342 research outputs found

    Diagnostic criteria for bipolarity based on an international sample of 5,635 patients with DSM-IV major depressive episodes

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    To assess the clinical validity of individual DSM-IV criteria for hypomania. In an international sample of 5,635 patients with major depressive episodes (Bridge Study), DSM-IV criteria for hypomania (stem questions, number and quality of symptoms, duration and exclusion criteria) were systematically assessed and their validity analysed on the basis of clinical data including family history, course, and other clinical characteristics. Three stem questions for hypomania, irritability, elevated mood and the added question of increased activity, showed comparable validity. The results support the current DSM-IV requirement for a higher symptom threshold (4 of 7 hypomanic symptoms) in cases of irritable mood. Longer durations of hypomanic episodes were associated with higher scores on all validators. The results did not support the DSM-IV durational requirements for hypomanic episodes (4days) and manic episodes (7days). Brief hypomanic episodes of 1, 2 or 3days were valid and would meet validity criteria for inclusion. The three exclusion criteria in DSM-IV (hypomania due to the use of antidepressants or of other substances, or to other medical conditions) were found to exclude patients with bipolar depression and should therefore not be retained. These results support several revisions of the DSM-IV concept of hypomanic episodes: specifically, the inclusion of increased activity as a gate question, the inclusion of 1 or 2 to 3-day episodes and the elimination of all exclusion criteri

    In silicoAnalysis of the Structural Properties of PSMA and its Energetic Relationship with Zn as Cofactor

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    The prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane glycoprotein with enzymatic activity similar to the family of zinc-dependent exopeptidases. This protein is of great medical and pharmacological interest as overexpression in prostate cells is related to the progression of prostate cancer; therefore, it represents an important target for the design of radiopharmaceuticals. The presence of two Zn2+ ions in the active site is crucial to the enzymatic activity and the design of high-affinity inhibitors. The amino acid residues coordinating these ions are highly conserved in PSMA orthologs from plants to mammals, and site-mutagenesis assays of these residues show a loss of enzymatic function or reduction of the kinetic parameters. In the present work, we performed molecular dynamics simulation of PSMA with the purpose of characterizing it energetically and structurally. We elucidated the differences of PSMA with its two Zn+2 ions as cofactors and without them in the free energy profile, and in four structural parameters: root mean square deviations and root mean square fluctuations by atom and amino acid residue, radius of gyration, and solvent accessible surface area

    Luxación recidivante de prótesis total de cadera

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    Más del 50% de los casos de caderas inestables se pueden resolver mediante la reducción cerrada de la luxación. Un intento sistemático para entender la causa de la inestabilidad, normalmente suele conducir a un tratamiento eficaz del problema cuando hace falta cirugía. Los componentes constreñidos o de retención han mejorado las posibilidades de resolver los problemas difíciles de inestabilidad, pero los efectos negativos potenciales de estos componentes deben tenerse también en cuenta. Los implantes tripolares, cuyos resultados clínicos en la literatura son muy alentadores, ocupan un lugar de elección en el arsenal terapéutico de la inestabilidad protética

    Thinning of the Monte Perdido Glacier in the Spanish Pyrenees since 1981

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    This paper analyzes the evolution of the Monte Perdido Glacier, the third largest glacier in the Pyrenees, from 1981 to the present. We assessed the evolution of the glacier''s surface area by analysis of aerial photographs from 1981, 1999, and 2006, and changes in ice volume by geodetic methods with digital elevation models (DEMs) generated from topographic maps (1981 and 1999), airborne lidar (2010) and terrestrial laser scanning (TLS, 2011, 2012, 2013, and 2014) data. We interpreted the changes in the glacier based on climate data from nearby meteorological stations. The results indicate that the degradation of this glacier accelerated after 1999. The rate of ice surface loss was almost three times greater during 1999-2006 than during earlier periods. Moreover, the rate of glacier thinning was 1.85 times faster during 1999-2010 (rate of surface elevation change = -8.98 ± 1.80 m, glacier-wide mass balance = -0.73 ± 0.14 m w.e. yr-1) than during 1981-1999 (rate of surface elevation change = -8.35 ± 2.12 m, glacier-wide mass balance = -0.42 ± 0.10 m w.e. yr-1). From 2011 to 2014, ice thinning continued at a slower rate (rate of surface elevation change = -1.93 ± 0.4 m yr-1, glacier-wide mass balance = -0.58 ± 0.36 m w.e. yr-1). This deceleration in ice thinning compared to the previous 17 years can be attributed, at least in part, to two consecutive anomalously wet winters and cool summers (2012-2013 and 2013-2014), counteracted to some degree by the intense thinning that occurred during the dry and warm 2011-2012 period. However, local climatic changes observed during the study period do not seem sufficient to explain the acceleration of ice thinning of this glacier, because precipitation and air temperature did not exhibit statistically significant trends during the study period. Rather, the accelerated degradation of this glacier in recent years can be explained by a strong disequilibrium between the glacier and the current climate, and likely by other factors affecting the energy balance (e.g., increased albedo in spring) and feedback mechanisms (e.g., heat emitted from recently exposed bedrock and debris covered areas)

    Time lost due to an attack: a novel patient-reported outcome measure for acute migraine treatments

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    Objective We propose a new outcome measure to assess the efficacy of migraine treatments translating the approach of the Global Burden of Disease studies from a societal to an individual level: Instead of calculating "years lived with disability", we suggest estimating "time lost due to an attack".MethodsTime lost due to an attack is calculated by multiplying the duration and the degree of impaired functioning during an attack.ResultsTime lost due to an attack, different from other outcome measures, does not just focus on the short-term analgesic effects of treatments, but rather on the improvement of all migraine symptoms and restoration of functioning, also considering therapy-related impairment. Importantly, time lost due to an attack measures the entire time patients are not functioning normally, from onset to complete resolution.ConclusionsTime lost due to an attack represents a new paradigm to assess migraine burden in single patients for a patient-centered evaluation of both acute and prophylactic treatments.Paroxysmal Cerebral Disorder

    Evidence-based definitions of bipolar-I and bipolar-II disorders among 5,635 patients with major depressive episodes in the Bridge Study: validity and comorbidity

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    The definitions of bipolar-I (BP-I) and bipolar-II (BP-II) disorders are currently under revision by the APA and by the WHO. We provide evidence of a revised set of criteria for bipolar disorders and major depressive disorder (MDD) which could serve to strengthen the construct and predictive validity of both disorders and enable more incisive studies of treatments and courses of both disorders. In the diagnostic Bridge Study of 5,635 patients with major depressive episodes from 18 countries (Europe, North Africa, Near East and Far East) leading psychiatrists in each country assessed a pre-specified group of symptoms, illness course, family history and duration of episodes; these data allowed tests of several definitions of bipolarity. The primary revised specifier diagnosis of BP-I disorder included manic episodes based on an additional category A criterion (increased activity/energy) and did not apply any exclusion criteria. The revised BP-II disorders included hypomanic episodes of 1-3days. Family history and illness course validators (history of mania/hypomania among first degree relatives, 2 or more lifetime episodes and first symptoms having occurred before age 30) discriminated clearly between patients with bipolar-I or bipolar-II disorders meeting bipolarity specifier criteria and those with MDD. Specifier definitions provided better discrimination between MDD and the two bipolar subgroups. Patterns of concurrent comorbidities also differed significantly between patients meeting criteria for MDD compared with those meeting bipolar specifier criteria. Comorbidity patterns differed between bipolar-I and bipolar-II patients. This study provides evidence for the validity of modified (specifier) BP-I and BP-II definitions that incorporate illness course and family history which reduce ambiguities of major depressive episodes between bipolar-I and bipolar-II disorders and MD

    Wind speed variability over the Canary Islands, 1948-2014: focusing on trend differences at the land-ocean interface and below-above the trade-wind inversion layer

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    This study simultaneously examines wind speed trends at the land?ocean interface, and below?above the trade-wind inversion layer in the Canary Islands and the surrounding Eastern North Atlantic Ocean: a key region for quantifying the variability of trade-winds and its response to large-scale atmospheric circulation changes. Two homogenized data sources are used: (1) observed wind speed from nine land-based stations (1981?2014), including one mountain weather station (Izaña) located above the trade-wind inversion layer; and (2) simulated wind speed from two atmospheric hindcasts over ocean (i.e., SeaWind I at 30 km for 1948?2014; and SeaWind II at 15 km for 1989?2014). The results revealed a widespread significant negative trend of trade-winds over ocean for 1948?2014, whereas no significant trends were detected for 1989?2014. For this recent period wind speed over land and ocean displayed the same multi-decadal variability and a distinct seasonal trend pattern with a strengthening (late spring and summer; significant in May and August) and weakening (winter?spring?autumn; significant in April and September) of trade-winds. Above the inversion layer at Izaña, we found a predominance of significant positive trends, indicating a decoupled variability and opposite wind speed trends when compared to those reported in boundary layer. The analysis of the Trade Wind Index (TWI), the North Atlantic Oscillation Index (NAOI) and the Eastern Atlantic Index (EAI) demonstrated significant correlations with the wind speed variability, revealing that the correlation patterns of the three indices showed a spatio-temporal complementarity in shaping wind speed trends across the Eastern North Atlantic.C. A. -M. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 703733 (STILLING project). This research was also supported by the Research Projects: Swedish BECC, MERGE, VR (2014–5320), PCIN-2015-220, CGL2014-52135-C03-01 and Red de variabilidad y cambio climático RECLIM (CGL2014-517221-REDT). M.M is indebted to the Spanish Government for funding through the “Ramón y Cajal” program and supported by Grant PORTIO (BIA2015-70644-R

    Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study

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    Introduction: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. Methods: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as “poor” (κ ≤ 0.4), “moderate” or “good” (κ > 0.6). Results: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. Conclusion: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust

    Use of mixed methods designs in substance research: a methodological necessity in Nigeria

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    The utility of mixed methods (qualitative and quantitative) is becoming increasingly accepted in health sciences, but substance studies are yet to substantially benefit from such utilities. While there is a growing number of mixed methods alcohol articles concerning developed countries, developing nations are yet to embrace this method. In the Nigerian context, the importance of mixed methods research is yet to be acknowledged. This article therefore, draws on alcohol studies to argue that mixed methods designs will better equip scholars to understand, explore, describe and explain why alcohol consumption and its related problems are increasing in Nigeria. It argues that as motives for consuming alcohol in contemporary Nigeria are multiple, complex and evolving, mixed method approaches that provide multiple pathways for proffering solutions to problems should be embraced
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