Evidence of a novel type 2 diabetes locus 50 cM centromeric to NIDDM2 on chromosome 12q.
To replicate the recent finding of a type 2 diabetes locus (NIDDM2) on 12q, families segregating early-onset autosomal-dominant type 2 diabetes were screened for linkage. Included were 26 Caucasian and 6 non-Caucasian pedigrees with an average age at diabetes diagnosis of 37 +/- 18 years. Affected (n = 233) and nonaffected (n = 152) family members were genotyped for 17 markers covering 90 cM on chromosome 12q. While no evidence for linkage was detected at the NIDDM2 locus, a linkage peak was observed 50 cM centromeric to NIDDM2 at markers D12S375 and D12S1052. In a nonparametric analysis, the Z(all) score was 2.9 (P = 0.015) at D12S375, and increased to 3.8 (P = 0.007) among Caucasian families. Further increase in significance was observed in pedigrees with poor insulin response, with a maximum Z(all) of 6.2 (P = 0.002) at D12S375. Suggestive evidence of linkage was also detected by the parametric analysis, with the heterogeneity logarithm of odds score peaking at 2.5 (alpha = 0.15) between D12S375 and D12S1052. In summary, our data indicate that the NIDDM2 locus does not play a major role in early-onset autosomal-dominant type 2 diabetes. Rather, they strongly suggest that a previously undetected type 2 diabetes locus exists 50 cM from NIDDM2 on 12q.


Correlation among ultrasound, cross-sectional anatomy, and histology of the sciatic nerve: a review.
Efficient identification of the sciatic nerve (SN) requires a thorough knowledge of its topography in relation to the surrounding structures. Anatomic cross sections in similar oblique planes as observed during SN ultrasonography are lacking. A survey of sonoanatomy matched with ultrasound views of the major SN block sites will be helpful in pattern recognition, especially when combined with images that show the internal architecture of the nerve. From 1 cadaver, consecutive parts of the upper leg corresponding to the 4 major blocks sites were sectioned and deeply frozen. Using cryomicrotomy, consecutive transverse sections were acquired and photographed at 78-microm intervals, along with histologic sections at 5-mm intervals. Multiplanar reformatting was done to reconstruct the optimal planes for an accurate comparison of ultrasonography and gross anatomy. The anatomic and histologic images were matched with ultrasound images that were obtained from 2 healthy volunteers. By simulating the exact position and angulation as in the ultrasonographic images, detailed anatomic overviews of SN and adjacent structures were reconstructed in the gluteal, subgluteal, midfemoral, and popliteal regions. Throughout its trajectory, SN contains numerous fascicles with connective and adipose tissues. In this study, we provide an optimal matching between histology, anatomic cross sections, and short-axis ultrasound images of SN. Reconstructing ultrasonographic planes with this high-resolution digitized anatomy not only enables an overview but also shows detailed views of the architecture of internal SN. The undulating course of the nerve fascicles within SN may explain its varying echogenic appearance during probe manipulation.


Why is Misdiagnosis of von Willebrand Disease Still Prevalent and How Can We Overcome It? A Focus on Clinical Considerations and Recommendations.
Despite von Willebrand disease (VWD) being the most common inherited bleeding disorder, its accurate diagnosis is frequently shrouded by diagnostic pitfalls. VWD is frequently under-diagnosed, over-diagnosed and misdiagnosed, leading to significant avoidable patient morbidity and health care system burden. At the heart of this dilemma lies the heterogeneity and complexity of von Willebrand factor (VWF) and associated defects, and the necessity of coalescing clinical and laboratory features to obtain an accurate diagnosis. Common pitfalls include poor clinical and scientific understanding and familiarity with VWD, incomplete clinical history and lack of routine use of standardised bleeding assessment tools (BAT), difficulty in accessing a comprehensive repertoire of laboratory tests, significant pre-analytical, analytical and post-analytical issues, and lack of expertise in laboratory testing and interpretation. Errors, resulting in under-diagnosis, over-diagnosis, and misdiagnosis of VWD, are presented and discussed. Strategies to minimise errors include better education of clinicians and laboratory staff on VWD, routine use of validated BAT, utilising a comprehensive gamut of laboratory investigations according to a standardised algorithm, and repeating testing to minimise pre-analytical errors. Recommendations on appropriate patient selection for VWD testing, how VWD should be investigated in the laboratory, and how to ensure test results are accurately interpreted in the correct clinical context are detailed.


Testosterone-immunopositive primordial germ cells in the testis of the bullfrog, Rana catesbeiana.
In amphibia, steroidogenesis remains quiescent in distinct seasonal periods, but the mechanism by which spermatogenesis is maintained under low steroidogenic conditions is not clear. In the present study, testosterone location in the testes of Rana catesbeiana was investigated immunohistochemically during breeding (summer) and nonbreeding (winter) periods. In winter, the scarce interstitial tissue exhibited occasional testosterone immunopositivity in the interstitial cells but the cytoplasm of primordial germ cells (PG cells) was clearly immunopositive. By contrast, in summer, PG cells contained little or no immunoreactivity whereas strong immunolabelling was present in the well-developed interstitial tissue. These results suggest that PG cells could retain testosterone during winter. This androgen reservoir could be involved in the control of early spermatogenesis in winter and/or to guarantee spermiogenesis and spermiation in the next spring/summer. The weak or negative immunoreaction in the summer PG cells might reflect consumption of androgen reservoir by the intense spermatogenic activity from spring to summer. Thus, besides acting as stem cells, PG cells of R. catesbeiana could exert an androgen regulatory role during seasonal spermatogenesis.


[Structural and functional characteristics of angiotensin converting enzyme].
The structure and functions in various tissues of angiotensin converting enzyme (ACE, peptidyl dipeptidase A), a key enzyme in blood pressure regulation, are reviewed. The similarity and differences of two homologous catalytically active N- and C-domains of the ACE molecule are discussed, and different biological functions of these domains are suggested. Natural active single-domain forms of ACE are characterized.


Classification in schizophrenia.
Schizophrenia has been defined as an indentifiable disorder based on phenomenologic classification. Support for this concept is derived from consistent observations of a low frequency of the disorder in general populations throughout the world but substantially higher frequency of occurrence in siblings of affected individuals. The rates of concurrence in diagnosis for schizophrenia, surprisingly, vary in similar degree to those found for a series of physical disorders such as cervical cancer, emphysema and bronchitis, and electrocardiographic evaluations of cardiac disorder. The most recent findings from cross-national diagnostic studies of mental disorder uphold the need for a regular, more definitive classification system that is considered from both the service and research points of view.


Effects of a tailored mat-Pilates exercise program for older adults on pain, functioning, and balance in women with chronic non-specific low back pain: a randomized controlled trial.
Mat-Pilates exercise is effective for chronic non-specific low back pain (NSLBP), but its application in older women is understudied. To examine the effects of a 10-week mat-Pilates program on pain, disability, and balance in older women with chronic NSLBP. Sixty-three women (≥ 65 years) with chronic NSLBP were randomly assigned to intervention (IG) or control (CG) groups. IG received individualized mat-Pilates sessions (45 min, twice weekly), while CG followed a home-based general exercise program. Primary outcomes included visual analog scale (VAS) for pain, Roland-Morris Disability Questionnaire (RMDQ), timed up-and-go (TUG), and Berg Balance Scale (BBS) at baseline, 10 weeks, and 6 months post-intervention. Repeated measures multivariate analysis of covariance (MANCOVA) was used, adjusted for exercise adherence and analgesic use. IG significantly improved in VAS and RMDQ scores at 10 weeks and 6 months (p > 0.05). No significant differences were observed in TUG and BBS scores at any measurement point. No between-group differences were found in analgesic use or adherence to exercise during the 6-month follow-up. A 10-week mat-Pilates program reduced pain and improved disability in older women with chronic NSLBP, effects which persisted at 6 months. However, no impact on balance, analgesic use, or exercise adherence was observed. NCT04752579/February 12, 2021.


[Dystrophic and reparative changes in the cortical neurons of rat progeny in moderate prenatal alcoholization].
Dynamics of dystrophic and reparative changes of sensorimotor cortex neurons ultrastructure in 21, 30 and 60-days progeny of rat treated with moderate doses of alcohol during pregnancy was studied with these changes found in mature cortical neurons having their own dynamics in postnatal ontogenesis. Dystrophic changes are better expressed until the age of a month. Signs of reparative processes increase with age, but hypoxically ischemic dystrophic neuronal changes remain up to puberty, which indicates effectiveness of moderate prenatal action of alcohol.


Involvement of endothelial PECAM-1/CD31 in angiogenesis.
The adhesive interactions of endothelial cells with each other and the adhesion receptors that mediate these interactions are probably of fundamental importance to the process of angiogenesis. We therefore studied the effect of inhibiting the function of the endothelial cell-cell adhesion molecule, PECAM-1/ CD31, in rat and murine models of angiogenesis. A polyclonal antibody to human PECAM-1, which cross-reacts with rat PECAM-1, was found to block in vitro tube formation by rat capillary endothelial cells and cytokine-induced rat corneal neovascularization. In mice, two monoclonal antibodies against murine PECAM-1 prevented vessel growth into subcutaneously implanted gels supplemented with basic fibroblast growth factor (bFGF). Taken together these findings provide evidence that PECAM-1 is involved in angiogenesis and suggest that the interactions of endothelial cell-cell adhesion molecules are important in the formation of new vessels.


The involvement of cysteine proteases and protease inhibitor genes in the regulation of programmed cell death in plants.
Programmed cell death (PCD) is a process by which cells in many organisms die. The basic morphological and biochemical features of PCD are conserved between the animal and plant kingdoms. Cysteine proteases have emerged as key enzymes in the regulation of animal PCD. Here, we show that in soybean cells, PCD-activating oxidative stress induced a set of cysteine proteases. The activation of one or more of the cysteine proteases was instrumental in the PCD of soybean cells. Inhibition of the cysteine proteases by ectopic expression of cystatin, an endogenous cysteine protease inhibitor gene, inhibited induced cysteine protease activity and blocked PCD triggered either by an avirulent strain of Pseudomonas syringae pv glycinea or directly by oxidative stress. Similar expression of serine protease inhibitors was ineffective. A glutathione S-transferase-cystatin fusion protein was used to purify and characterize the induced proteases. Taken together, our results suggest that plant PCD can be regulated by activity poised between the cysteine proteases and the cysteine protease inhibitors. We also propose a new role for proteinase inhibitor genes as modulators of PCD in plants.


Apoptotic signaling induces hyperpermeability following hemorrhagic shock.
Hemorrhagic shock (HS) disrupts the endothelial cell barrier, resulting in microvascular hyperpermeability. Recent studies have also demonstrated that activation of the apoptotic signaling cascade is involved in endothelial dysfunction, which may result in hyperpermeability. Here we report involvement of the mitochondrial "intrinsic" pathway in microvascular hyperpermeability following HS in rats. HS resulted in the activation of the mitochondrial intrinsic pathway, as is evident from an increase in the proapoptotic Bcl-2 family member BAK, release of mitochondrial cytochrome c into the cytoplasm, and activation of caspase-3. This, along with the in vivo transfection of the proapoptotic peptide BAK (BH3), resulted in hyperpermeability (as visualized by intravital microscopy), release of mitochondrial cytochrome c into the cytoplasm, and activation of caspase-3. Conversely, transfection of the BAK (BH3) mutant had no effect on hyperpermeability. Together, these results demonstrate involvement of the mitochondrial intrinsic apoptotic pathway in HS-induced hyperpermeability and that the attenuation of this pathway may provide an alternative strategy in preserving vascular barrier integrity.


Gliosarcoma with chondroid and osseous differentiation.
We present the case of a 65-year-old woman with a short-term history of cognitive decline and neuropsychiatric symptoms. Neuroradiological examinations revealed a large left temporo-occipital cystic and calcified tumor mass measuring 6 cm in diameter, which was suspicious for an oligodendroglioma or a choroid plexus carcinoma. Neuropathological investigations finally revealed a gliosarcoma with extensive mesenchymal differentiation. The tumor demonstrated a biphasic pattern consisting of focal anaplastic glial components with vascular proliferation and necrosis. Adjacent sarcomatous tissue displayed pleomorphic fibroblastic cells surrounding metaplastic cartilage and osseous formation. Accounting for only approximately 2% of glioblastomas, gliosarcomas represent a rare entity of intrinsic CNS neoplasms. Exceedingly rare, the mesenchymal part of the gliosarcoma undergoes metaplastic transformation. Interestingly, in our case, the tumor exhibited features of both cartilaginous and osseous differentiation and multifocally showed a sharp transformation zone between highly malignant gliosarcomatous tumor areas and well-differentiated non-proliferative metaplastic regions.


Antioxidant activity of active tannoid principles of Emblica officinalis (amla).
The antioxidant activity of tannoid active principles of E. officinalis consisting of emblicanin A (37%), emblicanin B (33%), punigluconin (12%) and pedunculagin (14%), was investigated on the basis of their effects on rat brain frontal cortical and striatal concentrations of the oxidative free radical scavenging enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and lipid peroxidation, in terms of thiobarbituric acid-reactive products. The results were compared with effects induced by deprenyl, a selective monoamine oxidase (MAO) B inhibitor with well documented antioxidant activity. The active tannoids of E. officinalis (EOT), administered in the doses of 5 and 10 mg/kg, i.p., and deprenyl (2 mg/kg, i.p.), induced an increase in both frontal cortical and striatal SOD, CAT and GPX activity, with concomitant decrease in lipid peroxidation in these brain areas when administered once daily for 7 days. Acute single administration of EOT and deprenyl had insignificant effects. The results also indicate that the antioxidant activity of E. officinalis may reside in the tannoids of the fruits of the plant, which have vitamin C-like properties, rather than vitamin C itself.


Attainment of high resolution holographic fourier transform spectroscopy.
Two methods are described to attain high resolution holographic spectroscopy. One is an interferometer construction to record the localized interference fringes on the photographic plate directly. The limitation due to the use of an imaging lens is removed. The other is the application of heterodyning techniques to holographic spectroscopy. By this method, a hologram with high resolving power is recorded on relatively low resolution photographic film.


Helium bubble nucleation and growth in α-Fe: insights from first-principles simulations.
We have carried out a first-principles study on the nucleation and early-stage growth of He bubbles in Fe. The energetics, atomic and electronic structure of He-vacancy complexes, involving both a monovacancy and a nine-vacancy cluster, are examined. Based on the energetics, we then perform thermodynamics analysis to gain deeper insights into He bubble nucleation and growth. We have determined the energy cost for the nucleation of He bubbles and found that up to eight He atoms can be trapped at a single vacancy. In order to capture more He atoms, the vacancy has to emit Frenkel pairs to release the substantial stress building on the surrounding Fe lattice. Compared to the monovacancy, the nine-vacancy cluster has a lower energy cost for He bubble nucleation and growth. He atoms at the vacancy repel the surrounding electronic charge and redistribute it on the neighboring Fe atoms. The thermodynamic analysis reveals that He chemical potential provides a driving force for He bubble nucleation and growth. There are two critical He chemical potentials that are of particular importance: one of them marks the transition from single He occupation to multiple He occupation at a monovacancy while the other sets off He-induced superabundant vacancy formation.


Clinical application of presepsin as diagnostic biomarker of infection: overview and updates.
The appropriate identification of bacterial infection is the basis for effective treatment and control of infective disease. Among this context, an emerging biomarker of infection is presepsin (PSP), recently described as early marker of different infections. PSP secretion has been shown to be associated with monocyte phagocytosis and plasmatic levels of PSP increase in response to bacterial infection and decrease after antibiotic treatment, therefore it can be considered a marker of activation of immune cell response towards an invading pathogen. Different methods have been developed to measure PSP and this review will briefly describe the different clinical fields of application of PSP, ranging from intensive care to neonatal infection, to orthopedic and pulmonary infection as well as fungal infections and cardiovascular infections.


Changes in the practice of medicine.
In constructing this report, the author interviewed physicians to ask them how the practice of medicine has changed and what changes bother them most. She also talked to physician executives to find out how they were managing an increasingly disgruntled group of doctors. Four changes in the professional environment that physicians face dominated these conversations--lowered income, loss of control, the threat of litigation, and greatly increased paperwork. This article is a summary of comments in these four areas.


P311 Promotes Lung Fibrosis via Stimulation of Transforming Growth Factor-β1, -β2, and -β3 Translation.
Interstitial lung fibrosis, a frequently idiopathic and fatal disease, has been linked to the increased expression of profibrotic transforming growth factor (TGF)-βs. P311 is an RNA-binding protein that stimulates TGF-β1, -β2, and -β3 translation in several cell types through its interaction with the eukaryotic translation initiation factor 3b. We report that P311 is switched on in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and in the mouse model of bleomycin (BLM)-induced pulmonary fibrosis. To assess the in vivo role of P311 in lung fibrosis, BLM was instilled into the lungs of P311-knockout mice, in which fibrotic changes were significantly decreased in tandem with a reduction in TGF-β1, -β2, and -β3 concentration/activity compared with BLM-treated wild-type mice. Complementing these findings, forced P311 expression increased TGF-β concentration/activity in mouse and human lung fibroblasts, thereby leading to an activated phenotype with increased collagen production, as seen in IPF. Consistent with a specific effect of P311 on TGF-β translation, TGF-β1-, -β2-, and -β3-neutralizing antibodies downregulated P311-induced collagen production by lung fibroblasts. Furthermore, treatment of BLM-exposed P311 knockouts with recombinant TGF-β1, -β2, and -β3 induced pulmonary fibrosis to a degree similar to that found in BLM-treated wild-type mice. These studies demonstrate the essential function of P311 in TGF-β-mediated lung fibrosis. Targeting P311 could prove efficacious in ameliorating the severity of IPF while circumventing the development of autoimmune complications and toxicities associated with the use of global TGF-β inhibitors.


Three label-free thrombin aptasensors based on aptamers and [Ru(bpy)2(o-mopip)]2.
Early disease diagnosis is very important for the prevention or mitigation of metastasis. Effective and efficient methods are needed to improve the diagnosis and assessment of diseases. Thrombin is a biomarker for diagnosis of some diseases, such as pulmonary metastases and diseases associated with coagulation abnormalities. Lots of methods for detecting thrombin have been reported, however, most of them were based on a single aptamer and needed modification of aptamers, and label free sensors for thrombin detection based on an aptamer pair are challenging. In this work, we present three label free sensing platforms based on [Ru(bpy)2(o-mopip)]2+ (bpy = 2,2-bipyridine; o-mopip = 2-(2-methoxylphenyl)imidazo[4,5-f][1,10]phenanthroline) (OMO) and graphene oxide (GO) for thrombin detection. Thrombin detection using our three label free sensors is accomplished by specific target recognition based on aptamer pair TBA1/TBA2-thrombin, single aptamer TBA1-thrombin or TBA2-thrombin, respectively. Direct readouts of the target recognition is achieved by restoration of the fluorescence of OMO prequenched by GO. All of the three sensing platforms exhibited high sensitivity and selectivity. Furthermore, all sensing platforms were successfully applied to thrombin analysis in diluted bovine serum. According to the thrombin dependent response of the three platforms, the sensing platform based on aptamer pair TBA1 and TBA2 showed the highest sensitivity, widest linearity, best selectivity and recovery in diluted serum to thrombin. These results show that the sensing platform based on an aptamer pair have great potential for clinical diagnosis of disease-related biomarkers.


Homoharringtonine suppresses imatinib resistance via the Bcl-6/p53 pathway in chronic myeloid leukemia cell lines.
The anti-leukemic mechanism of homoharringtonine (HHT) differs from that of IM, and HHT is one of the most useful agents for use in patients with IM resistance or intolerance. The Bcl-6/p53 pathway has been shown to regulate the sensitivity of tumor cells to antitumor drugs. We tested whether HHT blocked the Bcl-6/p53 pathway in order to promote the apoptosis of IM-resistant cells in vitro and in vivo. Ph+ acute lymphoblastic leukemia (ALL) cells and IM-resistant chronic myeloid leukemia (CML) cells showed high expression of Bcl-6 protein. Bcl-6 mediated the upregulation of p53, and and Bcl-6 induced growth inhibition of IM-resistant cells as well as its apoptosis by targeting p53. In addition, Bcl-6 was downregulated moderately after HHT treatment in different cells. The Bcl-6 expression was significantly increased in patients with CML when compared with healthy subjects. Furthermore, the expression of Bcl-6 was higher in patients with CML-blastic phase (CML-BP) than in those with CML-chronic phase (CML-CP). The inhibitory effect of drugs on cell growth was detected by Cell Counting Kit-8 (CCK-8), The apoptosis rate and the cell cycle were investigated by flow cytometry. The expression of Bcl-6, p53, Bcl-2, caspase9, and caspase3 proteins was assayed by western blot, Real- Time PCR (qPCR) detect Bcl-6 and p53 mRNA. HHT can suppress the growth and induce apoptosis of IM-resistant cells, the mechanism of which is associated with blocking of the Bcl-6/p53 pathway. Our results could offer a theoretical explanation for HHT use in patients with IM resistance or intolerance.


Assessing the impact of mental health difficulties on young people's daily lives: protocol for a scoping umbrella review of measurement instruments.
An important consideration for determining the severity of mental health symptoms is their impact on youth's daily lives. Those wishing to assess 'life impact' face several challenges: First, various measurement instruments are available, including of global functioning, health-related quality of life and well-being. Existing reviews have tended to focus on one of these domains; consequently, a comprehensive overview is lacking. Second, the extent to which such instruments truly capture distinct concepts is unclear. Third, many available scales conflate symptoms and their impact, thus undermining much needed analyses of associations between the two. A scoping umbrella review will examine existing reviews of life impact measures for use with children and youth aged 6-24 years in the context of mental health and well-being research. We will systematically search six bibliographic databases (MEDLINE, Embase, APA PsycINFO, CINAHL, Web of Science, and the COSMIN database of systematic reviews of outcome measurement instruments), and conduct systematic record screening, data extraction and charting based on methodological guidance by the Joanna Briggs Institute. Data synthesis will involve the tabulation of scale characteristics, feasibility and measurement properties, and the use of summary statistics to synthesise how these instruments operationalise life impact. The protocol was registered prospectively with the Open Science Framework (osf.io/ers48). This study will provide a comprehensive road map for researchers and clinicians seeking to assess life impact in youth mental health, providing guidance in navigating available measurement options. We will seek to publish the findings in a leading peer-reviewed journal in the field. Formal research ethics approval will not be required.


GABAB Receptor-Mediated Impairment of Intermediate Progenitor Maturation During Postnatal Hippocampal Neurogenesis of Newborn Rats.
The neurotransmitter GABA and its receptors assume essential functions during fetal and postnatal brain development. The last trimester of a human pregnancy and early postnatal life involves a vulnerable period of brain development. In the second half of gestation, there is a developmental shift from depolarizing to hyperpolarizing in the GABAergic system, which might be disturbed by preterm birth. Alterations of the postnatal GABA shift are associated with several neurodevelopmental disorders. In this in vivo study, we investigated neurogenesis in the dentate gyrus (DG) in response to daily administration of pharmacological GABAA (DMCM) and GABAB (CGP 35348) receptor inhibitors to newborn rats. Six-day-old Wistar rats (P6) were daily injected (i.p.) to postnatal day 11 (P11) with DMCM, CGP 35348, or vehicle to determine the effects of both antagonists on postnatal neurogenesis. Due to GABAB receptor blockade by CGP 35348, immunohistochemistry revealed a decrease in the number of NeuroD1 positive intermediate progenitor cells and a reduction of proliferative Nestin-positive neuronal stem cells at the DG. The impairment of hippocampal neurogenesis at this stage of differentiation is in line with a significantly decreased RNA expression of the transcription factors Pax6, Ascl1, and NeuroD1. Interestingly, the number of NeuN-positive postmitotic neurons was not affected by GABAB receptor blockade, although strictly associated transcription factors for postmitotic neurons, Tbr1, Prox1, and NeuroD2, displayed reduced expression levels, suggesting impairment by GABAB receptor antagonization at this stage of neurogenesis. Antagonization of GABAB receptors decreased the expression of neurotrophins (BDNF, NT-3, and NGF). In contrast to the GABAB receptor blockade, the GABAA receptor antagonization revealed no significant changes in cell counts, but an increased transcriptional expression of Tbr1 and Tbr2. We conclude that GABAergic signaling via the metabotropic GABAB receptor is crucial for hippocampal neurogenesis at the time of rapid brain growth and of the postnatal GABA shift. Differentiation and proliferation of intermediate progenitor cells are dependent on GABA. These insights become more pertinent in preterm infants whose developing brains are prematurely exposed to spostnatal stress and predisposed to poor neurodevelopmental disorders, possibly as sequelae of early disruption in GABAergic signaling.


Pyrin-PSTPIP1 colocalises at the leading edge during cell migration.
A set of mutations in the MEditerranean FeVer (MEFV) gene causes familial Mediterranean fever (FMF), the most common auto-inflammatory disease. The gene encodes a protein named pyrin, which appears to play an important role in inflammatory pathways. Furthermore, pyrin, which is expressed in neutrophils, has been reported to interact with proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) and actin proteins. However, the relations between pyrin and PSTPIP1 during the cell migration have not yet been elucidated. In the present study, we constructed a cell migration assay method using HL-60 cells. Pyrin-PSTPIP1 interactions were analysed by immunofluorescence staining in control, differentiated and differentiated-stimulated HL-60 cells. In stimulated cells, pyrin-polymerised actin, PSTPIP1-polymerised actin and pyrin-PSTPIP1 were found to be colocalised. Pyrin has been shown to be colocalised with actin and PSTPIP1 at the leading edge of the migrating cell. For the first time, PSTPIP1 was found to interact with dynamic actin and pyrin at the site of polarisation.


Buruli ulcer treatment: Rate of surgical intervention differs highly between treatment centers in West Africa.
Antibiotic treatment proved itself as the mainstay of treatment for Buruli ulcer disease. This neglected tropical disease is caused by Mycobacterium ulcerans. Surgery persists as an adjunct therapy intended to reduce the mycobacterial load. In an earlier clinical trial, patients benefited from delaying the decision to operate. Nevertheless, the rate of surgical interventions differs highly per clinic. A retrospective study was conducted in six different Buruli ulcer (BU) treatment centers in Benin and Ghana. BU patients clinically diagnosed between January 2012 and December 2016 were included and surgical interventions during the follow-up period, at least one year after diagnosis, were recorded. Logistic regression analysis was carried out to estimate the effect of the treatment center on the decision to perform surgery, while controlling for interaction and confounders. A total of 1193 patients, 612 from Benin and 581 from Ghana, were included. In Benin, lesions were most frequently (42%) categorized as the most severe lesions (WHO criteria, category III), whereas in Ghana lesions were most frequently (44%) categorized as small lesions (WHO criteria, category I). In total 344 (29%) patients received surgical intervention. The percentage of patients receiving surgical intervention varied between hospitals from 1.5% to 72%. Patients treated in one of the centers in Benin were much more likely to have surgery compared to the clinic in Ghana with the lowest rate of surgical intervention (RR = 46.7 CI 95% [17.5-124.8]). Even after adjusting for confounders (severity of disease, age, sex, limitation of movement at joint at time of diagnosis, ulcer and critical sites), rates of surgical interventions varied highly. The decision to perform surgery to reduce the mycobacterial load in BU varies highly per clinic. Evidence based guidelines are needed to guide the role of surgery in the treatment of BU.


English to Arabic translation of the Composite Abuse Scale (CAS): a multi-method approach.
The composite abuse scale (CAS) is a comprehensive tool used to measure intimate partner violence (IPV). The aim of the present study is to translate the CAS from English to Arabic. The translation of the CAS was conducted in four stages using a multi-method approach: 1) preliminary forward translation, 2) discussion with a panel of bilingual experts, 3) focus groups discussion, and 4) back-translation of the CAS. The discussion included a linguistic validation by a comparison of the Arabic translation with the original English by assessing conceptual and content equivalence. In all the stages of translation, there was an agreement to remove the question from the CAS that asked women about the use of objects in the vagina. Wording, format and order of the items were refined according to comments and suggestions made by the experts' panel and focus groups' members. The back-translated CAS showed similar wording and language of the original English version. The Arabic version of the CAS will help to measure the problem of IPV among Saudi women and possibly other Arabic-speaking women in future studies. This is important, particularly, in longitudinal studies or intervention studies among abused women and it allows a comparison of the results of studies from different cultures. However, further validations studies are needed to ensure accurate and equivalent Arabic translation of the CAS.


Updates on Molecular and Biochemical Development and Progression of Prostate Cancer.
Prostate cancer (PCa) represents the most commonly non-cutaneous diagnosed cancer in men worldwide and occupies a very wide area of preclinical and clinical research. Targeted therapy for any cancer depends on the understanding of the molecular bases and natural behaviour of the diseases. Despite the well-known effect of androgen deprivation on PCa, many patients develop resistance either for antiandrogen therapy or other new treatment modalities such as checkpoint inhibitors and chemotherapy. Comprehensive understanding of the development of PCa as well as of the mechanisms underlying its progression is mandatory to maximise the benefit of the current approved medications or to guide the future research for targeted therapy of PCa. The aim of this review was to provide updates on the most recent mechanisms regarding the development and the progression of PCa. According to the current understanding, future treatment strategies should include more predictive genetic and biomarker analysis to assign different patients to the expected most appropriate and effective treatment.


Crowding effects on protein association: effect of interactions between crowding agents.
The cell cytoplasm is a dense environment where the presence of inert cosolutes can significantly alter the rates of protein folding and protein association reactions. Most theoretical studies focus on hard sphere crowding agents and quantify the effect of excluded volume on reaction rates. In this work the effect of interactions between the crowding agents on the thermodynamics of protein association is studied using computer simulation. Three cases are considered, where the crowding agents are (i) hard spheres, (ii) hard spheres with additional attractive or repulsive interactions, and (iii) chains of hard spheres. Reactants and products of the protein association are modeled as hard spheres. Although crowding effects are sensitive to the shape of the reaction product, in most cases the excess free energy difference between the product and reactants (nonideality factor) is insensitive to the interactions between crowding agents, due to a cancellation of effects. The simulations therefore suggest that the hard sphere model of crowding agents has a surprisingly large regime of validity and should be sufficient for a qualitative understanding of the thermodynamics of crowding effects when the interactions of associating proteins with crowding agents other than excluded volume interactions are not significant.


A systematic review of studies comparing health outcomes in Canada and the United States.
Differences in medical care in the United States compared with Canada, including greater reliance on private funding and for-profit delivery, as well as markedly higher expenditures, may result in different health outcomes. To systematically review studies comparing health outcomes in the United States and Canada among patients treated for similar underlying medical conditions. We identified studies comparing health outcomes of patients in Canada and the United States by searching multiple bibliographic databases and resources. We masked study results before determining study eligibility. We abstracted study characteristics, including methodological quality and generalizability. We identified 38 studies comparing populations of patients in Canada and the United States. Studies addressed diverse problems, including cancer, coronary artery disease, chronic medical illnesses and surgical procedures. Of 10 studies that included extensive statistical adjustment and enrolled broad populations, 5 favoured Canada, 2 favoured the United States, and 3 showed equivalent or mixed results. Of 28 studies that failed one of these criteria, 9 favoured Canada, 3 favoured the United States, and 16 showed equivalent or mixed results. Overall, results for mortality favoured Canada (relative risk 0.95, 95% confidence interval 0.92-0.98, p= 0.002) but were very heterogeneous, and we failed to find convincing explanations for this heterogeneity. The only condition in which results consistently favoured one country was end-stage renal disease, in which Canadian patients fared better. Available studies suggest that health outcomes may be superior in patients cared for in Canada versus the United States, but differences are not consistent.


Molecular and cytological responses of Medicago truncatula to Erysiphe pisi.
SUMMARY Powdery mildew is an economically important disease in a number of crop legumes; however, little is known about resistance to the disease in these species. To gain a better understanding of the genetics of resistance and plant responses to powdery mildew in legumes, we developed a pathosystem with Medicago truncatula and Erysiphe pisi. Screening accessions of M. truncatula identified genotypes that are highly susceptible, moderately resistant and highly resistant to the fungus. In the highly resistant genotype, fungal growth was arrested after appressorium development with no colony formation, while in the moderately resistant genotype a small number of colonies formed. Both resistant and moderately resistant genotypes produced hydrogen peroxide and fluorescent compounds at pathogen penetration sites, consistent with a hypersensitive response (HR), although the response was delayed in the moderately resistant genotype. Very little hydrogen peroxide or fluorescence was detected in the susceptible accession. Microarray analysis of E. pisi-induced early transcriptional changes detected 55 genes associated with the basal defence response that were similarly regulated in all three genotypes. These included pathogenesis-related genes and other genes involved in defence, signal transduction, senescence, cell wall metabolism and abiotic stress. Genes associated with the HR response included flavonoid pathway genes, and others involved in transport, transcription regulation and signal transduction. A total of 34 potentially novel unknown genes, including two legume-specific genes, were identified in both the basal response and the HR categories. Potential binding sites for two defence-related transcription regulators, Myb and Whirly, were identified in promoter regions of induced genes, and four novel motifs were found in promoter regions of genes repressed in the resistant interaction.


Sequential targeting of CFTR by BAC vectors generates a novel pig model of cystic fibrosis.
Cystic fibrosis (CF) is the most common lethal inherited disease in Caucasians and is caused by mutations in the CFTR gene. The disease is incurable and medical treatment is limited to the amelioration of symptoms or secondary complications. A comprehensive understanding of the disease mechanisms and the development of novel treatment options require appropriate animal models. Existing CF mouse models fail to reflect important aspects of human CF. We thus generated a CF pig model by inactivating the CFTR gene in primary porcine cells by sequential targeting using modified bacterial artificial chromosome vectors. These cells were then used to generate homozygous CFTR mutant piglets by somatic cell nuclear transfer. The homozygous CFTR mutants lack CFTR protein expression and display severe malformations in the intestine, respiratory tract, pancreas, liver, gallbladder, and male reproductive tract. These phenotypic abnormalities closely resemble both the human CF pathology as well as alterations observed in a recently published CF pig model which was generated by a different gene targeting strategy. Our new CF pig model underlines the value of the CFTR-deficient pig for gaining new insight into the disease mechanisms of CF and for the development and evaluation of new therapeutic strategies. This model will furthermore increase the availability of CF pigs to the scientific community.


Gut Microbiota-Related Evidence Provides New Insights Into the Association Between Activating Transcription Factor 4 and Development of Salt-Induced Hypertension in Mice.
Activating transcription factor 4 (ATF4), which regulates genes associated with endoplasmic reticulum stress, apoptosis, autophagy, the gut microbiome, and metabolism, has been implicated in many diseases. However, its mechanistic role in hypertension remains unclear. In the present study, we investigated its role in salt-sensitive hypertensive mice. Wild-type (WT) C57BL/6J mice were used to establish Atf4 knockout (KO) and overexpression mice using CRISPR-Cas9 and lentiviral overexpression vectors. Then, fecal microbiota transplantation (FMT) from Atf4 ± mice and vitamin K2 (VK2) supplementation were separately carried out in high-salt-diet (8% NaCl)-induced mice for 4 weeks. We found that Atf4 KO inhibited and Atf4 overexpression enhanced the increase in blood pressure and endothelial dysfunction induced by high salt intake in mice, while regulating the gut microbiota composition and VK2 expression. It was further verified that ATF4 is involved in the regulation of salt-sensitive hypertension and vascular endothelial function, which is achieved through association with gut microbiota and may be related to VK2 and different bacteria such as Dubosiella. In addition, we found that VK2 supplementation prevents the development of salt-sensitive hypertension and maintains vascular endothelial function; moreover, VK2 supplementation increases the abundance of intestinal Dubosiella and downregulates the relative expression of Atf4 in the thoracic aorta of mice. We conclude that ATF4 plays an important role in regulating gut microbiota and VK2 production, providing new insights into the association between ATF4 and development of salt-induced hypertension in mice, meanwhile contributing to the development for a new preventive strategy of hypertension.


Arterial pressure, left ventricular mass, and aldosterone in essential hypertension.
The purpose of the present study was to evaluate the relationship of aldosterone to blood pressure and left ventricular size in black American (n=109) and white French Canadian (n=73) patients with essential hypertension. Measurements were obtained with patients off antihypertensive medications and included 24-hour blood pressure monitoring, plasma renin activity and aldosterone, and an echocardiogram. Compared with the French Canadians, the black Americans had higher body mass indexes, higher systolic blood pressures, attenuated nighttime reduction of blood pressure, and lower serum potassium concentrations (P:<0.01 for each). Left ventricular mass index, posterior wall thickness, interventricular septal thickness, and relative wall thickness were also greater (P:<0.01 for each) in the black American patients. Supine and standing plasma renin activity was lower (P:<0.01 and P:<0.05, respectively) in the black Americans, whereas supine plasma aldosterone concentrations did not differ, and standing plasma aldosterone was greater (P:<0.05) in the black Americans (9.2+/-0.7 ng/dL) than in the French Canadians (7.3+/-0.6 ng/dL). In the black Americans, supine plasma aldosterone was positively correlated with nighttime systolic (r=0.30; P:<0.01) and diastolic (r=0.39; P:<0.001) blood pressures and inversely correlated with the nocturnal decline of systolic (r=-0.29; P:<0.01) and diastolic (r=-0.37; P:<0.001) blood pressures. In the black Americans, standing plasma aldosterone was positively correlated with left ventricular mass index (r=0.36; P:<0.001), posterior wall thickness (r=0.33; P:<0.01), and interventricular septal thickness (r=0.26; P:<0.05). When the black American patients were divided into obese and nonobese groups, significant correlations between plasma aldosterone and both blood pressure and cardiac mass were observed only in the obese. In the French Canadians, overall, plasma aldosterone did not correlate with either blood pressure or any measures of heart size. However, among obese French Canadians, supine plasma aldosterone correlated with nighttime diastolic (r=0.53, P:<0.02) and systolic (r=0.44, P:<0.01) blood pressures but not with cardiac mass. These results are consistent with the hypothesis that aldosterone contributes to elevated arterial pressure in obese black American and obese white French Canadian patients with essential hypertension and to the attenuated nocturnal decline of blood pressure and left ventricular hypertrophy in obese, hypertensive black Americans.


Practical 24-fs, 1-μJ, 1-MHz Yb-fiber laser amplification system.
We develop a practical femtosecond polarization-maintaining fiber laser amplification system with a standard double-cladding fiber technique, enabling 24-fs transform-limited pulses with 1-μJ pulse energy at a 1-MHz repetition rate. The laser system is based on a hybrid amplification scheme. Chirped-pulse amplification is employed in the pre-amplifier stage to supply high-quality pulses with enough energy for the main-amplifier, where nonlinear amplification is utilized to broaden the output spectrum. To obtain a dechirped pulse with high quality and short duration, a pre-shaper is inserted between the two amplification stages to adjust the pre-chirp, central wavelength, and pulse energy of the signal pulses in the main amplifier for optimizing pulse evolution. As a result, temporal pedestal free sub-ten-cycle high-energy laser pulses can be routinely obtained. In the end, the advantages of this novel laser source are demonstrated in the experiments on enhanced damage effect to cells co-cultured with gold nanorods.


Ste20-like Kinase Is Critical for Inhibitory Synapse Maintenance and Its Deficiency Confers a Developmental Dendritopathy.
The size and structure of the dendritic arbor play important roles in determining how synaptic inputs of neurons are converted to action potential output. The regulatory mechanisms governing the development of dendrites, however, are insufficiently understood. The evolutionary conserved Ste20/Hippo kinase pathway has been proposed to play an important role in regulating the formation and maintenance of dendritic architecture. A key element of this pathway, Ste20-like kinase (SLK), regulates cytoskeletal dynamics in non-neuronal cells and is strongly expressed throughout neuronal development. However, its function in neurons is unknown. We show that, during development of mouse cortical neurons, SLK has a surprisingly specific role for proper elaboration of higher, ≥ third-order dendrites both in male and in female mice. Moreover, we demonstrate that SLK is required to maintain excitation-inhibition balance. Specifically, SLK knockdown caused a selective loss of inhibitory synapses and functional inhibition after postnatal day 15, whereas excitatory neurotransmission was unaffected. Finally, we show that this mechanism may be relevant for human disease, as dysmorphic neurons within human cortical malformations revealed significant loss of SLK expression. Overall, the present data identify SLK as a key regulator of both dendritic complexity during development and inhibitory synapse maintenance.SIGNIFICANCE STATEMENT We show that dysmorphic neurons of human epileptogenic brain lesions have decreased levels of the Ste20-like kinase (SLK). Decreasing SLK expression in mouse neurons revealed that SLK has essential functions in forming the neuronal dendritic tree and in maintaining inhibitory connections with neighboring neurons.


The Francisella pathogenicity island protein PdpD is required for full virulence and associates with homologues of the type VI secretion system.
Francisella tularensis is a highly infectious, facultative intracellular bacterial pathogen that is the causative agent of tularemia. Nearly a century ago, researchers observed that tularemia was often fatal in North America but almost never fatal in Europe and Asia. The chromosomes of F. tularensis strains carry two identical copies of the Francisella pathogenicity island (FPI), and the FPIs of North America-specific biotypes contain two genes, anmK and pdpD, that are not found in biotypes that are distributed over the entire Northern Hemisphere. In this work, we studied the contribution of anmK and pdpD to virulence by using F. novicida, which is very closely related to F. tularensis but which carries only one copy of the FPI. We showed that anmK and pdpD are necessary for full virulence but not for intracellular growth. This is in sharp contrast to most other FPI genes that have been studied to date, which are required for intracellular growth. We also showed that PdpD is localized to the outer membrane. Further, overexpression of PdpD affects the cellular distribution of FPI-encoded proteins IglA, IglB, and IglC. Finally, deletions of FPI genes encoding proteins that are homologues of known components of type VI secretion systems abolished the altered distribution of IglC and the outer membrane localization of PdpD.


The activation of CTP: phosphocholine cytidylyltransferase from rat liver by polyunsaturated phospholipid.
Experimental evidence is reported that the addition in vitro of a polyunsaturated soybean phospholipid material (EPL) to a CTP:PC cytidylyltransferase preparation from rat liver (E.C. 220.127.116.11) produces noticeable stimulation of this enzymatic activity. Preincubation for different time intervals of EPL under air or oxygen further stimulates the activating effects. Little influence is exerted on the same enzyme by saturated lipids, such as dipalmitoyl-sn-glycero-3-phosphorylcholine and distearoyl-sn-glycero-3-phosphorylcholine. It is proposed that the lipid components of the EPL which exert the stimulatory action may be lyso-phospholipid moieties derived from EPL upon preincubation or directly present in the product. The biological significance of these activations in liver tissue is discussed.


Progressive systemic sclerosis and nervous system involvement. A review of 14 cases.
Nervous system involvement in progressive systemic sclerosis (PSS) has been considered rare compared to other collagen diseases. We present 14 additional cases of PSS with neurological manifestations. Primary involvement of the peripheral nerves could be detected in 4 of 14 patients and is documented by electromyo- and electroneurographical examinations. Central nervous system (CNS) manifestations directly related to PSS are a rarity, which may reflect the lack of collagen in the brain, histological differences between cerebral and other arteries and the immunological particularity of the brain. There may have been a direct relationship between CNS involvement and PSS in only one patient presenting with an overlap-syndrome.


Hodgkin's disease in Kenya.
A total of 136 patients with Hodgkin's disease (HD) seen at a national referral hospital in Kenya over a 15-year period were studied. The overall male-to-female ratio was 2.6:1, with 65% of patients younger than 20 years of age. The bimodal incidence of HD frequently seen in the developed nations was absent, and the histologic pattern of the disease was similar to that seen in other African countries. Fifty percent of patients had advanced-stage disease when first seen. Over two thirds of patients treated had a clinical remission, and the relapse rate in all stages was approximately 30%. Therapy-related complications were common, with frequent myelosuppression and younger patients more susceptible.


Validity of the British system for anticoagulant control using the national reagent.
The national system for anticoagulant control depends on drawing the best line obtained by visual comparison of the points representing corresponding prothrombin ratios with the British comparative thromboplastin in the local reagent. This line is then used to correct subsequent values using the local laboratory method of corresponding values in terms of the British comparative thromboplastin.A study has been made of the statistical validity of the recommended system for anticoagulant control using the Quick one-stage test by comparing the line drawn by inspection with the confidence limits of the regression line. There was little difference between the best straight line by visual comparison and the calculated line for the majority of hospitals. The recommended procedure, therefore, provides an adequate conversion of the local method to the British comparative thromboplastin without the need for calculation. The significance of aberrant points is discussed and it is suggested that when more than two of the 12 results fall in this category the standardization procedure should be repeated.


Eating Behaviours of Preadolescent Children over Time: Stability, Continuity and the Moderating Role of Perceived Parental Feeding Practices.
The links between childhood eating behaviours and parental feeding practices are well-established in younger children, but there is a lack of research examining these variables in a preadolescent age group, particularly from the child's perspective, and longitudinally. This study firstly aimed to examine the continuity and stability of preadolescent perceptions of their parents' controlling feeding practices (pressure to eat and restriction) over a 12 month period. The second aim was to explore if perceptions of parental feeding practices moderated the relationship between preadolescents' eating behaviours longitudinally. Two hundred and twenty nine preadolescents (mean age at recruitment 8.73 years) completed questionnaires assessing their eating behaviours and their perceptions of parental feeding practices at two time points, 12 months apart (T1 and T2). Preadolescents' perceptions of their parental feeding practices remained stable. Perceptions of restriction and pressure to eat were continuous. Perceptions of parental pressure to eat and restriction significantly moderated the relationships between eating behaviours at T1 and T2. The findings from this study suggest that in a preadolescent population, perceptions of parental pressure to eat and restriction of food may exacerbate the development of problematic eating behaviours.


[Quantitative electroencephalography in healthy school-age children: analysis of band power].
Quantitative EEG aspects are studied with respect to age, sex and sociocultural parameters. A total of 162 children, from 7 to 11 years, neurologically and intellectually normal was studied. They were submitted to anamnesis, neurological examination, Raven test, school performance test, digital electroencephalogram and quantitative electroencephalogram analysis. There was a decrease in absolute and relative delta and theta power and an increase in alpha 2 relative power with the increase of age. These findings are similar to those observed in studies from Europe, Asia and North America. Absolute delta and alpha power were higher in children with better scores in school performance test. There were no significant differences in quantitative electroencephalographic parameters according to sex and the mother's educational level.


Repeated loss of coloniality and symbiosis in scleractinian corals.
The combination of coloniality and symbiosis in Scleractinia is thought to confer competitive advantage over other benthic invertebrates, and it is likely the key factor for the dominance of corals in tropical reefs. However, the extant Scleractinia are evenly split between zooxanthellate and azooxanthellate species. Most azooxanthellate species are solitary and nearly absent from reefs, but have much wider geographic and bathymetric distributions than reef corals. Molecular phylogenetic analyses have repeatedly recovered clades formed by colonial/zooxanthellate and solitary/azooxanthellate taxa, suggesting that coloniality and symbiosis were repeatedly acquired and/or lost throughout the history of the Scleractinia. Using Bayesian ancestral state reconstruction, we found that symbiosis was lost at least three times and coloniality lost at least six times, and at least two instances in which both characters were lost. All of the azooxanthellate lineages originated from ancestors that were reconstructed as symbiotic, corroborating the onshore-offshore diversification trend recorded in marine taxa. Symbiotic sister taxa of two of these descendant lineages are extant in Caribbean reefs but disappeared from the Mediterranean before the end of the Miocene, whereas extant azooxanthellate lineages have trans-Atlantic distributions. Thus, the phyletic link between reef and nonreef communities may have played an important role in the dynamics of extinction and recovery that marks the evolutionary history of scleractinians, and some reef lineages may have escaped local extinction by diversifying into offshore environments. However, this macroevolutionary mechanism offers no hope of mitigating the effects of climate change on coral reefs in the next century.


Long-term prognosis in men and women coming to the emergency department with chest pain or other symptoms suggestive of acute myocardial infarction.
The aim of this study was to describe mortality, mode of death and risk indicators for death during 5 years of follow-up among men and women coming to the emergency department with chest pain or other symptoms raising suspicion of acute myocardial infarction (AMI). During the 21 months of the study, all patients who came to the medical emergency department of one single hospital with chest pain or other symptoms suggestive of AMI were prospectively followed for 5 years. A total of 5362 patients came on 7157 occasions; men accounted for 55% of the admissions. The 5-year mortality rate was 25.6% for men compared with 25.7% for women. The women were older and had a higher prevalence of known congestive heart failure and hypertension, whereas the prevalence of previous myocardial infarction was higher in men. When correcting for dissimilarities in age and clinical history, male gender appeared as an independent predictor of death. In terms of mode of death men differed from women: more frequently dying at home, more frequently dying in association with ventricular fibrillation and less frequently dying in association with congestive heart failure. However, these differences were to some extent explained by differences in age. Independent risk indicators for death during 5 years of follow-up differed in men and women. It was concluded that in a consecutive series of patients with chest pain or other symptoms suggesting AMI in the emergency department, male gender was an independent risk indicator for death during a 5-year follow-up. This might be explained by a higher occurrence of coronary artery disease in men than in women in this patient population.


An inferior alveolar intraneural cyst: a case example and an anatomical explanation to support the articular theory within cranial nerves.
The authors describe the case of an intraneural ganglion cyst involving a cranial nerve (V3), which was found to have a joint connection in support of an articular origin within the cranial nerves. An inferior alveolar intraneural cyst was incidentally discovered on a plain radiograph prior to edentulation. It was resected from within the mandibular canal with no joint connection perceived at surgery. Histologically, the cyst was confirmed to be an intraneural ganglion cyst. Reinterpretation of the preoperative CT scan showed the cyst arising from the temporomandibular joint. This case is consistent with the articular (synovial) theory of intraneural ganglion cysts. An anatomical explanation and potential joint connection are provided for this case as well as several other cases of intraneural cysts in the literature, and thus unifying cranial nerve involvement with accepted concepts of intraneural ganglion cyst formation and propagation.


Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder.
We investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3- to 4-year-old children with autism spectrum disorder (ASD; n = 77) and developmental delay without autism (DD; n = 34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n = 45), DD (n = 14), and a group of children with typical development (TD; n = 25) were also assessed by magnetic resonance imaging. Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus.


MFBCNNC: Momentum factor biogeography convolutional neural network for COVID-19 detection via chest X-ray images.
By October 6, 2020, Coronavirus disease 2019 (COVID-19) was diagnosed worldwide, reaching 3,355,7427 people and 1,037,862 deaths. Detection of COVID-19 and pneumonia by the chest X-ray images is of great significance to control the development of the epidemic situation. The current COVID-19 and pneumonia detection system may suffer from two shortcomings: the selection of hyperparameters in the models is not appropriate, and the generalization ability of the model is poor. To solve the above problems, our team proposed an improved intelligent global optimization algorithm, which is based on the biogeography-based optimization to automatically optimize the hyperparameters value of the models according to different detection objectives. In the optimization progress, after selecting the immigration of suitable index vector and the emigration of suitable index vector, we proposed adding a comparison operation to compare the value of them. According to the different numerical relationships between them, the corresponding operations are performed to improve the migration operation of biogeography-based optimization. The improved algorithm (momentum factor biogeography-based optimization) can better perform the automatic optimization operation. In addition, our team also proposed two frameworks: biogeography convolutional neural network and momentum factor biogeography convolutional neural network. And two methods for detection COVID-19 based on the proposed frameworks. Our method used three convolutional neural networks (LeNet-5, VGG-16, and ResNet-18) as the basic classification models for chest X-ray images detection of COVID-19, Normal, and Pneumonia. The accuracy of LeNet-5, VGG-16, and ResNet-18 is improved by 1.56%, 1.48%, and 0.73% after using biogeography-based optimization to optimize the hyperparameters of the models. The accuracy of LeNet-5, VGG-16, and ResNet-18 is improved by 2.87%, 6.31%, and 1.46% after using the momentum factor biogeography-based optimization to optimize the hyperparameters of the models. Under the same experimental conditions, the performance of the momentum factor biogeography-based optimization is superior to the biogeography-based optimization in optimizing the hyperparameters of the convolutional neural networks. Experimental results show that the momentum factor biogeography-based optimization can improve the detection performance of the state-of-the-art approaches in terms of overall accuracy. In future research, we will continue to use and improve other global optimization algorithms to enhance the application ability of deep learning in medical pathological image detection.


Authorship policies of scientific journals.
We analysed the authorship policies of a random sample of 600 journals from the Journal Citation Reports database. 62.5% of the journals we sampled had an authorship policy. Having an authorship policy was positively associated with impact factor. Journals from the biomedical sciences and social sciences/humanities were more likely to have an authorship policy than journals from the physical sciences, engineering or mathematical sciences. Among journals with a policy, the most frequent type of policy was guidance on criteria for authorship (99.7%); followed by guidance on acknowledgments (97.3%); requiring that authors make substantial contributions to the research (94.7%); requiring that authors be accountable for the research as a whole (84.8%); guidance on changes in authorship (77.9%); requiring that authors give final approval to the manuscript (77.6%); requiring that authors draft or critically revise the manuscript (71.7%); providing guidance on corporate authorship (58.9%); prohibiting gift, guest or ghost authorship (31.7%); requiring authors to describe their contributions (5.3%); limiting the number of authors for some types of articles (4.0%) and requiring authors to be accountable for their part in the research (1.1%). None of the policies addressed equal contribution statements. Journals that do not have authorship policies should consider adopting or developing ones.


Occurence of internet addiction in a general population sample: a latent class analysis.
Prevalence studies of Internet addiction in the general population are rare. In addition, a lack of approved criteria hampers estimation of its occurrence. This study conducted a latent class analysis (LCA) in a large general population sample to estimate prevalence. A telephone survey was conducted based on a random digit dialling procedure including landline telephone (n=14,022) and cell phone numbers (n=1,001) in participants aged 14-64. The Compulsive Internet Use Scale (CIUS) served as the basis for a LCA used to look for subgroups representing participants with Internet addiction or at-risk use. CIUS was given to participants reporting to use the Internet for private purposes at least 1 h on a typical weekday or at least 1 h on a day at the weekend (n=8,130). A 6-class model showed best model fit and included two groups likely to represent Internet addiction and at-risk Internet use. Both groups showed less social participation and the Internet addiction group less general trust in other people. Proportions of probable Internet addiction were 1.0% (CI 0.9-1.2) among the entire sample, 2.4% (CI 1.9-3.1) in the age group 14-24, and 4.0% (CI 2.7-5.7) in the age group 14-16. No difference in estimated proportions between males and females was found. Unemployment (OR 3.13; CI 1.74-5.65) and migration background (OR 3.04; CI 2.12-4.36) were related to Internet addiction. This LCA-based study differentiated groups likely to have Internet addiction and at-risk use in the general population and provides characteristics to further define this rather new disorder.


Japanese Guideline for Adult Asthma 2014.
Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting 02-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled 02-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and coughvariant asthma are also important issues that need to be considered.


Infrared absorption of CH3OSO detected with time-resolved Fourier-transform spectroscopy.
A step-scan Fourier-transform spectrometer coupled with a multipass absorption cell was employed to detect temporally resolved infrared absorption spectra of CH(3)OSO produced upon irradiation of a flowing gaseous mixture of CH(3)OS(O)Cl in N(2) or CO(2) at 248 nm. Two intense transient features with origins near 1152 and 994 cm(-1) are assigned to syn-CH(3)OSO; the former is attributed to overlapping bands at 1154 ± 3 and 1151 ± 3 cm(-1), assigned to the S=O stretching mixed with CH(3) rocking (ν(8)) and the S=O stretching mixed with CH(3) wagging (ν(9)) modes, respectively, and the latter to the C-O stretching (ν(10)) mode at 994 ± 6 cm(-1). Two weak bands at 2991 ± 6 and 2956 ± 3 cm(-1) are assigned as the CH(3) antisymmetric stretching (ν(2)) and symmetric stretching (ν(3)) modes, respectively. Observed vibrational transition wavenumbers agree satisfactorily with those predicted with quantum-chemical calculations at level B3P86∕aug-cc-pVTZ. Based on rotational parameters predicted at that level, the simulated rotational contours of these bands agree satisfactorily with experimental results. The simulation indicates that the S=O stretching mode of anti-CH(3)OSO near 1164 cm(-1) likely makes a small contribution to the observed band near 1152 cm(-1). A simple kinetic model of self-reaction is employed to account for the decay of CH(3)OSO and yields a second-order rate coefficient k=(4 ± 2)×10(-10) cm(3)molecule(-1)s(-1).


Super multi-view near-eye display to solve vergence-accommodation conflict.
A super multi-view (SMV) technique is applied to near-eye displays to solve the vergence-accommodation conflict that causes visual fatigue. The proposed SMV near-eye display employs a high-speed spatial light modulator (SLM), a two-dimensional (2D) light source array, and an imaging optics for each eye. The imaging optics produces a virtual image of the SLM and real images of the light sources to generate a 2D array of viewpoints. The SMV images are generated using a time-multiplexing technique: the multiple light sources sequentially emit light while the SLM synchronously displays corresponding parallax images. A monocular experimental system was constructed using a ferroelectric liquid crystal display and an LED array. A full-parallax SMV image generation with 21 viewpoints was demonstrated and a comparison of full-parallax and horizontal parallax SMV images provided.


Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab.
Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant's condition was successfully treated with prednisolone and infliximab.


Hhex regulates Kit to promote radioresistance of self-renewing thymocytes in Lmo2-transgenic mice.
Lmo2 is an oncogenic transcription factor that is frequently overexpressed in T-cell acute leukemias, in particular poor prognosis early T-cell precursor-like (ETP-) acute lymphoblastic leukemia (ALL). The primary effect of Lmo2 is to cause self-renewal of developing CD4(-)CD8(-) (double negative, DN) T cells in the thymus, leading to serially transplantable thymocytes that eventually give rise to leukemia. These self-renewing thymocytes are intrinsically radioresistant implying that they may be a source of leukemia relapse after therapy. The homeobox transcription factor, Hhex, is highly upregulated in Lmo2-transgenic thymocytes and can phenocopy Lmo2 in inducing thymocyte self-renewal, implying that Hhex may be a key component of the Lmo2-induced self-renewal program. To test this, we conditionally deleted Hhex in the thymi of Lmo2-transgenic mice. Surprisingly, this did not prevent accumulation of DN thymocytes, nor alter the rate of overt leukemia development. However, deletion of Hhex abolished the transplantation capacity of Lmo2-transgenic thymocytes and overcame their radioresistance. We found that Hhex regulates Kit expression in Lmo2-transgenic thymocytes and that abrogation of Kit signaling phenocopied loss of Hhex in abolishing the transplantation capacity and radioresistance of these cells. Thus, targeting the Kit signaling pathway may facilitate the eradication of leukemia-initiating cells in immature T-cell leukemias in which it is expressed.


Design and Evaluation of Tretinoin Fatty Acid Vesicles for the Topical Treatment of Psoriasis.
The goal of the current study was to explore the potential benefits of Tretinoin (Tre) fatty acid vesicles (Tre-FAV) as a prospective antipsoriatic topical delivery system. This promising system can counteract the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Tre-loaded fatty acid vesicles were successfully developed and entirely characterised. The selected formulation was investigated for in vitro release, ex vivo skin retention and psoriasis efficacy studies. The characterisation results of Tre-FAV showed it has a globular shape with a particle size of 126.37 ± 1.290 nm (0.188 ± 0.019 PDI). The entrapment efficiency and zeta potential were discovered to be 84.26 ± 0.816% and -28.9 ± 1.92 mV, respectively. Encapsulation of the drug in the fatty acid vesicles was also strengthened by differential scanning calorimetric and powder FTIR diffraction studies. In vitro release results showed that Tre-FAV significantly increased skin absorption and retention in comparison to the Tre solution. The topical application of Tre-FAV to a mouse model confirmed that it has superior in vivo antipsoriatic properties in terms of well-demarcated papules, erythema and reduced epidermal thickness in comparison to other treatments. The weight of the spleen and the levels of the cytokines IL-17 and IL-6 decreased after treatment. In conclusion, FAV dramatically increased the water solubility and skin permeability of Tre and its anti-psoriasis activity.


[Clinical aspects of the pathology of neuromuscular transmission].
On the basis of analyzing clinical reports, the results of the author's own studies, and respective information published in literature, principal problems concerning the clinical course, the mechanism of development, the methods of treatment and organization of the therapeutic and prophylactic aid to patients with neuromuscular transmission pathologies are discussed. The main myasthenic syndromes, as well as problems of myasthenia differential diagnosis are described. A question on the role of autoimmune disturbances in the formation of muscular disturbances in cases of a neuromuscular transmission pathology is raised. Data characterizing the role of anticholinesterase drugs, hormones, surgical and radiotherapeutic methods in the treatment of myasthenia and myasthenic disturbances are presented.


Ischemia/reperfusion injury of the liver: pathophysiologic hypotheses and potential relevance to human hypoxic hepatitis.
For the last decade, numerous experimental studies have demonstrated that the main part of liver injury caused by low or no flow states does not occur at the time of hypoxia, but during reperfusion. These experimental studies have a crucial clinical impact, because ischemia/reperfusion injury is involved in situations such as temporary vascular exclusion during liver surgery for trauma or tumors, preservation injury before liver transplantation, and liver cell necrosis observed in hypoxic (ischemic) hepatitis. The aim of the present review is to clarify the sequence of pathophysiological events responsible for ischemia/reperfusion injury of the liver, and to examine the potential contribution of liver ischemia/reperfusion injury to the syndrome of human hypoxic hepatitis.


A calibrated diversity assay for nucleic acid libraries using DiStRO--a Diversity Standard of Random Oligonucleotides.
We have determined diversities exceeding 10(12) different sequences in an annealing and melting assay using synthetic randomized oligonucleotides as a standard. For such high diversities, the annealing kinetics differ from those observed for low diversities, favouring the remelting curve after annealing as the best indicator of complexity. Direct comparisons of nucleic acid pools obtained from an aptamer selection demonstrate that even highly complex populations can be evaluated by using DiStRO, without the need of complicated calculations.


Performance and Limitation of Machine Learning Algorithms for Diabetic Retinopathy Screening: Meta-analysis.
Diabetic retinopathy (DR), whose standard diagnosis is performed by human experts, has high prevalence and requires a more efficient screening method. Although machine learning (ML)-based automated DR diagnosis has gained attention due to recent approval of IDx-DR, performance of this tool has not been examined systematically, and the best ML technique for use in a real-world setting has not been discussed. The aim of this study was to systematically examine the overall diagnostic accuracy of ML in diagnosing DR of different categories based on color fundus photographs and to determine the state-of-the-art ML approach. Published studies in PubMed and EMBASE were searched from inception to June 2020. Studies were screened for relevant outcomes, publication types, and data sufficiency, and a total of 60 out of 2128 (2.82%) studies were retrieved after study selection. Extraction of data was performed by 2 authors according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), and the quality assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis of diagnostic accuracy was pooled using a bivariate random effects model. The main outcomes included diagnostic accuracy, sensitivity, and specificity of ML in diagnosing DR based on color fundus photographs, as well as the performances of different major types of ML algorithms. The primary meta-analysis included 60 color fundus photograph studies (445,175 interpretations). Overall, ML demonstrated high accuracy in diagnosing DR of various categories, with a pooled area under the receiver operating characteristic (AUROC) ranging from 0.97 (95% CI 0.96-0.99) to 0.99 (95% CI 0.98-1.00). The performance of ML in detecting more-than-mild DR was robust (sensitivity 0.95; AUROC 0.97), and by subgroup analyses, we observed that robust performance of ML was not limited to benchmark data sets (sensitivity 0.92; AUROC 0.96) but could be generalized to images collected in clinical practice (sensitivity 0.97; AUROC 0.97). Neural network was the most widely used method, and the subgroup analysis revealed a pooled AUROC of 0.98 (95% CI 0.96-0.99) for studies that used neural networks to diagnose more-than-mild DR. This meta-analysis demonstrated high diagnostic accuracy of ML algorithms in detecting DR on color fundus photographs, suggesting that state-of-the-art, ML-based DR screening algorithms are likely ready for clinical applications. However, a significant portion of the earlier published studies had methodology flaws, such as the lack of external validation and presence of spectrum bias. The results of these studies should be interpreted with caution.


Self-assembly of an aspartate-rich sequence from the adenovirus fiber shaft: insights from molecular dynamics simulations and experiments.
The self-assembly of short peptides into fibrous nanostructures (such as fibrils and tubes) has recently become the subject of intense theoretical and experimental scrutiny, as such assemblies are promising candidates for nanobiotechnological applications. The sequences of natural fibrous proteins may provide a rich source of inspiration for the design of such short self-assembling peptides. We describe the self-assembly of the aspartate-rich undecapeptide (NH3(+)-LSGSDSDTLTV-NH2), a sequence derived from the shaft of the adenovirus fiber. We demonstrate that the peptide assembles experimentally into amyloid-type fibrils according to widely accepted diagnostic criteria. In addition, we investigate an aqueous solution of undecapeptides by molecular dynamics simulations with an implicit (GB) solvent model. The peptides are frequently arranged in intermolecular β-sheets, in line with their amyloidogenic propensity. On the basis of both experimental and theoretical insights, we suggest possible structural models of the fibrils and their potential use as scaffolds for templating of inorganic materials.


Reaction of a diaryldigermyne with ethylene.
Reaction of the stable digermyne BbtGe[triple bond, length as m-dash]GeBbt (Bbt = 2,6-[CH(SiMe3)2]2-4-[C(SiMe3)3]-C6H2) with ethylene initially afforded the corresponding 1,2-digermacyclobutene. Depending on the reaction conditions applied, further reaction of this 1,2-digermacyclobutene with ethylene furnished two different reaction products: a 1,4-digermabicyclo[2.2.0]hexane or a bis(germiranyl)ethane. Combined experimental and theoretical results suggested that the 1,4-digermabicyclo[2.2.0]hexane and the bis(germiranyl)ethane are the thermodynamic and kinetic reaction products, respectively. A reaction mechanism in agreement with these results was proposed.


Genetic Basis of Altered Platelet Counts and Gestational Thrombocytopenia in Pregnancy.
Platelet counts reduction occurs throughout pregnancy, with 5-12% of pregnancies being diagnosed with gestational thrombocytopenia (GT), characterized by a decrease in platelet count during pregnancy. However, the underlying biological mechanism behind this altered platelet count phenomenon and GT remains unclear. Here, we utilized sequencing data from non-invasive prenatal test (NIPT) among 100,186 Chinese pregnancies and conducted the hitherto largest-scale genome-wide association studies (GWAS) on platelet counts at five periods of pregnancy (the first, second, and third trimesters, delivery, and the postpartum period), as well as two GT statuses (GT: platelet count < 150 × 109/L and severe GT: platelet count < 100 × 109/L). Our analysis revealed 138 genome-wide significant loci, explaining 10.4 to 12.1% of the observed variation. Attractively, we identified previously unknown changes in genetic effects on platelet counts during pregnancy for variants present in PEAR1 and CBL, with PEAR1 variants specifically associated with a faster decline in platelet counts. Furthermore, we found that variants present in PEAR1 and TUBB1 increased susceptibility to GT and severe GT. Our study provides the first insight into the genetic basis of platelet counts and GT in pregnancy, highlighting the critical role of PEAR1 in decreasing platelet counts during pregnancy and the occurrence of GT. Pregnancies carrying specific variants associated with declining platelet counts may experience a more pronounced decrease, thereby elevating the risk of GT. These findings lay the groundwork for further investigation into the biological mechanisms and causal implications of GT.


Anterior compartment prolapse: what's new?
The purpose of this review is to summarize the treatment options for anterior compartment prolapse, describe the role that apical suspension plays in the correction of anterior vaginal wall prolapse, and assess the risks and benefits of biologic and synthetic graft use in anterior compartment repair. In 2016, The Cochrane Review published a review of 37 trials including 4023 participants finding that compared to native tissue repair, the use of synthetic mesh resulted in reduced symptomatic prolapse recurrence, anatomic recurrence, and repeat prolapse surgery. There was insufficient evidence regarding quality of life improvement or the use of biologic grafts. Of note the differences between native tissue and mesh kit repairs were not large. A strong consideration should be on the correction of apical prolapse when present; isolated anterior wall repairs should be pursued with caution. The surgeon may consider the use of augmenting materials in their repair of anterior vaginal wall prolapse, although the available evidence is not strongly supportive of their use given potential risks.


Nanoparticle-induced morphology and hydrophilicity of structured surfaces.
Nanoparticles have been applied into the construction of micro- and nanoscaled surface structures with extreme wettability over the past few years. However, the details of processing and employing colloidal nanosuspensions for this purpose have not yet been fully investigated. In this work, we study the surface structures formed via nanosuspensions, in which nanoparticles of solid phase are presented, and the caused surface wettability. We disperse silica nanoparticles with different sizes into pure ethanol to prepare nanosuspensions with a series of concentrations. The suspensions are ultrasonically processed to prompt uniform distribution of nanoparticles before application. The deposited nanosuspensions are thermally treated to assist the regulation of surface patterns based on nanoparticles. Hence, the investigation explores a variety of experimental conditions that will lead to distinctive surface structures and wettabilities. Accordingly, the wettability of the induced surfaces is investigated using contact angle measurement, and the structures of those surfaces are mainly revealed by atomic force microscopy (AFM). Superhydrophilicity is observed on many of such formed surfaces, and the pattern of surface structures in micro- and nanoscale is closely related to the processing conditions and the size of nanoparticles. Thus, we report the characteristics of the surface patterns based on nanoparticles and the formed wettability.


Chapter 24: Anaphylaxis.
Anaphylaxis is a sudden-onset, immediate reaction that implies a risk of death. Think of a "rule of 2's" for anaphylaxis implying that reactions usually begin within 2 minutes to 2 hours after injection, infusion, ingestion, contact, or inhalation. Fatalities can be from asphyxiation from laryngeal or oropharyngeal swelling, collapse from hypotensive shock, cardiac arrest, or acute severe bronchoconstriction causing respiratory failure and arrest. When there is activation of mast cells and basophils in anaphylaxis, chemical mediators are detectable. The preformed mediators from mast cells include histamine, tryptase, carboxypeptidase A, and proteoglycans (heparin and chondroitin sulfates). Newly synthesized mediators include prostaglandin D(2), leukotriene D(4), and platelet-activating factor. Crucial actions of the mediators include an abrupt increase in vascular permeability, vascular smooth muscle relaxation, and bronchial smooth muscle contraction. Anaphylaxis can be classified into immunologic, nonimmunologic, or idiopathic based on the associated mechanism. For example, immunologic causes of anaphylaxis are those mediated by IgE antibodies acting through the FcεR I (foods, insect venom, and beta-lactam antibiotics) whereas non-IgE immunologic anaphylaxis is mediated without presence of antiallergen IgE antibodies or via FcεRI activation (radiographic contrast material). Nonimmunologic anaphylaxis involves mast cell mediator release such as occurs with exercise, cold temperature exposure, or from medications such as opioids or vancomycin. Idiopathic anaphylaxis involves mast cell activation (acutely elevated urine histamine or serum tryptase) and activated lymphocytes. Because anaphylaxis is a medical emergency, the drug of choice is epinephrine, not H(1)-receptor antagonists.


Probabilistic inference of molecular networks from noisy data sources.
Information on molecular networks, such as networks of interacting proteins, comes from diverse sources that contain remarkable differences in distribution and quantity of errors. Here, we introduce a probabilistic model useful for predicting protein interactions from heterogeneous data sources. The model describes stochastic generation of protein-protein interaction networks with real-world properties, as well as generation of two heterogeneous sources of protein-interaction information: research results automatically extracted from the literature and yeast two-hybrid experiments. Based on the domain composition of proteins, we use the model to predict protein interactions for pairs of proteins for which no experimental data are available. We further explore the prediction limits, given experimental data that cover only part of the underlying protein networks. This approach can be extended naturally to include other types of biological data sources.


New data on the vision of South American Indians.
A total of 466 males and 437 females from four Brazilian Indian tribes were tested for color blindness with Ishihara's plates. Defective persons were found in three of the four tribes, but when these and other groups are considered the evidence suggests that the frequency of this trait is lower among Amerindians than among Caucasian populations. Visual acuity tests were performed on 296 Yanomama Indians. Their visual acuity was apparently not as sharp as that of the Cayapo or Xavante. But the scarcity among the Yanomama of persons with serious visual impairment of subcutaneous nodules suggests that the focus of onchocerciasis discovered among them is of recent origin.


Gastrointestinal bacterial transmission among humans, mountain gorillas, and livestock in Bwindi Impenetrable National Park, Uganda.
Habitat overlap can increase the risks of anthroponotic and zoonotic pathogen transmission between humans, livestock, and wild apes. We collected Escherichia coli bacteria from humans, livestock, and mountain gorillas (Gorilla gorilla beringei) in Bwindi Impenetrable National Park, Uganda, from May to August 2005 to examine whether habitat overlap influences rates and patterns of pathogen transmission between humans and apes and whether livestock might facilitate transmission. We genotyped 496 E. coli isolates with repetitive extragenic palindromic polymerase chain reaction fingerprinting and measured susceptibility to 11 antibiotics with the disc-diffusion method. We conducted population genetic analyses to examine genetic differences among populations of bacteria from different hosts and locations. Gorilla populations that overlapped in their use of habitat at high rates with people and livestock harbored E. coli that were genetically similar to E. coli from those people and livestock, whereas E. coli from gorillas that did not overlap in their use of habitats with people and livestock were more distantly related to human or livestock bacteria. Thirty-five percent of isolates from humans, 27% of isolates from livestock, and 17% of isolates from gorillas were clinically resistant to at least one antibiotic used by local people, and the proportion of individual gorillas harboring resistant isolates declined across populations in proportion to decreasing degrees of habitat overlap with humans. These patterns of genetic similarity and antibiotic resistance among E. coli from populations of apes, humans, and livestock indicate that habitat overlap between species affects the dynamics of gastrointestinal bacterial transmission, perhaps through domestic animal intermediates and the physical environment. Limiting such transmission would benefit human and domestic animal health and ape conservation.


A Ty1 cell-type-specific regulatory sequence is a recognition element for a constitutive binding factor.
Ty transposable-element insertion mutations of Saccharomyces cerevisiae can cause cell-type-dependent activation of adjacent-gene expression. Several cis-acting regulatory regions within Ty1 are responsible for the effect of Ty1 on adjacent-gene expression. One of these is the block II sequence that was defined by its homology to mammalian enhancers and to the yeast a1-alpha 2 control site. Tandem copies of a 57-base-pair region encompassing block II caused an additive increase in expression of the CYC7 reporter gene in the absence of other Ty1 sequences. The activation of gene expression by the multiple repeats was abolished in a/alpha diploid cells. A specific complex between a constitutive factor in whole-cell extracts and the DNA regulatory element was observed. The protein-binding site for the constitutive factor coincided with the block II element. Base-pair substitutions within the binding site abolished the ability of the block II element to function as a component of the Ty1 activator and to form the factor-DNA complex. The correlation between complex formation and reporter gene expression indicates that factor binding to the cis-acting element is essential for this element to function as a component of the Ty1 activator.


Induction of colitis causes inflammatory responses in fat depots: evidence for substance P pathways in human mesenteric preadipocytes.
Intracolonic administration of trinitrobenzene sulfonic acid in mice causes inflammation in the colon that is accompanied by increased expression of proinflammatory cytokines and of the substance P (SP), neurokinin 1 receptor (NK-1R) in the proximal mesenteric fat depot. We also investigated whether human mesenteric preadipocytes contain NK-1R and examined the functional consequences of exposure of these cells to SP as it relates to proinflammatory signaling. We found that human mesenteric preadipocytes express NK-1R both at the mRNA and protein levels. Exposure of human mesenteric preadipocytes to SP increased NK-1R mRNA and protein expression by 3-fold, and stimulated IL-8 mRNA expression and protein secretion. This effect was abolished when these cells were pretreated with the specific NK-1R antagonist CJ 012,255. Moreover, human mesenteric preadipocytes transfected with a luciferase promoter/reporter system containing the IL-8 promoter with a mutated NF-kappaB site lost their ability to respond to SP, indicating that SP-induced IL-8 expression is NF-kappaB-dependent. This report indicates that human mesenteric preadipocytes contain functional SP receptors that are linked to proinflammatory pathways, and that SP can directly increase NK-1R expression. We speculate that mesenteric fat depots may participate in intestinal inflammatory responses via SP-NK-1R-related pathways, as well as other systemic responses to the presence of an ongoing inflammation of the colon.


Nanocombing Effect Leads to Nanowire-Based, in-Plane, Uniaxial Thin Films.
The fabrication of thin films comprising ordered nanowire assemblies with emerging, precisely defined properties and adjustable functionalities enables highly integrated technologies in the fields of microelectronics and micro system technology, as well as for efficient power generation, storage, and utilization. Shear force, theoretically, is deemed the most promising method for obtaining in-plane, uniaxial thin films comprising nanowires. The success depends largely on the assembly process, and uniform structural control throughout multiple length scales can be achieved only if a rational strategy is executed. Here, we report that in shearing processes dopants such as lyotropic cellulose nanorods can give rise to the uniaxial alignment of V2O5· nH2O nanowires. Our systematic study indicates that this finding, namely, the nanocombing effect, can be a general principle for the continuous production of uniaxial thin films comprising densely packed nanowires varying in chemical composition and aspect ratios. Conversion of the V2O5· nH2O constituents via in situ oxidative polymerization leads to in-plane, uniaxial polyaniline (PANI) thin films with anisotropic electric and optical properties, which are otherwise difficult to fabricate due to the poor processability of PANI. The uniaxial PANI thin films can be utilized to fabricate flexible gas sensors for distinguishing various analytes, including similar homologues such as methanol and ethanol. We expect the methodology to be applied to a broad spectrum of synthetic and biogenic nanowires for the integration of their collective properties in high-performance electronic devices.