Regional Distribution of Interstitial Cells of Cajal (ICC) in Human Stomach.
We elucidated the distribution of interstitial cells of Cajal (ICC) in human stomach, using cryosection and c-Kit immunohistochemistry to identify c-Kit positive ICC. Before c-Kit staining, we routinely used hematoxylin and eosin (HE) staining to identify every structure of human stomach, from mucosa to longitudinal muscle. HE staining revealed that the fundus greater curvature (GC) had prominent oblique muscle layer, and c-Kit immunostaining c-Kit positive ICC cells were found to have typical morphology of dense fusiform cell body with multiple processes protruding from the central cell body. In particular, we could observe dense processes and ramifications of ICC in myenteric area and longitudinal muscle layer of corpus GC. Interestingly, c-Kit positive ICC-like cells which had morphology very similar to ICC were found in gastric mucosa. We could not find any significant difference in the distribution of ICC between fundus and corpus, except for submucosa where the density of ICC was much higher in gastric fundus than corpus. Furthermore, there was no significant difference in the density of ICC between each area of fundus and corpus, except for muscularis mucosa. Finally, we also found similar distribution of ICC in normal and cancerous tissue obtained from a patient who underwent pancreotomy and gastrectomy. In conclusion, ICC was found ubiquitously in human stomach and the density of ICC was significantly lower in the muscularis mucosa of both fundus/corpus and higher in the submucosa of gastric fundus than corpus.


[Spatial characteristics of the reaction of the inferior colliculi in the cat to movement of the sound source].
The EP-series response of the inferior colliculus to clicks simulating sound source motion, reflects characteristics of this "motion" ("the motion effect", ME). ME distribution over the inferior colliculus practically coincided with the spatial distribution in cases when contralateral stimulation was more effective than the ipsilateral one. The spatial distribution in cases with no ME was identical with the distribution of cases of equal effectiveness of the contra and ipsilateral stimulations. The ME was shown to be connected with the binaural inhibitory effects and might probably be related to the activity of two main neuronal groups (the principal and multipolar ones).


Glucagon release: paradoxical stimulation by glucose during calcium deprivation.
During calsium deprivation, the rate of glucagon release by the isolated perfused rat pancreas is positively related to the glucose concentration of the perfusion medium. It is suggested that such a paradoxical behavior, which is reminiscent of the abnormality of glucagon secretion recently disclosed in diabetic subjects, results from a perturbation in the normal structural and functional bridging between pancreatic alpha and beta cells.


The importance of moral emotions for effective collaboration in culturally diverse healthcare teams.
Moral emotions shape the effectiveness of culturally diverse teams. However, these emotions, which are integral to determining ethically responsive patient care and team relationships, typically go unrecognised. The contribution of emotions to moral deliberation is subjugated within the technorational environment of healthcare decision-making. Contemporary healthcare organisations rely on a multicultural workforce charged with the ethical care of vulnerable people. Limited extant literature examines the role of moral emotions in ethical decision-making among culturally diverse healthcare teams. Moral emotions are evident in ethnocentric moral perspectives that construct some colleagues' practices as 'other'. This article examines how moral emotions are evoked when cultural dissonance influences nurses' moral perceptions. We use a qualitative investigation of teamwork within culturally diverse healthcare organisations. We use Haidt's () account of moral emotions to examine practice-based accounts of 36 internationally educated and 17 New Zealand educated nurses practising in New Zealand. The study provides evidence that moral emotions are frequently elicited by communication and care practices considered 'foreign'. The main implication is that although safe practice in healthcare organisations is reliant on highly functioning teams, collaboration is challenged by interprofessional power relations of contested culturally shaped values. We address practice-based strategies that enable engagement with moral emotions to enhance effective teamwork.


Kimura's disease--cytodiagnostic pointers: a case report.
Kimura's disease is an entity which is common in Asia with predilection for males. Earliest reports were from China. Kimura et al reported the case in detailfrom Japan 1948. Cytological diagnosis of Kimura's helps in allaying fears of malignancies in clinicians and patients. When all the cytological features are seen, this diagnosis should be borne in mind, and the differential diagnosis should be ruled out. Here we report 2 cases of Kimura's disease diagnosed on cytology and confirmed on biopsy. The etiology of Kimura's is unknown but a hypersensitivity etiology has been proposed.


The Mr 93,000 polypeptide of the postsynaptic glycine receptor complex is a peripheral membrane protein.
The glycine receptor of mammalian spinal cord is an oligomeric membrane protein that, after affinity purification on aminostrychnine-agarose or immobilized antibody, contains three polypeptides of Mr 48,000, 58,000, and 93,000. Here, the association and the properties of the polypeptides of the rat glycine receptor were investigated. Upon phase partitioning in the nonionic detergent Triton X-114, the three receptor polypeptides behaved as a hydrophilic protein complex exhibiting phospholipid binding. Sucrose gradient centrifugation or gel filtration in the presence of dithiothreitol and Triton X-100 separated the Mr 93,000 polypeptide from the Mr 48,000 and 58,000 polypeptides, which harbor the antagonist binding site of the glycine receptor. Alkaline or dimethylmaleic acid anhydride treatment of crude synaptic membrane fractions resulted in extraction of the Mr 93,000 polypeptide. Lectin binding was observed for the Mr 48,000 and 58,000 glycine receptor subunits but not the Mr 93,000 polypeptide. These results indicate that the Mr 93,000 polypeptide is a peripheral membrane protein that is located at the cytoplasmic face of the postsynaptic glycine receptor complex.


Quantitative Evaluation of the Relationship between T-Wave-Based Features and Serum Potassium Level in Real-World Clinical Practice.
Proper management of hyperkalemia that leads to fatal cardiac arrhythmia has become more important because of the increased prevalence of hyperkalemia-prone diseases. Although T-wave changes in hyperkalemia are well known, their usefulness is debatable. We evaluated how well T-wave-based features of electrocardiograms (ECGs) are correlated with estimated serum potassium levels using ECG data from real-world clinical practice. We collected ECGs from a local ECG repository (MUSE™) from 1994 to 2017 and extracted the ECG waveforms. Of about 1 million reports, 124,238 were conducted within 5 minutes before or after blood collection for serum potassium estimation. We randomly selected 500 ECGs and two evaluators measured the amplitude (T-amp) and right slope of the T-wave (T-right slope) on five lead waveforms (V3, V4, V5, V6, and II). Linear correlations of T-amp, T-right slope, and their normalized feature (T-norm) with serum potassium levels were evaluated using Pearson correlation coefficient analysis. Pearson correlation coefficients for T-wave-based features with serum potassium between the two evaluators were 0.99 for T-amp and 0.97 for T-right slope. The coefficient for the association between T-amp, T-right slope, and T-norm, and serum potassium ranged from -0.22 to 0.02. In the normal ECG subgroup (normal ECG or otherwise normal ECG), there was no correlation between T-wave-based features and serum potassium level. T-wave-based features were not correlated with serum potassium level, and their use in real clinical practice is currently limited.


The zeta potential of extended dielectrics and conductors in terms of streaming potential and streaming current measurements.
The electrical characterization of surfaces in terms of the zeta potential (ζ), i.e., the electric potential contributing to the interaction potential energy, is of major importance in a wide variety of industrial, environmental and biomedical applications in which the integration of any material with the surrounding media is initially mediated by the physico-chemical properties of its outer surface layer. Among the different existing electrokinetic techniques for obtaining ζ, streaming potential (V(str)) and streaming current (I(str)) are important when dealing with flat-extended samples. Mostly dielectric materials have been subjected to this type of analysis and only a few papers can be found in the literature regarding the electrokinetic characterization of conducting materials. Nevertheless, a standardized procedure is typically followed to calculate ζ from the measured data and, importantly, it is shown in this paper that such a procedure leads to incorrect zeta potential values when conductors are investigated. In any case, assessment of a reliable numerical value of ζ requires careful consideration of the origin of the input data and the characteristics of the experimental setup. In particular, it is shown that the cell resistance (R) typically obtained through a.c. signals (R(a.c.)), and needed for the calculations of ζ, always underestimates the zeta potential values obtained from streaming potential measurements. The consideration of R(EK), derived from the V(str)/I(str) ratio, leads to reliable values of ζ when dielectrics are investigated. For metals, the contribution of conductivity of the sample to the cell resistance provokes an underestimation of R(EK), which leads to unrealistic values of ζ. For the electrical characterization of conducting samples I(str) measurements constitute a better choice. In general, the findings gathered in this manuscript establish a measurement protocol for obtaining reliable zeta potentials of dielectrics and conductors based on the intrinsic electrokinetic behavior of both types of samples.


Ion channels and neuronal excitability in polyglutamine neurodegenerative diseases.
Polyglutamine (polyQ) diseases are a family composed of nine neurodegenerative inherited disorders (NDDs) caused by pathological expansions of cytosine-adenine-guanine (CAG) trinucleotide repeats which encode a polyQ tract in the corresponding proteins. CAG polyQ repeat expansions produce neurodegeneration via multiple downstream mechanisms; among those the neuronal activity underlying the ion channels is affected directly by specific channelopathies or indirectly by secondary dysregulation. In both cases, the altered excitability underlies to gain- or loss-of-function pathological effects. Here we summarize the repertoire of ion channels in polyQ NDDs emphasizing the biophysical features of neuronal excitability and their pathogenic role. The aim of this review is to point out the value of a deeper understanding of those functional mechanisms and processes as crucial elements for the designing and targeting of novel therapeutic avenues.


Evolutionary and genetic insights for clinical psychology.
Recent advances in genetics, and new applications of evolutionary biology, are transforming psychology and psychiatry. The purpose of this article is to review and synthesize the progress in these two areas that is most salient to the practice of clinical psychology. First, I describe how the results of genome-wide studies have elucidated the genetic architectures of psychiatric disorders. These genetic results can be applied to generate polygenic risk scores, identify rare causal mutations, evaluate gene by environment interactions, and help determine the specific causes of psychiatric disorders for each individual, all of which can help to guide therapies and treatments. Second, I explain how evolutionary theory, applied to human development, the human psyche, and mental disorders, leads to novel insights relevant to therapy. Evolutionary thinking for psychiatry and psychology is consilient with contemporary schools of thought in clinical psychology, but also provides novel, non-intuitive, and clinically-useful insights. Effects of the genome in development, and functioning of the adult psyche, are both usefully conceived as dynamical, non-linear systems, regulated by feedbacks, that can become disordered in predictable yet individualistic ways. The merging of genetic, neurological, psychological, and evolutionary approaches is set to transform clinical psychology and psychiatry, but requires increased emphasis on cross-disciplinary thinking and research.


Interpretation of left ventricular wall motion during stress testing.
This article describes the obstacles to stress echocardiographic interpretation, and reviews the techniques currently available that offer a more objective approach to stress wall motion analysis than the conventional visual methodology. These techniques include Doppler-based methods, such as myocardial Doppler velocity and strain rate imaging, as well as automated border detection techniques, such as acoustic quantification and color kinesis.


Microbial endogenous response to acute inhibitory impact of antibiotics.
Enhanced endogenous respiration was observed as the significant/main response of the aerobic microbial culture under pulse exposure to antibiotics: sulfamethoxazole, tetracycline and erythromycin. Peptone mixture and acetate were selected as organic substrates to compare the effect of complex and simple substrates. Experiments were conducted with microbial cultures acclimated to different sludge ages of 10 and 2 days, to visualize the effect of culture history. Evaluation relied on modeling of oxygen uptake rate profiles, reflecting the effect of all biochemical reactions associated with substrate utilization. Model calibration exhibited significant increase in values of endogenous respiration rate coefficient with all antibiotic doses. Enhancement of endogenous respiration was different with antibiotic type and initial dose. Results showed that both peptone mixture and acetate cultures harbored resistance genes against the tested antibiotics, which suggests that biomass spends cellular maintenance energy for activating the required antibiotic resistance mechanisms to survive, supporting higher endogenous decay rates. [Formula: see text]: maximum growth rate for XH (day-1); KS: half saturation constant for growth of XH (mg COD/L); bH: endogenous decay rate for XH (day-1); kh: maximum hydrolysis rate for SH1 (day-1); KX: hydrolysis half saturation constant for SH1(mg COD/L); khx: maximum hydrolysis rate for XS1 (day-1); KXX: hydrolysis half saturation constant for XS1 (mg COD/L); kSTO: maximum storage rate of PHA by XH (day-1); [Formula: see text]: maximum growth rate on PHA for XH (day-1); KSTO: half saturation constant for storage of PHA by XH (mg COD/L); XH1: initial active biomass (mg COD/L).


Monodisperse, submicrometer droplets via condensation of microfluidic-generated gas bubbles.
Microfluidics (MFs) can produce monodisperse droplets with precise size control. However, the synthesis of monodisperse droplets much smaller than the minimum feature size of the microfluidic device (MFD) remains challenging, thus limiting the production of submicrometer droplets. To overcome the minimum micrometer-scale droplet sizes that can be generated using typical MFDs, the droplet material is heated above its boiling point (bp), and then MFs is used to produce monodisperse micrometer-scale bubbles (MBs) that are easily formed in the size regime where standard MFDs have excellent size control. After MBs are formed, they are cooled, condensing into dramatically smaller droplets that are beyond the size limit achievable using the original MFD, with a size decrease corresponding to the density difference between the gas and liquid phases of the droplet material. Herein, it is shown experimentally that monodisperse, submicrometer droplets of predictable sizes can be condensed from a monodisperse population of MBs as generated by MFs. Using perfluoropentane (PFP) as a representative solvent due to its low bp (29.2 °C), it is demonstrated that monodisperse PFP MBs can be produced at MFD temperatures >3.6 °C above the bp of PFP over a wide range of sizes (i.e., diameters from 2 to 200 μm). Independent of initial size, the generated MBs shrink rapidly in size from about 3 to 0 °C above the bp of PFP, corresponding to a phase change from gas to liquid, after which they shrink more slowly to form fully condensed droplets with diameters 5.0 ± 0.1 times smaller than the initial size of the MBs, even in the submicrometer size regime. This new method is versatile and flexible, and may be applied to any type of low-bp solvent for the manufacture of different submicrometer droplets for which precisely controlled dimensions are required.


Exome sequencing is a useful diagnostic tool for complicated forms of hereditary spastic paraplegia.
Hereditary spastic paraplegias constitute a heterogeneous group of neurodegenerative diseases encompassing pure and complicated forms, for which at least 52 loci and 31 causative genes have been identified. Although mutations in the SPAST gene explain approximately 40% of the pure autosomal dominant forms, molecular diagnosis can be challenging for the sporadic and recessive forms, which are often complicated and clinically overlap with a broad number of movement disorders. The validity of exome sequencing as a routine diagnostic approach in the movement disorder clinic needs to be assessed. The main goal of this study was to explore the usefulness of an exome analysis for the diagnosis of a complicated form of spastic paraplegia. Whole-exome sequencing was performed in two Spanish siblings with a neurodegenerative syndrome including upper and lower motor neuron, ocular and cerebellar signs. Exome sequencing revealed that both patients carry a novel homozygous nonsense mutation in exon 15 of the SPG11 gene (c.2678G>A; p.W893X), which was not found in 584 Spanish control chromosomes. After many years of follow-up and multiple time-consuming genetic testing, we were able to diagnose these patients by making use of whole-exome sequencing, showing that this is a cost-efficient diagnostic tool for the movement disorder specialist.


Subdural hematoma in spontaneous CSF hypovolemia.
Of 67 consecutive patients with spontaneous CSF hypovolemia (SCH), 11 (16.4%) had subdural hematoma (SDH). Patients with SDH were older (p = 0.005), more likely to be male (p = 0.035), and displayed longer time to diagnosis of SCH (p = 0.019) than those without SDH. All patients with SDH showed the findings of pseudo-subarachnoid hemorrhage on CT and responded favorably to epidural blood patches and neurosurgical drainage.


Decanalization of weight and stature during childhood and adolescence.
The probabilities that children and adolescents alter their positions to non-adjacent canals (decanalization) on the current NCHS growth charts have been estimated. In this context, canals are the zones between the major percentile levels (5th, 10th, 25th, 50th, 75th, 90th, and 95th) that are shown on the charts. These probabilities were calculated for one- and 2-year intervals, beginning at each annual age from 3-16 years, using serial data for weight and stature from 329 male and 303 female participants in the Fels Longitudinal Study. The probabilities of particular types of decanalizations, categorized by the initial canal and the direction of the change in relative level (decrease/loss; increase/gain) are presented. The probabilities for 1-year intervals were very low and, therefore, they are not presented. Additionally, probabilities were calculated for transitions from the canal between the 5th and 10th percentiles to the zone below the 5th percentile and from the canal between the 90th and 95th percentiles to the zone above the 95th percentile. Both these transitions are shifts to levels that are outside the normal range, and are more common than decanalization. The probabilities of decanalization and of transitions from the normal range were generally larger for weight than for stature except for transitions from the canal between the 90th and 95th percentiles to the zone beyond the 95th percentile. The probabilities for both weight and stature tended to be larger for changes toward the medians than for changes from the medians. Decanalizations that involved increases in level were significantly related to advanced skeletal maturation at ages younger than the usual age of peak height velocity and to retarded skeletal maturation at ages older than the usual age of peak height velocity. Am. J. Hum. Biol. 10:351-359, 1998. © 1998 Wiley-Liss, Inc.


Impaired brain glucose metabolism in cirrhosis without overt hepatic encephalopathy: a retrospective 18F-FDG PET/CT study.
There are subclinical neurologic deficits in cirrhotic patients without overt hepatic encephalopathy. We aimed to use F-fluorodeoxyglucose PET/computed tomography to explore the impaired brain glucose metabolism of subclinical hepatic encephalopathy in cirrhosis. Thirty-seven patients with hepatitis B virus-related cirrhosis without overt hepatic encephalopathy and 49 controls were enrolled in the study. The patients' Model for End-Stage Liver Disease scores were calculated. All participants underwent resting state F-fluorodeoxyglucose PET/computed tomography. Between-group comparisons of brain PET/computed tomography data were conducted with two-sample t-tests and multivariate tests with Statistical Parametric Mapping 8 software. Most of the patients (30/37) had a Model for End-Stage Liver Disease score of less than 20. The patients and controls did not significantly differ in baseline characteristics, such as sex, age, plasma glucose level, smoking history or BMI, but they did significantly differ in blood uric acid level and serum levels of bilirubin, albumin, total protein, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase (P < 0.0001). Relative to brain glucose metabolism in the controls, that in the patients involved both hyper- and hypometabolic regions (P < 0.001). The relative hypometabolic regions included the parietal, occipital and limbic lobes, and the hypermetabolic regions included the hippocampus, parahippocampal gyri, right basal ganglia and circumventricular organs. Patients with cirrhosis have characteristic patterns of brain glycometabolic impairment. F-fluorodeoxyglucose PET/computed tomography may serve as a preclinical biomarker for brain damage in cirrhosis.


The hidden dragons.
Most multinational corporations are fascinated with China. Carried away by the number of potential customers and the relatively cheap labor, firms seeking a presence in China have traditionally focused on selling products, setting up manufacturing facilities, or both. But they've ignored an important development: the emergence of Chinese firms as powerful rivals--in China and also in the global market. In this article, Ming Zeng and Peter Williamson describe how Chinese companies like Haier, Legend, and Pearl River Piano have quietly managed to grab market share from older, bigger, and financially stronger rivals in Asia, Europe, and the United States. Global managers tend to offer the usual explanations for why Chinese companies don't pose a threat: They aren't big enough or profitable enough to compete overseas, the managers say, and these primarily state-owned companies are ill-financed and ill-equipped for global competition. As the government's policies about the private ownership of companies changed from forbidding the practice to encouraging it, a new breed of Chinese companies evolved. The authors outline the four types of hybrid Chinese companies that are simultaneously tackling the global market. China's national champions are using their advantages as domestic leaders to build global brands. The dedicated exporters are entering foreign markets on the strength of their economies of scale. The competitive networks have taken on world markets by bringing together small, specialized companies that operate in close proximity. And the technology upstarts are using innovations developed by China's government-owned research institutes to enter emerging sectors such as biotechnology. Zeng and Williamson identify these budding multinationals, analyze their strategies, and evaluate their weaknesses.


Nutrient profiling: the new environment.
The 2005 Dietary Guidelines for Americans (DGA) recommends that individuals choose nutrient-dense foods to help meet nutrient needs without consuming excess calories, a concept that is supported by health professionals and nutrition organizations. With an increased emphasis on nutrient density, the 2005 Dietary Guidelines Advisory Committee, in their Technical Report, called for more research to develop a valid and scientific method for defining the nutrient density of foods that can ultimately be useful on labels to help people build healthier diets [1]. Nutrient profiling is the science of ranking foods based on nutrient composition. Over the past years, numerous nutrient-profiling systems have emerged to provide guidance on improving diet quality, resulting in a heightened awareness of a need for a standardized definition of nutrient density. While nutrient-profiling systems are meant to help individuals make healthier food choices, their introduction to the marketplace leaves many unanswered questions regarding both the development of a scientific definition of nutrient density and its consumer application. The goal of this article is to review the roles of nutrient density and nutrient profiling in providing consumer guidance. Specifically, this review will summarize the current nutrition environment and address the need for future research around nutrient-profiling systems as a means to define nutrient density.


Benign fibrous histiocytoma of bone: a case report.
Benign fibrous histiocytoma (BFH) occurs commonly in soft tissues with very few cases of BFH of bone on record. We report a case of BFH of tibia in fifty year old male who presented with supracondylar fracture femur due to trivial fall and a brief review of literature.


Diterpenoids with thioredoxin reductase inhibitory activities from Jatropha multifida.
Chemical investigation of the Jatropha multifida has led to the isolation of nine diterpenoids (1-9), including a new jatromulone A, four podocarpane diterpenoids (2-5), two lathyrane-type diterpenoids (6 and 7) and two dinorditerpenoids (8 and 9). Their structures were elucidated by spectroscopic analysis, and the absolute configurations of 1 were determined by CD analysis. All of the diterpenoids were screened for inhibitory activity against thioredoxin reductase (TrxR), which is a potential target for cancer chemotherapy with redox balance and antioxidant functions. Compounds 6 and 7 exhibited stronger activity (IC50: 23.4 and 10.6 μM, respectively) than the positive control, curcumin (IC50 = 25.0 μM). Compounds 2-9 were isolated from J. multifida for the first time.


[HOMA-IR and related clinical parameters].
Metabolic syndrome (MS) is based on visceral obesity and insulin resistance (IR) and, shows abnormalities in fat and glucose metabolism as well as hypertension. We investigated the relationship between IR and various risk factors for atherosclerosis in 378 male subjects (averaged age: 63.8 +/- 15.2 years) and 509 female subjects (averaged age: 67.1 +/- 13.5 years) recruited from a health check examination. Homeostasis model assessment (HOMA-IR) was used as an indicator of IR. Body mass index (BMI), triglyceride (TG), remnant-like particle cholesterol (RLP-C) and C-reactive protein (CRP) showed a good correlation (r > 0.2) with HOMA-IR. LDL cholesterol(LDL-C), small dense LDL(sdLDL) and HbA1c showed less stringent (r < 0.2) but still significant correlation with HOMA-IR. In contrast, oxidized LDL (oxLDL) and systolic blood pressure did not show any correlation. A multiple regression analysis indicated that BMI, RLP-C, HDL-C, HbA1c and CRP were independently correlated with HOMA-IR. These observations suggested that, among the three new lipid parameters (i.e., RLP-C, sdLDL and oxLDL), RLP-C was the most closely related to the IR status.


Complex Multiplanar Fracture of the Distal Femur with an Undescribed Pattern: A Case Report and Review of the Literature.
Distal femur fractures in younger age groups are associated with high-impact injury leading to severe comminution and soft tissue injuries. Most of the intra-articular distal femur fractures occur as a result of axial loading accompanied by a variable amount of flexion. An 18-year-old male patient who had met with a road traffic accident was brought to the trauma center. Radiographic examination revealed a fracture of the distal femur, predominantly involving the lateral condyle without any evidence of metaphyseal comminution, and lateral view showed a complete separation of both the condyles from the proximal shaft. This type of fracture pattern did not fit into any of the current classification systems of distal femoral fractures. The medial and lateral approaches were carried out simultaneously instead of the anterior midline approach, owing to the poor skin condition over the anterior aspect of the knee. These fractures are difficult to treat due to high articular involvement and present a tedious task for the surgeon. Anatomical reduction with preserved articular cartilage is the key to a good outcome in such complex fractures. Atypical fracture types are not uncommon, and they can be incorporated into existing or future classification systems, which may contribute to a better understanding and management of these fractures.


Protein phosphatase 1 binds to the RNA recognition motif of several splicing factors and regulates alternative pre-mRNA processing.
Alternative splicing emerges as one of the most important mechanisms to generate transcript diversity. It is regulated by the formation of protein complexes on pre-mRNA. We demonstrate that protein phosphatase 1 (PP1) binds to the splicing factor transformer2-beta1 (tra2-beta1) via a phylogenetically conserved RVDF sequence located on the RNA recognition motif (RRM) of tra2-beta1. PP1 binds directly to tra2-beta1 and dephosphorylates it, which regulates the interaction between tra2-beta1 and other proteins. Eight other proteins, including SF2/ASF and SRp30c, contain an evolutionary conserved PP1 docking motif in the beta-4 strand of their RRMs indicating that binding to PP1 is a new function of some RRMs. Reducing PP1 activity promotes usage of numerous alternative exons, demonstrating a role of PP1 activity in splice site selection. PP1 inhibition promotes inclusion of the survival of motoneuron 2 exon 7 in a mouse model expressing the human gene. This suggests that reducing PP1 activity could be a new therapeutic principle to treat spinal muscular atrophy and other diseases caused by missplicing events. Our data indicate that the binding of PP1 to evolutionary conserved motifs in several RRMs is the link between known signal transduction pathways regulating PP1 activity and pre-mRNA processing.


Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia.
Aging of immune organs, termed as immunosenescence, is suspected to promote systemic inflammation and age-associated disease. The cause of immunosenescence and how it promotes disease, however, has remained unclear. We report that the Drosophila fat body, a major immune organ, undergoes immunosenescence and mounts strong systemic inflammation that leads to deregulation of immune deficiency (IMD) signaling in the midgut of old animals. Inflamed old fat bodies secrete circulating peptidoglycan recognition proteins that repress IMD activity in the midgut, thereby promoting gut hyperplasia. Further, fat body immunosenecence is caused by age-associated lamin-B reduction specifically in fat body cells, which then contributes to heterochromatin loss and derepression of genes involved in immune responses. As lamin-associated heterochromatin domains are enriched for genes involved in immune response in both Drosophila and mammalian cells, our findings may provide insights into the cause and consequence of immunosenescence during mammalian aging. PAPERFLICK:


Everolimus eluting bioresorbable vascular scaffolds; can we absorb the risk in complex PCI?
BVS, as compared with DES, have higher stent thrombosis (ST) rates. BVS may prove reasonable in patients with complex anatomy. Future trials will be necessary to guide clinicians regarding whether BVS are equivalent to DES in patients with noncomplex or complex coronary anatomy.


Concurrent midurethral sling excision or lysis at the time of repeat sling for treatment of recurrent or persistent stress urinary incontinence.
Limited evidence guides operative technique in primary midurethral sling (MUS) lysis or excision at the time of repeat sling placement for persistent or recurrent stress urinary incontinence (SUI). Our objective is to compare subjective improvement in patients undergoing repeat MUS placement with and without concurrent primary sling lysis or removal. This was a retrospective cohort study with a prospective survey of patients who underwent two MUS placements for SUI at a single institution from January 1996 to December 2015. After patient identification, the electronic record was queried for demographic and perioperative data. Subjects then completed the Urogenital Distress Index, (UDI-6), Incontinence Severity Index (ISI), and the Incontinence Impact Questionnaire (IIQ-7). Subjects were also asked if they would choose to undergo repeat MUS surgery again. Sixty-one patients were included. 17 out of 61 (28%) underwent concomitant primary sling lysis or excision, and 44 out of 61 (72%) did not. Fifty-seven percent (n = 35) completed the survey. Of the respondents, the median ISI score was 4 (1-8), with no difference between groups; 14 out of 35 (40%) reported the presence of bothersome urge incontinence, 11 out of 35 (31%) reported bothersome stress urinary incontinence, and 8 out of 35 (23%) reported symptoms of voiding dysfunction, with no difference between groups. 57% of patients (20 out of 35) would undergo repeat MUS placement again. In a small cohort, concurrent excision of the primary sling at the time of repeat MUS did not improve subjective outcomes. Many patients reported urinary urgency and voiding symptoms, and only about half of patients would choose to undergo the surgery again if given the choice.


A Qualitative Study of Knowledge, Attitude and Practice towards Pharmacovigilance among Doctors and Nursing Staff in a Tertiary Care Hospital in India.
Pharmacovigilance is the branch of science that deals with the detection, assessment, understanding and prevention of adverse reactions to medicines (i.e., adverse drug reactions or ADRs). The purpose of pharmacovigilance is to implement the safe and rational use of medicines, which ultimately helps in improving patient care. To investigate the Knowledge, Attitude And Practice (KAP) of clinicians, residents and nursing staff towards pharmacovigilance and Adverse Drug Events (ADE) reporting and to identify possible reasons for underreporting and to receive suggestions to improve the ADE reporting. This was a qualitative study, conducted at Shree Krishna Hospital, attached to Pramukhswami Medical Collage, Karamsad, Gujarat, India. 'Focused Group Discussions' were organized which consisted of 5-10 clinicians and residents of the same departments and 10-15 nursing staff members. Their KAP regarding ADE reporting were assessed by using a structured open ended questionnaire. Data were analysed with qualitative methods. Total six sessions of Focused group discussion were conducted consisting of 42 clinicians and residents (16 were faculty members and 26 were residents) and seven sessions of Focused group discussion were conducted, consisting of 89 nursing staff members. Most of the participants knew the meaning of ADR and importance of ADR reporting. They all agreed that it's their responsibility also to report ADE. Some of the participants admitted, forgetfulness and workload as major constraints. There was a suggestion of display phone number of department of Pharmacology for coordination and maintaining a separate register for ADEs in each ward. In spite of awareness and willingness for reporting of ADEs amongst the clinicians and residents, the practice is lacking because they do not consider this work as their priority.


Close to home. Interview by Terese Hudson.
The hospital is an integral part of the community, according to James May, CEO and president of Legacy Portland (OR) Hospitals. May has put this principle to work concretely by loaning employees money for initial costs on homes near Emanuel Hospital and Health Center in northeast Portland. Now in its second year, the program has already helped 25 employees purchase homes in a 19-square-mile area targeted for redevelopment. Loans of up to $5,000 for homes with a purchase price of $65,000 or lower are available. The loans can be used for down payments, pre-paid reserves or closing costs. Legacy forgives 20 percent of a loan's outstanding balance each year to employees in good standing. This encourages employees to stay for at least five years. Only the interest payments on the outstanding balance are paid back to Legacy. May spoke recently with Senior Editor Terese Hudson about the program's genesis.


Diabetes Self-Care Activities and Their Relationship With Glycemic Control in Patients Visiting Hayatabad Medical Complex, Peshawar.
Background A significant portion of the Pakistani population is affected by diabetes, which has emerged as a global healthcare concern. Objective This study aimed to assess the correlation between glycemic control in diabetes patients and their engagement in diabetes self-care activities (DSCA). Methodology Cross-sectional research was conducted at Hayatabad Medical Complex in Peshawar between June 2019 and May 2020. A total of 280 carefully selected patients with type 2 diabetes mellitus (T2DM) were included. Data collection involved an interviewer-administered questionnaire encompassing sociodemographic information, diabetes-related data, and the summary of the Diabetes Self-Care Activities (SDSCA) scale. Descriptive statistics and Pearson's chi-square test were employed for data analysis. Results The study observed that the majority of participants (40.36%) were females, and the age range of the participants was between 42 and 53 years (68.22%). According to the study, 55.00% of participants had a normal body mass index (BMI), and 71.08% of participants had diabetes in their family. Regarding glycemic control, 55.71% of individuals exhibited good control based on fasting blood sugar (FBS) levels while 74.64% showed poor control according to hemoglobin A1C (HbA1c) values. HbA1c was substantially linked with a general diet (healthy eating plan), physical activities, and adherence to medication ((odds ratios (OR): 3.12), (95% confidence interval (CI): 1.02 - 8.78), (P value: 0.031)); ((OR: 2.19, 95%), (CI:1.18 - 3.79), (P value: 0.003)); ((OR: 2.85), (95% CI: 1.22 - 6.59), P value: 0.021)). Conclusion The findings indicated that health professionals need to create health education programs on DSCA in order to increase DSCA adherence in people with T2DM while maintaining glycemic control.


Hunting for glueballs in electron-positron annihilation.
We calculate the cross section for the exclusive production of J(PC)=0(++) glueballs G0 in association with the J/psi in e(+)e(-) annihilation using the perturbative QCD factorization formalism. The required long-distance matrix element for the glueball is bounded by CUSB data from a search for resonances in radiative Upsilon decay. The cross section for e(+)e(-)-->J/psi+G0 at sqrt[s]=10.6 GeV is similar to exclusive charmonium-pair production e(+)e(-)-->J/psi+h for h=eta(c) and chi(c0), and is larger by a factor of 2 than that for h=eta(c)(2S). As the subprocesses gamma(*)-->(cc)(cc) and gamma(*)-->(cc)(gg) are of the same nominal order in perturbative QCD, it is possible that some portion of the anomalously large signal observed by Belle in e(+)e(-)-->J/psiX may actually be due to the production of charmonium-glueball J/psiG(J) pairs.


Tumor cell prothrombotic properties.
Thrombin generation and fibrin formation are constantly determined in patients with malignancy, who are at increased risk of thromboembolic complications. Most importantly, fibrin formation is also involved in the processes of tumor spread and metastasis. Activation of blood coagulation in cancer is a complex phenomenon, involving many different pathways of the hemostatic system and numerous interactions of the tumor cell with other blood cells, including platelet, monocyte and endothelial cell. Tumor cells possess the capacity to interact with all parts of the hemostatic system. They can directly activate the coagulation cascade by producing their own procoagulant factors or they can stimulate the prothrombotic properties of other blood cell components. All of the mechanisms are not entirely understood, however research studies in the last ten years have greatly improved our knowledge of tumor-promoted pro-thrombotic functions.


CAT administration of language placement examinations.
This article describes the development of a computerized adaptive test for Cegep de Jonquiere, a community college located in Quebec, Canada. Computerized language proficiency testing allows the simultaneous presentation of sound stimuli as the question is being presented to the test-taker. With a properly calibrated bank of items, the language proficiency test can be offered in an adaptive framework. By adapting the test to the test-taker's level of ability, an assessment can be made with significantly fewer items. We also describe our initial attempt to detect instances in which "cheating low" is occurring. In the "cheating low" situation, test-takers deliberately answer questions incorrectly, questions that they are fully capable of answering correctly had they been taking the test honestly.


Pituitary Adenoma Apoplexy in an Adolescent: A Case Report and Review of the Literature.
We present a 13-year-old boy who was admitted with complaints of a state of progressive sleepiness and a sudden headache with vomiting and fever. Laboratory testing showed hypoglycemia, multiple pituitary hormonal deficiencies, and an elevated C-reactive protein level. A cranial magnetic resonance imaging (MRI) showed an opaque sphenoid sinus and an intrasellar mass suggesting hemorrhage, so that we suspected pituitary apoplexy (PA) originating from a non-functioning adenoma, although a pituitary abscess could not completely be excluded. The boy was treated with antibiotics, hydrocortisone, and levothyroxine. Due to his rapid clinical improvement, no surgery was performed and we considered the diagnosis of PA as confirmed. At follow-up, the MRI scan showed a small residual lesion. Pituitary deficiencies of growth hormone, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, and vasopressin persisted. A literature search of all well-documented cases of PA in children or adolescents (n=30, 13 boys and 17 girls) indicated that this condition is rare below 20 years of age but must be considered when a patient experiences headache with or without visual disturbances, even in the presence of clinical and laboratory signals suggestive of pituitary abscess. MRI neuroimaging is helpful in the differential diagnosis. In both conditions, the possibility of ACTH deficiency should always be considered, investigated, and treated. In cases without severe neuro-ophthalmological deficits and/or with a rapid and positive response to acute medical management, one can abstain from surgical treatment.


Perceived Effectiveness of Differing Health Warning Label Messaging Strategies among Adults in the Republic of Georgia: One Size Does Not Fit All.
Background: While pictorial health warning labels (HWLs) are evidence-based, the different messaging strategies are understudied. Methods: We analyzed 2014 national survey data from 1163 Georgian adults to examine: (1) perceived effectiveness of pictorial vs. text-only HWLs; (2) pictorial HWL themes; and (3) correlates of perceived effectiveness of different pictorial themes. Participants were randomized to evaluate the effectiveness of either Set A or Set B of HWLs (each contained half pictorial, half text-only). Results: All but 2 pictorial HWLs were perceived as more effective than text-only. Factor analyses identified one factor among Set A ("benign") and two in Set B pictorial HWLs ("benign", "gruesome"). Among Set A pictorial HWLs, correlates of greater perceived effectiveness included being female, rural residence, not having children, and nonsmoker status. Among smokers, correlates included being female and unmarried, fewer smoking friends, and higher quitting importance. Among Set B, 43.8% rated gruesome pictorial HWLs more effective, 12.9% benign more effective, and 43.4% equally effective. Correlates of perceiving benign more effective included fewer smoking friends and higher income. Among smokers, lower income predicted gruesome being perceived as more effective; fewer smoking friends and higher quitting importance predicted perceiving benign as more effective. Conclusion: A variety of pictorial HWL strategies should be used.


Emerging Two-Dimensional Nanomaterials for Electrocatalysis.
Over the past few decades, the design and development of advanced electrocatalysts for efficient energy conversion technologies have been subjects of extensive study. With the discovery of graphene, two-dimensional (2D) nanomaterials have emerged as some of the most promising candidates for heterogeneous electrocatalysts due to their unique physical, chemical, and electronic properties. Here, we review 2D-nanomaterial-based electrocatalysts for selected electrocatalytic processes. We first discuss the unique advances in 2D electrocatalysts based on different compositions and functions followed by specific design principles. Following this overview, we discuss various 2D electrocatalysts for electrocatalytic processes involved in the water cycle, carbon cycle, and nitrogen cycle from their fundamental conception to their functional application. We place a significant emphasis on different engineering strategies for 2D nanomaterials and the influence these strategies have on intrinsic material performance, such as electronic properties and adsorption energetics. Finally, we feature the opportunities and challenges ahead for 2D nanomaterials as efficient electrocatalysts. By considering theoretical calculations, surface characterization, and electrochemical tests, we describe the fundamental relationships between electronic structure, adsorption energy, and apparent activity for a wide variety of 2D electrocatalysts with the goal of providing a better understanding of these emerging nanomaterials at the atomic level.


Role of superoxide dismutase in otitis media with effusion.
The concentration of superoxide dismutase (SOD) in middle ear effusion (MEE) was measured by the electron spin resonance trapping method in order to clarify the role of SOD in otitis media with effusion (OME) in children. The SOD levels in mucoid MEEs were significantly higher than those in serous and purulent MEEs. There was no significant difference in the levels of SOD between neutrophil-dominant MEEs and mononuclear cell-dominant MEEs, and the levels were negatively correlated with the number of neutrophils in the MEEs. Moreover, the levels were significantly increased in patients having recurrence of MEE within 3 months compared with patients without recurrence of MEE. Although it is known that SOD plays an important role in protecting the host from oxygen radicals, the findings in this study suggest that SOD might be related to the chronicity of OME.


Mechanisms of brief contact interventions in clinical populations: a systematic review.
Brief Contact Interventions (BCIs) have been of increasing interest to suicide prevention clinicians, researchers and policy makers. However, there has been no systematic assessment into the mechanisms underpinning BCIs. The aim of the current paper is to provide a systematic review of the proposed mechanisms underpinning BCIs across trial studies. A systematic review was conducted of trials using BCIs (post-discharge telephone contacts; emergency or crisis cards; and postcard or letter contacts) for suicide or self-harm. Following PRISMA guidelines, we searched CENTRAL, MEDLINE, EMBASE, and the reference lists of all past reviews in the area. Secondary searches of reference lists were undertaken. Sixteen papers provided a description of possible mechanisms which we grouped into three main areas: social support; suicide prevention literacy, and; learning alternative coping behaviours. After assessment of the studies and considering the plausibility of mechanisms, we suggest social support and improved suicide prevention literacy are the most likely mechanisms underpinning BCIs. Researchers need to better articulate and measure the mechanisms they believe underpin BCIs in trial studies. Understanding more about the mechanisms of BCIs' will inform the development of future interventions for self-harm and suicide.


10-year follow-up after standardised treatment for Achilles tendinopathy.
Achilles tendinopathy is a common and often long-lasting injury. We present a 10-year follow-up on a pragmatic study on Achilles tendinopathy treated with controlled exercises supplemented with corticosteroid injections if necessary in order to continue training. All patients who completed the original study (n=93) were invited for a 10-year follow-up. 83% participated. Patients were evaluated with ultrasound scanning (n=58) and with a questionnaire (n=77) using the same outcome measures as in the primary study. The 10-year overall outcome on a 4-point scale (excellent, good, fair, poor), other treatments and adverse event and present activity level were recorded. Excellent outcome was reported in 63% and good outcome in 27%. 76% reported an activity level at 75%-100% of preinjury level. The average Victorian Institute of Sports Assessment-Achilles score for all patients was 84 (SD 19). 16% had surgery. Three ruptures occurred 5-8 years after the primary study. The improvement from entry to 6 months in the primary study was maintained until 10-year follow-up. Insertional tendinopathy did not differ from mid-substance tendinopathy in any outcome measure (short term and long term). We encountered no prognostic markers on ultrasound for the long-term outcome; however, present heterogeneity and increased flow resemble present pain. Thickened tendons seem to maintain their thickness despite improvement of symptoms. One to two corticosteroid injections are a safe and effective supplement to controlled exercises in the treatment of Achilles tendon pain with no signs of deterioration in the very long term. Mid-substance and insertional tendinopathies benefit equally from this treatment.


A bank of protein family patterns for rapid identification of possible functions of amino acid sequences.
A method and software tool to develop patterns of protein families has been designed. These patterns are intended for the identification of local similarities in arbitrary amino acid sequences with proteins of the SWISS-PROT bank. The method is based on the physical, chemical and structural properties of amino acids. It assembles a 'best set' of elements (a pattern) for a given group of aligned related proteins. These elements provide discrimination between proteins of a family and representatives of other families or random sequences. The method combines the advantages of BLOCKS (automatic generation of multiple elements for protein groups), PROSITE (simplicity of element presentation) and matrices/profiles (different distinctions between amino acids for different positions of aligned sequences). Using our method, a data bank of protein family patterns, PROF_PAT, is produced. This data bank is based on the 27,752 amino acid sequences of SWISS-PROT bank release 24. The characteristics of patterns of 743 related protein groups are described. The results of comparisons of PROF_PAT patterns with the proteins of the SWISS-PROT bank are discussed.


Regulation of store-operated Ca2+ entry by IP3 receptors independent of their ability to release Ca2.
Loss of endoplasmic reticular (ER) Ca2+ activates store-operated Ca2+ entry (SOCE) by causing the ER localized Ca2+ sensor STIM to unfurl domains that activate Orai channels in the plasma membrane at membrane contact sites (MCS). Here, we demonstrate a novel mechanism by which the inositol 1,4,5 trisphosphate receptor (IP3R), an ER-localized IP3-gated Ca2+ channel, regulates neuronal SOCE. In human neurons, SOCE evoked by pharmacological depletion of ER-Ca2+ is attenuated by loss of IP3Rs, and restored by expression of IP3Rs even when they cannot release Ca2+, but only if the IP3Rs can bind IP3. Imaging studies demonstrate that IP3Rs enhance association of STIM1 with Orai1 in neuronal cells with empty stores; this requires an IP3-binding site, but not a pore. Convergent regulation by IP3Rs, may tune neuronal SOCE to respond selectively to receptors that generate IP3.


Biosynthesis and Characterization of Zinc Oxide Nanoparticles and Their Impact on the Composition of Gut Microbiota in Healthy and Attention-Deficit Hyperactivity Disorder Children.
Attention-deficit hyperactivity disorder (ADHD) seriously affects children's health, and the gut microbiome has been widely hypothesized to play a role in the regulation of ADHD behavior. The present study aims to the biosynthesize of zinc oxide nanoparticles (ZnONPs) by using Acinetobacter johnsonii strain RTN1, followed by their characterization through state-of-the-art material characterization techniques, viz., UV-vis spectroscopy, Fourier transform infrared spectroscopy, and transmission and scanning electron microscopic analyses with energy dispersive spectrometry. Moreover, we investigated and compared the population composition of gut microbiota and their susceptibility to biogenic ZnONPs between healthy and ADHD children based on the traditional plate method and 16S rRNA amplicon sequence analysis. The antibacterial effect of ZnONPs against gut bacteria was also determined by measurement of live cell number, living/dead bacterial staining test, and flow cytometry observation. The present study revealed that the number of live gut bacteria in healthy children was more than 10-fold higher than that in ADHD children; however, the community structure of gut bacteria has changed, while greater diversity was found in gut bacteria from ADHD children. In addition, we found that the number of live gut bacteria in healthy and ADHD children was reduced by ZnONPs, which shows an increased and reduced effect in composition of gut bacteria from healthy and ADHD children, respectively. It was also noted that the main mechanism of ZnONPs may be to inhibit the growth of gut bacteria rather than to kill them, while the nanoparticle-resistant strains in healthy children is also different from that in ADHD children. Some representative bacteria, in particular nanoparticle-resistant bacteria, were successfully isolated and identified. Overall, this study revealed the potential correlation of ADHD with gut bacteria and provided a new possibility to prevent ADHD by the combination of nanoparticle and its resistant bacteria.


[Research progress of stenosing tenosynovitis of radial styloid process based on anatomical structure].
Stenosing tenosynovitis of styloid process of radius(de Quervain's disease) which abductor pollicis longus and extensor pollicis brevis in the first extensor chamber are affected by resistance when sliding, the incidence is affected by anatomical variations. Symptoms, signs and auxiliary examinations can diagnose the disease. Slight dQS can be improved by rest, brace, restriction activities, and oral medications. Chinese medicine and physiotherapy also reduce the disease. Needle knife therapy is a Traditional Chinese medicine minimally invasive surgery, which is also a step-by-step treatment between conservative treatment and open surgery to loosening the compression of the first extensor chamber. Steroid injection is a more common treatment in this disease, and its efficacy is related to the accuracy of the injection and is affected by the severity of the patient's anatomical variation. Identifying the spacing within the first extensor chamber under ultrasound can help patients better choose conservative or surgical treatment. Surgical treatment can more completely change the condition of dQD from anatomical structure, and clinical should pay attention to the choice of surgical procedure to improve the efficacy and reduce the occurrence of surgical complications. This article discusses the pathogenesis, diagnosis and treatment of the disease from the perspective of anatomical structure. It mainly analyzes the therapeutic targets and the clinical application, which aims to provide reference for the diagnosis and treatment of de Quervain disease.


Twin studies advance the understanding of gene-environment interplay in human nutrigenomics.
Investigations into the genetic architecture of diet-disease relationships are particularly relevant today with the global epidemic of obesity and chronic disease. Twin studies have demonstrated that genetic makeup plays a significant role in a multitude of dietary phenotypes such as energy and macronutrient intakes, dietary patterns, and specific food group intakes. Besides estimating heritability of dietary assessment, twins provide a naturally unique, case-control experiment. Due to their shared upbringing, matched genes and sex (in the case of monozygotic (MZ) twin pairs), and age, twins provide many advantages over classic epidemiological approaches. Future genetic epidemiological studies could benefit from the twin approach particularly where defining what is 'normal' is problematic due to the high inter-individual variability underlying metabolism. Here, we discuss the use of twins to generate heritability estimates of food intake phenotypes. We then highlight the value of discordant MZ pairs to further nutrition research through discovery and validation of biomarkers of intake and health status in collaboration with cutting-edge omics technologies.


Solitary Oxygen Dopant Emission from Carbon Nanotubes Modified by Dielectric Metasurfaces.
All-dielectric metasurfaces made from arrays of high index nanoresonators supporting strong magnetic dipole modes have emerged as a low-loss alternative to plasmonic metasurfaces. Here we use oxygen-doped single-walled carbon nanotubes (SWCNTs) as quantum emitters and couple them to silicon metasurfaces to study effects of the magnetic dipole modes of the constituent nanoresonators on the photoluminescence (PL) of individual SWCNTs. We find that when in resonance, the magnetic mode of the silicon nanoresonators can lead to a moderate average PL enhancement of 0.8-4.0 of the SWCNTs, accompanied by an average increase in the radiative decay rate by a factor of 1.5-3.0. More interestingly, single dopant polarization experiments show an anomalous photoluminescence polarization rotation by coupling individual SWCNTs to silicon nanoresonators. Numerical simulations indicate that this is caused by modification of near-field polarization distribution at certain areas in the proximity of the silicon nanoresonators at the excitation wavelength, thus presenting an approach to control emission polarization. These findings indicate silicon nanoresonators as potential building blocks of quantum photonic circuits capable of manipulating PL intensity and polarization of single photon sources.


Growth-supporting activities of fibronectin on hematopoietic stem/progenitor cells in vitro and in vivo: structural requirement for fibronectin activities of CS1 and cell-binding domains.
Fibronectin (FN) is supposed to play important roles in various aspects of hematopoiesis through binding to very late antigen 4 (VLA4) and VLA5. However, effects of FN on hematopoietic stem cells are largely unknown. In an effort to determine if FN had a growth-supporting activity on hematopoietic stem cells, human CD34(+)/VLA4(bright)/VLA5(dull) hematopoietic stem cells and a murine stem cell factor (SCF)-dependent multipotent cell line, EML-C1, were treated with or without FN in a serum and growth-factor-deprived medium, and then subjected to clonogenic assay in the presence of hematopoietic growth factors. The pretreatment of the CD34(+) cells with FN gave rise to significantly increased numbers of granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst colony-forming units, and mixed erythroid-myeloid colony-forming units. In addition, the numbers of blast colony-forming units and CFU-GM that developed after culture of EML-C1 cells with SCF and the combination of SCF and interleukin-3, respectively, were augmented by the pretreatment with FN. The augmented colony formation by FN was completely abrogated by the addition of CS1 fragment, but not of GRGDSP peptide, suggesting an essential role of FN-VLA4 interaction in the FN effects. Furthermore, the effects of various FN fragments consisting of RGDS-containing cell-binding domain (CBD), heparin-binding domain (HBD), and/or CS1 portion were tested on clonogenic growth of CD34(+) cells. Increased colony formation was induced by CBD-CS1 and CBD-HBD-CS1 fragments, but not with other fragments lacking CBD or CS1 domains, suggesting that both CS1 and CBD of FN were required for the augmentation of clonogenic growth of hematopoietic stem/progenitor cells in vitro. In addition to the in vitro effects, the in vivo administration of CBD-CS1 fragment into mice was found to increase the numbers of hematopoietic progenitor cells in bone marrow and spleen in a dose-dependent manner. Thus, FN may function on hematopoietic stem/progenitor cells as a growth-supporting factor in vitro and in vivo.


Effects of digitalis on the exercise electrocardiogram in normal adult subjects.
Controversy continues regarding the effects of administration of digitalis upon the exercise electrocardiogram. Thus, maximal treadmill exercise tests were performed before and two weeks after administration of 0.25 mg of digoxin daily in 15 normal subjects (documented by cardiac catheterization and coronary arteriographic studies). Administration of digitalis induced abnormal findings on exercise tests in all 14 subjects with serum levels of digoxin greater than or equal to 0.5 ng/ml; however, at workloads greater than 75 to 90 percent of maximal predicted heart rate, the changes in the ST segment reverted to a normal configuration in all subjects, thereby providing differentiation of digitalis-induced ST-segment alterations from those due to myocardial ischemia at maximal treadmill stress.


Dermatofibrosarcoma Protuberans of Lumbar Region with Metastasis to Lung: A Rare Presentation.
Dermatofibrosarcoma protuberans (DFSP) is a cutaneous slow growing soft tissue sarcoma associated with a high local recurrence rate. Common site of presentation is trunk followed by proximal extremity and head and neck region. A case of recurrent DFSP of left lumbar region with metastasis in lung in a 50-year-old woman presented here. Absence of symptoms often leads to a delay in diagnosis. DFSP is often mistaken for other skin conditions, particularly in its early stages.


Oxaliplatin, an anticancer agent that affects both Na+ and K+ channels in frog peripheral myelinated axons.
The use of oxaliplatin, a relatively new chemotherapeutic agent, is somewhat limited since it produces a specific peripheral neuropathy regarding other neurotoxic anticancer platinum analogues. In order to investigate the mechanism of such a peripheral neuropathy, the effects of 1-100 micromol/l oxaliplatin were assessed on the nodal ionic currents of single frog myelinated axons as a model of peripheral excitable membranes. Oxaliplatin decreased both Na(+) and K(+) currents in a dose-dependent manner and within 5-10 min, without producing any marked changes in the current kinetics. It was about three to eight times more effective in reducing the Na(+) than the K(+) current. In addition, it shifted the voltage-dependence of both Na(+) and K(+) conductances towards negative membrane potentials. A negative shift in the steady-state inactivation-voltage curve of the peak Na(+) current was also observed in the presence of oxaliplatin. These effects were not reversed by washing the myelinated axons with an oxaliplatin-free solution for at least 30 min. It is concluded that oxaliplatin modifies the voltage-dependent ionic channels mainly by altering the external surface membrane potential. The knowledge of such a mechanism may help to counteract the neurotoxic action of this anticancer agent.


4,4'Dimethoxychalcone: a natural flavonoid that promotes health through autophagy-dependent and -independent effects.
The age-induced deterioration of the organism results in detrimental and ultimately lethal pathologies. The process of aging itself involves a plethora of different mechanisms that should be subverted concurrently to delay and/or prevent age-related maladies. We have identified a natural compound, 4,4'-dimethoxychalcone (DMC), which promotes longevity in yeast, worms and flies, and protects mice from heart injury and liver toxicity. Interestingly, both the DMC-mediated lifespan extension and the cardioprotection depend on macroautophagy/autophagy whereas hepatoprotection does not. DMC induces autophagy by inhibiting specific GATA transcription factors (TFs), independently of the TORC1 kinase pathway. The autophagy-independent beneficial effects of DMC might involve its antioxidative properties. DMC treatment results in a phylogenetically conserved, systemic impact on the metabolome, which is most prominently characterized by changes in cellular amino acid composition. Altogether, DMC exerts multiple, geroprotective effects by igniting distinct pathways, and thus represents a potential pharmacological agent that delays aging through multipronged effects.


Adherence to a healthy Nordic food index and risk of myocardial infarction in middle-aged Danes: the diet, cancer and health cohort study.
For decades, the Mediterranean diet has been in focus regarding healthy eating as it has been associated with reduced risk of non-communicable diseases. Less interest has been given to health benefits of other regional diets. The aim of the present study was to assess whether adherence to a healthy Nordic food index was associated with lower risk of myocardial infarction (MI) among middle-aged Danes. Data were obtained from the Danish Diet, Cancer and Health cohort study of 57 053 men and women aged 50-64 years recruited between 1993 and 1997. The healthy Nordic food index comprised healthy Nordic food items selected a priori (fish, cabbage, rye bread, oatmeal, apple and pears and root vegetables). Information on incident MI was ascertained through linkage with national registries. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated from sex-specific Cox proportional hazard models. In total, 1669 men and 653 women developed MI during follow-up (13.6 median years). In adjusted models, those with an index score of 5-6 points (highest scores) had significantly lower MI risk (men: HR=0.77, 95% CI=0.62, 0.97; women: HR=0.55, 95% CI=0.37, 0.82) relative to those scoring 0 points in the index (lowest score). A significantly lower MI risk was found per 1-point increment in the index in both men (HR=0.95, 95% CI=0.92, 0.99) and women (HR=0.93, 95% CI=0.88, 0.98). A healthy Nordic diet is associated with lower MI risk among middle-aged Danes, suggesting that Nordic diets should be considered in recommendations for dietary changes in the promotion of coronary health.


[Propensity-score-matched Comparison of Postoperative Pain Between Young and Elderly Patients Who Underwent Video-assisted Thoracoscopic Surgery for Spontaneous Pneumothorax].
Video-assisted thoracoscopic surgery (VATS) is the standard treatment for spontaneous pneumothorax(SP). Although VATS has decreased the postoperative pain in comparison with conventional thoracotomy, the procedure still often requires sufficient postoperative pain management especially for young patients, and the present study on the postoperative pain management focused on the age difference was designed. Using the numerical rating scale, we compared postoperative pain between the young group(36 patients) and the elderly group (36 patients) selected by propensity score matching in order to adjust for the patients' backgrounds. Although the young group had significantly stronger pain than the elderly group immediately after surgery(4.9±2.5 vs.3.2±2.4, p=0.002), it improved promptly. Moreover, the young group required significantly more frequent continuous infusions of opioids after surgery( p=0.001). In conclusion, it is considered that the postoperative pain management in the pneumothorax surgery should be customized according to the age.


Comparison of Tc-99m MDP and Sm-153 EDTMP bone scan.
A 72-year-old male, a known case of carcinoma of prostate, had bilateral orchidectomy in 2002 and while on hormones developed multiple bone metastases in 2010. He was treated with (153)Samarium ethylene diamine tetra methylene phosphonate (EDTMP). The author compares the features of (99m)Tc methylene diphosphonate (MDP) scan and (153)Sm EDTMP bone scan, highlighting the similarities of skeletal uptake.


Evaluation of amino penicillins in experimental infections in mice.
The therapeutic activity of bacampicillin compared to that of ampicillin and amoxycillin was evaluated against experimental infections in mice. Median curative doses (CD50) were determined in groups of animals challenged with bacterial suspensions injected intraperitoneally together with mucin and treated orally with the penicillins. When treated directly after the infection bacampicillin was slightly more active than ampicillin, whereas it was significantly more active than ampicillin and at least as active as amoxycillin when the treatment was instituted not until four hours after infection. Bacterial counts made on various organ homogenates from infected animals four hours after the infection showed that a generalized infection with high bacterial concentrations had developed. Penicillin administration caused a significant reduction in the bacterial counts and the bactericidal activity in vivo obtained after administration of bacampicillin appeared as good as that of amoxycillin.


Assessment of individual bioequivalence using sufficient bootstrap procedure.
This paper proposes a sufficient bootstrap method, which uses only the unique observations in the resamples, to assess the individual bioequivalence under 2 × 4 randomized crossover design. The finite sample performance of the proposed method is illustrated by extensive Monte Carlo simulations as well as a real-experimental data set, and the results are compared with those obtained by the traditional bootstrap technique. Our records reveal that the proposed method is a good competitor or even better than the classical percentile bootstrap confidence limits.


Updates on hepatitis C virus therapy in the direct-acting antiviral era.
Hepatitis C virus (HCV) is a major cause of clinical burden in the United States and worldwide, as a percentage of patients can develop complications such as cirrhosis and hepatocellular carcinoma. Therapy for chronic HCV infection was previously interferon-based, but with the advent of direct-acting antivirals (DAAs), there has been a dramatic improvement in eradicating the virus with favourable side effect profiles. Emerging data are demonstrating new successful agents in difficult-to-manage populations. This review is aimed to provide a brief overview of currently accepted therapy, as well providing new information on upcoming therapeutic agents available for practioners going forward.


The failure to diagnose inborn errors of metabolism in New Zealand: the case for expanded newborn screening.
Expanded newborn screening uses a new technology, tandem mass spectrometry, to diagnose an additional 20 plus rare treatable inborn errors of metabolism based on the further analysis of the current newborn Guthrie card blood sample. The purpose of this study was to investigate the incidence of these disorders in New Zealand, based on clinical diagnosis rates, and compare these to the incidence, based on the established expanded newborn screening programme, in New South Wales, Australia. Over a 3-year period, the cases of inborn errors of metabolism notified to the New Zealand Paediatric Surveillance Unit and/or identified by the relevant metabolic laboratories were recorded and compared to the incidence rates during the same period in New South Wales. There were 175,000 and 270,000 births in New Zealand and New South Wales respectively during the study period. Eight cases of treatable inborn errors (potentially diagnosable by newborn screening) were diagnosed in New Zealand compared to 41 (including two prior to screening) in New South Wales. The disorder medium chain acyl Co-A dehydrogenase deficiency was diagnosed twice in New Zealand and in 24 newborn infants in New South Wales. Without expanded newborn screening, inborn errors of metabolism are under-diagnosed in New Zealand. This study supports the recent establishment of screening in New Zealand.


Iodine-125 interstitial irradiation of virally induced dog brain tumours.
Brain tumours were induced by intracerebral inoculation of beagle puppies with Avian sarcoma virus (ASV) suspension. The inoculation produced solitary or multiple sarcomas in three dogs and intraventricular anaplastic gliomas in four dogs. At the time of the first tumour positive CT-control Iodine-125 seeds (activity 8.5-10.5 mCi) were placed into the lesion. The radioactive Iodine-125 implants produced sharply delineated calcifying necroses with vital unaffected tumour outside the necrosis. The necrotizing and calcifying effect was apparent after 18 days and complete after 97 days when a transitional zone was no longer detectable. The response of neoplastic tissue to low dose rate interstitial irradiation was distinctly different in terms of the volume of necrosis when compared with Iodine-125 radionecroses in healthy brain tissue.


Resokaempferol-mediated anti-inflammatory effects on activated macrophages via the inhibition of JAK2/STAT3, NF-κB and JNK/p38 MAPK signaling pathways.
The excessive or prolonged production of inflammatory mediators can result in numerous chronic diseases, such as rheumatoid arthritis, atherosclerosis, diabetes, and cancer. Therefore, for many inflammatory-related diseases, pharmaceutical intervention is required to restrain the excessive release of such inflammatory mediators. Novel therapeutics and mechanistic insight are sought for the management of chronic inflammatory diseases. Resokaempferol (RES) is a type of flavonoid recently reported to demonstrate anti-cancer properties. However, the anti-inflammatory capacity of RES has not been studied to date. Therefore, this study investigated whether RES is capable of suppressing the inflammatory response to lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the mechanism by which this is achieved. We found that RES attenuated the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1) and IL-6. RES also inhibited the nuclear translocation of signal transducer and activator of transcription (STAT) 3 and reduced the LPS-mediated phosphorylation of Janus kinase (JAK) 2 and STAT3 at the sites of Ser727 and Tyr705. RES also inhibited the activation of NF-κB and JNK/p38 MAPK signaling pathways in LPS-induced RAW264.7 cells. Additionally, RES inhibited the activation of the JAK2/STAT3 pathway in exogenous IL-6-activated RAW264.7 macrophages. We conclude that RES inhibits the inflammatory response in activated macrophages by blocking the activation of the JAK2/STAT3 pathway by both LPS and IL-6 signaling.


Low-calcium epileptiform activity in the hippocampus in vivo.
It has been clearly established that nonsynaptic interactions are sufficient for generating epileptiform activity in brain slices. However, it is not known whether this type of epilepsy model can be generated in vivo. In this paper we investigate low-calcium nonsynaptic epileptiform activity in an intact hippocampus. The calcium chelator EGTA was used to lower [Ca2+]o in the hippocampus of urethane anesthetized rats. Spontaneous and evoked field potentials in CA1 pyramidal stratum and in CA1 stratum radiatum were recorded using four-channel silicon recording probes. Three different types of epileptic activity were observed while synaptic transmission was gradually blocked by a decline in hippocampal [Ca2+]o. A short latency burst, named early-burst, occurred during the early period of EGTA application. Periodic slow-waves and a long latency high-frequency burst, named late-burst, were seen after synaptic transmission was mostly blocked. Therefore these activities appear to be associated with nonsynaptic mechanisms. Moreover, the slow-waves were similar in appearance to the depolarization potential shifts in vitro with low calcium. In addition, excitatory postsynaptic amino acid antagonists could not eliminate the development of slow-waves and late-bursts. The slow-waves and late-bursts were morphologically similar to electrographic seizure activity seen in patients with temporal lobe epilepsy. These results clearly show that epileptic activity can be generated in vivo in the absence of synaptic transmission. This type of low-calcium nonsynaptic epilepsy model in an intact hippocampus could play an important role in revealing additional mechanisms of epilepsy disorders and in developing novel anti-convulsant drugs.


Hypertrophic pulmonary osteoarthropathy in pulmonary metastasis--a case report.
Hypertrophic pulmonary Osteoarthropathy is most commonly encountered in association with bronchogenic carcinoma and tumours of the pleura. Its association with pulmonary metastasis from extrathoracic neoplasms is rare. We report a 33 years old male Ethiopian who presented with Cannon ball lesions, clubbing of the digits, periostitis, gynaecomastia, acromegalic features and bilateral knee arthritis. Related literature is briefly reviewed.


Plasma variables, meat quality, and glycolytic potential in broilers stunned with different carbon dioxide concentrations.
This study aimed to investigate the effects of different CO(2) concentrations on blood variables, glycolytic potential (GP), and meat quality of hot-boned muscles in broilers. Thirty broilers were exposed to one of the following 5 gas mixtures for 90 s: 40% CO(2) + 30% O(2) + N(2) (control), 30% CO(2) + 21% O(2) + N(2) (G30%), 40% CO(2) + 21% O(2) + N(2) (G40%), 50% CO(2) + 21% O(2) + N(2) (G50%), and 60% CO(2) + 21% O(2) + N(2) (G60%). Samples were taken from the pectoralis major (PM), musculus iliofibularis (MI), and tibialis anterior muscles 45 min postmortem. The ultimate pH in both the PM (vs. G30% and G40%) and MI (vs. G40%) was decreased with G60% (P < 0.05), whereas drip loss in the PM (vs. G30%, P = 0.01) was increased with G60%. Drip loss in the MI (vs. control and G30%, P < 0.01) was increased with G50%. Lightness after 24 h in PM (vs. G30% and G40%, P < 0.01) was increased with G50%. In MI, lightness after 24 h was slightly decreased with G40% compared with the control (P < 0.10). The GP value in the PM was lower in the G30% and G40% than in G60% (P < 0.05), and the GP value in the tibialis anterior was the lowest in G30% (P < 0.01). Plasma corticosterone, plasma glucose, and meat quality (pH, lightness, redness, yellowness) 45 min postmortem were not affected by CO(2) levels (P > 0.05). In conclusion, stunning broilers with low CO(2) levels (30 and 40%) improved meat quality but had no advantage in animal welfare compared with high CO(2) levels (50 and 60%).


Status of immunity against poliomyelitis in the acute flaccid paralysis (AFP) cases in Romania between 2009-2012.
Poliovirus (PV), a member of the Enterovirus genus, is the etiological agent of poliomyelitis, an acute paralytic disease. No poliovirus strain has been isolated in Romania since 2009. A serosurvey study carried out between 2009-2012, that involved 76 serum samples from acute flaccid paralysis (AFP) cases, showed a low protection level in the examined subjects against type 1 (80%), type 2 (79%) and type 3 (71%) poliovirus Sabin strains. Samples with titers ≥ 1:8 were considered positive. Suboptimal seroprevalence in the AFP cases confirmed that a high level of immunization against polio must be assured in our country, because the risk of importation and subsequent transmission of the poliovirus remains until polio is globally eradicated.


Obesity is associated with increased red blood cell folate despite lower dietary intakes and serum concentrations.
Folates are essential cofactors in metabolic pathways that facilitate biological methylation and nucleotide synthesis, and therefore have widespread effects on health and diseases. Although obesity is prevalent worldwide, few studies have investigated how obesity interacts with folate status. Based on data from the NHANES, this study aims to examine the association between body mass index (BMI) and obesity-related metabolic factors with blood folate status. A nationally representative sample of 3767 adults from the NHANES (2003-2006) was used as the study population. Regression analyses, with and without adjustment for demographic factors and dietary intakes, were performed to examine associations between BMI and metabolic factors with serum and RBC folate. The results indicate serum folate concentrations were lower in obese groups compared to the desirable BMI and overweight categories, paralleling lower intakes in this group. In contrast, RBC folate increased incrementally with BMI. Regression analyses demonstrated an inverse relation between BMI and serum folate but a positive relation for RBC folate (P < 0.01). Waist circumference, serum triglycerides, and fasting plasma glucose each displayed significant positive relations with RBC folate (P < 0.01), although relations with serum folate were not significant and consistent. In summary, obesity is associated with decreased serum folate, which parallels decreased folate intakes. In contrast, obesity is positively associated with RBC folate. Therefore, RBC folate, in addition to serum folate, should also be considered as a critical biomarker for folate status, especially in the obese population. Future research is needed to understand how obesity differentially alters serum and RBC folate status because they are associated with a variety of medical complications.


Investigation of the improved effects of 2-hydroxypropyl-beta-cyclodextrin on solubility, dissolution rate, and intestinal absorptive profile of tanshinone IIA in rats.
In this paper, the effect of the chemically modified cyclodextrin [namely, 2-hydroxypropyl-beta-cyclodextrin, (HP-beta-CD)] on the aqueous solubility, dissolution rate, and intestinal permeability of the tanshinone IIA (TS) was investigated. The corresponding inclusion complex of TS-HP-beta-CD at the molar ratio of 1:1 was obtained by coevaporation. The solubility of complexed TS in water at 37+/-0.1 centi-degree was 17 times greater than that for the uncomplexed drug. The dissolution rate of TS was significantly increased by the complexation with HP-beta-CD, due to its solubilizing activity. The everted intestinal sac technique in rats was used to study the absorption behavior studies of TS and this complexation through the intestinal tissues. The permeability rates of TS across the intestinal epithelial membrane were enhanced by the formation of inclusion complex with HP-beta-CD about 89, 97 and 82 times of the uncomplexed TS in duodenum, jejunum and ileum, respectively. It was revealed that the absorption rate-limiting step of TS might be the dissolution process. The present results indicated the potential use of HP-beta-CD to improve the gastrointestinal tract absorption of TS.


IL-1β induced HIF-1α inhibits the differentiation of human FOXP3+ T cells.
Differentiation of regulatory Treg (Treg) in the periphery is critical to control inflammatory processes. Although polarization of inducible Treg (iTreg) often occurs in an inflammatory environment, the effects exerted by inflammation on human iTreg differentiation have not been extensively studied. We observed that IL-1β significantly reduced the frequency of FOXP3+ T cells under iTreg-polarizing conditions. Mechanistically, we show that IL-1β activated mTORC1 and downstream upregulated hypoxia inducible factor-1 (HIF-1α) expression. Using specific inhibitors, we demonstrated that both steps were critical in the deleterious effect of IL-1β on Treg differentiation. Chemical stabilization of HIF-1α by Dimethyloxalylglycine (DMOG) also significantly impaired iTreg differentiation. Interestingly, while IL-1β-treated cells exhibited only minor changes in metabolism, DMOG treatment decreased iTreg mitochondrial respiration and increased their glycolytic capacity. In conclusion, exposure to inflammatory stimuli profoundly inhibits human Treg differentiation HIF-1α dependent, suggesting that targeting HIF-1α could be a strategy to foster iTreg differentiation in an inflammatory milieu. However, IL-1β deleterious effect does not appear to be completely driven by metabolic changes. These data thus suggest that several mechanisms contribute to the regulation of iTreg differentiation, but the timing and respective requirement for each pathway vary depending on the milieu in which iTreg differentiate.


Infrared optical constants of black powders determined from reflection measurements.
The real and imaginary parts of the complex index of refraction have been measured in the 3-14-microm region for nine black powders. Data were obtained from specular reflection measurements on pressed powder disks. A vintage prism spectrometer was considerably modified for this study. Polarized radiation, detected with a cooled photoconductor, was used to generate isoreflectance curves from which the optical properties were extracted. With the exception of a bone charcoal sample, the optical constants of the black powders exhibited no spectral features in the wavelength range considered. Measured values were generally in agreement with published data on similar materials. Surface effects were found not to produce a significant limitation on the results of our method.


Insights into Recent Advances of Biomaterials Based on Microbial Biomass and Natural Polymers for Sustainable Removal of Pharmaceuticals Residues.
Pharmaceuticals are acknowledged as emerging contaminants in water resources. The concentration of pharmaceutical compounds in the environment has increased due to the rapid development of the pharmaceutical industry, the increasing use of human and veterinary drugs, and the ineffectiveness of conventional technologies to remove pharmaceutical compounds from water. The application of biomaterials derived from renewable resources in emerging pollutant removal techniques constitutes a new research direction in the field. In this context, the article reviews the literature on pharmaceutical removal from water sources using microbial biomass and natural polymers in biosorption or biodegradation processes. Microorganisms, in their active or inactive form, natural polymers and biocomposites based on inorganic materials, as well as microbial biomass immobilized or encapsulated in polymer matrix, were analyzed in this work. The review examines the benefits, limitations, and drawbacks of employing these biomaterials, as well as the prospects for future research and industrial implementation. From these points of view, current trends in the field are clearly reviewed. Finally, this study demonstrated how biocomposites made of natural polymers and microbial biomass suggest a viable adsorbent biomaterial for reducing environmental pollution that is also efficient, inexpensive, and sustainable.


Report on an anti-doping operation in Guadeloupe: High number of positive cases and inferences about doping habits.
Anti-doping controls in non-major events are relatively infrequent and athletes that compete only in these events are less likely to be controlled. The French Anti-Doping Agency carried out an anti-doping operation during a regional cycling competition in Guadeloupe. The urine and serum samples were analysed by the French anti-doping laboratory. Out of 42 athletes, 7 were positive for one or more substances prohibited by the World Anti-Doping Agency. Four serum samples contained continuous erythropoietin receptor activator (CERA) and one a recombinant erythropoietin. However, no traces were found in the corresponding urines. One of the athletes positive for CERA was also positive for growth hormone (GH), identified using the GH isoform test. The same serum was negative with the GH biomarkers test, probably because of the brief interval between injection and control (less than a day). The stimulants heptaminol and dimethylbutylamine, as well as the glucocorticoid prednisone and its metabolite prednisolone, were also found. Strikingly, 16.6% of the controlled athletes were using one or more prohibited drugs. These findings indicate that doping is widespread in athletes competing regionally and that CERA is still a popular drug for endurance sports. They underline the need for more controls, particularly blood sampling during non-major competitions. Copyright © 2017 John Wiley & Sons, Ltd.


Medication therapy management services in North Carolina community pharmacies: current practice patterns and projected demand.
To evaluate the types of cognitive services offered and the number of patients being served in community pharmacies, determine the number of pharmacies that plan to offer medication therapy management (MTM) services under the Medicare Part D prescription drug benefit, and assess whether current and expected practices will meet the potential needs of enrollees. Cross-sectional study. North Carolina in January 2005. 1,593 community pharmacy managers. Survey using a Web-based tool. Provision of cognitive services and number of patients for whom services are provided. A total of 262 (16%) pharmacy managers provided usable responses. Approximately 42% of respondents (n = 110) indicated that they provide some type of cognitive service. Comprehensive MTM services, or services consistent with the professionwide consensus definition, were provided by 31% of respondents (n = 81). Independent pharmacies were more likely to offer some type of service compared with chain pharmacies (58% versus 31%, respectively; P < .001). Pharmacy managers with a doctor of pharmacy degree were less likely than pharmacy managers with a bachelor's degree to offer services in their pharmacies (P = .02), and pharmacies with pharmacists on staff who had received certificate training were more likely to offer cognitive services (P = .03). Of all respondents, 28% (n = 73) indicated that they planned to offer MTM services under the Medicare Part D prescription drug benefit. Comparing these results with those of a 1999 survey of North Carolina pharmacists that used some of the same items, the percentage of community pharmacies that provide cognitive services has increased in the intervening years but remains low. Among the services being offered in 2005, most were focused on patient education and training, coordinating and integrating care, and medication regimen reviews. Implementation of MTM services under the Medicare Part D prescription drug benefit should hasten the development and offering of these services in community pharmacies.


Acid-Responsive Poly(glyoxylate) Self-Immolative Star Polymers.
Self-immolative polymers have significant potential for applications such as drug or gene delivery. However, to realize this potential, such materials need to be customized to respond to specific variations in biological conditions. In this work, we investigated the design of new star-shaped self-immolative poly(ethyl glyoxylate)s (PEtGs) and their incorporation into responsive nanoparticles. PEtGs are a subclass of stimulus-responsive self-immolative polymers, which can be combined with different stimuli-responsive functionalities. Two different tetrathiol initiators were used for the polymerization in combination with a variety of potential pH-responsive end-caps, yielding a library of star PEtG polymers which were responsive to pH. Characterization of the depolymerization behavior of the polymers showed that the depolymerization rate was controlled by the end caps rather than the architecture of the polymer. A selection of the star polymers were modified with amines to allow introduction of charge-shifting properties. It was shown that pH-responsive nanoparticles could be prepared from these modified polymers and they demonstrated pH-dependent particle disruption. The pH responsiveness of these particles was studied by dynamic light scattering and 1H nuclear magnetic resonance spectroscopy.


[Efficacy and safety of levofloxacin treatment of community--acquired pneumonia in hospitalized patients].
The aim of this prospective study was to determine the efficacy and safety of levofloxacin in the treatment of community-aquired pneumonia (CAP) in outpatient with ineffective antibiotic management, requiring hospitalization. The examined group included 25 patients (11 M, 14 F) of mean age 70+/-17,5 years with abnormalities in X-ray on admission to hospital. Risk factors for pneumonia and previous antibacterial therapy were analyzed. In the hospital they were treated for 7 days with levofloxacin 500 mg twice a day administred intravenously. Body temperature, blood cell count, ESR, CRP, AST, ALT, LDH, CPK, creatine, urea, potassium, sodium, ABG, and ECG were measured on admission and in the 3-rd and 7- th day of therapy. The chest X-rays were performed and analyzed on hospital discharge. 18 patients were aged > 65 yrs, cardiovascular diseases co-existed in 14, COPD in 9, smoking habit in 12, renal failure in 3, diabetes in 3 and alkohol addiction in 1 cases. On admission 4 patients had respiratory failure, 10 hypoxaemia. During therapy a decrease of body temperature (p<0,001), concentration of CRP (p<0,004) and LDH (p<0,03), CPK (p<0,04) and increase of PaO2 (p<0,012) were observed. The changes of other parameters were not statistically significant. We did not observe any changes in ECG. On discharge from the hospital in 16 patients complete regression and in 6 patients partial regression of lesions in chest X-ray examination were observed. In 3 patients levofloxacin therapy was noneffective: in 2 because of persistent high body temperature after 3 days of treatment and in 1 patients because of recurrent of fever. Adverse events were mild. Transient exacerbation of renal failure was observed in 3 patients. Our study demonstrates that levofloxacine ni dose 2x500 mg given intravenously for 7 days is effective and safe in treatment of CAP in patients with previously ineffective antibacterial therapy.


Immunity and immune response, pathology and pathologic changes: progress and challenges in the immunopathology of yellow fever.
Yellow fever is a viral hemorrhagic fever, which affects people living in Africa and South America and is caused by the yellow fever virus, the prototype species in the Flavivirus genus (Flaviviridae family). Yellow fever virus infection can produce a wide spectrum of symptoms, ranging from asymptomatic infection or oligosymptomatic illness to severe disease with a high fatality rate. In this review, we focus in the mechanisms associated with the physiopathology of yellow fever in humans and animal models. It has been demonstrated that several factors play a role in the pathological outcome of the severe form of the disease including direct viral cytopathic effect, necrosis and apoptosis of hepatocyte cells in the midzone, and a minimal inflammatory response as well as low-flow hypoxia and cytokine overproduction. New information has filled several gaps in the understanding of yellow fever pathogenesis and helped comprehend the course of illness. Finally, we discuss prospects for an immune therapy in the light of new immunologic, viral, and pathologic tools.


Regulation of human CYP2C9 by the constitutive androstane receptor: discovery of a new distal binding site.
The CYP2C subfamily metabolizes many clinically important drugs. These genes respond to prototypical inducers such as phenobarbital and rifampicin, yet little has been reported on the mechanisms of induction. This report examines the regulation of CYP2C9 with respect to two specific receptors thought to be involved in phenobarbital (PB) induction, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Transfection of either mouse CAR (mCAR) or human CAR (hCAR) into HepG2 cells results in increased CYP2C9 mRNA content. Inducers further increased this response in CAR transfected cells. mCAR but not hCAR conferred drug inducibility to the proximal -2145 bp of the CYP2C9 promoter in luciferase assays. Further examination of a -2925-bp promoter construct revealed that hCAR cotransfection increased activity 20-fold. Gel shift assays confirmed the presence of a distal PB-responsive enhancer module-like enhancer module, CAR-responsive enhancer (CAR-RE), between -2900 and -2841 bp consisting of two DR-5 nuclear receptor binding motifs capable of binding hCAR, mCAR, and, to a lesser extent, human PXR. The majority of binding and hCAR activation is derived from the NR1 portion of the CAR-RE. PB treatment did not further increase the hCAR activation in any of the constructs. In summary, a new CAR/PXR binding site was identified in the CYP2C9 promoter, and this site seems to constitutively regulate transcription via a CAR-dependent mechanism; however, it could not be shown to account for PB inducibility of the gene.