Bioinformatics analysis of disordered proteins in prokaryotes.
A significant number of proteins have been shown to be intrinsically disordered, meaning that they lack a fixed 3 D structure or contain regions that do not posses a well defined 3 D structure. It has also been proven that a protein's disorder content is related to its function. We have performed an exhaustive analysis and comparison of the disorder content of proteins from prokaryotic organisms (i.e., superkingdoms Archaea and Bacteria) with respect to functional categories they belong to, i.e., Clusters of Orthologous Groups of proteins (COGs) and groups of COGs-Cellular processes (Cp), Information storage and processing (Isp), Metabolism (Me) and Poorly characterized (Pc). We also analyzed the disorder content of proteins with respect to various genomic, metabolic and ecological characteristics of the organism they belong to. We used correlations and association rule mining in order to identify the most confident associations between specific modalities of the characteristics considered and disorder content. Bacteria are shown to have a somewhat higher level of protein disorder than archaea, except for proteins in the Me functional group. It is demonstrated that the Isp and Cp functional groups in particular (L-repair function and N-cell motility and secretion COGs of proteins in specific) possess the highest disorder content, while Me proteins, in general, posses the lowest. Disorder fractions have been confirmed to have the lowest level for the so-called order-promoting amino acids and the highest level for the so-called disorder promoters. For each pair of organism characteristics, specific modalities are identified with the maximum disorder proteins in the corresponding organisms, e.g., high genome size-high GC content organisms, facultative anaerobic-low GC content organisms, aerobic-high genome size organisms, etc. Maximum disorder in archaea is observed for high GC content-low genome size organisms, high GC content-facultative anaerobic or aquatic or mesophilic organisms, etc. Maximum disorder in bacteria is observed for high GC content-high genome size organisms, high genome size-aerobic organisms, etc. Some of the most reliable association rules mined establish relationships between high GC content and high protein disorder, medium GC content and both medium and low protein disorder, anaerobic organisms and medium protein disorder, Gammaproteobacteria and low protein disorder, etc. A web site Prokaryote Disorder Database has been designed and implemented at the address http://bioinfo.matf.bg.ac.rs/disorder, which contains complete results of the analysis of protein disorder performed for 296 prokaryotic completely sequenced genomes. Exhaustive disorder analysis has been performed by functional classes of proteins, for a larger dataset of prokaryotic organisms than previously done. Results obtained are well correlated to those previously published, with some extension in the range of disorder level and clear distinction between functional classes of proteins. Wide correlation and association analysis between protein disorder and genomic and ecological characteristics has been performed for the first time. The results obtained give insight into multi-relationships among the characteristics and protein disorder. Such analysis provides for better understanding of the evolutionary process and may be useful for taxon determination. The main drawback of the approach is the fact that the disorder considered has been predicted and not experimentally established.


Waste for Waste: Interface-Intensified Durable Superhydrophilic-Superoleophobic Collagen Fiber Membrane for Efficient Separation of Cationic Surfactant-Stabilized Oil-in-Water Emulsions.
Cationic surfactant-stabilized oil-in-water emulsions pose a significant challenge in separation due to the presence of surfactants. Herein, we develop a collagen-fiber-based CFM-PMDA-TiO2 membrane with unique infiltration properties capable of efficiently separating cationic surfactant-stabilized oil-in-water emulsions by exploiting the charge-demulsification effect. The membrane exhibits superhydrophilic and submerged superoleophobic properties, making it highly suitable for separating a wide range of commercially available cationic surfactant-stabilized oil-in-water microemulsions and nanoemulsions, which demonstrates an exceptional separation efficiency as high as 99.86% and an impressive flux of up to 1436.40 L m-2 h-1. Furthermore, even after a strong subjecting of the membrane to sandpaper abrasion and a full 15 time use, the separation efficacy of oil-in-water emulsions is retained, highlighting the durability, reusability, and economic viability. We propose that these features are enabled by the electrostatic interactions triggered from pyromellitic dianhydride (PMDA) and superhydrophilic-superoleophobic membrane intensified by the TiO2 on the unique collagen fiber membrane. Outcomes emphasize the versatility and potential of our membrane in addressing emulsified oily wastewater hurdles.


[A possible role of phosphoprotein p53 in the mechanism of autostimulation of tumor cell proliferation].
It has been shown that phosphoprotein p53 may participate in the DNA-synthesis stimulation in the mixed culture of tumour cells and syngeneic embryonic mouse cells (10 days of pregnancy). This effect has been eliminated by the preliminary treatment of embryonic cells in vitro by the monoclonal antibodies to p53 (pAb421) in the model system. A conclusion is drawn that p53-epitopes of embryonic cell surface membrane take part in the formation of the determinant which is recognized by receptors of tumour cells. The stimulation of DNA-synthesis in tumour cells is resulted by this process.


Metabolic considerations in reconstitution of the small intestine after jejunoileal bypass.
Intestinal bypass is a reversible procedure which has been used with success in the surgical treatment of morbid obesity. Nine patients with intestinal bypass were forced to undergo reconstitution of the gastrointestinal tract due to severe symptoms of short gut syndrome. Meticulous attention to detail must be exercised in the preoperative preparation of this type of patient. Parenteral hyperalimentation may be necessary to return the patient to adequate nutrition. No attempt at revision should be made until the patient is nutritionally and metabolically reconstituted.


Automated sleep apnea quantification based on respiratory movement.
Obstructive sleep apnea (OSA) is a prevalent and treatable disorder of neurological and medical importance that is traditionally diagnosed through multi-channel laboratory polysomnography(PSG). However, OSA testing is increasingly performed with portable home devices using limited physiological channels. We tested the hypothesis that single channel respiratory effort alone could support automated quantification of apnea and hypopnea events. We developed a respiratory event detection algorithm applied to thoracic strain-belt data from patients with variable degrees of sleep apnea. We optimized parameters on a training set (n=57) and then tested performance on a validation set (n=59). The optimized algorithm correlated significantly with manual scoring in the validation set (R2=0.73 for training set, R2=0.55 for validation set; p<0.05). For dichotomous classification, the AUC was >0.92 and >0.85 using apnea-hypopnea index cutoff values of 5 and 15, respectively. Our findings demonstrate that manually scored AHI values can be approximated from thoracic movements alone. This finding has potential applications for automating laboratory PSG analysis as well as improving the performance of limited channel home monitors.


Primary vomerine osteotomy with gingivoperiosteoplasty for bilateral cleft lip and palate patients with protrusion and/or torsion of the premaxilla.
In patients with bilateral cleft lip and palate (BCLP) with protrusion and/or torsion of the premaxilla, achieving a favorable outcome with adequate facial and maxillary development remains challenging. In the present study, we report a retrospective cohort of patients with complete BCLP who were treated between 2017 and 2020 at a single center in Japan. We investigated the effects and complications of primary vomerine osteotomy (PVO) with gingivoperiosteoplasty (GPP) following pre-surgical orthodontics (PSO) for premaxillary protrusion and/or torsion. For patients with residual premaxillary protrusion and/or torsion after PSO, PVO, and GPP were performed. The distances and angles of the premaxilla were measured on dental casts before PSO, on the day of PVO, after PVO, and on the day of palatoplasty after cheiloplasty. We further assessed postoperative complications. From a total of 36 patients with complete BCLP after PSO, seven patients underwent PVO with GPP. Proper positioning of the premaxilla was achieved in all seven patients. The distance between the anterior edge of the premaxilla and the anterior edge of the lateral segment and the length of the premaxillary-lateral segment on both sides continued to decrease over time. Loosening of GPP sutures occurred in two cases, although no major complications such as necrosis of the premaxilla or fistula formation occurred. Vomerine osteotomy with GPP before primary cheiloplasty is a potential treatment option in BCLP when the premaxilla still protrudes despite PSO or because PSO cannot be applied.


Renal cell carcinoma: screening, diagnosis, and prognosis.
Kidney cancer is most often diagnosed incidentally at the time of radiographic imaging for other complaints. Although numerous improvements and greater use of screening measures have occurred in the setting of renal cell carcinoma (RCC), screening for this disease is usually only carried out for patients who have been identified as having one of the known genetic lineages linked with specific RCC subtypes. This article reviews key concepts in the screening, diagnosis, and prognosis of patients with RCC.


Clinical staging in chronic heart failure associated with low vitamin D and elevated parathormone levels.
Growing evidence in the literature suggests a relationship between heart failure and vitamin D-parathormone cascade. The aim of the present study was to investigate the association of the clinical stage of the heart failure with vitamin D-parathormone levels. Ninety consecutive patients, who were admitted to our clinic from December 2012 to May 2013, were included in the present study. The patients with heart failure were clinically classified into four stages (stage A through stage D). Vitamin D and parathormone levels were measured and echocardiographic recordings were obtained from each patient. The patients with heart failure had significantly lower vitamin D levels compared to the control group (14.5 ng/ml versus 38 ng/ml, P < 0.001). In the four subgroups of patients with heart failure, vitamin D levels significantly decreased (30 ng/ml, 25 ng/ml, 13.5 ng/ml, and 6 ng/ml in stages A, B, C, and D, respectively), and parathormone levels significantly increased (50 pq/ml, 44 pq/ml, 70 pq/ml, and 98.5 pg/ml, respectively) with progression in the heart failure from stage A to stage D (P < 0.001). The log10 EF (B = -2.39, 95% CI = -3.36-1.42, P < 0.001), log10 BNP (B = 0.405, 95% CI = 0.13-0.69, P = 0.005, log10 vitamin D (B = -0.75, 95% CI = -1.18-0.31, P = 0.001) were the independent predictors of heart failure stage in multivariate regression analysis. Vitamin D and parathormone levels were closely associated with the stage of heart failure. There was a significant decrease in vitamin D levels and a significant increase in serum parathormone levels with clinical deterioration in heart failure.


Characterization of chromosome 17 abnormalities in medulloblastomas.
Loss of portions of chromosome 17p, usually through the formation of i(17qp) is a well-known finding in medulloblastomas. Loss of heterozygosity (LOH) studies, however, occasionally demonstrate loss of the more distal portions of 17p, a pattern which is more consistent with a terminal deletion. Here we use a combination of routine karyotyping, fluorescence in situ hybridization (FISH) and LOH studies on four medulloblastoma cell lines and one xenograft to demonstrate the spectrum of chromosome 17 abnormalities which occur in these tumors. Cell line D-556 Med showed a typical dicentric i(17q) and cell line D-721 Med showed two normal copies of chromosome 17 by all methods. Cell line D-425 Med showed loss of terminal 17p by LOH, while the karyotype showed what appeared to be an i(17q). FISH and chromosome 17 painting, however, demonstrated that the abnormal chromosome 17 was actually formed through an unbalanced translocation involving two copies of chromosome 17, with breakpoints at p12 and q11-1, an explanation which reconciled the cytogenetic and LOH findings. Cell line D 581 Med had a terminal deletion at 17p11.2. The finding of two cells with i(17q) in this case by interphase FISH suggests that the terminal deletion arose from breakage of an i(17q). Finally, xenograft D 690 Med showed LOH for regions distal to 17p12, whereas karyotyping, FISH using probes on 17p, and chromosome 17 painting showed two intact copies of chromosome 17. This pattern can be explained by homologous recombination. These data support the concept that the critical deletion of 17p can occur through a variety of mechanisms in the medulloblastoma. The losses may occur through typical i(17q), as well as other mechanisms such as terminal deletions, possibly through breakage of i(17q), unbalanced translocations and homologous recombination.


Cellular retinoic acid-binding protein in virus-induced Shope papillomas of rabbit skin.
Cellular retinoic acid-binding protein (cRABP) was detected in the cytosol of virus-induced papilloma (Shope) of rabbit skin. The Shope papilloma cRABP showed the same ligand specificity and sedimentation value (2S) as was found in other animal species. The level of cRABP in the papillomatous tissue was significantly higher than that in the normal rabbit skin and increased in accordance with the growth and development of the tumor, reaching a peak about 40 days after the inoculation of the Shope papilloma virus. Although this binding capacity was about 15 times greater than in the normal skin, the level of cRABP in the transplantable carcinomas Vx2 and Vx7, both originating from the virus-induced papillomas over 20 years ago, was much the same as in normal rabbit skin.


Flexible bronchoscopic management of airway foreign bodies in children.
To evaluate experience with the flexible bronchoscopic management of tracheobronchial foreign bodies (TFBs) in children (age < or = 16 years). All pediatric bronchoscopies performed by the bronchoscopy section at Mayo Clinic Rochester from 1990 through June 2001 for the suspicion of TFBs were reviewed. Information analyzed included the types of bronchoscope (rigid vs flexible) and techniques used, success rates of extraction of TFBs, and complications. Of the 94 children suspected of having TFBs, 39 children (28 boys and 11 girls; mean age, 47.3 months) were found to have 40 TFBs. The flexible bronchoscope was used exclusively to extract TFBs in 24 patients, and in 2 patients in whom the rigid bronchoscopic procedure was unsuccessful. Flexible bronchoscopy was performed through an endotracheal tube in 19 children. In the other five children, the procedure was accomplished through a laryngeal mask airway (LMA). In two additional patients in whom the rigid bronchoscopic procedure was unsuccessful, the instrument served as a conduit for the passage of the flexible bronchoscope. The extraction instruments employed included ureteral stone baskets and stone forceps. Since 1994, all extractions of TFBs were successfully accomplished with the flexible bronchoscope. Complications occurred in four patients who underwent rigid bronchoscopy, and included postbronchoscopy laryngeal edema manifested by stridor, cough, and respiratory distress. These resolved quickly with medical therapy. Flexible bronchoscopic extraction of pediatric TFBs can be performed safely with minimal risks and complications. In our experience, it was successful in all children in whom it was employed. Nevertheless, we caution that provisions be made to provide immediate rigid bronchoscopic management, should the attempts at flexible bronchoscopic extraction fail.


[Epidemics and colonial medicine in West Africa].
We studied colonial medical practices and health policies in West Africa, which has faced endemics and epidemics that have affected entire societies. We found that attempts to centralize the organization of colonial medicine, which began in the late 19th Century, were limited until the end of World War I. Research and control programs expanded after 1920, concentrating on epidemics, but largely ignoring many major health problems, such as measles, whooping cough and malnutrition, the importance of which were not recognized until after World War II. This appraisal of colonial medicine highlights the difficulties of introducing modern medicine and its ideas into African societies. There have been various social reactions, resulting in the current duality in which traditional and modern medicine coexist.


Potential bioremediation of lead and phenol by sunflower seed husk and rice straw-based biochar hybridized with bacterial consortium: a kinetic study.
Environmental pollution is a global phenomenon and troublesome fact that poses a grave risk to all living entities. Via coupling carbonaceous feedstocks with outstanding microbial activity, kinetic experiments were established using the consortium of Proteus mirabilis and Raoultella planticola, biochar-derived sunflower seed husk (SHB) and rice straw (RSB), and their composites, which investigated at 30 °C (150 rpm) to eliminate 700 mg L-1 lead (120 h) and phenol (168 h) from synthetic wastewater. The derived biochars physicochemical properties of were studied. According to adsorption capacity (qe), consortium-SHB composites and consortium-RSB composites removed lead completely (70 mg g-1) within 48 h and 66 h, respectively. Besides, phenol was remediated entirely after 42 h and 48 h by both composite systems (69.90 mg g-1), respectively, comparing with bacterial consortium only or parent SHB and RSB. Moreover, four kinetic models were studied to describe the bioremediation process. Fractional power and Elovich models could be recommended for describing the adsorption kinetics for lead and phenol removal by the studied biomaterials with high correlation coefficient (R2 ≥ 0.91 for Pb2+ and ≥ 0.93 for phenol) and lower residual root mean square error (RMSE) and chi-square (X2). Overall, bacterial consortium-biochar composites exhibited greater remediation of lead and phenol than the sum of each single bacterial consortium and biochar systems; reflecting synergistic interaction of adsorptive capability of biochar and metabolic performance of bacterial consortium, as denoted by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The current study addressed the successful design of employing functional remediating consortium immobilized on waste biomass-derived biochar as a conducive alternative eco-sorbent and economic platform to detoxify organic and inorganic pollutants.


Spontaneous regression of cancer evaluated by computerized data.
Where immunologic intergrity wanes, clinicians observe a greatly increased incidence of neoplasia. Factors in this phenomenon are reviewed. With complete and detailed recorded data on patients who have exhibited spontaneous regression of cancer, a systematic data-reduction approach becomes a practical reality, without the inherent handicaps of missing details in patient histories or anecdotal and often conjectural observations. Presented here is the plea for detailed recording of complete histories of all carcinoma patients who exhibit the phenomenon of spontaneous regression. Physicans of several decades ago generally considered as unrelated much data deemed important to us today.


Evaluation of urgent esophagectomy in esophageal perforation.
Esophageal trauma is considered one of the most severe lesions of the digestive tract. There is still much controversy in choosing the best treatment for cases of esophageal perforation since that decision involves many variables. The readiness of medical care, the patient's clinical status, the local conditions of the perforated segment, and the severity of the associated injuries must be considered for the most adequate therapeutic choice. To demonstrate and to analyze the results of urgent esophagectomy in a series of patients with esophageal perforation. A retrospective study of 31 patients with confirmed esophageal perforation. Most injuries were due to endoscopic dilatation of benign esophageal disorders, which had evolved with stenosis. The diagnosis of perforation was based on clinical parameters, laboratory tests, and endoscopic images. The main surgical technique used was transmediastinal esophagectomy followed by reconstruction of the digestive tract in a second surgical procedure. Patients were evaluated for the development of systemic and local complications, especially for the dehiscence or stricture of the anastomosis of the cervical esophagus with either the stomach or the transposed colon. Early postoperative evaluation showed a survival rate of 77.1% in relation to the proposed surgery, and 45% of these patients presented no further complications. The other patients had one or more complications, being pulmonary infection and anastomotic fistula the most frequent. The seven patients (22.9%) who underwent esophageal resection 48 hours after the diagnosis died of sepsis. At medium and long-term assessments, most patients reported a good quality of life and full satisfaction regarding the surgery outcomes. Despite the morbidity, emergency esophagectomy has its validity, especially in well indicated cases of esophageal perforation subsequent to endoscopic dilation for benign strictures.


Mites infesting commensal rodents in Shebin El Kom, Menoufia G., Egypt.
Rodent populations markedly increased in many Egyptian Governorates particularly commensal ones which live in close association with man and his domestic animals. In this paper, commensal rodents; M. musculus R. r. alexandrinus, and R. norvegicus were examined for the mites infesting them. Four species of mites were recovered; Ornithonyssus bacoti; Laelaps nuttalli, Dermanyssus gallinae and Allodermanyssus sanguineus. The medical and economic importance was discussed. It was concluded that mites and their environmental problem should be tackled.


Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling.
The Wnt pathway regulates cell fate, proliferation, and apoptosis, and defects in the pathway play a key role in many cancers. Although Wnts act to stabilize beta-catenin levels in the cytosol and nucleus, a multiprotein complex containing adenomatous polyposis coli, glycogen synthase kinase 3beta, and Axin1 or its homolog Axin2/Axil/conductin promotes beta-catenin phosphorylation and subsequent proteasomal degradation. We found that the rat Axil gene was strongly induced upon neoplastic transformation of RK3E cells by mutant beta-catenin or gamma-catenin or after ligand-induced activation of a beta-catenin-estrogen receptor fusion protein. Expression of Wnt1 in murine breast epithelial cells activated the conductin gene, and human cancers with defective beta-catenin regulation had elevated AXIN2 gene and protein expression. Expression of AXIN2/Axil was strongly repressed in cancer cells by restoration of wild type adenomatous polyposis coli function or expression of a dominant negative form of T cell factor (TCF)-4. TCF binding sites in the AXIN2 promoter played a key role in the ability of beta-catenin to activate AXIN2 transcription. In contrast to AXIN2/Axil, expression of human or rat Axin1 homologs was nominally affected by beta-catenin-TCF. Because Axin2 can inhibit beta-catenin abundance and function, the data implicate AXIN2 in a negative feedback pathway regulating Wnt signaling. Additionally, although Axin1 and Axin2 have been thought to have comparable functions, the observation that Wnt pathway activation elevates AXIN2 but not AXIN1 expression suggests that there may be potentially significant functional differences between the two proteins.


Cannabidiol (CBD) with 4',7-Isoflavandiol (Equol) Efficacy is Greater than CBD or Equol Treatment Alone via Human Skin Gene Expression Analysis.
While cannabidiol (CBD) and 4',7-isoflavandiol (Equol) have been examined individually in various skin studies, the present investigation tested whether topically applied CBD with Equol may yield enhanced effects on human skin biomarkers. After 24 hours exposure human skin gene expression was measured by quantitative polymerase chain reaction-messenger ribonucleic acid (qPCR-mRNA) analysis across 9 functional skin categories covering 97 biomarkers. In general, among the biomarkers analyzed the CBD with Equol treatment displayed greater efficacy compared to CBD only or the Equol treatment alone (e.g., 4 out 5 for anti-acne, 15 out of 17 for anti-aging [e.g., collagen, elastin, calcium binding protein A7, tissue inhibitor of matrix metalloproteinase 1 (TIMP 1), etc.], 19 out of 21 for anti-inflammatory (pain), 10 out of 11 for antioxidants to protect against oxidative stress, 6 out of 6 for circadian rhythm regulation for cell repair/restoration, 10 out of 15 for anti-pigmentation properties, 4 out of 5 for skin hydration, 6 out of 6 for tissue integrity, and 11 out of 12 for wound healing properties). CBD with Equol displayed synergistic effects that may be an effective topical treatment for dermatology and cosmetic applications to improve human skin health and reduce photo-aging.


The EBV transforming protein, latent membrane protein 1, mimics and cooperates with CD40 signaling in B lymphocytes.
Latent membrane protein 1 (LMP1) is required for EBV-induced immortalization of human B cells, and expression of the protein in the absence of other viral proteins leads to an activated phenotype in B cells. It has been well documented that LMP1 causes B cells to up-regulate adhesion molecules, such as LFA-1 and ICAM-1, and coactivation molecules, such as B7-1 and CD23, as well as to activate NF-kappaB. Ligation of the endogenous B cell CD40 molecule also induces these and other activated phenotypic changes. Here, we report that expression of LMP1 also activates B cells to secrete Ig and IL-6 and rescues them from B cell receptor-mediated growth arrest analogous to CD40 signaling. Furthermore, an HLA-A2LMP1 chimeric construct demonstrates that the oligomerization of the carboxyl-terminal 200 amino acids of LMP1 is sufficient for B cell signaling. Finally, we demonstrate that LMP1 and CD40 signaling pathways interact cooperatively in inducing B cell effector functions.


Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients.
Though the dysfunction of central dopaminergic system has been proposed, the etiology or pathogenesis of schizophrenia is still uncertain partly due to limited accessibility to dopamine receptor. The purpose of this study was to define whether or not the easily accessible dopamine receptors of peripheral lymphocytes can be the peripheral markers of schizophrenia. 44 drug-medicated schizophrenics for more than 3 years, 28 drug-free schizophrenics for more than 3 months, 15 drug-naïve schizophrenic patients, and 31 healthy persons were enrolled. Sequential reverse transcription and quantitative polymerase chain reaction of the mRNA were used to investigate the expression of D3 and D5 dopamine receptors in peripheral lymphocytes. The gene expression of dopamine receptors was compared in each group. After taking antipsychotics in drug-free and drug-naïve patients, the dopamine receptors of peripheral lymphocytes were sequentially studied 2nd week and 8th week after medication. In drug-free schizophrenics, D3 dopamine receptor mRNA expression of peripheral lymphocytes significantly increased compared to that of controls and drug-medicated schizophrenics, and D5 dopamine receptor mRNA expression increased compared to that of drug-medicated schizophrenics. After taking antipsychotics, mRNA of dopamine receptors peaked at 2nd week, after which it decreases but the level was above baseline one at 8th week. Drug-free and drug-naïve patients were divided into two groups according to dopamine receptor expression before medications, and the group of patients with increased dopamine receptor expression had more severe psychiatric symptoms. These results reveal that the molecular biologically-determined dopamine receptors of peripheral lymphocytes are reactive, and that increased expression of dopamine receptor in peripheral lymphocyte has possible clinical significance for subgrouping of schizophrenis.


Design and Evaluation of a Contextual Model for Information Retrieval From Web-Scale Discovery Services to Improve Evidence-Based Practice by Health Care Practitioners: Mixed Methods Study.
Practicing evidence-based health care is challenging because of overwhelming results presented to practitioners by Google-like Web-scale discovery (WSD) services that index millions of resources while retrieving information based on relevancy algorithms with limited consideration for user information need. On the basis of the user-oriented theory of information need and following design science principles, this study aimed to develop and evaluate an innovative contextual model for information retrieval from WSD services to improve evidence-based practice (EBP) by health care practitioners. We identified problems from literature to support real-world requirements for this study. We used design science research methodology to guide artefact design. We iteratively improved prototype of the context model using artificial formative evaluation. We performed naturalistic summative evaluation using convergent interviewing of health care practitioners and content analysis from a confirmatory focus group consisting of health researchers to evaluate the model's validity and utility. The study iteratively designed and applied the context model to a WSD service to meet 5 identified requirements. All 5 health care practitioners interviewed found the artefact satisfied the 5 requirements to successfully evaluate the model as having validity and utility. Content analysis results from the confirmatory focus group mapped top 5 descriptors per requirement to support a true hypothesis that there is significant discussion among participants to justify concluding that the artefact had validity and utility. The context model for WSD satisfied all requirements and was evaluated successfully for information retrieval to improve EBP. Outcomes from this study justify further research into the model.


Isolation of a 240-kilodalton actin-binding protein from Dictyostelium discoideum.
A high molecular weight actin-binding protein with subunit mass of 240 kilodaltons has been purified from vegetative amoebae of Dictyostelium discoideum. Briefly, a cell extract was prepared by homogenizing vegetative amoebae in 5 mM EGTA, 5 mM 1,4-piperazineethanesulfonic acid, 1 mM dithiothreitol, 0.02% NaN3, pH 7.0, followed by ultracentrifugation at 114,000 X g for 1 h. The 240-kDa protein in this extract was separated from actin by chromatography on ATP-saturated DEAE-cellulose and further purified by chromatography on hydroxylapatite and Sephacryl S-300. The 240-kDa protein increases the low shear viscosity of F-actin. Covalent cross-linking with dimethyl suberimidate demonstrates that the 240-kDa protein can form dimers in high salt (500 mM NaCl). Hydrodynamic studies in high salt demonstrate the presence of an asymmetric dimer (Stokes' radius = 8.6 nm, sedimentation coefficient = 12 S, native molecular weight = 434,000, and frictional ratio = 1.7). Rotary shadowing demonstrates that the monomer is a flexible rod of approximately 70 nm in length that can associate end to end to form a dimer of approximately 140 nm in length. The 240-kDa protein cross-reacts with antibodies to chicken gizzard filamin. The properties of the 240-kDa protein suggest that it is a member of the filamin class of actin-associated proteins.


Clathrin promotes incorporation of cargo into coated pits by activation of the AP2 adaptor micro2 kinase.
Endocytic cargo such as the transferrin receptor is incorporated into clathrin-coated pits by associating, via tyrosine-based motifs, with the AP2 complex. Cargo-AP2 interactions occur via the mu2 subunit of AP2, which needs to be phosphorylated for endocytosis to occur. The most likely role for mu2 phosphorylation is in cargo recruitment because mu2 phosphorylation enhances its binding to internalization motifs. Here, we investigate the control of mu2 phosphorylation. We identify clathrin as a specific activator of the mu2 kinase and, in permeabilized cells, we show that ligand sequestration, driven by exogenous clathrin, results in elevated levels of mu2 phosphorylation. Furthermore, we show that AP2 containing phospho-mu2 is mainly associated with assembled clathrin in vivo, and that the level of phospho-mu2 is strongly reduced in a chicken B cell line depleted of clathrin heavy chain. Our results imply a central role for clathrin in the regulation of cargo selection via the modulation of phospho-mu2 levels.


Simultaneous carcinoma involving the endometrium and the ovary. A clinicopathologic, immunohistochemical, and DNA flow cytometric study of 18 cases.
Eighteen carcinomas involving both the endometrium and the ovary were studied. Stage, size, bilaterality and pattern of ovarian involvement, histologic types and grades, presence of endometrial hyperplasia or ovarian endometriosis, myometrial, tubal, lymphatic and blood vessel invasion, and follow-up of the patients were all evaluated. Accordingly, the cases were classified as follows: Group A (nine cases), two separate primary tumors; and Group B (nine cases), uterine primaries with ovarian metastasis or ovarian primaries with uterine metastasis. Immunohistochemical stains (CAM 5.2, wide-spectrum keratin, vimentin, carcinoembryonic antigen (CEA), CA 12.5, CA 19.9) were performed in all cases. Flow cytometric determination of nuclear DNA was done in 13 (seven Group A and six Group B tumors). Of the nine cases with independent primary tumors, seven showed different immunohistochemical profiles in the ovarian and uterine tumors, whereas only four of the nine metastatic ones had similar staining characteristics. Five cases with independent primary tumors, but only one of the metastatic group, exhibited different aneuploid stemlines in the endometrial and ovarian tumors. The other seven (two independent and five metastatic) cases had similar DNA indexes in both tumors. Immunohistochemical and DNA flow cytometric study may be of some value for the distinction between metastatic and independent tumors, but differential diagnosis must presently rely largely upon conventional clinicopathologic criteria.


Effect of basiliximab use on the risk of postoperative infection and death after heart transplantation: An observational study.
Heart transplantation (HT) has become the preferred treatment for end-stage heart disease, but postoperative complications such as infection still threaten the prognosis of HT patients. Basiliximab can help minimize immune rejection. However, there is a lack of relevant information to compare the prognosis of different immunosuppression regimens. This study aimed to investigate the risk factors associated with death and infection after HT surgery. We also provide some insightful information on the administration of basiliximab to improve the prognosis of HT patients. In total, 70 patients were included in this retrospective observational study. All participants underwent primary HT and were administered immunosuppressive agents postoperatively. Of these, 38 received additional basiliximab. There was a 6-month follow-up period after HT during which clinical outcomes were monitored. Logistic regression and cox-proportional hazard regression analyses were performed to determine the relationship between basiliximab use and the clinical outcomes of HT. Logistic regression analysis revealed that basiliximab use (odds ratio [OR] = 0.07, P = .014) was an independent risk factor for death after HT. d-Dimer (OR = 9.05, P = .002) and basiliximab use (OR = 0.15, P = .004) were independent risk factors for death after HT. Moreover, patients treated with basiliximab had shorter hospital lengths of stay (23.58 ± 13.89 vs 39.41 ± 24.43, P = .001) and intensive care unit lengths of stay (4.76 ± 2.85 vs 11.25 ± 5.79, P < .001). Furthermore, patients administered basiliximab had lower rates of death (1 [5.4%] vs 9 [28.1%], P = .007) and infection (6 [15.8%] vs 19 [59.4%], P < .001). The postoperative survival rate (hazard ratio 0.08, 95% confidence interval 0.01-0.65, P = .018) and survival against infection (hazard ratio 0.24, 95% confidence interval 0.09-0.64, P = .004) were significantly higher among patients receiving basiliximab treatment than among those not receiving treatment. Our study showed that basiliximab use was closely associated with the rate of postoperative death and infection after HT. HT patients with additional basiliximab administration as immunosuppressive treatment had a better clinical prognosis.


Navigating the FDA regulatory landscape.
Recent research and technological developments have led to an expanding number of novel and rapidly acting therapeutics being developed across a variety of neuropsychiatric disorders. Novel medical devices range from implantable and non-invasive brain stimulating and recording technologies to digital therapeutics. This perspective provides an overview of FDA regulatory oversight for medical devices, including a discussion of regulatory pathways and the review of neuromodulation devices for psychiatric disorders. We highlight the importance of early engagement with FDA and special programs that may be useful to device developers participating in interactions with the FDA that are solution focused. We explore current novel and rapid treatments for psychiatric disorders and those on the horizon. Lastly, we provide considerations for developers in navigating the regulatory landscape for neuromodulation devices intended for psychiatric disorders, including approaches to incorporating patient perspectives.


Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate.
Monitoring general disease marker such as angiogenesis may contribute to the development of personalized medicine and improve therapy outcome. Readily availability of positron emitter based imaging agents providing quantification would expand clinical positron emission tomography (PET) applications. Generator produced 68Ga provides PET images of high resolution and the half-life time frame is compatible with the pharmacokinetics of small peptides comprising arginine-glycine-aspartic acid (RGD) sequence specific to αvβ3 integrin receptors. The main objective of this study was to develop a method for 68Ga-labeling of RGD containing bicyclic octapeptide ([68Ga]Ga-DOTA-RGD) with high specific radioactivity and preclinically assess its imaging potential. DOTA-RGD was labeled using generator eluate preconcentration technique and microwave heating. The binding and organ distribution properties of [68Ga]Ga-DOTA-RGD were tested in vitro by autoradiography of frozen tumor sections, and in vivo in mice carrying a Lewis Lung carcinoma graft (LL2), and in non-human primate (NHP). Another peptide with aspartic acid-glycine-phenylalanine sequence was used as a negative control. The full 68Ga radioactivity eluted from two generators was quantitatively incorporated into 3-8 nanomoles of the peptide conjugates. The target binding specificity was confirmed by blocking experiments. The specific uptake in the LL2 mice model was observed in vivo and confirmed in the corresponding ex vivo biodistribution experiments. Increased accumulation of the radioactivity was detected in the wall of the uterus of the female NHP probably indicating neovascularization. [68Ga]Ga-DOTA-RGD demonstrated potential for the imaging of angiogenesis.


The Scottish perinatal neuropathology study: clinicopathological correlation in early neonatal deaths.
A proportion of neonatal deaths from asphyxia have been shown to be associated with pre-existing brain injury. (a) To compare the epidemiology of infants displaying signs of birth asphyxia with those not showing signs; (b) to examine the neuropathology and determine if possible the timing of brain insult comparing asphyxiated with non-asphyxiated infants; (c) to compare the clinical features of those born with birth asphyxia with and without pre-labour damage. Over a two year period, all 22 Scottish delivery units collected clinical details on early neonatal deaths. Requests for post mortem included separate requests for detailed neuropathological examination of the brain. Infants were classified into two groups: birth asphyxia and non-birth asphyxia. Clinicopathological correlation was used to attempt to define the time of brain insult. Detailed clinical data were available on 137 of 174 early neonatal deaths that met the inclusion criteria. Seventy of 88 parents who had agreed to post mortem examination consented to a detailed examination of additional samples from the brain; in 53 of these cases the infant was born in an asphyxiated condition. All asphyxiated and encephalopathic infants, 38% of mature and 52% of preterm infants with features of birth asphyxia but without encephalopathy, and only one of 12 infants without any signs of birth asphyxia showed damage consistent with onset before the start of labour. In a large proportion of neonatal deaths, brain injury predates the onset of labour. This is more common in infants born in an asphyxiated condition.


Constructing ion channels from water-soluble α-helical barrels.
The design of peptides that assemble in membranes to form functional ion channels is challenging. Specifically, hydrophobic interactions must be designed between the peptides and at the peptide-lipid interfaces simultaneously. Here, we take a multi-step approach towards this problem. First, we use rational de novo design to generate water-soluble α-helical barrels with polar interiors, and confirm their structures using high-resolution X-ray crystallography. These α-helical barrels have water-filled lumens like those of transmembrane channels. Next, we modify the sequences to facilitate their insertion into lipid bilayers. Single-channel electrical recordings and fluorescent imaging of the peptides in membranes show monodisperse, cation-selective channels of unitary conductance. Surprisingly, however, an X-ray structure solved from the lipidic cubic phase for one peptide reveals an alternative state with tightly packed helices and a constricted channel. To reconcile these observations, we perform computational analyses to compare the properties of possible different states of the peptide.


Inhibition of prostaglandin E synthesis augments glucose-induced insulin secretion is cultured pancreas.
Monolayer cultures of neonatal rat pancreatic cells were examined to ascertain whether they synthesize prostaglandin E (PGE) and to determine the effects on insulin secretion caused by PGE and drugs that inhibit its synthesis. PGE release into the medium was observed. Sodium salicylate and ibuprofen (at drug concentrations similar to those achieved therapeutically in humans in vivo) inhibited PGE synthesis in a dose-responsive fashion to a maximum of 70-80% inhibition. Inhibition of PGE synthesis was accompanied by augmented insulin secretion. Both PGE synthesis inhibitors shifted the glucose dose-insulin response curves to the left at low glucose concentrations and augmented maximal insulin release at high glucose concentrations. Increments in glucose-induced insulin secretion induced by sodium salicylate correlated well (r = 0.89) with inhibition of PGE synthesis and addition of exogenous PGE1 to the cultures reversed the augmenting effects of the drug on insulin secretion. It is concluded that cultures of pancreatic cells synthesize PGE and that a function of PGE in these cultures appears to be a tonic negative modulation of glucose-induced insulin secretion.


Concordance among gene-expression-based predictors for breast cancer.
Gene-expression-profiling studies of primary breast tumors performed by different laboratories have resulted in the identification of a number of distinct prognostic profiles, or gene sets, with little overlap in terms of gene identity. To compare the predictions derived from these gene sets for individual samples, we obtained a single data set of 295 samples and applied five gene-expression-based models: intrinsic subtypes, 70-gene profile, wound response, recurrence score, and the two-gene ratio (for patients who had been treated with tamoxifen). We found that most models had high rates of concordance in their outcome predictions for the individual samples. In particular, almost all tumors identified as having an intrinsic subtype of basal-like, HER2-positive and estrogen-receptor-negative, or luminal B (associated with a poor prognosis) were also classified as having a poor 70-gene profile, activated wound response, and high recurrence score. The 70-gene and recurrence-score models, which are beginning to be used in the clinical setting, showed 77 to 81 percent agreement in outcome classification. Even though different gene sets were used for prognostication in patients with breast cancer, four of the five tested showed significant agreement in the outcome predictions for individual patients and are probably tracking a common set of biologic phenotypes.


Cytotoxicity evaluation of luting resin cements on bovine dental pulp-derived cells (bDPCs) by real-time cell analysis.
To evaluate the cytotoxicity of resin cements on dental pulp-derived cells (bDPCs), Bifix QM (BQM), Choice 2(C2), RelyX U200(RU200), Maxcem Elite(ME), and Multilink Automix(MA) were tested. The materials were incubated in DMEM for 72 h. A real-time cell analyzer was used to evaluate cell survival. The statistical analyses used were one-way ANOVA and Tukey-Kramer tests. BQM, RU200, and ME demonstrated a significant decrease in the bDPCs' index at 24 and 72 h (p≤0.001). These materials were found to be the most toxic resin cements, as compared to the control and other tested materials (C2 and MA). However, C2 and MA showed a better survival rate, compared to BQM, RU200, and ME, and had lower cell index than the control group. The cytotoxic effects of resin cements on pulpa should be evaluated during the selection of proper cements.


Opioid prescription underfilling among retail pharmacies.
Prescription opioid abuse is a major public health problem in the United States. Physicians who prescribe opioid analgesics are sometimes confronted with patients who request early refills, claiming that they have been "shorted" by their pharmacy. While a substantial differential diagnosis exists for apparent opioid overuse, the underfilling of opioid prescriptions at the level of retail pharmacies has not yet been systematically investigated. The goals of the present study were to: 1) determine the incidence and magnitude of opioid prescription underfilling among retail pharmacies in Northeast Florida and 2) to compare the rates of under- and overfilling with noncontrolled substance prescription controls. Patients receiving opioid prescriptions were recruited for this study during routine primary care office visits. These patients, blinded to the study goals, filled their prescriptions, and returned to the clinic with unopened medication bag(s) for dosage unit counts. One hundred and twenty-one patients filled 134 opioid prescriptions from 103 unique pharmacies. Dosage unit counts revealed three slight opioid prescription underfills (1-3 dosage units) and three slight opioid prescription overfills (1-3 dosage units). We found no statistically significant differences between opioids and noncontrolled substance controls with regard to prescription underfills. There was no evidence supporting patients' claims of significant opioid analgesic underfilling by retail pharmacies. Patients who repeatedly report medication shortages should be evaluated for opioid use disorders.


Serum-to-urine renalase ratio and renalase fractional excretion in healthy adults and chronic kidney disease patients.
Renalase is a flavoprotein that plays a protective role in chronic kidney disease (CKD) and cardiovascular diseases. The secretion and way of action of this protein are still discussed. The aim of our study was to estimate the balance between serum and urine renalase in healthy individuals and CKD patients, using two parameters: fractional excretion (FE) and serum-to-urine renalase ratio (StURR). Our study involved 28 healthy volunteers and 62 patients with CKD in stages I to IV. The concentration of renalase in serum and urine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (EIAab, Wuhan, China). We analyzed associations between renalase levels in urine and serum, and other parameters: sex, age, GFR, presence of hypertension, diabetes, and proteinuria, and determined the serum-to-urine renalase ratio and fractional excretion of renalase. Renalase and serum-to-urine ratio were significantly higher in CKD patients in comparison with the control group. Fractional excretion was lower in CKD patients but this difference did not reach the statistical significance (p = 0.092). Multivariate analysis performed in the CKD group showed, that from mentioned parameters, serum renalase was the only significant independent factor strongly positively associated with urinary renalase concentration. The serum-to-urine ratio is significantly and about 6.5-fold higher in CKD patients, and the fractional excretion of renalase is 3-fold, but not significantly lower in CKD patients. Renalase levels in both serum and urine are not related to the glomerular filtration rate and not associated with blood pressure.


Proteomic Analysis of Endothelial Cells Exposed to Ultrasmall Nanoparticles Reveals Disruption in Paracellular and Transcellular Transport.
The large interactive surfaces of nanoparticles (NPs) increase the opportunities to develop NPs for vascular targeting. Proteomic analysis of endothelial cells exposed to NPs reveals the cellular response and turns the focus into the impairment of the endothelial permeability. Here, quantitative proteomics and transcriptome sequencing are combined to evaluate the effects of exposure to sub-lethal concentrations of TiO2 -USNPs and TiO2 -NPs on human dermal microvascular endothelial cells. Endothelial cells react to preserve the semi-permeable properties that are essential for vascular tissue fluid homeostasis, vascular development, and angiogenesis. The main impact of the exposure was alteration of functional complexes involved in cell adhesion, vesicular transport, and cytoskeletal structure. Those are the core cellular structures that are linked to the permeability and the integrity of the endothelial tissue. Moreover, the extracellular proteins uptake along wih the NPs into the endothelial cells escape the lysosomal degradation pathway. These findings improve the understanding of the interaction of NPs with endothelial cell. The effects of the studied NPs modulating cell-cell adhesion and vesicular transport can help to evaluate the distribution of NPs via intravenous administration.


Electromagnetic fields increase in vitro and in vivo angiogenesis through endothelial release of FGF-2.
Pulsed electromagnetic fields (PEMF) have been shown to be clinically beneficial, but their mechanism of action remains unclear. The present study examined the impact of PEMF on angiogenesis, a process critical for successful healing of various tissues. PEMF increased the degree of endothelial cell tubulization (sevenfold) and proliferation (threefold) in vitro. Media from PEMF cultures had a similar stimulatory effect, but heat denaturation ablated this activity. In addition, conditioned media was able to induce proliferative and chemotactic changes in both human umbilical vein endothelial cells and fibroblasts, but had no effect on osteoblasts. Angiogenic protein screening demonstrated a fivefold increase in fibroblast growth factor beta-2 (FGF-2), as well as smaller increases in other angiogenic growth factors (angiopoietin-2, thrombopoietin, and epidermal growth factor). Northern blot analysis demonstrated an increase in FGF-2 transcription, and FGF-2 neutralizing antibody inhibited the effects of PEMF. In vivo, PEMF exposure increased angiogenesis more than twofold. We conclude that PEMF augments angiogenesis primarily by stimulating endothelial release of FGF-2, inducing paracrine and autocrine changes in the surrounding tissue. These findings suggest a potential role for PEMF in therapeutic angiogenesis.


Experimental studies of adaptation in Clarkia xantiana. II. Fitness variation across a subspecies border.
Because the range boundary is the locale beyond which a taxon fails to persist, it provides a unique opportunity for studying the limits on adaptive evolution. Adaptive constraints on range expansion are perplexing in view of widespread ecotypic differentiation by habitat and region within a species' range (regional adaptation) and rapid evolutionary response to novel environments. In this study of two parapatric subspecies, Clarkia xantiana ssp. xantiana and C. x. ssp. parviflora, we compared the fitness of population transplants within their native region, in a non-native region within the native range, and in the non-native range to assess whether range expansion might be limited by a greater intensity of selection on colonists of a new range versus a new region within the range. The combined range of the two subspecies spans a west-to-east gradient of declining precipitation in the Sierra Nevada of California, with ssp. xantiana in the west being replaced by ssp. parviflora in the east. Both subspecies had significantly higher fitness in the native range (range adaptation), whereas regional adaptation was weak and was found only in the predominantly outcrossing ssp. xantiana but was absent in the inbreeding ssp. parvifilora. Because selection intensity on transplants was much stronger in the non-native range relative to non-native regions, there is a larger adaptive barrier to range versus regional expansion. Three of five sequential fitness components accounted for regional and range adaptation, but only one of them, survivorship from germination to flowering, contributed to both. Flower number contributed to regional adaptation in ssp. xantiana and fruit set (number of fruits per flower) to range adaptation. Differential survivorship of the two taxa or regional populations of ssp. xantiana in non-native environments was attributable, in part, to biotic interactions, including competition, herbivory, and pollination. For example, low fruit set in ssp. xantiana in the east was likely due to the absence of its principal specialist bee pollinators in ssp. parviflora's range. Thus, convergence on self-fertilization may be necessary for ssp. xantiana to invade ssp. parviflora's range, but the evolution of outcrossing would not be required for ssp. parviflora to invade ssp. xantiana's range.


Improving patient follow-up in incidental screening through referral letters.
The effects of referral letters on increasing the likelihood of patients obtaining hypertension follow-up assessments are presented. Seventy-four patients with elevated diastolic blood pressure (between 95 and 120 mm Hg), who were administratively ineligible for longitudinal care from the Veterans Administration, were randomized into one of four groups: a patient letter; a physician letter; both patient and physician letters; or no letter (control group). No evidence of interaction between the patient and physician letters was found. Results revealed that nearly twice as many patients (63%) receiving the patient letter returned for a hypertension evaluation as compared with those who did not (33%). No difference was found between the physician letter and no physician letter conditions. These findings suggest that patient-directed referral letters can increase the likelihood of follow-up in both previously detected and newly detected cases.


Different types of hysterectomy in the radio-surgical treatment of early cervical cancer (FIGO Ib-IIa).
Surgery and radiotherapy achieved equivalent results for FIGO stages Ib-IIa invasive cervical carcinoma. The integration of radiotherapy and surgery provided the same results for a selected series of patients without increasing the rate of complications. The aim of the study was to verify if, applying a radio-surgical protocol, the reduction of the surgery extension on the parametrium in one of two consecutive series might achieve the same results in terms of survival and recurrence rates with fewer complications. We analysed actuarial survival (with >10-year follow-up), local control rates and morbidity of 390 patients who had different the kinds of surgery applied in the radio-surgical treatment protocol: Protocol A: brachytherapy plus type III radical hysterectomy vs Protocol B: brachytherapy plus type II radical hysterectomy. Patients were all included in an analysis of complications according to the French-Italian glossary. Analyses showed no differences in terms of survival, patterns of recurrences and onset time within the two protocols. Urinary complications were more frequent and severe in protocol A vs protocol B (G2: 26.5% vs. 6.1%; G3: 5.3% vs. 3.6%). Our study pointed out that the reduction of the surgery extension allowed the same overall survival and relapses with fewer complications particularly in terms of grade of severity.


A Validation Study of the Rainbow Model of Integrated Care-Measurement Tool for Patients in China.
The original Rainbow Model of Integrated Care Measurement Tool (RMIC-MT) is based on the Rainbow Model of Integrated Care (RMIC), which provides a comprehensive theoretical framework for integrated care. The aim of this paper is to modify the original patient version of the RMIC-MT for the Chinese primary care context and validate its psychometric properties. The translation and adaptation processes were performed in four steps, forward and back-translation, experts review and pre-testing. We conducted a cross-sectional study with 386 patients with diabetes attending one of 20 community health stations in the Nanshan district. We analyzed the distribution of responses to each item to study the psychometric sensitivity. Exploratory factor analysis with principal axis extraction method was used to assess the construct validity. Confirmation factor analysis was used to evaluate model fit of the modified version. Cronbach's alpha was used to ascertain the internal consistency reliability. During the translation and adaptation process, all 24 items were retained with some detailed modifications. No item was found to have psychometric sensitivity problems. Five factors (person-centeredness, clinical integration, professional integration, team-based coordination, organizational integration) with 15 items were determined by exploratory factor analysis, accounting for 53.51% of the total variance. Good internal consistency was achieved with each item correlated the highest on an assigned subscale and Cronbach's alpha score of 0.890. Moderately positive associations (r≥ 0.4, p<0.01) between the score of the scale and these correlations indicate good construct validity. The results showed initial satisfactory psychometric properties for the validation of the Chinese RMIC-MT patient version. Its application in China will promote the development of people-centered integrated primary care. However, future studies with diverse samples crossing regions would be needed to test its psychometric properties for the various Chinese primary care contexts.


Frequency distribution of HLA DQ2 and DQ8 in celiac patients and first-degree relatives in Recife, northeastern Brazil.
The aim of this study was to evaluate the frequencies of the HLA genotypes DQ2 and DQ8 and the alleles A1*05, A1*0201, B1*0201 and B1*0302 in individuals with celiac disease in Recife, northeastern Brazil. HLA DQ2 and DQ8 genotyping was performed for 73 individuals with celiac disease and 126 first-degree relatives with negative transglutaminase serology. The alleles DQA1*05, DQA1*0201, DQB1*02 and DQB1*0302 were identified by sequencing using specific primers and the EU-DQ kit from the Eurospital Laboratory, Trieste, Italy and double-checked by the All Set SPP kit (Dynal). Among the 73 cases, 50 (68.5%) had the genotype DQ2, 13 (17.8%) had DQ8, 5 (6.8%) had DQ2 and DQ8, and 5 did not have any of these genotypes. Among the 5 negative individuals, four had the B1*02 allele and one did not have any of the alleles studied. B1*02 was the most frequent allele in both groups (94% in the patients and 89% in the control relatives). In this study, celiac disease was associated with the genotypes DQ2 and DQ8. DQ2 predominated, but the distribution of the frequencies was different from what has been found in European populations and was closer to what has been found in the Americas. The high frequencies of the HLA genotypes DQ2 and DQ8 that were found in first-degree relatives would make it difficult to use these HLA genotypes for routine diagnosis of celiac disease in this group.


Assessing the Determinants of Compliance with Contribution Payments to the National Health Insurance Scheme among Informal Workers in Indonesia.
This study aimed to investigate the determinants of compliance with contribution payments to the National Health Insurance (NHI) scheme among informal workers in Bogor Regency, West Java Province, Indonesia. Surveys of 418 informal workers in Bogor Regency from April to May 2023 were conducted. Multivariate logistic regression analyses were performed to assess the factors associated with informal workers' compliance with NHI contribution payments. The results revealed that being female, having lower secondary education or below, perceiving good health of family members, having negative attitudes toward and poor knowledge of the NHI, experiencing financial difficulties, preferring to visit health facilities other than public ones, and utilizing fewer outpatient services were significantly associated with the noncompliance of informal workers with NHI contribution payments. It was concluded that economic factors alone cannot contribute to informal workers' payment compliance and that motivational factors (knowledge, attitudes toward the insurance system, and self-related health status) also encourage them to comply with contribution payments. Improving people's knowledge, especially on the risk-sharing concept of the NHI, should be done through extensive health insurance education using methods that are appropriate for the population's characteristics.


Self-Assembled Core-Shell Structure MgO@TiO2 as a K2CO3 Support with Superior Performance for Direct Air Capture CO2.
Traditional carbon capture and storage technologies for large point sources can at best slow the rate of increase in atmospheric CO2 concentrations. In contrast, direct capture of CO2 from ambient air, or "direct air capture" (DAC), offers the potential to become a truly carbon-negative technology. Composite solid adsorbents fabricated by impregnating a porous matrix with K2CO3 are promising adsorbents for the adsorption capture of CO2 from ambient air. Nevertheless, the adsorbent can be rapidly deactivated during continuous adsorption/desorption cycles. In this study, MgO-supported, TiO2-stabilized MgO@TiO2 core-shell structures were prepared as supports using a novel self-assembled (SA) method and then impregnated with 50 wt % K2CO3 (K2CO3/MgO@TiO2, denoted as SA-KM@T). The adsorbent exhibits a high CO2 capture capacity of ∼126.6 mg CO2/g sorbent in direct air adsorption and maintained a performance of 20 adsorption/desorption cycles at 300 °C mid-temperature, which was much better than that of K2CO3/MgO. Analysis proved that the core-shell structure of the support effectively inhibited the reaction between the active component (K2CO3) and the main support (MgO) by the addition of TiO2, resulting in higher reactivity, thermal stability, and antiagglomeration properties. This work provides an alternative strategy for DAC applications using adsorbents.


The relationship between copper, homocysteine and early vascular disease in lean women with polycystic ovary syndrome.
This study investigates copper (Cu) levels and vascular dysfunction in lean women with polycystic ovary syndrome (PCOS). 44 subjects with PCOS, diagnosed according to Rotterdam criteria, and 42 healthy subjects matched for body mass index and age. Comparison of serum Cu, homocysteine, carotid intima-media thickness (CIMT), brachial artery flow mediated dilation (FMD) was carried out between PCOS patients and the control group. Clinical study was done in Namik Kemal University School of Medicine. The CIMT and concentration of Cu in PCOS patients was significantly higher than the healthy controls. FMD levels in PCOS patients were significantly lower than those in controls. In PCOS patients, CIMT was correlated with estrogen and Cu levels. However, FMD was correlated with age and Cu levels. Among these contributing factors, Cu levels were correlated with a change in CIMT and FMD. CIMT and FMD in PCOS patients were related to Cu levels as well as several cardiovascular risk factors. Thus, increased Cu levels may be responsible for the increased risk of early vascular disease in women with PCOS.


Whose Right Is It Anyway? The Duties Owed to a Deceased and to Surviving Family Members When Dealing with a Corpse: Brennan v City of Bradford Metropolitan District Council and Leeds Teaching Hospitals NHS Trust [2021] 1 WLUK 429.
This commentary considers the case of Brennan, in which surviving family members successfully brought a Human Rights Act 1998 (HRA) claim against a hospital and a council for the way in which they both treated a body post-mortem. Their failure to freeze it led to such a state of decomposition that it was unfit for viewing. The family argued this constituted an unjustified interference with their rights to family and private life. After a review of Strasbourg case law, the Leeds County Court found for them and awarded them damages under section 8 of the HRA. This commentary evaluates both the Strasbourg law and the way it was utilised and interpreted domestically. While agreeing with the outcome, the authors conclude that the Strasbourg case law does not line up four square-and instead they suggest that a different approach, accepting the legitimacy of a claim based on 'memory-securing', is warranted on the facts. The commentary also questions whether the court was correct in seeing the rights reposed in the surviving family, and offers the view that greater coherence to the law might be achieved if we conceive of the survivors as the vehicle for the exercise of rights by the deceased.


BUBR1 deficiency results in abnormal megakaryopoiesis.
The physiologic function of BUBR1, a key component of the spindle checkpoint, was examined by generating BUBR1-mutant mice. BUBR1(-/-) embryos failed to survive beyond day 8.5 in utero as a result of extensive apoptosis. Whereas BUBR1(+/-) blastocysts grew relatively normally in vitro, BUBR1(-/-) blastocysts exhibited impaired proliferation and atrophied. Adult BUBR1(+/-) mice manifested splenomegaly and abnormal megakaryopoiesis. BUBR1 haploinsufficiency resulted in an increase in the number of splenic megakaryocytes, which was correlated with an increase in megakaryocytic, but a decrease in erythroid, progenitors in bone marrow cells. RNA interference-mediated down-regulation of BUBR1 also caused an increase in polyploidy formation in murine embryonic fibroblast cells and enhanced megakaryopoiesis in bone marrow progenitor cells. However, enhanced megakaryopoiesis in BUBR1(+/-) mice was not correlated with a significant increase in platelets in peripheral blood, which was at least partly due to a defect in the formation of proplatelet-producing megakaryocytes. Together, these results indicate that BUBR1 is essential for early embryonic development and normal hematopoiesis.


Scattering of a Gaussian beam from a row of cylinders with rectangular cross section.
The transverse magnetic Gaussian beam diffraction from a finite number, equally spaced and rectangular cross section dielectric cylinder row is studied. The infinitely long cylinders' axes are perpendicular to the beam's direction of propagation. The cylinder row, with dielectric constant εc=nc2, is treated as a periodic inhomogeneous film, with period ax and thickness wy, bounded by two semi-infinite homogeneous media. With this restriction, the method is valid only for square or rectangular cross section cylinders. The supercell and the plane wave expansion methods are used to calculate the eigenfrequencies and eigenvectors supported for a one-dimensional photonic crystal. Then, these eigenfrequencies and eigenvectors are used to expand the field in the inhomogeneous film. Numerical results are presented for ax greater than λ (the incident light wavelength), wx (the cylinder width), and wg (Gaussian beam waist). Two cases are studied. In the first (second) case, the unit cell contains one cylinder (a cylinder row), which simulates the scattering from a single cylinder (an inhomogeneous thin film). The total integrated scattering in transmission (reflection) shows three well-defined minima (maxima), which are due to interference effects. Its positions can be approximately obtained with the formula λk=4ncwy/k, with k=3, 4, and 6. The total integrated scattering in transmission decreases linearly as a function of the cylinder number.


An investigation of Salmonella Fluntern illnesses linked to leopard geckos-United States, 2018.
Reptile contact can result in zoonotic non-typhoidal salmonellosis. In April 2018, Oregon Public Health Division contacted CDC about a cluster of four Salmonella serovar Fluntern (SF) illnesses in four states (OR, CA, IA, NY); patients reported contact with geckos, a popular reptile pet. PulseNet, the national molecular subtyping network of food-borne disease surveillance, subsequently identified additional SF clinical isolates. Twelve cases in 11 states were identified; median age was 5 years (range: <1-58 years). Three patients were hospitalized; no deaths were reported. Of those with exposure information (n = 10), all reported reptile exposure; 9 (90%) specified contact with leopard geckos. No common source of geckos was identified from reported purchase locations. Los Angeles County (LAC) health officials isolated SF from one patient's leopard gecko. Five reptile/gecko isolates were identified from the USDA National Veterinary Services Laboratories (NVSL) from 2015 to 2018. Five countries responded to an Epidemic Intelligence Information System post by PulseNet; reptile isolate sequence data were received from Czech Republic. A clinical case from England was identified through the National Center for Biotechnology Information pathogen detection pipeline; the patient did not report contact with leopard geckos. Whole genome sequencing analysis revealed substantial genetic diversity between clinical and animal isolates; however, gecko and clinical isolates from LAC were highly related (1 allele difference). This investigation linking SF illnesses to leopard geckos highlights an important public health risk from pets. A better understanding of how geckos are distributed by the pet industry in the United States could improve traceability to points of origin and mitigate Salmonella transmission at gecko breeders. Earlier NVSL reports of SF isolates from geckos suggest the risk of human SF infection from geckos is not new. This investigation demonstrates a need to educate gecko breeders, retailers and gecko owners about the continued Salmonella infection risk from pet geckos.


The processing of antigen and anti-Ig by antigen-specific B cells.
B lymphocytes are very efficient antigen-presenting cells when they bear surface receptors for the antigen in question. However, there is very little known about the intracellular events occurring between the time B cells bind native antigen and present it in processed form to T cells. To analyze internalization and degradation of antigen versus anti-Ig or anti-MHC antibodies by B cells, we have used highly purified resting antigen-specific B lymphocytes that bind the hapten, trinitrophenyl. These cells were treated with [125I]-labeled trinitrophenylated antigens or with [125I]-labeled antibodies reactive with either cell surface immunoglobulin or major histocompatibility complex (MHC) (class I or class II) molecules. The fate of these proteins was followed by measuring the amount of acid soluble and insoluble radioactivity associated with the cells or released into the incubation medium. The cell-associated and released radioactivity was further analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Our results demonstrate that the kinetics of degradation of specific antigen into acid soluble fragments which are released into the culture medium closely parallel those with which B cells acquire the ability to specifically conjugate to carrier-specific T cells. In contrast, degradation of anti-Ig is more complete than the degradation of antigen but requires a longer period of time to reach completion. Furthermore, the initial release of soluble fragments of anti-Ig as compared to antigen into the culture medium is marginally slower. Finally, there is significant intracellular accumulation of degradation intermediates when anti-Ig is processed, but this is not the case with antigen.(ABSTRACT TRUNCATED AT 250 WORDS)


A monitoring system for axonal growth dynamics using micropatterns of permissive and Semaphorin 3F chemorepulsive signals.
Neurons reach their correct targets by directional outgrowth of axons, which is mediated by attractive or repulsive cues. Growing axons occasionally cross a field of repulsive cues and stop at intermediate targets on the journey to their final destination. However, it is not well-understood how individual growth cones make decisions, and pass through repulsive territory to reach their permissive target regions. We developed a microcontact printing culture system that could trap individual axonal tips in a permissive dot area surrounded by the repulsive signal, semaphorin 3F (Sema3F). Axons of rat hippocampal neurons on the Sema3F/PLL dot array extended in the checkboard pattern with a significantly slow growth rate. The detailed analysis of the behaviors of axonal growth cones revealed the saccadic dynamics in the dot array system. The trapped axonal tips in the permissive area underwent growth cone enlargement with remarkably spiky filopodia, promoting their escape from the Sema3F constraints with straight extension of axons. This structured axonal growth on the dot pattern was disrupted by increased inter-dot distance, or perturbing intracellular signaling machineries. These data indicate that axons grow against repulsive signals by jumping over the repulsive cues, depending on contact signals and intracellular milieu. Our study suggests that our dot array culture system can be used as a screening system to easily and efficiently evaluate ECM or small molecule inhibitors interfering growth cone dynamics leading to controlling axonal growth.


Preconception maternal posttraumatic stress and child negative affectivity: Prospectively evaluating the intergenerational impact of trauma.
The developmental origins of psychopathology begin before birth and perhaps even prior to conception. Understanding the intergenerational transmission of psychopathological risk is critical to identify sensitive windows for prevention and early intervention. Prior research demonstrates that maternal trauma history, typically assessed retrospectively, has adverse consequences for child socioemotional development. However, very few prospective studies of preconception trauma exist, and the role of preconception symptoms of posttraumatic stress disorder (PTSD) remains unknown. The current study prospectively evaluates whether maternal preconception PTSD symptoms predict early childhood negative affectivity, a key dimension of temperament and predictor of later psychopathology. One hundred and eighteen women were recruited following a birth and prior to conception of the study child and were followed until the study child was 3-5 years old. Higher maternal PTSD symptoms prior to conception predicted greater child negative affectivity, adjusting for concurrent maternal depressive symptoms and sociodemographic covariates. In exploratory analyses, we found that neither maternal prenatal nor postpartum depressive symptoms or perceived stress mediated this association. These findings add to a limited prospective literature, highlighting the importance of assessing the mental health of women prior to conception and providing interventions that can disrupt the intergenerational sequelae of trauma.


Radioiodine concentration by the thymus in differentiated thyroid carcinoma: report of five cases.
The radioactive iodine has been used with great value as a diagnostic and therapeutic method in patients with differentiated thyroid carcinoma previously submitted to total thyroidectomy. False-positive whole-body scans may occur due to misinterpretation of the physiologic distribution of the radioisotope or lack of knowledge on the existence of other pathologies that could eventually present radioiodine uptake. Thymic uptake is an uncommon cause of false-positive whole-body scan, and the mechanism through which it occurs is not completely understood. The present paper reports five cases of patients with differentiated thyroid cancer who presented a mediastinum uptake of radioiodine in a whole-body scan during follow-up. The patients had either histological or radiological confirmation of the presence of residual thymus gland. It is very important to know about the possibility of iodine uptake by the thymus in order to avoid unnecessary treatment, such as surgery or radioiodine therapy.


Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated protein 145 and inhibits splicing prior to the first catalytic step.
The multifunctional herpes simplex virus type 1 (HSV-1) protein IE63 (ICP27) interacts with the essential pre-mRNA splicing factor, spliceosome-associated protein 145 (SAP145), and in infected cells IE63 and SAP145 colocalize. This interaction was reduced or abrogated completely using extracts from cells infected with IE63 viral mutants, with mutations in IE63 KH and Sm homology domains, which do not exhibit host shutoff or inhibit splicing. In the presence of IE63, splicing in vitro was inhibited prior to the first catalytic step and the B/C complex formed during splicing was shifted up in mobility and reduced in intensity. With the use of splicing extracts, IE63 and SAP145 both comigrated with the B/C complex, suggesting that they interact within this complex to inhibit B/C complex formation or conversion. The inhibition of splicing may facilitate the export of viral or cellular transcripts, possibly via other protein partners of IE63. These data provide important new insights into how IE63 influences pre-mRNA processing during HSV-1 infection.


Chemogenetic attenuation of neuronal activity in the entorhinal cortex reduces Aβ and tau pathology in the hippocampus.
High levels of the amyloid-beta (Aβ) peptide have been shown to disrupt neuronal function and induce hyperexcitability, but it is unclear what effects Aβ-associated hyperexcitability may have on tauopathy pathogenesis or propagation in vivo. Using a novel transgenic mouse line to model the impact of human APP (hAPP)/Aβ accumulation on tauopathy in the entorhinal cortex-hippocampal (EC-HIPP) network, we demonstrate that hAPP overexpression aggravates EC-Tau aggregation and accelerates pathological tau spread into the hippocampus. In vivo recordings revealed a strong role for hAPP/Aβ, but not tau, in the emergence of EC neuronal hyperactivity and impaired theta rhythmicity. Chronic chemogenetic attenuation of EC neuronal hyperactivity led to reduced hAPP/Aβ accumulation and reduced pathological tau spread into downstream hippocampus. These data strongly support the hypothesis that in Alzheimer's disease (AD), Aβ-associated hyperactivity accelerates the progression of pathological tau along vulnerable neuronal circuits, and demonstrates the utility of chronic, neuromodulatory approaches in ameliorating AD pathology in vivo.


MRI-visible perivascular space volumes, sleep duration and daytime dysfunction in adults with cerebrovascular disease.
Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior. We analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index. Individuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38-22.26, p = 0.018). Individuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.


[Experience of a psychiatric unit in a pediatric hospital in the Province of Córdoba (Argentina): Between epidemiological and legislative changes].
In the past decades, several epidemiological changes have been observed in the demand for child mental health care with an increase in the number of visits as well as hospitalizations due to mental causes. These changes, together with the sanitary guidelines related to mental health, lead to the implementation of a mental health care unit at a pediatric hospital, which required the adjustment of the infrastructure as well as the professional resources available. The diagnosis of the situation and the sanitary context that led to the implementation of the care unit are presented. The performance/management indicators of the psychiatric unit for the period 2009-2015 are: hospitalization cause, psychopathological diagnosis and prolonged hospitalization cause. The hospitalization of children with mental disorders at a pediatric hospital occurs at the crossroads of two paradigms: mental health and pediatrics.


The trend of marriage, childbearing, and divorce and its determinants of socio-economic factors on divorce in Yazd province 2016-2021: A cross-sectional study.
In recent decades, families and their stability as an important social institution have changed significantly. This study aimed to investigate the marriage trends, childbearing, and divorce changes in Yazd province from 2016 to 2021 to estimate the effect of socioeconomic factors on divorce. A cross-sectional study was done in 2 phases. In the first phase, an ecological (time trend) was conducted to investigate the 5 yr trend in the occurrence of marriage, childbearing, and divorce, as well as the factors affecting the occurrence of divorce in the second phase. For the second phase of the study, 600 participants were selected. 300 divorced and 300 married applicants were chosen between 2016 and 2021. A binary logistic regression model was used to find the related factors affecting the occurrence of divorce. The results showed a declining marriage (p = 0.05) and childbearing trend (p = 0.84), as well as an increasing trend in divorces (p = 0.02) in Yazd. Logistic regression analysis showed that college education (OR = 0.22, CI: 0.116-0.430, p < 0.001) and being self-employed (OR = 0.48, CI: 0.255-0.934, p = 0.03) could reduce the odds of divorce. In addition, nonresidents (OR = 2.1, CI: 1.314-3.562, p < 0.001), with > 10-yr age differences (OR = 3.8, CI: 1.803-8.213, p < 0.001) or the woman being older than her husband (OR = 3.4, CI: 1.981-5.848, p < 0.001) could increase the odds of divorce. Our results confirmed that a combination of socioeconomic characteristics affects the stability of family institutions.


Science of nanofibrous scaffold fabrication: strategies for next generation tissue-engineering scaffolds.
Native extracellular matrix (ECM) provides structural support to the multicellular organism on a macroscopic scale and establishes a unique microenvironment (niche) to tissue- and organ-specific cell types. Both these functions are critical for optimal function of the organism. These natural ECMs comprise predominantly fibrillar proteins, collagen and elastin and are synthesized as monomers but undergo hierarchical organization into well-defined nanoscaled structural units. The interaction between the cells and ECM is dynamic, reciprocal and essential for tissue development, maintenance of function, repair and regeneration processes. Tissue-engineering scaffolds are synthetic, biomimetic ECM analogues that have great promise in regenerative medicine. Ongoing efforts in mimicking the native ECM in terms of composition and dimension have resulted in three strategies that permit the generation of scaffolds in nanometer dimensions. Although excellent reviews regarding the applications of these strategies in tissue engineering are available, a comprehensive review of the science behind these fabrication techniques does not exist. This review intends to fill this critical gap in the existing knowledge in the fast-expanding field of nanofibrous scaffolds. A thorough understanding of the fabrication processes would enable us to better exploit available technologies to produce superior tissue-engineering scaffolds.


Does urbanization make emergence of zoonosis more likely? Evidence, myths and gaps.
Rapid urbanization in the global South is adding epidemiological and nutritional challenges and increasing disease and health burdens for citizens. Greater movement of people, animals, food and trade often provides favourable grounds for the emergence of infectious diseases, including zoonoses. We conduct a rapid evidence scan to explore what is known and hypothesized about the links between urbanization and zoonosis emergence. This points to rapid demographic growth, migration and density, increased movement of people and animals, and changes in land uses as the main processes linked to the prevalence of zoonosis in the urban global South. We argue that this emerging global health challenge is also deeply connected with the urbanization of poverty and inequalities within cities. Tackling the micro-level causal relationships between urbanization and zoonosis requires urgent attention to living conditions, as well as the wider socioenvironmental transitions and structural drivers that produce and reproduce risk accumulation in urban settings.


Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis.
Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages. A cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes. Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability. Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease.


HPLC separation of amino acid enantiomers and small peptides on macrocyclic antibiotic-based chiral stationary phases: a review.
The search for new and effective chiral selectors capable of separating a wide variety of enantiomeric compounds is an ongoing process. In the past decade, macrocyclic antibiotics have proved to be an exceptionally useful class of chiral selectors for the separation of enantiomers of biological and pharmacological importance by means of HPLC, TLC and electrophoresis. More chiral analytes have been resolved through the use of glycopeptides than with all the other macrocyclic antibiotics combined (ansamycins, thiostrepton, aminoglycosides, etc.). The glycopeptides avoparcin, teicoplanin, ristocetin A and vancomycin have been extensively used as chiral selectors in the form of chiral bonded phases in HPLC, and HPLC stationary phases based on these glycopeptides have been commercialized. Teicoplanin, vancomycin, their analogs and ristocetin A seem to be the most useful glycopeptide HPLC bonded phases for the enantioseparation of proteins and unusal native and derivatized amino acids. In fact, the macrocyclic glycopeptides are to some extent complementary to one another: where partial enantioresolution is obtained with one glycopeptide, there is a high probability that baseline or better separation can be obtained with another. This review sets out to characterize the physicochemical properties of these antibiotics and their application in the enantioseparations of amino acids. The mechanism of separation, the sequence of elution of the stereoisomers and the relation to the absolute configuration are also discussed.


Head turn in 1-eyed and normally sighted individuals during monocular viewing.
To determine the incidence and magnitude of head turn in persons unilaterally enucleated at an early age and in normally sighted persons patched monocularly. The Hospital for Sick Children, Toronto, Ontario. Fifty-two unilaterally enucleated children and adults without nystagmus (median age, 10 years) who were enucleated at an early age (median age, 18 months) due to retinoblastoma and 28 normally sighted children and adults. Enucleated subjects were videotaped while walking 15 m toward a camera under 2 conditions: (1) fixation relaxed (just looking at the camera) and (2) fixation forced (trying to identify a small fixation target on the camera). Control subjects were tested in the fixation forced condition only. Head turn incidence and magnitude were independently rated. Three categories of head turn were used: "obvious" (> 10 degrees), "small" (5 degrees-10 degrees), and "no" (0 degree-4 degrees). In the fixation relaxed condition, 22 (42%) of 52 enucleated subjects exhibited head turn; when fixation was forced, the incidence increased to 25 (58%) of 43 subjects. Head turn was virtually always in the direction of the missing eye. Incidence and magnitude of head turn were unrelated to age at enucleation or number of years since enucleation. In the control group, there was no consistent finding of head turn across subjects when 1 eye was patched. One-eyed children frequently exhibit head turn unrelated to the presence of nystagmus. The direction of the head turn is "adaptive" because occlusion by the nose in the lower contralateral field is reduced.


Site-specific incorporation of the mucin-type N-acetylgalactosamine-alpha-O-threonine into protein in Escherichia coli.
Glycosylation is a prevalent posttranslational process capable of augmenting and modulating protein function. Efficient synthesis of high-purity, homogeneous glycoproteins is essential for the study of unique protein glycoforms and for the manufacture of therapeutically relevant forms. A promising new strategy for controlled in vivo synthesis of glycoproteins was recently established using suppressor tRNA technology. Using an evolved tRNA aminoacyl synthetase-tRNA pair from Methanococcus jannaschii, the glycosyl amino acid, N-acetylglucosamine-beta-O-serine (GlcNAc-beta-Ser), was site-specifically introduced into proteins cotranslationally in Escherichia coli. Herein, we report the evolution of a new tRNA aminoacyl synthetase-tRNA pair that has expanded the repertoire of glycoproteins that can be expressed in E. coli to contain the other major O-linked glycan, N-acetylgalactosamine-alpha-O-threonine (GalNAc-a-Thr).


Colour Doppler Evaluation of Extracranial Carotid Arteries: A Clinical and Radiological Correlation.
Atherosclerosis (i.e. hardening and thickening of arteries) causes vascular remodeling, obstruction of lumen, abnormalities of blood flow and reduced oxygenation of target tissues. Manifestation of atherosclerosis in the form of either Myocardial Infarction or Stroke is the major cause of morbidity and mortality. This study evaluated extracranial carotid arteries of patients (>60 years) who presented with risk factors of atherosclerosis and determined the association of risk factors with carotid abnormalities. To evaluate the prevalence of atherosclerosis, haemodynamic and morphological changes that take place in extra cranial portion of carotid arteries in patients with risk factors of atherosclerosis (Diabetes Mellitus, Hypertension, Smoking, Stroke, Coronary Artery Disease, Hypercholesterolaemia) and determine the association of risk factors with carotid abnormalities. The prospective cross-sectional analytical study included the examination of Extracranial carotid arteries of 1043 patients over a period of 2 years (2013-2015) using duplex ultrasound. Assessment of CCA-IMT, ICA-IMT and percent stenosis was done using a linear probe of 8-12 MHz. Correlation between risk factors of atherosclerosis, wall thickness of common carotid (CCA-IMT), internal carotid arteries (ICA-IMT) and stenosis was studied using statistical tools like multiple logistic regression analysis and analysis of variance (p<0.05) using SPSS 17.0. Maximum percent stenosis increased with increase in age. Prevalence of severe stenosis (>70%) was low while the prevalence of mild stenosis (<50%) was quite high. In all age groups, stenosis was more prevalent and more severe in men as compared to women. Hypertension showed the strongest positive correlation with all three measures of interest CCA-IMT, ICA-IMT and maximum percent stenosis. Stroke history showed strong positive correlation with CCA-IMT and stenosis. Smoking, Diabetes Mellitus, Hypercholesterolaemia, Heart disease showed strong association with all three measures as well. Atherosclerotic plaques were mostly found at the site of carotid bifurcation. CCA-IMT was strongly associated with hypertension, smoking and diabetes mellitus. ICA-IMT was strongly associated with hypertension and history of heart disease. Percent stenosis was strongly associated with smoking and history of heart disease.


Mindful movement and skilled attention.
Bodily movement has long been employed as a foundation for cultivating mental skills such as attention, self-control or mindfulness, with recent studies documenting the positive impacts of mindful movement training, such as yoga and tai chi. A parallel "mind-body connection" has also been observed in many developmental disorders. We elaborate a spectrum of mindfulness by considering ADHD, in which deficient motor control correlates with impaired (disinhibited) behavioral control contributing to defining features of excessive distractibility and impulsivity. These data provide evidence for an important axis of variation for wellbeing, in which skillful cognitive control covaries with a capacity for skillful movement. We review empirical and theoretical literature on attention, cognitive control, mind wandering, mindfulness and skill learning, endorsing a model of skilled attention in which motor plans, attention, and executive goals are seen as mutually co-defining aspects of skilled behavior that are linked by reciprocal inhibitory and excitatory connections. Thus, any movement training should engage "higher-order" inhibition and selection and develop a repertoire of rehearsed procedures that coordinate goals, attention and motor plans. However, we propose that mindful movement practice may improve the functional quality of rehearsed procedures, cultivating a transferrable skill of attention. We adopt Langer's spectrum of mindful learning that spans from "mindlessness" to engagement with the details of the present task and contrast this with the mental attitudes cultivated in standard mindfulness meditation. We particularly follow Feldenkrais' suggestion that mindful learning of skills for organizing the body in movement might transfer to other forms of mental activity. The results of mindful movement training should be observed in multiple complementary measures, and may have tremendous potential benefit for individuals with ADHD and other populations.