Chikungunya Comeback in Sri Lanka: A Glimpse into its Epidemiology, Socioeconomic Toll, and the Double Trouble with Dengue

Mitochondria are at the center of neural biogenergetics, and ApoE4 is the single most impactful risk factor for AD. We investigated the impact of ApoE on insulin sensitivity, on mitochondrial substrate utilization and bioenergetics. Persons with ApoE4 have reduced brain carbohydrate metabolism. To test for ApoE4 conferred neural mitochondrial metabolic differences, we constructed a novel stable-ApoE 2,3 and 4 N2a cell model, and tested ApoE's effects on Insulin sensitivity, and mitochondrial glucose, lipid and ketone oxidation. Binding of ApoE isoforms E2, E3 and E4 to Insulin Receptor (IR) was measured by BLI and Co-IP, the impact of ApoE isoforms on mitochondrial glucose and lipid oxidation was measured by Seahorse. ApoE3 was found to sensitize to insulin about 2-fold more potently than ApoE4. ApoE isoforms directly bind Insulin Receptor; the binding constants was in the range 200-300nM. Consistent with the previous insulin-sensitivity finding, ApoE3 caused a significant increase of the glycolytic rate and glucose oxidation relative to ApoE4. As there was no difference in oxidation of TCA cycle intermediates substrates in permeabilized cells, we infer ApoE3's glucose advantage is the result of increased insulin sensitivity. ApoE4 contributed a significant palmitate oxidation defect relative to ApoE2 and ApoE3. As this palmitate oxidation defect was observed in both mitochondria and cells it is likely to occur at or within mitochondria. We observed that the relative defect in ApoE4-dependent glucose and palmitate oxidation can be overcome by 5mM BHB. Thus, at the neural cell level, the metabolic defects contributed by ApoE 4 appear to be rescued by a ketogenic molecule, BHB, that requires neither insulin nor apolipoprotein particle to reach neural mitochondria and provide alternative metabolic support. ApoE4 confers 'double trouble' in mitochondrial glucose and lipid oxidation. ApoE4 confers a defect in mitochondrial lipid oxidation relative to all other isoforms. Simultaneously, ApoE4 lacks the benefit in glucose oxidation conferred by ApoE3, which appears to be driven by the reduced insulin sensitization potency of ApoE4. We also find that BHB can be an alternative source of neural bioenergy that enters mitochondria directly and thus is not affected by ApoE4 'double trouble'.

Eight percent of the U.S. population has been diagnosed with diabetes mellitus (DM), while another large percentage has gone undiagnosed. As the epidemiology of this disease constitutes a larger percentage of the American population, another factor presents a dangerous dilemma that can exacerbate the hazardous effects imposed by DM. Excessive alcohol consumption concerns the health of more than 50% of all adults. When this heavy-alcohol-drinking population overlaps with DM and its complications, the effects can be dangerous. In this review, we term it as "double trouble." We provide evidence of alcohol-induced exacerbation of organ damage in diabetic conditions. In certain cases, we have explained how diabetes and alcohol induce similar pathological effects. Known exacerbated complications include those related to heart diseases, liver damage, kidney dysfunction, as well as retinal and neurological impairment. Often, pathophysiological damage concludes with end-stage disorders and even mortality. The metabolic, cell signaling, and pathophysiological changes associated with "double trouble" would lead to the identification of novel therapeutic targets. This review summarizes the epidemiology, diagnosis, pathophysiology, metabolic, and cell signaling alterations and finally brushes upon issues and strategies to manage the "double trouble."

Diabetes, Liver Cancer, and Cirrhosis: What Next?

Non-alcoholic fatty liver disease (NAFLD) increases risk of mortality from liver and cardiovascular disease (CVD) and is the major cause of hepatocellular carcinoma (HCC), which may develop without cirrhosis. NAFLD predicts type 2 diabetes, even independently of obesity. Globally, the prevalence of NAFLD averages 25% and is as common as the metabolic syndrome. The majority of patients with type 2 diabetes have NAFLD. The challenge for the diabetologist is to identify patients at risk of advanced liver disease and HCC. At a minimum, liver function tests (LFTs), despite being neither specific nor sensitive, should be performed in all patients with the metabolic syndrome or type 2 diabetes. Increases in LFTs, for which the updated reference values are lower (serum ALT ≈30U/l in men and ≈20U/l in women) than those hitherto used in many laboratories, should prompt assessment of fibrosis biomarkers and referral of individuals at risk to a NAFLD/hepatology clinic. Preferably, evaluation of NAFLD should be based on measurement of steatosis biomarkers or ultrasound if easily available. A large number of individuals carry the patatin-like phospholipase domain containing 3 (PNPLA3) I148M variant (30-50%) or the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant (11-15%). These variants increase the risk of advanced liver disease and HCC but not of diabetes or CVD. Genotyping of selected patients for these variants is recommended. Many patients have 'double trouble', i.e. carry both a genetic risk factor and have the metabolic syndrome. Excess use of alcohol could be a cause of 'triple trouble', but such patients would be classified as having alcoholic fatty liver disease. This review summarises a presentation given at the symposium 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by John Jones, DOI: 10.1007/s00125-016-3940-5 ) and a commentary by the Session Chair, Michael Roden (DOI: 10.1007/s00125-016-3911-x ).

International law plotted an incremental and cautious expansion of inchoate liability in the anti-terrorism treaties of the 1970s to 1990s, but the UN Security Council's response to the terrorist attacks of 11 September 2001 stepped up a gear. In resolution 1373 (2001), the Council required all states to criminalize new pre-inchoate terrorism offences of financing, planning and preparation, and support for terrorism, while resolution 2178 (2014) also required states to criminalize a range of conduct related to the travel. The result might be depicted as 'double trouble'. Many of the operative terms of criminal liability used by the Security Council are woefully under-defined. As a result, states enjoy a very wide discretion in implementing these offences, and some have seized the opportunity to over-broaden criminal liability to encompass acts that may not be objectively harmful or morally wrongful, often compromising the principles of legality and human rights.

Elite Sport and Leisure Sport in Hungary: The Double TroubleThe main purpose of this study is to give insight into the current status of two big areas of sport in Hungary: elite sport and leisure sport. As the expression ‘double trouble’ in the title indicates, in Hungary there are several problems in both areas.Hungary is a small country, but its Olympic teams were traditionally very successful in the Games. However, at the 29th Olympic Games in Beijing, Hungarian athletes performed below expectations, winning only three gold medals. The sport's political leaders and the public were very disappointed, therefore many experts tried to analyse the main reasons for the failure. They suggested that there were four problems in the background: the continuous disintegration of the sport clubs system; the low prestige of coaches and professionals working in sport; insufficient financial support and its inadequate timing; and the deficiency of sports science and its health care background. The second trouble concerns the sporting habits of Hungarian society. The country has faced the same problem for many decades: only a very low percentage of the Hungarian population takes part regularly in leisure sport programs. The latest empirical research shows that more than 60% of Hungarians do not do sports with suitable regularity. In comparing previous research results, there are a few changes among Hungarians according to gender, age and status of residence.How can this double trouble be resolved, or at least, how could both areas be somewhat improved? In Hungary, it is not really an easy task.

Techniques in Double-Bundle Anterior Cruciate Ligament Reconstruction: As Simple as ABC, or Putting the Cart Before the Horse?

ObjectiveTo perform a systematic review, and if possible a meta-analysis, to establish whether depressed patients with co-morbid chronic somatic illnesses are a high risk “double trouble” group for depressive recurrence.MethodThe databases PubMed, EMbase and PsycINFO were systematically searched until the 4th of December 2012 by using MeSH and free text terms. Additionally, reference lists of retrieved publications and treatment guidelines were reviewed, and experts were consulted. Inclusion criteria were: depression had to be measured at least twice during the study with qualified instruments and the chronic somatic illness had to be assessed by self-report or by a medical professional. Information on depressive recurrence was extracted and additionally risk ratios of recurrence were calculated.ResultsThe search generated four articles that fulfilled our inclusion criteria. These studies showed no differences in recurrence over one- two- three- and 6.5 years of follow-up for a total of 2010 depressed patients of which 694 patients with a co-morbid chronic somatic illness versus 1316 patients without (Study 1: RR = 0.49, 95% CI, 0.17–1.41 at one year follow-up and RR = 1.37, 95% CI, 0.78–2.41 at two year follow-up; Study 2: RR = 0.94, 95% CI, 0.65–1.36 at two year follow-up; Study 3: RR = 1.15, 95% CI, 0.40–3.27 at one year follow-up; RR = 1.07, 95% CI, 0.48–2.42 at two year follow-up and RR = 0.99, 95% CI,0.55–1.77 at 6.5 years follow-up; Study 4: RR = 1.16, 95% CI, 0.86–1.57 at three year follow-up).ConclusionWe found no association between a heightened risk for depressive recurrence and co-morbid chronic somatic illnesses. There is a need for more longitudinal studies to justify the current specific treatment advice such as long-term pharmacological maintenance treatment for this presumed “double trouble” group.

A Novel Method of Laparoscopic Approach in A Giant Bladder Diverticulum With Renal Cell Carcinoma "Double Trouble" - Literature Review and Case Study

September 01 2015 Twins in African and Diaspora Cultures: Double Trouble, Twice Blessed Twins in African and Diaspora Cultures: Double Trouble, Twice Blessed Edited by Philip M.PeekBloomington: Indiana university Press, 2011. 366 pages, 36 b&w illustrations, 2 maps, index. $27.95 paper; $22.95 ebook Author and Article Information Online Issn: 1937-2108 Print Issn: 0001-9933 © 2015 by the Regents of the University of California.2015 African Arts (2015) 48 (3): 93–94. https://doi.org/10.1162/AFAR_r_00244 Cite Icon Cite Permissions Share Icon Share Facebook Twitter LinkedIn MailTo Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Search Site Citation Twins in African and Diaspora Cultures: Double Trouble, Twice Blessed. African Arts 2015; 48 (3): 93–94. doi: https://doi.org/10.1162/AFAR_r_00244 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsAfrican Arts Search Advanced Search This book's subtitle could well be—not intended, strictly speaking, as an homage to Claude Levi-Strauss—“twins are good to think.” The book's sixteen excellent essays are not so much about the lives of actual human twins, a subject that is only briefly discussed in a few chapters, but rather about African ideas concerning twins as they relate to broader conceptions of the cosmos, the social order, and humans’ place within it. In the introduction, editor Philip Peek reviews some prior literature on African twins, focusing mainly on twentieth century anthropological literature and more recent work. He (and later in the volume, Jan-Lodewijk Grootaers) discusses E.E. Evans Pritchard's writings on the Nuer, where twins are the symbolic equivalents to birds. Like snakes, mentioned in many of the essays, birds and twins straddle two worlds—earth and sky, human and spirit. Peek also notes the contribution of Victor Turner who, like many other social... You do not currently have access to this content.

G.P.82 ‘Double Trouble’: Diagnostic challenges in DMD in patients with an additional hereditary skeletal dysplasia

Dentists in Double Trouble: The (Un)Fairness of Punishing for the Same Mistake Twice

INTRODUCTION: Healthcare-associated infections (HAIs) contribute to mortality and morbidity in critical care units. The influence of the ongoing coronavirus disease (COVID-19) pandemic on the already existing silent pandemic of antimicrobial resistance, especially in a critical care setting in our experience, is discussed here in this perspective.MATERIALS AND METHODS: In our prospective single-centred study over three months (July to September 2020), 123 COVID-19-positive patients admitted in the medical and surgical intensive care units (ICUs) were enrolled after institutional ethical clearance and informed consent. Patient characteristics and risk factors for HAIs were studied using univariate analysis. Antimicrobial usage was monitored based on high-end antibiotic usage monitoring policy.RESULTS: Of 123 COVID-19 patients, 98 were mechanically ventilated and 47% (46/98) developed ventilator-associated pneumonia (VAP) with predominant strain of multidrug-resistant (MDR) Klebsiella pneumoniae. In patients with central line, 26% (10/38) developed central line-associated bloodstream infection (CLABSI) with coagulase-negative Staphylococcus. In catheterised patients, 51% (23/45) developed catheter-associated urinary tract infection (CAUTI) with predominant MDR K. pneumoniae and Acinetobacter baumannii complex. The significant risk factors for VAP were acute respiratory distress syndrome (ARDS), acute kidney injury, duration of mechanical ventilation, steroid therapy and longer ICU length of stay. Patients with CAUTI had diabetes and chronic kidney disease, were on steroids and had a longer ICU stay. Patients with CLABSI had more ARDS, had diabetes, were mechanically ventilated longer and had longer ICU stay. A 57%–84% increase in consumption of antibiotics was seen in our set-up with Azithromycin, Colistin, Meropenem and newer β-lactam/β-lactamase inhibitor combinations like Ceftazidime/Avibactam.CONCLUSION: HAIs in a critical setting with patients admitted with COVID-19 need special focus in terms of prevention and control. In our study, we highlight the incidence of VAP and a need to monitor these key quality indicators including antimicrobial prescription practices.

Objectives: Several studies have pointed at a co-occurrence between severe mental problems and relative poverty. Also users refer to their strained financial situation as one of their main problems. We lack knowledge about how persons ‒ still characterised in diagnostic manuals as having difficulty with their sense of reality and their ability to carry out goal-oriented actions ‒ manage the ‘double trouble’ of having a strained financial situation and mental problems.Method: Sixteen persons diagnosed with severe mental illness were interviewed about how they managed poverty in their everyday life. The interviews were tape-recorded and analysed using the thematic analysis method.Results: The overarching theme that emerged was ‘managing a life on the margin’, with three sub-themes: ‘staying within limits’, ‘widening the boundaries’ and ‘indulging in the unnecessary’. The ways the interviewees coped with their strained financial situation are similar in many respects to those found in poverty research among people who do not have severe mental health problemsConclusions and implication for practice: Professionals should strive to take the individual’s social context into consideration, both when examining each person and in practicing share decision-making. Adopting a contextual approach would help us to see the user as an agent and better understand the onset and development of severe mental problems. Phenomena considered as symptoms might then be better understood as rational coping with the reality of poverty.

The aim of this study was to report a case of iridodialysis repair along with cataract extraction and iris claw lens implantation in a case of superior iridodialysis with subluxated cataractous lens following a blunt ocular trauma.