Signs and symptoms of disordered eating in pregnancy: A Delphi consensus study

Background: This study aimed to establish consensus on the expression and distinction of disordered eating inpregnancy to improve awareness across various health professions and inform the development of a pregnancyspecific assessment instrument.Methods: A three-round modified Delphi method was used with two independent panels. International cliniciansand researchers with extensive knowledge on and/or clinical experience with eating disorders formed the firstpanel and were recruited using structured selection criteria. Women who identified with a lived experience ofdisordered eating in pregnancy formed the second panel and were recruited via expressions of interest from studyadvertising on pregnancy forums and social media platforms. A systematic search of academic and grey literatureproduced 200 sources which were used to pre-populate the Round I questionnaire. Additional items were includedin Round II based on panel feedback in Round I. Consensus was defined as 75% agreement on an item.Results: Of the 102 items presented to the 26 professional panel members and 15 consumer panel members, 75reached consensus across both panels. Both panels clearly identified signs and symptoms of disordered eating inpregnancy and endorsed a number of clinical features practitioners should consider when delineating disorderedeating symptomatically from normative pregnancy experiences.Conclusion: A list of signs and symptoms in consensus was identified. The areas of collective agreement may beused to guide clinicians in clinical practice, aid the development of psychometric tools to detect/assess pregnancyspecific disordered eating, in addition to serving as starting point for the development of a core outcome set tomeasure disordered eating in pregnancy

Die Surfactantkonversion als enzymatischer Prozeß : Ist das Surfactantprotein SP-B ein Substrat der Konvertase?

Das in der Alveole der Säugerlungen vorkommende Surfactantmaterial kann in sogenannte small und large surfactant aggregates aufgetrennt werden. Zu den large surfactant aggregates zählen Lamellarkörperchen und tubuläres Myelin, also die biophysikalisch hochaktiven Präkursoren des interfacialen Surfactantfilms. Unter den Prämissen einer akuten respiratorischen Insuffizienz ist wiederholt festgestellt worden, dass die Verteilung zwischen den large surfactant aggregates und small surfactant aggregates sehr zugunsten der small surfactant aggregates verschoben ist. Hieraus resultierend findet sich ein Übergewicht dieser, biophysikalisch weitgehend inaktiven, Abbauprodukte des Grenzflächenfilms. Vor diesem Hintergrund wurde in der vorliegenden Doktorarbeit der Fragestellung nachgegangen, wodurch die alveoläre Umwandlung der large in die small surfactant aggregates, ein als Surfactantkonversion bezeichneter Vorgang, vermittelt wird, und ob diese Surfactantkonversion ein enzymatisch getriggerter Prozess ist. Zur Beantwortung dieser Frage wurde als Ausgangsmaterial eine gepoolte bronchoalveoläre Lavage von gesunden Kaninchen, sowie ein rekonstituiertes Surfactantmaterial verwendet. Methodisch kamen weiterhin chromatographische, elektrophoretische, biophysikalische Verfahren, sowie Enzymaktivitäts-Assays zur Anwendung. Zunächst einmal konnte festgestellt werden, dass für die weitreichende Konversion von Surfactant in vitro in der Tat die Gegenwart einer Esterase notwendig ist. Weiterhin ergab sich im Rahmen der Rekonstitutionsversuche mit variablen Surfactant-Apoproteinen ebenfalls der Hinweis, dass vor allen Dingen der relative Gehalt an SP-B einen weitreichenden Einfluss auf den Konversionsgrad ausübt. Bei der Untersuchung der Herkunft der Esteraseaktivität in der BAL zeigte sich, dass im Überstand der resuspendierten Zellen der bronchoalveolären Lavage, wie auch im Zelllysat erhebliche Mengen an Esteraseaktivität nachweisbar waren. Weiterhin wurde festgestellt, dass unter den Bedingungen einer in vitro Konversion die Esteraseaktivität in den Subfraktionen alveolären Surfactans zeitabhängig abfiel. So war in den large surfactant aggregates 42 min nach Beginn der in vitro Konversion überhaupt keine Esteraseaktivität und nur noch etwa ein Viertel der Amidaseaktivität nachweisbar. Auf der Suche nach dem möglichen Substrat dieser Esterase wurde sowohl für die natürliche, wie auch für isoliert mit - an Sepharose gekoppelter - Esterase inkubiertem Surfactantprotein B der Nachweis erbracht, dass im Rahmen des Konversionsprozesses das dimere SP-B abgebaut und ein Spaltprodukt in einem Molekulargewichtsbereich von 11-14 kDa neu auftritt. Eine aminoterminale Sequenzierung dieses Spaltproduktes ergab zweifelsfrei den Nachweis eines Surfactantprotein B entstammenden Proteins und zwar des aminoterminalen Anteils des SP-B. Dieses Spaltprodukt konnte durch ein neu entwickeltes HPLC-Verfahren zur Auftrennung der hydrophoben Surfactantproteine aus der BAL weiter aufgereinigt werden. Zusammenfassend ergibt sich auf der Basis der hier vorliegenden Daten der Befund, dass die Umwandlung von large in small surfactant aggregates und der hiermit verbundene Verlust der Oberflächenaktivität nicht nur von der Größe der Oberflächenveränderung, sondern zudem von der Gegenwart einer enzymatischen Aktivität abhängig sind. Im Rahmen der hier durchgeführten Untersuchung konnte der Nachweis einer Esteraseaktivität sowohl in den Zellen der BAL, wie auch im zellfreien Überstand erbracht werden. Als mögliches Substrat dieser Aktivität konnte das Surfactantprotein B identifiziert werden, für welches das Auftreten eines 11-14 kDa großen Spaltproduktes einwandfrei belegt werden konnte. Aus der Kenntnis dieser Ergebnisse leiten sich mögliche neue Therapieoptionen für das Acute Respiratory Distress Syndrome, wie auch für den Ventilator Induced Lung Injury ab, bei denen Verschiebungen des alveolären Surfactantpools zugunsten der small surfactant aggregates wiederholt beschrieben worden sind.The alveolar surfactant pool can be separated into the \u27large surfactant aggregates\u27 (LSA) and the \u27small surfactant aggregates\u27 (SSA). The LSA, including lamellar bodies and tubular myelin, represent the biophysically highly active precursors of the interfacial surfactant film. Under cyclic area changes LSA are converted into the SSA (surfactant conversion). In contrast to LSA the SSA are clearly less surface active. Under clinical conditions of the acute respiratory distress syndrome, the balance of LSA to SSA is found to be switched in favour of SSA. Under these conditions, the alveolar surfactant pool predominantly consists of the largely inactive small surfactant aggregates, thus favouring impairment of gas exchange and lung function. Drawn against this background we aimed to elucidate the mechanisms of the conversion process. To answer this question pooled bronchoalveolar lavages of healthy rabbits and reconstituted surfactant preparations were subjected to repetitive surface area changes in vitro and extend of conversion was analysed. Besides chromatographic, electrophoretic and biophysical techniques, enzyme activity assays were applied for experimental investigations. It was found that an esterase activity is necessary for the induction of surfactant conversion under cyclic surface area changes. Experiments with various concentrations of the different surfactant proteins SP-A, SP-B or SP-C in reconstituted lipid mixtures revealed that only SP-B has a profound impact on the extent of in vitro conversion. Enzyme activity assays showed high esterase activity in complete cell suspensions of bronchoalveolar lavage and cell lysates. Under conditions of in vitro conversion, the esterase activity was found to decline in dependency of the incubation time, resulting in complete loss of esterase activity after 42 min of in vitro conversion. With emphasis on the potential role of surfactant proteins as substrates of esterase activity, we could show that in vitro conversion of BAL as well as incubation of isolated SP-B with sepharose linked esterase would result in a cleavage of dimeric SP-B and detection of a new protein band with a molecular range of 11-14 kilodalton. Amino terminal sequencing revealed that this protein truly represents a cleavage product of the amino terminal part of SP-B. Further purification of the cleavage product was performed by a new developed HPLC method for separation from other hydrophobic surfactant proteins and phospholipids. In summary the presented data support the conclusion that conversion of large surfactant aggregates to small surfactant aggregates not only depends on cyclic changes of the air-liquid interface, but also on the presence of an esterase activity. This esterase activity was detected in the cytosolic fraction of BAL cells, mostly alveolar macrophages. A SP-B cleavage product with a molecular range of 11-14 kilodalton was identified upon in vitro incubation of esterase with SP-B and after in vitro conversion of a rabbit BAL pool, suggesting that SP-B is a substrate of the alveolar esterase. These data may help to identify new molecular targets to treat acute respiratory distress syndrome and ventilator induced lung injury

Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children with hematuria

To assess the detection rate of nutcracker syndrome in children with isolated hematuria, renal Doppler ultrasound examinations were routinely performed on 216 consecutive children (176 microscopic hematuria and 40 gross hematuria). Renal Doppler ultrasound was also performed on 32 healthy normal children. The peak velocity (PV) was measured at the hilar portion of the left renal vein (LRV) and at the LRV between the aorta and the superior mesenteric artery. The PV at the aortomesenteric portion (P=0.003) and the PV ratios of the LRV (P=0.003) were significantly higher in children with hematuria than in normal children, while the PV at the hilar portion was not different. If a PV ratio of the LRV of at least 4.1 (the cut-off level set at the mean ±2 SD of the value for the normal children) was defined as abnormal, 72 cases (33.3%) in children with hematuria and no cases in normal children were diagnosed as having nutcracker syndrome. The prevalence of nutcracker syndrome is relatively high in children with isolated hematuria, and the inclusion of renal Doppler ultrasound as a screening examination has a substantial effect on the detection of nutcracker syndrome

Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. The VANISH Randomized Clinical Trial

IMPORTANCE: Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. OBJECTIVE: To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. INTERVENTIONS: Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). MAIN OUTCOMES AND MEASURES: The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. RESULTS: A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). CONCLUSIONS AND RELEVANCE: Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ISRCTN 20769191

The Drosophila melanogaster PeptideAtlas facilitates the use of peptide data for improved fly proteomics and genome annotation

<p>Abstract</p> <p>Background</p> <p>Crucial foundations of any quantitative systems biology experiment are correct genome and proteome annotations. Protein databases compiled from high quality empirical protein identifications that are in turn based on correct gene models increase the correctness, sensitivity, and quantitative accuracy of systems biology genome-scale experiments.</p> <p>Results</p> <p>In this manuscript, we present the <it>Drosophila melanogaster </it>PeptideAtlas, a fly proteomics and genomics resource of unsurpassed depth. Based on peptide mass spectrometry data collected in our laboratory the portal <url>http://www.drosophila-peptideatlas.org</url> allows querying fly protein data observed with respect to gene model confirmation and splice site verification as well as for the identification of proteotypic peptides suited for targeted proteomics studies. Additionally, the database provides consensus mass spectra for observed peptides along with qualitative and quantitative information about the number of observations of a particular peptide and the sample(s) in which it was observed.</p> <p>Conclusion</p> <p>PeptideAtlas is an open access database for the <it>Drosophila </it>community that has several features and applications that support (1) reduction of the complexity inherently associated with performing targeted proteomic studies, (2) designing and accelerating shotgun proteomics experiments, (3) confirming or questioning gene models, and (4) adjusting gene models such that they are in line with observed <it>Drosophila </it>peptides. While the database consists of proteomic data it is not required that the user is a proteomics expert.</p

Factors associated with severe dry eye in primary Sjögren´s syndrome diagnosed patients

Introduction Primary Sjögren?s syndrome (pSS) is an autoimmune disease, characterized by lymphocytic infiltration of exocrine glands and other organs, resulting in dry eye, dry mouth and extraglandular systemic findings. Objective To explore the association of severe or very severe dry eye with extraocular involvement in patients diagnosed with primary Sjögren?s syndrome. Methods SJOGRENSER registry is a multicenter cross-sectional study of pSS patients. For the construction of our main variable, severe/very severe dry eye, we used those variables that represented a degree 3?4 of severity according to the 2007 Dry Eye Workshop classification. First, bivariate logistic regression models were used to identify the effect of each independent variable on severe/very severe dry eye. Secondly, multivariate analysis using regression model was used to establish the independent effect of patient characteristics. Results Four hundred and thirty-seven patients were included in SJOGRENSER registry; 94% of the patients complained of dry eye and 16% developed corneal ulcer. Schirmer?s test was pathological in 92% of the patients; 378 patients presented severe/very severe dry eye. Inflammatory articular involvement was significantly more frequent in patients with severe/very severe dry eye than in those without severe/very severe dry eye (82.5 vs 69.5%, p = 0,028). Inflammatory joint involvement was associated with severe/very severe dry eye in the multivariate analysis, OR 2.079 (95% CI 1.096?3.941). Conclusion Severe or very severe dry eye is associated with the presence of inflammatory joint involvement in patients with pSS. These results suggest that a directed anamnesis including systemic comorbidities, such as the presence of inflammatory joint involvement or dry mouth in patients with dry eye, would be useful to suspect a pSS

GB virus-C – a virus without a disease: We cannot give it chronic fatigue syndrome

BACKGROUND: Chronic fatigue syndrome (CFS) is an illness in search of an infectious etiology. GB virus-C (GBV-C) virus is a flavivirus with cell tropism and host defense induction qualities compatible with a role in producing the syndrome. The GBV-C genome is detectable in 4% of the population and 12% of the population is seropositive. The present study evaluated the association between infection with GBV and CFS. METHODS: We used a commercial EIA to detect antibodies against the GBV-C E2 protein and a quantitative real-time RT-PCR assay to detect active GBV-C infection. Sera were from a case control study of CFS in Atlanta, Georgia. The Fisher's exact two-tailed test was used for statistical analysis. RESULTS: Two of 12 CFS patients and one of 21 controls were seropositive for prior GBV-C infection and one control had viral RNA detected, indicating active infection. The results are not statistically different. CONCLUSION: We found no evidence that active or past infection with GBV is associated with CFS

β-Lactam Resistance Response Triggered by Inactivation of a Nonessential Penicillin-Binding Protein

It has long been recognized that the modification of penicillin-binding proteins (PBPs) to reduce their affinity for β-lactams is an important mechanism (target modification) by which Gram-positive cocci acquire antibiotic resistance. Among Gram-negative rods (GNR), however, this mechanism has been considered unusual, and restricted to clinically irrelevant laboratory mutants for most species. Using as a model Pseudomonas aeruginosa, high up on the list of pathogens causing life-threatening infections in hospitalized patients worldwide, we show that PBPs may also play a major role in β-lactam resistance in GNR, but through a totally distinct mechanism. Through a detailed genetic investigation, including whole-genome analysis approaches, we demonstrate that high-level (clinical) β-lactam resistance in vitro, in vivo, and in the clinical setting is driven by the inactivation of the dacB-encoded nonessential PBP4, which behaves as a trap target for β-lactams. The inactivation of this PBP is shown to determine a highly efficient and complex β-lactam resistance response, triggering overproduction of the chromosomal β-lactamase AmpC and the specific activation of the CreBC (BlrAB) two-component regulator, which in turn plays a major role in resistance. These findings are a major step forward in our understanding of β-lactam resistance biology, and, more importantly, they open up new perspectives on potential antibiotic targets for the treatment of infectious diseases

Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk

The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p <0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range