Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study

A set of cross-sectional surveys carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India reveal the prevalence and between-country variation in mild cognitive impairment at a population level

Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and -2 in different phases of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) can evolve in prematurely born infants who require mechanical ventilation because of hyaline membrane disease (HMD). The development of BPD can be divided in an acute, a regenerative, a transitional, and a chronic phase. During these different phases, extensive remodeling of the lung parenchyma with re-epithelialization of the alveoli and formation of fibrosis occurs. Matrix metalloproteinase-1 (MMP-1) is an enzyme that is involved in re-epithelialization processes, and dysregulation of MMP-1 activity contributes to fibrosis. Localization of MMP-1 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, were investigated in lung tissue obtained from infants who died during different phases of BPD development. In all studied cases (n = 50) type-II pneumocytes were found to be immunoreactive for MMP-1, TIMP-1, and TIMP-2. During the acute and regenerative phase of BPD, type-II pneumocytes re-epithelialize the injured alveoli. This may suggest that MMP-1 and its inhibitors, expressed by type-II pneumocytes, play a role in the re-epithelialization process after acute lung injury. Although MMP-1 staining intensity remained constant in type-II pneumocytes during BPD development, TIMP-1 increased during the chronic fibrotic phase. This relative elevation of TIMP-1 compared with MMP-1 is indicative for reduced collagenolytic activity by type-II pneumocytes in chronic BPD and may contribute to fibrosis. Fibrotic foci in chronic BPD contained fibroblasts immunoreactive for MMP-1 and TIMP-1 and -2. This may indicate that decreased collagen turnover by fibroblasts contributes to fibrosis in BPD development

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to examine the influence of the <it>catechol-O-methyltranferase (COMT) </it>gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the <it>apolipoprotein E gene (APOE)</it>.</p> <p>A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups.</p> <p>The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined <it>COMT </it>Val158 Met and <it>APOE </it>genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI.</p> <p>Results</p> <p>Neither <it>COMT </it>alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with <it>APOE ε4 </it>allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p < 0.001 and OR = 6.71, 95%CI 3.36-13.41, p < 0.001 respectivily). In AD patients this effect was greater in women.</p> <p>In MCI patients such as synergistic effect was only found between AG and <it>APOE ε4 </it>allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95%CI 1.69-20.42, p < 0.01).</p> <p>Conclusion</p> <p><it>COMT </it>(Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with <it>APOE ε4 </it>allele that proves greater in women with AD.</p

Growth and retreat of the last British–Irish Ice Sheet, 31 000 to 15 000 years ago: the BRITICE-CHRONO reconstruction

The BRITICE-CHRONO consortium of researchers undertook a dating programme to constrain the timing of advance, maximum extent and retreat of the British?Irish Ice Sheet between 31?000 and 15?000?years before present. The dating campaign across Ireland and Britain and their continental shelves, and across the North Sea included 1500?days of field investigation yielding 18?000?km of marine geophysical data, 377 cores of sea floor sediments, and geomorphological and stratigraphical information at 121 sites on land; generating 690 new geochronometric ages. These findings are reported in 28 publications including synthesis into eight transect reconstructions. Here we build ice sheet-wide reconstructions consistent with these findings and using retreat patterns and dates for the inter-transect areas. Two reconstructions are presented, a wholly empirical version and a version that combines modelling with the new empirical evidence. Palaeoglaciological maps of ice extent, thickness, velocity, and flow geometry at thousand-year timesteps are presented. The maximum ice volume of 1.8?m sea level equivalent occurred at 23?ka. A larger extent than previously defined is found and widespread advance of ice to the continental shelf break is confirmed during the last glacial. Asynchrony occurred in the timing of maximum extent and onset of retreat, ranging from 30 to 22?ka. The tipping point of deglaciation at 22?ka was triggered by ice stream retreat and saddle collapses. Analysis of retreat rates leads us to accept our hypothesis that the marine-influenced sectors collapsed rapidly. First order controls on ice-sheet demise were glacio-isostatic loading triggering retreat of marine sectors, aided by glaciological instabilities and then climate warming finished off the smaller, terrestrial ice sheet. Overprinted on this signal were second order controls arising from variations in trough topographies and with sector-scale ice geometric readjustments arising from dispositions in the geography of the landscape. These second order controls produced a stepped deglaciation. The retreat of the British?Irish Ice Sheet is now the world?s most well-constrained and a valuable data-rich environment for improving ice-sheet modelling

The structure and function of Alzheimer's gamma secretase enzyme complex

The production and accumulation of the beta amyloid protein (Aβ) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer’s disease (AD). A multi-subunit enzyme complex, referred to as gamma (γ) secretase, plays a pivotal role in the generation of Aβ from its parent molecule, the amyloid precursor protein (APP). Four core components (presenilin, nicastrin, aph-1, and pen-2) interact in a high-molecular-weight complex to perform intramembrane proteolysis on a number of membrane-bound proteins, including APP and Notch. Inhibitors and modulators of this enzyme have been assessed for their therapeutic benefit in AD. However, although these agents reduce Aβ levels, the majority have been shown to have severe side effects in pre-clinical animal studies, most likely due to the enzymes role in processing other proteins involved in normal cellular function. Current research is directed at understanding this enzyme and, in particular, at elucidating the roles that each of the core proteins plays in its function. In addition, a number of interacting proteins that are not components of γ-secretase also appear to play important roles in modulating enzyme activity. This review will discuss the structural and functional complexity of the γ-secretase enzyme and the effects of inhibiting its activity

Probability of Major Depression Classification Based on the SCID, CIDI and MINI Diagnostic Interviews : A Synthesis of Three Individual Participant Data Meta-Analyses

Three previous individual participant data meta-analyses (IPDMAs) reported that, compared to the Structured Clinical Interview for the DSM (SCID), alternative reference standards, primarily the Composite International Diagnostic Interview (CIDI) and the Mini International Neuropsychiatric Interview (MINI), tended to misclassify major depression status, when controlling for depression symptom severity. However, there was an important lack of precision in the results.To compare the odds of the major depression classification based on the SCID, CIDI, and MINI.We included and standardized data from 3 IPDMA databases. For each IPDMA, separately, we fitted binomial generalized linear mixed models to compare the adjusted odds ratios (aORs) of major depression classification, controlling for symptom severity and characteristics of participants, and the interaction between interview and symptom severity. Next, we synthesized results using a DerSimonian-Laird random-effects meta-analysis.In total, 69,405 participants (7,574 [11%] with major depression) from 212 studies were included. Controlling for symptom severity and participant characteristics, the MINI (74 studies; 25,749 participants) classified major depression more often than the SCID (108 studies; 21,953 participants; aOR 1.46; 95% confidence interval [CI] 1.11-1.92]). Classification odds for the CIDI (30 studies; 21,703 participants) and the SCID did not differ overall (aOR 1.19; 95% CI 0.79-1.75); however, as screening scores increased, the aOR increased less for the CIDI than the SCID (interaction aOR 0.64; 95% CI 0.52-0.80).Compared to the SCID, the MINI classified major depression more often. The odds of the depression classification with the CIDI increased less as symptom levels increased. Interpretation of research that uses diagnostic interviews to classify depression should consider the interview characteristics

Emergency Management of Gallbladder Disease: Are Acute Surgical Units the New Gold Standard?

Introduction Since 2011, all acute general surgical admissions have been managed by the consultant-led emergency general surgery service (EGS) at our institution. We aim to compare EGS management of acute biliary disease to its preceding model. Materials and methods Retrospective review of prospectively collated databases was performed to capture consecutive emergency admissions with biliary disease from 1st February 2009 to 31st January 2013. Patient demographics, surgical intervention, use of diagnostic radiology, histological diagnosis, complications and hospital length of stay (LOS) were retrieved. Results A total of 566 patients were included (pre-EGS 254 vs. EGS 312). In the EGS period, the number of patients having surgery on index admission increased from 43.7 to 58.7 % (p 1) imaging modalities for diagnosis was noted (p = 0.003). There was a positive trend in reduction of bile leaks but no significant difference in the overall morbidity and mortality. Time to theatre was reduced by 1 day [pre-EGS 2.7 (IQR 1.5–5.0) vs. EGS 1.7 (IQR 1.2–2.6) p < 0.001]. The overall hospital LOS was reduced by 1.5 days [pre-EGS 5.0 (IQR 3–7) vs. EGS 3.5 (IQR 2–5) p < 0.001]. Conclusion Since the advent of EGS, more judicious use of diagnostic radiology, reduced complications, reduced LOS, reduced time to theatre and an increased rate of definitive management during the index admission were demonstrated