Rapid Sampling of Escherichia coli After Changing Oxygen Conditions Reveals Transcriptional Dynamics.
Escherichia coli is able to shift between anaerobic and aerobic metabolism by adapting its gene expression, e.g., of metabolic genes, to the new environment. The dynamics of gene expression that result from environmental shifts are limited, amongst others, by the time needed for regulation and transcription elongation. In this study, we examined gene expression dynamics after an anaerobic-to-aerobic shift on a short time scale (0.5, 1, 2, 5, and 10 min) by RNA sequencing with emphasis on delay times and transcriptional elongation rates (TER). Transient expression patterns and timing of differential expression, characterized by delay and elongation, were identified as key features of the dataset. Gene ontology enrichment analysis revealed early upregulation of respiratory and iron-related gene sets. We inferred specific TERs of 89 operons with a mean TER of 42.0 nt/s and mean delay time of 22.4 s. TERs correlate with sequence features, such as codon bias, whereas delay times correlate with the involvement of regulators. The presented data illustrate that at very short times after a shift in oxygenation, extensional changes of the transcriptome, such as temporary responses, can be observed. Besides regulation, TERs contribute to the dynamics of gene expression.


Gene Recruitments and Dismissals in the Argonaut Genome Provide Insights into Pelagic Lifestyle Adaptation and Shell-like Eggcase Reacquisition.
The paper nautilus or greater argonaut, Argonauta argo, is a species of octopods which is characterized by its pelagic lifestyle and by the presence of a protective spiral-shaped shell-like eggcase in females. To reveal the genomic background of how the species adapted to the pelagic lifestyle and acquired its shell-like eggcase, we sequenced the draft genome of the species. The genome size was 1.1 Gb, which is the smallest among the cephalopods known to date, with the top 215 scaffolds (average length 5,064,479 bp) covering 81% (1.09 Gb) of the total assembly. A total of 26,433 protein-coding genes were predicted from 16,802 assembled scaffolds. From these, we identified nearly intact HOX, Parahox, Wnt clusters, and some gene clusters that could probably be related to the pelagic lifestyle, such as reflectin, tyrosinase, and opsin. The gene models also revealed several homologous genes related to calcified shell formation in Conchiferan mollusks, such as Pif-like, SOD, and TRX. Interestingly, comparative genomics analysis revealed that the homologous genes for such genes were also found in the genome of the shell-less octopus, as well as Nautilus, which has a true outer shell. Therefore, the draft genome sequence of Arg. argo presented here has helped us to gain further insights into the genetic background of the dynamic recruitment and dismissal of genes to form an important, converging extended phenotypic structure such as the shell and the shell-like eggcase. Additionally, it allows us to explore the evolution of from benthic to pelagic lifestyles in cephalopods and octopods.


Diagnosing and treating hemophagocytic lymphohistiocytosis in the tropics: systematic review from the Indian subcontinent.
Hemophagocytic lymphohistiocytosis (HLH) is a catastrophic syndrome of unrestrained immune activation. Evaluation and management of HLH in the tropics is challenging. To examine the reported etiologies and management of HLH reported from the sub-continent. Systematic review of all published cases from the Indian sub-continent. We found only 156 published cases of HLH from the sub-continent. HLH was reported from the immediate perinatal period to 46 years of age. Infection-associated HLH (IAHS) constituted 46.8% of all cases of HLH (44% and 51% in children and adults respectively). In adults, tropical infections triggered 51% of these cases of IAHS. Steroids were used in 47% of children and 10% of adults. Etoposide and/or cyclosporine were used in 8% children and 8% of adults only. Intravenous immunoglobulin was used in another 30% of children and 4% of the adults. HLH-related mortality occurred in 31.8% and 28% of children and adults respectively. HLH is under-reported in the sub-continent and has high mortality. Cyclosporine and etoposide are seldom administered early despite diagnosis of HLH. Larger cohorts with IAHS triggered by tropical infections are urgently needed to understand its natural history and implications of this differing prescription pattern on mortality.


[Walnut-shell moxibustion for dry eye symptoms: a randomized controlled trial].
To evaluate the effects of walnut-shell moxibusiton on dry eye symptoms. A total of 67 patients with dry eye symptoms were randomized into a walnut moxibustion group and a sodium hyaluronate eye drops group. In the walnut moxibustion group, the walnut moxibustion was used, once every two days, 3 times a week, for 4 weeks totally. In the sodium hyaluronate eye drops group, sodium hyaluronate eye drops were selected, 4 times a day, one drop instilled in each eye each time, for 4 weeks totally. At the baseline (before treatment) and in 4 weeks of treatment, the score of the ocular surface disease index (OSDI), the score of visual analogous scale (VAS) for eye symptoms, the tear film break-up time (BUT), the cornea fluorescent pigmentation (FL) and SchirmerⅠ(SchⅠ) were evaluated. In 1-month follow-up after treatment termination, the changes of OSDI and VAS scores were evaluated in the two groups. In 4 weeks of treatment and the follow-up, OSDI scores were reduced as compared with those before treatment in the two groups (P<0.001, P<0.05). In 4 weeks of treatment and the follow-up, the change values of OSDI were (-16.03±17.42) and (-13.47±21.41) as compared with those before treatment in the walnut moxibustion group; and were (-9.58±23.45) and (-13.90±20.92) in the sodium hyaluronate eye drops group separately. The differences were not significant between the two groups (all P>0.05). In 4 weeks of treatment and the follow-up, VAS scores were reduced as compared with those before treatment in the two groups (all P<0.001). In 4 weeks of treatment, BUT was increased as compared with that before treatment in the two groups (both P<0.05), the results of FL and SchⅠ did not change significantly before and after treatment in the two groups (all P>0.05). The differences were not significant in the above indexes between the two groups (all P>0.05). There was no obvious adverse reaction in the two groups. The walnut-shell moxibustion is available likely for the subjective symptoms in the patients with dry eye syndrome and contributes to the tear film stabilization. The therapeutic effects need to be further evaluated with the adequate sample size in the randomized controlled trial.


Intermittency in the isotropic component of helical and nonhelical turbulent flows.
We analyze the isotropic component of turbulent flows spanning a broad range or Reynolds numbers. The aim is to identify scaling laws and their Reynolds number dependence in flows under different mechanical forcings. To this end, we applied an SO(3) decomposition to data stemming from direct numerical simulations with spatial resolutions ranging from 64(3) to 1024(3) grid points, and studied the scaling of high order moments of the velocity field. The study was carried out for two different flows obtained forcing the system with a Taylor-Green vortex or the Arn'old-Beltrami-Childress flow. Our results indicate that helicity has no significant impact on the scaling exponents as obtained from the generalized structure functions. Intermittency effects increase with the Reynolds number in the range of parameters studied, and in some cases are larger than what can be expected from several models of intermittency in the literature. The observed dependence of intermittency with the Reynolds number decreases if extended self-similarity is used to estimate the exponents.


Roles of antimicrobial peptides such as defensins in innate and adaptive immunity.
A number of antimicrobial peptides such as defensins have multiple functions in host defence. Defensins are produced not only by phagocytic cells and lymphocytes, but also by the epithelial cell lining of the gastrointestinal and genitourinary tracts, the tracheobronchial tree, and keratinocytes. Some are produced constitutively, whereas others are induced by proinflammatory cytokines and exogenous microbial products. Defensins produced by cells in the course of innate host defence serve as signals which initiate, mobilise, and amplify adaptive immune host defences. Administration of defensins with antigens to mice enhances both cellular (Th1-dependent) and humoral (Th2-dependent) cytokine production and immune responses. Linkage of defensins to weak tumour antigens potentiates their immunoadjuvant effects. Defensins use multiple cellular receptors, which endows them with the capacity to marshall adaptive host defences against microbial invaders.


Implantable pacemakers for cardiac tachyarrhythmias.
The vast horizons opened by the newer knowledge gained from specialized electrophysiologic studies have led to the increasing use of implanted pacemakers for the management of a variety of tachyarrhythmias which are either drug-resistant or better controlled electrically. The ideal pacemaker should be custom-made, i.e., fit to the (predetermined) patient's needs, and should be self-activated. In addition, external programmability of pacing rates and modes is a very desirable feature.


Prosthetic valve endocarditis presenting as meningoencephalitis complicated by pseudo-aneurysms in a remote Aboriginal healthcare setting in Australia: a case report.
The Australian Aboriginal population has a high burden of cardiac conditions predisposing patients to infective endocarditis. Pseudo-aneurysms are a rare and potentially fatal complication of both prior valvular surgery and endocarditis. A 31-year-old female with a history of bicuspid aortic valve requiring valve replacement presented with meningoencephalitis. Transoesophageal echo and positive blood cultures for Staphylococcus aureus confirmed prosthetic valve endocarditis (PVE). Aortic root mycotic pseudo-aneurysms developed during antimicrobial therapy and two large pseudo-aneurysms remain post-redo valve, root and arch replacement. Complications associated with PVE are common, especially due to S. aureus. Redo cardiac surgery is high risk, percutaneous treatments may be technically difficult due to altered post-operative anatomy, and medication adherence issues and lack of healthcare engagement further compromise optimal care in this patient population.


Effect of pregnancy in myopia progression: the SUN cohort.
PurposePrevious studies have suggested that pregnancy may induce myopia progression. However, no longitudinal study with a large sample size and long-term follow-up has assessed this association. Our objective was to investigate whether pregnancy was related to mid- or long-term myopic refraction changes.Patients and methodsA prospective study was conducted in a Mediterranean cohort. The study included 10 401 women (20-50 years old) from the SUN Project. SUN project is a multipurpose, prospective, and dynamic cohort of university graduates conducted in Spain. The recruitment of participants started in 1999 and it is permanently open. All participants in this cohort had university studies. Participants were followed up for a period of up to 14 years, and pregnancy and refractive changes were assessed through baseline and biennial questionnaires. Pregnancies and myopia were repeatedly assessed in each biennial follow-up questionnaire during a total of 14 years of follow-up.ResultsPregnancy was inversely associated with the risk of myopia development or progression during each of the 2 years periods, with fully adjusted hazard ratio=0.61; (95% confidence interval=0.49-0.75) after adjusting for known potential confounders.ConclusionTo our knowledge this is the first large-longitudinal assessment in young adult women, showing that pregnancy is inversely associated with myopia development or progression. Further studies are needed to confirm these epidemiological findings.


Induction of L-histidine decarboxylase in a human mast cell line, HMC-1.
Histamine is an important mediator in allergic reactions, gastric acid secretions, and neurotransmission in the central nervous system. Basophils and mast cells are the main sources of histamine, which is formed from L-histidine by histidine decarboxylase (HDC). However, the regulatory mechanism of HDC in these cells remains unclear. We examined the regulation of HDC activity and gene expression using a unique human mast cell line, HMC-1, after stimulation with phorbol 12-myristate 13-acetate (PMA) or ionomycin. HDC activity was increased from 52.1+/-0.4 (mean+/-standard deviation) to 154+/-6.9, or 105.6+/-6.2 pmol/min/mg protein (n = 3), 4 hours after stimulation with PMA (10 ng/mL) or ionomycin (10[-6] M). Although actinomycin D had no effect on this increase, cycloheximide completely inhibited the increase caused by these stimuli. The population of HMC-1 cells containing HDC protein was increased after stimulation with either PMA or ionomycin as evaluated by immunocytochemical analysis with anti-HDC antibody as a marker. HMC-1 constitutively expressed HDC mRNA, and its level was not increased with these stimuli. These results suggest that the increase of HDC activity in HMC-1 induced by PMA or ionomycin is regulated at the translational level.


Arsenic speciation in rice bran: Agronomic practices, postharvest fermentation, and human health risk assessment across the lifespan.
Arsenic (As) exposure is a global public health concern affecting millions worldwide and stems from drinking water and foods containing As. Here, we assessed how agronomic practices and postharvest fermentation techniques influence As concentrations in rice bran, and calculated health risks from consumption. A global suite of 53 rice brans were tested for total As and speciation. Targeted quantification of inorganic As (iAs) concentrations in rice bran were used to calculate Target Hazard Quotient (THQ) and Lifetime Cancer Risk (LCR) across the lifespan. Mean iAs was highest in Thailand rice bran samples (0.619 mg kg-1) and lowest in Guatemala (0.017 mg kg-1) rice bran samples. When comparing monosodium-methanearsonate (MSMA) treated and the Native-soil counterpart under the irrigation technique Alternate Wetting and Drying (AWD) management, the MSMA treatment had significantly higher total As (p = 0.022), and iAs (p = 0.016). No significant differences in As concentrations were found between conventional and organic production, nor between fermented and non-fermented rice bran. Health risk assessment calculations for the highest iAs-rice bran dosage scenario for adults, children and infants exceeded THQ and LCR thresholds, and LCR was above threshold for median iAs-rice bran. This environmental exposure investigation into rice bran provides novel information with food safety guidance for an emerging global ingredient.


The effect of corticosteroid treatment on bilateral idiopathic granulomatous mastitis.
Idiopathic granulomatous mastitis (IGM) is the commonly encountered form of granulomatous mastitis that may result into repetitive infections and/or abscess formation. Mastitis may develop secondary to a systemic disorder such as tuberculosis, diabetes mellitus, or rheumatoid arthritis, or it may develop as an idiopathic disorder. Idiopathic granulomatous mastitis is the most frequent form of all granulomatous diseases affecting the breast. This disorder frequently presents as painful and fast-growing mass in the breast. Biopsy is required to confirm diagnosis. Surgical excision and immunosuppressive treatment with corticosteroids are employed for therapeutic management. Here we present 3 female cases of bilateral IGM who were followed up and treated successfully with 1 mg/kg/day prednisolone.


Surveillance of molecular markers of antimalarial drug resistance in Plasmodium falciparum and Plasmodium vivax in Federally Administered Tribal Area (FATA), Pakistan.
This molecular epidemiological study was designed to determine the antimalarial drug resistance pattern, and the genetic diversity of malaria isolates collected from a war-altered Federally Administered Tribal Area (FATA), in Pakistan. Clinical isolates were collected from Bajaur, Mohmand, Khyber, Orakzai and Kurram agencies of FATA region between May 2017 and May 2018, and they underwent DNA extraction and amplification. The investigation of gene polymorphisms in drug resistance genes (dhfr, dhps, crt, and mdr1) of Plasmodium falciparum and Plasmodium vivax was carried out by pyrosequencing and Sanger sequencing, respectively. Out of 679 PCR-confirmed malaria samples, 523 (77%) were P. vivax, 121 (18%) P. falciparum, and 35 (5%) had mixed-species infections. All P. falciparum isolates had pfdhfr double mutants (C59R+S108N), while pfdhfr/pfdhps triple mutants (C59R+S108N+A437G) were detected in 11.5% of the samples. About 97.4% of P. falciparum isolates contained pfcrt K76T mutation, while pfmdr1 N86Y and Y184F mutations were present in 18.2% and 10.2% of the samples. P. vivax pvdhfr S58R mutation was present in 24.9% of isolates and the S117N mutation in 36.2%, while no mutation in the pvdhps gene was found. Pvmdr1 F1076L mutation was found in nearly all samples, as it was observed in 98.9% of isolates. No significant anti-folate and chloroquine resistance was observed in P. vivax; however, mutations associated with antifolate-resistance were found, and the chloroquine-resistant gene has been observed in 100% of P. falciparum isolates. Chloroquine and sulphadoxine-pyrimethamine resistance were found to be high in P. falciparum and low in P. vivax. Chloroquine could still be used for P. vivax infection but need to be tested in vivo, whereas a replacement of the artemisinin combination therapy for P. falciparum appears to be justified.


Screening of Key Genes in Severe Burn Injury at Different Stages via Analyzing Gene Expression Data.
Microarray analysis was performed to investigate the changes in gene expression profiles after severe burn injury at the early and middle stages, further discovering therapeutic targets for severe burn injury. Microarray data (GSE19743) were downloaded from Gene Expression Omnibus. First, differentially expressed genes (DEGs) at different stages were screened using limma package. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were then performed using DAVID. Protein-protein interaction (PPI) networks were also constructed using String database. Additionally, transcription factor binding site was detected using the Whole-Genome rVISTA. Compared with the healthy controls, 160 DEGs were identified in patients with early-stage burn injury and 261 DEGs were obtained in patients with middle-stage burn injury. Only 10 genes showed differential expression between the early and middle stages. KEGG functional analysis indicated that DEGs detected at the early stage were mainly enriched in the immune response, kinase activity, and signaling pathways and DEGs detected at the middle stage were involved in the immune response, protein and fat metabolism, and programmed cell death pathways. Three PPI networks were constructed and hub proteins with high degrees of connection were screened, such as lactotransferrin, interleukin 8, and perforin-1. Additionally, many transcription factor binding sites that may be involved in the regulation of these DEGs were also detected. A number of DEGs were identified in patients with early- and middle-stage burn injury, which helps to deepen the understanding about the molecular mechanism underlying severe burn injury.


Xylose fermentation as a challenge for commercialization of lignocellulosic fuels and chemicals.
Fuel ethanol production from lignocellulosic materials is at a level where commercial biofuel production is becoming a reality. The solubilization of the hemicellulose fraction in lignocellulosic-based feedstocks results in a large variety of sugar mixtures including xylose. However, allowing xylose fermentation in yeast that normally is used for fuel ethanol production requires genetic engineering. Moreover, the efficiency of lignocellulosic pretreatment, together with the release and generation of inhibitory compounds in this step, are some of the new challenges faced during second generation ethanol production. Successful advances in all these aspects will improve ethanol yield, productivity and titer, which will reduce the impact on capital and operating costs, leading to the consolidation of the fermentation of lignocellulosic biomass as an economically feasible option for the production of renewable fuels. Therefore the development of yeast strains capable of fermenting a wide variety of sugars in a highly inhibitory environment, while maintaining a high ethanol yield and production rate, is required. This review provides an overview of the current status in the use of xylose-engineered yeast strains and describes the remaining challenges to achieve an efficient deployment of lignocellulosic-based ethanol production.


Tyrosine hydroxylase immunoreactivity in the retina of the diabetic sand rat Psammomys obesus.
The pattern of tyrosine hydroxylase (TH)-immunoreactivity, which labels dopamine neurons in the retina, is described in a diurnal sand rat Psammomys obesus. As in other rodent species, dopamine innervation is composed of large neurons located in the amacrine cell layer and sending processes mainly to sublamina 1 of the inner plexiform layer, where they form ring-like structures around unlabeled cell bodies. Thin varicose axon-like processes running to sublamina 3 are also present in significant number like in other diurnal animals. A few interplexiform cells are observed. Psammomys obesus rapidly develops hyperglycemia when held in captivity and fed normal synthetic laboratory rat diet, providing a model for the study of diabetes related impairment of dopamine metabolism in the retina. The pathomorphological analysis of TH-immunoreactivity was achieved in a population of diabetic Psammomys and compared with the normal. It indicates that moderate hyperglycemia induces a decrease of TH-immunoreactivity in dopamine dendrites only, while severe hyperglycemia can provoke dopamine neuron degeneration.


Clinical Use and Molecular Action of Corticosteroids in the Pediatric Age.
Corticosteroids are the mainstay of therapy for many pediatric disorders and sometimes are life-saving. Both endogenous and synthetic derivatives diffuse across the cell membrane and, by binding to their cognate glucocorticoid receptor, modulate a variety of physiological functions, such as glucose metabolism, immune homeostasis, organ development, and the endocrine system. However, despite their proved and known efficacy, corticosteroids show a lot of side effects, among which growth retardation is of particular concern and specific for pediatric age. The aim of this review is to discuss the mechanism of action of corticosteroids, and how their genomic effects have both beneficial and adverse consequences. We will focus on the use of corticosteroids in different pediatric subspecialties and most common diseases, analyzing the most recent evidence.


Sth1, the Key Subunit of the RSC Chromatin Remodeling Complex, Is Essential in Maintaining Chromosomal Integrity and Mediating High Fidelity Chromosome Segregation in the Human Fungal Pathogen Candida albicans.
Chromatin architecture influences gene expression and makes specialized chromatin domains. Factors including histone variants, histone modifiers and chromatin remodelers that define chromatin architecture impact chromosome related processes in Candida albicans. In this context, we sought to investigate the roles of the ATP-dependent chromatin remodeler, Remodel the Structure of Chromatin (RSC) in chromosome segregation of C. albicans. Sth1 is the key ATPase component of RSC and has profound roles in different cellular processes in Saccharomyces cerevisiae. We demonstrate that STH1 is an essential gene in C. albicans. The depletion of Sth1 induces pseudohyphal cells, abnormal spindle morphology, sensitivity toward anti-mitotic drugs and global cohesion defect suggesting an important role of Sth1 in kinetochore-microtubule related processes in C. albicans. Strikingly, Sth1 is required to maintain clustered kinetochores revealing the fact that RSC is required in kinetochore integrity. Taken together, we show that RSC plays an important role in various chromatin-templated processes including chromosome segregation in C. albicans.


Resistance to thyroid hormone accompanied by atrial fibrillation
Resistance to thyroid hormone (RTH), which is primarily caused by mutations in the thyroid hormone (TH) receptor beta (THRB) gene, is dominantly inherited syndrome of variable tissue hyposensitivity to TH. We herein describe a case involving a 22-year-old Japanese man with RTH and atrial fibrillation (AF) complaining of palpitation and general fatigue. Electrocardiography results revealed AF. He exhibited elevated TH levels and an inappropriately normal level of thyroidstimulating hormone (TSH). Despite being negative for anti-TSH receptor antibody, thyroid-stimulating antibody and anti-thyroperoxidase antibody, the patient was positive for anti-thyroglobulin (Tg) antibody. Genetic analysis of the THRB gene identified a missense mutation, F269L, leading to the diagnosis of RTH. Normal sinus rhythm was achieved after 1 week of oral bisoprolol fumarate (5 mg/day) administration. After 3 years on bisoprolol fumarate, the patient had been doing well with normal sinus rhythm, syndrome of inappropriate secretion of TSH (SITSH) and positive titer of anti-Tg antibody. Learning points: •• Atrial fibrillation can occur in patients with RTH. •• Only a few cases have been reported on the coexistence of RTH and atrial fibrillation. •• No consensus exists regarding the management of atrial fibrillation in patients with RTH. •• Administration of bisoprolol fumarate, a beta-blocker, can ameliorate atrial fibrillation in RTH.


Spiritual coping in rehabilitation - a comparative study: part 1.
Chronic illness is defined as a long-term disease that challenges a person's physical, psychological and spiritual wellbeing. However, individuals may adapt to their condition by adopting spiritual coping strategies that may or may not include religiosity. Part 1 of this article presents the methodology of this cross-sectional comparative study, which explored the spiritual coping of patients with chronic illness receiving rehabilitation services in Malta (n=44: lower limb amputation n=10; chronic heart disease n=9; osteoarthritis-in an institution n=10 and in the community n=15); and in Norway (n=16: post-hip/shoulder surgery n=5; chronic heart disease n=5; chronic pain n=6). Data were collected from seven purposive samples during focus group sessions. Roy's Adaptation Model (1984) and Neuman's Systems Model (2010) guided the study. While acknowledging the limitations of this study, the findings presented in Part 2 identify commonalities in the spiritual coping of patients irrespective of cultural differences between Malta and Norway. A set of recommendations address clinical practice, education and further research.


Computer-assisted surgery of the paranasal sinuses: technical and clinical experience with 368 patients, using the Vector Vision Compact system.
This paper presents our experience with a navigation system for functional endoscopic sinus surgery. In this study, we took particular note of the surgical indications and risks and the measurement precision and preparation time required, and we present one brief case report as an example. Between 2000 and 2004, we performed functional endoscopic sinus surgery on 368 patients at the Ludwig Maximilians University, Munich, Germany. We used the Vector Vision Compact system (BrainLAB) with laser registration. The indications for surgery ranged from severe nasal polyps and chronic sinusitis to malignant tumours of the paranasal sinuses and skull base. The time needed for data preparation was less than five minutes. The time required for preparation and patient registration depended on the method used and the experience of the user. In the later cases, it took 11 minutes on average, using Z-Touch registration. The clinical plausibility test produced an average deviation of 1.3 mm. The complications of system use comprised one intra-operative re-registration (18 per cent) and one complete failure (5 per cent). Despite the assistance of an accurate working computer, the anterior ethmoidal artery was incised in one case. However, in all 368 cases, we experienced no cerebrospinal fluid leaks, optic nerve lesions, retrobulbar haematomas or intracerebral bleeding. There were no deaths. From our experience with computer-guided surgical procedures, we conclude that computer-guided navigational systems are so accurate that the risk of misleading the surgeon is minimal. In the future, their use in certain specialized procedures will be not only sensible but mandatory. We recommend their use not only in difficult surgical situations but also in routine procedures and for surgical training.


Spitz's nevus arising on a nevus spilus.
The first case of a solitary dermal Spitz's nevus arising on a nevus spilus is described. The special variant of a combined Spitz's nevus may cause difficulties in differential diagnosis from malignant melanoma in association with a nevus spilus.


Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature.
Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs) in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5) and postnatal (P0, P3, P7) kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage), and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1) VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2) their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3) peritubular capillary VE-PTP expression is down-regulated in adult kidneys, suggesting a role of VE-PTP in the development of peritubular capillaries.


Cdo suppresses canonical Wnt signalling via interaction with Lrp6 thereby promoting neuronal differentiation.
Canonical Wnt signalling regulates expansion of neural progenitors and functions as a dorsalizing signal in the developing forebrain. In contrast, the multifunctional co-receptor Cdo promotes neuronal differentiation and is important for the function of the ventralizing signal, Shh. Here we show that Cdo negatively regulates Wnt signalling during neurogenesis. Wnt signalling is enhanced in Cdo-deficient cells, leading to impaired neuronal differentiation. The ectodomains of Cdo and Lrp6 interact via the Ig2 repeat of Cdo and the LDLR repeats of Lrp6, and the Cdo Ig2 repeat is necessary for Cdo-dependent Wnt inhibition. Furthermore, the Cdo-deficient dorsal forebrain displays stronger Wnt signalling activity, increased cell proliferation and enhanced expression of the dorsal markers and Wnt targets, Pax6, Gli3, Axin2. Therefore, in addition to promoting ventral central nervous system cell fates with Shh, Cdo promotes neuronal differentiation by suppression of Wnt signalling and provides a direct link between two major dorsoventral morphogenetic signalling pathways.


[Supracondylar humerus fracture in childhood--an efficacy study. Results of a multicenter study by the Pediatric Traumatology Section of the German Society of Trauma Surgery--I: Epidemiology, effectiveness evaluation and classification].
In this retrospective study of the pediatric trauma group of German trauma society, issued to investigate the state of the art treatment of the supracondylar fracture of the humerus, 13 clinics took part. In this first part of our study we tested the epidemiology and effectivity of therapeutic interventions based on the classification of v. Laer. 886 fractures were included with an average patients age of 5.8 years (+/- 2.9). Causes of trauma was in 45% playing, followed by school/kindergarden and sports injuries. Fractures were initially classified according to v. Laer and showed following displacement: 35.4% Type I, 21.9% Type II, 18.1% Type III and 24.6% Type IV. 10 of the 886 cases (1.1%) were open fractures. Damages to nerves were described in 45 patients (5.1%) and only 7 (0.7%) had primary vessel lesions. 476 patients were treated by reduction of fragments, 72% using a closed technical approach and 28% using an open approach. 6% underwent a second resposition-maneuver, which was mainly observed after crossed Kirschner-wire in type-III-and-IV-fractures. Therapy was changed in 5.1% mostly of the cases were initially closed reduced and then fixed with a collar and cuff sling. 540 patients were seen at follow-up (61%). 81.1% of these patients showed symmetrical axis compared to the uninjured arm. A varus-deformity was noted in 11.7%, a valgus-deformity in 7.2%. Analysis of effectivity showed that the primarily used classification was not sufficient for prediction of the outcome after reposition and retention. Therefore the classification was modified based on 4 groups: Type I undisplaced, Type II displacement in one plane, Type III displacement in two planes and Type IV displacement in three spatial planes. Using this classification we could found that in group II 25% of reduction an 7% of retentions were ineffective. For group III and IV we found that > 20% of the retention proofed to be ineffective.


Skill sharing and delegation practice in two Queensland regional allied health cancer care services: a comparison of tasks.
Objective Delegation and skill sharing are emerging service strategies for allied health (AH) professionals working in Queensland regional cancer care services. The aim of the present study was to describe the consistency between two services for the types and frequency of tasks provided and the agreement between teams in the decision to delegate or skill share clinical tasks, thereby determining the potential applicability to other services. Methods Datasets provided by two similar services were collated. Descriptive statistical analyses were used to assess the extent of agreement. Results In all, 214 tasks were identified as being undertaken by the services (92% agreement). Across the services, 70 tasks were identified as high frequency (equal to or more frequently than weekly) and 29 as not high frequency (46% agreement). Of the 68 tasks that were risk assessed, agreement was 66% for delegation and 60% for skill sharing, with high-frequency and intervention tasks more likely to be delegated. Conclusions Strong consistency was apparent for the clinical tasks undertaken by the two cancer care AH teams, with moderate agreement for the frequency of tasks performed. The proportion of tasks considered appropriate for skill sharing and/or delegation was similar, although variation at the task level was apparent. Further research is warranted to examine the range of factors that affect the decision to skill share or delegate. What is known about the topic? There is limited research evidence regarding the use of skill sharing and delegation service models for AH in cancer care services. In particular, the extent to which decisions about task safety and appropriateness for delegation or skill sharing can be generalised across services has not been investigated. What does this paper add? This study investigated the level of clinical task consistency between two similar AH cancer care teams in regional centres. It also examined the level of agreement with regard to delegation and skill sharing to provide an indication of the level of local service influence on workforce and service model decisions. What are the implications for practitioners? Local factors have a modest influence on delegation and skill sharing decisions of AH teams. Practitioners need to be actively engaged in decision making at the local level to ensure the clinical service model meets local needs. However, teams should also capitalise on commonalities between settings to limit duplication of training and resource development through collaborative networks.


[Adverse seizure reactions after electroconvulsive therapy. Study of personal cases and review of the literature].
To determine what are the risk factors for the occurrence of unwanted seizures after an ECT session, and what is the best attitude regarding future ECT. We have reviewed all the case reports published in the literature between 1946 and 1995 and have carried out a prospective case-control study of all incidental seizure type side effects among a group of 43 patients treated consecutively using the same procedure within the same institution in 1993. Results from the literature are presented in tables I to IV and results from our case-control study in tables V to VIII. Twenty seven seizure type side effects are reported in 22 published papers reporting the case of 24 patients. Most accidents occur during the first ECT and the occurrence of non convulsive seizures is greatly increased in case of coexisting EEG-monitoring. In our own study the overall incidence is 0.95%. Risk factors are neurologic disease, psychotropic medication, history of prolonged seizure during previous ECT. It appears that no unique risk factor but a summation of several risks (personal or family history of seizure, psychotropic medications, high energy level of electric stimuli) for specific subjects increases the risk for seizures after ECT. ECT can be resumed if necessary after occurrence of a post ECT seizure with addition of anti-epileptic medication.


[Hand-arm vibration syndrome in a nurse carrying out gypsum cutting operations].
A professional nurse, employed mainly on gypsum cutting operations, developed a hand-arm vibration syndrome with Raynaud's phenomenon, neurosensitive disorders and impairment of the bone and joints apparatus of the hand and arm. The nurse underwent diagnostic investigations (cold test, X-ray of the upper limbs, blood tests); also the vibration levels transmitted from instrument were measured and the exposure times were established. Clinical investigations showed the presence of a hand-arm vibration syndrome with secondary Raynaud's phenomenon and environmental surveys revealed very high vibration levels, such as could be associated with the disease with a causal relationship. In the literature no reports exist of the vibration syndrome being associated with health care workers in orthopaedic departments. The case described in this study occurred because of peculiar organisational factors that most likely have never occurred in other hospitals or orthopaedic departments.


Effect of two educational interventions on primary school teachers' knowledge and self-reported practice regarding emergency management of traumatic dental injuries.
The present study evaluated the effect of two educational interventions on the knowledge and self-reported practice of primary school teachers regarding emergency management of traumatic dental injuries (TDIs). All primary school teachers (n = 664) of Arak, Iran were asked to participate in the study. Based on geographic regions, all participants were enrolled in two groups: educational leaflet and oral presentation. At baseline, teachers in both groups were asked to complete an anonymous self-administrated questionnaire consisting of demographics, eight questions on knowledge, and four paper cases on self-reported practice about TDIs. After collecting the questionnaires, interventions, including an oral presentation and an educational leaflet whose contents were prepared based on the most recent scientific evidence, were implemented. One and six months after the interventions, the questionnaire was completed by the teachers again. Repeated measures ANOVA and a linear regression model were used for statistical analysis. Two hundred and ninety-two teachers participated in all stages of the study (response rate = 64.5%). In one-month follow-up, in both groups, the mean score of knowledge was significantly higher compared to baseline and six-month scores (P < 0.001 and P < 0.001, respectively). Moreover, in six-month follow-up, the mean score of knowledge was higher compared to baseline (P < 0.001) in both intervention groups. No statistically significant difference existed in the mean score of knowledge in three evaluations between two groups (P < 0.05). In one-month follow-up, the mean score of self-reported practice was significantly higher compared to baseline and six-month scores in both interventional groups (P < 0.001 and P < 0.001, respectively). There was no significant difference in the mean score of self-reported practice between the one-month and six-month follow-up (P = 0.53). There was no statistical significant difference in the mean score of self-reported practice in three evaluation phases between two groups (P < 0.05). No significant relationship was observed between the difference in knowledge and self-reported practice scores and demographic factors. Both educational interventions regarding emergency management of TDIs-educational leaflet and oral presentation- were effective in increasing knowledge and self-reported practice of teachers in the short-term follow-up. In long-term evaluation, educational leaflet resulted in more positive changes in teachers' knowledge compared to their self-reported practice.


Signatures of COVID-19 Severity and Immune Response in the Respiratory Tract Microbiome.
Viral infection of the respiratory tract can be associated with propagating effects on the airway microbiome, and microbiome dysbiosis may influence viral disease. Here, we investigated the respiratory tract microbiome in coronavirus disease 2019 (COVID-19) and its relationship to disease severity, systemic immunologic features, and outcomes. We examined 507 oropharyngeal, nasopharyngeal, and endotracheal samples from 83 hospitalized COVID-19 patients as well as non-COVID patients and healthy controls. Bacterial communities were interrogated using 16S rRNA gene sequencing, and the commensal DNA viruses Anelloviridae and Redondoviridae were quantified by qPCR. We found that COVID-19 patients had upper respiratory microbiome dysbiosis and greater change over time than critically ill patients without COVID-19. Oropharyngeal microbiome diversity at the first time point correlated inversely with disease severity during hospitalization. Microbiome composition was also associated with systemic immune parameters in blood, as measured by lymphocyte/neutrophil ratios and immune profiling of peripheral blood mononuclear cells. Intubated patients showed patient-specific lung microbiome communities that were frequently highly dynamic, with prominence of Staphylococcus. Anelloviridae and Redondoviridae showed more frequent colonization and higher titers in severe disease. Machine learning analysis demonstrated that integrated features of the microbiome at early sampling points had high power to discriminate ultimate level of COVID-19 severity. Thus, the respiratory tract microbiome and commensal viruses are disturbed in COVID-19 and correlate with systemic immune parameters, and early microbiome features discriminate disease severity. Future studies should address clinical consequences of airway dysbiosis in COVID-19, its possible use as biomarkers, and the role of bacterial and viral taxa identified here in COVID-19 pathogenesis. IMPORTANCE COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the respiratory tract, results in highly variable outcomes ranging from minimal illness to death, but the reasons for this are not well understood. We investigated the respiratory tract bacterial microbiome and small commensal DNA viruses in hospitalized COVID-19 patients and found that each was markedly abnormal compared to that in healthy people and differed from that in critically ill patients without COVID-19. Early airway samples tracked with the level of COVID-19 illness reached during hospitalization, and the airway microbiome also correlated with immune parameters in blood. These findings raise questions about the mechanisms linking SARS-CoV-2 infection and other microbial inhabitants of the airway, including whether the microbiome might regulate severity of COVID-19 disease and/or whether early microbiome features might serve as biomarkers to discriminate disease severity.


Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice.
Control db/+ and diabetic db/db mice at 6 and 12 wk of age were subjected to echocardiography to determine whether contractile function was reduced in vivo and restored in transgenic db/db-human glucose transporter 4 (hGLUT4) mice (12 wk old) in which cardiac metabolism has been normalized. Systolic function was unchanged in 6-wk-old db/db mice, but fractional shortening and velocity of circumferential fiber shortening were reduced in 12-wk-old db/db mice (43.8 +/- 2.1% and 8.3 +/- 0.5 circs/s, respectively) relative to db/+ control mice (59.5 +/- 2.3% and 11.8 +/- 0.4 circs/s, respectively). Doppler flow measurements were unchanged in 6-wk-old db/db mice. The ratio of E and A transmitral flows was reduced from 3.56 +/- 0.29 in db/+ mice to 2.40 +/- 0.20 in 12-wk-old db/db mice, indicating diastolic dysfunction. Thus a diabetic cardiomyopathy with systolic and diastolic dysfunction was evident in 12-wk-old diabetic db/db mice. Cardiac function was normalized in transgenic db/db-hGLUT4 mice, indicating that altered cardiac metabolism can produce contractile dysfunction in diabetic db/db hearts.


Identification of Ftr1 and Zrt1 as iron and zinc micronutrient transceptors for activation of the PKA pathway in Saccharomyces cerevisiae.
Multiple types of nutrient transceptors, membrane proteins that combine a transporter and receptor function, have now been established in a variety of organisms. However, so far all established transceptors utilize one of the macronutrients, glucose, amino acids, ammonium, nitrate, phosphate or sulfate, as substrate. This is also true for the Saccharomyces cerevisiae transceptors mediating activation of the PKA pathway upon re-addition of a macronutrient to glucose-repressed cells starved for that nutrient, re-establishing a fermentable growth medium. We now show that the yeast high-affinity iron transporter Ftr1 and high-affinity zinc transporter Zrt1 function as transceptors for the micronutrients iron and zinc. We show that replenishment of iron to iron-starved cells or zinc to zinc-starved cells triggers within 1-2 minutes a rapid surge in trehalase activity, a well-established PKA target. The activation with iron is dependent on Ftr1 and with zinc on Zrt1, and we show that it is independent of intracellular iron and zinc levels. Similar to the transceptors for macronutrients, Ftr1 and Zrt1 are strongly induced upon iron and zinc starvation, respectively, and they are rapidly downregulated by substrate-induced endocytosis. Our results suggest that transceptor-mediated signaling to the PKA pathway may occur in all cases where glucose-repressed yeast cells have been starved first for an essential nutrient, causing arrest of growth and low activity of the PKA pathway, and subsequently replenished with the lacking nutrient to re-establish a fermentable growth medium. The broadness of the phenomenon also makes it likely that nutrient transceptors use a common mechanism for signaling to the PKA pathway.


Is there a difference in cognitive development between preschool singletons and twins born after intracytoplasmic sperm injection or in vitro fertilization?
To explore whether there exist differences in cognitive development between singletons and twins born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). A total of 566 children were recruited for the study, including 388 children (singletons, n=175; twins, n=213) born after IVF and 178 children (singletons, n=87; twins, n=91) born after ICSI. The cognitive development was assessed using the Chinese-Wechsler Intelligence Scale for Children (C-WISC). For all pre-term offspring, all the intelligence quotient (IQ) items between singletons and twins showed no significant differences no matter if they were born after IVF or ICSI. There was a significant difference in the cognitive development of IVF-conceived full-term singletons and twins. The twins born after IVF obtained significantly lower scores than the singletons in verbal IQ (containing information, picture & vocabulary, arithmetic, picture completion, comprehension, and language), performance IQ (containing maze, visual analysis, object assembly, and performance), and full scale IQ (P<0.05). The cognitive development of full-term singletons and twins born after ICSI did not show any significant differences. There was no significant difference between the parents of the singletons and twins in their characteristics where data were collected, including the age of the mothers, the current employment status, the educational backgrounds, and areas of residence. There were also no consistent differences in the duration of pregnancy, sex composition of the children, age, and height between singletons and twins at the time of our study although there existed significant differences between the two groups in the sex composition of the full-term children born after ICSI (P<0.05). Compared to the full-term singletons born after IVF, the full-term twins have lower cognitive development. The cognitive development of full-term singletons and twins born after ICSI did not show any significant differences. For all pre-term offspring, singletons and twins born after IVF or ICSI, the results of the cognitive development showed no significant differences.


Attributable mortality of Stenotrophomonas maltophilia bacteremia.
A systematic evaluation of the attributable mortality of Stenotrophomonas maltophilia bacteremia was undertaken in a matched, retrospective, case-control study. We determined the attributable mortality rate (26.7%) and mortality risk ratio (an 8-fold increase) of S. maltophilia bacteremia. The attributable mortality rate for S. maltophilia bacteremia is similar to the attributable mortality rate for other nosocomial bloodstream infections.


Ovsynch Plus protocol improves ovarian response in anovular Murrah buffaloes in low-breeding season.
The objective of the study was to evaluate the efficacy of ovarian response and pregnancy rate in anovular buffaloes following Ovsynch and Ovsynch Plus protocols. Buffaloes (n = 55) were divided into two groups: Ovsynch group (n = 26): GnRH (10 μg, GnRH1) on Day 0, PGF2 α (25 mg) on Day 7, GnRH (10 μg, GnRH2) on Day 9; Ovsynch Plus group (n = 29): 500 IU equine chorionic gonadotropin (eCG) 72 hr (day -3) prior to Ovsynch protocol, followed by fixed timed artificial insemination (FTAI) 6 and 24 hr after GnRH2 injection in bot groups. Transrectal ultrasonography was performed daily, that is, from day 0 and -3 in Ovsynch and Ovsynch Plus group, respectively for ovarian response and pregnancy diagnosis at day 30 post-insemination. In Ovsynch Plus group, administration of eCG prior to GnRH1 increased (p < .001) the diameter (mm) of dominant follicle (DF) from 10.15 ± 0.26 to 12.23 ± 0.34 within 72 hr of treatment resulting higher ovulatory response to GnRH1. Ovulation after GnRH1 was higher (p < .01) in Ovsynch Plus group (96.6%) than Ovsynch group (61.5%). However, ovulation rate to GnRH2 was similar (p > .05) between groups (Ovsynch group: 76.9% vs. Ovsynch Plus group: 70.0%). Mean DF diameter (mm) that ovulated to both GnRHs was higher (p < .01) than non-ovulated counterparts in both groups (Ovsynch group: 10.80 ± 0.27 vs. 8.47 ± 0.53; Ovsynch Plus group: 11.99 ± 0.24 vs. 9.5 ± 0.63). Pregnancy was established in buffaloes which responded to both GnRHs, irrespective of groups, being higher (p = .52) in Ovsynch Plus group (34.5%) than Ovsynch group (23.1%), though non-significant. In summary, this study showed that eCG inclusion prior to Ovsynch regimen improves ovulatory response in anovular buffaloes during low-breeding season.


Methods and initial findings of the Observational Study of Ostomy Consumers Registry.
Longitudinal patient-reported data are limited for people living with an ostomy. The Observational Study of Ostomy Consumers (OSO) registry collects data from individuals living with an ostomy. Self-reported data were collected via repeated electronic surveys completed by adults living with an ostomy in the United States (US) and United Kingdom (UK). Baseline data, collected between October 2018 and February 2021, were available for 299 individuals from the US (77.9%) and UK (22.1%). Most participants reported using a 2-piece pouching system (55.5%) rather than a 1-piece system (44.4%), and using a convex barrier (54.4%) or flat barrier (44.3%). The most commonly reported barrier wear times were ≥ 3 to < 4 days for 36.6% of participants in the US and ≥ 1 to < 2 days for 42.4% of participants in the UK. Despite self-reports of leakage and peristomal skin conditions, quality of life remained positive. A majority of participants (92.0%) reported being very satisfied or somewhat satisfied with their ostomy product. The Observational Study of Ostomy Consumers registry allows for a continuous data stream that can be mined to help understand the patient experience over time. Understanding patient experiences will help to inform clinical practice and research, health care utilization, and product innovation.


Recurarization after sugammadex reversal in an obese patient.
We report a case that involved immediate postoperative respiratory failure necessitating tracheal intubation, which was possibly related to recurarization after sugammadex reversal. A 54-yr-old woman weighing 115-kg was scheduled for laparoscopic repair of abdominal dehiscence under general anesthesia. Muscle relaxation was induced and maintained with rocuronium (170 mg iv total dose). At the end of the 170-min procedure, two twitches were visualized after supramaximal train-of-four (TOF) stimulation at the adductor pollicis muscle, and the patient's central core temperature was 35.6°C. Sugammadex 200 mg iv (1.74 mg·kg(-1)) was administered. With the patient fully awake, a TOF ratio 0.9 was obtained five minutes later. The tracheal tube was then removed, and the patient was transferred to the postanesthesia care unit. Ten minutes later, the patient presented respiratory failure necessitating tracheal intubation and sedation with propofol. One TOF response only was visualized at the adductor pollicis muscle. Another dose of sugammadex 200 mg iv was administered. Forty-five minutes later, the patient was fully awake and her trachea was extubated after repeated measures of the TOF ratio (≥ 0.9) at the adductor pollicis muscle. The patient fully recovered without sequelae, further complication, or prolonged hospital stay. Shortly after tracheal extubation, an obese patient experienced respiratory failure necessitating tracheal intubation and an additional dose of sugammadex. This occurred despite initial reversal of neuromuscular blockade with an appropriate dose of sugammadex 2 mg·kg(-1) iv given at two responses to TOF stimulation.


Antimicrobial Effects of Garcinia Mangostana on Cariogenic Microorganisms.
Garcinia mangostana commonly called as Mangosteen fruit has been used as an antibacterial agent since age old times. The mangosteen pericarp has proven to have antibacterial effect, but the effect of the same on cariogenic organisms has not been explored. The present study was an attempt to gain a better understanding of the antibacterial effect of mangosteen pericarp on the cariogenic bacteria, to unravel the therapeutic potential for the same. The aim of the study was to assess the antibacterial efficacy of the crude chloroform extract of mangosteen pericarp against cariogenic bacteria. The study was done under laboratory settings using an in vitro design. The microorganisms namely Streptococcus mutans, Streptococcus sanguis, Streptococcus salivarius, Streptococcus oralis and Lactobacillus acidophilus were procured from American Type Cell Culture (ATCC) and Microbial Type Culture Collection (MTCC) were revived and lawn cultured. The antibacterial effect of mangosteen pericarp was tested using agar well diffusion method on Trypticase Soy Agar-Blood Agar (TSA-BA) and de Man, Rogosa and Sharpe (MRS) agar media. The standard antiplaque agent chlorhexidine was used as the positive control. This cross-sectional, experimental study was done in Central Research laboratory, Meenakshi Ammal Dental College for period of eight weeks. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values were determined by microbroth dilution method. Statistical analysis was done by calculating the mean of the zones of inhibition on tested microorganisms. Mann-Whitney test was done to compare the zones of inhibition of mangosteen and chlorhexidine. The antibacterial bioassay showed the highest activity for Lactobacillus acidophilus (13.6 mm) and Streptococcus sanguis (13.6 mm), whereas, it showed a medium and low activity for Streptococcus oralis (11.3 mm), Streptococcus mutans (10.6 mm) and Streptococcus salivarius (3 mm) respectively. The MBC and MIC values were lowest for Lactobacillus acidophilus (MIC 25 mg/ml, MBC 50 mg/ml) and Streptococcus oralis (MIC 50 mg/ml, MBC 100 mg/ml). Mangosteen pericarp extract had a higher zone of inhibition against the tested microorganisms which suggests its potent antibacterial action against cariogenic organisms. However, further analytical studies are needed to isolate the key molecules of mangosteen pericarp, to explore its anticariogenic therapeutic potential on gram negative oral microorganisms.


Axonal morphological changes following impulse activity in mouse peripheral nerve in vivo: the return pathway for sodium ions.
Conduction in myelinated axons involves substantial ion movements that must be reversed to restore homeostasis. The pathway taken by sodium ions returning to their original location and the potential osmotic consequences are currently unknown. We report striking morphological changes in axons following sustained impulse conduction that appear to result from osmosis and to indicate accumulation of ions in the periaxonal space followed by their release at the paranode. We conclude that the morphological changes illustrate a hitherto unrecognized part of normal axonal physiology that may also indicate the return pathway for the sodium ions involved in impulse formation. Myelinated axons can conduct sustained trains of impulses at high frequency, but this involves substantial ion movements that must be reversed to restore homeostasis. Little attention has been paid to the potential osmotic consequences of the ion movements or to the pathway taken by sodium ions returning to their original endoneurial location, given that the axolemmal Na(+)-K(+)-ATPase extrudes these ions into the periaxonal space beneath the myelin rather than into the endoneurium. Serial confocal imaging of fluorescent axons conducting at sustained physiological frequencies in vivo has revealed surprising morphological changes that may illuminate these problems. Saphenous nerves and spinal roots of anaesthetized transgenic mice expressing axoplasmic yellow fluorescent protein were stimulated electrically or pharmacologically (veratridine). Within 2 h, the axon herniated on one or both sides of the nodal membrane, displacing the paranodal myelin and widening the nodal gap. The herniated axoplasm became directed back towards the internode, forming a 'cap' up to 30 μm long. Concurrently, the fluid in the expanded periaxonal space accumulated into droplets that appeared to travel to the paranode, where they escaped. No such alterations occurred in axons treated with sodium channel or Na(+)-K(+)-ATPase inhibitors. Remarkably, impulse conduction continued throughout, and all these changes reversed spontaneously over hours or days. The morphological changes were verified ultrastructurally, and occurred in virtually all myelinated axons. The findings appear to reveal an overlooked part of the physiological repertoire of nerve fibres, and here they are interpreted in terms of osmotic changes that may illuminate the pathway by which sodium ions return to the endoneurial space after they have entered the axon during impulse conduction.


Human immunodeficiency virus type 1-related pulmonary Mycobacterium xenopi infection: a need to treat?
We report treatment decisions and outcomes for 20 patients who were infected with human immunodeficiency virus type 1 (HIV-1) and were receiving highly active antiretroviral therapy (HAART) who had respiratory symptoms and from whom Mycobacterium xenopi was isolated. All patients also had coexisting pulmonary pathologic conditions. The median blood T cell CD4 count was 37 cells/microL (range, 2-480 cells/microL). Fifteen of 20 patients received no antimycobacterial therapy and remain healthy after a median of approximately 4 years of follow-up, and 2 patients required treatment specifically for M. xenopi infection, both showing clinical improvement. We conclude that pulmonary M. xenopi isolation in HIV-1 patients receiving HAART does not usually require specific treatment.


Therapeutic Implications of Molecular Subtyping for Pancreatic Cancer.
The prognosis of metastatic pancreatic adenocarcinoma has recently begun to improve. In the last several years, first-line therapy with gemcitabine plus nab-paclitaxel or a regimen of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has boosted the median overall survival (OS) duration to 8.5 months and 11 months, respectively, in patients with metastatic pancreatic cancer, compared with a historic OS of only 6 months prior to 2011. Moreover, sequencing these two regimens improved median OS to an unprecedented 18 months. Notably, as newer agents become available and undergo testing, there is some indication that certain subgroups of patients may benefit dramatically from therapies targeting specific pathways in pancreatic cancer. There have been several attempts to assess the molecular differences in the driving mechanisms of pancreatic cancers, and to link these to specific therapies that could be remarkably effective in selected patients. These molecular analyses-based primarily on assessment of DNA mutations but also incorporating RNA sequencing and, in some cases, protein expression analysis-are beginning to reveal specific subtypes of pancreatic adenocarcinoma. Identification of the appropriate therapy for these subtypes may lead to further improved OS in the relevant patient populations. In this article, we review seminal articles that have evaluated the molecular architecture of pancreatic cancer. We compare the methods used and the molecular subtypes defined, and assess the predominant subgroups in order to better understand which therapies may improve patient outcomes.


Medical students: learning experience in physical medicine and rehabilitation.
Every medical student at Mayo Medical School participates in a three-week training program in the department of physical medicine and rehabilitation. Since 1974-1975, approximately 40 students have had this experience each academic year. In addition to lectures, the learning experience includes clinical cases involving hospitalized patients and outpatients. Students are evaluated by written and oral examinations. At the end of the course, the students submit a list of patients seen during their rotation and another list of procedures they learned. For the classes of 1980, 1981, and 1982, the frequency of medical conditions seen and procedures learned by the medical students have been computed. The most common conditions seen by the 116 students were low back pain (92.2%), hemiplegia (87.9%), paraplegia (85.3%), quadriplegia (81%), and tension myalgia (79.3%). The procedures learned and demonstrated most frequently were crutch gaits (95.7%), muscle testing (94%), and goniometry (94%). Sixty students returned course evaluation forms at the conclusion of the program, the results of which indicated that high value is placed on this educational program.


Binding of Tat protein to TAR region of human immunodeficiency virus type 1 blocks TAR-mediated activation of (2'-5')oligoadenylate synthetase.
The TAR sequence of the 5' leader of HIV-1 long terminal repeat-directed mRNA was found to be able to bind to and to activate double-stranded RNA-dependent (2'-5')A synthetase. Binding of TAR to the purified synthetase in vitro was abolished by addition of HIV-1 Tat protein, which binds to this sequence with a high affinity. Inhibition of TAR-mediated activation of (2'-5')A synthetase by Tat was prevented in the presence of the Zn2+ and Cd2+ chelators o-phenanthroline and penicillamine, which did not impair TAR-synthetase interaction. Transient expression assays of bacterial chloramphenicol acetyltransferase (CAT) gene in HeLa cells revealed that the levels of both CAT mRNA and CAT protein decreased after treatment of the cells with interferon, if CAT gene was linked to HIV-1 TAR segment. Cotransfection of the cells with a tat sequence containing plasmid rendered CAT gene expression insensible to the action of interferon.


[Protective effects of Ginkgo biloba extract on focal cerebral ischemia and thrombogenesis of carotid artery in rats].
Rat focal cerebral ischemia induced by occlusion and thrombogenesis of middle cerebral artery(MCAO) was used as experimental model to study the effects of extract of Ginkgo biloba (EGb) and the positive control drugs were urokinase and nimodipine on cerebral infarct size and neurological deficits. The results showed that cerebral ischemia and neurological deficits appeared in rat focal cerebral ischemic models, and the degree was of cerebral ischemia larger in occlusion model than in thrombogenesis model. The cerebral infarct size was significantly smaller and neurological deficits greatly improved at large dose of EGb(200 mg.kg-1, i.v.), the preventive effect appeared to be better than the treatment effect. The positive control drugs urokinase and nimodipine were also shown to distinctly decrease the cerebral infarct size and improve the neurological deficits in the models. Small dose of EGb(100 mg.kg-1, i.v.) was found to decrease the cerebral infarct size of thrombogenesis model, and improve neurological deficits of both thrombogenesis and occlusion model. EGb was also shown to inhibit the thrombogensis of rat common carotid artery stimulated by electrical current in dose-dependent manner. This experiment indicates that EGb might have beneficial effects on prevention and treatment of ischemic stroke and thrombogenesis.


Accounting for treatment use when validating a prognostic model: a simulation study.
Prognostic models often show poor performance when applied to independent validation data sets. We illustrate how treatment use in a validation set can affect measures of model performance and present the uses and limitations of available analytical methods to account for this using simulated data. We outline how the use of risk-lowering treatments in a validation set can lead to an apparent overestimation of risk by a prognostic model that was developed in a treatment-naïve cohort to make predictions of risk without treatment. Potential methods to correct for the effects of treatment use when testing or validating a prognostic model are discussed from a theoretical perspective.. Subsequently, we assess, in simulated data sets, the impact of excluding treated individuals and the use of inverse probability weighting (IPW) on the estimated model discrimination (c-index) and calibration (observed:expected ratio and calibration plots) in scenarios with different patterns and effects of treatment use. Ignoring the use of effective treatments in a validation data set leads to poorer model discrimination and calibration than would be observed in the untreated target population for the model. Excluding treated individuals provided correct estimates of model performance only when treatment was randomly allocated, although this reduced the precision of the estimates. IPW followed by exclusion of the treated individuals provided correct estimates of model performance in data sets where treatment use was either random or moderately associated with an individual's risk when the assumptions of IPW were met, but yielded incorrect estimates in the presence of non-positivity or an unobserved confounder. When validating a prognostic model developed to make predictions of risk without treatment, treatment use in the validation set can bias estimates of the performance of the model in future targeted individuals, and should not be ignored. When treatment use is random, treated individuals can be excluded from the analysis. When treatment use is non-random, IPW followed by the exclusion of treated individuals is recommended, however, this method is sensitive to violations of its assumptions.


Cellular automaton model for the simulation of laser dynamics.
The classical modeling approach for laser study relies on the differential equations. In this paper, a cellular automaton model is proposed as an alternative for the simulation of population dynamics. Even though the model is simplified it captures the essence of laser phenomenology: (i) there is a threshold pumping rate that depends inversely on the decaying lifetime of the atoms and the photons; and (ii) depending on these lifetimes and on the pumping rate, a constant or an oscillatory behavior can be observed. More complex behaviors such as spiking and pattern formation can also be studied with the cellular automaton model.


Possible Role of Polymorphisms in TNFA, NFKB1, and CASP8 Gene Promoter Areas in the Development of Chronic Lymphocytic Leukemia.
We studied the relationship between polymorphisms rs1800629 (-308G>A), rs28362491 (-94ins>del), and rs3834129 (-652ins>del) in the promoter regions of TNFA, NFKB1, and CASP8 genes, respectively, encoding TNF-α, nuclear transcription factor κB1 (NF-κB1), and caspase 8 (CASP8), and the risk and stages of chronic lymphocytic leukemia in ethnic Russians, residents of the Vyatka region of Russia. Allele -308A, genotype -308AA, and -308A genotypes (-308AA/-308AG) were associated with the risk of this pathology (OR=1.64, 95%CI 1.14-2.37, p=0.007; OR=4.48, 95%CI 1.20-16.80, p=0.02, and OR=1.57, 95%CI 1.05-2.36, p=0.03). In addition, NFKB1 allele -94del and genotype -94del/del were associated with advanced stages of the disease at the time of diagnosis (OR=0.66, 95%CI 0.46-0.97, p=0.03 and OR=0.43, 95%CI 0.20-0.92, p=0.03). These data suggest that -308G>A and -94ins>del polymorphisms of genes TNFA and NFKB1, respectively, can be involved in the pathogenesis of chronic lymphocytic leukemia.


Temporomandibular Joint Dislocation in an 18-month-old Child.
Temporomandibular joint (TMJ) dislocation in children is extremely rare. In our case, an 18-month-old child presented with a history of inability to close her mouth. To confirm the clinical diagnosis, a computed tomogram was taken. Clinical examination and X-ray of the TMJ revealed bilateral TMJ dislocation. Bilateral TMJ reduction was achieved manually after giving analgesia and procedural sedation. This is one of the few case reports of an acute dislocation in a toddler.


Size-Dependent Cytotoxicity and Reactive Oxygen Species of Cerium Oxide Nanoparticles in Human Retinal Pigment Epithelia Cells.
The use of cerium oxide nanoparticles (CeO2 NPs), a lanthanide element oxide and bivalent compound, has been growing continuously in industry and biomedicine. Due to their wide application, the potential human health problems of CeO2 NPs have attracted attention, but studies on the toxicity of this compound to human eyes are lacking. This study investigated the cytotoxicity and reactive oxygen species (ROS) of CeO2 NPs in human retinal pigment epithelial cells (ARPE-19 cells). Using the transmission electron microscope (TEM), the size distribution and shape of CeO2 NPs were characterized. To explore the effect of CeO2 NP size on ophthalmic toxicity in vitro, three sizes (15, 30 and 45 nm) of CeO2 NPs were investigated using ATP content measurement, LDH release measurement and cell proliferation assay in ARPE-19 cells. ROS values and mitochondrial membrane potential depolarization were evaluated by H2DCF-DA staining and JC-1 staining. Morphology changes were detected using a phase-contrast microscope. The cytotoxicity of 15 nm CeO2 NPs was found to be the highest and hence was further explored. Treatment with 15 nm CeO2 NPs caused the morphology of ARPE-19 cells to change in a dose- and time-dependent manner. Moreover, the treatment induced excessive ROS generation and mitochondrial membrane potential depolarization. In addition, cytotoxicity was attenuated by the application of a ROS scavenger N-acetyl-L- cysteine (NAC). CeO2 NPs induced cytotoxicity in ARPE-19 cells and excessive production of ROS and decreasing mitochondrial membrane potential. The Overproduction of ROS partially contributes to CeO2 NP-induced cytotoxicity.


Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Dupilumab in Healthy Adult Subjects.
Dupilumab is a fully human monoclonal antibody directed against the interleukin (IL)-4 receptor α subunit (IL-4Rα) of IL-4 heterodimeric type I and type II receptors that mediate IL-4/IL-13 signaling through this pathway. Blockade of these receptors broadly suppresses type 2 inflammation associated with atopic/allergic diseases, including atopic dermatitis and asthma. Six phase 1 studies investigated the pharmacokinetics, pharmacodynamics, safety, and tolerability of dupilumab in healthy subjects. Two randomized, double-blind, placebo-controlled, sequential studies assessed safety and tolerability of single escalating dupilumab doses administered intravenously or subcutaneously (one included various racial groups, and one included exclusively Japanese subjects); 3 randomized, parallel-group, single-dose studies compared the pharmacokinetic profiles of different dupilumab products and formulations after single subcutaneous doses; and one study assessed dupilumab administered as fast versus slow subcutaneous injections. Dupilumab concentrations in serum were measured in all studies, and total immunoglobulin E (IgE) and thymus- and activation-regulated chemokine (TARC) concentrations were measured in 2 studies as pharmacodynamic markers. Across the phase 1 studies, dupilumab exhibited target-mediated pharmacokinetics consisting of parallel linear and nonlinear elimination, with the target-mediated phase highly dominated by nonlinearity at lower drug concentrations. Systemic exposure and tolerability of dupilumab were consistent irrespective of differences in product, formulation, or racial background. Dupilumab reduced circulating concentrations of total IgE and TARC, indicating blockade of IL-4Rα-mediated signaling. Dupilumab had a favorable safety profile across the wide range of doses administered. Together, these findings support the continued development and use of dupilumab in treatment of type 2 diseases.


Age Predicts Disruption of the Articular Surface of the Femoral Condyles in Knee OCD: Can We Reduce Usage of Arthroscopy and MRI?
The purpose of this study was to determine if patient age could accurately identify disrupted articular cartilage overlying an osteochondritis dissecans (OCD) lesion of the femoral condyle in adolescents. This could have important implications for imaging and treatment decisions. All patients from 2001 to 2014 who were arthroscopically treated for a femoral condyle OCD were included in this Institutional Review Board-approved study. Exclusion criteria were trochlear and patellar OCD lesions, idiopathic arthritis, and traumatic osteochondral injuries. Arthroscopy was performed to visualize and probe the articular surface. Arthroscopic and magnetic resonance imaging (MRI) findings were recorded as "intact" or "disrupted" cartilage. Extra-articular drilling was performed when the articular cartilage was intact. There were 119 patients (81 male, 68%) with 139 OCD lesions in 136 knees. The mean age at time of surgery was 13.0 years (range, 7.2 to 19.3 y). At arthroscopy, 115 knees had intact cartilage and 24 had disrupted cartilage. There was a significant difference in age between patients with intact versus disrupted cartilage at arthroscopy (12.5 vs. 15.3 y; P<0.0001). Eighty-eight OCD lesions had MRIs preoperatively, showing 69 as intact and 19 (24%) disrupted. MRI reading for cartilage status had 94% sensitivity and 97% specificity. Multivariable regression analysis revealed that age (P<0.01) and MRI status (P<0.0001) were strong predictors of cartilage status. Sixteen years was the critical age in which both sensitivity was maximized and false positive probability was minimized. Over the age of 17 years, 7 of 7 (100%) had disrupted cartilage. Age alone was 100% sensitive for children below the age of 10, and 96% sensitive below the age of 13. Age was a good predictor of cartilage status in both younger (<13 y) and older (≥17 y) patients in this study. For patients in the mid-range group (13 through 16 y), age alone is not an adequate predictor of cartilage status, but adding MRI increased accuracy. Age can be used to stratify patients and thereby influence diagnostic and treatment strategies. Level IV.


Pharmacokinetics of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women.
Estetrol (E4) is a natural fetal estrogen. In this open-label, multiple-rising-dose study, the pharmacokinetic effects of E4 in postmenopausal women were investigated as a secondary objective. In total, 49 postmenopausal women were randomized to receive either 2 mg E4 or 2 mg estradiol valerate (E2V) for 28 days, or were (non-randomized) assigned to 10, 20, or 40 mg E4. The main outcome measures were: E4 plasma concentrations at trough, and on days 1 and 28; and E4 pharmacokinetic parameters AUC, Cmax and tmax on days 1 and 28. After oral administration, E4 showed a very fast absorption, followed by a multiphasic elimination with an initial rapid decline, gradually continuing with a slower elimination, suggesting a long terminal half-life. Steady state was reached within 2 weeks of dosing and pharmacokinetic results were generally proportional to the dose. Estetrol concentrations on day 28 were slightly higher compared to day 1, indicating some accumulation. The pharmacokinetic profile of estetrol is characterized by a very fast absorption phase, followed by an initial rapid decline, and a slow terminal elimination phase. Based on its kinetic properties, estetrol seems suitable for use as a once-daily oral drug.


Relationship between the extent of chromosomal losses and the pattern of CpG methylation in gastric carcinomas.
The extent of unilateral chromosomal losses and the presence of microsatellite instability (MSI) have been classified into high-risk (high- and baseline-level loss) and low-risk (low-level loss and MSI) stem-line genotypes in gastric carcinomas. A unilateral genome-dosage reduction might stimulate compensation mechanism, which maintains the genomic dosage via CpG hypomethylation. A total of 120 tumor sites from 40 gastric carcinomas were examined by chromosomal loss analysis using 40 microsatellite markers on 8 chromosomes and methylation analysis in the 13 CpG (island/non-island) regions near the 10 genes using the bisulfite-modified DNAs. The high-level-loss tumor (four or more losses) showed a tendency toward unmethylation in the Maspin, CAGE, MAGE-A2 and RABGEF1 genes, and the other microsatellite-genotype (three or fewer losses and MSI) toward methylation in the p16, hMLH1, RASSF1A, and Cyclin D2 genes (p<0.05). The non-island CpGs of the p16 and hMLH1 genes were hypomethylated in the high-level-loss and hypermethylated in the non-high-level-loss sites (p<0.05). Consequently, hypomethylation changes were related to a high-level loss, whereas the hypermethylation changes were accompanied by a baseline-level loss, a low-level loss, or a MSI. This indicates that hypomethylation compensates the chromosomal losses in the process of tumor progression.


Human immunodeficiency virus and hepatitis B virus co-infections among tuberculosis patients attending a Model Rural Health Research Unit in Ghatampur, North India.
This prospective cross-sectional hospital-based study was carried out in order to assess the prevalence of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections among patients with active tuberculosis (TB) disease attending an Outpatient Department (OPD) at the Model Rural Health Research Unit in Ghatampur, a rural village in Kanpur district. The socio-demographic features and clinical profile of the TB patients were analysed in the context of symptoms at the time of testing. The HIV and HBV status were determined and correlated with clinical features at the time of testing. In our study, the prevalence of HIV infection among TB patients is 1.48% (18/1215) and that of HBsAg reactivity was found to be 2.96% (36/1215). During 2007-2010, the HIV-positivity varied between 1.5% and 1.45% whereas HBV reactivity ranged between 2.4% and 3.63%.A substantial percentage of the TB patients attending the OPD in Ghatampur harbour HIV and HBV infections, which otherwise would remain undiagnosed without serological screening. Co infection with HBV among TB patients potentiate the risk of anti-tuberculous therapy-induced hepatotoxicity, therefore, exercising caution and carefully monitoring the patients for drugs associated hepatotoxicity is essential. There is an urgent need to perform population-based surveys of HIV and hepatitis infections among TB patients to assess the true extent of the problem. Efforts should be made to make physicians aware of the peculiarities and manage these patients effectively.


GaN Epitaxial Layer Grown with Conductive Al(x)Ga(1-x)N Buffer Layer on SiC Substrate Using Metal Organic Chemical Vapor Deposition.
This study investigated GaN epitaxial layer growth with a conductive Al(x)Ga(1-x)N buffer layer on n-type 4H-SiC by high-temperature metalorganic chemical vapor deposition (HT-MOCVD). The Al composition of the Al(x)Ga(1-x)N buffer was varied from 0% to 100%. In terms of the crystal quality of the GaN layer, 79% Al was the optimal composition of the Al(x)Ga(1-x)N buffer layer in our experiment. A vertical conductive structure was fabricated to measure the current voltage (I-V) characteristics as a function of Al composition, and the I-V curves showed that the resistance increased with increasing Al concentration of the Al(x)Ga(1-x)N buffer layer.


The Evidence Paradox of the Effectiveness between the Paediatric and Adult Stone-Forming Population: A Narrative Review.
To identify trends in the evidence base regarding the effectiveness of using α-blockers in children versus adults and compare outcomes. A literature search up using the key words including urolithiasis/renal/ureteric stone in children/paediatric population, medical expulsive treatment (MET), α-blocker/alfuzosin/tamsulosin/doxazosin. Included were randomized or controlled clinical trials in paediatric stone formers (aged ≤18 years). Outcome measures for assessment included the overall stone expulsion rate, expulsion time, the number of pain episodes and adverse drug effects and/or reactions. Further comparison of efficacy levels using respective studies from the adult population was performed in order to identify trends, similarities and differences. A total of 8,259 articles were identified. Full text evaluation was possible for 28 articles. Although the picture is clearer in the paediatric group, the lack of reproducible results in adults certainly poses serious questions about data collection, analysis and interpretation in each individual study. The apparent paradox is due to the methodological differences between studies. The effectiveness of α-blockers and other medication as MET needs to be studied in multi-institutional, double-blind, placebo-controlled studies that would aim to prove superiority to placebo in contemporary clinical situations, with realistic end points and standardized outcome measure determination.


[Professional development of nurses in promoting health].
This research aims to help the nursing staff and it will help them to develop the skills to use among the school community. On top of her ordinary skills and beyond simple prescriptions, a nurse also has to teach and promote health. It is believed that there is a link between the professional and the personal development. This research deals with the different approaches of (N=30) nurses working within different schools in « Ille et Vilaine ». Nurses ?experiences have been questioned to identify how this professional development centered on three issues : awareness ; identity process and what group they belong to. This qualitive research lies on varied tools that use a compared analysis based on two different types : an oral interview and a pondering written part.


Cold agglutinin formation in patients undergoing haemodialysis. A possible relationship to dialyser re-use.
Cold agglutinins with anti-N characteristics were shown to develop in as short a time as four months in patients on home dialysis. It appeared that the development of such antibodies is related to dialyser re-use. Those who were treated without re-using their dialyser did not develop these antibodies. Anti-N may cause early graft failure associated with agglutination in a cold allograft. Moreover, if these antibodies develop in patients on dialysis there may be problems with extracorporeal dialysis and blood transfusion.


To avoid or eliminate: cestode infections in copepods.
The outcome of a parasite infection is the result of the interaction between the host and the parasite. In the system we studied, there are 3 critical stages for the outcome of infection of the (intermediate) host, the copepod Macrocyclops albidus, with the cestode Schistocephalus solidus. During the establishment phase of the parasite, the host may firstly avoid ingesting the parasite and, secondly, may prevent the parasite from entering the body cavity and, thirdly, during the growth phase of the parasite, the host's immune system may eliminate the parasite from the body cavity. We were able to study the growth phase separately from the establishment phase. The establishment phase was influenced by characteristics of the host as well as characteristics of the parasites. Small copepods and males performed poorly; they were more often infected and had a lower survival. Parasites from different sib-groups differed in infectivity. During the growth phase some disappearance of parasites was observed. However, this could not be related to any of the studied characteristics of the host, and the sib-groups of parasites did not seem to differ in their likelihood to disappear. Instead, we suggest that disappearance of parasites, once they have entered the body cavity, may be due to intrinsic mortality of the parasites, independent of the host or the sib-group that the parasites belong to. This indicates that the crucial interactions between host and parasite determining the outcome of infection takes place in the short time-period between ingestion and penetration of the gut-wall.


Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies.
Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors. To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function. Furthermore, we discuss the technologies that are available for the genetic diagnosis of obesity. Several studies reported that single gene variants cause Mendelian forms of obesity, determined by mutations of major effect in single genes. Rare, non-syndromic forms of obesity are a result of loss-of-function mutations in genes that act on the development and function of the hypothalamus or the leptin-melanocortin pathway. These variants disrupt enzymes and receptors that play a role in energy homeostasis, resulting in severe early-onset obesity and endocrine dysfunctions. Different approaches and technologies have been used to understand the genetic background of obesity. Currently, whole genome and whole exome sequencing are important diagnostic tools to identify new genes and variants associated with severe obesity, but other approaches are also useful at individual or population levels, such as linkage analysis, candidate gene sequencing, chromosomal microarray analysis, and genome-wide association studies. The understanding of the genetic causes of obesity and the usefulness and limitations of the genetic diagnostic approaches can contribute to the development of new personalized therapeutic targets against obesity.


Phosducin and betagamma-transducin interaction I: effects of post-translational modifications.
The interaction between phosducin and betagamma-transducin plays regulatory roles in light adaptation of photoreceptors. Both phosducin and betagamma-transducin undergo post-translational modifications, with phosducin modified by phosphorylation and the gamma subunit of betagamma-transducin by farnesylation and carboxylmethylation. In this study we exploited the electrophoretic mobilities of these native proteins to develop a micro binding assay and examined the effects of post-translational modifications on binding affinities. It was found that decarboxylmethylation of gamma-transducin increased the mobility of betagamma-transducin during native gel electrophoresis, but decreased the apparent affinity for phosducin by about 2-fold. Phosphorylation of phosducin by protein kinase A increased the mobility but decreased the apparent affinity for betagamma-transducin by at least 3-fold.


Technogenic Magnetic Particles in Alkaline Dusts from Power and Cement Plants.
During this study, we investigated the mineralogical characterization of technogenic magnetic particles (TMPs) contained in alkaline industrial dust and fly ash emitted by coal burning power plants and cement plants. The reaction of tested dust samples varied between values of pH 8 and pH 12. Their magnetic properties were characterized by measurement of magnetic susceptibility (χ), frequency dependence of magnetic susceptibility (χ(fd)), and temperature dependence of magnetic susceptibility. Mineralogical and geochemical analyses included scanning electron microscopy with energy dispersive spectroscopy, microprobe analysis and X-ray diffraction. The TMPs in fly ash from hard coal combustion have the form of typical magnetic spherules with a smooth or corrugated surface as well as a skeletal morphology, composed of iron oxides (magnetite, maghemite, and magnesioferrite) that occurred in the form of incrustation on the surface of mullite, amorphous silica, or aluminosilicate particles. The TMPs observed in fly ash from lignite combustion have a similar morphological form but a different mineralogical composition. Instead of magnetite and magnesioferrite, maghemite and hematite with lower χ values were the prevailing magnetic minerals, which explains the much lower magnetic susceptibility of this kind of ash in comparison with the ash from hard coal combustion, and probably results from the lower temperature of lignite combustion. Morphology and mineralogical composition of TMPs in cement dust is more diverse. The magnetic fraction of cement dust occurs mostly in the form of angular and octahedral grains of a significantly finer granulation (<20 μm); however, spherules are also present. A very characteristic magnetic form for cement dust is calcium ferrite (CaFe(3)O(5)). The greatest impact on the magnetic susceptibility of cement dust results from iron-bearing additives (often waste materials from other branches of industry), which should be considered the most dangerous to the environment. Stoichiometric analysis of micro-particles confirmed the presence of heavy metals such as Pb, Mn, Cd, and Zn connected with TMPs, which are carriers of magnetic signals in atmospheric dust. Therefore, in some cases, their presence in topsoil when detected by magnetic measurement can be treated as an indicator of inorganic soil contamination.


Attitudes toward illegal immigration: a cross-national methodological comparison.
This research is an examination of the generalizability of a Likert-type scale originally devised to measure attitudes toward illegal immigrants (IA) in the United States. The current authors administered this scale across 4 national samples using several methodological procedures. Undergraduate students (631) responded to the IA scale (R. Ommundsen & K. S. Larsen, 1997) at the University of Oslo, Oregon State University, the University of Copenhagen, and Vrije University of Amsterdam. The authors' main purpose was to evaluate the adequacy of the 20-item IA scale by examining possible problems with method and translation. A translation study carried out with the Danish, Norwegian, and Dutch samples (N = 299) showed that the various national versions were fairly accurate and contained largely the same meanings. The use of procrustes analysis of the IA scale yielded 3 factors in all 4 national samples. The coefficient of congruence of these 3 orthogonally rotated factor matrices, with the U.S. factor matrix as target, varied from .80 to .95, supporting the cross-national robustness of the scale. In the search for a more economical cumulative scale, a Mokken analysis yielded a 5-item scale that represented the aforementioned 3 factors and was stable across national samples.


[Psychotherapy in treatment and rehabilitation of patients with multiple sclerosis].
Presented is a review of the use of psychotherapy and psychological intervention methods in treatment and rehabilitation of patients with multiple sclerosis (MS). Main indications for psychotherapy in MS are anxiety and depression, asthenia, movement disorders, cognitive decline or sleep disturbances. The applied methods of psychotherapy refer to behavioral, cognitive, humanistic, combined or alternative approaches. Individual and group sessions are most frequently used forms of psychotherapy. Positive effects of psychotherapy in MS patients are confirmed by data of randomized studies and neuroimaging. Psychotherapy should be included into complex multidisciplinary programs of treatment and rehabilitation of MS patients.


Modeling solute transport in karst fissure dual porosity system and application: A case study in an arsenic contamination site.
Fractures and fracture networks are key conduits for migration of hydrothermal fluids, water and contaminants in groundwater systems Modeling is widely used to understand the environmental risk associated with migration of pollutant for different hydrogeological conditions. In this paper, we proposed a conceptual and mathematical model of flow and transport phenomena in fractured rock systems, and applied in a arsenic contaminate site as a case study. The groundwater flow model and arsenic migration model in fissure-matrix dual system were established. The results show that the velocity of groundwater is positively correlated with inlet pressure, but not with the porosity of the fracture. When the velocity of groundwater is relatively high, arsenic is transported along with the current in a finger-like manner. The distribution of arsenic concentration on the fracture surface is heterogeneous and the phenomenon of diffusion from the fracture to the matrix is not obvious. Indeed, when the velocity of groundwater is relatively small, the arsenic moves forward slowly, the concentration distribution on the crack surface is relatively uniform, and the diffusion phenomenon from the crack to the matrix is more significant.


beta-Thromboglobulin levels in plasma of jaundiced neonates exposed to phototherapy.
It has been suggested that changes take place in human platelets when they are exposed to fluorescent light of 10.8W/m2/sec at 460 nm. Loss of ability to aggregate and increase in turnover rate have been reported. However, studies of the effect of fluorescent light on adult platelets when exposed to the level of irradiance used clinically (3.5W/m2/sec) for 60 min did not reveal this effect. A study was therefore designed to compare the effects of bilirubin and phototherapy alone and in combination on cord and adult blood platelets obtained from jaundiced neonates. Using beta-thromboglobulin as the indicator of platelet damage, no significant change was found in platelet poor plasma from cord or adult blood following exposure to bilirubin and/or light, nor was any change found in the plasma of jaundiced neonates before and after therapy. Although the duration of exposure to light in this study was short, the results suggest that the lower levels of irradiance used clinically are not harmful to platelets and that the results of studies done with three times as much irradiance have little clinical relevance.