Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation.

Metabolic syndrome, today affecting more than 20% of the US population, is a group of 5 conditions that often coexist and that strongly predispose to cardiovascular disease. How these conditions are linked mechanistically remains unclear, especially two of these: obesity and elevated blood pressure. Here, we show that high fat consumption in mice leads to the accumulation of lipid droplets in endothelial cells throughout the organism and that lipid droplet accumulation in endothelium suppresses endothelial nitric oxide synthase (eNOS), reduces NO production, elevates blood pressure, and accelerates atherosclerosis. Mechanistically, the accumulation of lipid droplets destabilizes eNOS mRNA and activates an endothelial inflammatory signaling cascade that suppresses eNOS and NO production. Pharmacological prevention of lipid droplet formation reverses the suppression of NO production in cell culture and in vivo and blunts blood pressure elevation in response to a high-fat diet. These results highlight lipid droplets as a critical and unappreciated component of endothelial cell biology, explain how lipids increase blood pressure acutely, and provide a mechanistic account for the epidemiological link between obesity and elevated blood pressure.

Circadian regulation of lung repair and regeneration.

Optimal lung repair and regeneration are essential for recovery from viral infections, including influenza A virus (IAV). We have previously demonstrated that acute inflammation and mortality induced by IAV is under circadian control. However, it is not known whether the influence of the circadian clock persists beyond the acute outcomes. Here, we utilize the UK Biobank to demonstrate an association between poor circadian rhythms and morbidity from lower respiratory tract infections, including the need for hospitalization and mortality after discharge; this persists even after adjusting for common confounding factors. Furthermore, we use a combination of lung organoid assays, single-cell RNA sequencing, and IAV infection in different models of clock disruption to investigate the role of the circadian clock in lung repair and regeneration. We show that lung organoids have a functional circadian clock and the disruption of this clock impairs regenerative capacity. Finally, we find that the circadian clock acts through distinct pathways in mediating lung regeneration - in tracheal cells via the Wnt/ß-catenin pathway and through IL-1ß in alveolar epithelial cells. We speculate that adding a circadian dimension to the critical process of lung repair and regeneration will lead to novel therapies and improve outcomes.

Sex-dependent compensatory mechanisms preserve blood pressure homeostasis in prostacyclin receptor-deficient mice.

Inhibitors of microsomal prostaglandin E synthase 1 (mPGES-1) are in the early phase of clinical development. Deletion of mPges-1 in mice confers analgesia, restrains atherogenesis, and fails to accelerate thrombogenesis, while suppressing prostaglandin E2 (PGE2), but increasing the biosynthesis of prostacyclin (PGI2). In low-density lipoprotein receptor-deficient (Ldlr-/-) mice, this last effect represents the dominant mechanism by which mPges-1 deletion restrains thrombogenesis, while suppression of PGE2 accounts for its antiatherogenic effect. However, the effect of mPges-1 depletion on blood pressure (BP) in this setting remains unknown. Here, we show that mPges-1 depletion significantly increased the BP response to salt loading in male Ldlr-/- mice, whereas, despite the direct vasodilator properties of PGI2, deletion of the I prostanoid receptor (Ipr) suppressed this response. Furthermore, combined deletion of the Ipr abrogated the exaggerated BP response in male mPges-1-/- mice. Interestingly, these unexpected BP phenotypes were not observed in female mice fed a high-salt diet (HSD). This is attributable to the protective effect of estrogen in Ldlr-/- mice and in Ipr-/- Ldlr-/- mice. Thus, estrogen compensates for a deficiency in PGI2 to maintain BP homeostasis in response to high salt in hyperlipidemic female mice. In male mice, by contrast, the augmented formation of atrial natriuretic peptide (ANP) plays a similar compensatory role, restraining hypertension and oxidant stress in the setting of Ipr depletion. Hence, men with hyperlipidemia on a HSD might be at risk of a hypertensive response to mPGES-1 inhibitors.

Loss of circadian protection against influenza infection in adult mice exposed to hyperoxia as neonates.

Adverse early-life exposures have a lasting negative impact on health. Neonatal hyperoxia that is a risk factor for bronchopulmonary dysplasia confers susceptibility to influenza A virus (IAV) infection later in life. Given our previous findings that the circadian clock protects against IAV, we asked if the long-term impact of neonatal hyperoxia vis-à-vis IAV infection includes circadian disruption. Here, we show that neonatal hyperoxia abolishes the clock-mediated time of day protection from IAV in mice, independent of viral burden through host tolerance pathways. We discovered that the lung intrinsic clock (and not the central or immune clocks) mediated this dysregulation. Loss of circadian protein, Bmal1, in alveolar type 2 (AT2) cells recapitulates the increased mortality, loss of temporal gating, and other key features of hyperoxia-exposed animals. Our data suggest a novel role for the circadian clock in AT2 cells in mediating long-term effects of early-life exposures to the lungs.

Circadian control of lung inflammation in influenza infection.

Influenza is a leading cause of respiratory mortality and morbidity. While inflammation is essential for fighting infection, a balance of anti-viral defense and host tolerance is necessary for recovery. Circadian rhythms have been shown to modulate inflammation. However, the importance of diurnal variability in the timing of influenza infection is not well understood. Here we demonstrate that endogenous rhythms affect survival in influenza infection. Circadian control of influenza infection is mediated by enhanced inflammation as proven by increased cellularity in bronchoalveolar lavage (BAL), pulmonary transcriptomic profile and histology and is not attributable to viral burden. Better survival is associated with a time dependent preponderance of NK and NKT cells and lower proportion of inflammatory monocytes in the lung. Further, using a series of genetic mouse mutants, we elucidate cellular mechanisms underlying circadian gating of influenza infection.

Recent changes of trans-boundary air pollution over the Yellow Sea: Implications for future air quality in South Korea.

The influence of air pollutants originating from the Chinese region on air quality over South Korea has been a major concern for policymakers. To investigate the inter-annual trends of the long-distance transport of air pollutants from China to South Korea, multi-year trend analysis was carried out for Aerosol Optical Depth (AOD, as a proxy of particulate matter), and CO (a water-insoluble air pollutant) and SO2 (a partially water-soluble air pollutant), over three regions in Northeast Asia. Air pollutants are typically long-range transported from the highly polluted parts of China to South Korea through the Yellow Sea. Taking advantage of this geographical merit, we carried out the multi-year trend analysis with a special focus on the Yellow Sea region. Decreasing trends of about 5-10%, 13-17% and 55-61% during the last decade were observed in surface CO, AOD and tropospheric SO2 columns over the North China Plain (NCP), Yellow Sea (YS), and South Korea (SK), respectively. Such decreasing trends were also found consistently during the last three, five, and seven years, indicating that the changes in pollution levels are likely in response to recent policy measures taken by the Chinese and Korean governments to improve air quality over the regions. Due to these efforts, the amounts of air pollutants transported from China to South Korea are expected to decrease in future years, to the likely rates of 1.50 ppb yr-1, 0.05 DU yr-1, and 0.56 µg m-3 yr-1 over the YS region for CO, SO2, and PM2.5, respectively. Given the ambitious plans recently announced by the Chinese government for the 21st meeting of Conference of Parties (COP21) and its co-control effects, the suggested percentage rates may even be conservative numbers. This analysis is expected to provide South Korean policymakers with valuable information to establish new air pollution policies in South Korea.

Triggering of Acute Coronary Occlusion by Episodes of Vigorous Physical Exertion.

BACKGROUND: There is increasing recognition that heavy exertion can occasionally trigger an acute myocardial infarction (MI), although some uncertainties exist regarding the link. The primary aim of this study was to compare the relative risk (RR) of MI following vigorous exertion between those with confirmed coronary occlusion and those with a non-occluded culprit artery on acute angiography. Secondary aims were to determine if the risk of coronary occlusion is modified by the type of exercise (dynamic or isometric resistance), the frequency of regular exertion or whether the exertion was emotionally charged. METHODS: Seven hundred sixty-two (762) participants with MI (410 with coronary occlusion TIMI 0,1), and 352 (46%) with a non-occluded culprit artery (TIMI 2,3) completed a questionnaire within 4days of admission, detailing episodes of physical exertion in the 28hours prior to symptom onset and the usual frequency of such exertion. Exertion exposures within 1hour prior to symptom onset were compared to subjects' usual yearly exposure, with case-crossover methodology. RESULTS: The RR of symptom onset following heavy physical exertion level ≥6 (exertion scale 1-8), was higher in those with TIMI 0,1 compared to those with TIMI 2,3 flow (RR 6.30, 95% CI 4.70-8.50 vs 3.93, 2.89-5.30). The increased risk of coronary occlusion following vigorous exertion was observed following both dynamic exertion and isometric resistance, and did not differ between exertion types. The highest risk of coronary occlusion following exertion was observed in those who were sedentary (regular vigorous exertion <1day weekly) (RR=77, 95% CI 46-132), whereas in those who frequently perform regular vigorous physical exertion (>4days weekly), the RR of symptom onset during exertion was significantly lower, RR 2.3 (95% CI 1.5-3.6). There was no significant difference in relative risk based on whether the exertion was reported as emotionally charged. CONCLUSIONS: The relative risk that heavy exertion will trigger a non-fatal MI with an occluded artery is greater than for a non-occluded culprit artery. Both dynamic and isometric exertion increase the relative risk of event, while exposure to regular vigorous exertion reduces the relative risk.

Flexible and transparent films produced from cellulose nanowhisker reinforced agarose.

Transparent and flexible nanocomposite films with a range of Agarose to Cellulose Nano-Whisker (CNW) ratios were produced using never-dried CNWs. The incorporation of never-dried CNWs within Agarose played an important role in the surface roughness (Ra 7-15 nm) and light transparency of the films (from 84 to 90%). Surface induced crystallisation of Agarose by CNWs was also found with increasing percentage of crystallinity (up to 79%) for the nanocomposite films, where CNW acted as nucleating sites. The enhanced tensile strength (ca. 30% increase) and modulus (ca. 90% increase) properties of the nanocomposite films compared to the control Agarose film indicated the effectiveness of the nanowhiskers incorporation. The storage modulus of the nanocomposite films increased also to be tripled Agarose alone as the CNWs content reached 43%. The swelling kinetics of the nanocomposites revealed that addition of CNWs reduced the long-term swelling capacity and swelling rate of the nanocomposite.

Synthetic Diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates Induce Apoptosis.

BACKGROUND: The Hantzsch ester, diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5- dicarboxylate, has been used as a hydride donor and its various biological effects have been reported. To identify chemotherapeutic agents with apoptotic effects, 21 diethyl 2,6-dimethyl-1,4- dihydropyridine-3,5-dicarboxylates were designed and synthesized; they have not been reported as apoptosis inducers thus far. Their structure-cytotoxicity relationships were investigated. Further biological experiments were performed on the title compound. METHODS: The cytotoxicities of the current synthetic compounds were measured using a clonogenic assay in HCT116 human colon cancer cells. An annexin V staining assay was used to confirm if the title compound induced apoptosis. To identify the synthetic compounds, Nuclear Magnetic Resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS) were conducted. As molecular symmetry was observed in the NMR spectroscopic data, the three dimensional structures were determined from ab initio calculations and X-ray crystallography. RESULTS: The results obtained from NMR spectroscopy, ab initio calculations, and X-ray crystallography revealed that the diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate derivatives synthesized in this research have symmetric structures. The cytotoxicities of the 21 derivatives were tested in the HCT116 human colon cancer cell lines, and their half-maximal cell growth inhibitory concentrations ranged between 16.29 and 68.88 µM. Structure-cytotoxicity relationships demonstrated that bulky substitutions were preferred, para-positioned substituents tended to have better cytotoxic values, and the polarity may have a function as well. The cytotoxicity of the title compound in HCT116 colon cancer cells was mediated through apoptotic cell death. CONCLUSION: To obtain chemotherapeutic agents that induce apoptosis, 21 diethyl 2,6-dimethyl- 1,4-dihydropyridine-3,5-dicarboxylates were designed and synthesized. NMR spectroscopy, ab initio calculations, and X-ray crystallography demonstrated that the diethyl 2,6-dimethyl-1,4- dihydropyridine-3,5-dicarboxylate derivatives synthesized in this research had symmetric structures. Even if the half-maximal cell growth inhibitory concentrations of the 21 derivatives did not show dramatic inhibitory activity against HCT116 human colon cancer cells, small changes in the structure affected the anticancer activities. Treatment with diethyl 4-(4-chlorophenyl)-2,6- dimethyl-1,4-dihydropyridine-3,5-dicarboxylate substantially reduced the cell viability and the cytotoxicity against HCT116 colon cancer cells was mediated through apoptotic cell death. As the ability of diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates to induce apoptosis has not been previously reported, we have now reported their design, synthesis, cytotoxicity, and structureactivity relationships.

Triggering of acute myocardial infarction by respiratory infection.

BACKGROUND: Respiratory infection has been associated with an increased short-term risk of myocardial infarction (MI). However, previous studies have predominantly been conducted without angiographic confirmation of MI. The possibility can therefore not be excluded that raised troponin levels or electrocardiogram abnormalities that may be seen with respiratory infections are due to non-ischaemic causes. AIMS: To investigate the association between respiratory infection and angiographically confirmed MI. METHODS: Interviews were conducted within 4 days of hospitalisation in 578 patients with angiographically confirmed MI, to assess for recent exposure to respiratory infection symptoms and the usual annual frequency of these symptoms. Using case-crossover methodology, exposure to respiratory infection prior to the onset of MI was compared against the usual frequency of exposure in the past year. RESULTS: Symptoms of respiratory infection were reported by 100 (17%) and 123 (21%) within 7 and 35 days, respectively, prior to MI. The relative risk (RR) for MI occurring within 1-7 days after respiratory infection symptoms was 17.0 (95% confidence interval (CI) 13.2-21.8), and declined with subsequent time periods. In a subgroup analysis, the RR tended to be lower in groups taking regular cardiac medications. For those who reported milder, upper respiratory tract infection symptoms, the RR for the 1-7-day time period was 13.5 (95% CI 10.2-17.7). CONCLUSION: These findings confirm that respiratory infection can trigger MI. Further study is indicated to identify treatment strategies to decrease this risk, particularly in individuals who may have increased susceptibility.

Benzoflavonoids Structure Hinders Human Colon Cancer Clonogenicity.

BACKGROUND: Since flavonoids fused by benzene have been known for their potent chemopreventive effects, in this study, we examined the relationship between the structures and activities of benzoflavones, benzoflavanones, benzochalcones, and benzochalcone derivatives bearing the pyrazole moiety against human colon cancer cells. METHODS: We investigated the effect of 34 benzoflavonoids on the inhibition of colon cancer cells based on the clonogenicity. The biological activity values used for the quantitative structure-activity relationship (QSAR) calculations were obtained from the cell growth inhibition on the basis of clonogenicity. 3D-QSAR calculations were performed using comparative molecular field analyses (CoMFA) and comparative molecular similarity index analyses (CoMSIA). RESULTS: Of several CoMFA and CoMSIA models, the best models showing the highest cross validated correlation coefficient were selected and validated. The cell growth inhibition values were calculated using the above models. The structural conditions to show good cell growth inhibitory effects on human colon cancer cells were analyzed by CoMFA and CoMSIA contour maps. The contribution of steric fields remarkably decreased without any change in the contribution of the electrostatic field, which means that electrostatic contribution is more crucial than the steric contribution in the modification of benzoflavonoids. Furthermore, the increase in the hydrogen bond donor contribution was approximately proportional to the decrease in steric field contribution. CONCLUSION: This study demonstrated that benzoflavonoids structure hinders colon cancer clonogenicity. Most of the benzoflavonoids structures comprised a C-3 linkage between the naphthalene and phenyl moieties, which contained diverse functional moieties such as oxygen-fused rings, double bonds, pyrazole rings, and sulfur constituents, and were able to exhibit great potential in diverse anticancer effects. Also, the positions of the hydroxyl group close to the naphthalene and phenyl rings were crucial for activity against colon cancer. The structural conditions obtained here may help us design potent benzoflavonoids against colon cancer cells and predict their activities.

Is research related to a country's economic development? An analysis of biomedical publications from several GCC and ASEAN countries from 1994-2013.

INTRODUCTION: Biomedical research has traditionally been the domain of developed countries. We aim to study the effects of the increased focus on biomedical and medical research on level 1-4 publications in several industrialised and newly industrialised countries endowed with petroleum and gas resources. METHODS: We identified all level 1-4 publications from 01/01/1994 to 31/12/2013 via PubMed using advanced options. The population and GDP (current US$) data from 1994-2013 were obtained through data provided by the World Bank and the raw data was normalised based on these two indicators. RESULTS: From 1994-2013, Saudi Arabia and Malaysia were responsible for the highest absolute number of level 1 to 4 biomedical and medical research publications with 2551 and 1951 publications respectively. When normalised to population, Kuwait and Qatar had the highest publication rates, with 7.84 and 3.99 publications per 100,000 inhabitants respectively in a five yearly average. Kuwait produced the largest number of publications per billion (current US$) of GDP, at 2.92 publications, followed by Malaysia at 2.82 publications in a five yearly average. CONCLUSION: The population size of a country as well as GDP can influence the number of level 1-4 publications in some countries. More importantly, effective government policy which stimulates research as well as a culture which actively promotes research as shown by Malaysia have proven to have a larger influence on the amount of level 1-4 biomedical and medical publications.

Routine aspiration thrombectomy improves the diagnosis and management of embolic myocardial infarction.

OBJECTIVES: Assess the effect of aspiration thrombectomy on diagnosis and management of embolic acute myocardial infarction. BACKGROUND: Discrimination of embolic acute myocardial infarction from atherosclerotic plaque rupture/erosion prompts oral anticoagulation treatment of source of embolus, as well as avoiding unnecessary stenting and dual antiplatelet therapy. However, detection is difficult without aspiration. METHODS: We compared rates of diagnosis of embolic infarction for 2.5 years prior to (pre-RAT) and 2.5 years post routine aspiration thrombectomy (post-RAT). Baseline demographics, outcomes, and treatment strategies were also compared between the embolic infarction and atherosclerotic infarction. RESULTS: Diagnosed embolic infarction rose from 1.2% in the pre-RAT era to 2.8% in the post-RAT period (P < 0.05). In addition, more successful removal of thrombus by aspiration led to less stenting (20% vs. 55% P < 0.05) in the post-RAT period thus avoiding the hazards of "triple therapy." Embolic infarction was more frequently associated with atrial fibrillation (55% vs. 8%), had higher mortality (17% vs. 4%), and had higher rates of embolic stroke (13% vs. 0.3%) when compared with atherosclerotic MI (all P < 0.05). CONCLUSIONS: Routine aspiration thrombectomy more readily identifies embolic infarction allowing more specific therapy and avoidance of stenting and triple anticoagulant therapy.

Triggering of acute coronary occlusion by episodes of anger.

AIMS: The aim of this study was to report the association between episodes of anger and acute myocardial infarction (MI) in patients with angiographically confirmed coronary occlusion. METHODS AND RESULTS: 313 participants with acute coronary occlusion (Thrombolysis In Myocardial Infarction 0 or 1 at emergency angiography) reported frequency of anger episodes in the 48 h prior to MI. In primary analysis, anger exposures within 2 h and 2-4 h prior to symptom onset were compared with subjects' own usual yearly exposure to anger using case-crossover methodology. Anger level ≥5 (on an anger scale of 1-7) was reported by seven (2.2%) participants within 2 h of MI. Compared with usual frequency, the relative risk of onset of MI symptoms occurring within 2 h of anger level ≥5 (defined as very angry) was 8.5 (95% confidence interval 4.1-17.6). Anger level <5 was not associated with onset of MI symptoms. Compared with 24-26 h pre MI, anxiety scores >75th percentile on State-Trait Personality Inventory were associated with a relative risk of 2.0 (95% confidence interval 1.1-3.8) and in those above the 90th percentile, the relative risk of MI symptom onset was 9.5 (95% confidence interval 2.2-40.8). CONCLUSION: Findings confirm that episodes of intense anger, defined as being 'very angry, body tense, clenching fists or teeth' (within 2 h) are associated with increased relative risk for acute coronary occlusion. Additionally, increased anxiety was associated with coronary occlusion. Further study, including the role of potential modifiers, may provide insight into prevention of MI during acute emotional episodes.

The prevalence of hearing loss in South Korea: data from a population-based study.

OBJECTIVES/HYPOTHESIS: In the present study, we aimed to determine the prevalence of hearing loss in the South Korean population and to understand the correlation between aging, sex, and hearing loss prevalence through the analysis of data collected from the Korea National Health and Nutrition Examination Survey (KNHANES). STUDY DESIGN: Cross-sectional epidemiological study. METHODS: The KNHANES is an ongoing population study that started in 1998. Examinations to detect diseases of the ear, nose, and throat, including audiological testing and otologic examinations, have been conducted since 2010. We included a total of 18,650 participants in the KNHANES, from 2010 to 2012, in the present study. Pure-tone audiometric testing was conducted in participants aged ≥ 12 years. The frequencies tested were 0.5, 1, 2, 3, 4, and 6 kHz. RESULTS: The prevalence of hearing loss in speech-relevant frequencies in the South Korean population was 9.31% for unilateral hearing loss and 13.42% for bilateral hearing loss. The overall hearing loss (unilateral or bilateral) was 22.73%. Male and older participants were more often affected by hearing loss than female and younger participants. High-frequency hearing loss appeared earlier than hearing loss at speech-relevant frequencies, and unilateral hearing loss showed a weaker correlation with aging than bilateral hearing loss. CONCLUSION: The prevalence of hearing loss in South Korea was higher in men and older participants according to the data collected from the KNHANES. The patterns of hearing loss differed between hearing loss at speech-relevant frequencies and at high frequencies.

The role of the laparoendoscopic single site totally extraperitoneal approach to inguinal hernia repairs: a review and meta-analysis of the literature.

BACKGROUND: Laparoendoscopic single site (LESS) surgery may have perceived benefits of reduced visible scarring compared to conventional laparoscopic (LAP) totally extraperitoneal (TEP) hernia repairs. We reviewed the literature to compare LESS TEP inguinal hernia repairs with LAP TEP repairs. METHODS: We searched electronic databases for research published between January 2008 and January 2012. RESULTS: A total of 13 studies reported on 325 patients. The duration of surgery was 40-98 minutes for unilateral hernia and 41-121 minutes for bilateral repairs. Three studies involving 287 patients compared LESS TEP (n = 128) with LAP TEP (n = 159). There were no significant differences in operative duration for unilateral hernias (p = 0.63) or bilateral repairs (p = 0.29), and there were no significant differences in hospital stay (p > 0.99), intraoperative complications (p = 0.82) or early recurrence rates (p = 0.82). There was a trend toward earlier return to activity in the LESS TEP group (p = 0.07). CONCLUSION: Laparoendoscopic single site surgery TEP hernia repair is a relatively new technique and appears to be safe and effective. Advantages, such as less visible scarring, mean patients may opt for LESS TEP over LAP TEP. Further studies with clear definitions of outcome measures and robust follow-up to assess patient satisfaction, return to normal daily activities and recurrence are needed to strengthen the evidence.

CONTEXTE: La chirurgie laparoendoscopique à orifice unique (LESS) a comme avantage perçu une réduction des cicatrices apparentes comparativement aux réparations laparoscopiques (LAP) classiques totalement extrapéritonéales (TEP) des hernies. Nous avons passé en revue la littérature afin de comparer les réparations des hernies inguinales par chirurgie LESS TEP et par LAP TEP. MÉTHODES: Nous avons interrogé les bases de données électroniques pour y recenser la recherche publiée entre janvier 2008 et janvier 2012. RÉSULTATS: En tout, 13 études ont porté sur 325 patients. La durée de la chirurgie a été de 40 à 98 minutes pour les réparations de hernies unilatérales et de 41 à 121 minutes pour les réparations de hernies bilatérales. Trois études regroupant 287 patients ont comparé la technique LESS TEP (n = 128) à la technique LAP TEP (n = 159). On n'a observé aucune différence significative quant à la durée de la chirurgie des réparations de hernies unilatérales (p = 0,63) ou bilatérales (p = 0,29) et aucune différence significative de durée des séjours hospitaliers (p > 0,99), de complications peropératoires (p = 0,82) ou de taux de récurrences précoces (p = 0,82). On a noté une tendance à un retour plus rapide aux activités dans le groupe soumis à la technique LESS TEP (p = 0,07). CONCLUSION: La réparation de hernie par chirurgie TEP laparoendoscopique à un seul orifice est une technique relativement nouvelle et semble sécuritaire et efficace. Ses avantages, par exemple des cicatrices moins apparentes, pourraient pousser les patients à opter pour la technique LESS TEP plutôt que LAP TEP. Il faudra procéder à d'autres études fondées sur des définitions paramétriques claires et comportant un suivi robuste pour évaluer la satisfaction des patients, la reprise des activités quotidiennes normales et les taux de récurrences afin de consolider les preuves.

Video-assisted thoracoscopic surgery for large Zenker's diverticulum: report of two cases.

INTRODUCTION: Zenker's diverticulum is a propulsion diverticulum in the pharynx. Current practice for the management of symptomatic pharyngeal pouches includes endoscopic pharyngeal stapling, performed trans-orally, and external approaches via a cervical incision. There is no published recommendation on how to approach diverticula with extension into the mediastinum, which may not be adequately treated with the above methods. CASES: We describe two cases in which thoracoscopic mobilisation of Zenker's diverticulum was performed using video-assisted thoracoscopic surgery together with traditional transcervical mobilisation and excision of the pouch. This allowed safe surgical access to the inferior limit of the pouch, and delivery of the sac into the neck incision following division of any inferior adhesions (to the great vessels in one case). DISCUSSION: In the first report of this technique, we describe a thorough, safe method of dissecting large diverticula that extend into the mediastinum, which minimises the risk to mediastinal structures.

Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment.

BACKGROUND: Defective copper regulation is implicated as a causative mechanism of organ damage in diabetes. Treatment with trientine, a divalent-copper-selective chelator, improves arterial and renal structure/function in diabetes, wherein it also ameliorates left-ventricular (LV) hypertrophy. However, direct in vivo evidence that trientine can improve cardiac function in heart failure has hitherto been lacking. METHODS: To determine whether trientine treatment could improve in vivo outcome, we measured cardiac function in groups of trientine-treated diabetic (TETA-DIA), non-drug-treated diabetic (DIA) and sham-treated control (SHAM) rats, by using in vivo high-field cardiac magnetic-resonance imaging (cMRI) and an ex vivo isolated-perfused working heart method. Forty age-matched animals underwent a cMRI scan after which 12 were randomized to the SHAM group and 28 underwent streptozotocin-injection; of these, 25 developed stable diabetes, and 12 were then randomized to receive no treatment for 16 weeks (DIA) and the other 13 to undergo 8-weeks' untreated diabetes followed by 8-weeks' drug treatment (TETA-DIA). Animals were studied again by cMRI at 8 and 16 weeks following disease induction, and finally by measurement of ex vivo cardiac function. RESULTS: After eight weeks diabetes, rats (DIA/TETA-DIA) had developed significant impairment of LV function, as judged by impairment of ejection fraction (LVEF), cardiac output (CO), and LV mass (LVM)/body-mass (all P < 0.001), as well as other functional indexes. LVEF, CO (both P < 0.001) and the other indexes deteriorated further at 16 weeks in DIA, whereas trientine (TETA-DIA) improved cardiac function by elevating LVEF and CO (both P < 0.001), and also partially reversed the increase in LVM/body-mass (P < 0.05). In ex vivo hearts from DIA, the CO response to increasing preload pressure was deficient compared with SHAM (P < 0.001) whereas the preload-CO relationship was significantly improved in TETA-DIA animals (P < 0.001). CONCLUSIONS: Trientine treatment significantly improved cardiac function in diabetic rats with substantive LV impairment. These results implicate impaired copper regulation in the pathogenesis of impaired cardiac function caused by diabetic cardiomyopathy, and support ongoing studies of trientine treatment in patients with heart failure.