bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of low frequency repetitive transcranial magnetic stimulation parameters on motor cortex excitability in normal subjects
Authors: Schrader Lara , Sadeghinejad Sima , Sadeghinejad Jalleh , Kazanchyan Movses , Koski Lisa , Stern John , Wu Allan , Iacoboni Marco , Nuwer Marc
Published: April 2016

Background/objectives Optimal low frequency repetitive transcranial magnetic stimulation (LF-rTMS) parameters for treating epilepsy and other brain disorders are unknown. To address this question, a systematic study of the effects of LF-rTMS frequency and intensity on cortical excitability was performed.

Methods Using a four-period crossover design, subjects were scheduled for four LF-rTMS sessions that were at least four weeks apart. LF-rTMS was delivered as 900 pulses directed at primary motor cortex using four protocols: 0.5 Hz at 90% resting motor threshold (RMT), 0.5 Hz at 110% RMT, 1 Hz at 90% RMT, and 1 Hz at 110% RMT. Motor evoked potential (MEP) amplitude, resting motor threshold (RMT), and cortical silent period (CSP) were measured before, immediately after, and 60 min after LF-rTMS. Each of the four protocols was analyzed separately to compare baseline measurements to those after LF-rTMS.

Results None of the four LF-rTMS protocols produced a trend or significant change in MEP amplitude, RMT, or CSP.

Conclusion The lack of significant effect from the four LF-rTMS protocols indicates that none produced evidence for alteration of cortical excitability. The direct comparison of four LF-rTMS protocols is distinct to this investigation, as most similar studies were exploratory and studied only one or two protocols. The negative result relates only to the methods used in this investigation and does not indicate that LF-rTMS does not alter cortical excitability with other parameters. These results may be useful when designing additional investigations into the effect of LF-rTMS on epilepsy, other disorders, and cortical excitability.
Variability of the pubic arch architecture and its influence on the minimal levator hiatus area
Authors: Rostaminia Ghazaleh , Machiorlatti Michael , Shobeiri S. Abbas , Quiroz Lieschen H.
Published: April 2016

Objective

To investigate the association between the minimal levator hiatus (MLH) area at rest with its surrounding soft‐tissue and bony structures in nulliparous asymptomatic women with a normal levator ani muscle.

Methods

A subanalysis was undertaken of a prospective study of the appearance of the levator ani in asymptomatic nulliparous women conducted between September 2010 and September 2011. The subanalysis included women with a normal levator ani muscle. Three‐dimensional ultrasonography volumes were used to obtain pelvic floor measurements.

Results

The analysis included 56 women with mean age of 43.0 ± 13.4 years. The mean MLH area was 13.1 ± 1.8 cm2 (range 9.0–17.3). The pubic arch angle had no influence on the MLH area (Pearson correlation coefficient r = 0.13). Height and pubic arch length were positively correlated with the MLH area (r = 0.26 [P = 0.52] and r = 0.50 [P < 0.001], respectively).

Conclusion

The MLH size of nulliparous women varied widely and was positively correlated with the height and pubic arch length of the women. Therefore, caution is warranted when interpreting the MLH area as an indicator of a levator ani defect or a predictor of pelvic organ prolapse without taking a woman's pelvic bone characteristics into account.
There is an agreement between constipation referred and that documented by objective criteria?
Authors: Neto Isaac José Felippe Corrêa , Maneira Ana Luiza Chaves , Teixeira Noelle Breda , Vettorato Beatriz Doine , de Oliveira Mariana Campello , Menezes Tatielle Alves Trivelato , Robles Laercio
Published: April 2016

Introduction Chronic constipation is the most common digestive complaint at the doctor's office, with high prevalence in the population. However, many patients – and even those physicians not so familiar with pelvic floor disorders–define and consider constipation based on intestinal functionality and stool consistency. But symptoms of incomplete defecation, digital maneuvers, abdominal discomfort, and straining should not be overlooked.

Objectives To investigate the correlation between constipation referred and documented through objective criteria in patients admitted on a daytime-nursing ward basis at the Hospital Santa Marcelina, São Paulo.

Methodology This is a prospective study of a random sample of patients admitted on a daytime-ward hospitalization basis at Santa Marcelina Hospital to perform minor surgical procedures not related to functional disorders of the gastrointestinal tract in the period from September 2014 to June 2015; the only exclusion criterion was “not agreed to participate in the interview conducted by students of medicine at Santa Marcelina Medical School”.

Results 102 patients were randomly analyzed in the period considered (51% female) with a mean overall age of 48.6 (19–82) years. Constipation has been reported spontaneously by 17.6% of participants and denied by 82.4%. With the implementation of the Cleveland Clinic's criteria for the diagnosis of constipation, the compliance with the referred symptomatology was 88.9%; the same value was found with the use of the Rome III criteria (Kappa = 0.665). In addition, a higher incidence of constipation was observed in female patients (p = 0.002).

Conclusion A higher incidence of constipation was observed in female participants, with no statistical difference with respect to age. Furthermore, a substantial agreement was found between constipation referred and constipation documented through objective criteria.
Bioinformatics microarray analysis and identification of gene expression profiles associated with cirrhotic liver
Authors: Chan Kun‐Ming , Wu Tsung‐Han , Wu Ting‐Jung , Chou Hong‐Shiue , Yu Ming‐Chin , Lee Wei‐Chen
Published: April 2016

Cirrhosis is the endpoint of liver fibrosis that is accompanied by limited regeneration capacity and complications and is the ultimate cause of death in many patients. Despite this, few studies have thoroughly looked at the gene expression profiles in the cirrhotic liver. Hence, this study aims to identify the genes that were differentially expressed in the cirrhotic liver and to explore the putative related signaling pathway and interaction networks. The gene expression profiles of cirrhotic livers and noncirrhotic livers were examined and compared using microarray gene analysis. Proteins encoded by the differentially expressed genes were analyzed for functional clustering and signaling pathway involvement using MetaCore bioinformatics analyses. The Gene Ontology analysis as well as the Kyoto encyclopedia of Genes and Genomes pathway analysis were also performed. A total of 213 significant genes were differentially expressed at more than a two‐fold change in cirrhotic livers as compared to noncirrhotic livers. Of these, 105 upregulated genes and 63 downregulated genes were validated through MetaCore bioinformatics analyses. The signaling pathways and major functions of proteins encoded by these differentially expressed genes were further analyzed; results showed that the cirrhotic liver has a unique gene expression pattern related to inflammatory reaction, immune response, and cell growth, and is potentially cancer related. Our findings suggest that the microarray analysis may provide clues to the molecular mechanisms of liver cirrhosis for future experimental studies. However, further exploration of areas regarding therapeutic strategy might be possible to support metabolic activity, decrease inflammation, or enhance regeneration for liver cirrhosis.
miR‐200c and phospho‐AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis
Authors: Berlanga Pablo , Muñoz Lisandra , Piqueras Marta , Sirerol J. Antoni , Sánchez-Izquierdo María Dolors , Hervás David , Hernández Miguel , Llavador Margarita , Machado Isidro , Llombart-Bosch Antonio , Cañete Adela , Castel Victoria , Font de Mora Jaime
Published: April 2016

Lung metastasis is the major cause of death in osteosarcoma patients. However, molecular mechanisms underlying this metastasis remain poorly understood. To identify key molecules related with pulmonary metastasis of pediatric osteosarcomas, we analyzed high‐throughput miRNA expression in a cohort of 11 primary tumors and 15 lung metastases. Results were further validated with an independent cohort of 10 primary tumors and 6 metastases. In parallel, we performed immunohistochemical analysis of activated signaling pathways in 36 primary osteosarcomas. Only phospho‐AKT associated with lower overall survival in primary tumors, supporting its role in osteosarcoma progression. CTNNB1 expression also associated with lower overall survival but was not strong enough to be considered an independent variable. Interestingly, miR‐200c was overexpressed in lung metastases, implicating an inhibitory feed‐back loop to PI3K‐AKT. Moreover, transfection of miR200c‐mimic in U2‐OS cells reduced phospho‐AKT levels but increased cellular migration and proliferation. Notably, miR‐200c expression strongly correlated with miR‐141 and with the osteogenic inhibitor miR‐375, all implicated in epithelial to mesenchymal transition. These findings contrast epithelial tumors where reduced miR‐200c expression promotes metastasis. Indeed, we noted that osteosarcoma cells in the lung also expressed the epithelial marker CDH1, revealing a change in their mesenchymal phenotype. We propose that miR‐200c upregulation occurs late in osteosarcoma progression to provide cells with an epithelial phenotype that facilitates their integration in the metastatic lung niche. Thus, our findings identify phospho‐AKT in the primary tumor and miR‐200c later during tumor progression as prognostic molecules and potential therapeutic targets to prevent progression and metastasis of pediatric osteosarcomas.
Regional differences in political trust: Comparing the Vysocina and Usti Regions
Authors: Čermák Daniel , Mikešová Renáta , Stachová Jana
Published: April 2016

This article deals with the factors influencing the degree of trust in political institutions at three levels of government in the Czech Republic (national, regional and local) in two dissimilar regions in the time of economic crisis in 2009, the year when citizens of the Czech Republic experienced the negative impacts of growing unemployment and a substantial decline in real GDP. Two competitive theories - the cultural and the performance explanation - were used as a theoretical framework. The results show that there are significant differences among particular levels of government as well as regions. The influence of both institutional performance, including factors related to economic crisis, and cultural background were found. The influence of contextual factors was also confirmed.
EssC: domain structures inform on the elusive translocation channel in the Type VII secretion system
Authors: Zoltner Martin , Ng Wui M.A.V. , Money Jillian J. , Fyfe Paul K. , Kneuper Holger , Palmer Tracy , Hunter William N.
Published: April 2016

The membrane-bound protein EssC is an integral component of the bacterial Type VII secretion system (T7SS), which is a determinant of virulence in important Gram-positive pathogens. The protein is predicted to consist of an intracellular repeat of forkhead-associated (FHA) domains at the N-terminus, two transmembrane helices and three P-loop-containing ATPase-type domains, D1–D3, forming the C-terminal intracellular segment. We present crystal structures of the N-terminal FHA domains (EssC-N) and a C-terminal fragment EssC-C from Geobacillus thermodenitrificans, encompassing two of the ATPase-type modules, D2 and D3. Module D2 binds ATP with high affinity whereas D3 does not. The EssC-N and EssC-C constructs are monomeric in solution, but the full-length recombinant protein, with a molecular mass of approximately 169 kDa, forms a multimer of approximately 1 MDa. The observation of protomer contacts in the crystal structure of EssC-C together with similarity to the DNA translocase FtsK, suggests a model for a hexameric EssC assembly. Such an observation potentially identifies the key, and to date elusive, component of pore formation required for secretion by this recently discovered secretion system. The juxtaposition of the FHA domains suggests potential for interacting with other components of the secretion system. The structural data were used to guide an analysis of which domains are required for the T7SS machine to function in pathogenic Staphylococcus aureus. The extreme C-terminal ATPase domain appears to be essential for EssC activity as a key part of the T7SS, whereas D2 and FHA domains are required for the production of a stable and functional protein.
Norfolk: A case study in sea-level rise
Authors: Kramer David
Published: April 2016

A Virginia city that owes its livelihood to the sea is in danger of being engulfed by it.
Atomic hearts: A decade of US government-sponsored development
Authors: McKellar Shelley
Published: April 2016

As the public attained a heightened awareness of the risks associated with 1970s-era medical technologies, it increasingly perceived nuclear-powered artificial hearts as too dangerous to support.
Confidence assignment for mass spectrometry based peptide identifications via the extreme value distribution
Authors: Alves Gelio , Yu Yi-Kuo
Published: April 2016

Motivation : There is a growing trend for biomedical researchers to extract evidence and draw conclusions from mass spectrometry based proteomics experiments, the cornerstone of which is peptide identification. Inaccurate assignments of peptide identification confidence thus may have far-reaching and adverse consequences. Although some peptide identification methods report accurate statistics, they have been limited to certain types of scoring function. The extreme value statistics based method, while more general in the scoring functions it allows, demands accurate parameter estimates and requires, at least in its original design, excessive computational resources. Improving the parameter estimate accuracy and reducing the computational cost for this method has two advantages: it provides another feasible route to accurate significance assessment, and it could provide reliable statistics for scoring functions yet to be developed.

Results : We have formulated and implemented an efficient algorithm for calculating the extreme value statistics for peptide identification applicable to various scoring functions, bypassing the need for searching large random databases.

Availability and Implementation : The source code, implemented in C ++ on a linux system, is available for download at ftp://ftp.ncbi.nlm.nih.gov/pub/qmbp/qmbp_ms/RAId/RAId_Linux_64Bit

Contact:  yyu@ncbi.nlm.nih.gov

Supplementary information:  Supplementary data are available at Bioinformatics online.
Myoepithelioma of Soft Tissues
Authors: Domingo-Musibay Evidio , Oliveira Andre M. , Okuno Scott H. , Petersen Ivy A. , Rose Peter S. , Robinson Steven I.
Published: April 2016

Background:

Myoepithelioma of the soft tissues is a rare entity and little is known about how best to manage locally recurrent and high-grade disease. Here, we retrospectively examined outcomes of surgery, chemotherapy, and radiation therapy (RT) for treatment of low-grade and high-grade myoepithelioma of soft tissues.

Methods:

We reviewed 20 cases of myoepithelioma of soft tissues seen at Mayo Clinic between 1994 and 2014. The effect of histologic grade and therapies received on relapse and survival were assessed.

Results:

We identified 13 patients with low-grade disease and 7 patients with high-grade disease. We found that low-grade disease was frequently effectively managed with surgical resection alone, whereas high-grade disease frequently metastasized and was often fatal. The 5-year event-free survival was 88% (confidence interval, 46%-98%) for low-grade disease versus 36% (confidence interval, 7%-75%;P=0.04) for high-grade disease. The relapse rate in low-grade disease was 29% at 5 years versus 64% (P=0.04) in high-grade disease. No significant responses to chemotherapy were noted, however, excellent responses to perioperative RT were seen.

Conclusions:

Surgery continues as the primary modality of treatment for myoepithelioma of soft tissues. Our study did not show a clear benefit of chemotherapy in the metastatic disease setting, but supports the use of perioperative RT in the management of high-grade disease; further investigation is warranted.
Role of Exercise in Reducing Gestational Diabetes Mellitus
Authors: MOTTOLA MICHELLE F. , ARTAL RAUL
Published: April 2016

Exercise plays an important role in reducing the prevalence of gestational diabetes mellitus (GDM) in women with or without risk factors. GDM risk factors include obesity, family history of diabetes, high-risk ethnicity, increased maternal age, history of GDM, delivering a macrosomic infant, excessive gestational weight gain early in pregnancy (before glucose screening), sedentary behavior, low physical activity, and vitamin D deficiency. Most GDM patients can be managed with lifestyle modifications that include medical nutrition therapy and physical activity. When adherence is high and women are fully engaged in the exercise program, GDM can be effectively managed and prevented.
Graded Cycling Test Combined With the Talk Test Is Responsive in Cardiac Rehabilitation
Authors: Nielsen Susanne Grøn , Vinther Anders
Published: April 2016

PURPOSE:

To evaluate clinical assessment outcome of cardiac rehabilitation, a simple and reliable submaximal exercise test, not based on heart rate, is warranted. The Talk Test (TT) has been found to correlate well with the ventilatory threshold, and excellent reliability was observed for TT combined with the Graded Cycling Test (GCT-TT) in cardiac patients. The purpose was to investigate responsiveness of GCT-TT in cardiac rehabilitation patients.

METHODS:

Patients (n = 93) referred to 8 weeks of cardiac rehabilitation were included. Pre- and posttests were performed using GCT-TT. Mean test changes in watts (W) were compared with the standard error of measurement (SEM95) for groups and the smallest real difference (SRD) for individuals. Minimal clinically important difference was assessed by comparing patient perceived changes in physical fitness with the test changes.

RESULTS:

A statistically significant improvement of GCT-TT was observed; 18.1 ± 21.1 W (mean ± SD) (P < .001). This was close to the previously observed SEM95 of 18.3 W. Thirty-six percent of the patients exceeded SRD (2 test stages). The subgroup with a perceived “major change” improved 28.8 ± 20.7 W compared with the groups reporting “some” (P < .001) and “no or minor” change (P = .002). A change of 30 W (equivalent to 2 stages ≈ 1 metabolic equivalent task [MET]) in the present test protocol is suggested as the minimal clinically important difference.

CONCLUSIONS:

GCT-TT was responsive to changes of power output for these patients, and these changes were generally in agreement with patient perceived changes in physical fitness.
Disc-damage Likelihood Scale (DDLS) as a Clinical Indicator of the Presence of a Relative Afferent Pupillary Defect (RAPD)
Authors: Zhang Alice Y. , Lu Lan , Ali Mohsin , Rutnin Nont , Faria Bruno M. , Guzel Huseyin , Liang Liang , Martinez Patricia , Tawfik Mike , Spaeth George L.
Published: April 2016

Purpose:

To evaluate clinical parameters and their relationship to the presence of a relative afferent pupillary defect (RAPD).

Materials and Methods:

Retrospective chart review of 672 consecutive patients who presented to the Glaucoma Service at Wills Eye Hospital from January 1 through May 29, 2012. Swinging flashlight method (SFM) was used to test for RAPDs. Records of visual acuity, intraocular pressure (IOP), disc-damage likelihood scale (DDLS), cup/disc (C/D) ratio, visual field mean deviation (MD), optical coherence tomography (OCT), and Heidelberg retinal tomography (HRT) asymmetries were examined. We measured the prevalence of RAPDs as clinical asymmetries increase, calculated cut-off points for clinical asymmetries that optimized sensitivity and specificity in detecting RAPDs, and determined values of clinical asymmetries above which a RAPD always exists.

Results:

Upon exclusion, we studied 409 patients, 175 (42.8%) with RAPDs and 234 (57.2%) without. Age, visual acuity, IOP, DDLS, C/D ratio, MD, retina nerve fiber layer thickness by OCT, HRT C/D, and HRT rim area asymmetries all correlated with RAPD status (OCT and HRT parameters did not include enough patients for multivariable analysis or cut-off determination). Multivariable analysis indicated that IOP, DDLS, and MD asymmetries were significantly correlated with RAPD status (P-value<0.05). Although the optimal cut-off values for the variables retained in the final multivariable model had low sensitivity and moderate specificity, DDLS had the highest specificity of 0.86.

Conclusions:

IOP, DDLS, and MD asymmetries had the best correlation with RAPD status, and increased asymmetries in these parameters were associated with higher likelihood of RAPDs. DDLS score had the highest specificity in predicting a RAPD, and DDLS asymmetry scores ≥6 identified all cases of RAPDs.
Inadequate Bowel Cleansing Efficacy of Split-dose Polyethylene Glycol for Colonoscopy in Type 2 Diabetic Patients
Authors: Kim Young Hwan , Seo Eun Hee , Lee Jae Seung , Lee Seung Heon , Park Hee Seung , Choi Sung Ho , Park Ja Young , Lee Chang Won
Published: April 2016

Background/Aims:

Split-dose polyethylene glycol (PEG) is considered a standard bowel preparation regimen for colonoscopy in the general population. However, it is not clear whether the regimen is optimal for colonoscopy in diabetic patients. The aim of this study was to compare the efficacy and tolerability of split-dose PEG for diabetic versus nondiabetic patients.

Methods:

This is a single-center, prospective, investigator-blinded study. A total of 55 consecutive nondiabetic and 50 diabetic patients ingested 2 L PEG solution on the day before the procedure and then 2 L of the solution on the day of colonoscopy. The quality of bowel preparation was graded using the Ottawa scale.

Results:

There was a significant difference in bowel preparation quality, with a worse preparation except for mid colon in diabetic group (total score: 7.06±1.69 vs. 5.54±1.97, P<0.001; right colon: 2.28±0.57 vs. 1.81±0.72, P<0.001; mid colon: 1.70±0.54 vs. 1.56±0.66, P=0.253; rectosigmoid colon: 1.70±0.76 vs. 1.14±0.62, P<0.001; fluid volume: 1.38±0.53 vs. 1.01±0.59, P=0.001). About 70% of nondiabetic patients had an adequate preparation compared with only 40% of diabetic patients (P=0.003). Diabetic group had longer cecal intubation time (6.4±3.6 vs. 4.5±2.4, P=0.002) and total procedure time (22.1±7.6 vs. 18.1±8.5, P=0.015). Compliance and adverse events were not significantly different. In diabetic group, inadequate bowel preparation had a significant association with higher fasting plasma glucose (136.9±21.8 vs. 121.8±19.4 mg/dL, P=0.016).

Conclusions:

Diabetic patients had a worse preparation quality and longer cecal intubation and total procedure time compared with nondiabetic patients. These data suggest that split-dose PEG preparation regimen is not sufficient for optimal bowel preparation in diabetic patients undergoing colonoscopy.
Short-Term Public Health Impact of the July 22, 2011, Terrorist Attacks in Norway: A Nationwide Register-Based Study
Authors: Strand Linn Beate , Mukamal Kenneth J. , Halasz Jozsef , Vatten Lars J. , Janszky Imre
Published: April 2016

Objectives

To examine increases in several health outcomes after the July 22, 2011 terrorist attacks in Norway.

Methods

Retrospective analysis of nationwide registers (n = 4,953,000) where incidences of schizophrenia/psychosis hospitalizations, suicides, acute myocardial infarctions, and preterm births after the terrorist attacks were compared with corresponding periods the previous 3 years.

Results

Compared with the same period the preceding 3 years, the observed number of hospitalizations from schizophrenia/psychosis was 14% higher during the first 4 weeks after the terrorist attack (incidence ratio [IR] = 1.14, 95% confidence interval [CI] = 1.07–1.21). The corresponding IRs for the first 3 days and the first week were 1.26 (95% CI = 0.99–1.58) and 1.10 (95% CI = 0.96–1.24). The observed number of suicides was increased by 45% the first 4 weeks (IR = 1.45, 95% CI = 1.12–1.86), 163% the first 3 days (IR = 2.63, 95% CI = 1.15–5.20), and 105% the first week (IR = 2.05, 95% CI = 1.14–3.42). For acute myocardial infarction, there was an increase of 5% the first 4 weeks. There were also more births the 4 weeks (IR = 1.04, 95% CI = 1.01–1.07, but this increase was not seen in preterm births of less than 37 weeks of gestation (IR = 0.93, 95% CI = 0.83–1.04).

Conclusions

We observed a general nationwide increase of health outcomes investigated in this study the first 4 weeks after the terrorist attacks. These results may contribute to the growing body of evidence on the adverse health outcomes that may accompany national stressors.
Subgenual Cingulate Cortex Functional Connectivity in Relation to Depressive Symptoms and Cognitive Functioning in Type 1 Diabetes Mellitus Patients
Authors: van Duinkerken Eelco , Ryan Christopher M. , Schoonheim Menno M. , Barkhof Frederik , Klein Martin , Moll Annette C. , Diamant Michaela , IJzerman Richard G. , Snoek Frank J.
Published: April 2016

Objectives

Patients with Type 1 diabetes mellitus (T1DM) are at an increased risk for major depression, but its underlying mechanisms are still poorly understood. In nondiabetic participants, mood disturbances are related to altered subgenual cingulate cortex (SGC) resting-state functional connectivity. We tested for SGC connectivity alterations in T1DM, whether these alterations were related to depressive symptoms, and if depressive symptoms were associated with cognition.

Methods

A bilateral SGC seed-based resting-state functional magnetic resonance imaging analysis was performed in 104 T1DM patients and 49 controls without known psychiatric diagnosis or treatment. Depressive symptoms were self-reported using the Center for Epidemiological Studies Depression scale. Cognition was assessed with a battery of standardized tests.

Results

In patients versus controls, SGC to right inferior frontal gyrus and frontal pole connectivity was decreased (52 voxels, z valuepeak = 3.56, p
cluster-FWE = .002), whereas SGC to bilateral precuneus (33 voxels, z valuepeak = 3.34, p
cluster-FWE = .04) and left inferior parietal lobule (50 voxels, z valuepeak = 3.50, p
cluster-FWE = .003) connectivity was increased. In all participants, increased depressive symptoms was related to lower SGC to inferior frontal gyrus and frontal pole connectivity (β = −0.156, p = .053), and poorer general cognitive ability (β = −0.194, p = .023), information processing speed (β = −0.222, p = .008), and motor speed (β = −0.180, p = .035).

Conclusions

T1DM patients showed a pattern of SGC connectivity that is characterized by lower executive control and higher default mode network connectivity. Depressive symptoms are partially related to these alterations and seem to exacerbate T1DM-related cognitive dysfunction. Future studies should detail the effect of diagnosed major depressive disorder in this population and establish what alterations are diabetes specific.
Complex molecular mixtures under cycling gradients as basis for life’s origins
Authors: Spitzer Jan , Poolman Bert
Published: April 2016

We consider life as a cyclic physicochemical process that makes heredity and Darwinian evolution observable through living cells. We elaborate four principles that constrain current speculations about life’s emergence to natural processes driven by diurnal physicochemical gradients, primarily of temperature, water activity and electromagnetic radiation. First, Earth’s prebiotic chemical evolution is historically continuous with Darwinian evolution; second, cycling energies of solar radiation are primary drivers of chemical evolution; third, environmental molecular complexity must be high at the origin of life; and fourth, non-covalent molecular forces determine molecular recognition and cellular organization. Under normal physiological conditions of high ionic strength and high macromolecular crowding, hydration interactions (hydrogen bonding), screened electrostatic forces and excluded volume repulsions act over acommensuratedistance of about one nanometer. This intermolecular distance governs chemical coevolution of proto-biomacromolecular surfaces (nucleic acids, proteins and membranes) toward Darwinian thresholds and living states. The above physicochemical principles of life’s emergence are consistent with the second law of thermodynamics, and with the current facts of molecular microbiology and planetary sciences. New kinds of experimentation with crowded molecular mixtures under oscillating temperature gradients - a PCR-like mechanism of life’s origins - can further illuminate how living states come about.

Graphical abstract

Life’s emergence follows from chemical and Darwinian evolution, a high degree of molecular complexity and a high crowdedness, and non-covalent molecular forces that determine molecular recognition and cellular organization. The macromolecules divide the cytoplasm into dynamically crowded macromolecular regions and topologically complementary electrolyte pools. Small ions and ionic metabolites are transported vectorially between the electrolyte pools and through the (semi-conducting) electrolyte pathways of the crowded macromolecular regions.
LINES between species: Evolutionary dynamics of LINE-1 retrotransposons across the eukaryotic tree of life
Authors: Ivancevic Atma M. , Kortschak R. Daniel , Bertozzi Terry , Adelson David L.
Published: April 2016

LINE-1 (L1) retrotransposons are dynamic elements. They have the potential to cause great genomic change due to their ability to ‘jump’ around the genome and amplify themselves, resulting in the duplication and rearrangement of regulatory DNA. Active L1, in particular, are often thought of as tightly constrained, homologous and ubiquitous elements with well-characterised domain organisation. For the past 30 years, model organisms have been used to define L1s as 6-8kb sequences containing a 5’-UTR, two open reading frames working harmoniously incis, and a 3’-UTR with a polyA tail.

In this study, we demonstrate the remarkable and overlooked diversity of L1s via a comprehensive phylogenetic analysis of over 500 species from widely divergent branches of the tree of life. The rapid and recent growth of L1 elements in mammalian species is juxtaposed against their decline in plant species and complete extinction in most reptiles and insects. In fact, some of these previously unexplored mammalian species (e.g. snub-nosed monkey, minke whale) exhibit L1 retrotranspositional ‘hyperactivity’ far surpassing that of human or mouse. In contrast, non-mammalian L1s have become so varied that the current classification system seems to inadequately capture their structural characteristics. Our findings illustrate how both long-term inherited evolutionary patterns and random bursts of activity in individual species can significantly alter genomes, highlighting the importance of L1 dynamics in eukaryotes.
How strongly does appetite counter weight loss? Quantification of the homeostatic control of human energy intake
Authors: Polidori David , Sanghvi Arjun , Seeley Randy , Hall Kevin D.
Published: April 2016

Objective

To quantify the homeostatic feedback control of energy intake in response to long-term covert manipulation of energy balance in free-living humans.

Methods

We used a validated mathematical method to calculate energy intake changes during a 52 week placebo-controlled trial in 153 patients treated with canagliflozin, a sodium glucose co-transporter inhibitor that increases urinary glucose excretion thereby resulting in weight loss without patients being directly aware of the energy deficit. We analyzed the relationship between the body weight time course and the calculated energy intake changes using principles from engineering control theory.

Results

We discovered that weight loss leads to a proportional homeostatic drive to increase energy intake above baseline by ~100 kcal/day per kg of lost weight – an amount more than 3-fold larger than the corresponding energy expenditure adaptations.

Conclusions

While energy expenditure adaptations are often thought to be the main reason for slowing of weight loss and subsequent regain, feedback control of energy intake plays an even larger role and helps explain why long-term maintenance of a reduced body weight is so difficult.

Funding

This research was supported by the Intramural Research Program of the NIH, National Institute of Diabetes & Digestive & Kidney Diseases, using data from a study sponsored by Janssen Research & Development, LLC.

Disclosure

D.P. is a full-time employee of Janssen Research & Development, LLC. K.D.H. reports patent pending on a method of personalized dynamic feedback control of body weight (US Patent Application No. 13/754,058; assigned to the NIH) and has received funding from the Nutrition Science Initiative to investigate the effects of ketogenic diets on human energy expenditure. R.S. is a paid consultant for Janssen, Novo Nordisk, Takeda, Daichii Sankyo, Novartis, Pfizer, Nestle, Circuit Therapeutics and Ethicon. R.S., also has received research support from Novo Nordisk, Ethicon, Sanofiand Boehringer Ingelheim. A.S. reports no conflicts of interest.

What is already known about this subject?

Human body weight is believed to be regulated by homeostatic feedback control of both energy intake and energy expenditure.

Adaptations of energy expenditure to weight loss have been well-established, but the homeostatic control of energy intake has yet to be quantified.

What this study adds

We provide the first quantification of the homeostatic control of energy intake in free-living humans.

The increase in energy intake per kg of weight lost is several-fold larger than the known energy expenditure adaptations.

Homeostatic control of energy intake is likely the primary reason why it is difficult to achieve and sustain large weight losses.
Coherent synthesis of genomic associations with phenotypes and home environments
Authors: Lasky Jesse R. , Forester Brenna R. , Reimherr Matthew
Published: April 2016

Local adaptation is often studied via 1) multiple common garden experiments comparing performance of genotypes in different environments and 2) sequencing genotypes from multiple locations and characterizing geographic patterns in allele frequency. Both approaches aim to characterize the same pattern (local adaptation), yet the complementary information from each has not yet been coherently integrated. Here, we develop a genome-wide association model of genotype interactions with continuous environmental gradients (G×E),i.e.reaction norms. We present an approach to impute relative fitness, allowing us to coherently synthesize evidence from common garden and genome-environment associations. Our approach identifies loci exhibiting environmental clines where alleles are associated with higher fitness in home environments. Simulations show our approach can increase power to detect loci causing local adaptation. In a case study onArabidopsis thaliana, most identified SNPs exhibited home allele advantage and fitness tradeoffs along climate gradients, suggesting selective gradients can maintain allelic clines. SNPs exhibiting G×E associations with fitness were enriched in genic regions, putative partial selective sweeps, and associations with an adaptive phenotype (flowering time plasticity). We discuss extensions for situations where only adaptive phenotypes other than fitness are available. Many types of data may point toward the loci underlying G×E and local adaptation; coherent models of diverse data provide a principled basis for synthesis.
Comparison of the analgesic effect of patient‐controlled oxycodone and fentanyl for pain management in patients undergoing colorectal surgery
Authors: Jung Kyeo‐Woon , Kang Hyeon‐Wook , Park Chan‐Hye , Choi Byung‐Hyun , Bang Ji‐Yeon , Lee Soo‐Han , Lee Eun‐Kyung , Choi Byung‐Moon , Noh Gyu‐Jeong
Published: April 2016

Oxycodone is a μ‐opioid receptor agonist and is generally indicated for the relief of moderate to severe pain. The aim of this study was to compare the analgesic efficacy of patient‐controlled oxycodone and fentanyl for postoperative pain in patients undergoing colorectal surgery. Patients scheduled to undergo elective colorectal surgery (n=82) were allocated to receive oxycodone (n=41, concentration of 1 mg/mL) or fentanyl (n=41, concentration of 15 μg/mL) for postoperative pain management. After the operation, pain using a numerical rating scale (NRS), delivery to demand ratio, infused dose of patient‐controlled analgesia (PCA), side effects, and sedation levels were evaluated. Median (25%–75%) cumulative PCA dose of oxycodone group at 48 hours (66.9, 58.4–83.7 mL) was significantly less than that of fentanyl group (80.0, 63.4–103.3 mL, P=.037). Six hours after surgery, the mean (SD) NRS scores of the oxycodone and fentanyl groups were 6.2 (2.4) and 6.8 (1.9), respectively (P=.216). The mean equianalgesic potency ratio of oxycodone to fentanyl was 55:1. The groups did not differ in postoperative nausea, vomiting, and level of sedation. Patient‐controlled oxycodone provides similar effects for pain relief compared to patient‐controlled fentanyl in spite of less cumulative PCA dose. Based on these results, oxycodone can be a useful alternative to fentanyl for PCA in patients after colorectal surgery.
Lack of tumor necrosis factor alpha gene polymorphism ‐857c/t (rs1799724) association in Pakistani rheumatoid arthritis patients
Authors: Sadaf Tayyaba , John Peter , Bhatti Attya , Jahangir Sidrah , Kiani Aysha K. , Gill Farah A. , Malik Javed M.
Published: April 2016

Background

Rheumatoid arthritis (RA) is a common systemic autoimmune disease, influenced greatly by the pro‐inflammatory cytokine tumor necrosis factor‐ alpha (TNF‐α). Single nucleotide polymorphisms (SNPs) in regulatory regions of the TNF‐α gene play a significant role in disease development and pathogenesis. The aim of this study was to investigate the association of TNF‐α ‐857C/T (rs1799724) SNP with RA activity or severity in our Pakistani study group.

Methods

The study included 134 (116 women, 18 men) patients with RA and 134 ethnically matched healthy controls (108 women, 26 men). Each patient's disease activity was measured by Disease Activity Score of 28 joints. The genotypes were determined in all included individuals following allele‐specific polymerase chain reaction along with the prerequisite internal amplification controls. Statistical analysis including chi‐square/Fischer exact test and one‐way analysis of variance; nonparametric Kruskal–Wallis test was employed using Graphpad Prism 6 software for association study.

Results

The prevalence of TNF‐α ‐857C/T (rs1799724) polymorphism was not differentially distributed between RA patients and controls in either allele frequency, with odds ratio (95% CI) of 0.9661 (0.6714–1.390) and P‐value of 0.8527, or genotype frequency with χ2 of 0.5015 and P‐value of 0.7782. Moreover, no correlation was found when genotype frequency distribution was analyzed with disease severity (P = 0.6321 and Kruskal–Wallis statistics of 1.098).

Conclusion

The study demonstrated ‐857C/T (rs1799724) polymorphism may not have influenced RA susceptibility in our study group. However, investigations of genetic variability influence on disease outcome in large prospective cohorts are required, so the complicated interconnection of genetic and environmental elements can be emulated for better understanding.
Self‐assessment of skin tightness severity by scleroderma patients
Authors: Daungkum Kittikorn , Foocharoen Chingching , Mahakkanukrauh Ajanee , Suwannaroj Siraphop , Thinkhamrop Bandit , Nanagara Ratanavadee
Published: April 2016

Aims

Skin tightness progression determines the severity and mortality of systemic sclerosis (SSc). The modified Rodnan skin score (mRSS) is a skin tightness assessment tool, albeit inter‐physician variability is a limitation. Our objectives were to evaluate the correlation and agreement of skin tightness assessment between patient self‐assessment and physician‐assessment.

Methods

A descriptive study was conducted on the masked, self‐assessments of mRSS (at week 0, 4 and 12) by 23 Thai adult SSc patients seen at Srinagarind Hospital, KhonKaen University, between March 2014 and February 2015. Correlation between the physician and patient assessments was estimated using Pearson's. The intra‐class correlation coefficient (ICC) and limit of agreement by Bland‐Altman were determined.

Results

We included 23 SSc patients (female to male ratio being 1.1:1). All had the diffuse cutaneous SSc subset. The skin thickness assessment correlation was moderate at baseline (Pearson's r = 0.68) and improved to a good correlation at week 4 and 12 (r = 0.78 and 0.86, respectively). The ICC showed good agreement (0.761) at week 0 and increased to excellent at week 4 (0.846) and 12 (0.910). The patient self‐assessment score was higher than the physician assessment, which slightly decreased over time: mean difference = 4.30 (95% LOA;−9.54 to 18.14) at week 0, then 3.78 (95% LOA,−10.20 to 17.77) at week 4, and 3.16 (95% LOA,−7.78 to 14.10) at week 12.

Conclusion

The respective modified Rodnan skin score assessment by patient versus the physician was highly correlated with a high level of agreement. Validation of generalized patient self‐assessment needs to be confirmed.
Clinical characteristics of scleroderma overlap syndromes: comparisons with pure scleroderma
Authors: Foocharoen Chingching , Netwijitpan Sittichai , Mahakkanukrauh Ajanee , Suwannaroj Siraphop , Nanagara Ratanavadee
Published: April 2016

Background

Scleroderma with characteristics of other connective tissue diseases is called scleroderma overlap syndrome (SOV); the clinical features of which have yet to be investigated among Thai patients.

Objective

To determine the clinical differences between pure scleroderma and SOV.

Methods

A historical cohort study was conducted among patients with pure scleroderma versus those with SOV. Subjects were over 18 years of age and followed up at Srinagarind Hospital, Khon Kaen University, Thailand, between January 2006 and December 2011.

Results

Four hundred and three medical records were included (276 female vs. 127 male). SOV was found in 68 cases (16.9%): (i) scleroderma–polymyositis overlap (SOV‐PM), the most common type of SOV (48 cases; 70.6%); (ii) scleroderma–systemic lupus erythematosus overlap (11 cases; 16.2%); and (iii) scleroderma–rheumatoid arthritis overlap (nine cases; 13.2%). Mean age at onset of non‐systemic sclerosis symptoms was 46.9 ± 11.8 years (range, 19.8–74.3). Characteristically, sufferers of SOV as against pure scleroderma were younger, had less frequent anti‐topoisomerase I (ATA) and needed moderate‐ to high‐dose steroid and immunosuppressant therapy during follow‐up. SOV‐PM presented the clinical features of scleroderma at onset and during follow‐up looks like pure scleroderma having vasculopathy, severity of skin tightness, and gastrointestinal, cardiopulmonary and renal involvement. Anti‐Ro52 was the most common serology among sufferers of SOV (31.6%). ATA was associated with pure scleroderma patients (P = 0.047).

Conclusions

SOV rather than pure scleroderma presented in younger Thai scleroderma patients and SOV‐PM was the most common subtype and its clinical features were similar to those of pure scleroderma. ATA was strongly associated with the latter.
Immunoglobulin detection in wild birds: effectiveness of three secondary anti‐avian IgY antibodies in direct ELISAs in 41 avian species
Authors: Fassbinder‐Orth Carol A. , Wilcoxen Travis E. , Tran Tiffany , Boughton Raoul K. , Fair Jeanne M. , Hofmeister Erik K. , Grindstaff Jennifer L. , Owen Jen C.
Published: April 2016

1.Immunological reagents for wild, non‐model species are limited or often non‐existent for many species.

2. In this study, we compare the reactivity of a new anti‐passerine IgY secondary antibody with existing secondary antibodies developed for use with birds. Samples from 41 species from the following six avian orders were analysed: Anseriformes (1 family, 1 species), Columbiformes (1 family, 2 species), Galliformes (1 family, 1 species), Passeriformes (16 families, 34 species), Piciformes (1 family, 2 species) and Suliformes (1 family, 1 species). Direct ELISAs were performed to detect total IgY using goat anti‐passerine IgY, goat anti‐chicken IgY or goat anti‐bird IgY secondary antibodies.

3.The anti‐passerine antibody exhibited significantly higher IgY reactivity compared to the anti‐chicken and/or anti‐bird antibodies in 80% of the passerine families tested. Birds in the order Piciformes (woodpeckers) and order Suliformes (cormorants) were poorly detected by all three secondary antibodies. A comparison of serum and plasma IgY levels was made within the same individuals for two passerine species (house finch and white‐crowned sparrow), and serum exhibited significantly more IgY than the plasma for all three secondary antibodies. This result indicates that serum may be preferred to plasma when measuring total antibody levels in blood.

4.This study indicates that the anti‐passerine IgY secondary antibody can effectively be used in immunological assays to detect passerine IgY for species in most passerine families and is preferred over anti‐chicken and anti‐bird secondary antibodies for the majority of passerine species. This anti‐passerine antibody will allow for more accurate detection and quantification of IgY in more wild bird species than was possible with previously available secondary antibodies.
Hand‐held computers can help to distract children undergoing painful venipuncture procedures
Authors: Crevatin Franca , Cozzi Giorgio , Braido Elena , Bertossa Gabriella , Rizzitelli Patrizia , Lionetti Daniela , Matassi Daniela , Calusa Dorotea , Ronfani Luca , Barbi Egidio
Published: April 2016

Aim

Needle‐related procedures can be painful for children, and distraction provides ideal pain relief in blood‐drawing centres. This study assessed the effectiveness of playing a computer game during venipuncture, compared with low‐tech distraction by a nurse.

Methods

We conducted this prospective, randomised controlled trial at the blood‐drawing centre of a tertiary‐level children's hospital in Italy. Half of the 200 children played Angry Birds on a hand‐held computer while the other half were distracted by a second, specifically trained nurse who sang to them, read a book, blew bubbles or played with puppets. Pain was measured using a faces pain scale for children aged 4–7 years and a numeric scale for children aged 8–13 years.

Results

The 200 children had a median age of eight years. Children reported significant pain in 16 cases (16%) in the hand‐held computer distraction group and in 15 cases (15%) in the nurse‐led low‐tech distraction group (p = 0.85). The procedural success rate at the first attempt was not different in the two groups.

Conclusion

Playing a game on a hand‐held computer meant that only one in six children reported pain during venipuncture, but it was not superior to being distracted by nurses.