Moderately elevated blood pressure during pregnancy and odds of hypertension later in life: the POUCHmoms longitudinal study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/1/bjo14556-sup-0010-ICMJE7.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/2/bjo14556-sup-0007-ICMJE4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/3/bjo14556.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/4/bjo14556-sup-0008-ICMJE5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/5/bjo14556-sup-0001-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/6/bjo14556-sup-0002-TableS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/7/bjo14556-sup-0005-ICMJE2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/8/bjo14556-sup-0003-TableS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/9/bjo14556-sup-0006-ICMJE3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/10/bjo14556-sup-0009-ICMJE6.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/11/bjo14556_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/12/bjo14556-sup-0004-ICMJE1.pd

Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B

Apicomplexan parasites belong to a recently recognised group of protozoa referred to as Alveolata. These protists contain membranous sacs (alveoli) beneath the plasma membrane, termed the Inner Membrane Complex (IMC) in the case of Apicomplexa. During parasite replication the IMC is formed de novo within the mother cell in a process described as internal budding. We hypothesized that an alveolate specific factor is involved in the specific transport of vesicles from the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate specific Rab-GTPase that localises to the growing end of the IMC during replication of Toxoplasma gondii. Conditional interference with Rab11B function leads to a profound defect in IMC biogenesis, indicating that Rab11B is required for the transport of Golgi derived vesicles to the nascent IMC of the daughter cell. Curiously, a block in IMC biogenesis did not affect formation of sub-pellicular microtubules, indicating that IMC biogenesis and formation of sub-pellicular microtubules is not mechanistically linked. We propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature IMC of the growing daughter parasites

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Susceptibility to COPD:Differential Proteomic Profiling after Acute Smoking

Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease), yet only a subset of smokers develops COPD. Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as "susceptible individuals". Here we perform unbiased analyses of proteomic profiles to assess how "susceptible individuals" differ from age-matched "non-susceptible individuals" in response to cigarette smoking. Epithelial lining fluid (ELF) was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD. Controls at baseline were older healthy smoking and non-smoking individuals. Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ) in duplicate. Six proteins were selected and validated by ELISA or immunohistochemistry. After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment. SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1) decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures. Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking. We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD. This is the first study applying unbiased proteomic profiling to unravel the underlying mechanisms that induce COPD. Our data suggest that SerpinB3 and Uteroglobin could be interesting proteins in understanding the processes leading to COPD

Incidental sounds of locomotion in animal cognition

The highly synchronized formations that characterize schooling in fish and the flight of certain bird groups have frequently been explained as reducing energy expenditure. I present an alternative, or complimentary, hypothesis that synchronization of group movements may improve hearing perception. Although incidental sounds produced as a by-product of locomotion (ISOL) will be an almost constant presence to most animals, the impact on perception and cognition has been little discussed. A consequence of ISOL may be masking of critical sound signals in the surroundings. Birds in flight may generate significant noise; some produce wing beats that are readily heard on the ground at some distance from the source. Synchronization of group movements might reduce auditory masking through periods of relative silence and facilitate auditory grouping processes. Respiratory locomotor coupling and intermittent flight may be other means of reducing masking and improving hearing perception. A distinct border between ISOL and communicative signals is difficult to delineate. ISOL seems to be used by schooling fish as an aid to staying in formation and avoiding collisions. Bird and bat flocks may use ISOL in an analogous way. ISOL and interaction with animal perception, cognition, and synchronized behavior provide an interesting area for future study

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Maternal risk of hypertension 7–15 years after pregnancy: clues from the placenta

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/1/bjo16498-sup-0004-ICMJE2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/2/bjo16498-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/3/bjo16498-sup-0011-ICMJE9.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/4/bjo16498-sup-0008-ICMJE6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/5/bjo16498-sup-0005-ICMJE3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/6/bjo16498-sup-0003-ICMJE1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/7/bjo16498-sup-0010-ICMJE8.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/8/bjo16498-sup-0009-ICMJE7.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/9/bjo16498_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/10/bjo16498-sup-0006-ICMJE4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/11/bjo16498-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/12/bjo16498.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/13/bjo16498-sup-0007-ICMJE5.pd