Hyperhomocysteinemia Associated with Low Muscle Mass, Muscle Function in Elderly Hemodialysis Patients: An Analysis of Multiple Dialysis Centers.
The hyperhomocysteinemia was with high prevalence and has been considered as a risk factor for cardiovascular disease in hemodialysis patients. These patients also experienced a high risk of muscle wasting caused by the comorbidity, malnutrition, and low physical activity. We investigated the associations of homocysteinemia with muscle mass, muscle function in elderly hemodialysis patients. A clinical cross-sectional study was conducted on 138 hemodialysis patients aged 65 years and above in seven hospital-based hemodialysis centers in Taiwan. The data on anthropometry, laboratory, and 3-day dietary intake was examined. The skeletal muscle mass (SMM) was measured by the bioelectrical impedance analysis; the SMM was adjusted by height or weight as SMMHt2 (kg/m2) and SMMWt (%). Muscle function was defined as handgrip strength (HGS) (kg) measured by handgrip dynamometer. Statistical analyses were conducted using simple regression and multivariable stepwise regression analysis. In the total sample, 74.6 % of hemodialysis patients were hyperhomocysteinemia (≥ 15 μmol/L). The means of SMMHt2, SMMWt, arm lean mass, hand grip strength, and muscle quality were 8.7 ± 1.2, 37.7 ± 5.6, 1.7 ± 0.5, 21.1 ± 7.4, and 10.0 ± 3.0, respectively. The multivariable stepwise regression analysis showed that homocysteinemia level was significantly inversely associated with SMMWt (B-coeff. = -0.03, p = 0.02) in hemodialysis patients above 65 years old, but not with muscle function. Hyperhomocysteinemia is common and associated with decreased muscle mass in the elderly hemodialysis patients. Future studies are suggested to explore the impact of the homocysteine-lowering therapy on muscle decline.


Plant domestication, a unique opportunity to identify the genetic basis of adaptation.
Despite the fundamental role of plant domestication in human history and the critical importance of a relatively small number of crop plants to modern societies, we still know little about adaptation under domestication. Here we focus on efforts to identify the genes responsible for adaptation to domestication. We start from a historical perspective, arguing that Darwin's conceptualization of domestication and unconscious selection provides valuable insight into the evolutionary history of crops and also provides a framework to evaluate modern methods used to decipher the genetic mechanisms underlying phenotypic change. We then review these methods, framing the discussion in terms of the phenotype-genotype hierarchy. Top-down approaches, such as quantitative trait locus and linkage disequilibrium mapping, start with a phenotype of interest and use genetic analysis to identify candidate genes. Bottom-up approaches, alternatively, use population genetic analyses to identify potentially adaptive genes and then rely on standard bioinformatics and reverse genetic tools to connect selected genes to a phenotype. We discuss the successes, advantages, and challenges of each, but we conclude that bottom-up approaches to understanding domestication as an adaptive process hold greater promise both for the study of adaptation and as a means to identify genes that contribute to agronomically important traits.


Poly-N-isopropylacrylamide Nanogels and Microgels at Fluid Interfaces.
The confinement of colloidal particles at liquid interfaces offers many opportunities for materials design. Adsorption is driven by a reduction of the total free energy as the contact area between the two liquids is partially replaced by the particle. From an application point of view, particle-stabilized interfaces form emulsions and foams with superior stability. Liquid interfaces also effectively confine colloidal particles in two dimensions and therefore provide ideal model systems to fundamentally study particle interactions, dynamics, and self-assembly. With progress in the synthesis of nanomaterials, more and more complex and functional particles are available for such studies. In this Account, we focus on poly(N-isopropylacrylamide) nanogels and microgels. These are cross-linked polymeric particles that swell and soften by uptaking large amounts of water. The incorporated water can be partially expelled, causing a volume phase transition into a collapsed state when the temperature is increased above approximately 32 °C. Soft microgels adsorbed to liquid interfaces significantly deform under the influence of interfacial tension and assume cross sections exceeding their bulk dimensions. In particular, a pronounced corona forms around the microgel core, consisting of dangling chains at the microgel periphery. These polymer chains expand at the interface and strongly affect the interparticle interactions. The particle deformability therefore leads to a significantly more complex interfacial phase behavior that provides a rich playground to explore structure formation processes. We first discuss the characteristic "fried-egg" or core-corona morphology of individual microgels adsorbed to a liquid interface and comment on the dependence of this interfacial morphology on their physicochemical properties. We introduce different theoretical models to describe their interfacial morphology. In a second part, we introduce how ensembles of microgels interact and self-assemble at liquid interfaces. The core-corona morphology and the possibility to force these elements into overlap upon compression results in a complex phase behavior with a phase transition between microgels with extended and collapsed coronae. We discuss the influence of the internal particle architecture, also including core-shell microgels with rigid cores, on the phase behavior. Finally, we present new routes for the realization of more complex structures, resulting from multiple deposition protocols and from engineering the interaction potential of the individual particles.


UK podiatrists' experiences of podiatry services for people living with arthritis: a qualitative investigation.
Provision of podiatry services, like other therapies in the UK, is an area that lacks guidance by the National Institute for Health and Care Excellence. Many individuals living with arthritis in the UK are not eligible to access NHS podiatry services. The primary aim of this investigation was to understand the views of podiatry clinicians on their experiences of referral, access, provision and treatment for foot problems for patients who have arthritis. Focus groups were undertaken to explore, in-depth, individual views of podiatrists working in the UK to gain feedback on experiences of barriers and facilitators to referral, access, provision and treatment for foot problems for individuals living with arthritis. A purposive sampling strategy was adopted and two, semi-structured, focus group interviews conducted, involving 12 podiatrists from both NHS and independent sectors. To account for geographical variations one focus group took place in each of 2 predetermined 'zones' of the UK; Yorkshire and Hampshire. Thematic analysis was employed to identify key meanings and report patterns within the data. The key themes derived from the podiatry clinician focus groups suggest a variety of factors influencing demand for, and burden of, foot pain within the UK. Participants expressed frustration on having a service that accepts and treats patients according to their condition, rather than their complaint. Additionally, concern was conveyed over variations in the understanding of stakeholders' views of what podiatry is and what podiatrists aim to achieve for patients. Podiatrists interviewed believed that many individuals living with arthritis in the UK are not eligible to access NHS podiatry services and that this may be, in part, due to confusion over what is known about podiatry and access criteria. Essentially, podiatrists interviewed called for a timely renaissance of current systems, to newer models of care that meet the foot care needs of individual patients' circumstances and incorporate national multi-disciplinary guidance. Through this project, we have formulated key recommendations that are directed towards improving what other stakeholders (including GPs, commissioners and users of podiatry services) know about the effectiveness of podiatry and also to futureproof the profession of podiatry.


Obestatin and growth hormone reveal the interaction of central obesity and other cardiometabolic risk factors of metabolic syndrome.
Metabolic syndrome (MetS) is a multi-factorial disorder including central obesity (CO), insulin resistance, hyperglycemia, dyslipidemia and hypertension which increases the risk of diabetes mellitus and cardiovascular diseases. CO is considered as an essential component of MetS according to International Diabetes Federation (IDF), which may further modulate distinct signalling pathways compared with the other four MetS risk factors. Given that ghrelin signalling and the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis regulates energy balance and metabolic homeostasis, this study examined the changes in various ghrelin products and circulating hormones in response to the interaction between CO and other MetS components including blood pressure, fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol in 133 Hong Kong Chinese adults. Circulating obestatin and GH were increased and reduced, respectively, by either CO or the other 4-risk factor cluster. These changes were further augmented by the presence of all MetS risk factors. However, changes of ghrelin levels were not mediated by CO but the other MetS risk factors. Our findings suggest that CO does not predict all the dysregulation of signalling pathways in individuals with MetS. Although CO and other MetS may share common signalling targets (i.e., obestatin and GH), CO does not contribute to the perturbation of ghrelin signalling.


Alien insect dispersal mediated by the global movement of commodities.
Globalization and economic growth are recognized as key drivers of biological invasions. Alien species have become a feature of almost every biological community worldwide, and rates of new introductions continue to rise as the movement of people and goods accelerates. Insects are among the most numerous and problematic alien organisms, and are mainly introduced unintentionally with imported cargo or arriving passengers. However, the processes occurring prior to insect introductions remain poorly understood. We used a unique dataset of 1,902,392 border interception records from inspections at air, land, and maritime ports in Australia, New Zealand, Europe, Japan, USA, and Canada to identify key commodities associated with insect movement through trade and travel. In total, 8939 species were intercepted, and commodity association data were available for 1242 species recorded between 1960 and 2019. We used rarefaction and extrapolation methods to estimate the total species richness and diversity associated with different commodity types. Plant and wood products were the main commodities associated with insect movement across cargo, passenger baggage, and international mail. Furthermore, certain species were mainly associated with specific commodities within these, and other broad categories. More closely related species tended to share similar commodity associations, but this occurred largely at the genus level rather than within orders or families. These similarities within genera can potentially inform pathway management of new alien species. Combining interception records across regions provides a unique window into the unintentional movement of insects, and provides valuable information on establishment risks associated with different commodity types and pathways.


KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary.
The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere.


Human mutations in integrator complex subunits link transcriptome integrity to brain development.
Integrator is an RNA polymerase II (RNAPII)-associated complex that was recently identified to have a broad role in both RNA processing and transcription regulation. Importantly, its role in human development and disease is so far largely unexplored. Here, we provide evidence that biallelic Integrator Complex Subunit 1 (INTS1) and Subunit 8 (INTS8) gene mutations are associated with rare recessive human neurodevelopmental syndromes. Three unrelated individuals of Dutch ancestry showed the same homozygous truncating INTS1 mutation. Three siblings harboured compound heterozygous INTS8 mutations. Shared features by these six individuals are severe neurodevelopmental delay and a distinctive appearance. The INTS8 family in addition presented with neuronal migration defects (periventricular nodular heterotopia). We show that the first INTS8 mutation, a nine base-pair deletion, leads to a protein that disrupts INT complex stability, while the second missense mutation introduces an alternative splice site leading to an unstable messenger. Cells from patients with INTS8 mutations show increased levels of unprocessed UsnRNA, compatible with the INT function in the 3'-end maturation of UsnRNA, and display significant disruptions in gene expression and RNA processing. Finally, the introduction of the INTS8 deletion mutation in P19 cells using genome editing alters gene expression throughout the course of retinoic acid-induced neural differentiation. Altogether, our results confirm the essential role of Integrator to transcriptome integrity and point to the requirement of the Integrator complex in human brain development.


The biological functions of Naa10 - From amino-terminal acetylation to human disease.
N-terminal acetylation (NTA) is one of the most abundant protein modifications known, and the N-terminal acetyltransferase (NAT) machinery is conserved throughout all Eukarya. Over the past 50 years, the function of NTA has begun to be slowly elucidated, and this includes the modulation of protein-protein interaction, protein-stability, protein function, and protein targeting to specific cellular compartments. Many of these functions have been studied in the context of Naa10/NatA; however, we are only starting to really understand the full complexity of this picture. Roughly, about 40% of all human proteins are substrates of Naa10 and the impact of this modification has only been studied for a few of them. Besides acting as a NAT in the NatA complex, recently other functions have been linked to Naa10, including post-translational NTA, lysine acetylation, and NAT/KAT-independent functions. Also, recent publications have linked mutations in Naa10 to various diseases, emphasizing the importance of Naa10 research in humans. The recent design and synthesis of the first bisubstrate inhibitors that potently and selectively inhibit the NatA/Naa10 complex, monomeric Naa10, and hNaa50 further increases the toolset to analyze Naa10 function.


Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 9: lumbar fusion for stenosis with spondylolisthesis.
Patients presenting with stenosis associated with a spondylolisthesis will often describe signs and symptoms consistent with neurogenic claudication, radiculopathy, and/or low-back pain. The primary objective of surgery, when deemed appropriate, is to decompress the neural elements. As a result of the decompression, the inherent instability associated with the spondylolisthesis may progress and lead to further misalignment that results in pain or recurrence of neurological complaints. Under these circumstances, lumbar fusion is considered appropriate to stabilize the spine and prevent delayed deterioration. Since publication of the original guidelines there have been a significant number of studies published that continue to support the utility of lumbar fusion for patients presenting with stenosis and spondylolisthesis. Several recently published trials, including the Spine Patient Outcomes Research Trial, are among the largest prospective randomized investigations of this issue. Despite limitations of study design or execution, these trials have consistently demonstrated superior outcomes when patients undergo surgery, with the majority undergoing some type of lumbar fusion procedure. There is insufficient evidence, however, to recommend a standard approach to achieve a solid arthrodesis. When formulating the most appropriate surgical strategy, it is recommended that an individualized approach be adopted, one that takes into consideration the patient's unique anatomical constraints and desires, as well as surgeon's experience.


Supporting women in labor: a work sampling study of the activities of labor and delivery nurses.
Studies demonstrated that support during labor and birth has a positive impact on childbirth outcomes, and that women reported they received little supportive care from nurses during parturition. This study piloted a work sampling method that was adapted to determine the proportion of time the average intrapartum nurse at a Toronto teaching hospital spends in supportive care activities. Supportive care was operationally defined within four categories of activities: emotional support, physical comfort measures, instruction/information, and advocacy. Work sampling was an effective method of measuring support as a specific aspect of direct intrapartum care. The proportion of time that nurses spent in supportive versus all other activities was 9.9 percent (95% confidence interval 7.5% and 12%), based on a sample of 616 random observations of 18 nurses. Findings are discussed in terms of the social and political factors that affect the meaning and value of the supportive activities of work by obstetric nurses.


Non-medical prescribing in palliative care: a regional survey.
The United Kingdom is considered to be the world leader in nurse prescribing, no other country having the same extended non-medical prescribing rights. Arguably, this growth has outpaced research to evaluate the benefits, particularly in areas of clinical practice where patients have complex co-morbid conditions such as palliative care. This is the first study of non-medical prescribing in palliative care in almost a decade. To explore the current position of nurse prescribing in palliative care and establish the impact on practice of the 2012 legislative changes. An online survey circulated during May and June 2013. Nurse members (n = 37) of a regional cancer network palliative care group (61% response rate). While this survey found non-medical prescribers have embraced the 2012 legislative changes and prescribe a wide range of drugs for cancer pain, we also identified scope to improve the transition from qualified to active non-medical prescriber by reducing the time interval between the two. To maximise the economic and clinical benefit of non-medical prescribing, the delay between qualifying as a prescriber and becoming an active prescriber needs to be reduced. Nurses who may be considering training to be a non-medical prescriber may be encouraged by the provision of adequate study leave and support to cover clinical work. Further research should explore the patients' perspective of non-medical prescribing.


Epigallocatechin-3-gallate attenuates cadmium-induced chronic renal injury and fibrosis.
Cadmium (Cd) pollution is a serious environmental problem. Kidney is a main target organ of Cd toxicity. This study was undertaken to investigate the potential protective effects of epigallocatechin-3-gallate (EGCG) against chronic renal injury and fibrosis induced by CdCl2. Rat model was induced by exposing to 250 mg/L CdCl2 through drinking water. The renal function was evaluated by detecting the levels of blood urea nitrogen (BUN) and serum creatinine (SCR). The oxidative stress was measured by detecting the levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione/oxidized glutathione (GSH/GSSG) and renal enzymatic antioxidant status. Additionally, the renal levels of transforming growth factor-β1 (TGF-β1), Smad3, phosphorylation-Smad3 (pp-Smad3), α-smooth muscle actin (α-SMA), vimentin and E-cadherin were measured by western blot assay. Renal levels of microRNA-21 (miR-21), miR-29a/b/c and miR-192 were measured by quantitative RT-PCR. It was found that EGCG ameliorated the CdCl2-induced renal injury, inhibited the level of oxidative stress, normalized renal enzymatic antioxidant status and E-cadherin level, as well as attenuated the over generation of TGF-β1, pp-Smad3, vimentin and α-SMA. EGCG also decreased the production of miR-21 and miR-192, and enhanced the levels of miR-29a/b/c. These results showed that EGCG could attenuate Cd induced chronic renal injury.


Neurophysiological correlates of linearization in language production.
During speech production the planning of a description of several events requires, among other things, a verbal sequencing of these events. During this process, referred to as linearization during conceptualization, the speaker can choose between different types of temporal connectives such as 'Before' X did A, Y did B' or 'After' Y did B, X did A'. To capture the neural events of such linearization processes, event-related potentials (ERP) were measured in native speakers of German. Utterances were elicited by presenting a sequence of two pictures on a video screen. Each picture consists of an object that is associated with a particular action (e.g. book = reading). A coloured vocalization cue indicated to describe the sequence of two actions associated with the objects in chronological (e.g. red cue: 'After' I drove the car, I read a book) or reversed order (yellow cue). Brain potentials showed reliable differences between the two conditions from 180 ms after the onset of the vocalization prompt, with ERPs from the 'After' condition being more negative. This 'Before/After' difference showed a fronto-central distribution between 180 and 230 ms. From 300 ms onwards, a parietal distribution was observed. The latter effect is interpreted as an instance of the P300 response, which is known to be modulated by task difficulty. ERPs preceding overt sentence production are sensitive to conceptual linearization. The observed early, more fronto-centrally distributed variation could be interpreted as involvement of working memory needed to order the events according to the instruction. The later parietal distributed variation relates to the complexity in linearization, with the non-chronological order being more demanding during the updating of the concepts in working memory.


Chronology of fluctuating sea levels since the triassic.
Advances in sequence stratigraphy and the development of depositional models have helped explain the origin of genetically related sedimentary packages during sea level cycles. These concepts have provided the basis for the recognition of sea level events in subsurface data and in outcrops of marine sediments around the world. Knowledge of these events has led to a new generation of Mesozoic and Cenozoic global cycle charts that chronicle the history of sea level fluctuations during the past 250 million years in greater detail than was possible from seismic-stratigraphic data alone. An effort has been made to develop a realistic and accurate time scale and widely applicable chronostratigraphy and to integrate depositional sequences documented in public domain outcrop sections from various basins with this chronostratigraphic framework. A description of this approach and an account of the results, illustrated by sea level cycle charts of the Cenozoic, Cretaceous, Jurassic, and Triassic intervals, are presented.


Laparoscopic re-operation for failed Heller myotomy.
Laparoscopic Heller myotomy for achalasia has a 10-20% failure rate and may require re-operation to control persistent or recurrent symptoms. We report follow-up of 15 patients who underwent laparoscopic re-operation for failed Heller myotomy. Between 1993 and 2004, 15 patients underwent laparoscopic re-operation for failed Heller myotomy at our center. The mean duration between procedures was 23 months. Follow-up was completed at a mean duration of 30 months in 14 patients (93%) via a telephone questionnaire. Our overall failure rate for primary surgery (n = 106) was 5.6%. The mechanisms of failure were incomplete myotomy (33%), myotomy fibrosis (27%), fundoplication disruption (13%), too tight fundoplication (7%) and a combination of myotomy fibrosis and incomplete myotomy (20%). Significant symptom improvement was observed with postoperative symptom resolution seen in 71% of patients with dysphagia, 89% for regurgitation, 58% for heartburn and 40% for chest pain. Fifty percent reported excellent results and 79% would recommend the procedure to a friend. Subsequent dilations were performed in four patients (29%). Two patients required conversion to open surgery (13%). Three patients (20%) failed the re-operation and required further revisional surgery. Complications included intraoperative perforation in three (none of which resulted in postoperative morbidity) and a pneumothorax in one patient. Prior endoscopic therapies (pneumatic dilation or Botulinum toxin) were not associated with poor results. Laparoscopic re-operation for failed Heller myotomy is feasible and results are encouraging.


Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?
Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication regimens. Our work may provide useful information to enable further investigations in multimorbidity research within the scope of potential interactions and chronic pain.


Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients.
To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P < .001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45% , respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P < .001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%) . The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.


Role of Population Receptive Field Size in Complex Visual Dysfunctions: A Posterior Cortical Atrophy Model.
The neuronal mechanism of visual agnosia and foveal crowding that underlies the behavioral symptoms of several classic neurodegenerative diseases, including impaired holistic perception, navigation, and reading, is still unclear. A better understanding of this mechanism is expected to lead to better treatment and rehabilitation. To use state-of-the-art neuroimaging protocols to assess a hypothesis that abnormal population receptive fields (pRF) in the visual cortex underlie high-order visual impairments. Between April 26 and November 21, 2016, patients and controls were recruited from the Hadassah-Hebrew University medical center in a cross-sectional manner. Six patients with posterior cortical atrophy (PCA) were approached and 1 was excluded because of an inability to perform the task. Participants underwent functional magnetic resonance imaging-based cortical visual field mapping and pRF evaluation and performed a masked repetition priming task to evaluate visuospatial perception along the eccentricity axis. The association between pRF sizes and behavioral impairments was assessed to evaluate the role of abnormal pRF sizes in impaired visual perception. Posterior cortical atrophy is a visual variant of Alzheimer disease that is characterized by progressive visual agnosia despite almost 20/20 visual acuity. Patients with PCA are rare but invaluable for studying visual processing abnormalities following neurodegeneration, as atrophy begins in visual cortices but initially spares other brain regions involved in memory and verbal communication. Participants underwent a magnetic resonance imaging scan. Population receptive field sizes and their association with visual processing along the fovea-to-periphery gradient. Five patients with PCA (4 men [80%]; mean [SEM] age, 62.9 [3.5] years) were compared with 8 age-matched controls (1 man [25%]; mean [SEM] age, 63.7 [3.7] years) and demonstrated an atypical pRF mapping that varied along the eccentricity axis, which presented as abnormally small peripheral and large foveal pRFs sizes. Abnormality was seen in V1 (peripheral, 4.4° and 5.5°; foveal, 5.5° and 4.5° in patients and controls, respectively; P < .05) as well as in higher visual regions, but not in intermediate ones. Behaviorally, an atypical fovea-to-periphery gradient in visual processing was found that correlated with their pRF properties (r = 0.8; P < .01 for the correlation between pRF and behavioral fovea-to-periphery slopes). High-order visuocognitive functions may depend on abnormalities in basic cortical characteristics. These results may fundamentally change approaches to rehabilitation in such conditions, emphasizing the potential of low-level visual interventions.


Improved vertical optical fiber borehole strainmeter design for measuring Earth strain.
Fiber-based interferometers provide the means to sense very small displacements over long baselines, and have the advantage of being nearly completely passive in their operation, making them particularly well suited for geophysical applications. A new 250 m, interferometric vertical borehole strainmeter has been developed based completely on passive optical components. Details of the design and deployment at the Piñon Flat Observatory are presented. Power spectra show an intertidal noise level of -130 dB (re. 1 ϵ(2)/Hz), consistent within 1-3 dB between redundant components. Examination of its response to Earth tides and earthquakes relative to the areal strain recorded by an orthogonal pair of collocated, 730 m horizontal laser strainmeters yield a Poisson's ratio for local near surface material of 0.25 that is consistent with previous results.


Improvement of lithium anode deterioration for ameliorating cyclabilities of non-aqueous Li-CO2 batteries.
Herein, ruthenium (Ru) nanoparticles were anchored on carbon nanotubes (Ru/CNTs) functionalized as catalyst cathodes for non-aqueous Li-CO2 cells. For cycling tests through a low cut-off capacity (100 mA h g-1), the origin of battery deterioration resulted from the accumulation of Li2CO3 discharging products on catalytic surfaces, identical to the observations in previous studies. However, the Li-CO2 cells in this work showed a sudden death within several cycles of high cut-off capacity (500 mA h g-1), and no Li2CO3 residues were investigated on the cathode. In contrast, Li dendrites and passivation materials (LiOH and Li2CO3) were generated on Li anodes upon cycling at a limited capacity of 500 mA h g-1, which dominantly contributed to the battery degradation. A Li foil-replacement method was adopted to make the Ru/CNT cathode perform continuous 100 cycles under a cut-off capacity of 500 mA h g-1. These results indicate that not only Li2CO3 residues blocked on the active sites of the cathode but also Li dendrites and passivation materials produced on the anode caused Li-CO2 battery deterioration. Moreover, in the present work, a carbon thin film was deposited on Li metal (C/Li) by a sputtering system for suppressing the dendrite formation upon cycling and promoting the defense of the H2O attack from the electrolyte disintegration. The Li-CO2 cell with a Ru/CNT catalyst and a C/Li anode revealed an improved electrochemical stability of 115 cycles at a limited capacity of 500 mA h g-1. This proto strategy provided a significant research direction focusing on Li anodes for elevating the Li-CO2 battery durability.


Assembly and regulation of acetylcholinesterase at the vertebrate neuromuscular junction.
The collagen-tailed form of acetylcholinesterase (ColQ-AChE) is the major if not unique form of the enzyme associated with the neuromuscular junction (NMJ). This enzyme form consists of catalytic and non-catalytic subunits encoded by separate genes, assembled as three enzymatic tetramers attached to the three-stranded collagen-like tail (ColQ). This synaptic form of the enzyme is tightly attached to the basal lamina associated with the glycosaminoglycan perlecan. Fasciculin-2 is a snake toxin that binds tightly to AChE. Localization of junctional AChE on frozen sections of muscle with fluorescent Fasciculin-2 shows that the labeled toxin dissociates with a half-life of about 36 h. The fluorescent toxin can subsequently be taken up by the muscle fibers by endocytosis giving the appearance of enzyme recycling. Newly synthesized AChE molecules undergo a lengthy series of processing events before final transport to the cell surface and association with the synaptic basal lamina. Following co-translational glycosylation the catalytic subunit polypeptide chain interacts with several molecular chaperones, glycosidases and glycosyltransferases to produce a catalytically active enzyme that can subsequently bind to one of two non-catalytic subunits. These molecular chaperones can be rate limiting steps in the assembly process. Treatment of muscle cells with a synthetic peptide containing the PRAD attachment sequence and a KDEL retention signal results in a large increase in assembled and exportable AChE, providing an additional level of post-translational control. Finally, we have found that Pumilio2, a member of the PUF family of RNA-binding proteins, is highly concentrated at the vertebrate neuromuscular junction where it plays an important role in regulating AChE translation through binding to a highly conserved NANOS response element in the 3'-UTR. Together, these studies define several new levels of AChE regulation in electrically excitable cells.


Patient empowerment. Results of a randomized controlled trial.
The purpose of this study was to determine if participation in a patient empowerment program would result in improved psychosocial self-efficacy and attitudes toward diabetes, as well as a reduction in blood glucose levels. This study was conducted as a randomized, wait-listed control group trial. The intervention group received a six-session (one session per week) patient empowerment education program; the control group was assigned to a wait-list. At the end of 6 weeks, the control group completed the six-session empowerment program. Six weeks after the program, both groups provided follow-up data. The intervention group showed gains over the control group on four of the eight self-efficacy subscales and two of the five diabetes attitude subscales. Also, the intervention group showed a significant reduction in glycated hemoglobin levels. Within groups, analysis of data from all program participants showed sustained improvements in all of the self-efficacy areas and two of the five diabetes attitude subscales and a modest improvement in blood glucose levels. This study indicated that patient empowerment is an effective approach to developing educational interventions for addressing the psychosocial aspects of living with diabetes. Furthermore, patient empowerment is conducive to improving blood glucose control. In an ideal setting, patient education would address equally blood glucose management and the psychosocial challenges of living with diabetes.


Hemianopic and quadrantanopic field loss, eye and head movements, and driving.
To compare eye and head movements, lane keeping, and vehicle control of drivers with hemianopic and quadrantanopic field defects with controls, and to identify differences in these parameters between hemianopic and quadrantanopic drivers rated safe to drive by a clinical driving rehabilitation specialist compared with those rated as unsafe. Eye and head movements and lane keeping were rated in 22 persons with homonymous hemianopic defects and 8 with quadrantanopic defects (mean age, 53 years) who were ≥6 months post-injury and 30 persons with normal fields (mean age, 53 years). All were licensed to drive and were current drivers or aimed to resume driving. Participants drove a 6.3-mile route along non-interstate city roads under in-traffic conditions. Vehicle control was assessed objectively by vehicle instrumentation for speed, braking, acceleration, and cornering. As a group, drivers with hemianopic or quadrantanopic defects drove slower, exhibited less excessive cornering or acceleration, and executed more shoulder movements than the controls. Those drivers with hemianopic or quadrantanopic defects rated as safe also made more head movements into their blind field, received superior ratings regarding eye movement extent and lane position stability, and exhibited less sudden braking and drove faster than those rated unsafe. Persons with hemianopic and quadrantanopic defects rated as safe to drive compensated by making more head movements into their blind field, combined with more stable lane keeping and less sudden braking. Future research should evaluate whether these characteristics could be trained in rehabilitation programs aimed at improving driving safety in this population.


Principles for evaluating knowledge co-production in natural resource management: Incorporating decision-maker values.
A key reason for undertaking transdisciplinary processes such as knowledge co-production in natural resource management is to access and apply different knowledge systems to complex issues. However, the value of co-production is predominantly framed by academics. They have focused on research design and outcomes in the form of 'science informing policy'. In this paper we build a more inclusive and holistic framing of knowledge co-production incorporating values of non-academic participants, and values related to the participatory process. Specifically, we examine how knowledge is communicated and deliberated upon and the requirements for this to be done effectively. We draw upon empirical data from interviews with natural resource managers who participated in two case studies of knowledge co-production in Australia and South Africa. Their perspectives are captured in eight evaluation principles that build upon existing evaluation frameworks for public participation. Critically, decision-makers valued science-based outputs not just as salient knowledge sources, but to give legitimacy to their decisions. This need for legitimacy necessitates transparency, fairness and inclusivity in knowledge selection, participation and dialogue within knowledge co-production processes. The practice-based knowledge of decision-makers was important for contextualizing and applying science to specific decision contexts. Another key finding is that communicative competence is central to the process of knowledge co-production because it enables participants to critically explore and understand the knowledge claims of others.


Transcriptome assembly and quantification from Ion Torrent RNA-Seq data.
High throughput RNA sequencing (RNA-Seq) can generate whole transcriptome information at the single transcript level providing a powerful tool with multiple interrelated applications including transcriptome reconstruction and quantification. The sequences of novel transcripts can be reconstructed from deep RNA-Seq data, but this is computationally challenging due to sequencing errors, uneven coverage of expressed transcripts, and the need to distinguish between highly similar transcripts produced by alternative splicing. Another challenge in transcriptomic analysis comes from the ambiguities in mapping reads to transcripts. We present MaLTA, a method for simultaneous transcriptome assembly and quantification from Ion Torrent RNA-Seq data. Our approach explores transcriptome structure and incorporates a maximum likelihood model into the assembly and quantification procedure. A new version of the IsoEM algorithm suitable for Ion Torrent RNA-Seq reads is used to accurately estimate transcript expression levels. The MaLTA-IsoEM tool is publicly available at: http://alan.cs.gsu.edu/NGS/?q=malta Experimental results on both synthetic and real datasets show that Ion Torrent RNA-Seq data can be successfully used for transcriptome analyses. Experimental results suggest increased transcriptome assembly and quantification accuracy of MaLTA-IsoEM solution compared to existing state-of-the-art approaches.


Optimal seasonal timing of oral azithromycin for malaria.
Mass administration of azithromycin for trachoma has been shown to reduce malarial parasitemia. However, the optimal seasonal timing of such distributions for antimalarial benefit has not been established. We performed numerical analyses on a seasonally forced epidemic model (of Ross-Macdonald type) with periodic impulsive annual mass treatment to address this question. We conclude that when azithromycin-based trachoma elimination programs occur in regions of seasonal malaria transmission, such as Niger, the optimal seasonal timing of mass drug administration (MDA) may not occur during the season of maximum transmission.


Interaction, action, and reflection: how medics learn medical care in the Swedish Armed Forces.
The objective of this study is to examine how medics within the Swedish Armed Forces perceive their learning outcome following military prehospital training. A qualitative study with a phenomenographic approach was used to investigate how learning is perceived among military medics. At meta level, the results can be viewed as an interaction, i.e., being able to collaborate in the medical platoon, including the ability to interact within the group and being able to lead; an action, i.e., being able to assess and treat casualties, including the ability to communicate with the casualty, to prioritize, and to be able to act; and a reflection, i.e., having confidence in one's own ability in first aid, including being prepared and feeling confident. Interaction during the period of education is important for learning. Action, being able to act in the field, is based on a drill in which the subject progresses from simple to complex procedures. Reflection, learning to help others, is important for confidence, which in turn creates preparedness, thereby making the knowledge meaningful.


Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.


Development of urinary concentrating capacity: role of aquaporin-2.
The capacity to concentrate urine develops progressively during postnatal life in most mammalian species. Here we have examined whether low expression of the arginine vasopressin (AVP)-activated water channel aquaporin-2 (AQP-2) may be a limiting factor for the concentrating capacity in the infant rats. Urine osmolality in response to 24-h dehydration increased significantly from 10 to 40 days of age. The most rapid increase occurred during the weaning period, i.e., days 15-20. A similar developmental pattern was observed for AQP-2 mRNA levels in the renal medulla. AQP-2 protein levels also increased markedly from day 10 to 40. Immunohistochemistry revealed that AQP-2 was exclusively located in collecting duct principal cells both in infant and adult rats but that the signal was much weaker in infants. To further examine the relationship between urinary concentrating capacity and AQP-2 expression, we treated rats with a single injection of betamethasone, which is known to accelerate maturation in several organs. Twenty-four hours after treatment, there was an increase in urine osmolality, renal medullary AQP-2 mRNA, and AQP-2 protein levels in infant but not in adult rats. A single injection of a specific V2 agonist caused within 6 h significant increase of AQP-2 mRNA in both infant and adult. The expression of the mRNA of three other transporters involved in the concentrating process, medullary Na(+)-K(+)-ATPase alpha-subunit, Na-K-2Cl cotransporter, and epithelial chloride channel also increased during the weaning period and were upregulated by glucocorticoids. We conclude that there is a well-synchronized development of the many of the components that determine the concentrating capacity and that the low expression of AQP-2 is one of the limiting factors for low concentrating capacity in infants.


Responses of Antarctic soil microbial communities and associated functions to temperature and freeze-thaw cycle frequency.
Climatic changes will not only result in higher overall temperature, but also in greater variability in weather conditions. Antarctic soils are subjected to extremely variable conditions in the form of frequent freeze-thaw cycles (FTCs), but the importance of alteration in FTC frequency, compared with increases in average temperature and indirect vegetation-mediated effects on soil microorganisms, is still unknown. We therefore designed two complementary microcosm experiments using undisturbed soil cores from Signy Island (60 degrees 43'S, 45 degrees 38'W) in the maritime Antarctic. The experiments consisted of soil core incubations with or without the overlying vegetation at four different temperatures and six different FTC regimes. We assessed bacterial and fungal density and community structure, as well as the density of several key genes in microbial nutrient cycles using a combination of RNA- and DNA-based molecular fingerprinting and quantitative PCR approaches in addition to enzymatic activity assays. Results showed that bacteria were more affected by warming than by changes in FTC frequency. In contrast, fungal community structure and abundance were mostly influenced by FTC frequency, as well as the presence of vegetation cover. The relative densities of several bacterial gene families involved in key steps of the N-cycle were affected by FTCs, while warming had little or no effect. The FTCs and incubation temperature also strongly influenced laccase enzymatic activity in soil. In total, our results suggest that, in addition to climatic warming, increased climatic variability may also have a profound impact on Antarctic microbial communities. Although these effects are difficult to detect with assays of total bacterial community structure, they do become manifest in the analysis of key functional gene densities.


A prospective randomized double-blind study of pain control by topical calcium channel blockers versus placebo after Milligan-Morgan hemorrhoidectomy.
Post-hemorrhoidectomy pain is significantly associated with a hypertonicity of the internal anal sphincter. We evaluated the effects of topical diltiazem, a calcium channel blocker, in reducing pain after hemorrhoidectomy. Purpose of our study was to determine difference in extent of pain control by application of topical calcium channel blocker (diltiazem 2%) versus placebo ointment. This was a prospective randomized double-blind clinical study conducted at Sawai Man Singh Hospital, Jaipur, from May 2016 to May 2017. Sixty patients, who had undergone hemorrhoid, were randomly assigned to receive 2% diltiazem ointment (n = 30) or a placebo ointment (n = 30) postoperatively. Ointments were applied to the perianal region three times daily for 7 days. Pain scores were recorded using visual analog scale at 6, 24, and 48 h and seventh day postoperatively and number of analgesic doses consumed by patients in the first 3 days. Patients using the diltiazem ointment had significantly less pain and greater benefit than those in the placebo group throughout the first postoperative week (p < 0.001) except for reading at 6 h. Also, there was significantly less number of analgesic doses consumed in the diltiazem group compared to the placebo group. Perianal application of 2% diltiazem ointment after hemorrhoidectomy significantly reduces postoperative pain and is perceived as beneficial.


Tumor-penetrating peptide for systemic targeting of Tenascin-C.
Extracellular matrix in solid tumors has emerged as a specific, stable, and abundant target for affinity-guided delivery of anticancer drugs. Here we describe the homing peptide that interacts with the C-isoform of Tenascin-C (TNC-C) upregulated in malignant tissues. TNC-C binding PL3 peptide (amino acid sequence: AGRGRLVR) was identified by in vitro biopanning on recombinant TNC-C. Besides TNC-C, PL3 interacts via its C-end Rule (CendR) motif with cell-and tissue penetration receptor neuropilin-1 (NRP-1). Functionalization of iron oxide nanoworms (NWs) and metallic silver nanoparticles (AgNPs) with PL3 peptide increased tropism of systemic nanoparticles towards glioblastoma (GBM) and prostate carcinoma xenograft lesions in nude mice (eight and five-fold respectively). Treatment of glioma-bearing mice with proapoptotic PL3-guided NWs improved the survival of the mice, whereas treatment with untargeted particles had no effect. PL3-coated nanoparticles were found to accumulate in TNC-C and NRP-1-positive areas in clinical tumor samples, suggesting a translational relevance. The systemic tumor-targeting properties and binding of PL3-NPs to the clinical tumor sections, suggest that the PL3 peptide may have applications as a targeting moiety for the selective delivery of imaging and therapeutic agents to solid tumors.


Immunohistochemical study of thyroid transcription factor-1 and HER2/neu in non-small cell lung cancer: strong thyroid transcription factor-1 expression predicts better survival.
The relationship of thyroid transcription factor-1 (TTF-1) and HER2/neu expression in non-small cell lung cancer (NSCLC) with multiple parameters including survival were examined. Patients with primary NSCLC who had surgical resection and follow-up of at least 5 years were included in the study. There were 57 patients (38 men and 19 women), 44 to 75 years old (median age, 61 years); 28 patients had adenocarcinoma (AD) and 29 had squamous cell carcinoma. Tumors were examined for TTF-1 and HER2/neu expression using formalin-fixed, paraffin-embedded tissue. Clinical and follow-up data were obtained from the hospital records and Cancer Center database. Representative tumor sections were stained using standard immunohistochemical technique and commercial antibodies for TTF-1 (clone 8G7G3/1, Dako) and HER2/neu (polyclonal, Dako). Tumors were graded as negative (<5%), weak positive (5-49%), and strong positive (>50%), based on the percentage of positively stained tumor cells. Statistical analyses were performed using log-rank test, Pearson and Spearman correlations, and Kaplan-Meier survival curves. TTF-1 expression was seen in 45.6% of all tumors (80% of ADs and 14% of squamous cell carcinomas). Eighteen patients with tumors showing strong TTF-1 expression had significantly better survival compared with the 39 patients whose tumors showed negative or weak TTF-1 expression, although many more of the higher stage AD had strong TTF-1 staining than stage I AD. The TTF-1 expression did not correlate with tumor differentiation and was considered an independent predictor of survival. Seventeen of the 18 tumors with strong TTF-1 expression were ADs. Only eight of 57 (17%) tumors showed HER2/neu expression; seven of these eight were ADs. Although HER2/neu expression and survival did not show correlation, the majority of those ADs with weak or strong HER2/neu staining also had strong TTF-1 staining, were mostly stage I tumors. and had overall longer survival. All patients with stage I disease showed better 5-year survival compared with those with stages II and III. Hispanic patients had significantly worse survival compared with Caucasians and African Americans. The results of this study suggest that strong expression of TTF-1 is an independent predictor of better survival and may be a useful prognostic tool for evaluation of patients with NSCLC.


Do we consider Andermann syndrome in infants with agenesis of corpus callosum.
Andermann syndrome is characterized by agenesis of corpus callosum, anterior horn cell disease, a mixed sensory and motor neuropathy, and facial dysmorphism, and is inherited as an autosomal recessive trait. A 7-month-old boy was admitted with developmental retardation. Head control was not gained and he could not sit. He had high arched palate, elongated facies and large angle of the mandible, which were compatible with the Andermann syndrome. Moderate hypotonicity and absent tendon reflexes were also noted. Serum creatine kinase level was normal. Magnetic resonance imaging of the brain showed agenesis of the corpus callosum. Electromyographic examination revealed the presence of both sensory and motor neuropathy. The patient was diagnosed as having the Andermann syndrome according to the clinical and laboratory findings and he is reported due to rare presentation.


Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome.
Dietary fructose is implicated in metabolic syndrome, but intervention studies are confounded by positive caloric balance, changes in adiposity, or artifactually high amounts. This study determined whether isocaloric substitution of starch for sugar would improve metabolic parameters in Latino (n = 27) and African-American (n = 16) children with obesity and metabolic syndrome. Participants consumed a diet for 9 days to deliver comparable percentages of protein, fat, and carbohydrate as their self-reported diet; however, dietary sugar was reduced from 28% to 10% and substituted with starch. Participants recorded daily weights, with calories adjusted for weight maintenance. Participants underwent dual-energy X-ray absorptiometry and oral glucose tolerance testing on Days 0 and 10. Biochemical analyses were controlled for weight change by repeated measures ANCOVA. Reductions in diastolic blood pressure (-5 mmHg; P = 0.002), lactate (-0.3 mmol/L; P < 0.001), triglyceride, and LDL-cholesterol (-46% and -0.3 mmol/L; P < 0.001) were noted. Glucose tolerance and hyperinsulinemia improved (P < 0.001). Weight reduced by 0.9 ± 0.2 kg (P < 0.001) and fat-free mass by 0.6 kg (P = 0.04). Post hoc sensitivity analysis demonstrates that results in the subcohort that did not lose weight (n = 10) were directionally consistent. Isocaloric fructose restriction improved surrogate metabolic parameters in children with obesity and metabolic syndrome irrespective of weight change.


Striated myocyte structural integrity: Automated analysis of sarcomeric z-discs.
As sarcomeres produce the force necessary for contraction, assessment of sarcomere order is paramount in evaluation of cardiac and skeletal myocytes. The uniaxial force produced by sarcomeres is ideally perpendicular to their z-lines, which couple parallel myofibrils and give cardiac and skeletal myocytes their distinct striated appearance. Accordingly, sarcomere structure is often evaluated by staining for z-line proteins such as α-actinin. However, due to limitations of current analysis methods, which require manual or semi-manual handling of images, the mechanism by which sarcomere and by extension z-line architecture can impact contraction and which characteristics of z-line architecture should be used to assess striated myocytes has not been fully explored. Challenges such as isolating z-lines from regions of off-target staining that occur along immature stress fibers and cell boundaries and choosing metrics to summarize overall z-line architecture have gone largely unaddressed in previous work. While an expert can qualitatively appraise tissues, these challenges leave researchers without robust, repeatable tools to assess z-line architecture across different labs and experiments. Additionally, the criteria used by experts to evaluate sarcomeric architecture have not been well-defined. We address these challenges by providing metrics that summarize different aspects of z-line architecture that correspond to expert tissue quality assessment and demonstrate their efficacy through an examination of engineered tissues and single cells. In doing so, we have elucidated a mechanism by which highly elongated cardiomyocytes become inefficient at producing force. Unlike previous manual or semi-manual methods, characterization of z-line architecture using the metrics discussed and implemented in this work can quantitatively evaluate engineered tissues and contribute to a robust understanding of the development and mechanics of striated muscles.


Optimal supply chains and power sector benefits of green hydrogen.
Green hydrogen can help to decarbonize parts of the transportation sector, but its power sector interactions are not well understood so far. It may contribute to integrating variable renewable energy sources if production is sufficiently flexible in time. Using an open-source co-optimization model of the power sector and four options for supplying hydrogen at German filling stations, we find a trade-off between energy efficiency and temporal flexibility. For lower shares of renewables and hydrogen, more energy-efficient and less flexible small-scale on-site electrolysis is optimal. For higher shares of renewables and/or hydrogen, more flexible but less energy-efficient large-scale hydrogen supply chains gain importance, as they allow to temporally disentangle hydrogen production from demand via storage. Liquid hydrogen emerges as particularly beneficial, followed by liquid organic hydrogen carriers and gaseous hydrogen. Large-scale hydrogen supply chains can deliver substantial power sector benefits, mainly through reduced renewable curtailment. Energy modelers and system planners should consider the distinct flexibility characteristics of hydrogen supply chains in more detail when assessing the role of green hydrogen in future energy transition scenarios. We also propose two alternative cost and emission metrics which could be useful in future analyses.


Theoretical exploration of 2,2'-bipyridines as electro-active compounds in flow batteries.
Compounds from the 2,2'-bipyridine molecular family were investigated for use as redox-active materials in organic flow batteries. For 156 2,2'-bipyridine derivatives reported in the academic literature, we calculated the redox potential, the pKa for the second deprotonation reaction, and the solubility in aqueous solutions. Using experimental data on a small subset of derivatives, we were able to calibrate our calculations. We find that functionalization with electron-withdrawing groups leads to an increase of the redox potential and to an increase of the molecular acidity (as expressed in a reduction of the pKa value for the second deprotonation step). Furthermore, calculations of solubility in water indicate that some of the studied derivatives have adequate solubility for flow battery applications. Based on an analysis of the phyisco-chemical properties of the 156 studied compounds, we down-select five molecules with carbonyl- and nitro-based functional groups, whose parameters are especially promising for potential applications as negative redox-active materials in organic flow batteries.


Prevalence of drug use during sex among swingers and perceived benefits and risks - a cross-sectional internet survey in the Netherlands.
Drug use during sex has been associated with sexually transmitted infections (STI). While a growing body of research has investigated drug use during sex among men who have sex with men, data in swingers is limited. Swingers are heterosexual couples who have sex with others and singles who have sex with these couples. Our study assessed the prevalence of drug use during sex and perceived benefits and risks among swingers. In 2018, 1005 swingers completed an online questionnaire that was advertised at Dutch swinger-websites. We assessed the associations between drug use during sex <6 months (any drug use excluding alcohol and erection medicines) and sociodemographic characteristics, alcohol use and condomless sex using backward multivariable logistic regression analysis. We compared drug use, motives, beliefs and experienced effects between heterosexual male, bisexual male and female drug-using swingers using χ2-tests. Drug use during sex was reported by 44% (443/1005): 51% in women, 44% in bisexual men and 39% in heterosexual men (P<0.01). Condomless vaginal (46%) and anal sex (22%) was higher in drug-using swingers (vs 34% and 13% in non-drug-using swingers, P<0.001). Among drug-using swingers, XTC (92%), GHB (76%) and laughing gas (69%) were mostly used. Prolonging sex (68%) and increasing arousal (66%) were the most reported motives. Most reported positive effects were feeling happy (78%) and increasing energy (78%). Ninety-four per cent considered drug use to be pleasurable. The most reported negative effect was feeling tired (53%), 7% reported that they might become addicted or felt uncomfortable having sex without drugs. This study among a large group of swingers shows that drug use during sex is highly prevalent. STI clinics should discuss drug use during sex among swingers and provide information on safer sex and drug use, while acknowledging the perceived benefits, such as the increased quality of sex.


Towards integrated surveillance of zoonoses: spatiotemporal joint modeling of rodent population data and human tularemia cases in Finland.
There are an increasing number of geo-coded information streams available which could improve public health surveillance accuracy and efficiency when properly integrated. Specifically, for zoonotic diseases, knowledge of spatial and temporal patterns of animal host distribution can be used to raise awareness of human risk and enhance early prediction accuracy of human incidence. To this end, we develop a spatiotemporal joint modeling framework to integrate human case data and animal host data to offer a modeling alternative for combining multiple surveillance data streams in a novel way. A case study is provided of spatiotemporal modeling of human tularemia incidence and rodent population data from Finnish health care districts during years 1995-2012. Spatial and temporal information of rodent abundance was shown to be useful in predicting human cases and in improving tularemia risk estimates in 40 and 75% of health care districts, respectively. The human relative risk estimates' standard deviation with rodent's information incorporated are smaller than those from the model that has only human incidence. These results support the integration of rodent population variables to reduce the uncertainty of tularemia risk estimates. However, more information on several covariates such as environmental, behavioral, and socio-economic factors can be investigated further to deeper understand the zoonotic relationship.


NORMA-Gene: a simple and robust method for qPCR normalization based on target gene data.
Normalization of target gene expression, measured by real-time quantitative PCR (qPCR), is a requirement for reducing experimental bias and thereby improving data quality. The currently used normalization approach is based on using one or more reference genes. Yet, this approach extends the experimental work load and suffers from assumptions that may be difficult to meet and to validate. We developed a data driven normalization algorithm (NORMA-Gene). An analysis of the performance of NORMA-Gene compared to reference gene normalization on artificially generated data-sets showed that the NORMA-Gene normalization yielded more precise results under a large range of parameters tested. Furthermore, when tested on three very different real qPCR data-sets NORMA-Gene was shown to be best at reducing variance due to experimental bias in all three data-sets compared to normalization based on the use of reference gene(s). Here we present the NORMA-Gene algorithm that is applicable to all biological and biomedical qPCR studies, especially those that are based on a limited number of assayed genes. The method is based on a data-driven normalization and is useful for as little as five target genes comprising the data-set. NORMA-Gene does not require the identification and validation of reference genes allowing researchers to focus their efforts on studying target genes of biological relevance.


Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation.
Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1, CCM2, or PDCD10 Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kinase kinase 3 (MEKK3) signaling downstream of Toll-like receptor 4 (TLR4) stimulation by lipopolysaccharide derived from the gut microbiome. These findings suggest a gut-brain CCM disease axis but fail to define it or explain the poor prognosis of patients with PDCD10 mutations. Here, we demonstrate that the gut barrier is a primary determinant of CCM disease course, independent of microbiome configuration, that explains the increased severity of CCM disease associated with PDCD10 deficiency. Chemical disruption of the gut barrier with dextran sulfate sodium augments CCM formation in a mouse model, as does genetic loss of Pdcd10, but not Krit1, in gut epithelial cells. Loss of gut epithelial Pdcd10 results in disruption of the colonic mucosal barrier. Accordingly, loss of Mucin-2 or exposure to dietary emulsifiers that reduce the mucus barrier increases CCM burden analogous to loss of Pdcd10 in the gut epithelium. Last, we show that treatment with dexamethasone potently inhibits CCM formation in mice because of the combined effect of action at both brain endothelial cells and gut epithelial cells. These studies define a gut-brain disease axis in an experimental model of CCM in which a single gene is required for two critical components: gut epithelial function and brain endothelial signaling.


Prevalence of Bartonella infection in wild African lions (Panthera leo) and cheetahs (Acinonyx jubatus).
Bartonella species are emerging pathogens that have been isolated worldwide from humans and other mammals. Our objective was to estimate the prevalence of Bartonella infection in free-ranging African lions (Panthera leo) and cheetahs (Acinonyx jubatus). Blood and/or serum samples were collected from a convenience sample of 113 lions and 74 cheetahs captured in Africa between 1982 and 2002. Whole blood samples available from 58 of the lions and 17 of the cheetahs were cultured for evidence of Bartonella spp., and whole blood from 54 of the 58 lions and 73 of the 74 cheetahs tested for the presence of Bartonella DNA by TaqMan PCR. Serum samples from the 113 lions and 74 cheetahs were tested for the presence of antibodies against Bartonella henselae using an immunofluorescence assay. Three (5.2%) of the 58 lions and one (5.9%) of the 17 cheetahs were bacteremic. Two lions were infected with B. henselae, based on PCR/RFLP of the citrate synthase gene. The third lion and the cheetah were infected with previously unidentified Bartonella strains. Twenty-three percent of the 73 cheetahs and 3.7% of the 54 lions tested by TaqMan PCR were positive for Bartonella spp. B. henselae antibody prevalence was 17% (19/113) for the lions and 31% (23/74) for the cheetahs. The prevalence of seropositivity, bacteremia, and positive TaqMan PCR was not significantly different between sexes and age categories (juvenile versus adult) for both lions and cheetahs. Domestic cats are thus no longer the only known carriers of Bartonella spp. in Africa. Translocation of B. henselae seronegative and TaqMan PCR negative wild felids might be effective in limiting the spread of Bartonella infection.


SU-E-T-176: Improved Collimator Scattering Factor (Sc) Measurements for Small Fields Using Build-Up Caps in Robotic Radiosurgery.
The Monte Carlo calculation algorithm in the MultiPlan (Accuray, Palo Alto, CA) treatment planning system used for CyberKnife (Accuray) robotic radiosurgery requires in-air measurements. In this study, results were compared for the impact of build-up caps using a diode detector for small field in-air measurements. Two acrylic caps custom-made for the SFD diode detector (IBA, Germany) of two thicknesses were compared against free-in-air measurements. The 1.5 and 5 cm thicknesses correspond to Dmax and a depth beyond the range of electron contamination, respectively. A Blue Phantom (IBA) was used to position the diode 80 cm SAD. Measurements were made for all 12 fixed cones ranging from 5 to 60 mm. For the 5 mm cone, there is a 15.6% and 20.0% difference in the Sc factor between the 1.5 cm and 5 cm buildup caps, respectively, versus the free-in-air measurement. For the 7.5 mm cone, the difference is 6.3% and 10.4% for the 1.5 cm and 5 cm buildup caps, respectively, versus the free-in-air measurement. While generally decreasing, the Sc factor for either buildup cap does not agree within 2% to free-in-air measurements until the cone used is larger than 40 mm. Overall, the two buildup caps yield similar Sc factors and the differences observed are attributed to electron contamination. The Monte Carlo calculation algorithm used by the CyberKnife planning manual does not refer to any build-up caps. This study has shown that, particularly for small fields, there are large differences in Sc factors measured with and without buildup caps. In general, for fields smaller than 10 mm, build-up caps should be carefully chosen, especially in commissioning data.


An autopsy study of the incidence of lacunes in relation to age, hypertension, and arteriosclerosis.
We investigated selected features of lacunes in 1,086 necropsy cases. Lacunes were found in brains from patients above the age of 40 years and were most common in brains from persons in their sixties but decreased in number in brains from older persons. The most common site of lacunes was the frontal lobe white matter, followed by the putamen, pons, parietal lobe white matter, thalamus, and caudate nucleus in descending order of frequency. By dividing the 1,086 cases into three groups according to blood pressure, we found more lacunes in the hypertensive and borderline hypertensive groups than in the normotensive group; the average number of lacunes per brain in each group was 3.61, 2.77, and 1.15, respectively. Diastolic hypertension was more closely related to the number of lacunes than was systolic hypertension. The extent of arteriolosclerosis of the medullary arteries in the frontal lobe white matter was measured and compared with the number of lacunes. There was a close correlation between lacunes and arterioloslerosis in all age groups.


Satisfaction with epidural and intravenous patient-controlled analgesia.
Postoperative intravenous (i.v.) versus epidural morphine patient-controlled analgesia (PCA) were compared regarding maintenance of initial PCA route, pain levels, side effects, and levels of satisfaction. Additionally, the role of preoperative attitudinal expectations in predicting postoperative levels of satisfaction with pain management as well as maintenance of initial PCA route was evaluated. After either abdominal or thoracic surgery, 70 eligible patients were randomized to receive morphine either through an epidural route (n = 37) or an intravenous PCA pump (n = 33). A large tertiary university teaching hospital in a major northeastern city. Patients completed visual analogue rating scales 1 week before surgery regarding attitudes such as expectations of satisfaction with pain management after surgery and expectations of medication efficacy postsurgically. Postoperatively, beginning the day after surgery, patients were asked to complete visual analogue rating scales every 12 hours until they were discharged, for a maximum of 3 postoperative days. The scales evaluated included pain, ability to think, and satisfaction with pain control. There were no significant between-group differences on the postoperative visual analogue scales. Although the overall rate of changing the initial PCA route to which the patients were randomized was identical for both groups (30%), those patients who had thoracic surgery changed their route of PCA administration significantly less when their initial PCA route was epidural (20%) than when their initial PCA route was i.v. (46%) (P <.05). Patients who were satisfied with pain control postoperatively were more likely to have been started on i.v. PCA (P =.001), have lower preoperative expectations of postoperative satisfaction with pain (P <.001), and have higher preoperative expectations of medication effects on postoperative pain (P <.001). Additionally, older patients (P =.007) and patients with lower preoperative expectations of postoperative satisfaction with pain (P =.003) were more likely to adhere to their initial treatment protocol. Both techniques, i.v. and epidural PCA, result in high levels of satisfaction. Satisfaction with PCA can be accurately predicted in nearly three of four patients based on initial PCA route and preoperative attitudes. Additionally, maintaining the initial treatment plan can be accurately predicted based on age and preoperative attitudes. Patient expectations about pain relief should be addressed preoperatively, particularly with younger patients, for optimal results.


Oral versus inhaled antibiotics for bronchiectasis.
Bronchiectasis is a chronic inflammatory disease characterised by a recurrent cycle of respiratory bacterial infections associated with cough, sputum production and impaired quality of life. Antibiotics are the main therapeutic option for managing bronchiectasis exacerbations. Evidence suggests that inhaled antibiotics may be associated with more effective eradication of infective organisms and a lower risk of developing antibiotic resistance when compared with orally administered antibiotics. However, it is currently unclear whether antibiotics are more effective when administered orally or by inhalation. To determine the comparative efficacy and safety of oral versus inhaled antibiotics in the treatment of adults and children with bronchiectasis. We identified studies through searches of the Cochrane Airways Group's Specialised Register (CAGR), which is maintained by the Information Specialist for the group. The Register contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched ClinicalTrials.gov and the WHO trials portal. We searched all databases in March 2018 and imposed no restrictions on language of publication. We planned to include studies which compared oral antibiotics with inhaled antibiotics. We would have considered short-term use (less than four weeks) for treating acute exacerbations separately from longer-term use as a prophylactic (4 weeks or more). We would have considered both intraclass and interclass comparisons. We planned to exclude studies if the participants received continuous or high-dose antibiotics immediately before the start of the trial, or if they have received a diagnosis of cystic fibrosis (CF), sarcoidosis, active allergic bronchopulmonary aspergillosis or active non-tuberculous Mycobacterial infection. Two review authors independently applied study inclusion criteria to the searches and we planned for two authors to independently extract data, assess risk of bias and assess overall quality of the evidence using GRADE criteria. We also planned to obtain missing data from the authors where possible and to report results with 95% confidence intervals (CIs). We identified 313 unique records through database searches and a further 21 records from trial registers. We excluded 307 on the basis of title and abstract alone and a further 27 after examining full-text reports. No studies were identified for inclusion in the review. There is currently no evidence indicating whether orally administered antibiotics are more beneficial compared to inhaled antibiotics. The recent ERS bronchiectasis guidelines provide a practical approach to the use of long-term antibiotics. New research is needed comparing inhaled versus oral antibiotic therapies for bronchiectasis patients with a history of frequent exacerbations, to establish which approach is the most effective in terms of exacerbation prevention, quality of life, treatment burden, and antibiotic resistance.


Acemannan sponges stimulate alveolar bone, cementum and periodontal ligament regeneration in a canine class II furcation defect model.
Periodontal disease is a common infectious disease, found worldwide, causing the destruction of the periodontium. The periodontium is a complex structure composed of both soft and hard tissues, thus an agent applied to regenerate the periodontium must be able to stimulate periodontal ligament, cementum and alveolar bone regeneration. Recent studies demonstrated that acemannan, a polysaccharide extracted from Aloe vera gel, stimulated both soft and hard tissue healing. This study investigated effect of acemannan as a bioactive molecule and scaffold for periodontal tissue regeneration. Primary human periodontal ligament cells were treated with acemannan in vitro. New DNA synthesis, expression of growth/differentiation factor 5 and runt-related transcription factor 2, expression of vascular endothelial growth factor, bone morphogenetic protein-2 and type I collagen, alkaline phosphatase activity, and mineralized nodule formation were determined using [(3)H]-thymidine incorporation, reverse transcription-polymerase chain reaction, enzyme-linked immunoabsorbent assay, biochemical assay and alizarin red staining, respectively. In our in vivo study, premolar class II furcation defects were made in four mongrel dogs. Acemannan sponges were applied into the defects. Untreated defects were used as a negative control group. The amount of new bone, cementum and periodontal ligament formation were evaluated 30 and 60 d after the operation. Acemannan significantly increased periodontal ligament cell proliferation, upregulation of growth/differentiation factor 5, runt-related transcription factor 2, vascular endothelial growth factor, bone morphogenetic protein 2, type I collagen and alkaline phosphatase activity, and mineral deposition as compared with the untreated control group in vitro. Moreover, acemannan significantly accelerated new alveolar bone, cementum and periodontal ligament formation in class II furcation defects. Our data suggest that acemannan could be a candidate biomolecule for periodontal tissue regeneration.


Evaluation of the tensile strengths of four monofilament absorbable suture materials after immersion in canine urine with or without bacteria.
To evaluate the tensile strength, elongation, and degradation of 4 monofilament absorbable suture materials that undergo degradation by hydrolysis in specimens of canine urine with various physical characteristics. 4 monofilament absorbable sutures (polydioxanone, poliglecaprone 25, polyglyconate, and glycomer 631). Voided urine was collected from 6 healthy dogs, pooled, filter-sterilized, and prepared to provide 5 media: sterile neutral (pH, 7.0), sterile acidic (pH, 6.2), sterile basic (pH, 8.8), Escherichia coli-inoculated, and Proteus mirabilis-inoculated urine. Ten strands of each suture material were immersed in each of the media for 0 to 28 days. Tensile strength and elongation of each suture material were evaluated by use of a texture analyzer on days 0, 1, 3, 7, 10, 14, 21, and 28. Reduction in tensile strength was detected for all materials in all urine specimens over time. Polyglyconate and polydioxanone had superior tensile strengths in sterile neutral and E. coli-inoculated urine, and polydioxanone retained the greatest tensile strength throughout the study period. All suture materials disintegrated before day 7 in P. mirabilis-inoculated urine. Polydioxanone, polyglyconate, and glycomer 631 may be acceptable for urinary bladder closure in the presence of sterile neutral and E. coli-contaminated urine. Tensile strength of poliglecaprone 25 in urine may be unacceptable by the critical healing time for bladder tissue (14 to 21 days). During bladder surgery, exposure of suture material that degrades via hydrolysis to urine containing Proteus spp should be minimized.


Laboratory environments and rodents' behavioural needs: a review.
Laboratory housing conditions have significant physiological and psychological effects on rodents, raising both scientific and humane concerns. Published studies of rats, mice and other rodents were reviewed to document behavioural and psychological problems attributable to predominant laboratory housing conditions. Studies indicate that rats and mice value opportunities to take cover, build nests, explore, gain social contact, and exercise some control over their social milieu, and that the inability to satisfy these needs is physically and psychologically detrimental, leading to impaired brain development and behavioural anomalies (e.g. stereotypies). To the extent that space is a means to gain access to such resources, spatial confinement likely exacerbates these deficits. Adding environmental 'enrichments' to small cages reduces but does not eliminate these problems, and I argue that substantial changes in housing and husbandry conditions would be needed to further reduce them.


Role of the calcium-sensing receptor in parathyroid gland physiology.
The calcium-sensing receptor (CaSR) represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration and modulate parathyroid hormone (PTH) secretion to maintain serum calcium levels within a narrow physiological range. Much has been learned in recent years about the diversity of signal transduction through the CaSR and the various factors that affect receptor expression. Beyond its classic role as a determinant of calcium-regulated PTH secretion, signaling through the CaSR also influences both gene transcription and cell proliferation in parathyroid cells. The CaSR thus serves a broad physiological role by integrating several distinct aspects of parathyroid gland function. The current review summarizes recent developments that enhance our understanding of the CaSR and its fundamental importance in parathyroid gland physiology.


Efficacy and safety of two pegfilgrastim biosimilars: Tripegfilgrastim and pegteograstim.
Our aim was to compare the efficacy and safety of two recently developed biosimilars of pegfilgrastim, a pegylated form of the recombinant human granulocyte-colony stimulating factor (G-CSF) analog filgrastim with those of the reference pegfilgrastim. We retrospectively analyzed data from patients diagnosed with diffuse large B-cell lymphoma (DLBCL) who were treated with first-line R-CHOP chemotherapy and received pegylated G-CSF for primary prophylaxis. The following pegylated G-CSFs were analyzed in this study: reference pegfilgrastim (Neulasta® ) and two of its biosimilars (tripegfilgrastim; Dulastin® and pegteograstim; Neulapeg® ). In total, 296 patients were enrolled. The number of patients with at least one episode of neutropenia during R-CHOP chemotherapy was the lowest in the reference cohort (pegfilgrastim: 127 of 193 patients, 65.8%; tripegfilgrastim: 64 of 69 patients, 92.8%; pegteograstim: 28 of 34 patients, 82.4%, P < .001). The number of patients with at least one episode of febrile neutropenia was also lowest in the reference cohort (pegfilgrastim: 67 of 193 patients, 34.7%; tripegfilgrastim: 38 of 69 patients, 55.1%; pegteograstim: 16 of 34 patients, 47.1%, P = .009). There were no differences in the duration of neutropenia and febrile neutropenia or treatment outcomes (rate of complete response or relapse and survival). There were no reports of grade 3 or higher adverse events requiring discontinuation of prophylactic pegylated G-CSF in any group. The safety of the pegfilgrastim biosimilars for prophylactic purposes was comparable to that of the reference pegfilgrastim; however, in terms of their efficacy, the incidence of neutropenia and febrile neutropenia tended to be higher than that when using pegfilgrastim. The clinical relevance of these results in the biosimilar cohorts should be explored.


Total Synthesis of the Death Cap Toxin Phalloidin: Atropoisomer Selectivity Explained by Molecular-Dynamics Simulations.
Phallotoxins and amatoxins are a group of prominent peptide toxins produced by the death cap mushroom Amanita phalloides. Phalloidin is a bicyclic cyclopeptide with an unusual tryptathionin thioether bridge. It is a potent stabilizer of filamentous actin and in a fluorescently labeled form widely used as a probe for actin binding. Herein, we report the enantioselective synthesis of the key amino acid (2S,4R)-4,5-dihydroxy-leucine as a basis for the first total synthesis of phalloidin, which was accomplished by two different synthesis strategies. Molecular-dynamics simulations provided insights into the conformational flexibility of peptide intermediates of different reaction strategies and showed that this flexibility is critical for the formation of atropoisomers. By simulating the intermediates, rather than the final product, molecular-dynamics simulations will become a decisive tool in orchestrating the sequence of ring formation reactions of complex cyclic peptides.


Role of gastric antioxidant and anti-Helicobactor pylori activities in antiulcerogenic activity of plantain banana (Musa sapientum var. paradisiaca).
Studies with plantain banana (Musa sapientum var. paradisiaca) have indicated its ulcer protective and healing activities through its predominant effect on various mucosal defensive factors [Sanyal et.al, Arch Int Pharmacodyn, 149 (1964) 393; 155 (1965) 244]. Oxidative stress and Helicobactorpylori colonization are considered to be important factors in the pathogenesis of gastric ulcers. In the present study methanolic extract of plantain banana pulp (BE) was evaluated for its (i) antiulcer and antioxidant activities in 2 hr cold restraint stress and (ii) anti-H.pylori activity in vitro. The extract (BE, 50 mg/kg, twice daily for 5 days) showed significant antiulcer effect and antioxidant activity in gastric mucosal homogenates, where it reversed the increase in ulcer index, lipid peroxidation and super oxide dismutase values induced by stress. However it did not produce any change in catalase values, which was significantly decreased by stress. Further, in the in vitro study. BE (0.32-1,000 microg/ml) did not show any anti-H.pylori activity. The results suggest absence of anti-H. pyloric activity of methanolic extract of banana in vitro and its antioxidant activity may be involved in its ulcerprotective activity.


Interactions of polyamines with ion channels.
Endogenous polyamines, in particular spermine, have been found to cause block and modulation of a number of types of ion channel. Intracellular spermine is responsible for intrinsic gating and rectification of strong inward rectifier K+ channels by directly plugging the ion channel pore. These K+ channels control the resting membrane potential in both excitable and non-excitable cells, and control the excitability threshold in neurons and muscle cells. Intracellular spermine causes inward rectification at some subtypes of Ca2+-permeable glutamate receptors in the central nervous system, again by plugging the receptor channel pore, and spermine can even permeate the ion channel of these receptors. Extracellular spermine has multiple effects at the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor, including stimulation that increases the size of NMDA receptor currents, and voltage-dependent block. A number of polyamine-conjugated arthropod toxins and synthetic polyamine analogues are potent antagonists of glutamate receptors, and represent new tools with which to study these receptors. Interactions of polyamines with other types of cation channels have been reported. This area of research represents a new biology and a new pharmacology of polyamines.


Postoperative Prophylactic Antibiotics Reduce Surgical Site Infection Rates after Ventral Hernia Repair: A Systematic Review.
SSIs after ventral hernia repair (VHR) represent a significant complication. The impact of postoperative prophylactic antibiotics on the SSI rates after VHRs is unclear. A systematic review of PubMed and Web of Science databases from inception through March 2016 investigating the effect of postoperative prophylactic antibiotics after VHRs was performed. Strict inclusion and exclusion criteria were implemented, and the methodological quality of the included studies was assessed. After systematic independent assessment of 216 citations, four studies, involving 344 patients, met the inclusion criteria. Among the included studies, 164 patients received >24 hours of postoperative prophylactic antibiotics, whereas 180 patients were controls. The overall incidence of SSI among patients receiving postoperative antibiotics was 14.6 per cent (95% confidence interval [CI], 9.9 to 20.9) which compares favorably with the control group: 35.5 per cent (95% CI, 28.9 to 42.7) (odds ratio: 0.3, 95% CI: 0.2 to 0.5, P < 0.01). Among patient's receiving postoperative antibiotics, the pooled average duration of postoperative antibiotic treatment was 6.2 ± 0.4 days. Based on the available evidence, the use of postoperative prophylactic antibiotics seems to be associated with lower SSI rates after VHRs. Future prospective randomized controlled trials should be conducted to further confirm the efficacy of this prophylactic intervention.


Distance Education in Anesthesia Using Screen-Based Simulation - A Brief Integrative Review.
Screen-based simulation (SBS) using digital technology has been demonstrated to improve the cognitive and psychomotor skills of anesthesia trainees. As a method of education and evaluation, this form of simulation offers multiple advantages related to cost, availability, simplicity, repeatability, and scorability. Online use of SBS with software employing standard cloud-based peer-to-peer platforms allows for instruction at a distance of important anesthesia-related critical thinking skills including crisis management. Despite the fact that there are no studies concerning the application of SBS in anesthesia distance education, this form of instruction has increased as a result of quarantine measures associated with the coronavirus-2 pandemic that have disrupted traditional in-person mannequin-based simulation, and its usage likely will continue through the post-pandemic era for multiple reasons. Several options exist for asynchronous and synchronous teaching of anesthesia skills at a distance with SBS, and there are useful techniques that can assist in achieving these educational goals with this process.


Heart rate during exercise: mechanisms, behavior, and therapeutic and prognostic implications in heart failure patients with reduced ejection fraction.
Exercise intolerance is a typical manifestation of patients affected by heart failure with reduced ejection fraction (HFrEF); however, the relationship among functional capacity, mortality, and exercise-induced heart rate response during exercise remains unclear in either sinus rhythm or atrial fibrillation subjects. Heart rate increase during incremental load exercise has a typical pattern in normal subjects, whereas it is commonly compromised in HFrEF patients, mainly due to the imbalance of the autonomic nervous system. In the present review, we aim to describe the behavior of heart rate during exercise in normal subjects and in HFrEF patients in sinus rhythm and atrial fibrillation, understanding and explaining the mechanism leading to a different exercise performance and functional limitation. Moreover, the role of chronotropic incompetence and the need of standardizing the cutoff criteria are also discussed in order to clarify the clinical importance, the prognostic relevance, and the potential therapeutic implications of this condition. Looking into the relative contribution and interaction of heart rate response during exercise might represent an important issue to guide individualized therapeutic interventions and prognostic assessment in HFrEF patients.