bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of primary ciliary dyskinesia in European children: recommendations and clinical practice
Authors: Strippoli Marie-Pierre F. , Frischer Thomas , Barbato Angelo , Snijders Deborah , Maurer Elisabeth , Lucas Jane S.A. , Eber Ernst , Karadag Bulent , Pohunek Petr , Zivkovic Zorica , Escribano Amparo , O’Callaghan Chris , Bush Andrew , Kuehni Claudia E.
Published: January 2012

The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe.

Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2–9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country’s general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments.

In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.
Pregnancy outcomes in pulmonary arterial hypertension in the modern management era
Authors: Jaïs Xavier , Olsson Karen M. , Barbera Joan A. , Blanco Isabel , Torbicki Adam , Peacock Andrew , Vizza C. Dario , Macdonald Peter , Humbert Marc , Hoeper Marius M.
Published: January 2012

Previous studies have reported mortality rates of up to 56% associated with pregnancy in pulmonary arterial hypertension (PAH) but the management of this disease has changed considerably in recent years.

We compiled a multinational, prospective registry to examine the contemporary outcome of pregnancies in patients with PAH.

During a 3-yr period, the 13 participating centres reported 26 pregnancies. Three (12%) females died and one (4%) developed right heart failure requiring urgent heart–lung transplantation. There were eight abortions; two spontaneous and six induced. 16 (62%) pregnancies were successful,i.e.the females delivered healthy babies without complications. These females had well controlled PAH (pulmonary vascular resistance (PVR) 500±352 dyn·s·cm−5); eight of them were long-term responders to calcium channel blockers. In contrast, the females who died or required transplantation had poorly controlled PAH (PVR 1,667±209 dyn·s·cm−5).

Pregnancy remains associated with a substantial mortality rate in PAH. However, our results indicate that the outcome of pregnancy in PAH has improved, at least when PAH is well controlled, and particularly in long-term responders to calcium channel blockers. These data must be confirmed by larger series before the general recommendation to avoid pregnancy in all patients with PAH is reconsidered.
The chronic bronchitis phenotype in subjects with and without COPD: the PLATINO study
Authors: de Oca Maria Montes , Halbert Ronald J. , Lopez Maria Victorina , Perez-Padilla Rogelio , Tálamo Carlos , Moreno Dolores , Muiño Adrianna , Jardim José Roberto B. , Valdivia Gonzalo , Pertuzé Julio , Menezes Ana Maria B.
Published: January 2012

Little information exists regarding the epidemiology of the chronic bronchitis phenotype in unselected chronic obstructive pulmonary disease (COPD) populations. We examined the prevalence of the chronic bronchitis phenotype in COPD and non-COPD subjects from the PLATINO study, and investigated how it is associated with important outcomes.

Post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70 was used to define COPD. Chronic bronchitis was defined as phlegm on most days, at least 3 months per year for ≥2 yrs. We also analysed another definition: cough and phlegm on most days, at least 3 months per year for ≥2 yrs.

Spirometry was performed in 5,314 subjects (759 with and 4,554 without COPD). The proportion of subjects with and without COPD with chronic bronchitis defined as phlegm on most days, at least 3 months per year for ≥2 yrs was 14.4 and 6.2%, respectively. Using the other definition the prevalence was lower: 7.4% with and 2.5% without COPD. Among subjects with COPD, those with chronic bronchitis had worse lung function and general health status, and had more respiratory symptoms, physical activity limitation and exacerbations.

Our study helps to understand the prevalence of the chronic bronchitis phenotype in an unselected COPD population at a particular time-point and suggests that chronic bronchitis in COPD is possibly associated with worse outcomes.
Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort
Authors: Herth Felix J.F. , Noppen Marc , Valipour Arschang , Leroy Sylvie , Vergnon Jean-Michel , Ficker Joachim H. , Egan Jim J. , Gasparini Stefano , Agusti Carlos , Holmes-Higgin Debby , Ernst Armin
Published: January 2012

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort.

Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr® (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n=111) or medical management (n=60).

At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean±sdchange in forced expiratory volume in 1 s (7±20%versus0.5±19%; p=0.067), cycle ergometry (2±14 Wversus-3±10 W; p=0.04) and St George’s Respiratory Questionnaire (-5±14 pointsversus0.3±13 points; p=0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean±sdlobar volume reduction of -80±30% and >50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes.

Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.
Randomised controlled trial for emphysema with a selective agonist of the γ-type retinoic acid receptor
Authors: Stolk Jan , Stockley Robert A. , Stoel Berend C. , Cooper Brendan G. , Piitulainen Eeva , Seersholm Niels , Chapman Kenneth R. , Burdon Jonathan G.W. , Decramer Marc , Abboud Raja T. , Mannes Gregorius P.M. , Wouters Emiel F. , Garrett Jeffrey E. , Barros-Tizon Juan C. , Russi Erich W. , Lomas David A. , MacNee William A. , Rames Alexis
Published: January 2012

Palovarotene is an oral γ-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement.

REPAIR (Retinoid treatment of Emphysema in Patients on the α1-antitrypsin International Registry), was an investigator-initiated, double-blind, placebo-controlled randomised study to assess the safety and efficacy of 5 mg·day−1palovarotene given for 1 year to 262 patients with severe α1-antitrypsin deficiency and emphysema confirmed by computed tomography. Change in volume-adjusted 15th percentile point lung density from baseline in 1 year was the primary end-point; functional end-points were also regularly assessed.

We randomly assigned 133 and 129 patients to placebo or palovarotene, respectively. Both groups were well matched for all baseline characteristics, including respiratory medications. 88% and 85% of patients completed 1 year of treatment with placebo and palovarotene, respectively. Palovarotene was generally well tolerated. In the study completers population, the placebo-corrected difference of lung density was -0.45 HU at week 28 (p=0.64) and -0.25 HU at week 52 (p=0.94). A nonsignificant treatment difference in most functional parameters of the lung in favour of the drug was observed over time suggesting potential pharmacological effects of palovarotene.

Palovarotene 5 mg·day−1over 1 yr failed to show a significant benefit on lung density in moderate-to-severe emphysema secondary to severe α1-antitrypsin deficiency.
Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy
Authors: Keir Gregory J. , Maher Toby M. , Hansell David M. , Denton Christopher P. , Ong Voon H. , Singh Suveer , Wells Athol U. , Renzoni Elisabetta A.
Published: January 2012

In very severe interstitial lung disease associated with connective tissue disease (CTD-ILD), progressing despite maximal conventional immunosuppression, there is no effective medical rescue therapy.

The aim of the present study was to test whether rituximab, a monoclonal antibody that depletes peripheral B lymphocytes, is effective as rescue therapy in very severe CTD-ILD, unresponsive to conventional immunosuppression.

We performed a retrospective assessment of eight patients with severe and progressive CTD-ILD treated with rituximab. In six patients, change in pulmonary function tests (PFTs) compared with pre-rituximab levels, was assessed at 9–12 months post-treatment. In two patients, who were mechanically ventilated at the time of treatment, clinical and HRCT changes were assessed.

Seven out of eight patients had a favourable treatment response to rituximab, while in one patient disease severity did not change. In contrast with previous progression, we observed a median significant improvement of 22% in diffusing capacity for carbon monoxide (from a median baseline of 25%; range 16–32%; p=0.04), and a median significant improvement of 18% in forced vital capacity (from a median baseline of 45%; range 37–59%; p=0.03), in the 9–12 months following treatment with rituximab.

In very severe CTD-ILD unresponsive to conventional immunosuppression, rituximab may represent an effective, potentially life-saving, therapeutic intervention.
Mesothelioma incidence projections in South East England
Authors: Riaz Sharma P. , Coupland Victoria H. , Lüchtenborg Margreet , Peake Michael D. , Møller Henrik
Published: January 2012

We estimated the past and future age-standardised incidence rates of mesothelioma by birth cohort and by period of diagnosis in South East England.

We extracted data on patients diagnosed with mesothelioma (International Classification of Diseases-10 C45) between 1960 and 2009 from the Thames Cancer Registry. We calculated the age-standardised incidence rates using the European standard population. We used age-cohort and age-period modelling to estimate the age-specific incidence rates for the 1900 to 1950 birth cohorts and the 1935 to 2034 calendar periods.

A much more pronounced increase in mesothelioma incidence between 1972 and 2007 was observed in males than in females. In both sexes, the incidence rates increased in successive generations up to the 1945 birth cohort. Projection of rates in the future showed an increase in incidence in males until 2022 and a decrease thereafter. Among females, the incidence rate was predicted to increase gradually until reaching its maximum around 2027, and to remain stable thereafter.

The occurrence of mesothelioma is closely linked to occupational exposure to asbestos in the 1960s and 1970s and, due to the long latency period, the incidence of mesothelioma is projected to increase until the 2020s.
Airways dilate to simulated inspiratory but not expiratory manoeuvres
Authors: West Adrian R. , Thaya Needi Elangovan , Mitchell Howard W. , McFawn Peter K. , Noble Peter B.
Published: January 2012

In a healthy human, deep inspirations produce bronchodilation of contracted airways, which probably occurs due to the transient distension of the airway smooth muscle (ASM). We hypothesised that deep expiratory manoeuvres also produce bronchodilation due to transient airway wall and ASM compression.

We used porcine bronchial segments to assess the effects of deep inspirations, and maximal and partial expiration (submaximal) on airway calibre. Respiratory manoeuvres were simulated by varying transmural pressure using a hydrostatic pressure column: deep inspiration 5 to 30 cmH2O, maximal expiration 30 to -15 cmH2O, partial expiration 10 to -15 cmH2O; amidst a background of tidal oscillations, 5 to 10 cmH2O at 0.25 Hz. Changes in luminal cross-sectional area in carbachol-contracted airways were measured using video endoscopy.

Deep inspirations produce an immediate bronchodilation (∼40–60%, p=0.0076) that lasts for up to 1 min (p=0.0479). In comparison, after maximal expiration there was no immediate change in airway calibre; however, a delayed bronchodilatory response was observed from 4 s after the manoeuvre (p=0.0059) and persisted for up to 3 min (p=0.0182). Partial expiration had little or no effect or airway calibre.

The results observed demonstrate that the airway wall dilates to deep inspiration manoeuvres but is unresponsive to deep expiratory manoeuvres.
Long-term efficacy of psychological treatments for binge eating disorder
Authors: Hilbert Anja , Bishop Monica E. , Stein Richard I. , Tanofsky-Kraff Marian , Swenson Anne K. , Welch R. Robinson , Wilfley Denise E.
Published: January 2012

Background

The long-term efficacy of psychological treatments for binge eating disorder remains largely unknown.

Aims

To examine the long-term efficacy of out-patient group cognitive–behavioural therapy (CBT) and group interpersonal psychotherapy (IPT) for binge eating disorder and to analyse predictors of long-term non-response.

Method

Ninety people with binge eating disorder were assessed 4 years after treatment cessation within a randomised trial (trial registration: NCT01208272).

Results

Participants showed substantial long-term recovery, partial remission, clinically significant improvement and significant reductions in associated psychopathology, despite relapse tendencies in single secondary outcomes. Body mass index remained stable. While the IPT group demonstrated an improvement in eating disorder symptoms over the follow-up period, the CBT group reported a worsening of symptoms, but treatments did not differ at any time point.

Conclusions

The results document the long-term efficacy of out-patient CBT and IPT for binge eating disorder. Further research is warranted to elucidate the time course and mechanisms of change of these treatments for binge eating disorder.
Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: cross-sectional study
Authors: Nicholson Timothy R. J. , Ferdinando Sumudu , Krishnaiah Ravikumar B. , Anhoury Sophie , Lennox Belinda R. , Mataix-Cols David , Cleare Anthony , Veale David M. , Drummond Lynne M. , Fineberg Naomi A. , Church Andrew J. , Giovannoni Gavin , Heyman Isobel
Published: January 2012

Background

Symptoms of obsessive–compulsive disorder (OCD) have been described in neuropsychiatric syndromes associated with streptococcal infections. It is proposed that antibodies raised against streptococcal proteins cross-react with neuronal proteins (antigens) in the brain, particularly in the basal ganglia, which is a brain region implicated in OCD pathogenesis.

Aims

To test the hypothesis that post-streptococcal autoimmunity, directed against neuronal antigens, may contribute to the pathogenesis of OCD in adults.

Method

Ninety-six participants with OCD were tested for the presence of anti-streptolysin-O titres (ASOT) and the presence of anti-basal ganglia antibodies (ABGA) in a cross-sectional study. The ABGA were tested for with western blots using three recombinant antigens; aldolase C, enolase and pyruvate kinase. The findings were compared with those in a control group of individuals with depression (n= 33) and schizophrenia (n= 17).

Results

Positivity for ABGA was observed in 19/96 (19.8%) participants with OCD compared with 2/50 (4%) of controls (Fisher's exact testP= 0.012). The majority of positive OCD sera (13/19) had antibodies against the enolase antigen. No clinical variables were associated with ABGA positivity. Positivity for ASOT was not associated with ABGA positivity nor found at an increased incidence in participants with OCD compared with controls.

Conclusions

These findings support the hypothesis that central nervous system autoimmunity may have an aetiological role in some adults with OCD. Further study is required to examine whether the antibodies concerned are pathogenic and whether exposure to streptococcal infection in vulnerable individuals is a risk factor for the development of OCD.
Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin
Authors: Carhart-Harris R. L. , Leech R. , Williams T. M. , Erritzoe D. , Abbasi N. , Bargiotas T. , Hobden P. , Sharp D. J. , Evans J. , Feilding A. , Wise R. G. , Nutt D. J.
Published: January 2012

Background

Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences.

Aims

To test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo.

Method

Ten healthy participants received two functional magnetic resonance imaging scans (2mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis.

Results

Robust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective wellbeing at follow-up (P<0.01).

Conclusions

Evidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.
Nucleolar Sik-Similar Protein (Sik-SP) Is Required for the Maintenance of Uterine Estrogen Signaling Mechanism Via ERα
Authors: Chung Daesuk , Gao Fei , Ostmann Alicia , Hou Xiaonan , Das Sanjoy K.
Published: January 2012

Sik-similar protein (Sik-SP), a small nucleolar ribonucleoprotein, has been shown to be primarily involved in ribosome biogenesis. However, its role in the hormone-directed nuclear receptor signaling is largely unknown. Here, we provide novel evidence that Sik-SP is required for appropriate regulation of estrogen receptor (ER)α-mediated estradiol-17β (E2)-dependent uterine physiologic responses in mice. Studies by Western blotting using the newly developed antibodies for Sik-SP showed that this protein is up-regulated in both the ovariectomized wild-type and ERα null uteri by E2. Immunohistochemical analyses in uterine sections showed that this protein is induced in the epithelial and stromal cells. Coimmunoprecipitation studies revealed that E2 directs molecular interaction between Sik-SP and ERα. Furthermore, gel-mobility shift and chromatin immunoprecipitation analyses provided evidence that Sik-SP is recruited with ERα to estrogen-responsive uterine gene promoters. Overexpression of Sik-SP in vitro demonstrated a role for Sik-SP in cellular growth and viability. In a primary uterine epithelial-stromal coculture system, E2 exhibited early induction of Sik-SP in both the epithelial and stromal cells. Interestingly, suppression of Sik-SP in this coculture model, for the stromal but not epithelial cells, caused perturbation of E2-dependent proliferation in the epithelial cell layer. Similarly, in vivo uterine suppression of Sik-SP also caused inhibition of epithelial cell proliferation and aberrant prolongation of water imbibition in the late phase by E2. Finally, studies showed that Sik-SP is physiologically important during the onset of implantation by E2. In conclusion, Sik-SP, an early E2-responsive nucleolar protein, is necessary to induce E2-dependent ERα-mediated appropriate physiologic responses in the uterus.
Seeking the Voices of American Indian and Irish Schoolchildren (1820s–1920s): Autobiographical Reminiscence as Historical Source
Authors: Coleman Michael C.
Published: January 2012

During the nineteenth and early twentieth centuries (ca. 1820s–1920s) the US and British governments utilized elementary education as a tool of assimilation. Huge numbers of Indian and Irish children confronted educational systems designed to separate them from local cultural values. Much top-down official evidence is available for scholars seeking to understand the nature of these campaigns. However, the problem of finding the voices of those at the receiving end—and of attempting to discover pupil agency, as the recent paradigm in childhood research advocates—is especially severe for historians. Unlike anthropologists or sociologists, historians cannot observe or interview as children those whom they study. Occasionally evidence survives of pupils' voices of long ago. But often the historian must rely heavily on autobiographical reminiscences recorded decades later. This article suggests that by employing five critical tests we can use autobiography to gain some sense of narrators' earlier experiences as schoolchildren and of them as active agents in their own lives. Indeed, we often have little else to provide historical perspectives on assimilationist schooling “from the bottom up.”
Indigenous Autobiographyen Abyme: Indigenous Reflections on Representational Agency in the Case ofCrashing Thunder
Authors: Arndt Grant
Published: January 2012

This article shows that Crashing Thunder (1926), recognized as the first book-length American Indian autobiography published by an anthropologist, contains multiple, nested accounts of a pivotal moment in the life of its Ho-Chunk author, Sam Blowsnake: the killing of a man in 1903. Focusing on these nested accounts, the article seeks to develop an understanding of the context that led Blowsnake to include them—examples of autobiography en abyme—in his text. First, it draws on archival research into the killing and its legal consequences to examine Blowsnake's shifting accounts of his role in this event, showing how these differing accounts respond to the contexts of the tellings and how they resonate with recent theories of agency and autobiography. Second, it examines Blowsnake's autobiography in the context of his conversion to a new religion and its discursive practices and semiotic concerns. The conclusion suggests that a reexamination of the elements of autobiography en abyme in Crashing Thunder provides a framework for investigating the politics of culture and identity that shaped both Blowsnake's text and Paul Radin's ethnographic portrait of Ho-Chunk society and for thinking about the role of autobiography in the emergence of indigeneity.
Between Friends and Enemies: The Dynamics of Interethnic Relations in Amazonian Ecuador
Authors: Reeve Mary-Elizabeth , High Casey
Published: January 2012

This article examines the shifting nature of interethnic relations between two indigenous groups in Amazonian Ecuador, the Curaray River group of lowland Kichwa and the neighboring Waorani of the Curaray region. Waorani and Curaray Kichwa interaction from the 1930s to the present reveals a pattern marked by oscillations between hostilities and cautious friendship. These shifts are expressed in varied social relations described in the anthropological and historical scholarship on Amazonia, ranging from shamanic attack to marriage alliances. The paper explores this history and its linkage to wider social changes in the region brought about by Protestant evangelization and international economic interests. Our ethnographic analysis points to the maintenance of extended family linkages between Kichwa and Waorani in the Curaray River region as nodal relationships that potentiate shifts from hostilities to friendship between the two indigenous groups. These shifts occur within a regional interaction sphere that is bound together by extended family ties between specific household groups. By examining these relations through the lenses of both Waorani and Curaray Kichwa ethnography and of historical processes extending back almost a century, the article provides insights into a complex sociality involving distinct indigenous peoples across a multiethnic region of the Western Amazon.
In vitromodels for gluten toxicity: relevance for celiac disease pathogenesis and development of novel treatment options
Authors: Lindfors Katri , Rauhavirta Tiina , Stenman Satumarja , Mäki Markku , Kaukinen Katri
Published: January 2012

In genetically predisposed individuals, dietary gluten in wheat, rye and barley triggers celiac disease, a systemic autoimmune disorder hallmarked by an extensive small-bowel mucosal immune response. The current conception of celiac disease pathogenesis is that it involves components of both innate and adaptive immunity whose activation typically leads to small-bowel villous atrophy with crypt hyperplasia. Currently, the only effective treatment for celiac disease is a strict lifelong gluten-free diet excluding all wheat-, rye- and barley-containing food products. During the diet, the clinical symptoms improve and the small-bowel mucosal damage recovers, while re-introduction of gluten into the diet leads to re-appearance of the symptoms and deterioration of the small-bowel mucosal architecture. In view of the restricted nature of the diet, alternative treatment is warranted. Improved understanding of the molecular basis of celiac disease has enabled researchers to suggest other therapeutic approaches. Although there is no animal model reproducing all features of celiac disease, the use of in vitro approaches including a variety of cell lines and the celiac patient small-bowel mucosal biopsy organ culture has generated knowledge about pathogenesis of celiac disease. In these culture systems, gluten induces different effects that can be quantified, thus also enabling studies concerning the efficacy of candidate therapeutic compounds for celiac disease. This review describes the intestinal epithelial cell models, celiac patient T-cell lines and clones, as well as the small-bowel mucosal organ culture methods widely used in studies of celiac disease, and summarizes the major findings obtained with these systems.
My patient has no blood pressure: is their heart working?
Authors: Pishe Tushar , Ross Peter , Atkinson Paul
Published: January 2012

How can point-of-care (PoC) ultrasound be used to help the clinician identify cardiogenic and certain non-cardiogenic causes of undifferentiated, non-traumatic hypotension? Hypotension is a common emergency presentation in the emergency department and medical admissions unit. Due to the physiological complexities of this state, the aetiology is often unclear to clinicians at initial presentation. This has clear implications for treatment and outcomes of the patient. Clinical indicators such as vital signs and physical examination are often unreliable in distinguishing causes of hypotension, identifying the correct aetiology in only 25–50% of cases. PoC ultrasound (PoCUS) of the heart can help differentiate between cardiogenic causes such as left ventricular dysfunction, and obstructive causes such as cardiac tamponade, and can point towards other causes such as sepsis and hypovolaemia. Limited cardiac echocardiography or ‘echo in life support’ can be performed as a part of goal-directed protocols for undifferentiated, non-traumatic hypotension. Use of such protocols early can significantly improve the diagnostic accuracy to 80%, thereby reducing the time to diagnosis and the time to initiating appropriate therapies. In this article, we review our approach to PoCUS of the heart in the setting of hypotension.
Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs
Authors: Voellenkle Christine , van Rooij Jeroen , Guffanti Alessandro , Brini Elena , Fasanaro Pasquale , Isaia Eleonora , Croft Larry , David Matei , Capogrossi Maurizio C. , Moles Anna , Felsani Armando , Martelli Fabio
Published: January 2012

In order to understand the role of microRNAs (miRNAs) in vascular physiopathology, we took advantage of deep-sequencing techniques to accurately and comprehensively profile the entire miRNA population expressed by endothelial cells exposed to hypoxia. SOLiD sequencing of small RNAs derived from human umbilical vein endothelial cells (HUVECs) exposed to 1% O2or normoxia for 24 h yielded more than 22 million reads per library. A customized bioinformatic pipeline identified more than 400 annotated microRNA/microRNA* species with a broad abundance range: miR-21 and miR-126 totaled almost 40% of all miRNAs. A complex repertoire of isomiRs was found, displaying also 5′ variations, potentially affecting target recognition. High-stringency bioinformatic analysis identified microRNA candidates, whose predicted pre-miRNAs folded into a stable hairpin. Validation of a subset by qPCR identified 18 high-confidence novel miRNAs as detectable in independent HUVEC cultures and associated to the RISC complex. The expression of two novel miRNAs was significantly down-modulated by hypoxia, while miR-210 was significantly induced. Gene ontology analysis of their predicted targets revealed a significant association to hypoxia-inducible factor signaling, cardiovascular diseases, and cancer. Overexpression of the novel miRNAs in hypoxic endothelial cells affected cell growth and confirmed the biological relevance of their down-modulation. In conclusion, deep-sequencing accurately profiled known, variant, and novel microRNAs expressed by endothelial cells in normoxia and hypoxia.
Discovery of Pyrobaculum small RNA families with atypical pseudouridine guide RNA features
Authors: Bernick David L. , Dennis Patrick P. , Höchsmann Matthias , Lowe Todd M.
Published: January 2012

In the Eukarya and Archaea, small RNA-guided pseudouridine modification is believed to be an essential step in ribosomal RNA maturation. While readily modeled and identified by computational methods in eukaryotic species, these guide RNAs have not been found in most archaeal genomes. Using high-throughput transcriptome sequencing and comparative genomics, we have identified ten novel small RNA families that appear to function as H/ACA pseudouridylation guide sRNAs, yet surprisingly lack several expected canonical features. The new RNA genes are transcribed and highly conserved across at least six species in the archaeal hyperthermophilic genus Pyrobaculum. The sRNAs exhibit a single hairpin structure interrupted by a conserved kink-turn motif, yet only two of ten families contain the complete canonical structure found in all other H/ACA sRNAs. Half of the sRNAs lack the conserved 3′-terminal ACA sequence, and many contain only a single 3′ guide region rather than the canonical 5′ and 3′ bipartite guides. The predicted sRNA structures contain guide sequences that exhibit strong complementarity to ribosomal RNA or transfer RNA. Most of the predicted targets of pseudouridine modification are structurally equivalent to those known in other species. One sRNA appears capable of guiding pseudouridine modification at positions U54 and U55 in most or all Pyrobaculum tRNAs. We experimentally tested seven predicted pseudouridine modifications in ribosomal RNA, and all but one was confirmed. The structural insights provided by this new set of Pyrobaculum sRNAs will augment existing models and may facilitate the identification and characterization of new guide sRNAs in other archaeal species.
Multiattribute One-Switch Utility
Authors: Tsetlin Ilia , Winkler Robert L.
Published: January 2012

The one-switch property states that the preference between any two lotteries switches at most once as wealth increases. Working within the expected utility framework, we extend the one-switch notion to the multiattribute case and identify the families of multiattribute utility functions that are one-switch. We then show that all multiattribute one-switch utility functions can be approximated by a sum of two multiattribute exponential utilities (sumex utility). Finally, we discuss how the one-switch property, when appropriate, can simplify the assessment of multiattribute utility.

This paper was accepted by Peter Wakker, decision analysis.
Rational Herding in Microloan Markets
Authors: Zhang Juanjuan , Liu Peng
Published: January 2012

Microloan markets allow individual borrowers to raise funding from multiple individual lenders. We use a unique panel data set that tracks the funding dynamics of borrower listings on Prosper.com, the largest microloan market in the United States. We find evidence of rational herding among lenders. Well-funded borrower listings tend to attract more funding after we control for unobserved listing heterogeneity and payoff externalities. Moreover, instead of passively mimicking their peers (irrational herding), lenders engage in active observational learning (rational herding); they infer the creditworthiness of borrowers by observing peer lending decisions and use publicly observable borrower characteristics to moderate their inferences. Counterintuitively, obvious defects (e.g., poor credit grades) amplify a listing's herding momentum, as lenders infer superior creditworthiness to justify the herd. Similarly, favorable borrower characteristics (e.g., friend endorsements) weaken the herding effect, as lenders attribute herding to these observable merits. Follow-up analysis shows that rational herding beats irrational herding in predicting loan performance.

This paper was accepted by Pradeep Chintagunta, marketing.
Dynamics of Rate-of-Return Regulation
Authors: Nezlobin Alexander , Rajan Madhav V. , Reichelstein Stefan
Published: January 2012

Under rate-of-return regulation, a firm's product prices are constrained by the requirement that investors not earn more than an allowable return on the firm's assets. This paper examines the dynamic properties of the rate-of-return regulation process when the regulated firm periodically undertakes new capacity investments. Our analysis identifies prices that correspond to stationary values of the regulation process. It is shown that the underlying depreciation rules for property, plant, and equipment determine whether these stationary prices will be above, equal to, or below the long-run marginal cost of providing the regulated service. We provide conditions under which the rate-of-return regulation process is dynamically stable so that prices indeed converge to their stationary values. The overall efficiency of this regulation method is shown to depend on how well the applicable depreciation schedule matches the productivity pattern of the assets in use.

This paper was accepted by Gérard P. Cachon, accounting.
Hyperadiponectinemia protects against premature death in metabolic syndrome model mice by inhibiting AKT signaling and chronic inflammation
Authors: Otabe S , Wada N , Hashinaga T , Yuan X , Shimokawa I , Fukutani T , Tanaka K , Ohki T , Kakino S , Kurita Y , Nakayama H , Tajiri Y , Yamada K
Published: January 2012

We previously reported that transgenic (Tg) expression of adiponectin significantly prolonged the lifespan of normal mice. The aim of this study was to elucidate the mechanism involved in the longevity effects of adiponectin using KK/Ta mice, a murine model of metabolic syndrome. We established a Tg line of KK/Ta (Tg-KK/Ta) mice expressing human adiponectin in the liver, and assessed their lifespan. The cause of death was determined by macroscopic and microscopic examinations immediately after death. The expressions of SIRT1, C-reactive protein (CRP), inflammatory cytokines, AMPK, and AKT were measured by quantitative real-time PCR, ELISAs, and/or western blotting. KK/Ta mice had lower serum adiponectin levels and shorter lifespan (57.6±13.9 vs 106.5±18.3 weeks, P<0.0001) than C57BL/6N mice. Tg adiponectin expression significantly extended the lifespan of KK/Ta mice (73.6±16.6 weeks, P<0.001) without affecting body weight, daily food consumption, or plasma glucose levels. Neoplasms were observed in only three of 22 KK/Ta mice that died spontaneously because of tumors. Atherosclerotic lesions were not detected in any mice. SIRT1 levels were not significantly different between KK/Ta and Tg-KK/Ta mice. Gene expressions of Crp, Tnfα, Il6, and Nfκb were increased in KK/Ta mice, but they were significantly attenuated in Tg-KK/Ta mice. Phosphorylated AMPK levels were increased and phosphorylated AKT levels were decreased in Tg-KK/Ta mice. The anti-inflammatory effects of adiponectin, achieved by inhibiting the AKT signaling pathway, may explain how adiponectin slows the accelerated aging process associated with the metabolic syndrome.
Testosterone modulates platelet aggregation and endothelial cell growth through nitric oxide pathway
Authors: Campelo Adrián E , Cutini Pablo H , Massheimer Virginia L
Published: January 2012

The aim of the present study was to investigate the effect of testosterone on the modulation of cellular events associated with vascular homeostasis. In rat aortic strips, 5–20 min treatment with physiological concentrations of testosterone significantly increased nitric oxide (NO) production. The rapid action of the steroid was suppressed by the presence of an androgen receptor antagonist (flutamide). We obtained evidence that the enhancement in NO synthesis was dependent on the influx of calcium from extracellular medium, because in the presence of a calcium channel blocker (verapamil) the effect of testosterone was reduced. Using endothelial cell (EC) cultures, we demonstrated that androgen directly acts at the endothelial level. Chelerythrine or PD98059 compound completely suppressed the increase in NO production, suggesting that the mechanism of action of the steroid involves protein kinase C and mitogen-activated protein kinase pathways. It is known that endothelial NO released into the vascular lumen serves as an inhibitor of platelet activation and aggregation. We showed that testosterone inhibited platelet aggregation and this effect was dependent on endothelial NO synthesis. Indeed, the enhancement of NO production elicited by androgen was associated with EC growth. The steroid significantly increased DNA synthesis after 24 h of treatment, and this mitogenic action was blunted in the presence of NO synthase inhibitorN-nitro-l-arginine methyl ester. In summary, testosterone modulates vascular EC growth and platelet aggregation through its direct action on endothelial NO production.
Construção, adaptação e validação de escalas de silhuetas para autoavaliação do estado nutricional: uma revisão sistemática da literatura
Authors: Moraes Cristiane , Anjos Luiz Antonio dos , Marinho Sandra Mara Silva de Azevedo
Published: January 2012

A autoavaliação da imagem corporal é uma construção multidimensional por meio da qual os indivíduos descrevem as representações internas da estrutura corporal e da aparência física, em relação a si próprio e aos outros. As Escalas de Silhuetas são testes que viabilizam a autoavaliação, especialmente em pesquisas de campo, devido ao baixo custo e facilidade na administração do método. O objetivo deste trabalho foi resgatar as Escalas de Silhuetas construídas ou adaptadas desde 1983 e realizar uma revisão sistemática sobre a validação destas frente a medidas objetivas do estado nutricional. Foram identificados 33 estudos com grande variação na correlação com o estado nutricional de adultos, tanto para as Escalas de Silhuetas adaptadas (coeficientes de correlação de 0,66 a 0,87) quanto para as construídas (0,59 a 0,94). Já em crianças e adolescentes, as correlações entre as Escalas de Silhuetas e o estado nutricional não resultaram em valores satisfatórios em vários dos estudos. Muitos trabalhos utilizaram estatística inapropriada. Os dados da presente revisão indicam que deve-se ter cuidado no uso de Escalas de Silhuetas para estimar o estado nutricional com ou sem a medição antropométrica.
Medicamentos prescritos aos idosos em uma capital do Sul do Brasil e a Relação Municipal de Medicamentos
Authors: Aziz Marina Meneses , Calvo Maria Cristina Marino , d'Orsi Eleonora
Published: January 2012

O objetivo deste trabalho foi descrever os medicamentos prescritos aos idosos residentes na zona urbana do Município de Florianópolis, Santa Catarina, Brasil, nos 30 dias anteriores à entrevista e, a partir disto, comparar com a Relação Municipal de Medicamentos (REMUME). Foi realizado um estudo transversal populacional de base domiciliar, no qual os 1.705 idosos entrevistados relataram ter utilizado o total de 5.458 medicamentos prescritos e dentro dos critérios da pesquisa, que corresponderam a 374 princípios ativos diferentes. Os medicamentos mais utilizados foram os indicados para o sistema cardiovascular, sendo a classe farmacológica dos redutores de colesterol e triglicerídeos os mais prevalentes, apesar de não haver nenhum exemplar desta classe de medicamentos selecionado na REMUME. Embora haja algumas faltas, a REMUME coincide com a maior proporção dos medicamentos prescritos no Município de Florianópolis. A principal diferença entre as prescrições é que as oriundas do SUS estão em maior conformidade com a REMUME.
Community violence and childhood asthma prevalence in peripheral neighborhoods in Salvador, Bahia State, Brazil
Authors: Alves Guilherme da Costa , Santos Darci Neves , Feitosa Caroline Alves , Barreto Mauricio Lima
Published: January 2012

This study aimed to identify degrees of exposure to community violence reported by parents and guardians of children from four to 12 years of age and the association with childhood asthma symptoms. A cross-sectional study was conducted with 1,232 parents/guardians in 24 peripheral neighborhoods in Salvador, the capital of Bahia State, Brazil. The authors investigated asthma symptoms in children and acts of violence in the community. More than 75% of parents/guardians had been exposed to community violence in the previous year, with 20% reporting high levels of exposure. Children that were more exposed to violence showed higher asthma prevalence (28.4%) as compared to non-exposed children (16.4%). Children exposed to maximum levels of violence were nearly twice as likely to present asthma symptoms (adjusted OR = 1.94; 95%CI: 1.12-3.36). The study highlighted the relevance of community violence as a risk factor for asthma and the need for further research to elucidate methodological issues.
Uso de medicamentos entre idosos residentes em áreas urbanas e rurais de município no Sul do Brasil: um estudo de base populacional
Authors: Dal Pizzol Tatiane da Silva , Pons Emilia da Silva , Hugo Fernando Neves , Bozzetti Mary Clarisse , Sousa Maria da Luz Rosário de , Hilgert Juliana Balbinot
Published: January 2012

O objetivo foi verificar a prevalência de uso de medicamentos e de polifarmácia entre idosos de Carlos Barbosa, Rio Grande do Sul, Brasil, e comparar as características sociodemográficas e de saúde associadas ao uso, segundo o local de moradia. Foi avaliada uma amostra aleatória de 811 idosos com 60 anos ou mais, moradores na área urbana ou rural. Dados sociodemográficos, doenças crônicas, qualidade de vida e medicamentos autorreferidos foram coletados em entrevistas presenciais. Associação entre local de moradia e uso de medicamentos ou polifarmácia, ajustada para potenciais confundidores, foi avaliada por regressão de Poisson com ajuste robusto da variância. A prevalência de uso de medicamentos e de polifarmácia foi maior entre os idosos urbanos. Morar na área urbana apresentou associação positiva e independente com uso de medicamentos (RP = 1,10; IC95%: 1,02-1,20) e polifarmácia (RP = 1,83; IC95%: 1,27-2,65). Morar na área urbana está associado à maior prevalência de uso de medicamentos e de polifarmácia entre idosos.
Significados e práticas de saúde e doença entre a população em situação de rua em Salvador, Bahia, Brasil
Authors: Aguiar Maria Magalhães , Iriart Jorge Alberto Bernstein
Published: January 2012

O objetivo deste trabalho foi analisar práticas e significados atribuídos à saúde e à doença pela população em situação de rua em Salvador, Bahia, Brasil. Trata-se de um estudo qualitativo de enfoque antropológico com realização de observação participante e entrevistas semi-estruturadas com 13 indivíduos entre 30 e 66 anos. Os resultados apontam que as condições de vida e saúde deste grupo são muito precárias, sendo a violência sobressalente nas narrativas. Os principais problemas de saúde foram o abuso de substâncias psicoativas, HIV/AIDS, transtornos mentais, problemas odontológicos, dermatológicos e gastrointestinais. A saúde foi associada, entre outros significados, à capacidade de resistir ao cotidiano de dificuldades, enquanto a doença vinculou-se ao estado de debilidade impeditivo de lutar pela sobrevivência. Os serviços de saúde são procurados em situações graves e urgentes. Conclui-se pela necessidade de políticas específicas visando garantir condições de vida adequadas e acesso à saúde para esta população.
Characteristics of Oral Mucosal Events Related to Bevacizumab Treatment
Authors: Gavrilovic Igor T. , Balagula Yevgeniy , Rosen Alyx C. , Ramaswamy Vijay , Dickler Maura N. , Dunkel Ira J. , Lacouture Mario E.
Published: January 2012

Background.

Bevacizumab, a monoclonal antibody targeting a vascular endothelial growth factor (VEGF) protein, has been reported to induce mucosal toxicities. However, the clinical characteristics of these particular toxicities have not been well characterized. We aimed at providing a detailed clinical description of signs and symptoms limited to the tongue mucosa in patients treated with bevacizumab.

Methods.

A retrospective review of medical records and clinical photographs was performed with specific attention to clinical presentation, evolution, associated symptoms, concomitant medications, and treatment methods.

Results.

In total, four patients presented to the dermatology service with clinical findings characterized by multifocal, erythematous circinate and serpiginous erosions on the dorsal tongue surrounded by white hyperkeratotic rims that were temporally related to bevacizumab therapy. Associated increased sensitivity to spicy foods was frequently observed.

Conclusion.

These characteristic clinical findings are consistent with geographic tongue. However, large prospective evaluations are necessary to confirm this potential relationship. If bevacizumab is indeed associated with geographic tongue, increased awareness may result in improved reporting and characterization of this particular adverse event.