Beyond BMI: The “Metabolically healthy obese” phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality -- a systematic review

Background A subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population. Methods Pubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or subclinical CVD. Results A total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define “metabolically healthy”, while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study (14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts. Conclusions MHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.

Do Social Crises Cause Religious Revivals? What British Church Adherence Rates Show

Funding Some of author A’s research alluded to here was conducted while on a Leverhulme Senior Research Fellowship. Author B’s research is supported by the ESRC Research Centre XXX.

Condensation versus air density change as a major cause of airflow: experimental evidence, link to data files and videos

The dominant model of atmospheric circulation posits that hot air rises, creating horizontal winds. A second major driver has recently been proposed by Makarieva and Gorshkov in their biotic pump theory (BPT), which suggests that evapotranspiration from natural closed-canopy forests causes intense condensation, and hence winds from ocean to land. Critics of the BPT argue that air movement to fill the partial vacuum caused by condensation is always isotropic, and therefore causes no net air movement (Bunyard, 2015, hdl:11232/397). This paper explores the physics of water condensation under mild atmospheric conditions, within a purpose-designed square-section 4.8 m-tall closed-system structure. Two enclosed vertical columns are connected at top and bottom by two horizontal tunnels, around which 19.5 m**3 of atmospheric air can circulate freely, allowing rotary airflows in either direction. This air can be cooled and/or warmed by refrigeration pipes and a heating mat, and changes in airflow, temperature, humidity and barometric pressure measured in real time. The study investigates whether the "hot-air-rises" or an implosive condensation model can better explain the results of more than 100 experiments. The data show a highly significant correlation (R2 >0.96, p value <0.001) between observed airflows and partial pressure changes from condensation. While the kinetic energy of the refrigerated air falls short of that required in bringing about observed airflows by a factor of at least 30, less than a tenth of the potential kinetic energy from condensation is shown to be sufficient. The assumption that condensation of water vapour is always isotropic is therefore incorrect. Condensation can be anisotropic, and in the laboratory does cause sustained airflow.

Mandibular Torus : A Synthesis of New and Previously Reported Data and a Discusssion of its Cause

Using original data on 1,5000 mandibles, but mainly previously published data, I present a overview of the distribution characteristics of mandibular torus and a hypothesis concerning its cause. Pedigree studies have established that genetic factors influence torus development. Extrinsic factors are strongly implicated by other evidence: prevalence among Arctic peoples, effect of dietary change, age regression, preponderance in males and on the right side, effect of cranial deformation, concurrence with palatine torus and maxillary alveolar exostoses, and clinical evidence. I propose that the primary factor is masticatory stress. According to a mechanism suggested by orthodontic research, the horizontal component of bite force tips the lower canine, premolars and first molar so that their root apices exert pressure on the periodontal membrane, causing formation of new bone on the lingual cortical plate of the alveolar process. Thus formed, the hyperostosis is vulnerable to trauma and its periosteal covering becomes bruised causing additional deposition of bone. Genes influence torus indirectly through their effect on occlusion. A patern of increased expressivity with incidence suggests that a quasicontinuous model may provide a better fit to pedigree data than single locus models previously tested.

Presence and possible cause of periodicities in 20th-century extreme coastal surge: Belfast Harbour, Northern Ireland.

Identifying 20th-century periodic coastal surge variation is strategic for the 21st-century coastal surge estimates, as surge periodicities may amplify/reduce future MSL enhanced surge forecasts. Extreme coastal surge data from Belfast Harbour (UK) tide gauges are available for 1901–2010 and provide the potential for decadal-plus periodic coastal surge analysis. Annual extreme surge-elevation distributions (sampled every 10-min) are analysed using PCA and cluster analysis to decompose variation within- and between-years to assess similarity of years in terms of Surge Climate Types, and to establish significance of any transitions in Type occurrence over time using non-parametric Markov analysis. Annual extreme surge variation is shown to be periodically organised across the 20th century. Extreme surge magnitude and distribution show a number of significant cyclonic induced multi-annual (2, 3, 5 & 6 years) cycles, as well as dominant multi-decadal (15–25 years) cycles of variation superimposed on an 80 year fluctuation in atmospheric–oceanic variation across the North Atlantic (relative to NAO/AMO interaction). The top 30 extreme surge events show some relationship with NAO per se, given that 80% are associated with westerly dominant atmospheric flows (+ NAO), but there are 20% of the events associated with blocking air massess (− NAO). Although 20% of the top 30 ranked positive surges occurred within the last twenty years, there is no unequivocal evidence of recent acceleration in extreme surge magnitude related to other than the scale of natural periodic variation.

A Rare Cause of Myoclonus: A Cupric Conundrum

A woman aged 22 years presented with a 3-year history of jerks when brushing her teeth and a tremor when carrying drinks. Examination revealed a bilateral jerky tremor, stimulus-sensitive myoclonus, and difficulty with tandem gait. Thyroid and liver function test results were normal, but she had rapidly progressive renal failure. Serum copper, ceruloplasmin, and manganese levels were normal, but her urinary copper level was elevated on 2 occasions. Pathological findings on organ biopsy prompted genetic testing to confirm the diagnosis. The differential diagnosis, tissue biopsy findings, and final genetic diagnosis are discussed.

Assessing trends in land use change in the Borana rangeland Ethiopia as one cause of greenhouse gas emissions and carbon sequestration variations

Landnutzungsänderungen sind eine wesentliche Ursache von Treibhausgasemissionen. Die Umwandlung von Ökosystemen mit permanenter natürlicher Vegetation hin zu Ackerbau mit zeitweise vegetationslosem Boden (z.B. nach der Bodenbearbeitung vor der Aussaat) führt häufig zu gesteigerten Treibhausgasemissionen und verminderter Kohlenstoffbindung. Weltweit dehnt sich Ackerbau sowohl in kleinbäuerlichen als auch in agro-industriellen Systemen aus, häufig in benachbarte semiaride bis subhumide Rangeland Ökosysteme. Die vorliegende Arbeit untersucht Trends der Landnutzungsänderung im Borana Rangeland Südäthiopiens. Bevölkerungswachstum, Landprivatisierung und damit einhergehende Einzäunung, veränderte Landnutzungspolitik und zunehmende Klimavariabilität führen zu raschen Veränderungen der traditionell auf Tierhaltung basierten, pastoralen Systeme. Mittels einer Literaturanalyse von Fallstudien in ostafrikanischen Rangelands wurde im Rahmen dieser Studie ein schematisches Modell der Zusammenhänge von Landnutzung, Treibhausgasemissionen und Kohlenstofffixierung entwickelt. Anhand von Satellitendaten und Daten aus Haushaltsbefragungen wurden Art und Umfang von Landnutzungsänderungen und Vegetationsveränderungen an fünf Untersuchungsstandorten (Darito/Yabelo Distrikt, Soda, Samaro, Haralo, Did Mega/alle Dire Distrikt) zwischen 1985 und 2011 analysiert. In Darito dehnte sich die Ackerbaufläche um 12% aus, überwiegend auf Kosten von Buschland. An den übrigen Standorten blieb die Ackerbaufläche relativ konstant, jedoch nahm Graslandvegetation um zwischen 16 und 28% zu, während Buschland um zwischen 23 und 31% abnahm. Lediglich am Standort Haralo nahm auch „bare land“, vegetationslose Flächen, um 13% zu. Faktoren, die zur Ausdehnung des Ackerbaus führen, wurden am Standort Darito detaillierter untersucht. GPS Daten und anbaugeschichtlichen Daten von 108 Feldern auf 54 Betrieben wurden in einem Geographischen Informationssystem (GIS) mit thematischen Boden-, Niederschlags-, und Hangneigungskarten sowie einem Digitales Höhenmodell überlagert. Multiple lineare Regression ermittelte Hangneigung und geographische Höhe als signifikante Erklärungsvariablen für die Ausdehnung von Ackerbau in niedrigere Lagen. Bodenart, Entfernung zum saisonalen Flusslauf und Niederschlag waren hingegen nicht signifikant. Das niedrige Bestimmtheitsmaß (R²=0,154) weist darauf hin, dass es weitere, hier nicht erfasste Erklärungsvariablen für die Richtung der räumlichen Ausweitung von Ackerland gibt. Streudiagramme zu Ackergröße und Anbaujahren in Relation zu geographischer Höhe zeigen seit dem Jahr 2000 eine Ausdehnung des Ackerbaus in Lagen unter 1620 müNN und eine Zunahme der Schlaggröße (>3ha). Die Analyse der phänologischen Entwicklung von Feldfrüchten im Jahresverlauf in Kombination mit Niederschlagsdaten und normalized difference vegetation index (NDVI) Zeitreihendaten dienten dazu, Zeitpunkte besonders hoher (Begrünung vor der Ernte) oder niedriger (nach der Bodenbearbeitung) Pflanzenbiomasse auf Ackerland zu identifizieren, um Ackerland und seine Ausdehnung von anderen Vegetationsformen fernerkundlich unterscheiden zu können. Anhand der NDVI Spektralprofile konnte Ackerland gut Wald, jedoch weniger gut von Gras- und Buschland unterschieden werden. Die geringe Auflösung (250m) der Moderate Resolution Imaging Spectroradiometer (MODIS) NDVI Daten führte zu einem Mixed Pixel Effect, d.h. die Fläche eines Pixels beinhaltete häufig verschiedene Vegetationsformen in unterschiedlichen Anteilen, was deren Unterscheidung beeinträchtigte. Für die Entwicklung eines Echtzeit Monitoring Systems für die Ausdehnung des Ackerbaus wären höher auflösende NDVI Daten (z.B. Multispektralband, Hyperion EO-1 Sensor) notwendig, um kleinräumig eine bessere Differenzierung von Ackerland und natürlicher Rangeland-Vegetation zu erhalten. Die Entwicklung und der Einsatz solcher Methoden als Entscheidungshilfen für Land- und Ressourcennutzungsplanung könnte dazu beitragen, Produktions- und Entwicklungsziele der Borana Landnutzer mit nationalen Anstrengungen zur Eindämmung des Klimawandels durch Steigerung der Kohlenstofffixierung in Rangelands in Einklang zu bringen.

Étude de la toxicité causée par le gène C9orf72 dans la Sclérose Latérale Amyotrophique

La Sclérose Latérale Amyotrophique (SLA) est une maladie neurodégénérative qui affecte les neurones moteurs. 10% des cas sont des cas familiaux et l’étude de ces familles a mené à la découverte de plusieurs gènes pouvant causer la SLA, incluant SOD1, TARDBP et FUS. L’expansion de la répétition GGGGCC dans le gène C9orf72 est, à ce jour, la cause la plus connue de SLA. L’impact de cette expansion est encore méconnu et il reste à déterminer si la toxicité est causée par un gain de fonction, une perte de fonction ou les deux. Plusieurs gènes impliqués dans la SLA sont conservés entre le nématode Caenorhabditis elegans et l’humain. C. elegans est un vers transparent fréquemment utilisé pour des études anatomiques, comportementales et génétiques. Il possède une lignée cellulaire invariable qui inclue 302 neurones. Aussi, les mécanismes de réponse au stress ainsi que les mécanismes de vieillissement sont très bien conservés entre ce nématode et l’humain. Donc, notre groupe, et plusieurs autres, ont utilisé C. elegans pour étudier plusieurs aspects de la SLA. Pour mieux comprendre la toxicité causée par l’expansion GGGGCC de C9orf72, nous avons développé deux modèles de vers pour étudier l’impact d’une perte de fonction ainsi que d’un gain de toxicité de l’ARN. Pour voir les conséquences d’une perte de fonction, nous avons étudié l’orthologue de C9orf72 dans C. elegans, alfa-1 (ALS/FTD associated gene homolog). Les vers mutants alfa-1(ok3062) développent des problèmes moteurs causant une paralysie et une dégénérescence spécifique des neurones moteurs GABAergiques. De plus, les mutants sont sensibles au stress osmotique qui provoque une dégénérescence. D’autre part, l’expression de la séquence d’ARN contenant une répétition pathogénique GGGGCC cause aussi des problèmes moteurs et de la dégénérescence affectant les neurones moteurs. Nos résultats suggèrent donc qu’un gain de toxicité de l’ARN ainsi qu’une perte de fonction de C9orf72 sont donc toxiques pour les neurones. Puisque le mouvement du vers peut être rapidement évalué en cultivant les vers dans un milieu liquide, nous avons développé un criblage de molécules pouvant affecter le mouvement des vers mutants alfa-1 en culture liquide. Plus de 4 000 composés ont été évalués et 80 ameliore la mobilité des vers alfa-1. Onze molécules ont aussi été testées dans les vers exprimant l’expansion GGGGCC et huit diminuent aussi le phénotype moteur de ces vers. Finalement, des huit molécules qui diminent la toxicité causée par la perte de fonction de C9orf72 et la toxicité de l’ARN, deux restaurent aussi l’expression anormale de plusieurs transcrits d’ARN observée dans des cellules dérivées de patient C9orf72. Avec ce projet, nous voulons identifier des molécules pouvant affecter tous les modes de toxicité de C9orf72 et possiblement ouvrir de nouvelles avenues thérapeutiques

Mutations in CTC1, Encoding Conserved Telomere Maintenance Component 1, Cause Coats Plus

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.

Brooke-Spiegler Syndrome - an underrecognized cause of multiple familial scalp tumors: report of a new germline mutation

BACKGROUND: Brooke-Spiegler syndrome (BSS) is probably an underdiagnosed genodermatosis that predisposes for the development of cylindromas, spiradenomas and trichoepitheliomas mainly of the head and neck. Wide phenotypic variability regarding the number and type of lesions can be observed within a family. Mutations of the CYLD gene are identified in the vast majority of cases and play a key role in BSS pathogenesis. MAIN OBSERVATIONS: Two first degree relatives with numerous erythematous telangiectatic nodules of the scalp present for decades, with recurring tendency regardless the multiple previous excisions. Histopathological review of the lesions revealed predominantly "spiradenocylindromas" in the proband and cylindromas in her sister. The suspicion of BSS was confirmed after detection of a new nonsense germline mutation of CYLD (c.1783C>T pGln 595*) in the proband. CONCLUSIONS: BSS diagnosis can be challenging and is based on clinical-pathological correlation, positive familial association and identification of CYLD mutations. CYLD exerts antineoplastic effects by downregulating intracellular NF-κB signalling pathways. The reported mutation affecting the ubiquitin-specific protease domain leads to a truncated and catalytically inactive enzyme. Despite the expanding list of CYLD mutations no firm genotype-phenotype correlation is known so far. Early recognition and treatment of BSS avoid disfiguring changes like "turban tumor".

Les représentations de la femme dans le discours religieux du XIIIe au XVe siècle : une cause de la chasse aux sorcières?

[…] Le regard que nous porterons sur le discours religieux et ses représentations de la femme nous permettra de déterminer quel rôle il a joué dans la conception de la femme comme symbole et source du mal dans la société du temps et, par le fait même, dans le phénomène de la chasse aux sorcières. Comme nous le verrons, plusieurs causes peuvent être attribuées à ce phénomène, causes d'autant plus déterminantes que le discours religieux sur les femmes vient les renforcer. La démarche d'exposition de la problématique se déploiera dans quatre chapitres. Le premier chapitre nous permettra de dégager les sources d'influence des représentations de la femme dans le discours religieux du XIIIe au XVe siècle. Nous tenterons de démontrer que les théologiens médiévaux ont puisé dans ces sources, des citations virulentes qu'ils ont utilisées hors de leur visée contextuelle afin d'appuyer par des autorités reconnues leur thèse d'une nature inférieure chez la femme et de démontrer sans conteste qu'elle est un être destiné au mal. Avec le chapitre deux nous poserons notre regard sur le discours religieux; soit le discours théologique et les sermons populaires sur la femme à l'époque en cause. Nous découvrirons, qu'il révélé ses sources d'influence, et de surcroît qu'il reflète plus que jamais auparavant une profonde misogynie. La femme est désormais, et cela sans l'ombre d'un doute, l'incarnation du mal. Au chapitre trois, nous tenterons de démontrer quelle influence a eu ce discours, particulièrement les sermons populaires, dans l'intégration sociale des représentations de la femme. Comme nous le verrons, cette société a elle aussi participé à décrier la femme, à faire d'elle un être destiné au mal. Le dernier chapitre, le quatrième, vise à déterminer quel rôle a joué le discours religieux dans le phénomène de la chasse aux sorcières du XIIIe au XVe siècle. Cela en tenant compte d'un ensemble de facteurs, tous plus plausibles les uns que les autres. Certes, il nous faut remplir notre engagement. Pour ce faire, il nous faut surtout éviter de tomber dans la tentation de l'anachronisme, c'est-à-dire, de juger une Église, une société, une culture au nom d'une autre, à partir de la nôtre. Cet écueil nous estimons l'avoir évité. Certes, notre intérêt pour la promotion des femmes nous a guidé dans le choix de notre sujet, mais dans l'analyse de nos sources nous avons privilégié l'impartialité.

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015 : a systematic analysis for the Global Burden of Disease Study 2015

Arterial entrapment syndrome in the cubital fossa: a rare cause of acute stress-related arterial thrombosis in a patient with brachial artery duplication

Arterial entrapment syndrome (AES) at elbow level is very rare and to our knowledge no case of AES by lacertus fibrosus in the cubital fossa in presence of brachial artery duplication has been described to date. We describe a rare case of acute arterial thrombosis of one of two brachial arteries highlighted in the cubital fossa which developed after strenuous right elbow flexor muscle activity and hyper-extensions presumably related to AES by lacertus fibrosus at elbow level. A 43-year-old right-handed woman, experienced paleness, coldness and numbness of the right hand, after 8 consecutive hours of gardening. As she worked, her ipsilateral flexor elbow muscles remained in prolonged and inappropriate tension. Clinical examination evidenced the absence of radial artery pulse in the wrist and mild hypothermia in the second and third finger. During surgical exploration two anastomosed brachial arteries were detected in the cubital fossa under the lacertus fibrosus. The lateral superficial brachial artery was occluded. Intraoperative arteriography evidenced brachial artery duplication at the third superior of the arm and normal vascular pattern at the forearm level. In cases of unexplained atypical intermittent upper extremity claudication or acute ischemic symptoms an AES should always be ruled out, particularly when symptoms are exacerbated by strenuous upper extremity activity or when upper limb muscular hypertrophy is evident. In these cases a thorough dynamic clinical and instrumental examination is mandatory to confirm a diagnosis of AES and to avoid possible future ischemic complications.