018.
Article in English | MEDLINE | ID: mdl-30574088

ABSTRACT

Aims: Pulmonary arterial hypertension (PAH) is a disease characterized by an increase in pulmonary vascular resistance and right ventricular (RV) failure. We aimed to determine the effects of human mesenchymal stem cell (hMSC) therapy in a SU5416/hypoxia (SuH) mice model of PAH. Methods and Results: C57BL/6 mice (20-25 g) were exposure to 4 weeks of hypoxia combined vascular endothelial growth factor receptor antagonism (20 mg/kg SU5416; weekly s.c. injections; PAH mice). Control mice were housed in room air. Following 2 weeks of SuH exposure, we injected 5 × 105 hMSCs cells suspended in 50 µL of vehicle (0.6 U/mL DNaseI in PBS) through intravenous injection in the caudal vein. PAH mice were treated only with vehicle. Ratio between pulmonary artery acceleration time and RV ejection time (PAAT/RVET), measure by echocardiography, was significantly reduced in the PAH mice, compared with controls, and therapy with hMSCs normalized this. Significant muscularization of the PA was observed in the PAH mice and hMSC reduced the number of fully muscularized vessels. RV free wall thickness was higher in PAH animals than in the controls, and a single injection of hMSCs reversed RV hypertrophy. Levels of markers of exacerbated apoptosis, tissue inflammation and damage, cell proliferation and oxidative stress were significantly greater in both lungs and RV tissues from PAH group, compared to controls. hMSC injection in PAH animals normalized the expression of these molecules which are involved with PAH and RV dysfunction development and the state of chronicity. Conclusion: These results indicate that hMSCs therapy represents a novel strategy for the treatment of PAH in the future.

10.
Pharmacol Biochem Behav ; 175: 19-23, 2018 12.
Article in English | MEDLINE | ID: mdl-30193843

ABSTRACT

DHEA is reported to have beneficial effects for the elderly and for several pathologies because of its behavioral and anti-inflammatory properties. However, these properties have never been investigated in a young healthy population. The purpose of this double-blind, randomized study was therefore to investigate the effects of short-term DHEA administration (100 mg/day/4 weeks) on neuroendocrine (i.e., beta-endorphin and prolactin) and inflammatory (i.e., interleukin-6 and TNF-alpha) parameters in 10 young healthy female volunteers with regular sports practice. In parallel, the stress state was assessed with the Profile of Mood States (POMS) questionnaire. DHEA administration did not alter prolactin, interleukin-6 or TNF-alpha, and no significant change in tension, depression, anger, vigor, fatigue or confusion was noted. However, beta-endorphin levels increased significantly (p < 0.05) with the DHEA treatment. The results of this investigation indicate that short-term DHEA administration improves neuroendocrine modulation but does not affect the inflammatory status or psychological state in recreationally trained female athletes. Further studies are needed to determine the exact mechanisms and the responses of these parameters to DHEA administration at higher dosages and/or for longer durations, especially in response to physical/psychological stress.


Subject(s)
Dehydroepiandrosterone/administration & dosage , Inflammation/chemically induced , Neurosecretory Systems/drug effects , Double-Blind Method , Female , Humans , Stress, Physiological , Stress, Psychological , Young Adult
11.
Sci Total Environ ; 639: 910-920, 2018 Oct 15.
Article in English | MEDLINE | ID: mdl-29929329

ABSTRACT

Wastewater is now considered to be a vital reusable source of water reuse and saving energy. However, current wastewater has multiple limitations such as high energy costs, large quantities of residuals being generated and lacking in potential resources. Recently, great attention has been paid to microbial fuel cells (MFCs) due to their mild operating conditions where a variety of biodegradable substrates can serve as fuel. MFCs can be used in wastewater treatment facilities to break down organic matter, and they have also been analysed for application as a biosensor such as a sensor for biological oxygen which demands monitoring. MFCs represent an innovation technology solution that is simple and rapid. Despite the advantages of this technology, there are still practical barriers to consider including low electricity production, current instability, high internal resistance and costly materials used. Thus, many problems must be overcome and doing this requires a more detailed analysis of energy production, consumption, and application. Currently, real-world applications of MFCs are limited due to their low power density level of only several thousand mW/m2. Efforts are being made to improve the performance and reduce the construction and operating costs of MFCs. This paper explores several aspects of MFCs such as anode, cathode and membrane, and in an effort to overcome the practical challenges of this system.


Subject(s)
Bioelectric Energy Sources , Waste Disposal, Fluid/methods , Electricity , Electrodes , Oxygen , Wastewater
12.
Med Chem ; 14(8): 831-850, 2018.
Article in English | MEDLINE | ID: mdl-29807520

ABSTRACT

BACKGROUND: Histone deacetylases (HDAC) enzymes are emerging as potential targets for cancer treatments. In this study, several series of novel hydroxamic acids incorporating 1-((1H- 1,2,3-triazol-4-yl)methyl)-3-substituted-2-oxoindolines were explored. METHODS: The compounds were designed using Autodock Vina program, then synthesized and evaluated in vitro and in silico for their inhibitory activity against HDACs. The cytotoxicity was measured by SRB method. The enzyme inhibitory effects of the compounds were evaluated by the fluorescent assay. RESULTS: Biological evaluation showed that these hydroxamic acids were generally cytotoxic against four human cancer cell lines (SW620, colon; PC-3, prostate; AsPC-1, pancreas; NCI-H23, lung). Several compounds, e.g. 7g, 11c, and 11g, displayed up to 10-fold more potent than SAHA (suberoylanilide hydroxamic acid, vorinostat) in term of cytotoxicity. The synthesized compounds were also comparably potent to SAHA in inhibiting HDAC2. In particular, compound 11c displayed potential inhibitory effects against HDAC1, HDAC2, HDAC6, and HDAC8 with comparable or slightly higher potency than SAHA. Docking results on four class I and IIB isoenzymes indicated that these compounds tightly bound to HDACs at the active site with binding affinities much higher than that of SAHA. Finally, chemo-informatics approaches were employed to assess the pharmacokinetic and toxicity profiles of 7g and 11c. We identified degradation via phase II metabolism and toxicity two of the most serious problems that need further optimization. CONCLUSION: Taking altogether our findings are encouraging and current hydroxamate derivatives are worth being considered as potential HDAC inhibitors and could be useful for further research on the development of new anti-cancer agents.


Subject(s)
Antineoplastic Agents/pharmacology , Histone Deacetylase Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Indoles/pharmacology , Triazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Catalytic Domain , Cell Line, Tumor , Histone Deacetylase Inhibitors/chemical synthesis , Histone Deacetylase Inhibitors/chemistry , Humans , Hydroxamic Acids/chemical synthesis , Hydroxamic Acids/chemistry , Indoles/chemical synthesis , Indoles/chemistry , Molecular Docking Simulation , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistry , Vorinostat/pharmacology
13.
J Gerontol A Biol Sci Med Sci ; 73(9): 1158-1166, 2018 08 10.
Article in English | MEDLINE | ID: mdl-29790948

ABSTRACT

Pulmonary hypertension (PH) is a disease of women (female-to-male ratio 4:1), and is associated with cardiac and skeletal muscle dysfunction. Herein, the activation of a new estrogen receptor (GPER) by the agonist G1 was evaluated in oophorectomized rats with monocrotaline (MCT)-induced PH. Depletion of estrogen was induced by bilateral oophorectomy (OVX) in Wistar rats. Experimental groups included SHAM or OVX rats that received a single intraperitoneal injection of MCT (60 mg/kg) for PH induction. Animals received s.c. injection of either vehicle or G1, a GPER agonist, (400 µg/kg/day) for 14 days after the onset of disease. Rats with PH exhibited exercise intolerance and cardiopulmonary alterations, including reduced pulmonary artery flow, biventricular remodeling, and left ventricular systolic and diastolic dysfunction. The magnitude of these PH-induced changes was significantly greater in OVX versus SHAM rats. G1 treatment reversed both cardiac and skeletal muscle functional aberrations caused by PH in OVX rats. G1 reversed PH-related cardiopulmonary dysfunction and exercise intolerance in female rats, a finding that may have important implications for the ongoing clinical evaluation of new drugs for the treatment of the disease in females after the loss of endogenous estrogens.


Subject(s)
Cardiotonic Agents , Estrogens , Exercise Tolerance/drug effects , Muscle, Skeletal , Receptors, G-Protein-Coupled/metabolism , Ventricular Dysfunction/prevention & control , Animals , Cardiotonic Agents/metabolism , Cardiotonic Agents/pharmacology , Disease Models, Animal , Estrogens/metabolism , Estrogens/pharmacology , Female , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/physiopathology , Monocrotaline/pharmacology , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiopathology , Ovariectomy/methods , Pulmonary Artery/metabolism , Pulmonary Artery/physiopathology , Rats , Ventricular Dysfunction/metabolism , Ventricular Dysfunction/physiopathology , Ventricular Remodeling/drug effects
14.
J Dent Res ; 97(2): 226-236, 2018 02.
Article in English | MEDLINE | ID: mdl-28898113

ABSTRACT

Interferon regulatory factor 6 ( IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. Haploinsufficiency of IRF6 causes Van der Woude and popliteal pterygium syndrome, 2 syndromic forms of cleft lip and palate. Around 85% of patients with Van der Woude express pits on the lower lip that continuously or intermittently drain saliva, and patients with the common cleft lip and palate have a higher prevalence of dental caries and gingivitis. This study aims to identify the role of IRF6 in development of exocrine glands, specifically the major salivary glands. Our transgenic mouse model that expresses LacZ reporter under the control of the human IRF6 enhancer element showed high expression of IRF6 in major and minor salivary glands and ducts. Immunostaining data also confirmed the endogenous expression of IRF6 in the developing ductal, serous, and mucous acinar cells of salivary glands. As such, we hypothesized that Irf6 is important for proper development of salivary glands and potentially other exocrine glands. Loss of Irf6 in mice causes an increase in the proliferation level of salivary cells, disorganized branching morphogenesis, and a lack of differentiated mucous acinar cells in submandibular and sublingual glands. Expression and localization of the acinar differentiation marker MIST1 were altered in Irf6-null salivary gland and pancreas. The RNA-Seq analysis demonstrated that 168 genes are differentially expressed and confer functions associated with transmembrane transporter activity, spliceosome, and transcriptional regulation. Furthermore, expression of genes involved in the EGF pathway-that is, Ereg, Ltbp4, Matn1, Matn3, and Tpo-was decreased at embryonic day 14.5, while levels of apoptotic proteins were elevated at postnatal day 0. In conclusion, our data report a novel role of Irf6 in exocrine gland development and support a rationale for performing exocrine functional tests for patients with IRF6-damaging mutations.


Subject(s)
Interferon Regulatory Factors/metabolism , Pancreas/embryology , Salivary Glands/embryology , Animals , Cell Differentiation , Humans , Immunohistochemistry , Mice , Mice, Transgenic , Pancreas/metabolism , Real-Time Polymerase Chain Reaction , Salivary Glands/metabolism , Sequence Analysis, RNA
15.
Arch Pediatr ; 25(2): 129-131, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29248325

ABSTRACT

We report the case of a 14-year-old boy presenting to our unit because of a spontaneous left pneumothorax. Over the 3 preceding weeks, he described a rhythmic precordial click and the sensation of bubbles floating inside his chest. This noise, audible to the patient and his family without a medical device, proved to be the Hamman sign, a rare although typical sound formerly related to pneumomediastinum that can be exceptionally encountered in isolated left pneumothorax. Its pathophysiology remains unclear. Small pockets of air close to the heart may be pushed inside pleura and amplified by the chest wall, hence provoking a recurrent rhythmic sound. A small left pneumothorax must be suspected whenever the Hamman sign is elicited in the absence of pneumomediastinum. Chest tomography must be precociously considered if plain x-rays are not contributive.


Subject(s)
Pneumothorax/diagnosis , Adolescent , Humans , Male
16.
Oncogene ; 36(41): 5757-5767, 2017 10 12.
Article in English | MEDLINE | ID: mdl-28604748

ABSTRACT

Isoprenylcysteine carboxylmethyltransferase (ICMT) catalyzes the post-translational modification of RAB GTPases that contain C-terminal CXC motifs. However, the functional impact of this modification on RAB proteins has not been actively explored. We found that inhibition of ICMT significantly reduced cell migration in vitro and cancer invasion and metastasis in vivo. This role of ICMT was found to be mediated by RAB4A, an essential regulator of the fast recycling of integrin ß3. Integrin ß3 regulates cell polarity and migration when localized appropriately to the plasma membrane, thereby having an essential role in cancer metastasis. ICMT catalyzed carboxylmethylation is critical for RAB4A activation and interaction with effectors, its localization to endosomes and recycling vesicles, and hence important for RAB4A-dependent integrin ß3 recycling to plasma membrane. These findings bring attention to the effects of C-terminal carboxylmethylation on RAB GTPases and provide a rationale for targeting ICMT in the treatment of metastatic cancer.


Subject(s)
Integrin beta3/genetics , Neoplasms/genetics , Protein Methyltransferases/genetics , rab4 GTP-Binding Proteins/genetics , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Polarity , Chickens , Endosomes/enzymology , Humans , Integrin beta3/metabolism , Mice , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Neoplasm Metastasis , Neoplasms/physiopathology , Protein Methyltransferases/metabolism , Protein Processing, Post-Translational , rab4 GTP-Binding Proteins/metabolism
17.
Health Promot Chronic Dis Prev Can ; 37(1): 30-31, 2017 Jan.
Article in English, French | MEDLINE | ID: mdl-28102994

ABSTRACT

INTRODUCTION: Although fatality and hospitalization rates for burns in Canada have declined over time, less serious cases still commonly present to the emergency department (ED). METHODS: The Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) is an injury and poisoning surveillance system administered by the Public Health Agency of Canada, operating in emergency departments of 17 hospitals. RESULTS: Overall, cases reported in 2013 were scalds and contact burns from hot objects. The leading direct causes of scalds were hot beverages and hot water. The leading causes of contact burns were stoves/ovens and fireplaces/accessories. While the overall proportion of burns was highest among females, males comprised a higher proportion of burns from all mechanisms except scalds.


INTRODUCTION: Bien que les taux de mortalité et d'hospitalisation associés à des brûlures au Canada aient diminué avec le temps, des cas moins graves se présentent encore couramment aux services d'urgence. MÉTHODOLOGIE: Le Système canadien hospitalier d'information et de recherche en prévention des traumatismes (SCHIRPT) révèle les causes majeures de brûlures thermiques et échaudures en 2013. RÉSULTATS: Au total, la moitié des blessures déclarées cette même année étaient des échaudures et des brûlures résultant d'un contact avec un objet brûlant. Les deux principales causes d'échaudures étaient les boissons chaudes et l'eau chaude. Les deux principales causes directes des brûlures par contact étaient les cuisinières et fours.


Subject(s)
Burns/epidemiology , Emergency Service, Hospital , Adolescent , Adult , Age Distribution , Aged , Canada/epidemiology , Child , Child, Preschool , Female , Hospitalization , Humans , Infant , Infant, Newborn , Male , Middle Aged , Population Surveillance , Sex Distribution , Young Adult
18.
Health Promot Chronic Dis Prev Can ; 37(1): 1-23, 2017 Jan.
Article in English, French | MEDLINE | ID: mdl-28102992

ABSTRACT

INTRODUCTION: The number of children diagnosed with autism spectrum disorder (ASD) has been rapidly rising in the past decade. The etiology of this disorder, however, is largely unknown, although the environmental relative to the genetic contribution is substantial. We conducted a scoping review to comprehensively assess the current state of knowledge of the environmental factors present from preconception to early life associated with ASD, and to identify research gaps. METHODS: We searched electronic databases MEDLINE, PsycINFO and ERIC for articles on potential risk factors or protective factors from the physical and social environments associated with ASD and its subclassifications published between 1 January, 2003, and 12 July, 2013. We categorized articles into broad themes: chemical, physiological, nutritional and social factors, based on environmental exposure. RESULTS: We identified over 50 000 publications, but after ineligible studies were screened out, 315 articles remained. Most of these studies examined physiological factors, followed closely by chemical factors, and to a much lesser extent, nutritional and social factors, associated with ASD. Despite a vast literature and many heterogeneous studies, several risk factors emerged consistently: chemical factors such as traffic-related air pollutants; physiological factors including advanced parental age, preterm birth, low birth weight, hyperbilirubinemia and clustering of pregnancy complications; and maternal immigrant status. Despite extensive research on vaccines, findings overwhelmingly demonstrate no support for an association with ASD. CONCLUSION: The lack of consistency, temporality and specificity of associations between environmental factors and ASD remains the largest barrier to establishing causal relationships. More robust research is required to resolve inconsistencies in the literature. Future research should explore underlying mechanisms of associations between the risk factors that we identified and ASD.


INTRODUCTION: Le nombre d'enfants chez lesquels on diagnostique un trouble du spectre de l'autisme (TSA) grimpe rapidement depuis une décennie. L'étiologie de ce trouble est toutefois en grande partie inconnue, même si la contribution de l'environnement est importante par rapport à celle de la génétique. Nous avons procédé à une étude de délimitation pour évaluer en détail l'état actuel des connaissances sur les facteurs environnementaux présents depuis le stade de la préconception jusqu'au début de la vie que l'on associe au TSA et pour dégager les lacunes de la recherche. MÉTHODOLOGIE: Nous avons cherché dans les bases de données électroniques MEDLINE, PsycINFO et ERIC des articles portant sur des facteurs de risque potentiels ou des facteurs de protection des environnements physiques et sociaux associés au TSA et à ses sous-catégories entre le 1er janvier 2003 et le 12 juillet 2013. Nous avons regroupé les articles en thèmes généraux en fonction de l'exposition environnementale : facteurs chimiques, physiologiques, nutritionnels et sociaux. RÉSULTATS: Nous avons trouvé plus de 50 000 publications, mais après élimination des études inadmissibles il est resté 315 articles. La plupart de ces études portaient sur les facteurs psychologiques, suivis de près par les facteurs chimiques et, à un degré beaucoup moindre, les facteurs nutritionnels et sociaux associés au TSA. En dépit d'une masse importante de publications et de nombreuses études hétérogènes, quelques facteurs de risque se sont démarqués régulièrement : facteurs chimiques comme les polluants atmosphériques causés par la circulation; facteurs physiologiques, dont l'âge avancé des parents, les naissances prématurées, l'insuffisance de poids à la naissance, l'hyperbilirubinémie et les grappes de complications de la grossesse et enfin le statut de la mère vis-à-vis de l'immigration. En dépit de recherches poussées sur les vaccins, les faits révèlent de façon écrasante que rien n'appuie l'existence d'un lien avec le TSA. CONCLUSION: Le manque d'uniformité, de temporalité et de spécificité des liens entre les facteurs environnementaux et le TSA demeure l'obstacle le plus important dans l'établissement de liens de cause à effet. Une recherche plus robuste s'impose pour supprimer le manque d'uniformité dans les publications. Les recherches futures devraient porter sur des mécanismes sous-jacents des liens entre facteurs de risque que nous avons identifiés et le TSA.


Subject(s)
Autism Spectrum Disorder/etiology , Child , Child, Preschool , Environmental Exposure , Female , Humans , Male , Pregnancy , Pregnancy Complications , Risk Factors , Sociological Factors
20.
Health Promot Chronic Dis Prev Can ; 36(9): 194-8, 2016 Sep.
Article in English, French | MEDLINE | ID: mdl-27670922

ABSTRACT

INTRODUCTION: Excess weight is a key risk factor for chronic disease, and the systematic collection, analysis and reporting of key trends are important to surveillance of overweight and obesity. METHODS: We used univariate analyses to calculate current prevalence estimates of excess weight among Canadian children and youth. RESULTS: Almost 1 in 7 children and youth is obese. Rates vary based on sociodemographic factors such as age, sex, socioeconomic status and place of residence. Overall, the rates of excess weight have been relatively stable over the past decade. CONCLUSION: Ongoing monitoring of childhood obesity will provide useful information to assist with sustained actions to promote healthy weights.


INTRODUCTION: L'excès de poids est un facteur de risque important de maladies chroniques. La collecte, l'analyse et la diffusion systématiques des tendances clés dans ce domaine sont importantes pour la surveillance de l'embonpoint et de l'obésité. MÉTHODOLOGIE: Nous avons utilisé des analyses univariées pour calculer des estimations de la prévalence actuelle de l'excès de poids chez les enfants et les jeunes canadiens. RÉSULTATS: Près d'un enfant ou jeune sur sept est obèse. Les taux varient en fonction de facteurs sociodémographiques comme l'âge, le sexe, le statut socioéconomique et le lieu de résidence. Dans l'ensemble, les taux d'excès de poids sont demeurés relativement stables depuis dix ans. CONCLUSION: Faire le suivi de l'obésité juvénile fournit des renseignements utiles à la prise de mesures à long terme pour la promotion d'un poids santé.


Subject(s)
Pediatric Obesity , Adolescent , Canada/epidemiology , Child , Demography , Health Surveys , Humans , Male , Pediatric Obesity/diagnosis , Pediatric Obesity/epidemiology , Pediatric Obesity/prevention & control , Prevalence , Risk Factors , Socioeconomic Factors
SELECTION OF CITATIONS
SEARCH DETAIL