APAtrap: identification and quantification of alternative polyadenylation sites from RNA-seq data.
Alternative polyadenylation (APA) has been increasingly recognized as a crucial mechanism that contributes to transcriptome diversity and gene expression regulation. As RNA-seq has become a routine protocol for transcriptome analysis, it is of great interest to leverage such unprecedented collection of RNA-seq data by new computational methods to extract and quantify APA dynamics in these transcriptomes. However, research progress in this area has been relatively limited. Conventional methods rely on either transcript assembly to determine transcript 3' ends or annotated poly(A) sites. Moreover, they can neither identify more than two poly(A) sites in a gene nor detect dynamic APA site usage considering more than two poly(A) sites. We developed an approach called APAtrap based on the mean squared error model to identify and quantify APA sites from RNA-seq data. APAtrap is capable of identifying novel 3' UTRs and 3' UTR extensions, which contributes to locating potential poly(A) sites in previously overlooked regions and improving genome annotations. APAtrap also aims to tally all potential poly(A) sites and detect genes with differential APA site usages between conditions. Extensive comparisons of APAtrap with two other latest methods, ChangePoint and DaPars, using various RNA-seq datasets from simulation studies, human and Arabidopsis demonstrate the efficacy and flexibility of APAtrap for any organisms with an annotated genome. Freely available for download at https://apatrap.sourceforge.io. email@example.com or email@example.com. Supplementary data are available at Bioinformatics online.


Discrepancy between PCR based SARS-CoV-2 tests suggests the need to re-evaluate diagnostic assays.
We investigated the discrepancy between clinical and PCR-based diagnosis of COVID-19. We compared results of ten patients with mild to severe COVID-19. Respiratory samples from all cases were tested on the Roche SARS-CoV-2 (Cobas) assay, Filmarray RP2.1 (bioMereiux) and TaqPath™ COVID19 (Thermofisher) PCR assays. Laboratory records of ten patients with mild to severe COVID-19 were examined. Initially, respiratory samples from the patients were tested as negative on the SARS-CoV-2 Roche® assay. Further investigation using the BIOFIRE® Filmarray RP2.1 assay identified SARS-CoV-2 as the pathogen in all ten cases. To investigate possible discrepancies between PCR assays, additional testing was conducted using the TaqPath™ COVID19 PCR. Eight of ten samples were positive for SARS-CoV-2 on the TaqPath assay. Further, Spike gene target failures (SGTF) were identified in three of these eight cases. Discrepancy between the three PCR assays could be due to variation in PCR efficiencies of the amplification reactions or, variation at primer binding sites. Strains with SGTF indicate the presence of new SARS-CoV-2 variant strains. Regular modification of gene targets in diagnostic assays may be necessary to maintain robustness and accuracy of SARS-CoV-2 diagnostic assays to avoid reduced case detection, under-surveillance, and missed opportunities for control.


Enzyme evolution in the Enterobacteriaceae.
An immunological approach has been used for the study of alkaline phosphatase evolution in bacteria of the family Enterobacteriaceae. Antisera were prepared against alkaline phosphatase from Escherichia coli and Klebsiella aerogenes and tested against the unpurified alkaline phosphatases of 32 strains of enterobacteria by double diffusion and quantitative micro-complement fixation. The immunological relationships detected among the alkaline phosphatases of enterobacteria agree approximately with those reported for five other enzymes, as well as with the tryptic peptide pattern similarities found for two other enzymes, and with the relationships detected by interspecific deoxyribonucleic acid hybridization tests.


Molecular Characterization of Southern African Territories 2 (SAT2) Serotype of Foot-and-Mouth Disease Virus from Nigeria in 2017 to 2018.
This report describes the nucleotide sequences of eight Southern African Territories 2 (SAT2) serotype foot-and-mouth disease virus strains from 2017 to 2018 outbreaks in cattle in Nigeria. These viruses belong to topotype VII of SAT2 and were closely related to previous isolates from Nigeria and other West African countries.


Application of fresh and cryopreserved homografts harvested from transplant patients for correction of complex congenital heart disease.
In recent years, the use of homograft tissue in cardiac surgery has increased so that supply is limited. Since October 1990, aortic and/or pulmonary valves were collected from 17 transplant recipients at the Department of Cardiovascular Surgery of the University of Padova Medical School (11 male, 6 female, mean age 43.4 years, range 11 months to 61 years). The indications for transplant were dilated cardiomyopathy in 7, and end-stage ischemic heart disease in the remaining 10 patients. Twelve such valves have been subsequently reimplanted either as fresh or as cryopreserved valved homografts in the repair of different forms of congenital heart disease, by means of different tailoring techniques (7 male, 5 female; mean age 4.8 years [range 1 day to 18 years]; transposition of the great arteries = 5 cases; tetralogy of Fallot = 3 cases; hypoplastic left heart syndrome = 2 cases; double outlet right ventricle = 1 case; truncus arteriosus = 1 case). Overall, early mortality was 25%. None of these deaths could be related to the use of homografts. There have been no instances of valve related complications among nine patients surviving surgery at a mean follow-up of 11 months. All patients having heart explanted should be regarded as potential sources for aortic and pulmonary homografts.


Peptide-containing nerves in the human pregnant uterine cervix: an immunohistochemical study exploring the effect of RU 486 (mifepristone).
The presence of several neuropeptides (neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL), enkephalin (ENK), somatostatin (SOM) was established in the early pregnant human cervix using indirect immunofluorescence immunohistochemistry. Several peptides (VIP, NPY, CGRP, GAL) were present both in free nerves among smooth muscle cells and around blood vessels. Others (SP, SOM) were only seen as single varicosities among smooth muscle cells. Randomized treatment of patients with RU 486 (mifepristone) prior to surgical sampling revealed no clearcut differences in peptide immunoreactivities. After RU 486 treatment, however, there was a tendency towards a decrease of NPY- and VIP-immunoreactivity, and an increase of CGRP-immunoreactivity.


Emerging evidence for specific neuronal functions of auxiliary calcium channel α₂δ subunits.
In nerve cells the ubiquitous second messenger calcium regulates a variety of vitally important functions including neurotransmitter release, gene regulation, and neuronal plasticity. The entry of calcium into cells is tightly regulated by voltage-gated calcium channels, which consist of a heteromultimeric complex of a pore forming α₁, and the auxiliary β and α₂δ subunits. Four genes (Cacna2d1-4) encode for the extracellular membrane-attached α₂δ subunits (α₂δ-1 to α₂δ-4), out of which three isoforms (α₂δ-1 to -3) are strongly expressed in the central nervous system. Over the years a wealth of studies has demonstrated the classical role of α₂δ subunits in channel trafficking and calcium current modulation. Recent studies in specialized neuronal cell systems propose roles of α₂δ subunits beyond the classical view and implicate α₂δ subunits as important regulators of synapse formation. These findings are supported by the identification of novel human disease mutations associated with α₂δ subunits and by the fact that α₂δ subunits are the target of the anti-epileptic and anti-allodynic drugs gabapentin and pregabalin. Here we review the recently emerging evidence for specific as well as redundant neuronal roles of α₂δ subunits and discuss the mechanisms for establishing and maintaining specificity.


Restoration of Brain Acid Soluble Protein 1 Inhibits Proliferation and Migration of Thyroid Cancer Cells.
Brain acid soluble protein 1 (BASP1) is identified as a novel potential tumor suppressor in several cancers. However, its role in thyroid cancer has not been investigated yet. In the present study, the antitumor activities of BASP1 against the growth and migration of thyroid cancer cells were evaluated. BASP1 expression in thyroid cancer tissues and normal tissues were examined by immunohistochemical staining and the association between its expression and prognosis was analyzed. pcDNA-BASP1 carrying full length of BASP1 cDNA was constructed to restore the expression of BASP1 in thyroid cancer cell lines (BHT-101 and KMH-2). The cell proliferation in vitro and in vivo was evaluated by WST-1 assay and xenograft tumor models, respectively. Cell cycle distribution after transfection was analyzed using flow cytometry. Cell apoptosis after transfection was examined by annexin V/propidium iodide assay. The migration was examined using transwell assay. BASP1 expression was abundant in normal tissues while it is significantly decreased in cancer tissues (P = 0.000). pcDNA-BASP1 restored the expression of BASP1 and significantly inhibited the growth of BHT-101 and KMH-2 cells as well as xenograft tumors in nude mice (P = 0.000). pcDNA-BASP1 induced G1 arrest and apoptosis in BHT-101 and KMH-2 cells. In addition, pcDNA-BASP1 significantly inhibited the cell migration. Downregulation of BASP1 expression may play a role in the tumorigenesis of thyroid cancer. Restoration of BASP1 expression exerted extensive antitumor activities against growth and migration of thyroid cancer cells, which suggested that BASP1 gene might act as a potential therapeutic agent for the treatment of thyroid cancer.


[The value of arthroscopy in the management of anteromedial lesions of the knee joint. A therapy concept].
Based on the clinical findings from twenty-seven patients over a mean follow-up period of 27 months, a therapeutic management plan for anteromedial lesions of the knee is presented. This is based both on the usual instability tests in narcosis and on accurate arthroscopic evaluation of the lesion to the medial ligamentous apparatus. Additional open reconstruction of the posteromedial ligamentous apparatus was only performed in cases of arthroscopic lesions Type III after arthroscopic management of all internal knee-joint injuries. The average period of rehabilitation was 10 weeks in the case of Type I lesions and 16 weeks in the case of Type III lesions. This compares with results following conservative treatment. At follow-up, 66% of the knee-joints were found to be stable in the Lachman test, and 81.5% were stable in the abduction stress test. Excellent and good results were achieved in 96.2% of cases according to the Lysholm scoring scale. The advantages of arthroscopy lie not only in the possibility of treating all internal knee-joint injuries including the deeper layers of the medial ligamentous apparatus, but also in protecting the vastus medialis, which is of particular importance for the prognosis of anteromedial lesions.


Cyclosporine inhibits a direct interaction between cyclophilins and hepatitis C NS5A.
Hepatitis C Virus (HCV) infection is a leading indication for liver transplantation. HCV infection reoccurs almost universally post transplant, decreasing both graft longevity and patient survival. The immunosuppressant, cyclosporine A (CsA) has potent anti-HCV activity towards both HCV replicons and the genotype 2a cell culture infectious virus. Previously, we isolated mutations in the 1bN replicon with less sensitivity to CsA that mapped to both NS5A and NS5B regions of the virus. Mutations in NS5A alone conferred decreased CsA susceptibility regardless of NS5B mutations. We examined the mechanisms by which NS5A mutations contribute to CsA resistance and if they are strain dependent. Using in vitro mutagenesis, the amino acid position 321 mutation of NS5A was restored to the wild-type tyrosine residue conferring partial CsA susceptibility on the mutant replicon. The 321 mutation also alters CsA susceptibility of the JFH cell culture virus. Additionally, we demonstrated a novel CsA-sensitive interaction between NS5A and both cyclophilin A and B. Both the mutant NS5A and wild type NS5A bind cyclophilin in vitro. The NS5A: cyclophilin interaction requires both the NS5A region identified by the resistance mutants and cyclophilin catalytic residues. In cell culture, NS5A from CsA resistant mutant has an enhanced interaction with cyclophilin B. Additionally; NS5B facilitates a stronger binding of mutant NS5A to endogenous cyclophilin B than wild-type in cell culture. Collectively, this data suggests direct interactions between cyclophilins and NS5A are critical to understand for optimal use of cyclophilin inhibitors in anti-HCV therapy.


MRI study of the position of the conus medullaris in patients with lumbar spinal stenosis.
Substantial data exist from cadaveric and magnetic resonance imaging studies regarding the position of the conus medullaris in normally developed adults. However, no large studies have documented the position of the conus medullaris in patients with diagnosed lumbar spinal stenosis. To goal of the current study was to determine the position of the conus medullaris within a living adult population with existing pathology of lumbar spinal stenosis. In a retrospective study, 234 patients (110 women and 124 men; mean age, 48.8 years) with diagnosed lumbar spinal stenosis had their T2-weighted, midline, sagittal, spin-echo magnetic resonance imaging studies compared to assess and confirm the position of the conus medullaris. A straight line perpendicular to the long axis of the spinal cord in the median sagittal sequence was subtended to the adjacent vertebra or disk space, and the position was defined in relation to the vertebra or disk space. The conus medullaris position was labeled in relation to the upper, middle, and lower segments of the adjacent vertebral body or the adjacent disk space and assigned numerical values from 1 to 12. The position of the conus medullaris in patients with lumbar spinal stenosis followed a normal distribution. The mean conus medullaris position was mainly within the lower third of the L1 vertebral body (ranged from the middle third of T12 to the upper third of L3). No significant differences existed between men and women with lumbar spinal stenosis. The conus medullaris position was found to be unaffected by the pathology of lumbar spinal stenosis.


Comparing the ICERs in Medicine Reimbursement Submissions to NICE and PBAC-Does the Presence of an Explicit Threshold Affect the ICER Proposed?
The English National Institute for Health and Care Excellence (NICE) and the Australian Pharmaceutical Benefits Advisory Committee (PBAC) require evidence that a new medicine represents value for money before being publicly funded. NICE has an explicit threshold for cost effectiveness, whereas PBAC does not. We compared the initial incremental cost-effectiveness ratios (ICERs) presented by manufacturers in matched submissions to each decision-making body, with the aim of exploring the impact of an explicit threshold on these ICERs. Data were extracted from matched submissions from 2005 to 2015. The ICERs in these submissions were compared within each pair and with respect to a cost-effectiveness threshold. Fifty-eight pairs of matched submissions were identified. The median difference between the ICERs ($2635/quality-adjusted life year [QALY]) was significantly greater than zero (Wilcoxon signed-rank test, P = 0.0299), indicating that the proposed ICERs in the submissions to NICE were higher than those in the matched submissions to PBAC. On 93% of occasions, NICE ICERs were within -$17,772 to +$48,422 of the corresponding PBAC ones (Bland-Altman analysis), demonstrating poor agreement. When an implicit threshold of AUD$50,000/QALY was assumed for PBAC decision making, only eight pairs of submissions had discordant ICERs falling above or below the respective threshold. The significantly higher ICERs in the submissions to NICE than those to PBAC may be a consequence of NICE's explicit willingness-to-pay threshold, and/or other health system factors. Industry may be assuming an implicit threshold for PBAC when constructing their ICERs despite the lack of acknowledgement of such a threshold.


Retrospective analysis of sheep scrapie by western blotting with formalin-fixed paraffin-embedded (FFPE) tissues.
An abnormal isoform of prion protein (PrP(Sc)) was extracted from formalin-fixed paraffin-embedded (FFPE) tissues from sheep and analyzed by western blotting. PrP(Sc) immunoreactivity against anti-PrP monoclonal antibody T2, which recognizes discontinuous PrP sequences, differed amongst individual scrapie sheep cases. This may reflect structural differences in PrP(Sc) that have been formalin-fixed prior to their extraction. This study indicates that western blotting by using FFPE tissues is useful for the retrospective analysis of transmissible spongiform encephalopathies in which only formalin-fixed samples are available and in conducting transmissible spongiform encephalopathies surveillance where freezing system is insufficient.


Picosecond dynamics of the photoinduced spin polarization in epitaxial (Ga,Mn)as films.
Static and time-resolved magneto-optical spectra of the ferromagnetic semiconductor (Ga,Mn)As show that a pulsed photoexcitation with a fluence of 10 microJ/cm(2) is equivalent to the application of an external magnetic field of about 1 mT, which relaxes with a decay time of 30 ps. This relaxation is attributed to the spin relaxation of electrons in the conduction band and is found to be not affected by interactions with Mn ions.


The pattern and distribution of calcitonin gene-related peptide (CGRP) terminals in the rat dorsal following neonatal peripheral inflammation.
Neonatal peripheral inflammation has been shown to alter the neural circuitry of the spinal cord in adult rats. However, the temporal and spatial changes in the distribution of primary afferent terminals immediately following a neonatal inflammatory stimulus remains unclear. In the present study we found that intraplantar injection of complete Freund's adjuvant (CFA) or saline alone on postnatal day 1 (P1) causes CGRP immunoreactivity (CGRP-Ir) to gradually increase from P6 to P15 in laminae I and II, and return to baseline at P22. In laminae III and IV, CGRP-Ir markedly increased beginning at P6, and remained elevated thereafter. CGRP-Ir in lamina V remained unchanged throughout the observation period. These findings show that intraplantar CFA induces CGRP-fiber sprouting in laminae III and IV, but not in laminae I, II or V. We suggest that neonatal inflammation causes changes in the neural circuitry pattern in various regions of the dorsal horn during the critical neonatal development period in rats.


[Case of interstitial cystitis accompanied by food allergy].
A case is a 62 years old woman who consulted her family physicion with pollakiuria and sharp pain at the time of urinary bladder distention. Since anti-H1-antagonist but not antibiotics was partially effective against the symptoms and some specific food ingestion appeared to increase the bladder pain, she was referred to our hospital. Treatment with spulatast tosilate and elimination of food products that revealed the presence of specific IgE antibodies and positive skin reactiont resulted favorable clinical response. Cystoscopic examination showed reduction in bladder capacity, mucosal injection and vascularization, besides pinpoint submucosal hemorrage and linear ulcer by hydrodistension. The diagnosis of interstitial cystitis was established by those evidences and histological findings. The patient got apparent remission after the bladder hydrodistension and is now in steady state with an addition of suplatast tosilate, a Th2 cytokine inhibitor, on the treatment mentioned above. Interstitial cystitis is a very rare disease which is characterized by cystitis-symptoms with normal urinary finding and non-effectiveness of antibiotics. The pathogenesis of the disease is unclear but considered as allergic inflammation. We report a case of interstitial cystitis accompanied by food allergy.


[2 cases of enterorrhagia caused by Meckel's diverticulum. Problems of diagnosis and therapy].
The authors study two cases of enterorrhage due to Meckel's diverticulum. They particularly emphasize the importance of two instrumental inspections: enema and abdominal scintigraphy with 99mTcO4, in the diagnostics of this malformative pathology, and the treatment with H2-blocking substances with the purpose to stop hemorrhage, circumstantiate the diagnostic suspicion, and operate electively.


Ki-67 index value and progesterone receptor status can predict prognosis and suitable treatment in node-negative breast cancer patients with estrogen receptor-positive and HER2-negative tumors.
Gene profiling has identified at least 4 breast cancer subtypes, including Luminal A, Luminal B, HER2-enriched and basal-like, and immunohistochemistry is used as a guide to determine these subtypes. In the present study, patients with ER-positive, HER2-negative and negative nodes were classified into 4 groups according to the PgR and the Ki-67 status and were retrospectively examined. The analysis was based on the clinicopathological findings, and includes the recurrence score (RS) and disease-free survival (DFS) rates. Patients with invasive breast cancer (n=1866) were classified as LA (high PgR/low Ki-67), LB-1 (high PgR/high Ki-67), LB-2 (low PgR/high Ki-67), and LB-3 (low PgR/low Ki-67). In addition, 41 of the cases underwent a 21-gene expression assay. The data revealed that T1 tumors were more prevalent in the LA group and rare in the LB-2 group. Furthermore, nuclear grade 3 and p53 overexpression was revealed to be significantly correlated with LB-2. In terms of prognosis, LA had a significantly more favorable DFS; however, no differences were observed in the LB-3 group. LB-2 had a significantly worse DFS in all cases, and in the cases administered with endocrine therapy alone. Chemotherapy in combination with endocrine therapy was administered to cases with a higher risk of recurrence. In the LB-2 group, there was no difference in the DFS rates between the cases with endocrine therapy and chemo-endocrine therapy. These findings suggest that chemotherapy could improve the DFS in the LB-2 group. In addition, the majority of cases with LA, LB-3 and LB-1 had a RS of ≤25 and the majority of the LB-2 cases had a RS of >25. The patients with LA and LB-3 had a favorable DFS even in the group that received endocrine therapy alone. LB-2 was significantly correlated with a higher degree of malignancy and benefited from chemotherapy. These data suggest that the PgR and the Ki-67 status are effective in predicting prognosis, and for deciding on the most effective treatment strategy in patients with breast cancer.


Chest Deformity and Disability due to Tenofovir-Induced Hypophosphatemic Osteomalacia: Case Report and Call for Improved Global Access to Laboratory Testing.
Millions of people worldwide take tenofovir disoproxil fumarate (TDF) for the treatment of human immunodeficiency virus (HIV) and/or hepatitis B infection. Although generally safe and well tolerated, clinicians need to be aware that TDF can cause proximal renal tubular dysfunction and loss of bone mineral density, especially in patients with concomitant renal disease or other risk factors. We present the case of a patient with chronic HIV infection and urethral stricture who developed TDF-related proximal renal tubular dysfunction with hypophosphatemia and osteomalacia, presenting with bone pains, skeletal deformity, and disability. We review risk factors for TDF-related renal tubular toxicity and recommendations for monitoring creatinine, phosphate, alkaline phosphatase, and urinalysis.


Efficient evaluation of atom tunneling combined with electronic structure calculations.
Methodology for finding optimal tunneling paths and evaluating tunneling rates for atomic rearrangements is described. First, an optimal JWKB tunneling path for a system with fixed energy is obtained using a line integral extension of the nudged elastic band method. Then, a calculation of the dynamics along the path is used to determine the temperature at which it corresponds to an optimal Feynman path for thermally activated tunneling (instanton) and a harmonic approximation is used to estimate the transition rate. The method is illustrated with calculations for a modified two-dimensional Müller-Brown surface but is efficient enough to be used in combination with electronic structure calculations of the energy and atomic forces in systems containing many atoms. An example is presented where tunneling is the dominant mechanism well above room temperature as an H3BNH3 molecule dissociates to form H2. Also, a solid-state example is presented where density functional theory calculations of H atom tunneling in a Ta crystal give close agreement with experimental measurements on hydrogen diffusion over a wide range in temperature.


Immunohistochemical localization of carbonic anhydrase isoenzymes in salivary gland and intestine in adult and suckling pigs.
Localizations of carbonic anhydrase isoenzymes (CA I, CA II and CA III) were investigated immunohistochemically in the salivary glands and intestine of mature and suckling pigs. Carbonic anhydrase isoenzymes were not detected in the salivary glands of sucklings, but were present in the adult. Bicarbonate ion in saliva might be important for the digestion of solid foods in mature pigs, but unnecessary for the digestion of milk in sucklings. Expressions of CA I and CA II were detected strongly in the large intestine of the adult and sucklings, and faintly only at duodenum in the small intestine. CA I and CA II isoenzymes in the large intestine may be involved, at least in part, in ion absorption and water metabolism during digestion and absorption of milk in suckling pigs. In addition, CA I and CA II expression in the duodenal villus enterocyte may support the process of bicarbonate absorption in the duodenum.


Multicenter cohort study demonstrates more consolidation in upper lungs on initial CT increases the risk of adverse clinical outcome in COVID-19 patients.
Rationale: Chest computed tomography (CT) has been used for the coronavirus disease 2019 (COVID-19) monitoring. However, the imaging risk factors for poor clinical outcomes remain unclear. In this study, we aimed to assess the imaging characteristics and risk factors associated with adverse composite endpoints in patients with COVID-19 pneumonia. Methods: This retrospective cohort study enrolled patients with laboratory-confirmed COVID-19 from 24 designated hospitals in Jiangsu province, China, between 10 January and 18 February 2020. Clinical and initial CT findings at admission were extracted from medical records. Patients aged < 18 years or without available clinical or CT records were excluded. The composite endpoints were admission to ICU, acute respiratory failure occurrence, or shock during hospitalization. The volume, density, and location of lesions, including ground-glass opacity (GGO) and consolidation, were quantitatively analyzed in each patient. Multivariable logistic regression models were used to identify the risk factors among age and CT parameters associated with the composite endpoints. Results: In this study, 625 laboratory-confirmed COVID-19 patients were enrolled; among them, 179 patients without an initial CT at admission and 25 patients aged < 18 years old were excluded and 421 patients were included in analysis. The median age was 48.0 years and the male proportion was 53% (224/421). During the follow-up period, 64 (15%) patients had a composite endpoint. There was an association of older age (odds ratio [OR], 1.04; 95% confidence interval [CI]: 1.01-1.06; P = 0.003), larger consolidation lesions in the upper lung (Right: OR, 1.13; 95%CI: 1.03-1.25, P =0.01; Left: OR,1.15; 95%CI: 1.01-1.32; P = 0.04) with increased odds of adverse endpoints. Conclusion: There was an association of older age and larger consolidation in upper lungs on admission with higher odds of poor outcomes in patients with COVID-19.


COVID-19 and cancer research.
The COVID-19 pandemic has had a devastating effect on human lives and society. The accompanying editorial summarises some of the major effects on cancer patients and impacts on cancer research. These may be mitigated by appropriate responses from governments, research funders, charities, universities, industry and the public. It is already clear that different approaches to management have drastically different outcomes.


Proteome analysis of microdissected tumor tissue using a capillary isoelectric focusing-based multidimensional separation platform coupled with ESI-tandem MS.
This study demonstrates the ability to perform sensitive proteome analysis on the limited protein quantities available through tissue microdissection. Capillary isoelectric focusing combined with nano-reversed-phase liquid chromatography in an automated and integrated platform not only provides systematic resolution of complex peptide mixtures based on their differences in isoelectric point and hydrophobicity but also eliminates peptide loss and analyte dilution. In comparison with strong cation exchange chromatography, the significant advantages of electrokinetic focusing-based separations include high resolving power, high concentration and narrow analyte bands, and effective usage of electrospray ionization-tandem MS toward peptide identifications. Through the use of capillary isoelectric focusing-based multidimensional peptide separations, a total of 6866 fully tryptic peptides were detected, leading to the identification of 1820 distinct proteins. Each distinct protein was identified by at least one distinct peptide sequence. These high mass accuracy and high-confidence identifications were generated from three proteome runs of a single glioblastoma multiforme tissue sample, each run consuming only 10 microg of total protein, an amount corresponding to 20,000 selectively isolated cells. Instead of performing multiple runs of multidimensional separations, the overall peak capacity can be greatly enhanced for mining deeper into tissue proteomics by increasing the number of CIEF fractions without an accompanying increase in sample consumption.


Clinical pharmacy in a multidisciplinar team for chronic pain in adults.
The aim of this study was to evaluate the role and the impact of a clinical pharmacist as a member of a multidisciplinary pain team. Although physicians have a good knowledge of pharmacotherapy in the field of pain medication, pharmacy interventions were necessary to enhance the quality of prescribing. On a population of 93 patients, a total of 120 interventions were recorded. The different types of interventions included: provision of information (10.0%), clinical intervention (89.2%) and the provision of a specific product (0.8%). Out of the 107 clinical interventions, a total of 95.3 % interventions were accepted by the physicians. The results highlight the clinical importance of the pharmacy in optimizing drug therapy for adult patients with chronic pain.


[Prevalence of height-weight deficit in Tunisian boys of the Northern and Southern regions].
Malnutrition is owing to an alimentation regarding quantity and quality food. aim: To examine the different forms of malnutrition among Tunisian boys of the north and south regions, to form an idea about the state of their health and their living conditions. Our empirical investigation was carried out on 1082 northern boys and 1016 southern boys, aged from 10 to 14 years including 1057 non pubescent boys and 1041 prepubescent boys. Age, weight and height were recorded for the entire population according to the norms of the standard World Health Organization and the nutritional status of these young was described by two indices: Height for age and body mass index for age. The classification used to describe the build is the Cachera Rolland, Malnutrition are significantly more pronounced among the southern boys than their counterparts in the North. Particularly, short stature (19.2% vs 14.4%) and underweight (28% vs 22.5 %). However, the risk of overweight and obesity is more pronounced among the northern boys. However, the comparison between non pubescent and prepubescent boys shows that the prevalence of stunting increases with age. The mechanisms responsible for these inter-individual differences beings regions appear related to living conditions during the first year after birth, particularly, socio-economic status, family size, type of housing, and the education level of parents.


Monitoring polymer properties using shear horizontal surface acoustic waves.
Real-time, nondestructive methods for monitoring polymer film properties are increasingly important in the development and fabrication of modern polymer-containing products. Online testing of industrial polymer films during preparation and conditioning is required to minimize material and energy consumption, improve the product quality, increase the production rate, and reduce the number of product rejects. It is well-known that shear horizontal surface acoustic wave (SH-SAW) propagation is sensitive to mass changes as well as to the mechanical properties of attached materials. In this work, the SH-SAW was used to monitor polymer property changes primarily dictated by variations in the viscoelasticity. The viscoelastic properties of a negative photoresist film were monitored throughout the ultraviolet (UV) light-induced polymer cross-linking process using SH-SAW delay line devices. Changes in the polymer film mass and viscoelasticity caused by UV exposure produced variations in the phase velocity and attenuation of the SH-SAW propagating in the structure. Based on measured polymer-coated delay line scattering transmission responses (S(21)) and the measured polymer layer thickness and density, the viscoelastic constants c(44) and eta(44) were extracted. The polymer thickness was found to decrease 0.6% during UV curing, while variations in the polymer density were determined to be insignificant. Changes of 6% in c(44) and 22% in eta(44) during the cross-linking process were observed, showing the sensitivity of the SH-SAW phase velocity and attenuation to changes in the polymer film viscoelasticity. These results indicate the potential for SH-SAW devices as online monitoring sensors for polymer film processing.


Effect of packing motifs on the energy ranking and electronic properties of putative crystal structures of tricyano-1,4-dithiino[c]-isothiazole.
We present an analysis of putative structures of tricyano-1,4-dithiino[c]-isothiazole (TCS3), generated within the sixth crystal structure prediction blind test. Typical packing motifs are identified and characterized in terms of distinct patterns of close contacts and regions of electrostatic and dispersion interactions. We find that different dispersion-inclusive density functional theory (DFT) methods systematically favor specific packing motifs, which may affect the outcome of crystal structure prediction efforts. The effect of crystal packing on the electronic and optical properties of TCS3 is investigated using many-body perturbation theory within the GW approximation and the Bethe-Salpeter equation (BSE). We find that a structure with Pna21 symmetry and a bilayer packing motif exhibits intermolecular bonding patterns reminiscent of π-π stacking and has markedly different electronic and optical properties than the experimentally observed P21/n structure with a cyclic dimer motif, including a narrower band gap, enhanced band dispersion and broader optical absorption. The Pna21 bilayer structure is close in energy to the observed structure and may be feasible to grow.


A BW Reporter System for Studying Receptor-Ligand Interactions.
Interactions between receptors and ligands constitute a fundamental biological process. However, direct experiments with cells that express the native receptor and the ligand are challenging since the ligand of a specific receptor may be unknown and experimental procedures with the native ligand can be technically complicated. To address these obstacles, we describe a reporter system to detect the binding and activation of a specific receptor by a ligand of interest. In this reporter system, the extracellular domain of a specific receptor is conjugated to mouse CD3ζ and this chimeric protein is then expressed in mouse BW cells. These transfected BW cells can then be incubated with different targets (e.g., cells or antibodies). Activation of a transfected receptor leads to the secretion of mouse interleukin-2 (mIL-2) which can be detected by enzyme-linked immunosorbent assay (ELISA). This reporter system has the advantages of being sensitive and specific to a single receptor. In addition, the activation level of a specific receptor can easily be quantified and can be used even in cases where the ligand of the receptor is unknown. This system has been implemented successfully in many of our studies to characterize receptor-ligand interactions. We have recently employed this system to study the activation of human Fcγ receptors (FcγRs) by different monoclonal anti-CD20 antibodies in clinical use.


Patient-reported outcomes as hospital performance measures: the challenge of confounding and how to handle it.
It is highly appealing to use patient-reported outcomes (PROs) as hospital performance measures; however, so far, the attention to key methodological issues has been limited. One of the most critical challenges when comparing PRO-based performance measures across providers is to rule out confounding. In this paper, we explain confounding and why it matters when comparing across providers. Using examples from studies, we present potential strategies for dealing with confounding when using PRO data at an aggregated level. We aim to give clinicians an overview of how confounding can be addressed in both the design stage (restriction, matching, self-controlled design and propensity score) and the analysis stage (stratification, standardization and multivariable adjustment, including multilevel analysis) of a study. We also briefly discuss strategies for confounding control when data on important confounders are missing or unavailable.


Differential response of Cu,Zn superoxide dismutases in two pea cultivars during a short-term exposure to sulfur dioxide.
Pea cultivars Progress and Nugget have been shown previously to be differentially sensitive with respect to apparent photosynthesis in a short-term exposure to 0.8 microliters/l SO2. One possible contributing factor to the relative insensitivity of apparent photosynthesis of Progress to SO2 is an increase in superoxide dismutase (SOD) activities. We show here that both chloroplastic and cytoplastic Cu,Zn-SOD proteins increased in Progress on exposure to sulfur dioxide whereas both proteins decreased in Nugget. The increase in cytosolic Cu,Zn-SOD protein was greater than that of chloroplastic Cu,Zn-SOD protein. Using a gene-specific probe for the plastid SOD, northern blot analysis revealed an initial decrease in transcript abundance of the chloroplastic Cu,Zn-SOD gene in Progress on exposure to SO2 with an eventual recovery to pre-exposure levels. The transcript levels of the chloroplastic Cu,Zn-SOD decreased in Nugget over the time period of the exposure. These results suggest that a combination of translational and post-translational mechanisms may be involved in SO2-induced changes in cytosolic and plastidic Cu,Zn-SODs in pea.


Event related evoked potentials in dementia: role of vitamin E.
Dementia is a common cognitive syndrome reflecting a wide spread chronic progressive disease as an extension to normal aging process. Oxidative stress has been implicated in dementia and antioxidants have become attractive therapeutic agents. Among the antioxidants vitamin E is the most potent in the treatment of dementia. Study was conducted in 20 patients suffering from dementia in the age group of 66-74 and in 20 age and sex matched controls. Latency of the P3 component of event related evoked potential (ERP) showed an increase from 338.65 +/- 42.22 msec in control group to 348.9 +/- 46.38 msec in patients of dementia. In control group P3 latency decreased from 338.65 +/- 42.22 msec to 331.6 +/- 38.75 msec after Vitamin E therapy. In patients of dementia latency decreased significantly from 348.9 +/- 46.38 msec to 324.62 +/- 44.25 msec after vitamin therapy for one month. P3 amplitude in controls and demented was 7.2 +/- 3.62 mu v and 7.07 +/- 3.73 mu v respectively. After vitamin E therapy a statistically significant increase in amplitude (P < 0.05) was observed in controls (9.34 +/- 5.04 mu v) and in patients of dementia (9.58 +/- 5.24 mu v). The study suggests that the latency and amplitude of P3 were not significantly different in control and dementia patients, while vitamin E supplementation (oral 800 mg per day for 30 days) decreased the latency and increased the P3 amplitude in both the control and dementia patients. Our study further supports that Vitamin E supplementation, because of its antioxidant property might be decreasing oxidative stress, which may lead to improvement in cognitive pool of generator neurons of P3.


Efficacy and safety of simeprevir in combination with peginterferon and ribavirin for patients with hepatitis C genotype 1 infection: a meta-analysis of randomized trials.
A simeprevir (SMV)-based regimen has shown promising results in treating chronic hepatitis C virus (HCV) infection. This meta-analysis aimed to assess the efficacy and safety of simeprevir for treating HCV genotype 1 infection. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched, along with the reference lists of retrieved articles. The meta-analysis only included randomized controlled trials (RCTs) that compared the efficacy and safety of addition of SMV to peginterferon (PegIFN) and ribavirin (RBV) (triple regimen) with PegIFN/RBV alone (dual regimen) in treating chronic HCV genotype 1 infection. A total of seven RCTs involving 2,301 patients were included. The triple regimen had a higher pooled sustained virologic response (SVR) rate [odds ratio (OR) = 4.57; 95% confidence interval (CI): 3.34-6.27; p < 0.001)] and lower pooled relapse rate [relative risk (RR) = 0.41; 95% CI: 0.33-0.50; p < 0.001] than the dual regimen had. The pooled incidence of adverse events (AEs) was comparable between the two regimens (RR = 1.01; 95% CI: 0.99-1.03; p = 0.339), whereas the incidence of serious AEs in the triple regimen was lower (RR = 0.7; 95% CI: 0.50-0.98; p < 0.05). The meta-analysis demonstrates that the addition of SMV to pegIFN and RBV is effective and well-tolerated in treating chronic HCV genotype 1 infection, with a low incidence of AEs.


Microsatellite instability in Lactuca sativa chronically exposed to cadmium.
Cadmium (Cd) is a cytotoxic, mutagenic and carcinogenic metal. Mutagenesis is indicative of genetic instability and can be assayed by use of microsatellite markers (simple sequence repeats, SSRs). These are tandem-repeated tracts of DNA composed of units that are 1-6 base pairs (bp) long, spread throughout the genome and highly polymorphic. SSRs can be used in the detection of genomic DNA damage and/or mutational events (e.g. deletions, insertions, point mutations). In order to study chronic exposure to cadmium, Lactuca sativa L. seeds were germinated in distilled water and grown on modified Hoagland's medium, both supplemented with 0, 10 and 100microM Cd(NO(3))(2). After 28 days of exposure, the plants were harvested to assess shoot and root length and accumulation of cadmium. DNA was extracted from young and expanded leaves and roots in order to analyse microsatellite instability (MSI). Mutagenic effects of cadmium were evaluated on nine microsatellite loci. No MSI was found in leaves, but a 2-bp deletion in one lettuce root SSR was detected among the SSRs that were analysed. Thus, SSR analyses may provide a complementary tool in the assessment of different genotoxic effects of compounds on plants.


Biofilms Formed by Isolates from Recurrent Vulvovaginal Candidiasis Patients Are Heterogeneous and Insensitive to Fluconazole.
Vulvovaginal candidiasis (VVC) is a global health problem affecting ∼75% of women at least once in their lifetime. Here we examined the epidemiology of VVC in a patient cohort to identify the causative organisms associated with VVC. Biofilm-forming capacity and antifungal sensitivity profiles were also assessed. We report a shifting prevalence of Candida species with heterogeneous biofilm-forming capacity, which is associated with altered antifungal drug sensitivity.


Diffuse hemangioma of the rectum detected on multi-slice CT in an 18-year-old woman with Klippel-Trenaunay syndrome.
The paper reports a rare case of an 18-year-old woman with Klippel-Trenaunay syndrome, whose multi-phase multi-slice CT revealed diffuse colorectal hemangioma. The patient presented symptoms of consumption coagulopathy (Kasabach-Meritt syndrome) and intense collateral circulation in the course of portal hypertension. The CT lesions and possibilities of multiformat and 3D volume rendering reconstructions are presented. To our knowledge, this is the first report of diffuse hemangioma of the colon and rectum in a patient with KTS detected with multi-slice CT.


The differential mutagenicity of isoniazid in fluctuation assays and Salmonella plate tests.
The anti-tuberculostatic drug, isoniazid (INH) was evaluated for its mutagenic potential using Salmonella plate tests and fluctuation assays with various strains of bacteria, and different metabolic activation systems. In the Salmonella plate test INH proved to be a weak directly-acting base-substitution mutagen which was detoxified by S9-mix. S. typhimurium TA 1530 and TA 1535 were the sensitive strains, and this result confirmed some of the published data. In the present studies mutagenic activity was further diminished in the presence of larger concentrations of rat liver S9-mix. Furthermore, the reduction in mutagenic activity was observed with S9-mix derived from untreated, Aroclor 1254-treated or phenobarbitone/beta-naphthoflavone treated rats. In direct contrast, using the microtitre fluctuation assay, the mutagenic activity of INH was elevated in the presence of rat liver S9-mix, and continued to increase with increasing S9-concentration. This result was obtained irrespective of the S9-source. S. typhimurium strains TA 1530, TA 1535 and his G46, and E. coli strains TA 85, TA 86 and WP2 uvrA were all sensitive to the mutagenicity of INH after metabolic activation. The primary step in the metabolic activation of INH in the fluctuation test was mediated by a cytosolic enzyme, and the activity of dapsone as a competitive substrate implicated the involvement of an N-acetyl transferase. The rapid diffusion of the cytosolic enzyme into the basal agar layer, or the non-specific binding of the enzyme (or the active mutagenic INH metabolite) to components of the agar, may explain the contradictory data obtained in the Salmonella plate test. The modifying effects of agar on the distribution of drug metabolising enzymes within liver S9 fractions should be carefully considered when evaluating data from Salmonella plate tests.


Sending mixed signals: Cilia-dependent signaling during development and disease.
Molecular signals are the guiding force of development, imparting direction upon cells to divide, migrate, differentiate, etc. The mechanisms by which a cell can receive and transduce these signals into measurable actions remains a 'black box' in developmental biology. Primary cilia are ubiquitous, microtubule-based organelles that dynamically extend from a cell to receive and process molecular and mechanical signaling cues. In the last decade, this organelle has become increasingly intriguing to the research community due to its ability to act as a cellular antenna, receive and transduce molecular stimuli, and initiate a cellular response. In this review, we discuss the structure of primary cilia, emphasizing how the ciliary components contribute to the transduction of signaling pathways. Furthermore, we address how the cilium integrates these signals and conveys them into cellular processes such as proliferation, migration and tissue patterning. Gaining a deeper understanding of the mechanisms used by primary cilia to receive and integrate molecular signals is essential, as it opens the door for the identification of therapeutic targets within the cilium that could alleviate pathological conditions brought on by aberrant molecular signaling.


Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group.
When questioned, about 10% of the parents report suspected hypersensitivity to at least one drug in their children. However, only a few of these reactions can be confirmed as allergic after a diagnostic workup. There is still a lack of knowledge on drug hypersensitivity (DH) epidemiology, clinical spectrum, and appropriate diagnostic methods particularly in children. Meanwhile, the tools used for DH management in adults are applied also for children. Whereas this appears generally acceptable, some aspects of DH and management differ with age. Most reactions in children are still attributed to betalactams. Some manifestations, such as nonsteroidal anti-inflammatory drug-associated angioedema and serum sickness-like reactions, are more frequent among young patients as compared to adults. Risk factors such as viral infections are particularly frequent in children, making the diagnosis challenging. The practicability and validity of skin test and other diagnostic procedures need further assessment in children. This study presents an up-to-date review on epidemiology, clinical spectrum, diagnostic tools, and current management of DH in children. A new general algorithm for the study of these reactions in children is proposed. Data are presented focusing on reported differences between pediatric and adult patients, also identifying unmet needs to be addressed in further research.


A Stable Monomeric SiO2 Complex with Donor-Acceptor Ligands.
Isolation of a monomeric SiO2 compound 3 as a stable donor-acceptor complex with two different ligands -a σ-donating ligand (pyridine, dimethylaminopyridine, N-heterocyclic carbene) and a donor-acceptor ligand (iminophosphorane)-is presented. The SiO2 complex 3 is soluble in ordinary organic solvents and is stable at room temperature in solution and in the solid state. Of particular interest, 3 remains reactive and can be used as a stable and soluble unimolecular SiO2 reagent.


Serological survey in the Finnish human population implies human-to-human transmission of Ljungan virus or antigenically related viruses.
Ljungan virus (LV) is a picornavirus related to human parechoviruses (HPeV). The virus has been found in bank voles (Myodes glareolus) and several other rodent species, and suggested to have zoonotic potential. Thus far, seroepidemiological data on LV infections in humans are scarce. In this study, we aimed to characterize the demographic and geographical distribution of LV-reactive antibodies in Finland, and to investigate its occurrence in patients suspected of having a rodent-borne disease, nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV). Using an immunofluorescence assay (LV strain 145SLG), we screened human sera (n = 1378) and found LV-reactive antibodies in 36% of samples. The probability of possessing LV-reactive antibodies peaked at age of 14 years, suggesting that most infections occur in childhood. The prevalence of LV-reactive antibodies was significantly higher in the urbanized area surrounding Helsinki than in more rural Central Finland. These findings are uncharacteristic of a rodent-borne pathogen, and therefore we consider human-to-human transmission of one or several Ljungan-like viruses as a likely cause for most of the observed antibody responses.


Epidemiology of respiratory virus before and during COVID-19 pandemic.
The COVID pandemic has forcefully turned the spotlight on the importance of the diagnosis of respiratory virus infections. Viruses have always been a frequent and common cause of respiratory tract infections. Rapid molecular diagnostics applied to the diagnostics of respiratory virus infections has revolutionized microbiology laboratories only a few years ago. Few studies illustrate the epidemiology of respiratory viruses, and fewer still those that have compared the pre-pandemic to the pandemic period. During the first year of the pandemic (2020-2021) it was clear to everyone to witness a sudden disappearance of the circulation of all the other respiratory viruses, especially those typically isolated during the winter time, such as RSV and Influenza virus. In our study we wanted to verify this phenomenon and to study the epidemiology of our local reality, analyzing three consecutive flu seasons (2018-2019, 2019-2020, 2020-2021). The results lead us to note that the prevalence of positivity to respiratory virus infections went from 49.8% (2018-2019) and 39% (2019-2020) to 13.4% (2020-2021). This decrease is at least partly attributable to the security measures adopted (social distancing and mask), but it certainly opens up new scenarios when the restriction measures will be terminated. We believe such studies can provide real-world evidence of the effectiveness of public health interventions implemented during current and future pandemics.


Professional values held by baccalaureate and associate degree nursing students.
To determine the congruency in value orientation of graduating students in baccalaureate and associate degree programs. A survey design with a convenience sample of 1,450 graduating nursing students from all baccalaureate and associate degree nursing programs in Texas. Data were collected using the Nurses Professional Values Scale (NPVS). Descriptive and parametric statistics were used for analysis. ADN and BSN students did not differ significantly on the NPVS total score, however, ADN student scored higher on 5 of the 11 subscales than did their BSN counterparts. Men from both programs scored significantly lower than did women on the total scale and all subscales. Ethnic groups differed on the responses to three of the subscales representing nurses' values: respect for human dignity, safeguarding the client and public, and collaborating to meet public health needs. Professional values in graduating nursing students were significantly related to sex and ethnicity, regardless of educational program. Nursing faculty members are challenged to address these differences during the educational process and mentoring of students.


Helper activity of CD4+ alpha beta T cells is required for the avian gamma delta T cell response.
We have studied the in vitro activation of chicken gamma delta T cells. Both splenic alpha beta and gamma delta T cells obtained from complete Freund's adjuvant-primed chickens proliferated in vitro when stimulated with mycobacterial sonicate or purified protein derivative of Mycobacterium tuberculosis. When CD4+ cells or alpha beta T cell receptor (TcR)-positive cells were removed, both the proliferation and the blast formation of gamma delta T cells in response to mycobacterial antigens were abrogated. The response was restored if supernatant from concanavalin A (Con A)-activated lymphocyte cultures (CAS) as a source of helper factors was added together with the specific antigen purified protein derivative. The CD4- or alpha beta TcR-depleted cells still proliferated in response to Con A, although a decrease of the response was observed. To analyze the gamma delta T cell response more specifically we stimulated peripheral blood cells with immobilized monoclonal antibodies against T cell receptor. Anti-gamma delta TcR antibody alone did not induce significant proliferation. When CAS was added together with the anti-gamma delta TcR monoclonal antibody, a strong proliferation of gamma delta T cells was observed. In contrast, both V beta 1- and V beta 2-expressing alpha beta T cells proliferated in vitro in response to stimulation with the relevant anti-TcR monoclonal antibody alone. Depletion of either V beta 1+ or V beta 2+ T cell subset alone had no negative effect on the proliferation or blast formation of gamma delta T cells stimulated with mycobacterial antigens. Taken together our results suggest that CD4+ alpha beta T cells (both V beta 1- and V beta 2-expressing) play a role in the activation and response of chicken gamma delta T cells.


Outcomes in achalasia from a surgical unit where pneumatic dilatation is first-line therapy.
The management of achalasia remains controversial, with little consensus on the optimal patient treatment pathway. In our own esophageal unit, we offer pneumatic dilatation as the initial therapy in most patients as first-line therapy. In this study, we aimed to examine the safety and efficacy of our own approach to the management of patients with a diagnosis of achalasia, examining symptomatic outcomes, patient satisfaction, and need for further intervention, as well as examining patient factors associated with treatment failure. Sixty-seven consecutive patients underwent pneumatic dilatation as first-line therapy (53% male, mean age 46 years). All attended regular outpatient follow-up (mean 37, range 3-132 months). Twenty-five percent of patients required a second intervention because of symptom recurrence, at a median period of 4.5 months. Symptomatic outcomes were excellent or good in 80%. Significant predictors of treatment failure and poor symptom score included a younger age at the time of diagnosis and increased esophageal diameter on barium swallow. This study suggests that pneumatic dilatation is a safe and effective approach as first-line therapy in patients with newly diagnosed achalasia.


Combination of enzyme- and Lewis acid-catalyzed reactions: a new method for the synthesis of 6,7-dihydrobenzofuran-4(5H)-ones starting from 2,5-dimethylfuran and 1,3-cyclohexanediones.
The Lewis acid-catalyzed domino 1,2-addition/1,4-addition/elimination between (Z)-3-hexene-2,5-dione and 1,3-dicarbonyls delivers 3-methyl-6,7-dihydrobenzofuran-4(5H)-ones exclusively with yields up to 82%. The combination of this new process with the laccase-catalyzed formation of (Z)-3-hexene-2,5-dione by oxidative cleavage of 2,5-dimethylfuran allows for the synthesis of 6,7-dihydrobenzofuran-4(5H)-ones starting directly from 2,5-dimethylfuran.


Surveillance of traffic incident management-related occupational fatalities in Kentucky, 2005-2016.
Traffic incidents occurring on roadways require the coordinated effort of multiple responder and recovery entities, including communications, law enforcement, fire and rescue, emergency medical services, hazardous materials, transportation agencies, and towing and recovery. The objectives of this study were to (1) identify and characterize transportation incident management (TIM)-related occupational fatalities; (2) assess concordance of surveillance data sources in identifying TIM occupations, driver vs. pedestrian status, and occupational fatality incident location; and (3) determine and compare U.S. occupational fatality rates for TIM industries. The Kentucky Fatality Assessment and Control Evaluation (FACE) program analyzed 2005-2016 TIM occupational fatality data using multiple data sources: death certificate data, Collision Report Analysis for Safer Highways (CRASH) data, and media reports, among others. Literal text analysis was performed on FACE data, and a multiple linear regression model and SAS proc sgpanel were used to estimate and visualize the U.S. TIM occupational mortality trend lines and confidence bounds. There were 29 TIM fatalities from 2005 to 2015 in Kentucky; 41% of decedents were in the police protection occupation, and 21% each were in the fire protection and motor vehicle towing industries. Over one half of the TIM decedents were performing work activities as pedestrians when they died. Media reports identified the majority of the occupational fatalities as TIM related (28 of 29 TIM-related deaths); the use of death certificates as the sole surveillance data source only identified 17 of the 29 deaths as TIM related, and the use of CRASH data only identified 4 of the 29 deaths as TIM related. Injury scenario text analysis showed that law enforcement vehicle pursuit, towing and recovery vehicle loading, and disabled vehicle response were particular high-risk activities that led to TIM deaths. Using U.S. data, the motor vehicle towing industry had a significantly higher risk for occupational mortality compared to the fire protection and police protection industries. Multiple data sources are needed to comprehensively identify TIM fatalities and to examine the circumstances surrounding TIM fatalities, because no one data source in itself was adequate and undercounted the total number of TIM fatalities. The motor vehicle towing industry, in particular, is at elevated risk for occupational mortality, and targeted mandatory TIM training for the motor vehicle towing industry should be considered. In addition, enhanced law enforcement roadside safety training during vehicle pursuit and apprehension of suspects is recommended.


Complex Microsurgical Reconstruction After Tumor Resection in the Trunk and Extremities.
Reconstruction of soft tissue defects following tumor ablation procedures in the trunk and extremities can challenge the microsurgeon. The goal is not just to provide adequate soft tissue coverage but also to restore form and function and minimize donor site morbidity. Although the principles of the reconstructive ladder still apply in the trunk and extremities, free tissue transfer is used in many cases to optimally restore form and function. Microsurgery has changed the practice in soft tissue tumors, and amputation is less frequently necessary.


Large-scale organization of rat sensorimotor cortex based on a motif of large activation spreads.
Parcellation according to function (e.g., visual, somatosensory, auditory, motor) is considered a fundamental property of sensorimotor cortical organization, traditionally defined from cytoarchitectonics and mapping studies relying on peak evoked neuronal activity. In the adult rat, stimulation of single whiskers evokes peak activity at topographically appropriate locations within somatosensory cortex and provides an example of cortical functional specificity. Here, we show that single whisker stimulation also evokes symmetrical areas of suprathreshold and subthreshold neuronal activation that spread extensively away from peak activity, effectively ignoring cortical borders by spilling deeply into multiple cortical territories of different modalities (auditory, visual and motor), where they were blocked by localized neuronal activity blocker injections and thus ruled out as possibly caused by "volume conductance." These symmetrical activity spreads were supported by underlying border-crossing, long-range horizontal connections as confirmed with transection experiments and injections of anterograde neuronal tracer experiments. We found such large evoked activation spreads and their underlying connections regardless of whisker identity, cortical layer, or axis of recorded responses, thereby revealing a large scale nonspecific organization of sensorimotor cortex based on a motif of large symmetrical activation spreads. Because the large activation spreads and their underlying horizontal connections ignore anatomical borders between cortical modalities, sensorimotor cortex could therefore be viewed as a continuous entity rather than a collection of discrete, delineated unimodal regions, an organization that could coexist with established specificity of cortical organization and that could serve as a substrate for associative learning, direct multimodal integration and recovery of function after injury.


Temporal Dynamics of Smoking-Related Approach Biases: A Comparison Between Male Smokers and Nonsmokers.
Smokers often exhibit a stronger automatic approach bias toward smoking cues than nonsmokers on the Approach-Avoidance Task. However, previous research has often neglected the temporal dynamic of automatic processes in addiction and focused on immediate approach biases instead of delayed approach biases. Thirty-one male smokers and 30 healthy males were tested by an adapted Approach-Avoidance Task. In this task, immediate as well as delayed approach biases were assessed by manipulating cue-response time intervals. When exposed to smoking cues, smokers have significantly stronger approach bias than nonsmokers at a delay of 0 ms, 600 ms, and 900 ms rather than at 300 ms. This study found that smokers have a strong, immediate approach bias toward smoking-related cues. But this approach bias will keep changing with increased cognitive processing time. Temporal dynamics may be an important feature of the addiction-related approach bias.


Synthetic Biology and Ethics: Past, Present, and Future.
This article explores the ethical issues that have been identified in emerging technologies, from early genetic engineering to synthetic biology. The scientific advances in the field form a continuum, and some ethical considerations can be raised time and again when new developments occur. An underlying concern is the cumulative effect of scientific advances and ensuing technological innovation that can change our understanding of life and humanity.


Being-in-the-Chemotherapy-Suite versus Being-in-the-Oncology-Ward: An Analytical View of Two Hospital Sites Occupied by People Experiencing Cancer.
How do people with cancer occupy places within the health system during their journey through palliative care? The answer to this question was explored by the authors as part of a wider ethnographic study of eight people's journeys from referral to palliative care services to the end of life. This article reports on findings that have emerged from ongoing analysis that has been completed in the years proceeding data collection. An ethnographic research design was used to collect data about the participants and their family members over a three-year period. Data was collected using participant observation and semi-structured interviews. Over 380 transcripts based on field note entries and taped interviews were produced during the 1121 h of contact with participants and family members that made up the research period. Analysis of these texts identified two focal sites within Christchurch Hospital that were occupied by the participants. These were the Chemotherapy Suite and the Oncology Ward. Drawing on literature concerning previous anthropological analysis, research was conducted to understand how places affect people and how people affect places. The researchers have used a model outlined by the American ethnographer Miles Richardson to analyse two distinct sites within one hospital. As explained in Richardson's article, whose title is used to model the title of this article, a sense of place becomes apparent when comparing and contrasting two sites within the same location. Richardson's article is highly interpretative and relies not only on pre-existing theoretical frameworks but also on personal interpretation. The same approach has been used in the current article. Here, ethnographic methods require the researcher's interpretation of how participants occupied these sites. Following this approach, the Chemotherapy Suite is presented as a place where medicine dominates illness, and appears as distinct from the Oncology Ward, where disease predominates and death is secreted away.


A mental practice superiority effect: less retroactive interference and more transfer than physical practice.
Two experiments explored the benefits to retention and transfer conferred by mental practice. During familiarization, participants typed 4-digit numbers and took an immediate typing test on both old and new numbers. Participants then typed old 4-digit numbers, either physically or mentally, with either a different response configuration or the opposite hand from that used during familiarization. On a delayed test, participants physically typed both old and new numbers with the same response configuration and hand used during familiarization. Mental practice led to less retroactive interference and more transfer than did physical practice, supporting the hypothesis that mental practice strengthens an abstract representation that does not involve specific effectors.


Suppression of Aedes albopictus, the Asian tiger mosquito, using a 'hot spot' approach.
Recent changes in climate and human behavior have led to dramatic increases in the abundance and geographic expansion of invasive mosquito vectors such as Aedes albopictus. Although source reduction has been shown to be effective in reducing mosquito populations, thousands of backyards need to be inspected during door-to-door campaigns, which is labor intensive and expensive. We identified 'hot spots' as high (five or more female or male Ae. albopictus) adult mosquito populations at very focal locations. We tested whether hot spot source reduction efforts were effective in reducing mosquito populations in the early summer season (June to July). Analysis of historical data from the study sites indicated the proportion of hot spots in the control site relative to the intervention site was much greater in 2011, when hot spot treatments were applied to the intervention site, than in 2012, 2013 and 2014 combined, when no sites were treated [OR (95% CI) = 3.9 (1.8, 8.5), Z = 3.39, P < 0.001). Hot spot treatments can be incorporated into existing integrated mosquito management programs to increase effectiveness while reducing the time, cost and effort spent on methods such as door-to-door source reduction. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.


Targeting alpha-synuclein in Parkinson's disease.
alpha-Synuclein aggregation into fibrils is associated with the pathogenesis of Parkinson's disease (PD). Li et al. provide strong evidence that rifampicin interacts with alpha-synuclein and inhibits its fibrillization. Rifampicin could be a promising candidate for therapeutic application for PD.


Benzotriazole: An overview on its versatile biological behavior.
Discovered in late 1960, azoles are heterocyclic compounds class which constitute the largest group of available antifungal drugs. Particularly, the imidazole ring is the chemical component that confers activity to azoles. Triazoles are obtained by a slight modification of this ring and similar or improved activities as well as less adverse effects are reported for triazole derivatives. Consequently, it is not surprising that benzimidazole/benzotriazole derivatives have been found to be biologically active. Since benzimidazole has been widely investigated, this review is focused on defining the place of benzotriazole derivatives in biomedical research, highlighting their versatile biological properties, the mode of action and Structure Activity Relationship (SAR) studies for a variety of antimicrobial, antiparasitic, and even antitumor, choleretic, cholesterol-lowering agents.


"Side effects affected my daily activities a lot": a qualitative exploration of the impact of contraceptive side effects in Bangladesh.
In a country like Bangladesh that has made great progress in contraceptive use with one of the lowest levels of fertility and highest levels of contraceptive use, understanding what factors influence women's decisions to discontinue a contraceptive method and not switch to a new method is critical in designing interventions and programs that will help enable Bangladesh to reach its FP2020 goals. Research on side effects has focused on physical manifestations like headaches, moodiness, abdominal pain, and menstrual irregularities. While physical effects alone may stop women from continuing a contraceptive method, less is known about how side effects influence women's daily activities and lives. The purpose of this study is to understand the ways that side effects affect Bangladeshi women's participation in different social settings. Thirty-five in-depth interviews with married women who recently discontinued or switched to a different contraceptive method were conducted in Sylhet and Khulna Divisions. Interviews explored reasons for discontinuation including experience of side effects and impact of side effects on women's lives. Key themes emerged including that side effects are not only experienced physically but are barriers to women's participation in many aspects of their lives. The spheres of life that most commonly appeared to be influenced by side effects include religion, household, and sexual intimacy irrespective of method used or residence. Family planning providers need to be aware of these additional consequences associated with contraceptive side effects to provide tailored counseling that recognizes these issues and helps women to mitigate them. For Bangladesh to achieve its FP2020 goals, understanding the broader context in which family planning decisions are made vis-à-vis side effects is critical to design programs and interventions that meet all the needs of women beyond just their fertility intentions.


Interpersonal processes in paranoia: a systematic review.
Paranoid ideation is a core feature of psychosis, and models of paranoia have long proposed that it arises in the context of disturbances in the perception of the self. However, to develop targeted interventions, there is a benefit in clarifying further, which aspects of self-perception are implicated. Interpersonal sensitivity is a personality trait which has been associated with the risk of paranoid thinking in the general population. However, not all studies have found this link. We aimed to review the empirical literature assessing the association between interpersonal sensitivity and paranoia in both general population and clinical samples; and to explore if associations found differed depending on whether state or trait paranoia was assessed. The review followed PRISMA guidelines. Articles were identified through a literature search in OVID (PsychINFO, MEDLINE) and Web of Science up to December 2016. Fourteen studies with a total of 12 138 participants were included. All studies were of 'fair' or 'good' quality. A robust association was found between interpersonal sensitivity and paranoia in clinical and general population samples alike, regardless of the method of assessment of both paranoia and interpersonal sensitivity. Although this finding was more pronounced in studies of trait paranoia, it is likely that differences in study purpose, measurement, and power explain these differences. Findings from this review support the hypothesis that feelings of personal vulnerability and exaggerated socially evaluative concerns are central for both onset and maintenance of paranoid symptoms, suggesting avenues for future research in targeted interventions.


99mTc-diflunisal and the human iris: topical application reveals localization.
Following the instillation of a drug into the eye, drainage mechanisms will commence at once. In this report, an attempt was made to assess the dynamics of an instilled nonsteroidal anti-inflammatory drug (NSAID), diflunisal, labeled with 1 MBq 99mTc followed by twenty minutes of scintigraphy. The results obtained with this labeled drug were compared with instillation of the same volume and activity of 99mTcO4-. Although the pertechnetate anion is an excellent and innocuous indicator for detecting the external lacrimal drainage system of the eye, it cannot visualize the internal structures. A clear scintigraphic difference was noted between labeled diflunisal and the pertechnetate anion. Scintigraphic activity surrounding the pupil of the eye provides evidence of visualization of the iris/ciliary body. This seems reasonable as the cyclooxygenase enzyme is located in this structure, and NSAIDs exert their mechanism of action via this complex. With this technology, visualization of some internal structures of the eye may be facilitated.


Effect of exposure to high temperatures in the excretion of cadmium and lead.
This study aims to observe the effect on urine and sweat excretion levels of cadmium (Cd) and lead (Pb) in healthy men in a maximum incremental test until exhaustion and repeated exposure to heat. twenty-nine adult men divided into control group (CG; n = 14) and experimental group (EG; n = 15) performing two maximum tests until exhaustion in normothermia (22 °C) and hyperthermia (42 °C). EG experienced 9 sessions of heat exposure at high temperatures (100 °C) (HEHT). After the nine sessions, the initial tests were repeated in both groups. Urine samples were collected before and after each test. After the hyperthermia tests, sweat samples were gathered. Urinary Cd increased after initial tests in GC and in hyperthermia in EG (p < 0.05). Urinary excretion of Pb rose after HEHT (p < 0.05). Pb in sweat was higher in EG than in CG after HEHT (p < 0.05). Heat exercise and constant exposure to heat can be a valid method to increase the excretion of toxic metals.


[Nitrogen metabolism in elderly persons on a low-calorie diet].
The clinical trials covered 9 men aged 58-73 years with daily energy losses of 2200-2350 kcal and given for 10 days the diet (1128 kcal/day) containing different food ingredients. A study was made of the main parameters of nitrogenous metabolism. During the time of being kept on a low-caloric diet, the test subjects lost 2.1 kg body mass. Excretion of total nitrogen dropped 34%, urea 57%. Excretion of creatinine appreciably rose (208% of the initial). The calculation of nitrogenous balance demonstrated protein deficiency to be equal to 209 g during experiments. The concentration of free amino acids in blood plasma decreased: that of replaceable by 29.5%, that of essential ones by 37.6%. It is assumed that the tension of body metabolism affected protein synthesis, whereas the protein quota in the diet did not appear sufficient for elderly subjects.


[Role of probiotics in treatment of nonalcoholic fatty liver disease].
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in China and manifests as simple fatty liver, non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Studies have shown that intestinal flora can affect the development and progression of NAFLD via the "gut-liver axis" . Probiotics are active microorganisms with beneficial effects on the host, and more and more studies have found that probiotics play a positive role in improving NAFLD. They are cheaper, less harmful, and safer compared with antibiotics and surgery, and therefore, it may become a new method for the prevention and treatment of NAFLD. This article reviews the research advances in probiotics in the treatment of NAFLD, in order to provide a basis for the treatment of NAFLD using probiotics.


Electron microscopic study of Kudoa septempunctata infecting Paralichthys olivaceus (olive flounder).
Kudoa septempunctata is a myxosporean parasite of Paralichthys olivaceus (olive flounder) that causes more than 50 cases of foodborne illness in Japan each year. For quantitatively assessing the presence of K. septempunctata spores in the causative fish at food poisoning outbreaks, both a direct observation method using microscopy and a quantitative real-time PCR (qRT-PCR) method are officially accepted in Japan. However, lower correlations have been often noticed between the number of spores counted using the direct observation method and the DNA amount determined using the qRT-PCR method. To elucidate the cause of this discrepancy, we observed muscle tissues of infected olive flounders with K. septempunctata by transmission electron microscopy. The images demonstrated unsynchronized development of K. septempunctata spores in plasmodia found within myofibers; in other words, the plasmodium contained not only developed spores with completed shell valves but also developing spores (sporoblasts) composed of spore-forming cells without shell valves. Furthermore, the ratio between developed spores and sporoblasts varied at different parts of muscles. The direct microscopic observation method could count developed spores, whereas the qRT-PCR method could quantify the amount of not only spores but also sporoblastic cells regardless of the cellular development and differentiation. Considering that the food toxicity caused by K. septempunctata is induced by viable spores passing through the gastric environment, the direct observation method counting only developed spores is better than the qRT-PCR method for assessing the cause of foodborne illness at the outbreak as well as the risk of human illness in monitoring surveys of aquacultured or natural-water fish.


Pregnancy and fertilization potential of immature oocytes retrieved in intracytoplasmic sperm injection cycles.
The goal of this study was to evaluate the pregnancy potential of immature (metaphase I or germinal vesicle stage) oocytes retrieved in intracytoplasmic sperm injection (ICSI) cycles. A total of 1,871 couples with infertility underwent 2,984 ICSI cycles. Cycles in which three or fewer oocytes were retrieved were included in this study in order to evaluate the pregnancy potential of immature oocytes. Cycles were divided into five groups (group I-V), according to the maturation status of the oocytes at the time of cumulus cell removal and ICSI. The fertilization and pregnancy rates after ICSI were analyzed and compared among the study groups based on the maturation status of the retrieved oocytes. The retrieval of only immature oocytes was associated with a significant decrease in the fertilization rate (76.1%±37.3% vs. 49.0%±49.1%, 66.7%±48.7%; group I vs. group II, group III, respectively) and the average number of transferred embryos (1.5±0.7 vs. 1.1±0.4, 1.1±0.6). The cycle cancellation rate was significantly higher when only immature oocytes were retrieved. The clinical pregnancy rate decreased significantly when the transferred embryos had originated from immature oocytes (16.9% vs. 10.3%, 1.2%). In ICSI cycles, the fertilization potential and pregnancy potential of the immature oocytes retrieved in ICSI cycles were inferior to those of mature oocytes. Therefore, increasing the number of injectable oocytes and transferrable embryos by using immature oocytes after their spontaneous in vitro maturation does not necessarily improve pregnancy outcomes.


Comparison of Calcium Oxide and Calcium Peroxide Pretreatments of Wheat Straw for Improving Biohydrogen Production.
Wheat straw was pretreated with either CaO2 or CaO to improve biohydrogen production. Both CaO and CaO2 pretreatments improved the biodegradability of the wheat straw. CaO pretreatment raised the H2 yield by between 48.8 and 163.9% at CaO contents ranging from 2 to 4%. The highest H2 yield [144 mL/g total solid (TS)] was obtained at 121 °C and 6% CaO. In addition, the highest H2 yield from wheat straw pretreated at the same temperature and dosage of CaO2 was 71.8 mL/g TS, which was higher than that of the control group (43.2 mL/g TS), with hot water (121 °C) treatment. Considering pretreatment costs and H2 production potential, CaO was a better pretreatment agent than CaO2.


Synchrotron radiation μCT and histology evaluation of bone-to-implant contact.
The purpose of this study was to evaluate bone-to-implant contact (BIC) in two-dimensional (2D) histology compared to high-resolution three-dimensional (3D) synchrotron radiation micro computed tomography (SR micro-CT). High spatial resolution, excellent signal-to-noise ratio, and contrast establish SR micro-CT as the leading imaging modality for hard X-ray microtomography. Using SR micro-CT at voxel size 5 μm in an experimental goat mandible model, no statistically significant difference was found between the different treatment modalities nor between recipient and reconstructed bone. The histological evaluation showed a statistically significant difference between BIC in reconstructed and recipient bone (p < 0.0001). Further, no statistically significant difference was found between the different treatment modalities which we found was due to large variation and subsequently due to low power. Comparing histology and SR micro-CT evaluation a bias of 5.2% was found in reconstructed area, and 15.3% in recipient bone. We conclude that for evaluation of BIC with histology and SR micro-CT, SR micro-CT cannot be proven more precise than histology for evaluation of BIC, however, with this SR micro-CT method, one histologic bone section is comparable to the 3D evaluation. Further, the two methods complement each other with knowledge on BIC in 2D and 3D.


Do changes in mood and concerns about weight relate to smoking relapse in the postpartum period?
The majority of women who quit smoking during pregnancy will resume smoking during the postpartum period. Little is known, however, about the predictors of postpartum relapses to smoking. Changes in mood and increases in concerns about weight are common during the postpartum period, and these factors may affect women's postpartum smoking behavior. In this paper, we present a model of the relationship among mood, weight concerns and postpartum smoking. Data from previous postpartum relapse prevention trials are reviewed and evidence of a connection between changes in mood and weight concerns to postpartum relapse is presented. Directions for future research on the prevention of smoking relapses during the postpartum period, and the roles of mood and weight concerns in smoking relapse are presented.


The effect of lead on chemical- and viral-induced tumor production in mice.
Female Swiss mice were exposed to lead in the drinking water at concentrations ranging from 0 to 1000 ppm for 105 or 280 day periods of time. The effect of lead on urethan-induced pulmonary adenoma formation was evaluated in the 105 day study. Urethan-induced sleeping times observed following ip injection of urethan (1.5 mg/g) after 3 weeks of lead exposure were not altered by lead indicating that lead did not affect the rate of urethan elimination. Pulmonary adenoma formation was evaluated 84 days later. Lead exposure did not affect the number of tumors produced, nor did it alter the mean tumor diameter in the lead treatment groups. This suggests that the immunosuppressive activity of lead does not enhance urethan-induced adenoma formation. In the 280 day study, the incidence of spontaneous murine lymphocytic leukemia was evaluated. Leukemia was observed in all treatment groups. Mortality was greater in the lead-exposed mice. Mice exposed to 50 or 1000 ppm lead had 41.6% and 58.3% more deaths associated with the virus. The median survival time was also reduced in the lead-exposed mice. It appears that the immunosuppressive effects of lead allow for increased expression of the murine lymphocytic leukemia virus.


Effects of yeast cell-wall characteristics on 4-ethylphenol sorption capacity in model wine.
Saccharomyces cerevisiae is an efficient biosorbant, used in winemaking to reduce the concentration of undesirable molecules such as fatty acids. Volatile phenols such as 4-ethylphenol, which causes a horsy smell in wine, are particular targets of this type of curative process. This study demonstrates that the sorption capacity of 4-ethylphenol by yeasts is greatly influenced by strain nature, methods, and medium used for biomass production and drying after harvesting. S. cerevisiae mutant strains with deletion of genes encoding specific proteins involved in cell-wall structure and composition were studied, and a major role for mannoproteins in 4-ethylphenol sorption was identified. It was confirmed that 4-ethylphenol sorption occurs at the surface of the yeast wall and that not all mannoproteins are determinants of sorption: the sorption capacity of cells with deletion of the Gas1p-encoding gene was 75% lower than that of wild type. Physicochemical properties of yeast cell surface have been also studied.


Epigenetic regulation of integrin-linked kinase expression depending on adhesion of gastric carcinoma cells.
Cell adhesion to the extracellular matrix (ECM) regulates gene expressions in diverse dynamic environments. However, the manner in which gene expressions are regulated by extracellular cues is largely unknown. In this study, suspended gastric carcinoma cells showed higher basal and transforming growth factor-beta1 (TGFbeta1)-mediated acetylations of histone 3 (H3) and Lys(9) of H3 and levels of integrin-linked kinase (ILK) mRNA and protein than did fibronectin-adherent cells did. Moreover, the insignificant acetylation and ILK expression in adherent cells were recovered by alterations of integrin signaling and actin organization, indicating a connection between cytoplasmic and nuclear changes. Higher acetylations in suspended cells were correlated with associations between Smad4, p300/CBP, and Lys(9)-acetylated H3. Meanwhile, adherent cells showed more associations between HDAC3, Ski, and MeCP2. Chromatin immunoprecipitations with anti-acetylated H3, Lys(9)-acetylated H3, or p300/CBP antibody resulted in more coprecipitated ILK promoter, correlated with enhanced ILK mRNA and protein levels, in suspended cells. Moreover, ILK expression inversely regulated cell adhesion to ECM proteins, and its overexpression enhanced cell growth in soft agar. These observations indicate that cell adhesion and/or its related molecular basis regulate epigenetic mechanisms leading to a loss of ILK transcription, which in turn regulates cell adhesion property in a feedback linkage.


Temporal stability of the hybrid zone between Calocitta magpie-jays revealed through comparison of museum specimens and iNaturalist photos.
Hybrid zones are natural experiments for the study of avian evolution. Hybrid zones can be dynamic, moving as species adjust to new climates and habitats, with unknown implications for species and speciation. There are relatively few studies that have comparable modern and historic sampling to assess change in hybrid zone location and width over time, and those studies have generally found mixed results, with many hybrid zones showing change over time, but others showing stability. The white-throated magpie-jay (Calocitta formosa) and black-throated magpie-jay (Calocitta colliei) occur along the western coast of Mexico and Central America. The two species differ markedly in throat color and tail length, and prior observation suggests a narrow hybrid zone in southern Jalisco where individuals have mixed throat color. This study aims to assess the existence and temporal stability of this putative hybrid zone by comparing throat color between georeferenced historical museum specimens and modern photos from iNaturalist with precise locality information. Our results confirm the existence of a narrow hybrid zone in Jalisco, with modern throat scores gradually increasing from the parental ends of the cline toward the cline center in a sigmoidal curve characteristic of hybrid zones. Our temporal comparison suggests that the hybrid zone has not shifted its position between historical (pre-1973) and modern (post-2005) time periods-a surprising result given the grand scale of habitat change to the western Mexican lowlands during this time. An anomalous pocket of white-throated individuals in the northern range of the black-throated magpie-jay hints at the possibility of prehistorical long-distance introduction. Future genomic data will help disentangle the evolutionary history of these lineages and better characterize how secondary contact is affecting both the DNA and the phenotype of these species.


Waterborne outbreak of Norwalk-like virus gastroenteritis at a tourist resort, Italy.
In July 2000, an outbreak of gastroenteritis occurred at a tourist resort in the Gulf of Taranto in southern Italy. Illness in 344 people, 69 of whom were staff members, met the case definition. Norwalk-like virus (NLV) was found in 22 of 28 stool specimens tested. The source of illness was likely contaminated drinking water, as environmental inspection identified a breakdown in the resort water system and tap water samples were contaminated with fecal bacteria. Attack rates were increased (51.4%) in staff members involved in water sports. Relative risks were significant only for exposure to beach showers and consuming drinks with ice. Although Italy has no surveillance system for nonbacterial gastroenteritis, no outbreak caused by NLV has been described previously in the country.


An investigation of the diffusion-limited growth of animal cells around single hollow fibers.
To compare modeling with experimental data of cell growth surrounding individual fibers, the growth profiles of hybridoma cells in the extracapillary space of single hollow fiber bioreactors were examined. Agarose was provided in the extracapillary space to provide support and minimize convection. By sacrificing bioreactors at various time intervals, the growth profiles of cells surrounding a single hollow fiber could be monitored with increasing time. Using photomicroscopy and viable staining, areas of viable and nonviable cell growth were examined at various stages of development ranging from initial seeding to stable growth conditions. Cells were found to act as nucleation sites for the growth of individual colonies within the agarose. Profiles at stable growth conditions resulted in a thick cell mass near the surface of the fiber wall followed by cell colonies of decreasing size with increasing radial distance. A simplified theoretical model for cell growth was developed using mass balance equations for substrate penetration into individual cell colonies as well as away from the wall of a single fiber. The resulting profiles derived from theory were compared with experiments and found to be in good agreement for entering oxygen concentrations of 5% and 20%.


Extraskeletal intraspinal mesenchymal chondrosarcoma; 18F-FDG PET/CT finding.
Mesenchymal chondrosarcoma is a rare and aggressive form of chondrosarcoma. The extraskeletal intraspinal type is even rare among the mesenchymal chondrosarcoma cases. We presented a case of a 17-year-old boy pathologically diagnosed with intraspinal mesenchymal chondrosarcoma. MRI showed multiple intradural extramedullary masses with contrast enhancement, without the evidence of brain lesion. On F-FDG PET/CT, hypermetabolism was observed in the lesions matched with enhancement on spine MRI. The lesions were well differentiated from spinal cord. In the case of hypermetabolic lesion in intradural and extramedullary lesion of the spinal cord, mesenchymal chondrosarcoma should be considered for the differential diagnosis.


[Immunosorption of apolipoproteins B. Optimization of the method in an in vitro bench test].
The aim of the present study was to determine optimum conditions for preparation and use of immunoadsorbents for removal of apolipoprotein B from plasma. An in vitro study was carried out to optimize different chromatography parameters: linear flow rate, apo B quantity loaded, gel regeneration conditions. Specificity of removal of apo B, stability of antibody covalent linkage and possible multiple use of immunoadsorbents were assessed. No significant loss of adsorption capacity was observed after sterilization and storage of immunoadsorbents.


Sex and ethnic differences in the cardiovascular complications of type 2 diabetes.
Diabetes mellitus represents a global health concern affecting 463 million adults and is projected to rapidly rise to 700 million people by 2045. Amongst those with type 2 diabetes (T2D), there are recognised differences in the impact of the disease on different sex and ethnic groups. The relative risk of cardiovascular complications between individuals with and without T2D is higher in females than males. People of South Asian heritage are two to four times more likely to develop T2D than white people, but conversely not more likely to experience cardiovascular complications. Differences in the pathophysiological responses in these groups may identify potential areas for intervention beyond glycaemic control. In this review, we highlight key differences of diabetes-associated cardiovascular complications by sex and ethnic background, with a particular emphasis on South Asians. Evidence assessing therapeutic efficacy of new glucose lowering drugs in minority groups is limited and many major cardiovascular outcomes trials do not report ethnic specific data. Conversely, lifestyle intervention and bariatric surgery appear to have similar benefits regardless of sex and ethnic groups. We encourage future studies with better representation of women and ethnic minorities that will provide valuable data to allow better risk stratification and tailored prevention and management strategies to improve cardiovascular outcomes in T2D.


[Link between rheumatoid arthritis and cancer].
Because it is a systemic disorder, rheumatoid arthritis (RA) is known to predispose affected individuals to other organ manifestations as well as arthritic problems. The serious complications include pericarditis, pulmonary and cutaneous nodules, episcleritis, and rheumatoid vasculitis. Of late, a significantly increased incidence of lymphoma has also accumulated. The overall risk is about double than in the general population, but that in patients with the most severe arthritis is dramatically higher. Men with RA appear to have an extremely elevated risk of Hodgkin's disease, which has also been observed at a higher incidence among the children of affected patients. These lymphomas are not typically infected with EBV, though RA patients have a defective capacity to control systemic EBV infection. Increasing attention is being paid to the effect of RA treatments on development of lymphoma, and some patients with EBV-positive tumors who have been taking methotrexate have shown a positive response after just discontinuing this drug. More controversial is the question of whether anti-TNF alpha agents involve an increased risk of lymphoma; in light of the conflicting evidence this matter is still unresolved.