bluuebunny/crossref_metadata_2025 huggingface dataset:
The distribution of circulating microRNA and their relation to coronary disease
Authors: Freedman Jane E , Ercan Bahadir , Morin Kristine M , Liu Ching-Ti , Tamer Lulufer , Ayaz Lokman , Kanadasi Mehmet , Cicek Dilek , Seyhan Ali Ihsan , Akilli Rabia Eker , Camci Celalettin , Cengiz Beyhan , Oztuzcu Serdar , Tanriverdi Kahraman
Published: May 2013

Background: MicroRNAs (miRNAs) are small RNAs that regulate gene expression by suppressing protein translation and may influence RNA expression. MicroRNAs are detected in extracellular locations such as plasma; however, the extent of miRNA expression in plasma its relation to cardiovascular disease is not clear and many clinical studies have utilized array-based platforms with poor reproducibility.

Methods and Results: Initially, to define distribution of miRNA in human blood; whole blood, platelets, mononuclear cells, plasma, and serum from 5 normal individuals were screened for 852 miRNAs using high-throughput micro-fluidic quantitative RT-PCR (qRT-PCR). In total; 609, 448, 658, 147, and 178 miRNAs were found to be expressed in moderate to high levels in whole blood, platelets, mononuclear cells, plasma, and serum, respectively, with some miRNAs uniquely expressed. To determine the cardiovascular relevance of blood miRNA expression, plasma miRNA (n=852) levels were measured in 83 patients presenting for cardiac catheterization. Eight plasma miRNAs were found to have over 2-fold increased expression in patients with significant coronary disease (≥70% stenosis) as compared to those with minimal coronary disease (less than 70% stenosis) or normal coronary arteries. Expression of miR-494, miR-490-3p, and miR-769-3p were found to have significantly different levels of expression. Using a multivariable regression model including cardiovascular risk factors and medications, hsa-miR-769-3p was found to be significantly correlated with the presence of significant coronary atherosclerosis.

Conclusions: This study utilized a superior high-throughput qRT-PCR based method and found that miRNAs are found to be widely expressed in human blood with differences expressed between cellular and extracellular fractions. Importantly, specific miRNAs from circulating plasma are associated with the presence of significant coronary disease.
Adult onset recurrent seizures as the first presentation of primary hypoparathyroidism
Authors: Correia Pamela , Ranjan Rajeev , Agrawal Chandrashekhar
Published: May 2013

Introduction: Hypoparathyroidism leading to hypocalcemia is an important treatable cause of recurrent seizures. Primary hypoparathyroidism presenting for the first time as seizures in adulthood is quite infrequent. Patients may present with hypocalcemic seizures even in the absence of subtle hypocalcemic signs.

Case report: A 30 year old male, was presented to the emergency facility in an unconscious condition. He was intubated on the way to the hospital as he had suffered from two episodes of ventricular tachycardia. He had previous history of recurrent seizures for 6 years inspite of multiple anticonvulsants including phenytoin sodium, sodium valproate, and levetiracetam. The seizure frequency increased in the last year and he would have 5-6 episodes/ month. A MRI brain scan and EEG at the onset were both normal, as was the general examination but he had history of bilateral cataracts. There were no signs of tetany. Investigations revealed a normal hemoglobin and glucose level with normal electrolytes and both TLC and DLC levels were also normal. He had a serum calcium level of 3.3 mg% with a serum parathyroid hormone level of 1pg/ml, serum 25(OH) vitamin D levels of 6.6ng/ml and hypomagnesemia. NCCT head scan showed bilateral basal ganglia, and deep white matter calcification.

Conclusions: 1) Ironically, increasing reliance on high end investigations such as a MRI brain scan could lead to certain conditions being missed; conditions that could be easily identifiable by the humble CT scan. 2) All treatable metabolic conditions should be excluded at first before commencing with anticonvulsants; this will restrict patients from burdensome polytherapy and related side effects.
Long double stranded RNA is present in scrapie infected cells and tissues
Authors: Karapetyan Yervand E
Published: May 2013

Despite decades of research efforts, the nature of the infectious agent causing scrapie and other Transmissible Spongiform Encephalopathies (TSE) remains an enigma. The protein-only prion hypothesis posits that an abnormal conformer of a host protein is the infectious agent. Virus and virino theories include host-independent nucleic acids in the genome of the infectious agent, in addition to the protein component (a host protein in the case of virino, and a viral protein in the case of a virus).

Viral or sub-viral nucleic acids have long been sought in scrapie to explain the existence of multiple agent strains. Despite a plethora of different approaches to the search, no scrapie-specific nucleic acid sequences have been found in infected cells or tissues.

Most viruses induce synthesis of long double stranded RNA (dsRNA) during their replication in cells, and thus the presence of long dsRNA would be an indication of viral infection in cells. J2 monoclonal antibody against long dsRNA is a useful tool for easy screening of cells and tissues for the presence of suspected viral infection; however, this antibody has not previously been used for testing of scrapie infected tissues.

Here, we present evidence for long dsRNA in scrapie infected cells and tissues. Such dsRNA is also found in scrapie free tissue culture cells. We believe this may be the first evidence of viral infection in scrapie susceptible and infected cells.
Continuation of dual anti-platelet therapy after drug-eluting stents in primary angioplasty beyond 12 months
Authors: Mohasseb Iman , Gericke Christian A
Published: May 2013

In this correspondence we discuss the results of the meta-analysis by De Luca et al. (2012) in the Archives of Internal Medicine which found that late myocardial reinfarction and stent thrombosis is more common in drug-eluting stents than in bare-metal stents. We discuss the clinical implications of this paper for dual anti-platelet therapy which did not receive sufficient attention in the original publication and the accompanying editorial.
Impact of iron levels on cognitive functioning among dental students of Udaipur, Rajasthan (India)
Authors: Sareen Mohit , Sareen Rateesh , Khajuria Sarang , Roy Sayak
Published: May 2013

Health and intelligence are two closely related aspects of human well being. Nutrition, including iron levels, affects cognitive function and thereby may influence the occupational performance of an individual. Inadequate nutrition during adulthood may lead to decreased work efficiency, poor exercise tolerance and increased susceptibility to infections. The profession of dentistry requires keen recognizing abilities and decision making skills as well as ample physical stamina, which may be impaired in a state of malnourishment. Keeping this in view, this study was designed to assess the possible impact of iron levels on cognitive function among dental students. In this study 206 dental students (150 females and 56 males) participated and their cognitive functioning was determined by answering a questionnaire. The questionnaire evaluated the confidence level, work pattern and the tendency to be distracted by the physical environment of the study participants. Iron status was determined by estimating the hemoglobin level of the individuals. Each of the three cognitive traits was correlated with hemoglobin levels. The results revealed that that majority of dental students had good levels of confidence, work patterns with a low level of restriction and low levels of distraction by the physical environment. No significant correlations were found between any of the cognitive parameters and hemoglobin levels (p>0.05) in female participants. In male participants significant correlations were found in two out of three cognitive functioning tests, confidence levels and work pattern (p<0.05). The results of this study suggest that these three cognitive functions may not be influenced by hemoglobin levels in females and may be slightly or, due to the small male sample size which may have confounded the results, not influenced by hemoglobin in males.
The relationship between political ideology and mortality in Poland
Authors: Romaniuk Piotr , Paudyal Priyamvada , Krajewski-Siuda Krzysztof , Topór- Mądry Roman , Maddox Raglan , Gericke Christian A
Published: May 2013

Introduction: The political preference of voters has been shown to be associated with their health status. We investigated the relationship between political preferences and mortality in Poland around the time of the last three general elections.

Methods: We used the electoral data from the general elections held in 2001, 2005 and 2007. Indicators of political ideological preference were constructed based on the percentage of votes gathered by each party. Data on mortality, education and income level were obtained from 2002-2007 from the Polish Central Statistical Office. Pearson correlation was computed between standardised mortality ratios (SMR) and political preference. Finally, the influence of political preference on SMR was examined in a multivariate analysis controlling for socio-economic factors.

Results: SMR was positively correlated with liberal political views (0.26; p<0.05) and negatively correlated with both secondary education (-0.49; p<0.05) and monthly income (-0.239; p<0.05). The correlation between SMR and conservative political views was negative, although the result did not reach statistical significance. Education and income explained more of the variation in SMR than political views. In a multivariate regression, the liberal views factor and secondary education were significantly associated with the SMR (p<0.001 for both).

Conclusion: Our findings are consistent with earlier studies conducted in western countries showing a positive correlation between liberal political ideology and SMR, but differ in that an inverse relationship was found between conservative political orientation with education and income. The importance of socioeconomic and geographical factors in relation to political affiliation and health inequalities in Poland should be further explored.
Inhalational sevoflurane in severe bronchial obstruction unresponsive to multipharmacologic therapy: a case report
Authors: Weber Thomas , Schiebenpflug Christian , Deusch Engelbert
Published: May 2013

Introduction:Bronchial asthma with respiratory failure is a challenge for the intensivist as mechanical ventilation is often difficult due to bronchoconstriction and air-trapping. We describe a case of severe asthma with respiratory acidosis in a 10-year-old patient unresponsive to multipharmacologic broncholytic therapy. Only the initiation of sevoflurane inhalation resolved severe bronchoconstriction and dynamic hyperinflation, leading to complete recovery.

Case presentation:A 10-year-old Caucasian boy was intubated and mechanically ventilated due to an asthmatic attack. Bronchoconstriction and dynamic hyperinflation were severe while multipharmacological broncholytic therapy was unsuccessful. Inhalation with sevoflurane via an anaesthesia machine was the key intervention leading to gradual resolving of severe hypercapnia and respiratory acidosis. Furthermore bilateral pupil dilation occurred during hypercapnia, but no intracranial pathology could be detected. The patient made an uneventful recovery. To our knowledge this is the first case where hypercapnia and respiratory acidosis were so profound and long lasting yet the patient survived without any damage.

Conclusions:Inhalational anaesthetics must be considered as an early treatment option in ventilated asthmatic patients with bronchial obstruction unresponsive to conventional therapy even though their administration in intensive care units may be difficult.
Constraints, synergies and avenues for scaling up breastfeeding, antibiotics for pneumonia and IMCI interventions in the Cusco region, Peru
Authors: Sarganas Giselle , Scherpbier Robert , Gericke Christian A
Published: May 2013

Objective: The purpose of this qualitative case study was to assess the feasibility of scaling up exclusive breastfeeding for 6 months, antibiotics for pneumonia and integrated management of childhood illness (IMCI) child interventions in three districts of the Cusco region, Peru.

Methods: During field visits, constraints, synergies and solutions to the implementation of the selected interventions were collected through observational recording and interviews of mothers, health workers, and health managers/decision makers. Results are presented for each intervention according to the health system level where they occurred: mother/community, health worker, health centre, and political/managerial levels.

Findings: This case study demonstrates that it is feasible to scale up exclusive breastfeeding, antibiotics for pneumonia and IMCI interventions in poverty-stricken rural areas of a low-income country. Factors that helped and hindered the implementation were identified for each intervention.

Conclusions: The need for a coherent multi-sector approach that includes regulation, implementation and monitoring of health policies and education of all involved stakeholders was apparent. This study also demonstrates that global health interventions need to undergo local adaptation. Identifying local constraints and facilitating factors in a systematic way as proposed in this study is a useful step to increase their effectiveness and reach at the local level and to identify areas for improvement in the original intervention policies.
A rare case of monophasic pleuropulmonary synovial sarcoma
Authors: Sareen Rateesh , Chandralekha Pandey , Sareen Mohit , Dutt Akanksha
Published: May 2013

Pleuropulmonary synovial sarcoma is a diagnostic challenge. Synovial sarcoma is a soft tissue tumor of joints and extremities and are rarely seen in the mediastinum. We report this tumor at a very unusual location – the mediastinum in a 40-year-old female. The histopathology picture along with the location suggested a differential diagnosis of solitary fibrous tumor or mesothelioma, but immunohistochemistry helped in reaching the diagnosis of synovial sarcoma.
Introducing the global medical community to the information presented at local scientific conferences through nephrology blogs
Authors: Desai Tejas , Fang Xiangming , Ferris Maria
Published: May 2013

An increasing number of healthcare providers author medical blogs (bloggers) to educate the public and fellow physicians. Traditionally, many bloggers have assumed that readers are most interested in information presented at prestigious and popular scientific meetings. As a result, the readers and bloggers often ignore blogs of local scientific meetings. We hypothesize that blog readers will utilize blogs about local scientific meetings less than those about national meetings.

We examined nephrology-pertinent blogs from 2010-2012. Blogs were categorized as "local/regional" or "national/international" based on the majority of the audience that attended the live scientific meeting. We tracked the number of pageviews, reading time, and location of use per blog for the first 90-days after its first availability on the website. Wilcoxon testing was performed on all data.

There were 9 local/regional and 11 national/international scientific meetings for which blogs were available. The mean number of page views was significantly lower in blogs from local/regional than national/international conferences (84.7 versus 160.3, respectively; p < 0.01). However, the mean difference in total reading time between both categories of blogs was not significant (p = 0.25).

Data from this investigation do not fully support the hypothesis that readers utilized local/regional blogs less than national/international blogs. Although local/regional blogs attracted fewer readers (lower pageviews), the content in these blogs was compelling enough to keep the reader equally engaged as with national/international blogs.
High fidelity optogenetic control of individual prefrontal cortical pyramidal neurons in vivo
Authors: Nakamura Shinya , Baratta Michael V , Pomrenze Matthew B , Dolzani Samuel D , Cooper Donald C
Published: May 2013

Precise spatial and temporal manipulation of neural activity in specific genetically defined cell populations is now possible with the advent of optogenetics. The emerging field of optogenetics consists of a set of naturally-occurring and engineered light-sensitive membrane proteins that are able to activate (e.g. channelrhodopsin-2, ChR2) or silence (e.g. halorhodopsin, NpHR) neural activity. Here we demonstrate the technique and the feasibility of using novel adeno-associated viral (AAV) tools to activate (AAV-CaMKllα-ChR2-eYFP) or silence (AAV-CaMKllα-eNpHR3.0-eYFP) neural activity of rat prefrontal cortical prelimbic (PL) pyramidal neurons in vivo. In vivo single unit extracellular recording of ChR2-transduced pyramidal neurons showed that delivery of brief (10 ms) blue (473 nm) light-pulse trains up to 20 Hz via a custom fiber optic-coupled recording electrode (optrode) induced spiking with high fidelity at 20 Hz for the duration of recording (up to two hours in some cases). To silence spontaneously active neurons, we transduced them with the NpHR construct and administered continuous green (532 nm) light to completely inhibit action potential activity for up to 10 seconds with 100% fidelity in most cases. These versatile photosensitive tools, combined with optrode recording methods, provide experimental control over activity of genetically defined neurons and can be used to investigate the functional relationship between neural activity and complex cognitive behavior.
Rapid doubling of Alzheimer’s amyloid-β40 and 42 levels in brains of mice exposed to a nickel nanoparticle model of air pollution
Authors: Kim Soong Ho , Knight Elysse M , Saunders Eric L , Cuevas Azita K , Popovech Marusia , Chen Lung-Chi , Gandy Sam
Published: May 2013

Background: Over 20 genetic risk factors have been confirmed to associate with elevated risk for Alzheimer’s disease (AD), but the identification of environmental and/or acquired risk factors has been more elusive. At present, recognized acquired risks for AD include traumatic brain injury, hypercholesterolemia, obesity, hypertension, and type 2 diabetes.

Methods: Based on reports associating various inhalants with AD pathology, we investigated the possibility that air pollution might contribute to AD risk by exposing wild-type mice to a standard air pollution modeling system employing nickel nanoparticle-enriched atmosphere for 3 hr.

Results: Mice exposed to air pollution showed 72-129% increases in brain levels of both amyloid-β peptides Aβ40 and Aβ42, as well as Aβ42/40 (p <0.01).

Conclusions: These effects on elevation of brain Aβ exceed those associated with trisomy 21, a known risk for early onset AD pathology, raising the possibility that clinical importance might be attached. Further work is required to establish the molecular and physiological basis for these phenomena. The rapid, dramatic effect, if verified, would suggest that inhalant exposures should be evaluated for their possible roles in contributing to the environmental risk for common forms of AD.
New record of intraspecific nest parasitism by the Silky Starling (Sturnus sericeus)
Authors: Li Zhong-qiu , Wang Rong-rong , Jiang Xue-lei , Zhang Zhi-yuan
Published: May 2013

The Silky Starling (Sturnus sericeus) is endemic to East Asia and little is know about its’ breeding ecology. We found intraspecific nest parasitism (INP) by this species in a reproductive study conducted from March to June 2011. We found three nests were parasitized using the obvious morphological differences or partition of egg-laying. One egg appeared 3 days after the 26th female had finished laying eggs. One egg was different in color from the other five eggs in the 27th nest. The third instance was discovered in the 37th nest after the fledglings had fledged. Our findings confirmed INP by the Silky Starling.
Innate B cells: oxymoron or validated concept?
Authors: Ware Carl F , Benedict Chris
Published: May 2013

B lymphocytes promote the initial innate interferon response to viral pathogens without the need for antigen receptor activation. B cell dependent IFN production requires the cytokine, lymphotoxin-β. The LTβ pathway is well known to regulate lymphoid organogenesis and homeostasis by differentiating stromal cells and macrophages. However, in response to viral pathogens these same B cell-regulated populations rapidly produce type 1 interferons. Thus, B cells act as innate effector cells via LTβ homeostatic pathways, which serve as innate host barriers to viral pathogens.
III. Cellular ultrastructures in situ as key to understanding tumor energy metabolism: biological significance of the Warburg effect
Authors: Witkiewicz Halina , Oh Phil , Schnitzer Jan E
Published: May 2013

Despite the universality of metabolic pathways, malignant cells were found to have their metabolism reprogrammed to generate energy by glycolysis even under normal oxygen concentrations (the Warburg effect). Therefore, the pathway energetically 18 times less efficient than oxidative phosphorylation was implicated to match increased energy requirements of growing tumors. The paradox was explained by an abnormally high rate of glucose uptake, assuming unlimited availability of substrates for tumor growth in vivo. However, ultrastructural analysis of tumor vasculature morphogenesis showed that the growing tissue regions did not have continuous blood supply and intermittently depended on autophagy for survival. Erythrogenic autophagy, and resulting ATP generation by glycolysis, appeared critical to initiating vasculature formation where it was missing. This study focused on ultrastructural features that reflected metabolic switch from aerobic to anaerobic. Morphological differences between and within different types of cells were evident in tissue sections. In cells undergoing nucleo-cytoplasmic conversion into erythrosomes (erythrogenesis), gradual changes led to replacing mitochondria with peroxisomes, through an intermediate form connected to endoplasmic reticulum. Those findings related to the issue of peroxisome biogenesis and to the phenomenon of hemogenic endothelium. Mitochondria were compacted also during mitosis. In vivo, cells that lost and others that retained capability to use oxygen coexisted side-by-side; both types were important for vasculature morphogenesis and tissue growth. Once passable, the new vasculature segment could deliver external oxygen and nutrients. Nutritional and redox status of microenvironment had similar effect on metabolism of malignant and non-malignant cells demonstrating the necessity to maintain structure-energy equivalence in all living cells. The role of glycolysis in initiating vasculature formation, and in progression of cell cycle through mitosis, indicated that Warburg effect had a fundamental biological significance extending to non-malignant tissues. The approach used here could facilitate integration of accumulated cyber knowledge on cancer metabolism into predictive science.
Maintained consciousness during witnessed asystole after spinal anesthesia for Cesarean section
Authors: Rajput Kanishka , Woehlck Harvey J , Riess Matthias L
Published: May 2013

Despite its low incidence, cardiac arrest after spinal anesthesia carries a high mortality. Counterintuitively, young and healthy patients with low resting pulse are at increased risk. We report the case of a healthy 24 yr G2P0 at term scheduled for elective Cesarean section whose heart rate decreased to 30 bpm, followed by more than 30 seconds of asystole 3 minutes after spinal anesthesia with a T4 level block. Following atropine and epinephrine administration, the patient had several single heart beats when startled by the anesthesiologist’s loud voice and when touching her chest to prepare for chest compressions. Eventually, regular sinus rhythm returned with a heart rate of up to 160 bpm. The patient was rapidly prepped, and within 5 minutes, the fetus was delivered surgically with Apgar scores of 8 and 9. Most unusually, the patient remained responsive during the entire event and denied having lost consciousness. Supine position and volume loading may have contributed to venous pooling within the cerebral vasculature, so even in the absence of cerebral blood flow during asystole venous blood may still have been present and delayed cerebral hypoxia. Therefore, loss of consciousness in the supine position may occur considerably after the onset of asystole which may reduce the time available for treatment and contribute to its high mortality. Inspiration during the two startle reactions may have decreased vagal tone and permitted enough spontaneous cardiac activity to circulate the resuscitative drugs without CPR.
Case Report: Refractory hypotension during general anesthesia despite preoperative discontinuation of an angiotensin receptor blocker
Authors: Nabbi Raha , Woehlck Harvey J , Riess Matthias L
Published: May 2013

Due to their beneficial reduction in morbidity and mortality angiotensin receptor blockers (ARBs) have become increasingly popular to treat hypertension. However, similar to angiotensin converting enzyme inhibitors, they can lead to severe hypotension in conjunction with general anesthesia and thus have been recommended to be withheld in the morning of surgery. Here, we present a 51 year old female who developed severe refractory hypotension after induction of general anesthesia, although she had discontinued her medication 24 hours preoperatively as instructed. Therefore, halting ARBs for more than 24 hours before surgery may be necessary. Heightened awareness of this potential interaction and recognizing the need to treat with vasopressin is required when ARB-induced hypotension occurs.
Laryngeal mask airway insertion by classic and thumb insertion technique: a comparison
Authors: Goyal Monica , Dutt Akanksha , Khan Joad Anjum S
Published: May 2013

We evaluated the efficacy of an alternative technique, for insertion of the silicone laryngeal mask airway (LMA) Classic™ in 40 American Society of Anesthesiologists grade ASA I and II patients scheduled for elective surgery. In group I (Index Finger group), the LMA was inserted by the classic index finger technique and, in group T (Thumb Insertion group), the thumb insertion technique was used. Ease of insertion, fiberoptic laryngoscopic position, cuff pressures and laryngopharyngeal morbidity were assessed in both study groups. On statistical analysis, both groups were comparable in all respects. From our study it can be concluded that thumb insertion is an effective insertion technique for the LMA Classic™.
CO2 elevation improves photosynthetic performance in progressive warming environment in white birch seedlings
Authors: Zhang Shouren , Dang Qing-Lai
Published: May 2013

White birch (Betula paperifera Mash) seedlings were exposed to progressively warming in greenhouses under ambient and elevated CO2 concentrations for 5 months to explore boreal tree species’ potential capacity to acclimate to global climate warming and CO2 elevation. In situ foliar gas exchange, in vivo carboxylation characteristics and chlorophyll fluorescence were measured at temperatures of 26oC and 37oC. Elevated CO2 significantly increased net photosynthetic rate (Pn) at both measurement temperatures, and Pn at 37oC was higher than that at 26oC under elevated CO2. Stomatal conductance (gs) was lower at 37oC than at 26oC, while transpiration rate (E) was higher at 37oC than that at 26oC. Elevated CO2 significantly increased instantaneous water-use efficiency (WUE) at both 26oC and 37oC, but WUE was markedly enhanced at 37oC under elevated CO2. The effect of temperature on maximal carboxylation rate (Vcmax), PAR-saturated electron transport rate (Jmax) and triose phosphate utilization (TPU) varied with CO2, and the Vcmax and Jmax were significantly higher at 37oC than at 26oC under elevated CO2. However, there were no significant interactive effects of CO2 and temperature on TPU. The actual photochemical efficiency of PSII (DF/ Fm’), total photosynthetic linear electron transport rate through PSII (JT) and the partitioning of JT to carboxylation (Jc) were higher at 37oC than at 26oC under elevated CO2. Elevated CO2 significantly suppressed the partitioning of JT to oxygenation (Jo/JT). The data suggest that the CO2 elevation and progressive warming greatly enhanced photosynthesis in white birch seedlings in an interactive fashion.
Characteristics of exhaled particle production in healthy volunteers: possible implications for infectious disease transmission
Authors: Wurie Fatima , Le Polain de Waroux Olivier , Brande Matthew , DeHaan Wesley , Holdgate Katherine , Mannan Rishi , Milton Donald , Swerdlow Daniel , Hayward Andrew
Published: May 2013

The size and concentration of exhaled particles may influence respiratory infection transmission risk. We assessed variation in exhaled particle production between individuals, factors associated with high production and stability over time.

We measured exhaled particle production during tidal breathing in a sample of 79 healthy volunteers, using optical particle counter technology. Repeat measurements (several months after baseline) were obtained for 37 of the 79 participants.   Multilevel linear regression models of log transformed particle production measures were used to assess risk factors for high production.  Stability between measurements over time was assessed using Lin’s correlation coefficients.

Ninety-nine percent of expired particles were <1μm in diameter. Considerable variation in exhaled particle production was observed between individuals and within individuals over time. Distribution of particle production was right skewed.  Approximately 90% of individuals produce <150 particles per litre in normal breathing.  A few individuals had measurements of over 1000 particles per litre (maximum 1456). Particle production increased with age (p<0.001) and was associated with high tree pollen counts. Particle production levels did not remain stable over time [rho 0.14 (95%CI -0.10, 0.38, p=0.238)].

Sub-micron particles conducive to airborne rather than droplet transmission form the great majority of exhaled particles in tidal breathing. There is a high level of variability between subjects but measurements are not stable over time. Production increases with age and may be influenced by airway inflammation caused by environmental irritants. Further research is needed to determine whether the observed variations in exhaled particle production affect transmission of respiratory infection.
Introduction of structured physical examination skills to second year undergraduate medical students
Authors: Piryani Rano M , Shankar P Ravi , Thapa Trilok P , Karki Bal M , Kafle Rishi K , Khakurel Mahesh P , Bhandary Shital
Published: May 2013

Introduction: Effective learning of physical examination skills (PES) requires suitable teaching and learning techniques and assessment methods. The Tribhuvan University (Nepal) curriculum recommends involving the departments of Medicine and Surgery in PES training (PEST) for second year students as a part of early clinical exposure. The project was developed to make teaching/learning of PES structured, involving eight clinical sciences departments and using appropriate methods for teaching and assessment in KIST Medical College, Nepal.

Methods: Irby’s three stages of clinical teaching model (Preparation, Teaching, Reflection), was applied for teaching. Skill acquisition was based on Millers’ learning pyramid at “show how level” and Dreyfus’ competency model at “competent level”. Teaching/learning was conducted in small groups. A tutorial, demonstration and practice (TDS) model was developed for teaching/learning techniques based on a simple five-step method for teaching clinical skills. Assessment of effectiveness of training was done at “reaction level” as per Kirkpatrick’s model based on students’ feedback, “shows how level” as per Miller’s pyramid of learning by OSCE and “competent level” as per Dreyfus’ model using retro-pre questionnaire.

Results: The analysis of retro-pre questionnaire based on the Dreyfus model found the average skill score (max score 184), before the introduction of the project module as 15.9 (median = 13.5) and after as 116.5 (median = 116). A paired t-test showed the difference to be statistically significant (100.5±23 and 95% CI 95.45 – 105.59). The average overall feedback score for the students on PES training based on seven items on a five point Likert scale was found to be 4.30. The mean total objective structured clinical examination (OSCE) score was 3.77 (SD+/- 0.33) out of 5; 80% of students scored more than 70%.

Conclusion: Students learned most of the skills with the implementation of the structured PES module and did well in the OSCE. Students and faculty were satisfied with the training and assessment.
Use of synthetic polymer hydrogels to prepare scaffoldless 3D tissue constructs
Authors: Florez Gerson , Williams Eric , Saing Minn H , Khurana Jasvir S , Samuel Solomon
Published: May 2013

The use of 3-dimensional tissue cultures is gaining popularity in many fields including drug discovery, toxicity testing and tissue engineering. Currently most of the techniques used to prepare these 3D tissues are time consuming and cannot be reproduced easily. There is an urgent need to optimize the preparation of these 3D tissue cultures. This study evaluated the use of synthetic hydrogel polymers used to manufacture soft contact lenses to guide cells to form multicellular tissue-like structures. It was found that bovine chondrocytes and porcine dental pulp stem cells were able to form 3D tissue structures when placed inside a soft contact lens. Commercially available microarrays, 96 or 384 well plates manufactured using synthetic hydrogel polymers may help overcome many reproducibility issues and simplify the 3D tissue culture process.
ProfileGrids solve the large alignment visualization problem: influenza hemagglutinin example
Authors: Roca Alberto I , Abajian Aaron C , Vigerust David J
Published: May 2013

Large multiple sequence alignments are a challenge for current visualization programs. ProfileGrids are a solution that reduces alignments to a matrix, color-shaded according to the residue frequency at each column position. ProfileGrids are not limited by the number of sequences and so solves this visualization problem. We demonstrate the new metadata searching and grep filtering features of the JProfileGrid version 2.0 software on an alignment of 11,900 hemagglutinin protein sequences. JProfileGrid is free and available from http://www.ProfileGrid.org.
Memory enhancement produced by post-training exposure to sucrose-conditioned cues
Authors: Holahan Matthew R , White Norman M
Published: May 2013

A number of aversive and appetitive unconditioned stimuli (such as shock and food) are known to produce memory enhancement when they occur during the post-training period. Post-training exposure to conditioned aversive stimuli has also been shown to enhance memory consolidation processes. The present study shows for the first time that post-training exposure to conditioned stimuli previously paired with consumption of a sucrose solution also enhances memory consolidation. Male Long Evans rats were trained on a one-session conditioned cue preference (CCP) task on a radial arm maze. Immediately or 2 hours after training, rats consumed a sucrose solution or were exposed to cues previously paired with consumption of sucrose or cues previously paired with water. Twenty-four hours later, the rats were tested for a CCP. Immediate, but not delayed, post-training consumption of sucrose enhanced memory for the CCP. Immediate, but not delayed, post-training exposure to cues previously paired with sucrose, but not with water, also enhanced CCP memory. The possibility that rewarding and aversive conditioned stimuli affect memory by a common physiological process is discussed.
Neotendon infilling of a full thickness rotator cuff foot print tear following ultrasound guided liquid platelet rich plasma injection and percutaneous tenotomy: favourable outcome up to one year
Authors: Doss Arockia
Published: May 2013

This is a case report on excellent clinical outcome and neotendon infilling at one year follow up in a degenerative rotator cuff full thickness tear following percutaneous tenotomy and platelet rich plasma injection.
Concomitant caries and calculus formation from in situ dentin caries model
Authors: de Sousa Frederico B , Mangueira Pablo J , Tames David R , Vianna Sandra S , Santos-Magalhaes Neriede S
Published: May 2013

The aim of this study was to test the possibility of the concomitant formation of calculus deposits and caries fromin situdentin caries model for short time periods. Six volunteers wore palatal removal appliances with four polished dentin specimens protected from intra-oral mechanical forces for up to 14 days. Each volunteer applied a 50% sucrose solution (four times a day) on the specimens and performed a daily mouthwash with 0.05% NaF. Samples were removed after 2, 5, 9 and 14 daysin situ. Demineralization was analyzed by stereomicroscopy and SEM (secondary electrons and backscattered electrons modes) and calculus was analyzed by energy dispersive spectroscopy and fluorescence spectroscopy. Seventeen samples, at least one sample from each volunteer, presented dental calculus on both carious and non-carious ones, detected in all time intervals. Ca/P ratios of dental calculus ranged from 1.1 to 1.7. Some large calculus deposits on carious surfaces were confirmed by fluorescence. In conclusion, concomitant caries and calculus formation can be found in dentin caries formedin situ. This has important repercussions on the study of surface phenomena on the interface between hard dental tissues and dental plaque.
Construction and accessibility of a cross-species phenotype ontology along with gene annotations for biomedical research
Authors: Köhler Sebastian , Doelken Sandra C , Ruef Barbara J , Bauer Sebastian , Washington Nicole , Westerfield Monte , Gkoutos George , Schofield Paul , Smedley Damian , Lewis Suzanna E , Robinson Peter N , Mungall Christopher J
Published: May 2013

Phenotype analyses, e.g. investigating metabolic processes, tissue formation, or organism behavior, are an important element of most biological and medical research activities. Biomedical researchers are making increased use of ontological standards and methods to capture the results of such analyses, with one focus being the comparison and analysis of phenotype information between species.

We have generated a cross-species phenotype ontology for human, mouse and zebra fish that contains zebrafish phenotypes. We also provide up-to-date annotation data connecting human genes to phenotype classes from the generated ontology. We have included the data generation pipeline into our continuous integration system ensuring stable and up-to-date releases.

This article describes the data generation process and is intended to help interested researchers access both the phenotype annotation data and the associated cross-species phenotype ontology. The resource described here can be used in sophisticated semantic similarity and gene set enrichment analyses for phenotype data across species. The stable releases of this resource can be obtained from http://purl.obolibrary.org/obo/hp/uberpheno/.
A mutation in negative regulator of basal resistance WRKY17 of Arabidopsis increases susceptibility to Agrobacterium-mediated genetic transformation
Authors: Lacroix Benoît , Citovsky Vitaly
Published: May 2013

Agrobacterium is a phytopathogenic bacterium that induces crown gall disease in many plant species by transferring and integrating a segment of its own DNA (T-DNA) into its host genome. Whereas Agrobacterium usually does not trigger an extensive defense response in its host plants, it induces the expression of several defense-related genes and activates plant stress reactions. In the complex interplay between Agrobacterium and its host plant, Agrobacterium has evolved to take advantage of these plant defense pathways for its own purpose of advancement of the infection process. For example, Agrobacterium utilizes the host stress response transcriptional regulator VIP1 to facilitate nuclear import and proteasomal uncoating of its T-DNA during genetic transformation of the host cell. In Arabidopsis, the VIP1 gene expression is repressed by WRKY17, a negative regulator of basal resistance to Pseudomonas. Thus, we examined whether WRKY17 is also involved in plant susceptibility to genetic transformation by Agrobacterium. Using reverse genetics, we showed that a wrky17 mutant displays higher expression of the VIP1 gene in roots, but not in shoots. In a root infection assay, the wrky17 mutant plants were hyper-susceptible to Agrobacterium compared to wild type plants. WRKY17, therefore, may act as a positive regulator of Arabidopsis resistance to Agrobacterium. This notion is important for understanding the complex regulation of Agrobacterium-mediated genetic transformation; thus, although this paper reports a relatively small set of data that we do not plan to pursue further in our lab, we believe it might be useful for the broad community of plant pathologists and plant biotechnologists.
Longitudinal RNA sequencing of the deep transcriptome during neurogenesis of cortical glutamatergic neurons from murine ESCs
Authors: Hubbard Kyle S , Gut Ian M , Lyman Megan E , McNutt Patrick M
Published: May 2013

Using paired-end RNA sequencing, we have quantified the deep transcriptional changes that occur during differentiation of murine embryonic stem cells into a highly enriched population of glutamatergic cortical neurons. These data provide a detailed and nuanced account of longitudinal changes in the transcriptome during neurogenesis and neuronal maturation, starting from mouse embryonic stem cells and progressing through neuroepithelial stem cell induction, radial glial cell formation, neurogenesis, neuronal maturation and cortical patterning. Understanding the transcriptional mechanisms underlying the differentiation of stem cells into mature, glutamatergic neurons of cortical identity has myriad applications, including the elucidation of mechanisms of cortical patterning; identification of neurogenic processes; modeling of disease states; detailing of the host cell response to neurotoxic stimuli; and determination of potential therapeutic targets. In future work we anticipate correlating changes in longitudinal gene expression to other cell parameters, including neuronal function as well as characterizations of the proteome and metabolome. In this data article, we describe the methods used to produce the data and present the raw sequence read data in FASTQ files, sequencing run statistics and a summary flatfile of raw counts for 22,164 genes across 31 samples, representing 3-5 biological replicates at each timepoint. We propose that this data will be a valuable contribution to diverse research efforts in bioinformatics, stem cell research and developmental neuroscience studies.
Modulation of proinflammatory activity by the engineered cationic antimicrobial peptide WLBU-2
Authors: Paranjape Shruti M , Lauer Thomas W , Montelaro Ronald C , Mietzner Timothy A , Vij Neeraj
Published: May 2013

Background:Host-derived (LL-37) and synthetic (WLBU-2) cationic antimicrobial peptides (CAPs) are known for their membrane-active bactericidal properties. LL-37 is an important mediator for immunomodulation, while the mechanism of action of WLBU-2 remains unclear.

Objective:To determine if WLBU-2 induces an early proinflammatory response that facilitates bacterial clearance in cystic fibrosis (CF).

Methods:C57BL6 mice were given intranasal or intraperitoneal 1×106cfu/mLPseudomonas aeruginosa(PA) and observed for 2h, followed by instillation of LL-37 or WLBU-2 (2-4mg/kg) with subsequent tissue collection at 24h for determination of bacterial colony counts and quantitative RT-PCR measurement of cytokine transcripts. CF airway epithelial cells (IB3-1, ΔF508/W1282X) were cultured in appropriate media with supplements. WLBU-2 (25μM) was added to the media with RT-PCR measurement of TNF-α and IL-1β transcripts after 20, 30, and 60min. Flow cytometry was used to determine if WLBU-2 assists in cellular uptake of Alexa 488-labeled LPS.

Results:In murine lung exposed to intranasal or intraperitoneal WLBU-2, there was a reduction in the number of surviving PA colonies compared to controls. Murine lung exposed to intraperitoneal WLBU-2 showed fewer PA colonies compared to LL-37. After 24h WLBU-2 exposure, PA-induced IL-1β transcripts from lungs showed a twofold decrease (p<0.05), while TNF-α levels were unchanged. LL-37 did not significantly change transcript levels. In IB3-1 cells, WLBU-2 exposure resulted in increased TNF-α and IL-1β transcripts that decreased by 60min. WLBU-2 treatment of IB3-1 cells displayed increased LPS uptake, suggesting a potential role for CAPs in inducing protective proinflammatory responses. Taken together, the cytokine response, LPS uptake, and established antimicrobial activity of WLBU-2 demonstrate its ability to modulate proinflammatory signaling as a protective mechanism to clear infection.

Conclusions:The immunomodulatory properties of WLBU-2 reveal a potential mechanism of its broad-spectrum antibacterial activity and warrant further preclinical evaluation to study bacterial clearance and rescue of chronic inflammation.
Selection and validation of reference genes for quantitative gene expression studies in Erythroxylum coca
Authors: Docimo Teresa , Schmidt Gregor W , Luck Katrin , Delaney Sven K , D'Auria John C
Published: May 2013

Real-time quantitative PCR is a powerful technique for the investigation of comparative gene expression, but its accuracy and reliability depend on the reference genes used as internal standards. Only genes that show a high level of expression stability are suitable for use as reference genes, and these must be identified on a case-by-case basis.

Erythroxylum coca produces and accumulates high amounts of the pharmacologically active tropane alkaloid cocaine (especially in the leaves), and is an emerging model for the investigation of tropane alkaloid biosynthesis. The identification of stable internal reference genes for this species is important for its development as a model species, and would enable comparative analysis of candidate biosynthetic genes in the different tissues of the coca plant. In this study, we evaluated the expression stability of nine candidate reference genes in E. coca (Ec6409, Ec10131, Ec11142, Actin, APT2, EF1α, TPB1, Pex4, Pp2aa3). The expression of these genes was measured in seven tissues (flowers, stems, roots and four developmental leaf stages) and the stability of expression was assessed using three algorithms (geNorm, NormFinder and BestKeeper). From our results we conclude that Ec10131 and TPB1 are the most appropriate internal reference genes in leaves (where the majority of cocaine is produced), while Ec10131 and Ec6409 are the most suitable internal reference genes across all of the tissues tested.
Detection of Giardia lamblia stool samples: a comparison of two enzyme-linked immunosorbent assays
Authors: Jelinek Tomas , Neifer Stefan
Published: May 2013

Two commercially produced enzyme-immunosorbent assays (EIAs) to detect antigens ofGiardia lambliain stool specimens, Ridascreen Giardia and Serazym Giardia, were evaluated. A total of 88 stool specimens were collected from patients who presented for various medical complaints in our outpatient clinic. Every specimen was examined by a conventional microscopic examination (CME), PCR and tested by both EIA kits. When microscopy was used as the reference standard, the Ridascreen Giardia showed a sensitivity of 72.9% and a specificity of 100%. Serazym Giardia had a sensitivity of 93.8% and a specificity of 100%. Antigen detection by EIA has been established as a valuable tool to make parasite stool diagnostics more effective.