bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation
Authors: Broecker Felix , Klumpp Jochen , Schuppler Markus , Russo Giancarlo , Biedermann Luc , Hombach Michael , Rogler Gerhard , Moelling Karin
Published: October 2015

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infections (RCDIs). However, long-term effects on the patients’ gut microbiota and the role of viruses remain to be elucidated. Here, we characterized bacterial and viral microbiota in the feces of a cured RCDI patient at various time points until 4.5 yr post-FMT compared with the stool donor. Feces were subjected to DNA sequencing to characterize bacteria and double-stranded DNA (dsDNA) viruses including phages. The patient's microbial communities varied over time and showed little overall similarity to the donor until 7 mo post-FMT, indicating ongoing gut microbiota adaption in this time period. After 4.5 yr, the patient's bacteria attained donor-like compositions at phylum, class, and order levels with similar bacterial diversity. Differences in the bacterial communities between donor and patient after 4.5 yr were seen at lower taxonomic levels. C. difficile remained undetectable throughout the entire timespan. This demonstrated sustainable donor feces engraftment and verified long-term therapeutic success of FMT on the molecular level. Full engraftment apparently required longer than previously acknowledged, suggesting the implementation of year-long patient follow-up periods into clinical practice. The identified dsDNA viruses were mainly Caudovirales phages. Unexpectedly, sequences related to giant algae–infecting Chlorella viruses were also detected. Our findings indicate that intestinal viruses may be implicated in the establishment of gut microbiota. Therefore, virome analyses should be included in gut microbiota studies to determine the roles of phages and other viruses—such as Chlorella viruses—in human health and disease, particularly during RCDI.
De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif-containing protein 1 are associated with intellectual disability and developmental delay
Authors: Yang Hui , Douglas Ganka , Monaghan Kristin G. , Retterer Kyle , Cho Megan T. , Escobar Luis F. , Tucker Megan E. , Stoler Joan , Rodan Lance H. , Stein Diane , Marks Warren , Enns Gregory M. , Platt Julia , Cox Rachel , Wheeler Patricia G. , Crain Carrie , Calhoun Amy , Tryon Rebecca , Richard Gabriele , Vitazka Patrik , Chung Wendy K.
Published: October 2015

Whole-exome sequencing (WES) represents a significant breakthrough in clinical genetics, and identifies a genetic etiology in up to 30% of cases of intellectual disability (ID). Using WES, we identified seven unrelated patients with a similar clinical phenotype of severe intellectual disability or neurodevelopmental delay who were all heterozygous for de novo truncating variants in the AT-hook DNA-binding motif–containing protein 1 (AHDC1). The patients were all minimally verbal or nonverbal and had variable neurological problems including spastic quadriplegia, ataxia, nystagmus, seizures, autism, and self-injurious behaviors. Additional common clinical features include dysmorphic facial features and feeding difficulties associated with failure to thrive and short stature. The AHDC1 gene has only one coding exon, and the protein contains conserved regions including AT-hook motifs and a PDZ binding domain. We postulate that all seven variants detected in these patients result in a truncated protein missing critical functional domains, disrupting interactions with other proteins important for brain development. Our study demonstrates that truncating variants in AHDC1 are associated with ID and are primarily associated with a neurodevelopmental phenotype.
Uniqueness of the macromolecular crystallographic phase problem
Authors: Millane Rick P. , Arnal Romain D.
Published: October 2015

Uniqueness of the phase problem in macromolecular crystallography, and its relationship to the case of single particle imaging, is considered. The crystallographic problem is characterized by a constraint ratio that depends only on the size and symmetry of the molecule and the unit cell. The results are used to evaluate the effect of various real-space constraints. The case of an unknown molecular envelope is considered in detail. The results indicate the quite wide circumstances under whichab initiophasing should be possible.
Proactive treatment with calcipotriol reduces recurrence of plaque psoriasis
Authors: Ito Kotaro , Koga Monji , Shibayama Yoshitsugu , Tatematsu Saori , Nakayama Juichiro , Imafuku Shinichi
Published: October 2015

Topical calcipotriol is a widely used treatment for plaque‐type psoriasis worldwide, and has been shown to improve psoriatic plaques as well as very potent corticosteroids. However, there remains the practical question of whether calcipotriol application should continue on healed pigmentation/depigmentation associated with psoriatic plaques. Therefore, we conducted a pilot clinical study to answer this question. Plaque‐type psoriatic patients not receiving systemic treatment were enrolled and treated with calcipotriol for 8 weeks (stage I) to achieve maximum effect. The patients were then divided into two groups: group A continued to apply calcipotriol to the entirety of the previous lesion (including pigmentation/depigmentation) regardless of whether skin was healed or not, while group B applied calcipotriol to the remaining lesion only. Patients were followed for 12 weeks (stage II) and dates of plaque recurrence were recorded. A total of 29 patients (13 men, 16 women) were enrolled. During stage I, reductions in scores for redness, induration and scale occurred in 40%, 47% and 55% of patients, respectively. After stage II was completed, group A (n = 19) showed a significantly better Kaplan–Meier curve of non‐recurrence than group B (n = 8, P < 0.01). The mean non‐recurrence duration was 76.8 ± 11.8 in group A and 35.0 ± 12.0 in group B. Our study showed that applying topical calcipotriol on seemingly healed psoriatic plaque lesions suppresses recurrence better than applying it only on remaining plaques. This finding may be important for instructing psoriatic patients on topical calcipotriol treatment.
Advice, authority and autonomy in shared decision‐making in antenatal screening: the importance of context
Authors: Pilnick Alison , Zayts Olga
Published: October 2015

Shared decision‐making (SDM) has been widely advocated across many branches of healthcare, yet there is considerable debate over both its practical application and how it should be examined or assessed. More recent discussions of SDM have highlighted the important of context, both internal and external to the consultation, with a recognition that decisions cannot be understood in isolation. This paper uses conversation analysis (CA) to examine how decision‐making is enacted in the context of antenatal screening consultations in Hong Kong. Building on previous CA work (Collins et al. , Toerien et al. 2013), we show that, whilst previously identified formats are used here to present the need for a decision, the overriding basis professionals suggest for actually making a decision in this context is the level of worry or concern a pregnant woman holds about potential foetal abnormality. Professionals take an unknowing ‘epistemic stance’ (Heritage ) towards this worry, and hence step back from involvement in decision‐making. We argue that this is linked to the non‐directive ethos that prevails in antenatal screening services, and suggest that more research is needed to understand how the enactment of SDM is affected by wider professional contexts and parameters.
The Levant Company under Attack in Parliament, 1720–53
Authors: Wagner Michael
Published: October 2015

Parliamentary debates concerning the British chartered companies in the 18th century are an important resource which can provide a range of insights into the fate of the companies, the concerns of British economic policy, and the process of political decision making on economic issues. Of all the parliamentary debates concerning chartered companies in the 18th century, those concerning the Levant Company have received the least scholarly attention. This article examines a series of debates involving the Levant Company during the period 1720–53. These debates saw the company increasingly put on the defensive. By the middle of the century, there was, in the words of the duke of Bedford, ‘a very great outcry against companies of all kinds’. However, the debates concerning the Levant Company did not turn on competing views regarding political economy. War was an influence on the timing of the debates, but it was the economic impact of the company's deteriorating competitive position on its woollen cloth suppliers from the west country which was crucial. As French competition gained momentum, cloth exports fell and the political pressure on the company intensified. In the face of this, the company was far from defenceless in parliament. It had influential supporters and did not hesitate to pander to fears about the potential domination of its trade by jewish merchants. The company was forced to lower its admission fee in 1753, but survived and continued to operate into the 19th century.
Edwardian Conservatism and the Constitution: The Thought of Lord Hugh Cecil
Authors: Manton Kevin
Published: October 2015

This article presents an analysis of the political thought of Lord Hugh Cecil. It argues that in order to understand Cecil's thought it is necessary to emphasize the role of the constitution in his thinking. There are three reasons for this. First, his opposition to Chamberlain's tariff reform campaign was rooted in a view of the detrimental effects the policy would have on politics, evidence for which Cecil saw in the tactics used by the tariff reformers. Second, because his opposition to the Parliament Bill and to the home rule proposals, which lay behind the removal of the house of lords' veto, was similarly rooted in what he saw as the unconstitutional nature of these measures. Third, because Cecil was an active proponent of constitutional reforms that were designed to ensure that the second chamber could still exercise a restraining influence on government and so stand up for the interests of what he saw as the moderate majority of the people.
A toolbox for studying thermal heterogeneity across spatial scales: from unmanned aerial vehicle imagery to landscape metrics
Authors: Faye Emile , Rebaudo François , Yánez‐Cajo Danilo , Cauvy‐Fraunié Sophie , Dangles Olivier
Published: October 2015

A major barrier for the scientific community of climate change biologists is the spatial mismatch between the size of organisms and the resolution at which global climate data are collected and modelled. Thus, the development of integrative and quantitative tools for the monitoring and spatial characterization of microclimates across spatial scales is a key issue for climate change ecologists.

We proposed an integrative toolbox for quantifying the spatial heterogeneity in surface temperatures by bringing together procedures of unmanned aerial vehicles, thermal imagery, orthomosaic, GIS classification and spatial metrics. This toolbox permits to yield high‐resolution visual and infrared orthoimages that are processed into a GIS for selecting surfaces of interest in the landscape (e.g. soil, vegetation). Then, the thermal matrices of selected surfaces (i.e. temperature values of the pixels belonging to the selected surfaces only) are processed within r to generate a variety of thermal landscape metrics (e.g. thermal patch richness and density, thermal aggregation and cohesion index).

We applied this toolbox to the thermal characterization of mountainous agricultural landscapes in Ecuador with implications for ectothermic pest dynamics. UAV flights at a height of 60 m above‐ground level allowed us to acquired high‐resolution visual and thermal images (1 and 5 cm/pixel, respectively) for 12 potato fields with a mean surface of 1017 ± 117 m2. Landscape metrics on plant and soil surfaces showed that crop phenology drives the spatial patterns of surface temperatures and strongly modifies the overall thermal ecology of crop fields, with potential implications for ectothermic pest occurrence and dynamics.

Overall, our toolbox affords a timely and innovative methodological framework to better assess the thermal heterogeneity of natural landscapes across a wide range of spatial scales. In particular, this toolbox would be of topical interest for ecologists trying to bridge the gap between the resolution of their climatic data and the body size of their study organisms.
The Universal Floristic Quality Assessment (FQA) Calculator: an online tool for ecological assessment and monitoring
Authors: Freyman William A. , Masters Linda A. , Packard Stephen
Published: October 2015

Floristic Quality Assessments (FQAs) are measurements of a natural area's ecological integrity based on their plant species composition. Widely used by government agencies and conservation organizations to monitor and assess natural areas, FQA data bases have been developed for much of the United States and beyond.

Here, we present the Universal FQA Calculator (http://universalFQA.org), a free, open‐source web‐based FQA Calculator. The calculator offers 30 FQA data bases (with more being added regularly) from across the United States and Canada and has been used to calculate thousands of assessments. The Universal FQA Calculator's growing repository for site inventory and transect data is accessible via a REST API and represents a valuable resource for data on the occurrence and abundance of plant species.

We describe the features and implementation of the Universal FQA Calculator, provide a summary of its increasing usage and discuss the benefits of cloud‐based storage of ecological assessment data.
Neural substrates of cue reactivity: association with treatment outcomes and relapse
Authors: Courtney Kelly E. , Schacht Joseph P. , Hutchison Kent , Roche Daniel J. O. , Ray Lara A.
Published: October 2015

Given the strong evidence for neurological alterations at the basis of drug dependence, functional magnetic resonance imaging (fMRI) represents an important tool in the clinical neuroscience of addiction. fMRI cue‐reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the reward/motivation system in addiction and potentially offer a translational mechanism by which interventions and behavioral predictions can be tested. Thus, this review summarizes the research that has applied fMRI cue‐reactivity paradigms to the study of adult substance use disorder treatment responses. Studies utilizing fMRI cue‐reactivity paradigms for the prediction of relapse and as a means to investigate psychosocial and pharmacological treatment effects on cue‐elicited brain activation are presented within four primary categories of substances: alcohol, nicotine, cocaine and opioids. Lastly, suggestions for how to leverage fMRI technology to advance addiction science and treatment development are provided.
Morphology of the greater palatine grooves of the hard palate: a cone beam computed tomography study
Authors: Monsour P , Huang T
Published: October 2015

Background

There is increasing frequency of dentoalveolar and palatal implants placed in the posterior maxilla for prosthodontic and orthodontic purposes. The purpose of this study is to provide information on the location and morphology of the greater palatine grooves (GPG) in the hard palate and to promote awareness of this structure.

Methods

Eighty‐nine cone beam computed tomography (CBCT) scans were analysed for the presence of a groove, crest or bridging.

Results

This study on the morphology of the GPG in the maxillary first and second molar regions showed three distinct appearances: (1) no palatal groove; (2) one palatal groove; (3) two palatal grooves. The detection frequency of no palatal groove in the first molar region was 60%, 34% had one groove and 6% having two grooves. The detection frequency of no palatal groove in the second molar region was 72%, 26% had one groove and 2% had two grooves. The number of crests in the first and second molar regions ranged from 0 to 3.

Conclusions

The present study demonstrates a great variation in morphology of the GPG of the hard palate. Knowledge of the GPG will decrease possible complications of implant surgery, particularly palatal implant surgery and to not confuse the GPG with pathology.
Immunolocalization and distribution of proteoglycans in carious dentine
Authors: Stankoska K , Sarram L , Smith S , Bedran‐Russo AK , Little CB , Swain MV , Bertassoni LE
Published: October 2015

Background

Collagen type I, proteoglycans (PG) and non‐collagenous proteins represent important building blocks of the dentine matrix. While different PGs have been identified in dentine, changes in the distribution of these macromolecules with the progression of caries have been poorly characterized. The aim of this study was to compare the immunolocalization of three small collagen‐binding PGs (biglycan, fibromodulin and lumican) as well as collagen (types I and VI) in healthy versus carious dentine.

Methods

Longitudinal demineralized sections of extracted teeth were stained with antibodies recognizing specific PG core proteins and collagens, as well as glycosaminoglycans (GAGs) with toluidine blue.

Results

In healthy dentine, PGs appeared to be more abundant near the tubule walls and directly under the cusps. Conversely, in carious dentine, specific locations appeared to be more prone to PG degradation than others. These degradation patterns were well correlated with the progression of caries into the tissue, and also appeared to trigger interesting morphological changes in the tissue structure, such as the deformation of dentine tubules near highly infected areas and the lower concentration of PG in tertiary dentine.

Conclusions

This study presents new insights into the involvement of PGs in the progression of caries.
Rousseau on Freedom in Commercial Society
Authors: Rousselière Geneviève
Published: October 2015

Rousseau consistently declares that commercial society prevents us from being free because it makes us dependent on others and on endless desires in ways we cannot control. Yet, in Emile, Rousseau makes the surprising claim that it is possible for an elite to be free in commercial society. This possibility reveals a third way between the model of man and of citizen, that is, the model of natural man in society. I argue that it provides an original way of resisting dependence through a combination of distance from corrupt values and adaptation to the mechanisms of the economic market. Emile’s ultimate function, however, is critical in addition to being practical and pedagogical. By following Emile's experiences, the reader learns the unbearably high cost of commercial society: Freedom within it is impoverished and available only to the few.
Effects of renal denervation on renal pelvic contractions and connexin expression in rats
Authors: Koenen A. , Steinbach A. , Schaper K. , Zimmermann U. , Miehe B. , Kurt B. , Rettig R. , Grisk O.
Published: October 2015

Aims

The renal pelvis shows spontaneous rhythmic contractile activity. We assessed to what extent this activity depends on renal innervation and studied the role of connexins in pelvic contractions.

Methods

Rats underwent unilateral renal denervation or renal transplantation. Renal pelvic pressure and diuresis were measured in vivo. Spontaneous and agonist‐induced contractions of isolated renal pelves were investigated by wire myography. Rat and human renal pelvic connexin mRNA abundances and connexin localization were studied by real‐time PCR and immunofluorescence respectively.

Results

Renal denervation or transplantation increased renal pelvic pressure in vivo by about 60 and 150%, respectively, but did not significantly affect pelvic contraction frequency. Under in vitro conditions, isolated pelvic preparations from innervated or denervated kidneys showed spontaneous contractions. Pelves from denervated kidneys showed about 50% higher contraction frequencies than pelves from innervated kidneys, whereas contraction force was similar in pelves from denervated and innervated kidneys. There was no denervation‐induced supersensitivity to noradrenaline or endothelin‐1. Renal denervation did not increase pelvic connexin37, 40, 43 or 45 mRNA abundances. Gap junction blockade had no effect on spontaneous pelvic contractile activity.

Conclusions

The denervation‐induced effect on pelvic pressure may be the consequence of the enhanced diuresis. The mechanisms underlying the denervation‐induced effects on pelvic contraction frequency remain unknown. Our data rule out a major role for two important candidates, by showing that renal denervation neither induced supersensitivity to contractile agonists nor increased connexin mRNA abundance in the pelvic wall.
Smoking behaviour and knowledge of the health effects of smoking in patients with inflammatory bowel disease
Authors: De Bie C. , Ballet V. , Hendriks N. , Coenen S. , Weyts E. , Van Assche G. , Vermeire S. , Ferrante M.
Published: October 2015

Background

The detrimental effect of smoking on development and progression of Crohn's disease (CD) is generally accepted.

Aim

To evaluate the awareness of smoking risks in a Belgian inflammatory bowel disease (IBD) population.

Methods

In the out‐patient clinic of a tertiary referral centre, 625 consecutive patients with CD, 238 patients with ulcerative colitis (UC) and 289 non‐IBD controls, filled out a simple questionnaire. This questionnaire included data on smoking behaviour and awareness of smoking‐related health effects, including effects on IBD.

Results

At diagnosis, more CD patients were active smokers compared to UC (40% vs. 17%, P < 0.001). Remarkably, smoking cessation rates after diagnosis were similar for CD and UC (both 56%, P = 0.997). The great majority recognised a detrimental influence of smoking on general health (98–99%), lung cancer (95–97%), myocardial infarction (89–92%) and stroke (78–87%). Although CD patients more frequently acknowledged risks of smoking on their disease, only 37% were aware of a link with CD development, 30% of increased surgical rates and 27% of increased post‐operative CD recurrence. Active smokers more frequently denied an increased risk of surgery and higher post‐operative CD recurrence. Intriguingly, within the active smokers with CD, those not willing to quit smoking most often denied a potential bad influence of smoking. Taking into account disease duration, previous surgery, education level, working status and nicotine dependence, we were unable to define specific subgroups of patients requiring extra education.

Conclusion

Although patients with Crohn's disease were better informed on the detrimental effects of smoking, the awareness rate was still low.
Conception rates in farm mink (Neovison vison) in relation to first mating date, age and color variety
Authors: Felska‐Błaszczyk Lidia , Lasota Bogdan , Seremak Beata
Published: October 2015

The aim of the study was to analyze the effects of the first mating date, age and color variety on the conception rates in farm mink. We analyzed female mink reproductive performance in 492 Sapphire and 463 Standard Black females over 3 or 4 years. The analysis included the number of inefficient matings, the interval between the first inefficient mating and the efficient mating (copulation) and the conception rates. The results show a significant effect of female's age and color variety on the conception rates. The youngest, yearling females of either color needed a higher number of matings per conception, as compared to older, 2‐ and 3‐year‐old females. Black females demonstrated a higher number of inefficient matings (1.066), as compared with Sapphires (0.730). Yearling females were most often mated from 1 to 10 March, and older females from 11 to 20 March. Older females achieved better conception rates than the yearlings. Dates between 11 and 25 March proved to be the optimum for the first mating, since the highest conception rates were observed if the females had mated during this period.
Microscopic haematuria at time of diagnosis is associated with lower disease stage in patients with newly diagnosed bladder cancer
Authors: Ramirez Daniel , Gupta Amit , Canter Daniel , Harrow Brian , Dobbs Ryan W. , Kucherov Victor , Mueller Edward , Streeper Necole , Uhlman Matthew A. , Svatek Robert S. , Messing Edward M. , Lotan Yair
Published: October 2015

Objectives

To determine whether the severity of haematuria (microscopic or gross) at diagnosis influences the disease stage at presentation in patients diagnosed with bladder cancer.

Patients and Methods

We conducted a multi‐institutional observational cohort study of patients who were newly diagnosed with bladder cancer between August 1999 and May 2012. We reviewed the degree of haematuria, demographic information, clinical and social history, imaging, and pathology. The association of haematuria severity with incident tumour stage and grade was evaluated using logistic regression.

Results

Patients diagnosed with bladder cancer presented with gross haematuria (GH; 1 083, 78.3%), microscopic haematuria (MH; 189, 13.7%) or without haematuria (112, 8.1%). High‐grade disease was found in 64% and 57.1% of patients presenting with GH and MH, respectively, and severity of haematuria was not associated with higher grade disease. Stage of disease at diagnosis for patients presenting with MH was Ta/carcinoma in situ (CIS) in 68.8%, T1 in 19.6%, and ≥T2 in 11.6%. Stage of disease at diagnosis for patients presenting with GH was Ta/CIS in 55.9%, T1 in 19.6%, and ≥T2 in 17.9%. On multivariate analyses, GH was independently associated with ≥T2 disease at diagnosis (odds ratio 1.69, 95% confidence interval 1.05–2.71, P = 0.03).

Conclusions

Among patients with newly diagnosed bladder cancer, presentation with GH is associated with a more advanced pathological stage. Earlier detection of disease, before development of GH, could influence survival in patients with bladder cancer. Type of haematuria at presentation does not impact grade of disease.
Robot‐assisted partial nephrectomy with intracorporeal renal hypothermia using ice slush: step‐by‐step technique and matched comparison with warm ischaemia
Authors: Ramirez Daniel , Caputo Peter A. , Krishnan Jayram , Zargar Homayoun , Kaouk Jihad H.
Published: October 2015

Objectives

To outline our step‐by‐step technique for intracorporeal renal cooling during robot‐assisted partial nephrectomy (RAPN).

Patients and Methods

Patient selection was performed during a preoperative clinic visit. Cases where we estimated during preoperative assessment that warm ischaemia time would be >30 min, as determined by whether the patient had a complex renal mass, were selected. The special equipment required for this procedure includes an Ecolab Hush Slush machine (Microtek Medical Inc., Columbus, MS, USA) a Mon‐a‐therm needle thermocouple device (Covidien, Mansfield, MA, USA) and six modified 20‐mL syringes. Patients are arranged in a 60° modified flank position with the operating table flexed slightly at the level of the anterior superior iliac spine. For the introduction of a temperature probe and ice slush, an additional 12‐mm trocar is placed along the mid‐axillary line beneath the costal margin. Modified 10/20 mL syringes are prefilled with ice slush for instillation via an accessory trocar. Peri‐operative and 6‐month functional outcomes in the cold ischaemia group were compared with those of a cohort of patients who underwent RAPN with warm ischaemia in a 2:1 matched fashion. Matching was performed based on preoperative estimated glomerular filtration rate (GFR), ischaemia time and RENAL nephrometry score.

Results

Strategies for successful intracorporeal renal cooling include: (i) placement of accessory port directly over the kidney; (ii) uniform ice consistency and modified syringes; (iii) sequential clamping of renal artery and vein; (iv) protection of the neighbouring intestine with a laparoscopic sponge; and (v) complete mobilization of the kidney. Kidney temperature is monitored via a needle thermocoupler device, while core body temperature is concurrently monitored via an oesophageal probe in real time. Renal function was assessed by serum creatinine level, estimated GFR (eGFR) and mercaptoacetyltriglycine (MAG‐3) renal scan, peri‐operatively and at 6‐month follow‐up. In the separate matched analysis, cold ischaemia during RAPN was found to be associated with a 12.9% improvement in preservation of postoperative eGFR. No difference was seen in either group at 6‐month follow‐up.

Conclusions

We conclude that RAPN with intracorporeal renal hypothermia using ice slush is technically feasible and may improve postoperative renal function in the short term. Our technique for intracorporeal hypotheramia is cost‐effective, simple and highly reproducible.
Sleep Disturbance and Expressive Language Development in Preschool‐Age Children With Down Syndrome
Authors: Edgin Jamie O. , Tooley Ursula , Demara Bianca , Nyhuis Casandra , Anand Payal , Spanò Goffredina
Published: October 2015

Recent evidence has suggested that sleep may facilitate language learning. This study examined variation in language ability in 29 toddlers with Down syndrome (DS) in relation to levels of sleep disruption. Toddlers withDSand poor sleep (66%,n = 19) showed greater deficits on parent‐reported and objective measures of language, including vocabulary and syntax. Correlations between sleep and language were found in groups with equivalent medical and social backgrounds and after control for relevant behavioral comorbidities, including autism symptoms. These results emphasize the important role of quality sleep in all children's expressive language development, and may help increase our understanding of the etiology of language deficits in developmental disorders, potentially leading to new treatment approaches.
Lipoprotein(a) and apolipoprotein(a) in polycystic ovary syndrome
Authors: Enkhmaa Byambaa , Anuurad Erdembileg , Zhang Wei , Abbuthalha Adnan , Kaur Parneet , Visla Jasmeen , Karakas Sidika , Berglund Lars
Published: October 2015

Objective

Levels of lipoprotein(a), Lp(a), an independent risk factor for cardiovascular disease (CVD), are affected by sex hormones. Women with polycystic ovary syndrome (PCOS) have elevated androgen levels and are at increased CVD risk. We investigated the impact of PCOS‐related hormonal imbalance on Lp(a) levels in relation to apo(a) gene size polymorphism, a major regulator of Lp(a) level.

Design

Cross‐sectional.

Patients

Forty‐one Caucasian women with PCOS based on the NIH criteria.

Measurements

(1) Apo(a) gene size polymorphism measured as Kringle (K) 4 repeat number; (2) total plasma Lp(a) level; (3) allele‐specific apo(a) level assessing the amount of Lp(a) carried by an individual apo(a) allele/isoform; and (4) sex hormone levels.

Results

The mean age was 32 ± 6 years, and the mean BMI was 35 ± 8 with 66% of women classified as obese (BMI >30 kg/m2). LDL cholesterol was borderline high (3·37 mmol/l), and HDL cholesterol was low (1·06 mmol/l). The distribution of Lp(a) level was skewed towards lower levels with a median level of 22·1 nmol/l (IQR: 6·2–66·5 nmol/l). Lp(a) levels were not correlated with age, body weight or BMI. The median allele‐specific apo(a) level was 10·6 nmol/l (IQR: 3·1–31·2 nmol/l), and the median apo(a) size was 27 (IQR: 23–30) K4 repeats. Allele‐specific apo(a) levels were significantly and inversely correlated with K4 repeats (r = −0·298, P = 0·007). Neither Lp(a) nor allele‐specific apo(a) levels were significantly associated with testosterone or dehydroepiandrosterone sulphate levels.

Conclusions

The apo(a) genetic variability remains the major regulator of plasma Lp(a) levels in women with PCOS.
Gamma knife radiosurgery in patients with persistent acromegaly or Cushing's disease: long‐term risk of hypopituitarism
Authors: Cohen‐Inbar Or , Ramesh Arjun , Xu Zhiyuan , Vance Mary Lee , Schlesinger David , Sheehan Jason P.
Published: October 2015

Introduction

For patient with a recurrent or residual acromegaly or Cushing's disease (CD) after resection, gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long‐term follow‐up has hampered understanding of the latent risks of hypopituitarism in patients with acromegaly or CD. We report the long‐term risks of hypopituitarism for patients treated with GKRS for acromegaly or CD.

Methods

From a prospectively created, IRB‐approved database, we identified all patients with acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow‐up of 60 months were included. The median follow‐up is 159·5 months (60·1–278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow‐up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement.

Results

Sixty patients with either acromegaly or CD were included. Median tumour volume at time of GKRS was 1·3 cm3 (0·3–13·4), and median margin dose was 25 Gy (6–30). GKRS‐induced new pituitary deficiency occurred in 58·3% (n = 35) of patients. Growth hormone deficiency was most common (28·3%, n = 17). The actuarial overall rates of hypopituitarism at 3, 5 and 10 years were 10%, 21·7% and 53·3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12–160). Cavernous sinus invasion of the tumour was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (P = 0·018).

Conclusions

Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.
Maternal morbid obesity: financial implications of weight management
Authors: Caldas M. C. , Serrette J. M. , Jain S. K. , Makhlouf M. , Olson G. L. , McCormick D. P.
Published: October 2015

The objective of this study was to evaluate health outcomes and costs of pregnancies complicated by extreme maternal obesity (class III obesity, body mass index ≥ 40). We conducted a retrospective case‐control descriptive study comparing extremely obese women (cases) and their infants with randomly selected controls. Health outcomes were obtained from the medical records and costs from billing data. Total costs for each mother–infant dyad were calculated. Compared with 85 controls, the 82 cases experienced higher morbidity, higher costs and prolonged hospital stay. However, 26% of cases maintained or lost weight during pregnancy, whereas none of the controls maintained or lost weight during pregnancy. When mother/infant dyads were compared on costs, case subjects who maintained or lost weight experienced lower costs than those who gained weight. Neonatal intensive care consumed 78% of total hospital costs for infants of the obese women who gained weight, but only 48% of costs for infants of obese women who maintained or lost weight. For extremely obese women, weight management during pregnancy was achievable, resulted in healthier neonatal outcomes and reduced perinatal healthcare costs.
Impact of insulin initiation on glycaemic variability and glucose profiles in a primary healthcare Type 2 diabetes cohort: analysis of continuous glucose monitoring data from the INITIATION study
Authors: Manski‐Nankervis J. , Yates C. J. , Blackberry I. , Furler J. , Ginnivan L. , Cohen N. , Jenkins A. , Vasanthakumar S. , Gorelik A. , Young D. , Best J. , O'Neal D.
Published: October 2015

Aim

To use continuous glucose monitoring to examine the effects of insulin initiation with glargine, with or without glulisine, on glycaemic variability and glycaemia in a cohort of people with Type 2 diabetes receiving maximum oral hypoglycaemic agents in primary healthcare.

Methods

We conducted a post hoc analysis of continuous glucose monitoring data from 89 participants at baseline and at 24 weeks after insulin commencement. Indicators of glycaemic variability (standard deviation, J‐index and mean amplitude of glycaemic excursion) and glycaemia (HbA1c, mean glucose, area under the glucose–time curve) were assessed. Multi‐level regression analysis was used to identify the predictors of change.

Results

Complete glycaemic variability data were available for 78 participants. Of these participants, 41% were women, their mean (sd) age was 59.2 (10.4) years, the median (interquartile range) diabetes duration was 10.4 (6.5, 13.3) years and the median (interquartile range) baseline HbA1c was 82.5 (71.6, 96.7) mmol/mol [9.7 (8.7, 11.0)%]. At baseline, BMI correlated negatively with standard deviation (r = −0.30) and mean amplitude of glycaemic excursion (r = −0.26), but not with J‐index; HbA1c correlated with J‐index (r = 0.61) but not with mean amplitude of glycaemic excursion and standard deviation. After insulin initiation the mean (sd) glucose level decreased [from 12.0 (3.0) to 8.5 (1.6) mmol/l; P < 0.001], as did the median (interquartile range) J‐index [from 66.9 (47.7, 95.1) to 36.9 (27.6, 49.8) mmol/l; P < 0.001]. Baseline HbA1c correlated with a greater J‐index reduction (r = −0.45; P < 0.001). The mean amplitude of glycaemic excursion and standard deviation values were unchanged. The baseline temporal profile, showing elevated postprandial morning glucose levels, was unchanged after insulin initiation, despite an overall reduction in glycaemia.

Conclusion

Insulin initiation reduced hyperglycaemia but did not alter glycaemic variability in adults with Type 2 diabetes receiving maximum oral hypoglycaemic agents. The most significant postprandial excursions were seen in the morning, which identifies prebreakfast as the most effective target for short‐acting insulin therapy.
Effect of high‐dose atorvastatin on the cardiovascular risk associated with individual components of metabolic syndrome: a subanalysis of the Treating to New Targets (TNT) study
Authors: Deedwania P. C. , Shepherd J. , Breazna A. , DeMicco D. A. ,   on Behalf of the Treating to New Targets (TNT) Steering Committee Investigators
Published: October 2015

Aims

To investigate the impact of intensive lipid‐lowering with high‐dose atorvastatin on the cardiovascular risk associated with individual metabolic syndrome components [high body mass index (BMI), elevated triglycerides, low high‐density lipoprotein (HDL) cholesterol, hypertension and elevated fasting glucose] in patients with coronary heart disease (CHD).

Methods

Patients with clinically evident, stable CHD and low‐density lipoprotein (LDL) cholesterol <3.4 mmol/l (130 mg/dl) were randomized to double‐blind therapy with atorvastatin 10 mg/day (n = 5006) or 80 mg/day (n = 4995) after an 8‐week open‐label run‐in with atorvastatin 10 mg. The median follow‐up was 4.9 years. The impact of individual metabolic syndrome risk factors was tested on the primary endpoint, which was the occurrence of a first major cardiovascular event.

Results

On‐treatment LDL cholesterol was 2.6 mmol/l (101 mg/dl) with atorvastatin 10 mg and 2.0 mmol/l (77 mg/dl) with atorvastatin 80 mg. Among patients receiving atorvastatin 10 mg, the presence of each individual metabolic syndrome component significantly increased the risk of major cardiovascular events compared with the absence of each (BMI, p = 0.014; triglycerides, p = 0.006; HDL cholesterol, p = 0.0006; hypertension, p < 0.0001; and fasting glucose p < 0.0001). In patients receiving atorvastatin 80 mg, elevated triglycerides and fasting glucose were no longer significant predictors of major cardiovascular events. The predictive power of hypertension on the risk of major cardiovascular events was reduced in patients treated with atorvastatin 80 mg, although it remained a significant predictor.

Conclusions

Treatment with high‐dose atorvastatin to a mean LDL cholesterol level of 2.0 mmol/l (77 mg/dl) considerably attenuated the predictive power associated with three metabolic syndrome components.
Early renin‐angiotensin system intervention is more beneficial than late intervention in delaying end‐stage renal disease in patients with type 2 diabetes
Authors: Schievink B. , Kröpelin T. , Mulder S. , Parving H.‐H. , Remuzzi G. , Dwyer J. , Vemer P. , de Zeeuw D. , Lambers Heerspink H. J.
Published: October 2015

Aims

To develop and validate a model to simulate progression of diabetic kidney disease (DKD) from early onset until end‐stage renal disease (ESRD), and to assess the effect of renin‐angiotensin system (RAS) intervention in early, intermediate and advanced stages of DKD.

Methods

We used data from the BENEDICT, IRMA‐2, RENAAL and IDNT trials that assessed effects of RAS intervention in patients with type 2 diabetes. We built a model with discrete disease stages based on albuminuria and estimated glomerular filtration rate (eGFR). Using survival analyses, we assessed the effect of RAS intervention on delaying ESRD in early [eGFR>60 ml/min/1.73 m2 and albumin:creatinine ratio (ACR) <30 mg/g], intermediate (eGFR 30–60 ml/min/1.73 m2 or ACR 30–300 mg/g) and advanced (eGFR <30 ml/min/1.73 m2 or ACR >300 mg/g) stages of DKD for patients in different age groups.

Results

For patients at early, intermediate and advanced stage of disease, whose mean age was 60 years and who received placebo, the median time to ESRD was 21.4, 10.8 and 4.7 years, respectively. RAS intervention delayed the predicted time to ESRD by 4.2, 3.6 and 1.4 years, respectively. The benefit of early RAS intervention was more pronounced in younger patients; for example, for patients with a mean age of 45 years, RAS intervention at early, intermediate or advanced stage delayed ESRD by 5.9, 4.0 and 1.1 years versus placebo.

Conclusions

RAS intervention early in the course of proteinuric DKD is more beneficial than late intervention in delaying ESRD.
Genotypic differences in embryonic life history traits ofFolsomia quadrioculata(Collembola: Isotomidae) across a wide geographical range
Authors: SENGUPTA SAGNIK , ERGON TORBJØRN , LEINAAS HANS PETTER
Published: October 2015

1. Life history traits play a central role in adaptation to specific environmental conditions. Egg development time, hatchling, and egg batch size in 10 populations of the soil‐dwelling collembolan speciesFolsomia quadrioculata(Tullberg, 1871) from diverse habitats across arctic and temperate regions, ranging in latitude from 43 to 81°N were studied.

2. For all traits, 15 °C was used as the reference temperature. Phenotypic plasticity was studied by changing temperature to 10 and 20 °C in hatchling size, and to 20 °C in egg development time. The effect of latitude, climatic zone, and summer temperature at their sites of sampling was tested to address the hypotheses that populations from cooler areas would have (i) a faster temperature‐dependent egg development, (ii) a larger hatchling size, (iii) smaller egg batches and (iv) higher phenotypic plasticity

3. The first and fourth hypothesis were not supported, whereas the second and third were partly supported when including the whole latitudinal gradient, but not within regions. Plasticity showed a complex pattern, including large differences between populations from similar macroclimates and considerable similarity between some populations from contrasting climates. Small effects of latitude and macroclimatic variables emphasised that local climate and microhabitat should be taken into account when evaluating thermal conditions as possible drivers of population‐specific differences in soil‐dwelling ectotherms.

4. There was a trade‐off between egg batch and hatchling sizes. A weak correlation between the population mean egg development time and the mean hatchling size suggested that the populations are, or have been, exposed to differential selection.
Otolith elemental characteristics of whitefish (Coregonus lavaretus) from brackish waters of the Gulf of Bothnia, Baltic Sea
Authors: Hägerstrand Henry , Himberg Mikael , Jokikokko Erkki , von Numers Mikael , Mrówczyńska Lucyna , Vasemägi Anti , Wiklund Tom , Lill Jan‐Olof
Published: October 2015

To investigate whether European whitefish (Coregonus lavaretus) groups in the brackish (≤7%) Gulf of Bothnia (Baltic Sea) express specific otolith elemental characteristics, concentrations of elements (Ca, Ba, Sr, Zn, Mn, Fe) in whole otoliths were studied by inductively coupled plasma‐optical emission spectrometry. Whitefish (N = 67) were sampled from six different latitudinal sites; four in the sea and two in rivers along the west coast of Finland, and from a fresh water lake for comparison. The concentration of several elements showed significant differences among sampling sites. Otolith Ba concentrations were higher at the northern sampling sites compared to the southern ones, thereby showing negative association to capture‐habitat salinity. In contrast, otolith Sr and Zn concentrations were lower at the northern sampling sites, thereby associating positively to capture‐habitat salinity. Otolith Mn concentrations did not associate with latitude or salinity but markedly varied between sampling sites. Elevated Fe concentrations occurred in fish otoliths from the two northernmost sites. Ca concentrations were at the same levels in otoliths from all whitefish samples. Otoliths of whitefish from the lake had very high Ba and low Sr concentrations compared to concentrations in otoliths from whitefish in the sea and rivers. Our results show that otolith elemental characteristics of whitefish vary considerably at various geographic scales showing high potential for population identification using elemental fingerprints. Analysis of otolith elemental characteristics may therefore provide an efficient tool for the identification of main areas of residence, spawning locations, and migration routes, thus contributing towards the sustainable management of whitefish stocks.
Prevalence of migraine in persons with the 3243A>G mutation in mitochondrial DNA
Authors: Guo S. , Esserlind A.‐L. , Andersson Z. , Frederiksen A. L. , Olesen J. , Vissing J. , Ashina M.
Published: October 2015

Background and purpose

Over the last three decades mitochondrial dysfunction has been postulated to be a potential mechanism in migraine pathogenesis. The lifetime prevalence of migraine in persons carrying the 3243A>G mutation in mitochondrial DNA was investigated.

Methods

In this cross‐sectional study, 57 mDNA 3243A>G mutation carriers between May 2012 and October 2014 were included. As a control group, a population‐based cohort from our epidemiological studies on migraine in Danes was used. History of headache and migraine was obtained by telephone interview, based on a validated semi‐structured questionnaire, performed by trained physicians.

Results

The prevalence of migraine is significantly higher in persons carrying the 3243A>G mutation than in controls (58% vs. 18%; P < 0.001). This applies for both subforms of migraine, migraine without aura (47% vs. 12%; P < 0.001) and migraine with aura (18% vs. 6%; P < 0.001), and in females (58% vs. 24%; P < 0.001) and males (58% vs. 12%; P < 0.001) for any migraine.

Conclusions

A high prevalence of migraine in persons with the mDNA 3243A>G mutation was found. This finding suggests a clinical association between a monogenetically inherited disorder of mitochondrial dysfunction and susceptibility to migraine. Mitochondrial DNA aberrations may contribute to the pathogenesis of migraine.