Familial lethal skeletal dysplasia with cloverleaf skull and multiple anomalies of brain, eye, face and heart: a new autosomal recessive multiple congenital anomalies syndrome.
We report on a 'new' lethal familial short-limb bone dysplasia associated with multiple anomalies in three sibs born to Arabic-Muslim consanguineous healthy parents. Clinical abnormalities included short limbs and short hands, cloverleaf skull, frontal bossing, wide anterior fontanel, hypertelorism, bilateral microphthalmia, cataract, low-set ears, narrow chest, ambiguous genitalia, cardiac ventricular septal defect (VSD) and agenesis of the corpus callosum. Radiological abnormalities included cloverleaf skull, hypoplastic clavicles and scapulae, thin, wavy cupped ribs, flat vertebral bodies with coronal clefting and several unossified vertebral pedicles and hypo-ossification of the pubic bone. The main changes noted in the long bones consisted of short-bowed long bones with abnormal metaphyses and unossified epiphyses. Chondro-osseous morphology documented degenerating chondrocytes with disorganization of the hypertrophied cartilage and short disorganized columns of hypertrophied areas. An autosomal recessive mode of inheritance seems most likely.


Design and fabrication of biological wires.
Cardiac tissue engineering using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has facilitated the creation of in vitro diagnostic platforms to study novel small molecules and cardiac disease at the tissue level. Yet, due to the immaturity of hPSC-CMs, there is a low fidelity between tissue-engineered cardiac tissues and adult cardiac tissues. To address this challenge, we have developed a platform that combines both physical and electrical cues to guide hPSC-CMs towards a more mature state in vitro.


Prognostic value of a five-lncRNA signature in esophageal squamous cell carcinoma.
The aim of this study was to identify prognostic long non-coding RNAs (lncRNAs) and develop a multi-lncRNA signature for suvival prediction in esophageal squamous cell carcinoma (ESCC). The clinical and gene expression data from Gene Expression Omnibus database (GSE53624, n = 119) were obtianed as training set. A total of 98 paired ESCC tumor and normal tissues were detected by RNA sequencing and used as test set. Another 84 ESCC tissues were used for real-time quantitative PCR(qRT-PCR) and as an independent validation cohort. Survival analysis, Cox regression and Kaplan-Meier analysis were performed. We screened a prognostic marker of ESCC from the GSE53624 dataset and named it as the five-lncRNA signature including AC007179.1, MORF4L2-AS1, RP11-488I20.9, RP13-30A9.2, RP4-735C1.6, which could classify patients into high- and low-risk groups with significantly different survival(median survival: 1.75 years vs. 4.01 years, log rank P < 0.05). Then test dataset and validation dataset confirmed that the five-lncRNA signature can determine the prognosis of ESCC patients. Predictive independence of the prognostic marker was proved by multivariable Cox regression analyses in the three datasets (P < 0.05). In addition, the signature was found to be better than TNM stage in terms of prognosis. The five-lncRNA signature could be a good prognostic biomarker for ESCC patients and has important clinical value.


Remyelination in demyelinating diseases of the central nervous system.
It is well accepted that a thorough understanding of pathogenetic mechanisms involved in demyelination and remyelination of the central nervous system (CNS) is fundamental to a better understanding of the etiology and pathogenesis of clinical demyelinating disease. In this review, experimental and clinical models of demyelination are discussed in an attempt to elucidate the mechanism by which they cause breakdown of the myelin sheath and/or damage to the oligodendrocyte. An attempt is made to determine whether mechanisms operating during experimental diseases may be applicable to the human situation. In a similar fashion, the occurrence of remyelination within the CNS in experimental animals and its relationship to the potential for remyelination following not only demyelinating disease but also remyelination following trauma and other destructive lesions are explored. The evidence for meaningful remyelination in the clinical situation is assessed, and the importance of such theoretical factors as the ability of oligodendrocytes to proliferate and migrate is evaluated.


A novel system for studying mechanical strain waveform-dependent responses in vascular smooth muscle cells.
While many studies have examined the effects mechanical forces on vSMCs, there is a limited understanding of how the different arterial strain waveforms that occur in disease and different vascular beds alter vSMC mechanotransduction and phenotype. Here, we present a novel system for applying complex, time-varying strain waveforms to cultured cells and use this system to understand how these waveforms can alter vSMC phenotype and signaling. We have developed a highly adaptable cell culture system that allows the application of mechanical strain to cells in culture and can reproduce the complex dynamic mechanical environment experienced by arterial cells in the body. Using this system, we examined whether the type of applied strain waveform altered phenotypic modulation of vSMCs by mechanical forces. Cells exposed to the brachial waveform had increased phosphorylation of AKT, EGR-1, c-Fos expression and cytoskeletal remodeling in comparison to cells treated with the aortic waveform. In addition, vSMCs exposed to physiological waveforms had adopted a more differentiated phenotype in comparison to those treated with static or sinusoidal cyclic strain, with increased expression of vSMC markers desmin, calponin and SM-22 as well as increased expression of regulatory miRNAs including miR-143, -145 and -221. Taken together, our studies demonstrate the development of a novel system for applying complex, time-varying mechanical forces to cells in culture. In addition, we have shown that physiological strain waveforms have powerful effects on vSMC phenotype.


Organosulfur compounds and cancer.
There is evidence that organosulfur compounds can inhibit the induction and growth of cancer. Several organosulfur compounds are dietary constituents and Allium species are a rich source of such molecules. Some but not all epidemiological studies have suggested that consumption of garlic can decrease cancer incidence. There is substantial evidence that constituents of garlic including diallyl sulfides can inhibit the induction of cancer in experimental animals. Effects on both tumor initiation and promotion have been documented. Some effects may be mediated by modulation of carcinogen metabolism involving altered ratios of phase I and phase II drug metabolizing enzymes. 59,60 Inhibitory actions on the growth of tumor cells have been documented and, for some tumor cells, differentiating effects of diallyl sulfides can occur. A definitive mechanism of action has not been established and evidence exists for effects at several sites in carcinogen metabolism and regulation of tumor growth. It is not always clear that laboratory studies can be extrapolated to reasonable levels of consumption by humans of garlic or other Allium species.


Silibinin-induced apoptosis in MCF7 and T47D human breast carcinoma cells involves caspase-8 activation and mitochondrial pathway.
Silibinin, a natural flavonoid, under phase I/II clinical trial in prostate cancer patients was aimed to evaluate its chemotherapeutic potential in human breast cancer cell MCF7 and T47D. Results showed that T47D cells were found to be more sensitive to silibinin than MCF7 as observed by proliferation, clonogenic, and apoptotic assays, which was abrogated by pan-caspase inhibitor but remained unaffected by p53 inhibitor. Apoptotic events in both cell types differ temporally and also by magnitude that involved mitochondrial and caspase-8 activation pathway. These results have relevance in understanding silibinin treatment to breast tumor.


Complex threshold method for identifying pixels that contain predominantly noise in magnetic resonance images.
To create a robust means to remove noise pixels using complex data. A receiver operating characteristic (ROC) curve was used to determine the appropriate choice of magnitude and phase thresholds as well as connectivity values to determine what pixels represent noise in the image. To fine-tune the results, a spike removal and hole replacement operator is applied to reduce Type I error and remove small islands of noise. The use of phase information improves the magnitude-only thresholding approach by further recognizing pixels that contain only noise. The performance of the method is enhanced using local connectivity of magnitude and phase data. An ROC analysis on simulated data shows that the Type I and Type II errors are less than 10(-4) and 10(-3), respectively, without connectivity and 0 and 10(-3), respectively, with connectivity for a signal-to-noise ratio (SNR) of 3:1 or higher. The joint use of both magnitude and phase images helps to improve the removal of noise points in magnetic resonance images. This can prove useful in automating the visualization of phase images without the highly distractive phase noise in noise regions. Also, it is useful in susceptibility weighted imaging when taking the minimum intensity projections of variably sized regions.


A Microstructured Fiber with Defined Borosilicate Regions to Produce a Radial Micronozzle Array for Nanoelectrospray Ionization.
This work highlights the possibility of using microstructured fibres with predefined doped regions to produce functional microstructures at a fibre facet with differential chemical etching. A specially designed silica microstructured fibre (MSF) that possesses specific boron-doped silica regions was fabricated for the purpose of generating a radial micronozzle array. The MSF was drawn from a preform comprising pure silica capillaries surrounded by boron-doped silica rods. Different etching rates of the boron-doped and silica regions at the fiber facet produces raised nozzles where the silica capillaries were placed. Fabrication parameters were explored in relation to the fidelity and protrusion length of the nozzle. Using etching alone, the nozzle protrusion length was limited, and the inner diameter of the channels in the array is expanded. However with the addition of a protective water counter flow, nozzle protrusion is increased to 60 μm with a limited increase in hole diameter. The radial micronozzle array generated nine individual electrosprays which were characterized using spray current measurements and related to theoretical prediction. Signal enhancement for the higher charge state ions for two peptides showed a substantial signal enhancement compared to conventional emitter technology.


Identification of cytidine diphosphodiesters in erythrocytes from a patient with pyrimidine nucleotidase deficiency.
Pyrimidine 5'-nucleotidase deficient (PND) erythrocytes contain elevated levels of pyrimidine nucleotides and relatively normal purine nucleotide levels. The composition of this nucleotide pool has been examined by others, but not all of the abnormal red cell metabolites in this disorder were identified. We have isolated and positively confirmed the identity of cytidine diphosphate (CDP)-choline and CDP-ethanolamine from PND red cells using methods including proton FT-NMR, spectroscopy, and comparative mass spectrometry. The concentrations of these and other pyrimidine nucleotidase-deficient erythrocyte nucleotides were determined using anion-exchange high performance liquid chromatography and ultraviolet (u.v.) detection. The pyrimidine diphosphodiesters appear to be the most prominent abnormal pyrimidine nucleotides in PND red cells, accounting for 55% of the total red cell pyrimidine nucleotides in this disorder. It is proposed that these abnormal phosphodiesters may be related to the accelerated hemolysis in PND.


Nernst effect measurements of epitaxial Y0.95Ca0.05Ba2(Cu1-xZnx)3Oy and Y0.9Ca0.1Ba2Cu3Oy superconducting films.
We report Nernst effect data for crystalline films of Y0.95Ca0.05Ba2(Cu1-xZnx)3Oy (with x=0, 0.02, and 0.04) and Y0.9Ca0.1Ba2Cu3Oy grown by pulsed laser deposition. We show that our own results and published data for LSCO are consistent with the theory of Gaussian superconducting fluctuations. We also show that Zn doping increases the Nernst coefficient simply because it reduces the in-plane conductivity.


Isolation of a subtilisin-like serine protease gene (MyxSubtSP) from spores of Myxobolus cerebralis, the causative agent of whirling disease.
Proteases play important roles in parasite life cycles and host-parasite interactions. They are pathogenesis factors of many pathogenic organisms and are hence potential targets for chemotherapeutic treatment of disease. We identified a subtilisin-like serine protease gene, MyxSubtSP, expressed by Myxobolus cerebralis. After PCR with subtilisin-like serine protease primers, the gene was cloned, sequenced and aligned against the NCBI database. Its corresponding amino acid sequence included the putative conserved domains of Peptidase_S8, subtilase family and AprE, subtilisin-like serine proteases. Rapid amplification of 5' and 3' cDNA ends (RACE) was used to generate the full length (1385 bp) gene, with a 429 bp open reading frame. The gene encompasses coding regions for a catalytic triad formed by Asp-74, His-100 and Ser-110.


Induction of phloem unloading in Arabidopsis thaliana roots by the parasitic nematode Heterodera schachtii.
Phloem unloading of both the fluorescent probe carboxyfluorescein (CF) and 14C-labeled solutes was induced in Arabidopsis thaliana L. roots by the parasitic nematode Heterodera schachtii Schmidt. Confocal laser scanning microscopy demonstrated that anomalous unloading of CF from the sieve element companion cell complexes occurred specifically into the syncytium, the nematode-induced feeding structure located within the stele of the root. From this syncytial complex of modified root cells, both fluorescent and radioactive labels were withdrawn by feeding nematodes. Movement of CF was unidirectional from the phloem to the syncytium. A range of low-molecular-weight fluorescent probes (including CF) microinjected into the syncytium stayed in this structure, demonstrating that it is symplastically isolated from the surrounding root tissue. The mechanism of unloading in this host-pathogen relationship therefore appears to be apoplastic. Our results provide unequivocal evidence that sedentary cyst-forming nematodes have direct access to phloem-derived solutes.


An Experimental Test of the Host-Plant Range of Nonrecombinant Strains of North American Xylella fastidiosa subsp. multiplex.
Nonrecombinant strains of Xylella fastidiosa subsp. multiplex (those lacking evidence of significant intersubspecific homologous recombination) infect the xylem of a wide range of native and nonnative trees in North America. However, the degree to which different strains have a specialized host range remains poorly understood. We tested eight strains isolated from five different tree species (almond, olive, sweetgum, and plum in California and oak in Washington, DC). Experiments were conducted in greenhouses in Riverside, CA, and each strain was tested on 11 to 15 of the 17 plant species tested. Hosts infected by the most strains were plum (5 of 8 strains) and almond (4 of 8), while their congener peach was only infected by 1 of 8. No strains infected oleander or mulberry. All strains successfully infected their original host, with peach, olive (1 of 7), and sweetgum (2 of 6) only infected by such strains. Of the 90 total strain-novel-host combinations tested, 11 resulted in unambiguous infection, 2 gave ambiguous results, and the remaining 77 failed to result in symptoms or bacterial spread. All eight strains had a unique host range, including two pairs of strains with the same multilocus sequence typing sequence type, providing strong evidence of extensive plant-host specialization. There was little evidence that host relatedness was driving host specificity.


First assessment of diffusion coefficients in model cheese by fluorescence recovery after photobleaching (FRAP).
Mass transfer of solutes like salt, moisture and metabolites, is very important for the final quality of cheese, through the control of the brining and ripening processes. Numerous studies have reported salt and water transfer properties in cheese, but few have dealt with other solutes. Moreover, most diffusion coefficients have been obtained by macroscopic and destructive methods. We developed the fluorescence recovery after photobleaching (FRAP) technique on a confocal microscope to measure in situ and at the microscopic scale diffusion properties inside cheese. A model matrix based on ultrafiltrated milk was used. FITC-dextran molecules were chosen as models of migrant solutes. Diffusion coefficients were estimated with a modelling approach which takes into account diffusion during the bleach phase. The FITC-dextrans (4 and 20 kDa) were able to migrate in the proteinic network, but their mobility was 2.2-3 times lower than in water, depending on their size.


Progress in the development of selective inhibitors of Aurora kinases.
Errors in the mitotic process are thought to be one of the principal sources of the genetic instability that hallmarks cancer. Unsurprisingly, many of the proteins that regulate mitosis are aberrantly expressed in tumour cells when compared to their normal counterparts. These may represent a good source of targets for the development of novel anti-cancer agents. The Aurora kinases represent one such family of mitotic regulators. In recent years there has been intense interest in both understanding the role of the Aurora kinases in cell cycle regulation and also in developing small molecule inhibitors as potential novel anti-cancer drugs. With several companies now starting to take Aurora kinase inhibitors into clinical development, the time is right to review the medicinal chemistry contribution to developing the field, in particular to review the increasingly broad range of small molecule inhibitors with activity against this kinase family.


Genome-wide analysis of cotton GH3 subfamily II reveals functional divergence in fiber development, hormone response and plant architecture.
Auxin-induced genes regulate many aspects of plant growth and development. The Gretchen Hagen 3 (GH3) gene family, one of three major early auxin-responsive families, is ubiquitous in the plant kingdom and its members function as regulators in modulating hormonal homeostasis, and stress adaptations. Specific Auxin-amido synthetase activity of GH3 subfamily II genes is reported to reversibly inactivate or fully degrade excess auxin through the formation of amino acid conjugates. Despite these crucial roles, to date, genome-wide analysis of the GH3 gene family has not been reported in cotton. We identified a total of 10 GH3 subfamily II genes in G. arboreum, 10 in G. raimondii, and 20 in G. hirsutum, respectively. Bioinformatic analysis showed that cotton GH3 genes are conserved with the established GH3s in plants. Expression pattern analysis based on RNA-seq data and qRT-PCR revealed that 20 GhGH3 genes were differentially expressed in a temporally and spatially specific manner, indicating their diverse functions in growth and development. We further summarized the organization of promoter regulatory elements and monitored their responsiveness to treatment with IAA (indole-3-acetic acid), SA (salicylic acid), GA (gibberellic acid) and BL (brassinolide) by qRT-PCR in roots and stems. These hormones seemed to regulate the expression of GH3 genes in both a positive and a negative manner while certain members likely have higher sensitivity to all four hormones. Further, we tested the expression of GhGH3 genes in the BR-deficient mutant pag1 and the corresponding wild-type (WT) of CCRI24. The altered expression reflected the true responsiveness to BL and further suggested possible reasons, at least in part, responsible for the dramatic dwarf and shriveled phenotypes of pag1. We comprehensively identified GH3 subfamily II genes in cotton. GhGH3s are differentially expressed in various tissues/organs/stages. Their response to IAA, SA, BL and GA and altered expression in pag1 suggest that some GhGH3 genes might be simultaneously involved in multiple hormone signaling pathways. Taken together, our results suggest that members of the GhGH3 gene family could be possible candidate genes for mechanistic study and applications in cotton fiber development in addition to the reconstruction of plant architecture.


Evaluation of accuracy between extraoral Gothic arch tracing and various other methods assessing horizontal condylar guidance angle in completely edentulous patients: A systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to determine the accuracy of different methods of measuring horizontal condylar guidance (HCG) angle in comparison with extraoral Gothic arch tracing for completely edentulous patients. This was a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two reviewers searched the EBSCOhost, Cochrane Library, and PubMed/MEDLINE databases and the Google Scholar search engine for in vivo studies, randomized controlled trials, cross-sectional studies, and quasi-experimental studies published from January 2005 to December 2022 on various other methods of determining HCG angle in completely edentulous patients compared with extraoral Gothic arch tracing method. Meta-analysis was conducted from the reported quantitative data. A total of 513 articles were obtained from different electronic databases, of which 22 studies were included for qualitative synthesis and 20 studies were included for meta-analysis. For the right side, a statistically significant difference was observed for panoramic radiograph (P < 0.05, pooled mean difference = 5.08 [2.17, 7]) and cephalogram (P < 0.05, pooled mean difference = 10.65 [8.81, 12.49]), whereas no statistically significant difference was observed for cone-beam computed tomography (CBCT) (P = 0.41, pooled mean difference = 4.39 [-6.10, 14.87]) and protrusive interocclusal wax record (P = 0.92, pooled mean difference = -0.45 [-9.62, 8.72]) as compared with extraoral Gothic arch tracing method. For the left side, a statistically significant difference was observed for panoramic radiograph (P < 0.05, pooled mean difference = 5.07 [1.95, 8.18]) and cephalogram (P < 0.05, pooled mean difference = 10.24 [8.65, 11.83]), whereas no statistically significant difference was observed for CBCT (P = 0.31, pooled mean difference = 4.05 [-3.74, 11.84]) and protrusive interocclusal wax record (P = 0.72, pooled mean difference = -1.21 [-7.86, 5.43]) as compared with extraoral Gothic arch tracing method. The cephalogram and panoramic radiograph obtained higher HCG angles in completely edentulous patients than extraoral Gothic arch tracing.


Demographic histories, isolation and social factors as determinants of the genetic structure of Alpine linguistic groups.
Great European mountain ranges have acted as barriers to gene flow for resident populations since prehistory and have offered a place for the settlement of small, and sometimes culturally diverse, communities. Therefore, the human groups that have settled in these areas are worth exploring as an important potential source of diversity in the genetic structure of European populations. In this study, we present new high resolution data concerning Y chromosomal variation in three distinct Alpine ethno-linguistic groups, Italian, Ladin and German. Combining unpublished and literature data on Y chromosome and mitochondrial variation, we were able to detect different genetic patterns. In fact, within and among population diversity values observed vary across linguistic groups, with German and Italian speakers at the two extremes, and seem to reflect their different demographic histories. Using simulations we inferred that the joint effect of continued genetic isolation and reduced founding group size may explain the apportionment of genetic diversity observed in all groups. Extending the analysis to other continental populations, we observed that the genetic differentiation of Ladins and German speakers from Europeans is comparable or even greater to that observed for well known outliers like Sardinian and Basques. Finally, we found that in south Tyroleans, the social practice of Geschlossener Hof, a hereditary norm which might have favored male dispersal, coincides with a significant intra-group diversity for mtDNA but not for Y chromosome, a genetic pattern which is opposite to those expected among patrilocal populations. Together with previous evidence regarding the possible effects of "local ethnicity" on the genetic structure of German speakers that have settled in the eastern Italian Alps, this finding suggests that taking socio-cultural factors into account together with geographical variables and linguistic diversity may help unveil some yet to be understood aspects of the genetic structure of European populations.


Factors Predicting Adoption of the Nurses Improving Care of Healthsystem Elders Program.
Registered nurses are often underprepared with the knowledge and skills to care for hospitalized older adult patients. One strategy to bridge this gap is for hospitals to adopt the Nurses Improving Care for Healthsystem Elders (NICHE) program: A nurse-led interdisciplinary organizational intervention to improve care of hospitalized older adults. This study aimed to identify the market, organizational and managerial, and sociotechnical factors associated with the adoption of NICHE among U.S. hospitals in order to understand factors that promote and inhibit the adoption of models to improve care for elders and to provide a basis for future studies that evaluate the effects of NICHE participation on patient outcomes. We used an observational, retrospective design, linking three national administrative data sources, in a secondary analysis. Data included the 2012-2013 American Hospital Association Annual Survey, NICHE database, and the American Nurses Credentialing Center Magnet database. Multivariate logistic regression models were completed at the hospital level (n = 3,506). Statistically significant variables associated with hospital adoption of the NICHE program include using a medical home model, being in a network, having a pain services program, being in an urban location, and having over 100 beds. Understanding factors that promote the adoption of organizational interventions like NICHE holds promise for accelerating the use of evidence-based clinical practices to promote health, function, and well-being for older hospitalized adults. Our results provide a foundation for assessing the effects of NICHE participation on patient outcomes by identifying factors that account for membership in NICHE.


Probing sedimentation non-ideality of particulate systems using analytical centrifugation.
Analytical centrifugation is a versatile technique for the quantitative characterization of colloidal systems including colloidal stability. The recent developments in data acquisition and evaluation allow the accurate determination of particle size, shape anisotropy and particle density. High precision analytical centrifugation is in particular suited for the study of particle interactions and concentration-dependent sedimentation coefficients. We present a holistic approach for the quantitative determination of sedimentation non-ideality via analytical centrifugation for polydisperse, plain and amino-functionalized silica particles spanning over one order of magnitude in particle size between 100 nm and 1200 nm. These systems typically behave as neutral hard spheres as predicted by auxiliary lattice Boltzmann simulations. The extent of electrostatic interactions and their impact on sedimentation non-ideality can be quantified by the repulsion range, which is the ratio of the Debye length and the average interparticle distance. Experimental access to the repulsion range is provided through conductivity measurements. With the experimental repulsion range at hand, we estimate the effect of polydispersity on concentration-dependent sedimentation properties through a combination of lattice Boltzmann and Brownian dynamics simulations. Finally, we determine the concentration-dependent sedimentation properties of charge-stabilized, fluorescently-labeled silica particles with a nominal particle size of 30 nm and reduced interparticle distance, hence an elevated repulsion range. Overall, our results demonstrate how the influence of hard-sphere type and electrostatic interactions can be quantified when probing sedimentation non-ideality of particulate systems using analytical centrifugation even for systems exhibiting moderate sample heterogeneity and complex interactions.


Experiences of chronic stress and mental health concerns among urban Indigenous women.
We measured stress, depression and post-traumatic stress disorder (PTSD) levels of urban Indigenous women living with and without HIV in Ontario, Canada, and identified correlates of depression. We recruited 30 Indigenous women living with HIV and 60 without HIV aged 18 years or older who completed socio-demographic and health questionnaires and validated scales assessing stress, depression and PTSD. Descriptive statistics were conducted to summarize variables and linear regression to identify correlates of depression. 85.6 % of Indigenous women self-identified as First Nation. Co-morbidities other than HIV were self-reported by 82.2 % (n = 74) of the sample. High levels of perceived stress were reported by 57.8 % (n = 52) of the sample and 84.2 % (n = 75) had moderate to high levels of urban stress. High median levels of race-related (51/88, IQR 42-68.5) and parental-related stress (40.5/90, IQR 35-49) scores were reported. 82.2 % (n = 74) reported severe depressive symptoms and 83.2 % (n = 74) severe PTSD. High levels of perceived stress was correlated with high depressive symptoms (estimate 1.28 (95 % CI 0.97-1.58), p < 0.001). Indigenous women living with and without HIV reported elevated levels of stress and physical and mental health concerns. Interventions cutting across diverse health care settings are required for improving and preventing adverse health outcomes.


Patient-Reported Outcomes After Radiation Therapy in Men With Prostate Cancer: A Systematic Review of Prognostic Tool Accuracy and Validity.
To identify, through a systematic review, all validated tools used for the prediction of patient-reported outcome measures (PROMs) in patients being treated with radiation therapy for prostate cancer, and provide a comparative summary of accuracy and generalizability. PubMed and EMBASE were searched from July 2007. Title/abstract screening, full text review, and critical appraisal were undertaken by 2 reviewers, whereas data extraction was performed by a single reviewer. Eligible articles had to provide a summary measure of accuracy and undertake internal or external validation. Tools were recommended for clinical implementation if they had been externally validated and found to have accuracy ≥70%. The search strategy identified 3839 potential studies, of which 236 progressed to full text review and 22 were included. From these studies, 50 tools predicted gastrointestinal/rectal symptoms, 29 tools predicted genitourinary symptoms, 4 tools predicted erectile dysfunction, and no tools predicted quality of life. For patients treated with external beam radiation therapy, 3 tools could be recommended for the prediction of rectal toxicity, gastrointestinal toxicity, and erectile dysfunction. For patients treated with brachytherapy, 2 tools could be recommended for the prediction of urinary retention and erectile dysfunction. A large number of tools for the prediction of PROMs in prostate cancer patients treated with radiation therapy have been developed. Only a small minority are accurate and have been shown to be generalizable through external validation. This review provides an accessible catalogue of tools that are ready for clinical implementation as well as which should be prioritized for validation.


A dystonia-like movement disorder with brain and spinal neuronal defects is caused by mutation of the mouse laminin β1 subunit, Lamb1.
A new mutant mouse (lamb1t) exhibits intermittent dystonic hindlimb movements and postures when awake, and hyperextension when asleep. Experiments showed co-contraction of opposing muscle groups, and indicated that symptoms depended on the interaction of brain and spinal cord. SNP mapping and exome sequencing identified the dominant causative mutation in the Lamb1 gene. Laminins are extracellular matrix proteins, widely expressed but also known to be important in synapse structure and plasticity. In accordance, awake recording in the cerebellum detected abnormal output from a circuit of two Lamb1-expressing neurons, Purkinje cells and their deep cerebellar nucleus targets, during abnormal postures. We propose that dystonia-like symptoms result from lapses in descending inhibition, exposing excess activity in intrinsic spinal circuits that coordinate muscles. The mouse is a new model for testing how dysfunction in the CNS causes specific abnormal movements and postures.


The weakness of fragility index exposed in an analysis of the traumatic brain injury management guidelines: A meta-epidemiological and simulation study.
To perform fragility index (FI) analysis on the evidence that forms the basis of the guidelines for the management of severe traumatic brain injury (TBI), and develop a deeper understanding of the pitfalls associated with FI. Meta-epidemiological analysis and numerical simulations. The Brain Trauma Foundation guidelines (4th edition) for management of severe TBI were used to identify relevant randomised controlled trials (RCTs). FI based on Fisher's exact test and relative risk was performed on eligible RCTs. The relationship between FI, event counts and P values was explored by exhaustively considering different combinations of outcomes for studies of total size ranging from 80 to 10000. Sample size calculations were also performed for a range of power, baseline risk and relative risk, to determine the influence of study design on FI. FI analysis of the severe TBI management guidelines revealed that most studies were associated with a low FI. In the majority of studies, FI was of a similar magnitude to the number lost to follow-up. The simulations revealed that while FI was inversely related to P value, a wide range of FI may be associated with a given P value. FI is also affected by sample size, baseline risk and effect size. Sample size calculations suggest that aside from very high-powered studies, most are likely to yield low FI values in the range typically encountered in the literature. Many studies are underpowered and are expected to be associated with a small FI. Furthermore, FI over-simplifies the complex, non-linear relationships between sample size, effect size and P value, which hinder comparisons of FI between studies. FI places undue importance on the "significance" of P values and accordingly should only be used sparingly.


Value of pharmacy services in an outpatient, preoperative, anesthesia clinic.
This pilot study assessed the expansion of pharmacy services to a preoperative, anesthesia clinic. Tertiary care academic medical center. Medication histories were routinely obtained by clinic nurses, and pharmacy services were not available. A prospective, single-center, pilot study enrolled English-speaking patients aged 65 years or older in a preoperative clinic before a scheduled surgery. Patient attributes including health literacy and preparatory activities were measured using verbal and written questionnaires. Home medication lists were obtained by both clinic nurses (routine care) and a pharmacist (research), and the 2 lists were compared to identify medication discrepancies for each patient. Discrepancies were categorized by type and severity. This study evaluated the potential impact of medication histories obtained by pharmacists compared with those obtained by clinic nurses during geriatric preoperative clinic visits. Of the 44 patients who gave their consent and were included in this pilot study, 25% (n = 11) had limited/marginal written and verbal health literacy, and 20% (n = 9) had limited/marginal numerical health literacy. Of the 38 patients who completed the pharmacist medication history interview, only 21% (n = 8) brought a complete list of their current medications to the preoperative clinic, 95% (n = 36) had at least 1 medication discrepancy, and 61% (n = 23) had at least 1 clinically meaningful discrepancy. Clinically meaningful discrepancies were identified for 8% (35 of 459) of medications and occurred most commonly for blood pressure medications, nonsteroidal anti-inflammatory drugs, and beta blockers. In this study, medication history discrepancies identified by pharmacists suggest that the expansion of pharmacy services into the preoperative clinic is feasible and could potentially prevent meaningful medication errors among geriatric patients being admitted for a scheduled surgery.


Assigning mentors for new HSC faculty hires: A preliminary policy evaluation.
Effective practices for selecting mentors for new faculty at academic health centers (AHC) are currently unknown. The University of New Mexico's School of Medicine assigns a mentor to all new faculty at the time of hire. The effectiveness of this policy measure has not been previously evaluated. The research question was to determine the proportion of new faculty mentees who meet with their assigned mentors before their mandatory orientation held within their first year of hire. At the orientation, faculty are surveyed about their response to the institutional policy of assigning mentors upon their hire. The proportion of new faculty mentees who met their assigned mentors prior to the orientation event constituted the primary study outcome. Of the 289 new faculty surveyed, 79.9% met their assigned mentors prior to the orientation - most meetings were weekly (48.8%) or monthly (27.9%). Among those who had not yet met their mentors, 65% planned to meet them within the month of the survey. 5.5% of all faculty reported a change of mentor from their initial assignment and 2.8% stated that they needed a different mentor. Physicians were less likely to meet with their assigned mentors than non-physician faculty (p=0.02). The preliminary policy evaluation demonstrates that most new faculty either meet or plan to meet their assigned mentors. Most participants stated that they did not need to be assigned a different mentor. Assigning mentors for new faculty hires may be considered a best practice at an AHC.


PtdIns(4,5)P2-mediated cell signaling: emerging principles and PTEN as a paradigm for regulatory mechanism.
PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) is a relatively common anionic lipid that regulates cellular functions by multiple mechanisms. Hydrolysis of PtdIns(4,5)P2 by phospholipase C yields inositol trisphosphate and diacylglycerol. Phosphorylation by phosphoinositide 3-kinase yields PtdIns(3,4,5)P3, which is a potent signal for survival and proliferation. Also, PtdIns(4,5)P2 can bind directly to integral and peripheral membrane proteins. As an example of regulation by PtdIns(4,5)P2, we discuss phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in detail. PTEN is an important tumor suppressor and hydrolyzes PtdIns(3,4,5)P3. PtdIns(4,5)P2 enhances PTEN association with the plasma membrane and activates its phosphatase activity. This is a critical regulatory mechanism, but a detailed description of this process from a structural point of view is lacking. The disordered lipid bilayer environment hinders structural determinations of membrane-bound PTEN. A new method to analyze membrane-bound protein measures neutron reflectivity for proteins bound to tethered phospholipid membranes. These methods allow determination of the orientation and shape of membrane-bound proteins. In combination with molecular dynamics simulations, these studies will provide crucial structural information that can serve as a foundation for our understanding of PTEN regulation in normal and pathological processes.


Beta-adrenoceptor-sensitive adenylate cyclase is inhibited by activation of mu-opioid receptors in rat striatal neurons.
The beta-adrenoceptor-sensitive adenylate cyclase in primary cultures of rat striatal neurons was inhibited by opioids, unlike that in rat striatal slices. Isoprenaline (1 microM)-stimulated cyclic AMP production was dose dependently inhibited by the mu-opioid receptor agonist. [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, EC50 = 0.02 microM, 36% inhibition), and only slightly reduced by relatively high concentrations of the delta-opioid receptor agonist, [D-penicillamine2, D-penicillamine5]enkephalin (DPDPE, 1 microM). The highly selective and potent delta-opioid receptor agonist. [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET), and the kappa-opioid receptor agonist, U50-488, were ineffective in concentrations up to 3 microM. Naloxone reversed equally well the inhibitory effects of DPDPE and of DAGO, indicating the involvement of functional mu-opioid receptors. The isoprenaline (1 microM)-stimulated adenylate cyclase activity in cultured glial cells, which exceeded that in neurons about 10-fold, was not affected by opioids. Therefore, opioids were ineffective in rat brain slices probably due to the fact that cyclic AMP production induced by beta-adrenoceptor activation occurs primarily in the glial cells, where it is not subject to inhibition by opioids. These data indicate for the first time the existence of an interaction between functional mu-opioid receptors and beta-adrenoceptors on striatal neurons of the rat.


Genotypic variation for drought tolerance in Beta vulgaris.
Insufficient soil moisture during summer months is now the major cause of sugar beet yield losses in the UK. However, selection for increased drought tolerance has not been a breeding priority until recently. Genetic variation for drought tolerance is an essential prerequisite for the development of more stress-tolerant varieties, but commercial sugar beet varieties seem to have similar yield responses to drought. The objective of this study was to assess the degree of genotypic variation for drought tolerance within a wide range of sugar beet germplasm and genebank accessions within Beta. Thirty sugar beet genotypes were screened under field drought conditions, and putative drought tolerant and sensitive lines (in terms of yield reduction in polythene-covered vs. irrigated plots) were identified. Significant genotype x water treatment interactions were found for dry matter yield and relative leaf expansion rate. Genotypic differences for drought susceptibility index were also significant. Differential sensitivity of seedling shoot growth to water deficit was examined by comparing 350 genebank accessions in a simple growth chamber screen. Methods of data management were devised to highlight lines for entry into subsequent field tests. The results of the field and seedling screens indicate that there is variation for tolerance to water deficits within sugar beet and related types, and that there are lines that show greater drought tolerance than selected commercial varieties. Divergent lines showing contrasting behaviour should aid in the identification of key morpho-physiological traits that confer drought tolerance.


The development of attachment in new relationships: single subject analyses for 10 foster infants.
This paper presents single-subject analyses of newly developing attachment relationships in 10 foster infant-caregiver dyads. Using a diary methodology, at least 2 months of daily data were provided by foster parents on infants' attachment behaviors. Foster infant attachment was also assessed using the Strange Situation. Foster mother state of mind regarding attachment was measured using the Adult Attachment Interview. For eight infants, diary data revealed predominant patterns of attachment behavior emerging within 2 months of placement. In most cases, diary data predicted Strange Situation classifications. Both Strange Situation and diary data indicated that the three children placed in foster care before 12 months of age with foster parents having primary or secondary autonomous states of mind were classified as having secure attachments. The five children placed after 12 months of age showed predominantly insecure attachment behavior in the diary and were classified as insecure in the Strange Situation. Contingency analyses of behavioral sequences reported in the diary revealed that foster parents tended to complement their foster childrens' attachment behaviors.


Widespread expression of beta1 integrins in the developing chick retina: evidence for a role in migration of retinal ganglion cells.
During extension of axons, critical neuronal interactions with extracellular matrix (ECM) and other cells are thought to be mediated in part by heterodimeric beta1 integrin receptors. In this report, we examine the expression and function of beta1 integrins in the developing chick retina. Expression of the beta1 subunit, assayed by in situ hybridization and antibody staining of dissociated cells, was widespread in undifferentiated neuroepithelial cells, before the initiation of axons. Expression persisted in most retinal cell layers throughout embryonic development, during and after axon extension. The repertoire of beta1-associated alpha subunits was examined using reverse transcription-polymerase chain reaction. In addition to the alpha6 and alpha8 subunits previously reported, chick homologues of the alpha2 and alpha4 subunits were detected. Developmental Northern blots revealed varying patterns of integrin subunit expression and showed that expression of beta1 and the mRNAs of its associated alpha subunits are not always coregulated during retinal development. The timing and distribution of expression suggested that beta1 integrins may be involved in other developmental events in addition to axon extension. To address functions carried out by beta1 integrins in the early retina, explanted eye cups were incubated in the presence of function blocking anti-beta1 antibody and migration of newly born retinal ganglion cells (RGCs) was assessed. RGC migration from the ventricular zone to the vitreal border was significantly inhibited, suggesting that beta1 integrins play a role in neuroblast migration in the retina.


Examining cultural drifts in artworks through history and development: cultural comparisons between Japanese and western landscape paintings and drawings.
Research on cultural products suggest that there are substantial cultural variations between East Asian and European landscape masterpieces and contemporary members' landscape artwork (Masuda et al., 2008c), and that these cultural differences in drawing styles emerge around the age of 8 (Senzaki et al., 2014b). However, culture is not static. To explore the dynamics of historical and ontogenetic influence on artistic expressions, we examined (1) 17-20th century Japanese and Western landscape masterpieces, and (2) cross-sectional adolescent data in landscape artworks alongside previous findings of elementary school-aged children, and undergraduates. The results showed cultural variations in artworks and masterpieces as well as substantial "cultural drifts" (Herskovits, 1948) where at certain time periods in history and in development, people's expressions deviated from culturally default patterns but occasionally returned to its previous state. The bidirectional influence of culture and implications for furthering the discipline of cultural psychology will be discussed.


Developments in statistical analysis in quantitative genetics.
A remarkable research impetus has taken place in statistical genetics since the last World Conference. This has been stimulated by breakthroughs in molecular genetics, automated data-recording devices and computer-intensive statistical methods. The latter were revolutionized by the bootstrap and by Markov chain Monte Carlo (McMC). In this overview a number of specific areas are chosen to illustrate the enormous flexibility that McMC has provided for fitting models and exploring features of data that were previously inaccessible. The selected areas are inferences of the trajectories over time of genetic means and variances, models for the analysis of categorical and count data, the statistical genetics of a model postulating that environmental variance is partly under genetic control, and a short discussion of models that incorporate massive genetic marker information. We provide an overview of the application of McMC to study model fit, and finally, a discussion is presented on the development of efficient McMC updating schemes for non-standard models.


DNA barcoding and metabarcoding of standardized samples reveal patterns of marine benthic diversity.
Documenting the diversity of marine life is challenging because many species are cryptic, small, and rare, and belong to poorly known groups. New sequencing technologies, especially when combined with standardized sampling, promise to make comprehensive biodiversity assessments and monitoring feasible on a large scale. We used this approach to characterize patterns of diversity on oyster reefs across a range of geographic scales comprising a temperate location [Virginia (VA)] and a subtropical location [Florida (FL)]. Eukaryotic organisms that colonized multilayered settlement surfaces (autonomous reef monitoring structures) over a 6-mo period were identified by cytochrome c oxidase subunit I barcoding (>2-mm mobile organisms) and metabarcoding (sessile and smaller mobile organisms). In a total area of ∼ 15.64 m(2) and volume of ∼ 0.09 m(3), 2,179 operational taxonomic units (OTUs) were recorded from 983,056 sequences. However, only 10.9% could be matched to reference barcodes in public databases, with only 8.2% matching barcodes with both genus and species names. Taxonomic coverage was broad, particularly for animals (22 phyla recorded), but 35.6% of OTUs detected via metabarcoding could not be confidently assigned to a taxonomic group. The smallest size fraction (500 to 106 μm) was the most diverse (more than two-thirds of OTUs). There was little taxonomic overlap between VA and FL, and samples separated by ∼ 2 m were significantly more similar than samples separated by ∼ 100 m. Ground-truthing with independent assessments of taxonomic composition indicated that both presence-absence information and relative abundance information are captured by metabarcoding data, suggesting considerable potential for ecological studies and environmental monitoring.


Glucose-based peritoneal dialysis solution suppresses adiponectin synthesis through oxidative stress in an experimental model of peritoneal dialysis.
Accumulation of visceral fat is one of the major risk factors for the development of cardiovascular disease in peritoneal dialysis (PD) patients. Adiponectin, an adipokine commonly regarded as a negative indicator of metabolic disease, is reported to be downregulated in its gene level in end-stage renal disease patients. Since excessive fat deposit is involved in increased reactive oxygen species (ROS), PD solution (PDS) may contribute to ROS production, resulting in dysregulation of adiponectin. In this study, we tested our hypothesis that oxidative stress induced by PDS may play a role in the regulation of adiponectin. Commercial PDS containing 3.86% glucose (20 - 30 mL) was administered to SD rats for 12 weeks with and without N-acetylcysteine (NAC; 10 mmol/L). ELISA was used to quantify adiponectin in plasma and spent dialysate. For in vitro studies, fully differentiated 3T3-L1 adipocytes and adipocytes isolated from abdominal fat were treated with a high glucose solution, PDS, and H(2)O(2). Adiponectin levels in the conditioned media were measured by ELISA and immunoblot assays. The mRNA levels of adiponectin in mature adipocytes were examined using real-time RT-PCR. The levels of adiponectin in plasma and spent dialysate were significantly downregulated by PDS and this effect was suppressed by NAC. In 3T3-L1 adipocytes, adiponectin secretion was inhibited by 50 mmol/L glucose, PDS diluted 2-fold, and H(2)O(2) (200 μmol/L). In addition, H(2)O(2) downregulated expression of adiponectin mRNA and secretion of adiponectin oligomer complexes. Our data suggest that ROS induced by conventional glucose-based PDS may contribute to pathophysiological changes in abdominal fat and downregulate adiponectin secreted from adipocytes during long-term PD.


Probiotic supplementation in neonates with major gastrointestinal surgical conditions: a systematic review.
Neonates with major gastrointestinal surgical conditions frequently suffer from prolonged feed intolerance, infections, and need multiple courses of antibiotics. All these put them at risk of gut dysbiosis. Probiotic supplementation has the potential to minimise dysbiosis and improve clinical outcomes in such infants. Hence, we aimed to conduct a systematic review of probiotics in neonates with major surgical conditions of the gut. Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and other databases were searched in September 2016. Two randomised controlled trials (RCTs) were included; the first was conducted in 24 neonates with gastroschisis, the second in eight neonates with various surgical conditions. In the first study, the overall microbial communities were not significantly different between groups, though analysis of the final specimens demonstrated higher Bifidobacteriaceae, lower Clostridiaceae, and trends toward lower Enterobacteriaceae, Enterococcaceae, Staphylococcaceae, and Streptococcaceae in the probiotic group. In the second study, there were significantly more Streptcoccaceae in the faecal samples in the probiotic group and significantly more Bifidobacteriaceae in the no probiotic group (p < .05). There is limited evidence regarding the role of probiotics in neonates with gastrointestinal surgical conditions. Adequately powered RCTs are needed to address this issue.


Pulmonary resistance and dynamic compliance as functions of respiratory frequency.
The behavior of pulmonary resistance (RL) and that of dynamic compliance (Cdyn) as functions of respiratory frequency (f) were compared in normal subjects and in patients with chronic obstructive pulmonary disease (COPD). Although both RL and Cdyn varied with f in most COPD patients and in some normal subjects, Cdyn appeared to be more sensitive than RL to variations of frequency; no significant changes in RL could be demonstrated in subjects in whom Cdyn was frequency dependent. The degree of frequency dependence of Cdyn was correlated with the severity of respiratory impairment (as quantified by conventional pulmonary function tests); in contrast, RL was not detectably frequency dependent in some subjects with advanced COPD. Compared with Cdyn, RL was more commonly nonlinearly related to respiratory frequency, often increasing at high breathing rates. Our results indicate that changes in RL with frequency are less predictable and more difficult to detect than the corresponding changes in Cdyn.


End-of-Waste SiC-Based Flexible Substrates with Tunable Electrical Properties for Electronic Applications.
We demonstrated the suitability of polymer composites filled with silicon carbide (SiC) powders derived from a recycling process for applications in electronic devices manufacturing. SiC powders have been synthesized from the process byproducts and used as fillers in the formulation of polystyrene (PS)/SiC composites, which have been used in the preparation of substrates using the solution-casting technique. Different substrates have been prepared by changing the concentration of SiC in the composite in the range from 6.7 to 67 wt % and used in simple electronic devices by performing gold contacts in both planar and stacked configurations. The electrical behaviors of both stacked and planar devices were investigated in direct current (DC) and alternate current (AC) regimes. The experimental results showed that charge percolation could be considered an explanation for the abrupt change in the differential conductivity observed around 30 wt %. Fowler-Nordheim tunneling at high fields has been found to be compatible with static characteristics and with high-frequency AC measurements and, therefore, charge tunneling between SiC islands has been proposed as the physical mechanism provoking the changes in charge transport in the substrates investigated. From this first experimental analysis, it appears that SiC/PS composites could suit their use in tunneling-gate dielectrics (i.e., in transistors suitable for their applications in nonvolatile random-access memory) for low concentrations or as a continuous semiconducting media when SiC is dispersed in high-concentration composites.


Practical issues related to uterine pathology: endometrial stromal tumors.
Uterine mesenchymal tumors continue to be a challenge to diagnose due to their non-specific clinical presentation, often non-distinctive gross appearance, varied (and many times overlapping) morphologic appearance, and unsuspected pitfalls in immunohistochemical expression. This review will focus on endometrial stromal tumors and those features that help in their distinction. In particular, a practical approach to the diagnosis of endometrial stromal neoplasia will be covered including recognition as a stromal process in a biopsy/curettage and distinction from a highly cellular leiomyoma. In addition, distinction of a stromal nodule from a low-grade endometrial stromal sarcoma (LGESS) and stromal sarcoma with limited infiltration in a hysterectomy specimen will be covered. The salient features that help distinguish a LGESS from a uterine tumor resembling ovarian sex-cord tumor as well as high-grade endometrial stromal sarcoma, the latter a tumor recently reintroduced in the WHO classification will also be discussed. Finally, a practical approach to the diagnosis of undifferentiated uterine sarcoma (UUS) will be presented.


Frequent detection of Epstein-Barr virus DNA by the polymerase chain reaction in lymph node biopsies from patients with Hodgkin's disease without genomic evidence of B- or T-cell clonality.
This study of 52 Swiss patients with Hodgkin's disease (HD), including 17 cases with a high content of Sternberg-Reed (SR) and Hodgkin (H) cells, was performed to determine the percentage of cases harboring Epstein-Barr virus (EBV) DNA and/or clonal rearrangements of Ig and T-cell antigen receptor (TcR) genes in diagnostic lymph node biopsies. Special attention was drawn to the heavily infiltrated cases to detect a possible relationship between clonality and EBV DNA identification. EBV DNA was detected by the polymerase chain reaction (PCR) using three different sets of specific primers. The viral origin of the amplification products was confirmed by hybridization with a radiolabeled internal probe or demonstration of a specific Sma I restriction site. Genomic rearrangement of Ig and TcR genes was studied by Southern blot analysis. EBV DNA was identified by PCR in 38 of 48 cases (79%). Clonal rearrangements were identified in only 4 of 52 cases (Ig genes) and were independent of the degree of infiltration by SR cells and the presence of EBV DNA. The absence of EBV DNA in three cases with numerous SR cells (only one of them showed clonal rearrangement) and the presence of only a few viral copies in four further cases with numerous SR cells (semiquantitative analysis of viral DNA by PCR was performed in 26 EBV-positive cases) suggests that this virus is modulating rather than an etiologic agent in a considerable proportion of HD cases.


Antibodies Against Hypothalamus and Pituitary Gland in Childhood-Onset Brain Tumors and Pituitary Dysfunction.
Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.


What's wrong with total quality management?
There is nothing inherently wrong with TQM, says author C. Thomas Yarington, Jr., M.D. The problems come when management does not fully support the total integration of the practice into the quality improvement effort.


Pioneer microbial communities of the Fimmvörðuháls lava flow, Eyjafjallajökull, Iceland.
Little is understood regarding the phylogeny and metabolic capabilities of the earliest colonists of volcanic rocks, yet these data are essential for understanding how life becomes established in and interacts with the planetary crust, ultimately contributing to critical zone processes and soil formation. Here, we report the use of molecular and culture-dependent methods to determine the composition of pioneer microbial communities colonising the basaltic Fimmvörðuháls lava flow at Eyjafjallajökull, Iceland, formed in 2010. Our data show that 3 to 5 months post eruption, the lava was colonised by a low-diversity microbial community dominated by Betaproteobacteria, primarily taxa related to non-phototrophic diazotrophs such as Herbaspirillum spp. and chemolithotrophs such as Thiobacillus. Although successfully cultured following enrichment, phototrophs were not abundant members of the Fimmvörðuháls communities, as revealed by molecular analysis, and phototrophy is therefore not likely to be a dominant biogeochemical process in these early successional basalt communities. These results contrast with older Icelandic lava of comparable mineralogy, in which phototrophs comprised a significant fraction of microbial communities, and the non-phototrophic community fractions were dominated by Acidobacteria and Actinobacteria.


Characterization of a membrane protein from brain mediating the inhibition of inositol 1,4,5-trisphosphate receptor binding by calcium.
Inositol 1,4,5-trisphosphate (InsP3) is a component of the phosphoinositide second-messenger system which mobilizes Ca2+ from intracellular stores. Recently, an InsP3 receptor binding protein from rat cerebellar membranes was solubilized and purified to homogeneity. The potent inhibition by Ca2+ of [3H]InsP3 binding to the InsP3 receptor in cellular membranes is not apparent in the purified receptor. The Ca2+-dependent inhibition of [3H]InsP3 binding in the crude homogenate (concn. giving 50% inhibition = 300 nM) can be restored by addition of solubilized cerebellar membranes to the purified receptor. In the present study, we further characterize the protein in solubilized membranes which confers Ca2+-sensitivity to the receptor, and which we term 'calmedin'. Calmedin appears to be a neutral membrane protein with an estimated Mr of 300,000 by gel filtration in the presence of Triton X-100. Calmedin confers a Ca2+-sensitivity to InsP3 receptor binding, which can be completely reversed by 10 min incubation with EDTA and therefore does not represent Ca2+-dependent proteinase action. Calmedin effects on the purified InsP3 receptor depend on Ca2+ binding to the calmedin, although Ca2+ also binds directly to the InsP3 receptor. The regional distribution of calmedin differs from that of the InsP3 receptor in the brain, suggesting that it also mediates other Ca2+-dependent functions. Calmedin activity in peripheral tissues is much lower than in brain.


Management of mechanical ventilation in brain injury: hyperventilation and positive end-expiratory pressure.
The study intended to make a critical review on use of pulmonary hyperventilation maneuvers and the different positive end-expiratory pressures applied to traumatic brain injury patients. As a reference were used publications in English, Spanish and Portuguese, contained in the following databases: MedLine, SciELO and LILACS, from 2000 to 2007, we included all studies about the use of pulmonary hyperventilation maneuvers and the different positive end-expiratory levels used for adult patients with brain injury at acute or chronic stage. Thirty one trials were selected, 13 about pulmonary hyperventilation, as prophylaxis, prolonged or optimized and 9 shows the levels of positive end-expiratory pressures used, ranging from 0 to 15 cmH2O. The prophylactic hyperventilation maneuver in the first 24 hours can lead to an increase of cerebral ischemia; the prolonged hyperventilation must be avoided if intracranial pressure did not increase; however optimized hyperventilation seems to be the most promising technique for control of the intracranial pressure and cerebral perfusion pressure; the rise of the positive end-expiratory pressure, up to 15cmH2O, can be applied in a conscientious form aiming to increase arterial oxygen saturation in lung injury.


Pelvic factor infertility: diagnosis and prognosis of various procedures.
Infertile women are examined to exclude tubal occlusion or a pelvic factor through indirect tests, such as hysterosalpingography (HSG), sonohysterosalpingography/hysterosalpingosonography (SH), and/or laparoscopy (Lps). Assisted reproductive technologies (ART) are proposed to resolve infertility according to the results of the above-mentioned diagnostic procedures. Today, Lps still represents the second option after several failures of in vivo attempts and before moving to conceive in vitro. The aim of this study was to establish the diagnostic power of HSG and SH compared with that of Lps and the efficacy of ART when each single test is used as an inclusion criterion. We recruited 2560 infertile women (aged 20 to 35) to undergo diagnostic and therapeutic procedures to address their infertility in our clinical theatre. Of these, 1080 women underwent Lps and hysteroscopy (Group 1), 525 underwent HSG (Group 2), and 955 underwent SH (Group 3). The positive and negative predictive values of sonosalpingosonography were 75.8% and 91.2% and those of hysterosalpingography were 71.8% and 88.2%, respectively. Endometriosis (stage II-IV of the revised American Society for Reproductive Medicine [ASRM] classification) was diagnosed laparoscopically in 344 out of 1080 women (32%). Only 44 women (13%) with endometriosis showed bilateral tubal occlusion. Pelvic factors other than tubal occlusions are neither diagnosed nor treated in a timely manner by indirect tubal patency tests. The conventional use of HSG and/or SH may increase the time required to find an adequate treatment by which to achieve a successful pregnancy.


CRISPR-Cas9, A Promising Therapeutic Tool for Cancer Therapy: A Review.
Cancer is one of the most leading causes of mortality all over the world and remains a foremost social and economic burden. Mutations in the genome of individuals are taking place more frequently due to the excessive progress of xenobiotics and industrialization in the present world. With the progress in the field of molecular biology, it is possible to alter the genome and to observe the functional changes derived from genetic modulation using gene-editing technologies. Several therapies have been applied for the treatment of malignancy which affect the normal body cells; however, more effort is required to develop vsome latest therapeutic approaches for cancer biology and oncology exploiting these molecular biology advances. Recently, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated protein 9 (Cas9) system has emerged as a powerful technology for cancer therapy because of its great accuracy and efficiency. Genome editing technologies have demonstrated a plethora of benefits to the biological sciences. CRISPR- Cas9, a versatile gene editing tool, has become a robust strategy for making alterations to the genome of organisms and a potent weapon in the arsenal of tumor treatment. It has revealed an excellent clinical potential for cancer therapy by discovering novel targets and has provided the researchers with the perception about how tumors respond to drug therapy. Stern efforts are in progress to enhance its efficiency of sequence specific targeting and consequently repressing offtarget effects. CRISPR-Cas9 uses specific proteins to convalesce mutations at genetic level. In CRISPR-Cas9 system, RNA-guided Cas9 endonuclease harnesses gene mutation, DNA deletion or insertion, transcriptional activation or repression, multiplex targeting only by manipulating 20-nucleotide components of RNA. Originally, CRISPR-Cas9 system was used by bacteria for their defense against different bacteriophages, and recently this system is receiving noteworthy appreciation due to its emerging role in the treatment of genetic disorders and carcinogenesis. CRISPR-Cas9 can be employed to promptly engineer oncolytic viruses and immune cells for cancer therapeutic applications. More notably, it has the ability to precisely edit genes not only in model organisms but also in human being that permits its use in therapeutic analysis. It also plays a significant role in the development of complete genomic libraries for cancer patients. In this review, we have highlighted the involvement of CRISPR-Cas9 system in cancer therapy accompanied by its prospective applications in various types of malignancy and cancer biology. In addition, some other conspicuous functions of this unique system have also been discussed beyond genome editing.


High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients.
To evaluate the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency in HIV-positive patients, a population at risk for osteoporosis. Retrospective assessment of vitamin D levels by season and initiation of combined antiretroviral therapy (cART). 25(OH)D was measured in 211 HIV-positive patients: samples were taken before initiation of cART from February to April or from August to October as well as 12 (same season) and 18 months (alternate season) after starting cART. 1,25-Dihydroxyvitamin D [1,25(OH)2D] was measured in a subset of 74 patients. Multivariable analyses included season, sex, age, ethnicity, BMI, intravenous drug use (IDU), renal function, time since HIV diagnosis, previous AIDS, CD4 cell count and cART, in particular nonnucleoside reverse transcriptase inhibitor (NNRTI) and tenofovir (TDF) use. At baseline, median 25(OH)D levels were 37 (interquartile range 20-49) nmol/l in spring and 57 (39-74) nmol/l in the fall; 25(OH)D deficiency less than 30 nmol/l was more prevalent in spring (42%) than in fall (14%), but remained unchanged regardless of cART exposure. In multivariable analysis, 25(OH)D levels were higher in white patients and those with a longer time since HIV diagnosis and lower in springtime measurements and in those with active IDU and NNRTI use. 1-Hydroxylation rates were significantly higher in patients with low 25(OH)D. Hepatitis C seropositivity, previous AIDS and higher CD4 cell counts correlated with lower 1,25(OH)2D levels, whereas BMI and TDF use were associated with higher levels. In TDF-treated patients, higher 1,25(OH)2D correlated with increases in serum alkaline phosphatase. Based on the high rate of vitamin D deficiency in HIV-positive patients, systematic screening with consideration of seasonality is warranted. The impact of NNRTIs on 25(OH)D and TDF on 1,25(OH)2D needs further attention.


Identifying keys to success in clinical learning: a study of two interprofessional learning environments.
The aim of this study was to study the intrinsic system behind interprofessional clinical learning environments. Two health care units were selected on the basis of having received a reward for best clinical learning organization. Interviews were carried out with health care staff/clinical supervisors from different professions. The interviews were transcribed and analysed according to qualitative content analysis, and categories and themes were identified. Analysis revealed two different systems of clinical learning environments. In one, the interplay between the structural aspects dominated, and in the other, the interplay between the cultural aspects dominated. An important similarity between the environments was that a defined role for students in the organization and interprofessional teamwork around supervision across professional borders was emphasized.


The role of beta(2)-adrenergic receptors in inflammation and allergy.
Essential role of beta(2)-adrenoreceptor (beta(2)AR) in airway relaxation is well established. Nevertheless, beta(2)AR seems playing an actual role in allergy and inflammation. Interaction between beta(2)AR and proinflamatory cytokines in airway smooth muscle has been revealed. Being located on proinflamatory cells, beta(2)ARs may influence function of these cells in vivo. It was clear established, that stimulation of beta(2)AR inhibits release of proinflamatory mediators from mast cells, influences T-cell growth and function, eosinophil survival and function, including GM-CSF- or PAF-induced degranulation. Stimulation of beta(2)ARs, located on alveolar macrophages and epithelial cells, has ambiguity influence on their regulation and function, including phagocytosis and mediator secretion, in vivo. Vascular responses, resulting in inhibition of plasma exudation were confirmed, but modulation of sensory nerves via beta(2)AR is not certain yet. beta(2)AR-agonists are effective in treatment of immediate allergic reactions, but desensitisation of beta(2)ARs on inflammatory cells may result in paradoxical effects, especially in asthma. In summary, it is clear that beta(2)ARs may play an anti-inflammatory role in vitro. Unfortunately, in vitro data have shown limited applicability in vivo; therefore further research in this field is required.


Backscattered electron imaging and electron backscattered diffraction in the study of bacterial attachment to titanium alloy structure.
The application of secondary electron (SE) imaging, backscattered electron imaging (BSE) and electron backscattered diffraction (EBSD) was investigated in this work to study the bacterial adhesion and proliferation on a commercially pure titanium (cp Ti) and a Ti6Al4V alloy (Ti 64) with respect to substrate microstructure and chemical composition. Adherence of Gram-positive Staphylococcus epidermidis 11047 and Streptococcus sanguinis GW2, and Gram-negative Serratia sp. NCIMB 40259 and Escherichia coli 10418 was compared on cp Ti, Ti 64, pure aluminium (Al) and vanadium (V). The substrate microstructure and the bacterial distribution on these metals were characterised using SE, BSE and EBSD imaging. It was observed that titanium alloy-phase structure, grain boundaries and grain orientation did not influence bacterial adherence or proliferation at microscale. Adherence of all four strains was similar on cp Ti and Ti 64 surfaces whilst inhibited on pure Al. This work establishes a nondestructive and straight-forward statistical method to analyse the relationship between microbial distribution and metal alloy structure.


Do Sex and Violence Sell? A Meta-Analytic Review of the Effects of Sexual and Violent Media and Ad Content on Memory, Attitudes, and Buying Intentions.
It is commonly assumed that sex and violence sell. However, we predicted that sex and violence would have the opposite effect. We based our predictions on the evolution and emotional arousal theoretical framework, which states that people are evolutionarily predisposed to attend to emotionally arousing cues such as sex and violence. Thus, sexual and violent cues demand more cognitive resources than nonsexual and nonviolent cues. Using this framework, we meta-analyzed the effects of sexual media, violent media, sexual ads, and violent ads on the advertising outcomes of brand memory, brand attitudes, and buying intentions. The meta-analysis included 53 experiments involving 8,489 participants. Analyses found that brands advertised in violent media content were remembered less often, evaluated less favorably, and less likely to be purchased than brands advertised in nonviolent, nonsexual media. Brands advertised using sexual ads were evaluated less favorably than brands advertised using nonviolent, nonsexual ads. There were no significant effects of sexual media on memory or buying intentions. There were no significant effects of sexual or violent ads on memory or buying intentions. As intensity of sexual ad content increased, memory, attitudes, and buying intentions decreased. When media content and ad content were congruent (e.g., violent ad in a violent program), memory improved and buying intentions increased. Violence and sex never helped and often hurt ad effectiveness. These results support the evolution and emotional arousal framework. Thus, advertisers should consider the effects of media content, ad content, content intensity, and congruity to design and place more effective ads.


Interplay of structure and disorder in cochaperonin mobile loops.
Protein-protein interactions typically are characterized by highly specific interfaces that mediate binding with precisely tuned affinities. Binding of the Escherichia coli cochaperonin GroES to chaperonin GroEL is mediated, at least in part, by a mobile polypeptide loop in GroES that becomes immobilized in the GroEL/GroES/nucleotide complex. The bacteriophage T4 cochaperonin Gp31 possesses a similar highly flexible polypeptide loop in a region of the protein that shows low, but significant, amino acid similarity with GroES and other cochaperonins. When bound to GroEL, a synthetic peptide representing the mobile loop of either GroES or Gp31 adopts a characteristic bulged hairpin conformation as determined by transferred nuclear Overhauser effects in NMR spectra. Thermodynamic considerations suggest that flexible disorder in the cochaperonin mobile loops moderates their affinity for GroEL to facilitate cycles of chaperonin-mediated protein folding.


Aberrant expression of SOCS impairs the anti-leishmanial immune response.
Establishing a balance between Th1 and Th2 subsets and M1- and M2-type macrophages is essential for the control of Leishmania infection. The suppressors of cytokine secretion (SOCS) proteins, particularly SOCS1 and SOCS3, play a significant role in regulating cytokine-triggered signaling pathways, thereby impacting the macrophage-and effector T-cell mediated antileishmanial immune response. In addition to the pro-inflammatory cytokines, Leishmania-derived lipophosphoglycan (LPG) and CpG-DNA interact with TLR2 and TLR9 to trigger SOCS expression. The aberrant levels of SOCS1 and SOCS3 expression in Leishmania-infected macrophages impair macrophage-T-cell interaction perturbing the balance in macrophage subsets polarization. This hinders macrophage apoptosis and macrophage-mediated leishmanicidal activity, both support the establishment of infection and parasite replication. Furthermore, aberrant SOCS3 levels in T-cells disrupt Th1 differentiation and aid in parasite replication, lesion development, and pathological immune responses. Strategically, selective modulation of SOCS expression and function in immune effector cells may reduce parasite survival and prevent disease progression.


AN ELASTIC EXERCISE BAND MOUNTED WITH A BANDCIZER™ CAN DIFFERENTIATE BETWEEN COMMONLY PRESCRIBED HOME EXERCISES FOR THE SHOULDER.
Home-exercise is commonly prescribed for rehabilitation of the shoulder following injury. There is a lack of technology available to monitor if the patient performs the exercises as prescribed. The purpose of this study was to investigate the validity of using three dimensional (3D) gyroscope data recorded with the Bandcizer™ sensor to differentiate between three elastic band exercises performed in the shoulder joint: abduction, flexion, and external rotation. Concurrent validity study. This study was performed over two phases. In the first phase, 20 subjects performed three sets of 10 of shoulder abduction, external rotation and flexion exercises with a Thera-Band mounted with a Bandcizer, while supervised by a physical therapist. The Bandcizer has an inbuilt three-dimensional gyroscope, capable of measuring angular rotation. Gyroscope data were analyzed in Matlab, and a one-way ANOVA was used to test for significant differences between each of the three exercises. An algorithm was then created in Matlab based on the exercise-data from the gyroscope, to enable differentiation between the three shoulder exercises. Twenty new subjects were then recruited to cross-validate the algorithm and investigate if the algorithm could differentiate between the three different shoulder exercises. A blinded assessor using the Matlab algorithm could correctly identify 56 out of 60 exercise sets. The kappa agreement for the three exercises ranged between 0.86-0.91. The ability to differentiate between the home exercises performed by patients after shoulder injury has great implications for future clinical practice and research. When home exercises are the treatments-of-choice, clinicians will be able to quantify if the patient performed the exercise as intended. Further research should be aimed at investigating the feasibility of using the Bandcizer™ in a home-based environment. 2429. 2.


State of reporting of primary biomedical research: a scoping review protocol.
Incomplete or inconsistent reporting remains a major concern in the biomedical literature. Incomplete or inconsistent reporting may yield the published findings unreliable, irreproducible or sometimes misleading. In this study based on evidence from systematic reviews and surveys that have evaluated the reporting issues in primary biomedical studies, we aim to conduct a scoping review with focuses on (1) the state-of-the-art extent of adherence to the emerging reporting guidelines in primary biomedical research, (2) the inconsistency between protocols or registrations and full reports and (3) the disagreement between abstracts and full-text articles. We will use a comprehensive search strategy to retrieve all available and eligible systematic reviews and surveys in the literature. We will search the following electronic databases: Web of Science, Excerpta Medica Database (EMBASE), MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Our outcomes are levels of adherence to reporting guidelines, levels of consistency between protocols or registrations and full reports and the agreement between abstracts and full reports, all of which will be expressed as percentages, quality scores or categorised rating (such as high, medium and low). No pooled analyses will be performed quantitatively given the heterogeneity of the included systematic reviews and surveys. Likewise, factors associated with improved completeness and consistency of reporting will be summarised qualitatively. The quality of the included systematic reviews will be evaluated using AMSTAR (a measurement tool to assess systematic reviews). All findings will be published in peer-reviewed journals and relevant conferences. These results may advance our understanding of the extent of incomplete and inconsistent reporting, factors related to improved completeness and consistency of reporting and potential recommendations for various stakeholders in the biomedical community.


Liraglutide improves hippocampal synaptic plasticity associated with increased expression of Mash1 in ob/ob mice.
Consumption of high-fat diet exerts adverse effects on learning and memory formation, which is linked to impaired hippocampal function. Activation of glucagon-like peptide-1 (GLP-1) signalling ameliorates detrimental effects of obesity-diabetes on cognitive function; however, mechanisms underlying these beneficial actions remain unclear. This study examined effects of daily subcutaneous treatment with GLP-1 mimetic, Liraglutide, on synaptic plasticity, hippocampal gene expression and metabolic control in adult obese diabetic (ob/ob) mice. Long-term potentiation (LTP) induced by area CA1 was completely abolished in ob/ob mice compared with lean controls. Deleterious effects on LTP were rescued (P<0.001) with Liraglutide. Indeed, Liraglutide-treated mice exhibited superior LTP profile compared with lean controls (P<0.01). Expression of hippocampal brain-derived neurotropic factor and neurotrophic tyrosine kinase receptor-type 2 were not significantly different, but synaptophysin and Mash1 were decreased in ob/ob mice. Treatment with Liraglutide over 21 days increased expression of Mash1 in ob/ob mice (2.0-fold; P<0.01). These changes were associated with significantly reduced plasma glucose (21% reduction; P<0.05) and markedly improved plasma insulin concentrations (2.1- to 3.3-fold; P<0.05 to P<0.01). Liraglutide also significantly reduced the glycaemic excursion following an intraperitonal glucose load (area under curve (AUC) values: 22%; P<0.05) and markedly enhanced the insulin response to glucose (AUC values: 1.6-fold; P<0.05). O2 consumption, CO2 production, respiratory exchange ratio and energy expenditure were not altered by Liraglutide therapy. On day 21, accumulated food intake (32% reduction; P<0.05) and number of feeding bouts (32% reduction; P<0.05) were significantly reduced but simple energy restriction was not responsible for the beneficial actions of Liraglutide. Liraglutide elicits beneficial effects on metabolic control and synaptic plasticity in mice with severe obesity and insulin resistance mediated in part through increased expression of Mash1 believed to improve hippocampal neurogenesis and cell survival.


Recurrent spontaneous intracranial hypotension in early pregnancy.
Spontaneous intracranial hypotension (SIH) is an uncommon condition characterised by postural headache secondary to low cerebrospinal fluid pressure. Here we present a case of recurrence of SIH in early pregnancy in a 26-year-old woman. She first presented at the age of 21 years at 15 weeks' gestation with a history of headache, nausea, vomiting, neck stiffness and photophobia. Findings from a MRI brain scan led to a diagnosis of SIH. She was treated with autologous epidural blood patching and remained asymptomatic until her second pregnancy 5 years later, when she re-presented at 16 weeks' gestation with similar symptoms. She was again diagnosed with SIH and required a repeat treatment of autologous epidural blood patching. She subsequently remained symptom free and delivered a healthy boy at term.


First molecular detection of a novel Babesia species from Haemaphysalis hystricis in Taiwan.
Newly recorded ticks and emerging tick-borne pathogens have recently been reported in subtropical and tropical East Asia. In this study, a total of 1,615 ticks (259 Haemaphysalis hystricis, 1334 Rhipicephalus microplus, 19 H. flava, and 3 R. haemaphysaloides) were collected by flagging from vegetation in Taiwan during 2019-2021. All 1,615 captured tick samples tested negative for SFTSV and Borrelia, but 12 of 356 tick samples tested positive for PCR amplification of a fragment of the 18S rRNA gene of Babesia spp., with an infection rate of 3.37 % (12/356) and a minimum infection rate of 0.74 % (12/1,615). Among the 12 detected Babesia spp., 11 were identified as Babesia bigemina in R. microplus, and the other one, detected in H. hystricis, was classified as an unnamed novel Babesia sp. Interestingly, the 18S rRNA sequence from the isolate detected in H. hystricis shared 98.79 % to 99.50 % identity with those of recent isolates from Japan, China and Nigeria. The exact origin of the Babesia species is not known, but the findings highlight the importance of international cooperation and the exchange of information on ticks and tick-borne pathogens. This represents a rare report of a Babesia sp. identified in H. hystricis, a tick species that has been proposed as a novel vector for some Babesia spp. This study supports H. hystricis as a possible vector of Babesia spp.


Identifying contamination with advanced visualization and analysis practices: metagenomic approaches for eukaryotic genome assemblies.
High-throughput sequencing provides a fast and cost-effective mean to recover genomes of organisms from all domains of life. However, adequate curation of the assembly results against potential contamination of non-target organisms requires advanced bioinformatics approaches and practices. Here, we re-analyzed the sequencing data generated for the tardigrade Hypsibius dujardini, and created a holistic display of the eukaryotic genome assembly using DNA data originating from two groups and eleven sequencing libraries. By using bacterial single-copy genes, k-mer frequencies, and coverage values of scaffolds we could identify and characterize multiple near-complete bacterial genomes from the raw assembly, and curate a 182 Mbp draft genome for H. dujardini supported by RNA-Seq data. Our results indicate that most contaminant scaffolds were assembled from Moleculo long-read libraries, and most of these contaminants have differed between library preparations. Our re-analysis shows that visualization and curation of eukaryotic genome assemblies can benefit from tools designed to address the needs of today's microbiologists, who are constantly challenged by the difficulties associated with the identification of distinct microbial genomes in complex environmental metagenomes.


Syndrome of Headache Accompanied with Transient Neurologic Deficits and Cerebrospinal Fluid Lymphocytosis.
The syndrome of headache accompanied with transient neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL), is a rare, benign and self limiting syndrome. In the 2nd Edition of the International Classification of Headache Disorders, HaNDL syndrome was defined in secondary headache group as "Headache attributed to non-vascular intracranial disorder". The etiology of HaNDL is still unknown. In recent years, some authors have shown that ion channel autoimmunity might at least partially contribute to HaNDL pathogenesis. In this paper, the definition of HaNDL syndrome, clinical picture and epidemiology of HaNDL syndrome, etiopathogenesis, differential diagnosis and treatment will be reviewed with the recent literature.


Green Extraction of Carrageenans from Mastocarpus stellatus.
The recovery of biopolymers from natural resources using eco-friendly extraction technologies that enhance their mechanical properties has gained attention in recent years. In this context, this work deals with the isolation of hybrid carrageenans from Mastocarpus stellatus red seaweed using subcritical water extraction operating in a wide range of thermal conditions (70-190 °C). The extracted biopolymers were analyzed by means of either Fourier-Transform infrared, nuclear magnetic resonance, rheological or cell viability assays. In parallel, the fundamental chemical composition of the seaweed used as raw material, as well as the main phytochemical properties of the soluble liquid extracts, were also studied. Results indicated that thermal extraction conditions significantly affected the rheological behavior of the recovered hybrid carrageenans. The hybrid carrageenan extraction yields varied, with results between 10.2 and 30.2% being the highest values obtained at hydrothermal treatment of 130 °C. A wide palette of viscous features was identified for recovered hybrid carrageenans, with the strongest rheology properties observed at the same temperature. It should be remarked that the maximum inhibitory effect was also obtained at 130 °C for both the ovarian carcinoma cell line (A2780) (65%, IC50: 0.31 mg/mL) and lung carcinoma cell line (A549) (59%, IC50: 0.41 mg/mL).


Endogenous angiogenesis inhibitors.
When the FDA commissioner announced in February 2004 the approval of Avastin for the treatment of patients with colon cancer, he called angiogenesis inhibitors a fourth modality of anti-cancer therapy. Because angiogenesis inhibitors are relatively less toxic than conventional chemotherapy and have a lower risk of drug resistance, they may also represent a new class of anti-cancer agents, some of which have sufficiently reduced toxicity that they may be safely used long term. These include immunotherapy, vaccines, telomerase inhibitors, apoptosis inducers, low dose metronomic chemotherapy, novel hormonal therapies, gene therapy and others. However, at least 16 endogenous angiogenesis inhibitors have been discovered in the circulation, and/or in the extracellular matrix. These may become the safest and least toxic of anti-cancer therapies. Four are already being administered by injection in clinical trials for cancer. Recently, it has been reported that at least two endogenous angiogenesis inhibitors can be significantly increased in humans (endostatin), and in mice (thrombospondin), by oral administration of small molecules which themselves are already FDA approved for other uses. This finding suggests several new clinical applications for the future, including the possibility of guiding the use of angiogenesis inhibitors by blood or urinary biomarkers, currently being developed, that may detect the presence of cancer before it is symptomatic, or before it can be located by conventional methods.


Ecological speciation in Gambusia fishes.
Although theory indicates that natural selection can facilitate speciation as a by-product, demonstrating ongoing speciation via this by-product mechanism in nature has proven difficult. We examined morphological, molecular, and behavioral data to investigate ecology's role in incipient speciation for a post-Pleistocene radiation of Bahamas mosquitofish (Gambusia hubbsi) inhabiting blue holes. We show that adaptation to divergent predator regimes is driving ecological speciation as a by-product. Divergence in body shape, coupled with assortative mating for body shape, produces reproductive isolation that is twice as strong between populations inhabiting different predator regimes than between populations that evolved in similar ecological environments. Gathering analogous data on reproductive isolation at the interspecific level in the genus, we find that this mechanism of speciation may have been historically prevalent in Gambusia. These results suggest that speciation in nature can result as a by-product of divergence in ecologically important traits, producing interspecific patterns that persist long after speciation events have completed.


Pregnancy related symptomatic vertebral hemangioma.
Vertebral hemangiomas are benign vascular tumors of the spine that remain asymptomatic in most cases and incidentally encountered on imaging. Rarely, altered hemodynamic and hormonal changes during pregnancy may expand these benign lesions resulting in severe cord compression. The management of symptomatic vertebral hemangioma during pregnancy is controversial as modalities like radiotherapy and embolization are not suitable and surgery during pregnancy has a risk of preterm labor. Few cases of pregnancy related symptomatic vertebral hemangioma with marked epidural component have been reported in the literature. We report a case of 23-year-old primigravida who developed rapidly progressive paraparesis at 28 weeks of gestation and spine magnetic resonance imaging (MRI) revealed upper thoracic vertebral hemangioma with extensive extra-osseous extension and spinal cord compression. Laminectomy and surgical decompression of the cord was performed at 32 weeks of the pregnancy. There was significant improvement in muscle power after a week of surgery. Six weeks postoperatively she delivered a full term normal baby with subsequent improvement of neurologic deficit. Repeat MRI of dorsal spine performed at 3 months postoperatively showed reduced posterior and anterior epidural components of vertebral hemangioma.


The effects of curcumin on proliferation, apoptosis, invasion, and NEDD4 expression in pancreatic cancer.
Pancreatic cancer (PC) is one of the most fatal cancers worldwide. The incidence and death rates are still increasing for PC. Curcumin is the biologically active diarylheptanoid constituent of the spice turmeric, which exerts its anticancer properties in various human cancers including PC. In particular, accumulating evidence has proved that curcumin targets numerous therapeutically important proteins in cell signaling pathways. The neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) is an E3 HECT ubiquitin ligase and is frequently over-expressed in various cancers. It has reported that NEDD4 might facilitate tumorigenesis via targeting and degradation of multiple tumor suppressor proteins including PTEN. Hence, in the present study we explore whether curcumin inhibits NEDD4, resulting in the suppression of cell growth, migration and invasion in PC cells. We found that curcumin inhibited cell proliferation and triggered apoptosis in PC, which is associated with increased expression of PTEN and p73. These results suggested that inhibition of NEDD4 might be beneficial to the antitumor properties of curcumin on PC treatments.