Veterinary clinical nutrition: success stories: an overview.
In this overview of success stories in veterinary clinical nutrition topics in cats and dogs reviewed include the dietary management of chronic kidney disease, dissolution of urinary tract uroliths by dietary modification, the recognition that taurine and L-carnitine deficiencies can cause dilated cardiomyopathy; that clinical signs associated with feline hyperthyroidism (caused by a benign adenoma) can be controlled by a low-iodine diet alone; that dietary management of canine osteoarthritis can also reduce non-steroidal anti-inflammatory drug doses; and that disease-free intervals and survival times can be statistically longer in dogs with Stage III lymphoma managed with diet. As we discover more about nutrigenetics and nutrigenomics, and as we expand our basic understanding of idiopathic diseases we are bound to identify more nutritionally related causes, and be able to develop novel dietary strategies to manage disease processes, including the formulation of diets designed to alter gene expression to obtain beneficial clinical outcomes.


Insulin levels in the amniotic fluid and in maternal and fetal blood.
The effects of excessive maternal weight gain during pregnancy (five cases) and of glucose infusion in the mother (five cases) on insulin levels are compared with the insulin levels in a control group (19 normal pregnancies) by radioimmunologic determination of insulin levels in the amniotic fluid and in maternal and fetal blood. The mean values for insulin in the control group were as follows: mother, 23.9 +/- 2.23 muU per ml; fetus, 9.86 +/- 2.11 muU per ml; and amniotic fluid, 5.08 +/- 2.27 muU per ml. In patients with excessive weight gain during pregnancy, maternal insulin mean values were 38.45 +/- 4.16 muU per ml; fetal, 19.99 +/- 9.8 muU per ml; and amniotic fluid, 11.25 +/- 2.58 muU per ml. After an infusion of 25 mg of glucose in the mother, the mean maternal insulin values were 53.6 +/- 13.74 muU per ml; fetal, 24.7 +/- 6.67 muU per ml; and amniotic fluid, 14.3 +/- 5.52 muU per ml. Insulin concentrations in maternal blood (p less than 0.001), fetal blood (p less than 0.001) and amniotic fluid (p less than 0.001) were higher in pregnancies with excessive weight gain as compared to those in the control group, whereas the glucose infusion in the mother increased the concentration of insulin in the three components studied.


Exfoliative cutaneous lupus erythematosus in German shorthaired pointer dogs: disease development, progression and evaluation of three immunomodulatory drugs (ciclosporin, hydroxychloroquine, and adalimumab) in a controlled environment.
Six German shorthaired pointer dogs (two females, four males) with exfoliative cutaneous lupus erythematosus (ECLE) were studied in a controlled setting until disease progression necessitated euthanasia. During investigations into the heredity of disease, five dogs received immunomodulatory drugs to alleviate clinical signs (lameness, erythema, scaling, erosions/ulcers). One dog served as a control and received only baths and oral fatty acids. Four dogs received ciclosporin (5-10 mg/kg once daily) for 4.5 months to 2 years. Ciclosporin decreased erythema and arthralgia, but did not halt worsening of lesions. Three dogs received hydroxychloroquine (5-10 mg/kg once daily) for 8 weeks, 7 months, and 9 months, respectively, with no side effects. Hydroxychloroquine appeared to slow clinical progression in two dogs on extended treatment and normalized globulin levels in all three dogs while receiving the drug. Four dogs, including the control dog, were euthanized between 1 and 4.5 years of age. Two remaining male dogs received a tumour necrosis factor (TNF)-α antagonist, adalimumab, at 0.5 mg/kg every 2 weeks for 8 weeks then weekly for 8 weeks. Serum TNF-α levels were not significantly altered nor were quantifiable changes seen in skin lesions or lameness. Subsequently, the dogs were maintained on hydroxychloroquine for another year. This is the first study to evaluate the use of a TNF-α inhibitor for canine lupus and the first to address the safety of long-term administration of hydroxychloroquine, albeit in a small number of dogs. The study documents the progression of ECLE and generally poor response to therapy.


Acyclovir crystalluria.
Acyclovir crystals in the urine of a 28-year-old woman are described. The patient received intravenous acyclovir for herpes encephalitis. The crystalluria was accompanied by impairment of the renal tubules as evidenced by increased urinary beta-2-microglobulin excretion. Consecutive series of 60 patients on oral acyclovir and 20 patients on intravenous acyclovir were studied in order to define the frequency of acyclovir crystalluria. None of the patients studied had crystalluria, and none elevated serum creatinine levels. It is suggested that acyclovir crystalluria might be an early sign of acyclovir crystal nephropathy.


Dissociation of the ground state vinoxy radical and its photolytic precursor chloroacetaldehyde: electronic nonadiabaticity and the suppression of the H+ketene channel.
This work is a study of the competition between the two unimolecular reaction channels available to the vinoxy radical (CH(2)CHO), C-H fission to form H+ketene, and isomerization to the acetyl radical (CH(3)CO) followed by C-C fission to form CH(3) + CO. Chloroacetaldehyde (CH(2)ClCHO) was used as a photolytic precursor to the vinoxy radical in its ground state; photodissociation of chloroacetaldehyde at 193 nm produces vinoxy radicals with internal energies spanning the G3//B3LYP calculated barriers to the two available unimolecular reaction channels. The onset of the CH(3) + CO channel, via isomerization to the acetyl radical, was found to occur at an internal energy of 41 +/- 2 kcal/mol, agreeing well with our calculated isomerization barrier of 40.8 kcal/mol. Branching to the H+ketene channel was too small to be detected; we conclude that the branching to the H+ketene channel must be at least a factor of 200 lower than what is predicted by a RRKM analysis based on our electronic structure calculations. This dramatic result may be explained in part by the presence of a conical intersection at planar geometries along the reaction coordinate leading to H+ketene, which results in electronically nonadiabatic recrossing of the transition state.


Advances in Clinical Cardiology 2019: A Summary of Key Clinical Trials.
A large number of important clinical trials in cardiology were published or presented at major international conferences during 2019. This paper aims to offer a concise overview of these significant advances and to put them into clinical context. Trials presented at the major international cardiology meetings during 2019 were reviewed including The American College of Cardiology (ACC), Euro PCR, The European Society of Cardiology (ESC), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA). In addition to this a literature search identified several other publications eligible for inclusion based on their relevance to clinical cardiology, their potential impact on clinical practice and on future guidelines. A total of 70 trials met the inclusion criteria. New interventional and structural data include trials examining use of drug-coated balloons in patients with acute myocardial infarction (MI), interventions following shockable cardiac arrest, mechanical circulatory support in cardiogenic shock complicating MI, intervention in stable coronary artery disease, surgical or percutaneous revascularisation strategies in left main coronary artery disease, revascularisation strategy in ST elevation MI, transcatheter aortic valve replacement in low-risk patients, and percutaneous mitral or tricuspid valve interventions. Preventative cardiology data included the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors (dapagliflozin), proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors (evolocumab), bempedoic acid, and novel approaches to the management of hypertension. Antiplatelet data included trials evaluating both the optimal length of course and combination of antiplatelet agents and regimes including combination antithrombotic therapies for patients with atrial fibrillation. Heart failure data included trials of sacubitril-valsartan in heart failure with preserved ejection fraction and the use of SGLT2 inhibitors in patients with heart failure but without diabetes. Electrophysiology data included trials examining alcohol in atrial fibrillation and the use of wearable fitness devices for identifying atrial fibrillation. This article presents key clinical trials completed during 2019 and should be valuable to clinicians and researchers working in cardiology.


Towards numerical prediction of cavitation erosion.
This paper is intended to provide a potential basis for a numerical prediction of cavitation erosion damage. The proposed method can be divided into two steps. The first step consists in determining the loading conditions due to cavitation bubble collapses. It is shown that individual pits observed on highly polished metallic samples exposed to cavitation for a relatively small time can be considered as the signature of bubble collapse. By combining pitting tests with an inverse finite-element modelling (FEM) of the material response to a representative impact load, loading conditions can be derived for each individual bubble collapse in terms of stress amplitude (in gigapascals) and radial extent (in micrometres). This step requires characterizing as accurately as possible the properties of the material exposed to cavitation. This characterization should include the effect of strain rate, which is known to be high in cavitation erosion (typically of the order of several thousands s(-1)). Nanoindentation techniques as well as compressive tests at high strain rate using, for example, a split Hopkinson pressure bar test system may be used. The second step consists in developing an FEM approach to simulate the material response to the repetitive impact loads determined in step 1. This includes a detailed analysis of the hardening process (isotropic versus kinematic) in order to properly account for fatigue as well as the development of a suitable model of material damage and failure to account for mass loss. Although the whole method is not yet fully operational, promising results are presented that show that such a numerical method might be, in the long term, an alternative to correlative techniques used so far for cavitation erosion prediction.


Stop saying epileptic.
The purpose of this study was to evaluate the impact upon attitude and perceived stigma of using different terms for referring to persons with epilepsy among teenagers. High school students received one of two versions of a brief questionnaire and of the Stigma Scale of Epilepsy (SSE). The versions differed only in the term used: "people with epilepsy" (PWE) in the group-1 (N = 109) and "epileptics" in group-2 (N = 105). Group-1 responded that 62% of PWE and group-2, that 93% of epileptics have more difficulty finding employment. Group-1 responded that 37% of PWE and group-2, that 70% of epileptics have more difficulties at school. Group-1 responded that 41% of PWE and group-2, that 87% of epileptics are rejected by the society. None of individuals in group-1 indicated that they were prejudiced toward PWE, whereas 3% of group-2 indicated that they were prejudiced toward epileptics. The SSE score (range from 0 to 100, higher the score, higher the degree of perceived stigma) was 49 [confidence interval (CI) = 46.9-52.0] for group-2 and 45 (CI = 42.4-48.2) for group-1 (p = 0.03). In conclusion, the words we use can influence our perceptions and have consequences in terms of social stigma associated with epilepsy. We should refrain from using the term "epileptic" to refer to a person with epilepsy, and consider the importance of our choice of words as part of the effort to bring epilepsy out of the shadows.


Nuclear localization of p185neu tyrosine kinase and its association with transcriptional transactivation.
The rat neu protooncogene encodes a 185 kD transmembrane protein (p185neu), which is a member of the epidermal growth factor receptor (EGFr) family. In searching for the signaling transducer of p185neu by using a two-hybrid selection system, we found, surprisingly, that the cytoplasmic domain of p185neu, when fused to the DNA-binding domain of GAL4 (amino acids 1-147), functioned as a transcriptional activator. We subsequently observed nuclear localization of p185neu. Interestingly, nuclear p185neu has a much higher extent of tyrosine phosphorylation than its nonnuclear counterpart. Our results suggest that a transmembrane receptor tyrosine kinase may enter the nucleus and be involved in transcriptional activation. This novel finding unveils a clue in the understanding of the mechanism of receptor tyrosine kinase-mediated signal transduction.


[A discussion on Zhang Cigong's materia medica].
Zhang Cigong's Materia Medica, being compiled by the author after learning and studying exogenous cold disease and herbology for several decades, printed in 1949 with a capacity of 150,000 Chinese characters, is a book of practical and clinical significance, featuring adoration on the theory of cold pathogenic disease, preferential practical use, integration of Chinese and western medicine, pursuit of origin and evolution, discussion on the compatibility of drug application. It emphasizes the application of drugs utilized in Shang han lun (Treatise on Cold Pathogenic Disease) and advocating the ideas of absorbing extensively ancient and modern theories from various schools, especially consulting the pharmacology of Chinese and the west, embodying the author's advocacy of "developing the classical ideas and integrating new knowledge", "overcoming one's weak points by learning from others' strong points and making effort in inheriting and developing the science of traditional Chinese medicine". However, this book also bears some incorrect points which are not overall and comprehensive enough in the understanding of drugs, and thus, should be properly accepted and rejected.


The chemical composition of mineral trioxide aggregate.
Mineral trioxide aggregate (MTA) is composed of Portland cement, with 4:1 addition of bismuth oxide added so that the material can be detected on a radiograph. The cement is made up of calcium, silicon and aluminium. The main constituent phases are tricalcium and dicalcium silicate and tricalcium aluminate. There are two commercial forms of MTA, namely the grey and the white. The difference between the grey and the white materials is the presence of iron in the grey material, which makes up the phase tetracalcium alumino-ferrite. This phase is absent in white MTA. Hydration of MTA occurs in two stages. The initial reaction between tricalcium aluminate and water in the presence of calcium sulphate results in the production of ettringite. Tricalcium and dicalcium silicate react with water to produce calcium silicate hydrate and calcium hydroxide, which is leached out of the cement with time.


High-Throughput Analysis of Tissue-Embedded Single Cells by Mass Spectrometry with Bimodal Imaging and Object Recognition.
In biological tissues, cell-to-cell variations stem from the stochastic and modulated expression of genes and the varying abundances of corresponding proteins. These variations are then propagated to downstream metabolite products and result in cellular heterogeneity. Mass spectrometry imaging (MSI) is a promising tool to simultaneously provide spatial distributions for hundreds of biomolecules without the need for labels or stains. Technological advances in MSI instrumentation for the direct analysis of tissue-embedded single cells are dominated by improvements in sensitivity, sample pretreatment, and increased spatial resolution but are limited by low throughput. Herein, we introduce a bimodal microscopy imaging system combined with fiber-based laser ablation electrospray ionization (f-LAESI) MSI with improved throughput ambient analysis of tissue-embedded single cells (n > 1000) to provide insight into cellular heterogeneity. Based on automated image analysis, accurate single-cell sampling is achieved by f-LAESI leading to the discovery of cellular phenotypes characterized by differing metabolite levels.


Tracking difficulties after femtosecond laser flap creation with the LADARVision excimer laser system.
To describe a series of myopic patients in whom a LASIK flap was created with the IntraLase femtosecond laser. The LADARVision (Alcon Laboratories Inc) tracking system failed and resulted in postponement of surgery. Five myopic Asian patients with darkly pigmented irides underwent bilateral superior hinge flap creation with three different femtosecond laser (IntraLase Corp) pulse frequencies: 15, 30, and 60 kHz. Mean patient age, preoperative best spectacle-corrected visual acuity (BSCVA), and spherical equivalent refraction were 33 years, 20/20, and -6.25 diopters (D), respectively. Despite uncomplicated flap-lift and adequate pharmacologic dilated pupil diameter >7 mm, difficulty was experienced with LADARVision eye tracking in 9 of 10 eyes. Intraoperative manipulations (fluid application, levitation of the laser bed, and tracking through a repositioned flap) were attempted to facilitate eye tracking at the time of femtosecond laser flap creation, but without success. The flap was repositioned, and patients were asked to return 1 to 5 days later, at which time the flap was relifted, eye tracking was successfully achieved, and the surgery was completed. Mean postoperative uncorrected visual acuity was 20/18 and no eyes lost any lines of BSCVA at 1 year. Irregularities of the IntraLASIK stromal bed surface induce forward light scatter, and dark ocular pigmentation further reduces retinal reflectance, leading to tracking failure with the Alcon LADARVision platform. Delaying the surgery by 1 to 5 days may aid in reducing the light scatter, so that eye tracking can be achieved.


Effects of acoustic degradation on syntactic processing: implications for the nature of the resource system used in language processing.
This study investigated the effect of noise masking on on-line syntactic processing. Ninety college students were tested on measures of working memory and on-line sentence comprehension. Subjects were divided equally into three listening conditions: no noise masking, -3 dB signal-to-noise ratio (S:N), -4.5 dB S:N. The auditory moving windows (AMW) paradigm was used to measure on-line sentence processing. In the AMW paradigm, subjects pressed a button for the successive presentation of each phrase in two types of sentences (syntactically simple and complex), and listening times were recorded for each phrase. Previous studies have shown that the verb in the more complex sentence type is the most capacity demanding portion of the sentence. Listening times were longer overall with increased noise masking, and listening times were longer overall at the verb of the harder sentence type. However, the increase at the verb was not larger with increased noise masking. All three groups showed similar effects of syntactic structure in the on-line data. The on-line syntactic effects were not due to problems in word recognition. Correlational analyses did not indicate a relationship between the increase in processing time at the capacity demanding region of the harder sentence types and any of the measures of working memory capacity in any of the three listening conditions. Results indicate that on-line sentence processing is not affected by noise masking if lexical access (e.g., word recognition) remains intact.


Combination of TWEAK and TGF-β1 induces the production of TSLP, RANTES, and TARC in BEAS-2B human bronchial epithelial cells during epithelial-mesenchymal transition.
In patients with asthma, chronic inflammatory processes and the subsequent remodeling of the airways contribute to the symptoms and the pathophysiological changes. Epithelial-mesenchymal transition (EMT) is thought to play an important role in tissue remodeling. Previous reports show that tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a cytokine of the TNF superfamily, exerts pro-inflammatory effects, and enhances transforming growth factor (TGF)-β-induced EMT in bronchial epithelial cells. In this study, we investigated the TWEAK-induced cytokine and chemokine production in the human bronchial epithelial cell line BEAS-2B during EMT. Quantitative real-time RT-PCR, enzyme-linked immunosorbent assays, western blotting, and immunohistochemistry were used to define the production of cytokines and chemokines. We found that TWEAK increases mRNA and protein levels of thymic stromal lymphopoietin (TSLP), monocyte chemoattractant protein -1 (MCP-1), regulated upon activation normal T cell express sequence (RANTES), and IL-8 in BEAS-2B bronchial epithelial cells. Moreover, co-treatment with TWEAK and TGF-β1 induces not only features of EMT but also enhances the production of TSLP and RANTES. Thymus- and activation-regulated chemokines (TARC) production is induced by the co-treatment of TWEAK and TGF-β1 but not by TWEAK or TGF-β1 stimulation alone. Furthermore, the increased mRNA expression of TSLP and RANTES after co-treatment with TWEAK and TGF-β1 is prevented by inhibitors of Smad-independent signaling pathways. In the present study, we have revealed a novel mechanism for the production of asthma-related cytokines and chemokines in EMT driven by the co-stimulation with TWEAK and TGF-β1. We conclude that cellular EMT processes caused by TWEAK and TGF-β1 may contribute to chronic airway inflammation and remodeling.


Oriented to Multi-Branched Structure Unsupported 3D Printing Method Research.
For the traditional three-axis (3D) configuration of the additive manufacturing (AM) platform, when printing the target model with a multi-branched structure, it is imperative to construct adequate support structures. To eliminate the use of support during the printing process, a non-directional unsupported 3D printing method for five-axis AM is proposed in this paper. By carrying out the K-means clustering algorithm, the coarse partition of the model is obtained, and then the fine decomposition represented by a sequence of separating planes is determined by a local dynamic search adjustment algorithm according to manufacturing constraints. The multi-branched structure of the model is divided into simple subparts so that the general model can be built in different directions and be printed with its own parts as the support. Two case studies were carried out for verification. The experimental results showed that the branch-model can be printed without support using the non-directional unsupported 3D printing method, and the non-directional unsupported 3D printing can save 18.72-20.60% of materials and 20.60-23.33% of time compared to conventional 3D printing.


Prospective exploration of synthetically feasible, medicinally relevant chemical space.
We describe a novel approach to direct the exploration of chemical space in an effort to balance synthetic accessibility and medicinal relevancy prior to experimental work. Reaction transforms containing empirical reactivity and compatibility information are dynamically assembled into reaction sequences (vProtocols) utilizing commercially available starting material feedstock. These vProtocols are evolved and optimized by a genetic algorithm, which leverages fitness functions based on predicted properties of generated molecular products. We present the underlying concepts, methodology and initial results of this prospective approach.


p38 MAPK and NF-kappaB pathways are involved in naphtho[1,2-b] furan-4,5-dione induced anti-proliferation and apoptosis of human hepatoma cells.
Naphtho[1,2-b] furan-4,5-dione (NFD) was investigated for its anti-proliferation effect on human hepatocellular carcinoma (HCC), Hep3B, HepG(2), and Huh-7 cells. The effect of NFD on inhibiting proliferation and apoptosis was correlated with up-regulation of pro-apoptotic protein and down-regulation of pro-survival proteins. Remarkably, we found that NFD inhibited the nuclear translocation of NF-kappaB, likely accounting for the down-regulation of pro-survival Bcl-2 family. Furthermore, suppression of p38 MAPK activity by a specific inhibitor significantly rescued the cell proliferation inhibited by NFD. These findings suggest that signaling imbalance between p38 MAPK and NF-kappaB by NFD results in the proliferative inhibition and apoptosis of HCC tumor cells.


Los Alamos sequence analysis package for nucleic acids and proteins.
An interactive system for computer analysis of nucleic acid and protein sequences has been developed for the Los Alamos DNA Sequence Database. It provides a convenient way to search or verify various sequence features, e.g., restriction enzyme sites, protein coding frames, and properties of coded proteins. Further, the comprehensive analysis package on a large-scale database can be used for comparative studies on sequence and structural homologies in order to find unnoted information stored in nucleic acid sequences.


Light-driven catalysis with engineered enzymes and biomimetic systems.
Efforts to drive catalytic reactions with light, inspired by natural processes like photosynthesis, have a long history and have seen significant recent growth. Successfully engineering systems using biomolecular and bioinspired catalysts to carry out light-driven chemical reactions capitalizes on advantages offered from the fields of biocatalysis and photocatalysis. In particular, driving reactions under mild conditions and in water, in which enzymes are operative, using sunlight as a renewable energy source yield environmentally friendly systems. Furthermore, using enzymes and bioinspired systems can take advantage of the high efficiency and specificity of biocatalysts. There are many challenges to overcome to fully capitalize on the potential of light-driven biocatalysis. In this mini-review, we discuss examples of enzymes and engineered biomolecular catalysts that are activated via electron transfer from a photosensitizer in a photocatalytic system. We place an emphasis on selected forefront chemical reactions of high interest, including CH oxidation, proton reduction, water oxidation, CO2 reduction, and N2 reduction.


Solid pseudopapillary neoplasms of the pancreas: clinicopathologic features and surgical treatment of 19 cases.
Solid pseudopapillary neoplasms (SPNs) of the pancreas are very rare neoplasms. The present study is to summarize our experience of the diagnosis, surgical treatment and prognosis of SPNs. The clinical data of 19 cases that underwent surgery for pathologically confirmed SPNs, admitted in our hospital from Mar. 2007 to Mar. 2013, were analyzed retrospectively. The clinicopathologic feature, surgical treatment and prognosis were described in detail. The 19 patients were 17 females and 2 males, with a median age of 29 years. All patients had curative resections, including eight distal pancreatectomies with splenectomy, four spleen-preserving distal pancreatectomies, two pancreaticoduodenectomies, two pylorus-preserving pancreaticoduodenectomies, two duodenum-preserving pancreatic head resections and one central pancreatectomy. The tumors were 6.3 cm in diameter on average, and were mostly located in the body or tail of the pancreas (63.2%). Pathologically, the tumors contained a mixture of solid, cystic, and pseudopapillary patterns in various proportions. None of the patients had lymph nodes metastases and local invasion. All patients were alive and disease-free at a median follow-up of 38.4 months. SPNs are rare neoplasms, typically affecting young women without notable symptoms, with a low malignant potential but excellent prognosis. Radical surgical resection with clear margins is the treatment of choice.


A Sickle Cell Disease Patient with Severe Tricuspid Regurgitation and Early Developed Pulmonary Hypertension.
Pulmonary hypertension (PH) worsens the mortality of the patients with sickle cell disease (SCD). The exact mechanism of PH development/progression in SCD, including the role of tricuspid regurgitation (TR), remains unclear. We herein report an unusual SCD case, complicated by chronic thromboembolic disorder, who developed severe TR and an accelerated progression of PH. Tricuspid valve surgery significantly ameliorated the patient's symptoms and reduced hospital readmission. The early detection and management of the reversible disorder accelerating the PH development in SCD patients may alter the clinical course, improve the quality of life, and potentially affect the long-term outcome.


Predictive models for pressure ulcers from intensive care unit electronic health records using Bayesian networks.
We develop predictive models enabling clinicians to better understand and explore patient clinical data along with risk factors for pressure ulcers in intensive care unit patients from electronic health record data. Identifying accurate risk factors of pressure ulcers is essential to determining appropriate prevention strategies; in this work we examine medication, diagnosis, and traditional Braden pressure ulcer assessment scale measurements as patient features. In order to predict pressure ulcer incidence and better understand the structure of related risk factors, we construct Bayesian networks from patient features. Bayesian network nodes (features) and edges (conditional dependencies) are simplified with statistical network techniques. Upon reviewing a network visualization of our model, our clinician collaborators were able to identify strong relationships between risk factors widely recognized as associated with pressure ulcers. We present a three-stage framework for predictive analysis of patient clinical data: 1) Developing electronic health record feature extraction functions with assistance of clinicians, 2) simplifying features, and 3) building Bayesian network predictive models. We evaluate all combinations of Bayesian network models from different search algorithms, scoring functions, prior structure initializations, and sets of features. From the EHRs of 7,717 ICU patients, we construct Bayesian network predictive models from 86 medication, diagnosis, and Braden scale features. Our model not only identifies known and suspected high PU risk factors, but also substantially increases sensitivity of the prediction - nearly three times higher comparing to logistical regression models - without sacrificing the overall accuracy. We visualize a representative model with which our clinician collaborators identify strong relationships between risk factors widely recognized as associated with pressure ulcers. Given the strong adverse effect of pressure ulcers on patients and the high cost for treating pressure ulcers, our Bayesian network based model provides a novel framework for significantly improving the sensitivity of the prediction model. Thus, when the model is deployed in a clinical setting, the caregivers can suitably respond to conditions likely associated with pressure ulcer incidence.


Impact of dehydration and fasting on intraocular pressure and corneal biomechanics measured by the Ocular Response Analyzer.
To investigate the effects of dehydration and fasting on the intraocular pressure (IOP) and corneal biomechanics during Ramadan in healthy subjects. A total of 36 healthy fasting male volunteers with a mean age of 32.7 ± 5.1 years (range 28-38 years) were enrolled in the study. A Reichert Ocular Response Analyzer (ORA) was used to measure the corneal resistance factor (CRF), corneal hysteresis (CH), Goldman-correlated IOP (IOPg), and corneal-compensated IOP (IOPcc), additionally IOP with Goldmann applanation tonometer (IOP-GAT) was taken. All measurements were recorded at 8:00 am and 4:00 p.m. during Ramadan and during a 1-month follow-up after Ramadan was over. Statistical analysis demonstrated no difference in the ORA measurements including CH, CRF, IOPcc, and IOPg; CCT and CV values between fasting and non-fasting periods or within a single day (diurnal changes). Nine volunteers (25% of total subjects) were excluded because eyedrops were believed to disrupt the Ramadan fast consequently IOP-GAT could not be measured from these subjects. No statistically significant difference was noted between IOP-GAT and IOPg measurements of twenty-seven subjects at the different periods and time points. Our results reveal that fasting during Ramadan does not profoundly affect corneal biomechanics and IOP values in healthy volunteers without ocular diseases such as glaucoma. When planning corneal refractive surgery and determining IOP, the ORA measurements can be done safely during a Ramadan fast. Moreover, ORA may be a better alternative for patients that refuse IOP measurement via GAT for examining the accuracy of IOP during fasting. Further studies are needed to better understand the role of these parameters on corneal disease and glaucoma during fasting.


MicroRNA-181a suppresses parkin-mediated mitophagy and sensitizes neuroblastoma cells to mitochondrial uncoupler-induced apoptosis.
Damage to mitochondria often results in the activation of both mitophagy and mitochondrial apoptosis. The elimination of dysfunctional mitochondria is necessary for mitochondrial quality maintenance and efficient energy supply. Here we report that miR-181a is a novel inhibitor of mitophagy. miR-181a is downregulated by mitochondrial uncouplers in human neuroblastoma SH-SY5Y cells. Overexpression of miR-181a inhibits mitochondrial uncoupling agents-induced mitophagy by inhibiting the degradation of mitochondrial proteins without affecting global autophagy. Knock down of endogenous miR-181a accelerates the autophagic degradation of damaged mitochondria. miR-181a directly targets Parkin E3 ubiquitin ligase and partially blocks the colocalization of mitochondria and autophagosomes/lysosomes. Re-expression of exogenous Parkin restores the inhibitory effect of miR-181a on mitophagy. Furthermore, miR-181a increases the sensitivity of neuroblastoma cells to mitochondrial uncoupler-induced apoptosis, whereas miR-181a antagomir prevents cell death. Because mitophagy defects are associated with a variety of human disorders, these findings indicate an important link between microRNA and Parkin-mediated mitophagy and highlights a potential therapeutic strategy for human diseases.


Temporal Trends in Utilization of Transthoracic Echocardiography for Common Outpatient Pediatric Cardiology Diagnoses over the Past 15 Years.
No data exist regarding the temporal trends in utilization of transthoracic echocardiography (TTE) in an outpatient pediatric cardiology setting. This study evaluates the trends in utilization of TTE for common diagnoses known to have low diagnostic yield and the factors influencing these trends. Patients evaluated at our pediatric cardiology clinics from January 2000 to December 2014 and discharged with final diagnoses of innocent murmur, noncardiac chest pain, benign syncope, and palpitations were included. Variables collected retrospectively included patient age, sex, insurance type, distance from clinic, and ordering physician's years of experience since fellowship. Of the 74,881 patients seen by 35 physicians, 36,053 (48.1%) had a TTE. The TTE rates increased from the beginning of 2000 to the end of 2004 (5.2% per year; P < .001) and then steadily declined until the end of 2014 (1.6% per year; P < .001). Utilization for noncardiac chest pain remained the highest, and use in infants increased significantly during the study period (P < .001). After adjusting for all other factors, the following variables were associated with higher TTE utilization: younger age, males, Medicaid insurance, increased distance from clinic, and being seen by less experienced physicians. Temporal trends persisted after adjusting for all these factors. After an initial surge in TTE utilization from 2000 to 2004, there was a steady decline. This study identifies some important factors influencing these trends. This information could help design quality interventions, but additional factors need to be explored since the trends persist despite adjusting for these factors.


Expression of "myelomonocytic" antigens in mesotheliomas and adenocarcinomas involving the serosal surfaces.
Because of the demonstrated efficacy of Leu-M1 as a discriminant between malignant epithelioid mesothelioma (MEM) and adenocarcinomas involving the serosal surfaces (ACSs), the authors assessed the reactivities of related "myelomonocytic" antigens in this context. Paraffin sections from 41 MEMs and 43 ACSs (pulmonary, "serous surface papillary," and metastatic mammary adenocarcinomas) were evaluated for their expression of Leu-M1, LN1, LN2, and the Mac 387 antigen. Diagnoses were based in each case on the results of conventional histologic and electron microscopic examinations. Leu-M1 was detected only in minute foci of three peritoneal MEMs and was absent entirely in pleural mesotheliomas. Conversely, 38 of 43 ACSs expressed this marker. Three cases of peritoneal MEM and one pleural mesothelioma were multifocally LN2 positive, as were 39 of 43 ACSs. LN1 was the most frequently expressed antigen in MEM, being observed in 18 such tumors (10 pleural; 8 peritoneal); it was also detected in 37 of 43 ACSs. Mac 387 failed to label any of the neoplasms assessed in this series. These results demonstrate similar patterns of "myelomonocytic" antigen expression by diverse ACS and a general absence of Leu-M1 and LN2 in MEM. LN1 and the Mac 387 antigen appear to have no additional value when compared with Leu-M1 and LN2 in the immunohistochemical evaluation of serosal neoplasms.


Cavernoma of the conus medullaris mimicking transverse myelitis.
We present an interesting case of conus medullaris cavernoma that was initially treated as transverse myelitis. Haemorrhagic lumbar puncture led us to perform magnetic resonance (MR) imaging, which showed the presence of a cavernous angioma at the D12-L1 level. The total excision of the lesion was followed by dramatic improvement. We suggest that MR imaging be performed early in all suspected cases of transverse myelitis so that emergency surgical intervention can be offered before the development of permanent neurological deficits.


Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.
Our previous studies demonstrated that remote electro-stimulation (RES) increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R) injury in rat hearts. However, the role of various opioid receptors (OR) subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart. Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR) subtype receptors (KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively. The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.


The Impact of Criminal Record Stigma on Quality of Life: A Test of Theoretical Pathways.
Across multiple stigmatized groups, research suggests that stigma may negatively impact individual wellbeing. This impact often occurs through a sequential pathway that includes perceiving societal stigma, a diminished and stereotyped self-concept (i.e., internalized stigma), experiences of discrimination and rejection, and attempts to cope with stigma (e.g., secrecy or withdrawal). While prior research supports individual links within this pathway, no study has evaluated a model representing the relationships between all of these factors in relation to criminal record stigma. This study utilized cross-sectional data from an online survey of 198 adults to test the pathways through which criminal record-related stigma impacts individual quality of life. The results indicated that perceived stigma was a significant predictor of discrimination and rejection experiences, secrecy coping strategies, and decreased quality of life. There was also a significant indirect association between perceived stigma and quality of life through secrecy coping. Consistent with recent criminal record stigma research, internalized stigma was low among respondents. These findings point to the importance of reducing criminal record stigma and discrimination, so that individuals with criminal records have more opportunities to enhance their quality of life without having to withdraw from society or keep their record a secret.


Evaluation of lithium treatment in alcoholism.
In psychiatric practice, lithium prevents manic depressives recidivism. Lithium could also be useful in non-manic-depressive conditions with a reduction of aggression and impulsivity. From the observation that alcoholics often present mood swings and impulsivity, several authors studied the effects of maintenance doses of lithium on alcohol intake and the depressive symptoms of alcoholics. This article reviews all the published controlled and uncontrolled studies on the effects of lithium in chronic alcoholics. Wren, Kline and colleagues firs demonstrated that lithium treatment could significantly decrease the number of disabling alcoholic episodes and that its effect was independent of an effect on the depressive symptoms. These initial optimistic conclusions were not confirmed by later controlled studies involving a larger number of patients. Most of the recent studies failed to demonstrate a significant effect of lithium on the depressive symptoms of alcoholics. Thus, it is now established that lithium is not an effective treatment of affective disorders in alcoholics. The latest published studies also suggest that lithium treatment does not decrease alcohol intake or craving for alcohol in either depressed or non-depressed alcoholics.


Dispersion of the third-order optical nonlinearities in 2D (PEA)2PbI4 perovskite film.
We report the wavelength-dependent third-order optical nonlinearity of two-dimensional halide organic-inorganic perovskite (PEA)2PbI4 film experimentally. The high-quality two-dimensional (PEA)2PbI4 film prepared via confinement-assisted drop-casting process exhibits ultrafast optical response and large third-order optical nonlinearities, and the measured nonlinear refractive index is closer to the quantum perturbation model accounting for the excitonic effect. In addition, the wavelength-dependent optical response transition from self-focusing to self-defocusing, saturable absorption to reverse saturable absorption has been observed and investigated. The experimental results confirm the large third-order optical nonlinearities in (PEA)2PbI4 film and may make inroads toward developing cost-effective high-performance optoelectronic devices.


The Role of Genetics in Preterm Birth.
Preterm birth (PTB), defined as the birth of a child before 37 completed weeks gestation, affects approximately 11% of live births and is the leading cause of death in children under 5 years. PTB is a complex disease with multiple risk factors including genetic variation. Much research has aimed to establish the biological mechanisms underlying PTB often through identification of genetic markers for PTB risk. The objective of this review is to present a comprehensive and updated summary of the published data relating to the field of PTB genetics. A literature search in PubMed was conducted and English studies related to PTB genetics were included. Genetic studies have identified genes within inflammatory, immunological, tissue remodeling, endocrine, metabolic, and vascular pathways that may be involved in PTB. However, a substantial proportion of published data have been largely inconclusive and multiple studies had limited power to detect associations. On the contrary, a few large hypothesis-free approaches have identified and replicated multiple novel variants associated with PTB in different cohorts. Overall, attempts to predict PTB using single "-omics" datasets including genomic, transcriptomic, and epigenomic biomarkers have been mostly unsuccessful and have failed to translate to the clinical setting. Integration of data from multiple "-omics" datasets has yielded the most promising results.


[Exercise capacity after heart valve replacement].
Exercise capacity following heart-valve replacement is dependent on how close to normal the artificial device can restore valve function, to what degree a preoperative impaired myocardial function and/or an increased pulmonary vascular resistance is normalized. The postoperative functional result can be determined by the subjective improvement of the patient, his functional capacity, exercise capacity, the central hemodynamics at rest and during exercise, and the systolic and diastolic function of the left and right ventricular myocardium. The subjective improvement of individual symptoms is obviously dependent on the degree of postoperative normalization of hemodynamics, especially of pressures in the pulmonary circulation. Subjective improvement can be objectified by comparing the functional capacities before and after surgery. Post-operative normalization of central hemodynamics and myocardial function does not happen immediately but within 3 to more than 12 months. A 12-month period can generally be expected in patients with mitral stenosis and increased pulmonary vascular resistance (> 400 dyn.sec.cm-5) prior to surgery. In patients with mitral and aortic regurgitation as well as with aortic stenosis and preoperative decrease of their left ventricular ejection fraction during exercise, continuous improvement of left ventricular pump function also may need up to 12 months. Physiological hemodynamic conditions generally are not restored by valve replacement. All prostheses are stenotic to forward blood flow because of the obstruction created by the narrowing of the valve area by sewing cuff and valve poppet. This may result in a hemodynamically important stenosis, especially after atrio-ventricular valve implantation, and may limit subjective and functional improvement. Exercise capacity after aortic valve replacement depends mainly on whether or not myocardial damage persists postoperatively. A workload of 1.5 w/kg body weight (BW) has been performed by 100% of patients aged 45 to 55 years with prostheses implanted for aortic stenosis. The significant lower exercise capacity all patients with valve replacement for aortic regurgitation have experienced (0.4 w/kg BW) indicates that a substantial number of these patients has irreversible myocardial damage prior to surgery. The workload experienced by patients with mitral valve prostheses varies between 0.4 and 2.0 w/kg BW (mitral stenosis) and 0.3-2.3 w/kg BW (mitral regurgitation), respectively. To objectify the functional result of heart-valve replacement, hemodynamic-metabolic measurements of functional improvement, determination of left, eventually also of right-ventricular function by echocardiography and additional invasive measurements of the central hemodynamics and myocardial pump function parameters at rest and during exercise might be necessary.


The boron-boron triple bond? A thermodynamic and force field based interpretation of the N-heterocyclic carbene (NHC) stabilization procedure.
Recently, the NHC→B[triple bond, length as m-dash]B←NHC molecule 1 has been published in Science where it is described as a stabilized B2 molecule in its 1Σ excited state (B2*) (NHC = N-heterocyclic carbene C3N2H2(C6H3Pri 2-2,6)2). The bonding of 1 based on sophisticated calculations and the BB distances of the solid compound was discussed as the first example of a B2 triple bond in a stable molecule. Now we present an only experimentally based interpretation of 1 via detailed thermodynamic considerations, including its fragmentation to B2 molecules. Furthermore, from the vibrational spectrum force constants (f BB for the BB bond and f BC for the BC bond) were extracted, which are classical examples to indicate single, double and triple CC bonds in organic chemistry. The consequence of both properties of 1 (ΔE and f) generates a new interpretation which is in contrast to the triple bond donor-acceptor description visualized by arrows and which casts a critical light on the interpretation of any NHC "stabilized" molecule.


Prevention and treatment effects of edible berries for three deadly diseases: Cardiovascular disease, cancer and diabetes.
Cardiovascular disease (CVD), cancer and diabetes are serious threat to human health and more and more aroused people's attention. It is important to find the safe and effective prevention and treatment methods for the three deadly diseases. At present, a generally attention in the possible positive effects of edible berries for the three deadly diseases has been noted. Berry phytochemical compounds regulate different signaling pathways about cell survival, growth and differentiation. They contribute to the prevention and treatment of CVD, cancer and diabetes. This article reviews previous experimental evidence, several common berry phytochemical compounds and their possible mechanisms involved in three deadly diseases were summarized.


Ultrafast fluorescence resonance energy transfer in a reverse micelle: excitation wavelength dependence.
Fluorescence resonance energy transfer (FRET) from coumarin 480 (C480) to fluorescein 548 (F548) in a sodium dioctyl sulfosuccinate (AOT) reverse micelle is studied by picosecond and femtosecond emission spectroscopy. In bulk water, at the low concentration of the donor (C480) and the acceptor (F548), no FRET is observed. However, when the donor (C480) and the acceptor (F548) are confined in a AOT reverse micelle very fast FRET is observed. The time constants of FRET were obtained from the rise time of the emission of the acceptor (F548). In a AOT microemulsion, FRET is found to occur in multiple time scales--3, 200, and 2700 ps. The 3 ps component is assigned to FRET in the water pool of the reverse micelle with a donor-acceptor distance, 16 A. The 200 ps component corresponds to a donor-acceptor distance of 30 A and is ascribed to the negatively charged acceptor inside the water pool and the neutral donor inside the alkyl chains of AOT. The very long 2700 ps component may arise due to FRET from a donor outside the micelle to an acceptor inside the water pool and also from diffusion of the donor from bulk heptane to the reverse micelle. With increase in the excitation wavelength from 375 to 405 nm the relative contribution of the FRET due to C480 in the AOT reverse micelle (the 3 and 200 ps components) increases.


Prospective phase II study of preoperative chemoradiation with capecitabine in locally advanced rectal cancer.
Capecitabine is an attractive oral chemotherapeutic agent that has a radiosensitizing effect and tumor-selectivity. This study was performed to evaluate the efficacy and toxicity of preoperative chemoradiation therapy, when used with oral capecitabine, for locally advanced rectal cancer. A prospective phase II trial of preoperative chemoradiation for locally advanced adenocarcinomas of the lower two-thirds of the rectum was conducted. A radiation dose of 50 Gy over five weeks and a daily dose of 1650 mg/m(2) capecitabine in two portions was administered during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision four to six weeks after completion of the chemoradiation. Between January 2002 and September 2003, 61 patients were enrolled onto this prospective phase II trial. The pretreatment clinical stages were T3 in 64% (n=39), T4 in 36% (n=22) and N1-2 in 82% (n=50) of these patients. Fifty-six (92%) patients completed the chemoradiation as initially planned and a complete resection performed in 58 (95%). Down-staging was observed in 45 patients (74%) and a pathologic complete response in 6 (10%). Among the 37 patients with tumors located within 5 cm from the anal verge on colonoscopy, 27 (73%) underwent a sphincter-preserving procedure. No grade 3 and 4 proctitis or hematological toxicities were observed. Preoperative chemoradiation therapy with capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation, with a low toxicity profile. This combined modality can be regarded as a safe and effective treatment for locally advanced rectal cancer.


Improved progression-free and event-free survival in myeloma patients undergoing PBSCH receiving a cyclophosphamide + G-CSF regimen than G-CSF alone.
Two regimens are commonly used for peripheral blood hematopoietic stem cell harvesting (PBSCH) in multiple myeloma: high-dose cyclophosphamide (HD-CY) + granulocyte-colony stimulating factor (G-CSF), and G-CSF alone. The objective of the present study was to evaluate the anti-myeloma effect of the PBSCH regimen including HD-CY. We retrospectively assessed harvesting efficiency, complications, and anti-myeloma effects in 115 patients receiving HD-CY + G-CSF (HD-CY group) and 32 patients receiving G-CSF alone (G-alone group). We collected > 2 × 106 CD34-positive cells/kg from 93 and 75% of patients in the HD-CY and G-alone groups, respectively (P = 0.0079). The mean HSC count was also higher in the HD-CY group. No severe complications were observed in the G-alone group, whereas 66% of patients in the HD-CY group were treated with intravenous antibiotics. The median progression-free and event-free survival (PFS and EFS) were longer in the HD-CY group than in the G-alone group (28 vs. 18 months and 25 vs. 13 months, respectively; P = 0.0127 and 0.0139), with no difference in median overall survival. HD-CY showed anti-myeloma effect, as verified by prolonged EFS and PFS, when a vincristine, doxorubicin, and dexamethasone regimen was administered as induction before PBSCH.


Serine phosphorylation of the insulin-like growth factor I (IGF-1) receptor C-terminal tail restrains kinase activity and cell growth.
Insulin-like growth factor I receptor (IGF-1R) signaling is essential for cell, organ, and animal growth. The C-terminal tail of the IGF-1R exhibits regulatory function, but the mechanism is unknown. Here, we show that mutation of Ser-1248 (S1248A) enhances IGF-1R in vitro kinase activity, autophosphorylation, Akt/mammalian target of rapamycin activity, and cell growth. Ser-1248 phosphorylation is mediated by GSK-3β in a mechanism that involves a priming phosphorylation on Ser-1252. GSK-3β knock-out cells exhibit reduced IGF-1R cell surface expression, enhanced IGF-1R kinase activity, and signaling. Examination of crystallographic structures of the IGF-1R kinase domain revealed that the (1248)SFYYS(1252) motif adopts a conformation tightly packed against the kinase C-lobe when Ser-1248 is in the unphosphorylated state that favors kinase activity. S1248A mutation is predicted to lock the motif in this position. In contrast, phosphorylation of Ser-1248 will drive profound structural transition of the sequence, critically affecting connection of the C terminus as well as exposing potential protein docking sites. Decreased kinase activity of a phosphomimetic S1248E mutant and enhanced kinase activity in mutants of its predicted target residue Lys-1081 support this auto-inhibitory model. Thus, the SFYYS motif controls the organization of the IGF-1R C terminus relative to the kinase domain. Its phosphorylation by GSK-3β restrains kinase activity and regulates receptor trafficking and signaling.


Rotational diffusion of eosin-labeled pyruvate dehydrogenase complex of Escherichia coli.
The enzymatically reduced lipoyl residues of the transacetylase component of the pyruvate dehydrogenase complex from Escherichia coli were labeled with eosin maleimide. Using eosin as triplet probe, triplet-triplet absorption dichroism measurements were performed to obtain rotational correlation times of the complex in the microsecond time domain. It was found that the hydrodynamic properties determined from the correlation times are in very good agreement with those obtained with other methods of different origin. The results can be fully explained by eosin molecules rotating with the whole complex, which consists of a mixture of heavy (60 S) and light (20 S) particles. Since no independent mobility could be detected it is suggested that the (charged) chromophoric group is folded against the protein surface. Labeling with excess eosin maleimide tends to destabilize the complex, since the longer correlation time (60 S) decreases and the contribution of the shorter correlation time (20 S) becomes more significant upon labeling.


Signature effects of spin clustering and distribution of spin couplings on magnetization behaviour in Ni-Fe-Mo and Ni-Fe-W alloys.
Spontaneous magnetization as a function of temperature is investigated for a number of disordered Ni-Fe-Mo and Ni-Fe-W alloys using superconducting quantum interference device magnetometry, with a focus on the low-T behaviour as well as the critical exponents associated with the magnetic phase transition. While the low-T magnetization is found to be well described by Bloch's T(3/2) law, extraordinary enhancements of the spin-wave parameter B and the reduced coefficient B(3/2) = BT(C)(3/2) are observed with increasing Fe dilution as compared to conventional 3d ferromagnets, whereas the critical amplitudes are found to decrease systematically. Recent locally self-consistent calculations of finite-temperature spin dynamics in a generic diluted magnet provide an understanding in terms of two distinct energy scales associated with weakly coupled bulk spins in the ferromagnetic matrix and strongly coupled cluster spins. In view of the similar behaviour observed in diluted magnetic semiconductors and other ferromagnetic alloys, it is proposed that these distinctive features corresponding to the three important temperature regimes provide macroscopic indicators of signature effects of spin clustering on the magnetization behaviour in disordered ferromagnets.


Generic versus branded medicines: An observational study among patients with chronic diseases attending a public hospital outpatient department.
The concept of generic prescription is widely accepted in various parts of the world. Nevertheless, it has failed to gain popularity in India due to factors such as nonavailability and distrust on the product quality. However, since 2012, the Government of West Bengal, India, has initiated exclusive generic drug outlets called "fair price medicine shop" (FPMS) inside the government hospital premises in a "public-private-partnership" model. This study was undertaken to evaluate the experience and attitude of patients who were consuming generic drugs purchased from these FPMS. It was a questionnaire-based cross-sectional study where we have interviewed 100 patients each consuming generic and branded drugs, respectively. The perceived effectiveness, reported safety, medication adherence, cost of therapy, and availability of drugs was compared between two mentioned groups. Medication adherence was estimated through Drug Attitude Inventory-10. 93% of generic and 87% branded drug users believed that their drugs were effective (P = 0.238) in controlling their ailments. No significant difference (9% generic, 10% branded drug users, P = 1.000) was observed in reported adverse effects between generic and branded drug users. 82% and 77% of patients were adherent generic and branded drugs, respectively (P = 0.289). As expected, a significantly lower cost of generic drugs was observed compared to its branded counterpart. The policy of FPMS implemented by the Government of West Bengal, India appeared to be promising in terms of perceived effectiveness, safety, and adherence of generic drugs from FPMS compared to drugs purchased from open market retailers. Therefore, this study might act as an impetus for the policy-makers to initiate similar models across the country.


The impact of acetylation and deacetylation on the p53 pathway.
The p53 tumor suppressor is a sequence-specific transcription factor that undergoes an abundance of post-translational modifications for its regulation and activation. Acetylation of p53 is an important reversible enzymatic process that occurs in response to DNA damage and genotoxic stress and is indispensible for p53 transcriptional activity. p53 was the first non-histone protein shown to be acetylated by histone acetyl transferases, and a number of more recent in vivo models have underscored the importance of this type of modification for p53 activity. Here, we review the current knowledge and recent findings of p53 acetylation and deacetylation and discuss the implications of these processes for the p53 pathway.


Electrochemical Dynamics of a Single Platinum Nanoparticle Collision Event for the Hydrogen Evolution Reaction.
Chronoamperometry was used to study the dynamics of Pt nanoparticle (NP) collision with an inert ultramicroelectrode via electrocatalytic amplification (ECA) in the hydrogen evolution reaction. ECA and dynamic light scattering (DLS) results reveal that the NP colloid remains stable only at low proton concentrations (1.0 mm) under a helium (He) atmosphere, ensuring that the collision events occur at genuinely single NP level. Amperometry of single NP collisions under a He atmosphere shows that each discrete current profile of the collision event evolves from spike to staircase at more negative potentials, while a staircase response is observed at all of the applied potentials under hydrogen-containing atmospheres. The particle size distribution estimated from the diffusion-controlled current in He agrees well with electron microscopy and DLS observations. These results shed light on the interfacial dynamics of the single nanoparticle collision electrochemistry.


Host cell cytokines induced by Chlamydia pneumoniae decrease the expression of interstitial collagens and fibronectin in fibroblasts.
Chlamydia pneumoniae infection has been associated with chronic obstructive airway disease (COPD), asthma, and atherosclerosis. Inflammation and airway remodeling in asthma and COPD result in subepithelial fibrosis that is characterized by the deposition of interstitial collagens and fibronectin. The progression of atherosclerosis is also accompanied by an increased production of interstitial collagens in the intima. As shown by reverse transcription-PCR and immunoblotting, infection of human fibroblasts and smooth muscle cells by C. pneumoniae TW-183 downregulated the expression of type I and III collagen and fibronectin, whereas the level of type IV collagen remained unchanged. Conditioned medium from infected fibroblasts as well as epithelial WISH cells also reduced the expression of interstitial collagens and fibronectin in uninfected cells. In experiments using blocking antibodies, beta interferon was found to contribute to the inhibitory effects of conditioned medium collected from infected fibroblasts. In contrast, downregulation of matrix protein expression by conditioned medium from epithelial cells was caused by interleukin-1alpha, which was not secreted from fibroblasts following chlamydial infection. C. pneumoniae-mediated inhibition of collagen and fibronectin expression was diminished following transfection of fibroblasts with specific small interfering RNA targeting the transcription factor CCAAT/enhancer-binding protein beta. The downregulation of interstitial collagens and fibronectin by the Chlamydia-induced host cell cytokine response may modulate tissue remodeling processes in airway diseases. In atherosclerosis the inhibition of collagen synthesis by C. pneumoniae infection may promote plaque vulnerability, thereby increasing the risk of plaque rupture.


Bacterial bile metabolising gene abundance in Crohn's, ulcerative colitis and type 2 diabetes metagenomes.
We performed an analysis to determine the importance of bile acid modification genes in the gut microbiome of inflammatory bowel disease and type 2 diabetic patients. We used publicly available metagenomic datasets from the Human Microbiome Project and the MetaHIT consortium, and determined the abundance of bile salt hydrolase gene (bsh), 7 alpha-dehydroxylase gene (adh) and 7-alpha hydroxysteroid dehydrogenase gene (hsdh) in fecal bacteria in diseased populations of Crohn's disease (CD), Ulcerative Colitis (UC) and Type 2 diabetes mellitus (T2DM). Phylum level abundance analysis showed a significant reduction in Firmicute-derived bsh in UC and T2DM patients but not in CD patients, relative to healthy controls. Reduction of adh and hsdh genes was also seen in UC and T2DM patients, while an increase was observed in the CD population as compared to healthy controls. A further analysis of the bsh genes showed significant differences in the correlations of certain Firmicutes families with disease or healthy populations. From this observation we proceeded to analyse BSH protein sequences and identified BSH proteins clusters representing the most abundant strains in our analysis of Firmicute bsh genes. The abundance of the bsh genes corresponding to one of these protein clusters was significantly reduced in all disease states relative to healthy controls. This cluster includes bsh genes derived from Lachospiraceae, Clostridiaceae, Erysipelotrichaceae and Ruminococcaceae families. This metagenomic analysis provides evidence of the importance of bile acid modifying enzymes in health and disease. It further highlights the importance of identifying gene and protein clusters, as the same gene may be associated with health or disease, depending on the strains expressing the enzyme, and differences in the enzymes themselves.


Factors Associated With the Ultrasound Characteristics of the Lumbar Multifidus: A Systematic Review.
The first aim of this review was to investigate the association between age, sex, height, weight, physical activity level, posture, lumbar level and body side, and structural characteristics (cross-sectional area [CSA], thickness, linear dimensions, and echo intensity) of the lumbar multifidus (LM) measured by ultrasound. Second, differences between healthy individuals and patients with chronic low back pain (CLBP) were investigated. TYPE: Systematic review. PubMed, Embase and Web of Science were searched until September 2018. Studies were included if (a) full text was available in English, Dutch, or French; (b) participants were older than 18 years of age and were asymptomatic or had nonspecific CLBP; and (c) the relation between structural characteristics of the LM, measured by ultrasound, and at least one of the above-mentioned factors was described, and/or a comparison between a CLBP and control group was made. Data were extracted independently by two reviewers. Quality of studies was assessed using an adapted version of the Downs and Black checklist. Twenty-seven studies were included. Thickness and CSA of the LM do not correlate with age. Males have a larger LM size than females. Thickness and CSA of left and right LM are highly correlated in healthy subjects. More significant side-to-side differences are present in subjects with CLBP than in those without. Muscle size increases from proximal to caudal lumbar levels. The presence of CLBP is associated with muscle size and function. The association between the factors age, sex, height, weight, physical activity level, posture, lumbar level, body side, and presence of CLBP, and the ultrasound characteristics of the LM is discussed. These factors should be taken into account in future research on structural muscle characteristics, or when correlating with functional behavior or investigating the effect of a targeted intervention. I.


Hip prosthesis in sitting posture for bilateral transfemoral amputee after burn injury: a case report.
To overcome the challenges of rehabilitation of bilateral transfemoral amputees, we developed a novel "hip prosthesis in the sitting posture." Case Description and Methods: A 64-year-old male bilateral transfemoral amputee was transferred for rehabilitation 4 months following a burn injury. His wounds remained unhealed for 20 months; thus, he was unable to participate in standing training with the standard prosthetic sockets. Hip prosthesis in the sitting posture has very little friction between the sockets and residual limbs, which facilitated our patient to begin standing and walking exercises. Findings and Outcomes: The patient's refractory wounds healed 1 month after initiating exercises using hip prosthesis in the sitting posture, and he could begin rehabilitation with the standard prostheses. Hip prosthesis in the sitting posture enabled a bilateral transfemoral amputee with unhealed residual limbs to stand, walk, and begin balance training. Hip prosthesis in the sitting posture is an effective temporary prosthesis to prevent disuse until wounds are healed and to continue rehabilitation with standard prostheses. Clinical relevance Hip prosthesis in the sitting posture is useful for bilateral transfemoral amputees with unhealed residual limbs after burn injuries to prevent disuse and maintain motivation for walking.


[Insulin and C-peptide in chronic liver diseases during oral glucose tolerance testing].
Insulin and C-peptide in venous blood were determined during oral glucose tolerance testing in 59 non-manifest diabetics with histologically established chronic liver disease (fatty degeneration, chronic aggressive hepatitis, cirrhosis). Glucose tolerance was pathologic in 60-80% of patients. When compared to a control group patients with chronic liver disease showed significantly increased values of blood glucose (after glucose intake), of insulin and of C-peptide (fasting and after glucose intake). The C-peptide/insulin ratio, a measure of hepatic insulin degradation, was significantly decreased after glucose uptake. There were no significant differences of blood sugar, insulin and C-peptide among the various liver diseases. In chronic aggressive hepatitis and in cirrhosis the C-peptide/insulin ratio was partly significantly lower than in fatty degeneration. From the increased C-peptide values increased insulin secretion in chronic liver diseases can be deducted. In addition, the decreased C-peptide/insulin ratios show an impairment of insulin degradation in liver cirrhosis and other chronic hepatic diseases. However, in fatty liver degeneration this is clearly less pronounced than in more serious liver diseases.


Deficient attention is hard to find: applying the perceptual load model of selective attention to attention deficit hyperactivity disorder subtypes.
Whether selective attention is a primary deficit in childhood Attention Deficit Hyperactivity Disorder (ADHD) remains in active debate. We used the perceptual load paradigm to examine both early and late selective attention in children with the Primarily Inattentive (ADHD-I) and Combined subtypes (ADHD-C) of ADHD. No evidence emerged for selective attention deficits in either of the subtypes, but sluggish cognitive tempo was associated with abnormal early selection. At least some, and possibly most, children with DSM-IV ADHD have normal selective attention. Results support the move away from theories of attention dysfunction as primary in ADHD-C. In ADHD-I, this was one of the first formal tests of posterior attention network dysfunction, and results did not support that theory. However, ADHD children with sluggish cognitive tempo (SCT) warrant more study for possible early selective attention deficits.


Validity and reliability of the Turkish Adherence to Refills and Medications Scale.
The aim of the study was to create a Turkish version of the Adherence to Refills and Medications Scale (ARMS-7) and to examine its validity and reliability. The sample of this methodological type study consisted of 100 Turkish patients with chronic disease. In the evaluation of data, the content validity index, Cronbach α, test-retest, item total score correlation, exploratory and confirmatory factor analyses, and adherence statistics were used. The scale's content validity index was 0.94, its Kendal W goodness-of-fit test was 0.188 (P = .246), its Cronbach α coefficient was 0.75, and its item total score correlation was between 0.32 and 0.59 (P < .001). The test-retest reliability was also satisfactory with interclass correlation coefficients higher than 0.75. The Turkish version of the ARMS-7 is a reliable and valid instrument that can be used in the evaluation of attitudes to adherence to medications and refills based on self-reporting by the chronically ill.


Transcriptomics as a tool to discover new antibacterial targets.
The emergence of antibiotic-resistant pathogens, multiple drug-resistance, and extremely drug-resistant strains demonstrates the need for improved strategies to discover new drug-based compounds. The development of transcriptomics, proteomics, and metabolomics has provided new tools for global studies of living organisms. However, the compendium of expression profiles produced by these methods has introduced new scientific challenges into antimicrobial research. In this review, we discuss the practical value of transcriptomic techniques as well as their difficulties and pitfalls. We advocate the construction of new databases of transcriptomic data, using standardized formats in addition to standardized models of bacterial and yeast similar to those used in systems biology. The inclusion of proteomic and metabolomic data is also essential, as the resulting networks can provide a landscape to rationally predict and exploit new drug targets and to understand drug synergies.


Accelerated ventricular rhythm in healthy neonates.
Accelerated ventricular rhythm is similar in rate to the original sinus rhythm. Although 19 cases have been reported in healthy neonates without congenital disease, it is seen with some regularity at tertiary care paediatric cardiac centres. Accelerated ventricular rhythm carries good prognosis, but it is frequently misdiagnosed as ventricular tachycardia and is, thus, unnecessarily treated. The present report describes a case of a neonate who was not properly diagnosed after birth and who was inappropriately treated.


Genome-based reclassification of Caldicellulosiruptor lactoaceticus and Caldicellulosiruptor kristjanssonii as later heterotypic synonyms of Caldicellulosiruptor acetigenus.
The present study was carried out to re-clarify the taxonomic relationship of Caldicellulosiruptor acetigenus, Caldicellulosiruptor lactoaceticus and Caldicellulosiruptor kristjanssonii. The 16S rRNA sequence similarities between these species of the genus Caldicellulosiruptor were above the threshold values (98.65%) for bacterial species delineation. Similarly, the digital DNA-DNA hybridization and average nucleotide and amino acid identity values were greater than the thresholds for bacterial species delineation. In phylogenetic (based on 16S rRNA gene sequences) and phylogenomic trees Caldicellulosiruptor acetigenus, Caldicellulosiruptor lactoaceticus and Caldicellulosiruptor kristjanssonii clade together. The results of our analysis indicated that these three taxa are conspecific. Therefore, Caldicellulosiruptor lactoaceticus Mladenovska et al. 1997 and Caldicellulosiruptor kristjanssonii Bredholt et al. 1999 should be reclassified as later heterotypic synonyms of Caldicellulosiruptor acetigenus (Nielsen et al. 1994) Onyenwoke et al. 2006.


Resonant cavity phosphor.
While phosphors play an immensely important role in solid-state lighting and full-colour displays, it has been noted lately that their performance can be largely improved via structural engineering. Here, phosphor material is synergistically merged with yet another structurally engineered platform, resonant cavity (RC). When a 40-nm-thick colloidal quantum dot (CQD) film is embedded in a tailored RC with a moderate cavity quality factor (Q ≈ 90), it gains the ability to absorb the majority (~87%) of excitation photons, resulting in significantly enhanced CQD fluorescence (~29×) across a reasonably broad linewidth (~13 nm). The colour gamut covered by red and green pixels implemented using the RC phosphor-along with a broad bandwidth (~20 nm) blue excitation source-exceeds that of the sRGB standard (~121%). The simple planar geometry facilitates design and implementation of the RC phosphor, making it promising for use in real applications.


Arcanobacterium buesumense sp. nov., isolated from an anal swab of a male harbour seal (Phoca vitulina).
A polyphasic taxonomic study was performed on an unidentified previously described Arcanobacterium-like Gram-positive strain 2701T isolated from an anal swab of a dead male harbour seal. Comparative 16S rRNA sequencing showed that the bacterium belonged to the genus Arcanobacterium in the family Arcanobacteriaceae. The genome sequence of the strain was obtained by Borowiak et al. [1]. The genome had a G+C content of 49 mol% and a total length of 1.94 Mb. The presence of the major menaquinone MK-9(H4) supported the affiliation of the isolate with the genus Arcanobacterium. The polar lipid profile consisted of diphosphatidylglycerol and an unidentified phospholipid as major components and two unidentified lipids, a further unidentified phospholipid, two unidentified phosphoglycolipids as well as phosphatidylglycerol. The major fatty acids were C16 : 0, C18 : 1 and C18 : 0. Biochemical and phylogenetic analyses clearly distinguished the isolate from other members of the genus Arcanobacterium and closely related other species. Based on these results, it is proposed that the unknown Arcanobacterium sp. strain 2701T should be classified as representing a novel species with the name Arcanobacterium buesumense sp. nov. The type strain is 2701T (=DSM 112952T=LMG 32446T).


Altered oral microbiota composition associated with recurrent aphthous stomatitis in young females.
Oral microbiota has been implicated in pathogenesis of recurrent aphthous stomatitis (RAS), which is a common mucosal disorder with unclear etiology. This study has explored the association between oral microbiota disorder and RAS in high-risk young female population.Forty-five young females were enrolled, including 24 RAS patients and 21 healthy individuals. Oral microbiome was analyzed by Illumina Miseq sequencing.Oral microbiota associated with RAS was characterized by the lower alpha-diversity indices (Chao1 and ACE). Several infectious pathogens increased in RAS, such as genera Actinobacillus, Haemophilus, Prevotella and Vibrio. The PICRUSt analysis indicated that the oral microbiota might be related with the up-regulation of genes involving infectious and neurodegenerative diseases, environmental adaptation, the down-regulation of genes involving basal metabolism, such as carbohydrate, energy, and amino acid metabolism.This study indicated that oral microbiota may play a significant role in RAS development.


Properties of the interfaces generated by the competition between stable and unstable growth models.
Two different growing mechanisms, given by the Eden model (EM) and the unstable Eden model (UEM), are used to numerically explore the properties of the interface generated by a competitive dynamic process in which particles are aggregated according to the rules of the EM with probability (1-p) and following the UEM with probability p . Based on extensive numerical simulations, it is shown that the interface width exhibits a growing regime that at time t(x2) crosses over to a saturation state such that the width (Wsat) remains stationary. It is shown that Wsat and t(x2) depend on both the lattice size L and the probability p . This behavior can be rationalized by proposing new scaling relationships, which are tested numerically. Furthermore, the relevant exponents are determined showing that the instabilities of the UEM dominate the dynamics of the growing process.


"I didn't want to be in charge and yet I was": Bereaved caregivers' accounts of providing home care for family members with advanced cancer.
To describe bereaved caregivers' experiences of providing care at home for patients with advanced cancer, while interacting with home care services. Caregivers of patients who had completed a 4-month randomized controlled trial of early palliative care versus standard oncology care were recruited 6 months to 5 years after the patient's death. All patients except one (control) had eventually received palliative care. In semi-structured interviews, participants were asked about their experiences of caregiving. Grounded theory guided all aspects of the study. Sixty-one bereaved caregivers (30 intervention, 31 control) were interviewed, including spouses (33), adult children (19), and other family (9). There were no differences in themes between control and intervention groups. The core category of Taking charge encompassed caregivers' assumption of active roles in care, often in the face of inadequate formal support. There were 4 interrelated subcategories: (1) Navigating the system-navigating the complexities of the home care system to access resources and supports; (2) Engaging with professional caregivers-interacting with visiting personnel to advocate for consistency and quality of care; (3) Preparing for death-seeking out information about what to expect at the end of life; and (4) Managing after death-managing multiple administrative responsibilities in the emotionally charged period following death. Caregivers were often thrust into assuming control in order to compensate for deficiencies in formal palliative home care services. Policies, quality indicators, and guidelines are needed to ensure the provision of comprehensive, interdisciplinary home palliative care.


How network structure affects the dynamics of a network of stochastic spiking neurons.
Up to now, it still remains an open question about the relation between the structure of brain networks and their functions. The effects of structure on the dynamics of neural networks are usually investigated via extensive numerical simulations, while analytical analysis is always very difficult and thus rare. In this work, we explored the effects of a random regular graph on the dynamics of a neural network of stochastic spiking neurons, which has a bistable region when fully connected. We showed by numerical simulations that as the number of each neuron's neighbors decreases, the bistable region shrinks and eventually seems to disappear, and a critical-like transition appears. In the meantime, we made analytical analysis that explains numerical results. We hope this would give some insights into how structure affects the dynamics of neural networks from a theoretical perspective, rather than merely by numerical simulations.


Mechanisms of competitive adsorption of albumin and sodium myristate at the silicon oxide/aqueous interface.
The competitive adsorption of proteins and surfactants has applications to chromatographic systems and biological materials. Adsorption for systems of bovine serum albumin (BSA) and sodium myristate (SM) was investigated with in-situ ATR-IR spectroscopy and ex-situ ellipsometry. The results were used to determine quantitatively the surface densities of the adsorbates at the surface. For a mixture of SM and BSA at 25 degrees C in water, the adsorbed density of BSA is 0.3 mg/m2, which is much less than the value of 3.1 mg/m2 for BSA alone. Sodium myristate, some of which is protonated to myristic acid (MA) when adsorbed because of a pH decrease from 9.0 to 8.2, adsorbs to a surface density of 4.0 x 10(-6) mol/m2, which is greater than the value of 1.7 x 10(-6) mol/m2 from a solution of SM alone. Adsorbed SM and MA are removed, or desorbed, when the bulk mixture is replaced with water, with only a slight amount of SM remaining. When placed in contact with a layer of BSA, SM can displace most of the adsorbed protein, even when BSA is present in the bulk solution, with some BSA at 0.3 mg/m2 remaining adsorbed. Allowing BSA to adsorb to a layer of SM results in gamma(BSA) = 2.3 mg/m2, with little displacement of the SM layer. These results indicate that SM can remove some BSA from the surface by displacement, and that some BSA remains adsorbed in patches.


Trait schizotypy and the psychosis prodrome: Current standard assessment of extended psychosis spectrum phenotypes.
Schizotypy has become an increasingly important construct for elaborating psychotic disorders that vary along the schizophrenic spectrum. However, different schizotypy inventories vary in conceptual approach and measurement. In addition, commonly used schizotypy scales have been seen as qualitatively different from screening instruments for prodromal schizophrenia like the Prodromal Questionnaire-16 (PQ-16). Our study investigated the psychometric properties of three schizotypy questionnaires (the Schizotypal Personality Questionnaire-Brief, Oxford-Liverpool Inventory of Feelings and Experiences, and the Multidimensional Schizotypy Scale) as well as the PQ-16 in a cohort of 383 non-clinical subjects. We initially evaluated their factor structure using Principal Component Analysis (PCA) and used Confirmatory Factor Analysis (CFA) to test a newly proposed composition of factors. PCA results support a three-factor structure of schizotypy that accounts for 71 % of the total variance, but also shows cross-loadings of some schizotypy subscales. CFA of the newly composed schizotypy factors (together with an added neuroticism factor) shows good fit. Analyses including the PQ-16 indicate considerable overlap with measures of trait schizotypy, suggesting that the PQ-16 might not be quantitatively or qualitatively different from schizotypy measurements. Taken together, results indicate that there is good support for a three-factor structure of schizotypy but also that different schizotypy measurements grasp facets of schizotypy differently. This points towards the need for an integrative approach for assessing the construct of schizotypy.


Elevated resting blood pressure augments autonomic imbalance in posttraumatic stress disorder.
Posttraumatic stress disorder (PTSD) is characterized by increased sympathetic nervous system (SNS) activity, blunted parasympathetic nervous system (PNS) activity, and impaired baroreflex sensitivity (BRS), which contribute to accelerated cardiovascular disease. Patients with PTSD also have chronic stress-related elevations in resting blood pressure (BP), often in the prehypertensive range; yet, it is unclear if elevated resting blood pressure (ERBP) augments these autonomic derangements in PTSD. We hypothesized that compared with normotensive PTSD (N-PTSD), those with ERBP (E-PTSD) have further increased SNS, decreased PNS activity, and impaired BRS at rest and exaggerated SNS reactivity, PNS withdrawal, and pressor responses during stress. In 16 E-PTSD and 17 matched N-PTSD, we measured continuous BP, ECG, muscle sympathetic nerve activity (MSNA), and heart rate variability (HRV) markers reflecting cardiac PNS activity [standard deviation of R-R intervals (SDNN), root mean square of differences in successive R-R intervals (RMSSD), and high frequency power (HF)] during 5 min of rest and 3 min of mental arithmetic. Resting MSNA ( P = 0.943), sympathetic BRS ( P = 0.189), and cardiovagal BRS ( P = 0.332) were similar between groups. However, baseline SDNN (56 ± 6 vs. 78 ± 8 ms, P = 0.019), RMSSD (39 ± 6 vs. 63 ± 9 ms, P = 0.018), and HF (378 ± 103 vs. 693 ± 92 ms2, P = 0.015) were lower in E-PTSD versus N-PTSD. During mental stress, the systolic blood pressure response ( P = 0.011) was augmented in E-PTSD. Although MSNA reactivity was not different ( P > 0.05), the E-PTSD group had an exaggerated reduction in HRV during mental stress ( P < 0.05). PTSD with ERBP have attenuated resting cardiac PNS activity, coupled with exaggerated BP reactivity and PNS withdrawal during stress.


Extremely Large Magnetoresistance in a Topological Semimetal Candidate Pyrite PtBi_{2}.
While pyrite-type PtBi_{2} with a face-centered cubic structure has been predicted to be a three-dimensional (3D) Dirac semimetal, experimental study of its physical properties remains absent. Here we report the angular-dependent magnetoresistance measurements of a PtBi_{2} single crystal under high magnetic fields. We observed extremely large unsaturated magnetoresistance (XMR) up to (11.2×10^{6})% at T=1.8 K in a magnetic field of 33 T, which is comparable to the previously reported Dirac materials, such as WTe_{2}, LaSb, and NbP. The crystals exhibit an ultrahigh mobility and significant Shubnikov-de Hass quantum oscillations with a nontrivial Berry phase. The analysis of Hall resistivity indicates that the XMR can be ascribed to the nearly compensated electron and hole. Our experimental results associated with the ab initio calculations suggest that pyrite PtBi_{2} is a topological semimetal candidate that might provide a platform for exploring topological materials with XMR in noble metal alloys.


Cardiovascular Collapse Secondary to Beta-Blocker Administration in a Setting of Coexisting Thyroid Storm and Atrial Fibrillation: A Case Report.
A thyroid storm is a rare endocrinological emergency caused by severe hyperthyroidism. Reducing circulating levels of free T3 in blood and beta-adrenergic inhibition are the basis of medical treatment for thyroid storms. Propranolol, due to its additional effect of preventing the peripheral conversion of dormant T4 to active form T3, is the chosen drug for blockade in hyperthyroidism and thyroid storm. We describe a rare clinical case of cardiovascular collapse following propranolol administration in a setting of thyroid storm. The patient presented with symptoms of dyspnea and palpitations and had an ejection fraction of 10%. He was started on a calcium channel blocker (diltiazem). Further investigations revealed that the patient also had a thyroid storm and was immediately shifted to methimazole and propranolol. However, following the administration of a beta-blocker, the patient developed circulatory failure as a result of cardiac arrest, necessitating the use of vasopressors and inotropes. This implores the need for further investigations and treatment regimens for cardiovascular conditions, especially atrial fibrillation arising in thyrotoxicosis, as there are no solid treatment guides in the literature to the best of our knowledge.


Early detection of airway obstruction by impulse oscillometry system in methacholine challenge testing in preschool children.
Small airway hyperresponsiveness is a critical aspect in preschool children with asthmatic symptoms interms of asthma control. The aim of this study was to elucidate the relationship of changes in reactance (Xrs) and resistance (Rrs) of IOS and FEV1 with those in clinical parameters and to determine which IOS parameter is correlated with bronchial hyperresponsiveness before positive clinical endpoints. We performed the methacholine challenge test in ninety-four preschool children (4.2±1.1 years) with suspected asthma. The end of test (EOT+) was defined as one or more of the following: audible wheezing (PCw+), a fall in the oxygen saturation (w92%, PCs+) or development of respiratory symptoms (PCr+). Mean changes in FEV1, Xrs5, and Rrs5 in the EOT+ group were 39.2±14.3% (95% CI 35.1-43.2%), 176.8±78.0 (95% CI 154.9-198.8) and 53.6±30.2 (45.1-62.0), respectively. The changes of Xrs5 in three EOT+ groups exceeded 80% and were lowest in PCr+(median, 95.9, IQR;73.4 to 132.4), followed by PCw+ and PCs+. However, Rrs5 did not show greater than 40% changes in PCr+. Xrs5 showed a higher correlation with changes in saturation (r=-0.578) than Rrs5 (r=-0.426). A49% decrease in Xrs5 was the optimal point for predicting a 80% change of Xrs5 at the following step. When examining the 5 step methacholine challenge test in preschoolers, the use of clinical parameters alone as an endpoint is of little value. The reactance value of 5 Hz is a useful predictive marker for bronchial hyperresponsiveness.


[Chronic prostatitis with non-neurogenic detrusor sphincter dyssynergia: diagnosis and treatment].
To investigate the features of chronic prostatitis with non-neurogenic detrusor sphincter dyssynergia (NNDSD) and the effects of pelvic floor biofeedback in the treatment of the disease. We included in this study 113 male patients, aged 15 - 48 (mean 36) years and diagnosed as having chronic prostatitis for 1 -2 (mean 1.2) years based on such typical symptoms as frequent micturition, urgent micturition, voiding pain, difficult void, etc, that lasted over 3 months, and the score > or = 1 on the first and second parts of NIH-CPSI. Urethritis, interstitial cystitis, urethral stricture and neurogenic bladder were excluded. All the patients underwent urodynamic examinations for the uroflow curve, Q(max), Pdet. max and MUCP. Biofeedback was carried out for those with non-neurogenic detrusor sphincter dyssynergia, and the effects were evaluated at 10 weeks. Twenty-one (18.6%) of the 113 cases were found to be NNDSD. Biofeedback treatment achieved obvious decreases in Q(max) (8.2 +/- 4.1), Pdet. max (125.1 +/- 75.3), MUP (124.3 +/- 23.3) and MUCP (101.5 +/- 43.6), as compared with 15.1 +/- 7.3, 86.3 +/- 54.2, 65.4 +/- 23.0 and 43.5 +/- 16.7 before the treatment (P < 0.05). Statistically significant differences were observed between pre- and post-treatment scores on voiding pain (4.0 +/- 2.0 vs 2.2 +/- 1.7), urination (7.9 +/- 2.1 vs 2.2 +/- 1.9), life impact (9.6 +/- 2.7 vs 2.9 +/- 2.6) and total scores (21.7 +/- 4.8 vs 8.4 +/- 4.6) (P < 0.05). Chronic prostatitis patients with LUTS may have NNDSD, which is urodynamically characterized by low Q(max), high intra-bladder pressure and increased urethral pressure in some patients. Urodynamic examinations may contribute to definite diagnosis and appropriate choice of treatment. Pelvic floor biofeedback has satisfactory short-term effects in the treatment of these patients.


Effect of in utero exposure to anticonvulsants on craniofacial development and growth.
It has been widely reported that some children exposed to anticonvulsants in utero have a characteristic pattern of craniofacial anomalies including a broad, low nasal bridge with a short upturned nose, wide mouth, low set ears, epicanthal folds, and ocular hypertelorism, while others show no evidence of craniofacial abnormalities. The purpose of this paper is to define the craniofacial features in nine exposed children using anthropometric measurements and frontal and lateral cephalometric radiographs. These children were identified at birth as part of a prospective study of infants exposed to anticonvulsants at the Boston Hospital for Women (now part of the Brigham and Women's Hospital). At birth, none of these infants had any major malformations; at 4 to 10 years of age, none demonstrated any growth deficiency or mental deficiency, and all external craniofacial measurements were within the normal range. However, cephalometric analyses demonstrated a pattern of reduced bony interorbital distance, maxillary size, mandibular length, cranial base and skull size, and a reduction in nose dimensions when compared to data of normal populations. This study demonstrates the inadequacy of external measurements in determining the details of underlying craniofacial architecture. The data also suggest that a subtle craniofacial change occurs in exposed children which is characterized by a decrease in bony interorbital distance and the size of the cranial base and maxilla with concomitant decreases in nose and mandibular dimensions.


[The effect of marriage migration on the genetic structure of the Taimyr Nganasan population: genealogical analysis inferred from MtDNA markers].
The marriage structure of Nganasans during the time period from 1796 to 1991 and genealogy of carriers of mitochondrial DNA haplotypes was studied in a sample of 280 individuals. It was shown that, from the beginning of its formation to the late 1970s, the population exhibited high endogamy (1976, 83.8%; 1926, 88.4%; 1976, 74.3%). The main source of traditional marriage migration (preferentially female) was populations of Entsy and, indirectly, Nentsy. Intense assimilation of Nganasans by the immigrant population, and to a lesser extent, by Dolgans, in the second half of the 20th century resulted in a reduction of endogamy index in Avam Nganasans to 42.5% by 1991. Assimilation by the immigrants was predominantly paternal, promoting preservation of the historically formed genetic diversity of the Nganasan mitochondrial gene pool. Genealogical analysis of mtDNA haplotypes showed that a relatively high total frequency of Western Eurasian mtDNA haplogroups (20.4%) in the Mongoloid (according to anthropological type) Nganasan population is explained not only by the common ethnic origin with Entsy and Nentsy, but also by direct marriage migration from the Entsy population and indirect marriage migration, from the Nentsy population. This migration led to accumulation of Entsy-Nentsy maternal lineages in the genealogy of Avam Nganasans (38.9% of the total number). Of all mtDNA haplotypes, 28.6% were introduced to Avam Nganasans by female Entsy and Nentsy, whereas the total frequency of these haplotypes was 0.204. Genetic diversity of mitochondrial DNA haplotypes was 0.935.


Role of antibiotic prophylaxis for wound infection in percutaneous endoscopic gastrostomy (PEG): result of a prospective double-blind randomized trial.
A randomized, double-blind, controlled trial was carried out to determine the value of antibiotic prophylaxis in the prevention of wound infection in percutaneous endoscopic gastrostomy (PEG) procedures. The wound was evaluated using ASEPSIS method and categorized as disturbance of healing, minor or major wound infection on the 7th day and the 28th day. The rate of infection including major wound infection was lower in the prophylaxis group of patients at both seven and 28 days.