Renal hemodynamics and proteinuria in running and swimming beagle dogs.
In beagle dogs swimming, in contrast to treadmill running, was found to cause an increase in urine flow and urinary protein excretion. Renal blood flow measured by electromagnetic flow probes decreased by 13.0 +/- 4.9% when the treadmill gradient was 15% and arterial pressure was elevated by 11.6 +/- 4.9%. Immersion resulted in an immediate decrease in renal blood flow of 8.8 +/- 5.1% and a 24.6 +/- 6.9% increase in arterial pressure. Acid-base status indicated a respiratory alkalosis in all running experiments, no net change in five swimming experiments in which hyperventilation occurred, but a metabolic acidosis in eight swimming experiments without hyperventilation. During running there was a threefold increase in oxygen consumption. We conclude that swimming possibly induces more sympathetic nervous activity than treadmill running in dogs, while an alkalosis is consistently present during running, but acid-base response is variable during swimming.


Five new species of Ishiharella Dworakowska (Hemiptera: Cicadellidae: Typhlocybinae) with a key to worldwide species of the genus.
Detailed morphological descriptions and illustrations of five new species of the empoascine leafhopper genus Ishiharella Dworakowska (Typhlocybinae: Emposascini): I. dentidensa Yu & Yang, sp. nov., I. falcata Yu, Yang & Dietrich, sp. nov., I. hirsuta Yu, Yang & Dietrich, sp. nov., I. inflata Yu & Yang, sp. nov. and I. multiprotrusa Yu, Yang & Dietrich, sp. nov. are provided and a key to species of the genus is given.


Perfluoro-tert-butyl Group-Derived Capmatinib: Synthesis, Biological Evaluation and Its Application in 19 F Magnetic Resonance Imaging.
Capmatinib is an FDA-approved drug to treat metastatic non-small cell lung cancer with MET-exon 14 skipping. Herein, the perfluoro-tert-butyl group, which possesses nine chemically identical fluorine atoms, was introduced on Capmatinib to afford a targeted 19 F magnetic resonance imaging (MRI) probe, perfluoro-tert-butyl group-derived Capmatinib (9F-CAP). The 19 F MRI concentration limit was found to be 25 mM in FLASH sequence. Molecular docking simulation, surface plasmon resonance (SPR) (with a Kd of 40.7 μM), half-inhibitory concentration (with a IC50 of 168 nM), Annexin V, and cytotoxicity assays jointly demonstrated that the 9F-CAP targeted cMET protein specifically. Therefore, the targeted imaging capability of 9F-CAP is of great significance for the preoperative diagnosis of specific cancers.


Suppressing lossy-film-induced angular mismatches between reflectance and transmittance extrema: optimum optical designs of interlayers and AR coating for maximum transmittance into active layers of CIGS solar cells: erratum.
In my publication [Opt. Express, 22, A167-A178 (2014)], the vertical and horizontal axes on Fig. 6 were mislabeled. Here the corrected figure is presented.


Continuous haemofiltration maintains fluid balance and reduces haemodialysis requirement in acute renal failure.
We have used continuous arteriovenous haemofiltration with Amicon 20S Diafilters in combination with conventional haemodialysis as routine management for acute oliguric renal failure in fifteen patients. Haemofiltration provided a variable fluid output of up to eight litres daily, enabling unrestricted nutrition and reduced frequency of haemodialysis.


Dorsal-movement and ventral-form regions are functionally connected during visual-speech recognition.
Faces convey social information such as emotion and speech. Facial emotion processing is supported via interactions between dorsal-movement and ventral-form visual cortex regions. Here, we explored, for the first time, whether similar dorsal-ventral interactions (assessed via functional connectivity), might also exist for visual-speech processing. We then examined whether altered dorsal-ventral connectivity is observed in adults with high-functioning autism spectrum disorder (ASD), a disorder associated with impaired visual-speech recognition. We acquired functional magnetic resonance imaging (fMRI) data with concurrent eye tracking in pairwise matched control and ASD participants. In both groups, dorsal-movement regions in the visual motion area 5 (V5/MT) and the temporal visual speech area (TVSA) were functionally connected to ventral-form regions (i.e., the occipital face area [OFA] and the fusiform face area [FFA]) during the recognition of visual speech, in contrast to the recognition of face identity. Notably, parts of this functional connectivity were decreased in the ASD group compared to the controls (i.e., right V5/MT-right OFA, left TVSA-left FFA). The results confirmed our hypothesis that functional connectivity between dorsal-movement and ventral-form regions exists during visual-speech processing. Its partial dysfunction in ASD might contribute to difficulties in the recognition of dynamic face information relevant for successful face-to-face communication.


Ischemia alone is sufficient to induce TNF-alpha mRNA and peptide in the myocardium.
Over-production of tumor necrosis factor-alpha (TNF-alpha) following myocardial ischemia-reperfusion contributes to cardiac dysfunction, and anti-TNF-alpha has therapeutic potential for myocardial protection in cardiac surgery with obligatory ischemia. It remains unclear, however, whether myocardial TNF-alpha production occurs during ischemia and whether cardiac myocytes constitute a source of myocardial TNF-alpha. Ischemia alone has been shown to activate myocardial NF-kappaB. We hypothesized that ischemia alone is sufficient to induce myocardial TNF-alpha gene expression and peptide synthesis. We examined TNF-alpha production and NF-kappaB activation in the isolated rat heart subjected to global normothermic ischemia. Myocardial ischemia resulted in rapid IkappaB-alpha degradation and NF-kappaB activation. Immunofluorescence staining detected NF-KB intranuclear translocation primarily in myocardial interstitial cells. Ischemia alone induced a time-dependent increase in myocardial TNF-alpha. TNF-alpha peptide increased to 20.3+/-3.0 pg/mg after 25 min of ischemia (P < 0.05 vs 8.9+/-2.0 pg/mg in perfusion control). TNF-alpha was also localized to myocardial interstitial cells. Increased TNF-alpha peptide level correlated with TNF-alpha mRNA expression. We conclude that ischemia alone induces TNF-a gene expression and peptide synthesis in the myocardium that are associated with NF-kappaB activation. Non-myocytes constitute the main source of myocardial TNF-alpha following ischemia. The results suggest that therapeutic strategies attempting to decrease myocardial TNF-alpha production need to be applied before or in the early phase of ischemia.


Combination of nifedipine and subtherapeutic dose of cyclosporin additively suppresses mononuclear cells activation of patients with rheumatoid arthritis and normal individuals via Ca(2+) -calcineurin-nuclear factor of activated T cells pathway.
Abnormal Ca(2+) -mediated signalling contributes to the pathogenesis of rheumatoid arthritis (RA). However, the potential implication of calcium channel blocker in RA remained unknown. We hypothesized that nifedipine, an L-type calcium channel blocker, combined with a calcineurin inhibitor, could suppress T cell activation via targeting different level of the Ca(2+) signalling pathway. The percentage of activated T cells and the apoptotic rate of mononuclear cells (MNCs) was measured by flow cytometry. The MNC viability, cytokine production, cytosolic Ca(2+) level and activity of the nuclear factor of activated T cells (NFAT) were measured by enzyme-linked immunosorbent assay (ELISA). The NFAT-regulated gene expression, including interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF), was measured by real-time polymerase chain reaction (PCR). We found that the percentage of activated T cells in anti-CD3 + anti-CD28-activated MNC was higher in RA patients. High doses of nifedipine (50 µM) increased MNCs apoptosis, inhibited T cell activation and decreased T helper type 2 (Th1) (IFN-γ)/Th2 (IL-10) cytokine production in both groups. The Ca(2+) influx was lower in anti-CD3 + anti-CD28-activated MNC from RA patients than healthy volunteers and suppressed by nifedipine. When combined with a subtherapeutic dose (50 ng/ml) of cyclosporin, 1 µM nifedipine suppressed the percentage of activated T cells in both groups. Moreover, this combination suppressed more IFN-γ secretion and NFAT-regulated gene (GM-CSF and IFN-γ) expression in RA-MNCs than normal MNCs via decreasing the activity of NFATc1. In conclusion, we found that L-type Ca(2+) channel blockers and subtherapeutic doses of cyclosporin act additively to suppress the Ca(2+) -calcineurin-NFAT signalling pathway, leading to inhibition of T cell activity. We propose that this combination may become a potential treatment of RA.


An objective sperm cytotoxicity assay for male-specific antisera based on ATP levels of unlysed cells: application to assay of H-Y antigen.
We correlated the decrease in levels of ATP in spermatozoa with the extent of cytotoxicity elicited by antibodies against antigenic components on sperm. In the presence of concentrations of complement which did not cause cytolysis or influence the ATP content of epididymal sperm, addition of heat-in-activated sera from non-immunized mice, rats or rabbits did not result in sperm cytolysis or a fall in ATP content. In contrast, addition of rabbit anti-rat spermatocyte sera, which has previously been shown to react with rat spermatozoa (Tung, P.S. and Fritz, I.B. (1978) Dev. Biol. 64, 297-315), did cause sperm cytolysis and a decrease in ATP content. The titre of this antiserum for 50% cytolysis was between 1 : 128 and 1 : 256, as determined by the fall in ATP content. Using these criteria, we examined the cytotoxicity against sperm of different samples of anti H-Y sera. We examined the influence of monoclonal antibody against H-Y, mouse H-Y antisera and rat H-Y antisera raised in inbred females immunized with spleen cells from males of the same strains. In all cases, anti-H-Y lowered ATP levels and lysed sperm with a cytotoxic titre between 1 : 8 and 1 : 16. Measurements of the decrease in ATP content in sperm have been shown to provide an objective and reliable estimate of the percentage of spermatozoa lysed by H-Y antisera. Cytotoxic activity of H-Y antisera was removed by absorption with spleen cells from male mice but not by absorption with spleen cells from female mice.


Dynamic surface-enhanced Raman spectroscopy for the detection of acephate residue in rice by using gold nanorods modified with cysteamine and multivariant methods.
Dynamic surface-enhanced Raman spectroscopy (D-SERS) was employed for the rapid detection of acephate in rice with simply regulated gold nanorods. Gold nanorods modified with cysteamine were prepared to circumvent the weak affinity of acephate molecules to the gold surface for a gigantic and stable enhancement. D-SERS was adopted to measure spectra of acephate residue at a range of 100.2-0.5 mg/L in rice samples, and the low residue of 0.5 mg/L can be still detected. Multivariant methods in machine or deep learning were used to develop the regression models for the automatic analysis of acephate residue level. Partial least squares regression and principal component analysis obtained the optimal performance with the root-mean-square error (RMSE) of validation of 5.4776, coefficient of determination (R2) of validation of 0.9560, RMSE of prediction of 6.2845, and R2 of prediction of 0.9541. Thus, the proposed method provides accurate and sensitive detection for acephate in rice.


Instrumented indentation characterisation of mouth-guard materials.
The aim of the study was to investigate the mechanical properties and energy absorption behavior of mouth-guard materials. Interpretation of indentation force-displacement data has been used to determine these properties. An ultra micro-indentation system (UMIS) was used to determine near surface properties of mouth-guard materials with nanometer and micro-Newton displacement and force resolution. The measurement procedure was conducted with a small spherical steel indenter (R=500 microm), with impressions that were equally spaced (250 microm). Measurements of force-displacement response of surfaces at maximum forces of 10, 40 or 50 mN, 10 indentations were made at each of these forces. Tests were undertaken in two different modes to determine the mechanical properties, namely: (a) continuous load to the maximum force and then unload, (b) multiple loading and partially unloading sequence to the maximum load. The force-displacement results were analysed to determine the elastic modulus and contact pressure versus depth of penetration as well as the energy loss. Energy absorption for each material was determined from the ratio of the hysteresis energy loss to the total energy at maximum load and ranged from 10 to 24% among different mouth-guard materials. Energy absorption ratio, elastic modulus and contact pressure were significantly different between different materials with same thickness (FC, GC and C3) (p<0.01) and significantly different between materials with different thickness (C1 and C3) (p<0.01). The present approach provides a simple and efficient method to readily measure the elastic-plastic (hysteretic) response of mouth-guard materials. The indentation technique lends itself to investigate the influence of ageing, heat treatment, sterilisation, moisture etc in a simple systematic manner.


Advancement of nanoscience in development of conjugated drugs for enhanced disease prevention.
Nanoscience and nanotechnology is a recently emerging and rapid developing field of science and has also been explored in the fields of Biotechnology and Medicine. Nanoparticles are being used as tools for diagnostic purposes and as a medium for the delivery of therapeutic agents to the specific targeted sites under controlled conditions. The physicochemical properties of these nanoparticles give them the ability to treat various chronic human diseases by site specific drug delivery and to use in diagnosis, biosensing and bioimaging devices, and implants. According to the type of materials used nanoparticles can be classified as organic (micelles, liposomes, nanogels and dendrimers) and inorganic (including gold nanoparticles (GNPs), super-paramagnetic iron oxide nanomaterials (SPIONs), quantum dots (QDs), and paramagnetic lanthanide ions). Different types of nanoparticle are being used in conjugation with various types of biomoities (such as peptide, lipids, antibodies, nucleotides, plasmids, ligands and polysaccharides) to form nanoparticle-drug conjugates which has enhanced capacity of drug delivery at targeted sites and hence improved disease treatment and diagnosis. In this study, the summary of various types of nanoparticle-drug conjugates that are being used along with their mechanism and applications are included. In addition, the various nanoparticle-drug conjugates which are being used and which are under clinical studies along with their future opportunities and challenges are also discussed in this review.


Combined thoraco-laparoscopy for trans-diaphragmatic thoraco-abdominal enteric duplications.
During the last years, several thoracic and abdominal enteric duplications were resected in our institution by means of minimally invasive approaches [Rev Cir Infantil 1999;9(2):113-115]. Our last patient, however, had a giant thoraco-abdominal duodenal duplication, extending from the upper thoracic cavity to the pelvis, in a dumbbell fashion. Forty days after birth, a combined "thoraco-laparoscopy" was performed, achieving a complete resection of the cyst. The diaphragmatic defect was repaired as well. Recovery was uneventful. Based on this successful experience, we think that the thoraco-laparoscopic approach is suitable and reproducible for patients with these infrequent malformations, and even for patients with other kinds of thoraco-abdominal lesions. The purpose of this report was to describe the minimally invasive strategy used to approach the thorax and the abdomen in a single-stage procedure.


Analysis of viral microRNA expression by elephant endotheliotropic herpesvirus 1.
Elephant endotheliotropic herpesvirus 1 (EEHV1), a member of the Betaherpesvirinae subfamily, has recently emerged as an important viral pathogen of Asian elephants that can cause a severe, often fatal, hemorrhagic disease. EEHV1 does not replicate in culture and little is currently known about the molecular biology of this emerging pathogen, with the notable exception of its genomic DNA sequence. Here, we have used small RNA deep sequencing to determine whether EEHV1, like other human and murine betaherpesviruses, expresses viral microRNAs in infected tissues in vivo. Our data provide evidence supporting the existence of at least three novel viral microRNAs encoded by EEHV1 and one of these, miR-E3-5p, is shown to repress target mRNA expression. Moreover, miR-E3-5p expression was readily detectable in tissue samples derived from two infected elephants, including in whole blood. These data shed new light on the biology of EEHV1 and identify small RNAs that have the potential to be useful in the diagnosis of sub-clinical infections in captive Asian and African elephants.


Modification of the clinical and histopathologic expression of experimental allergic encephalomyelitis by the vasoactive amine antagonist cyproheptadine.
Experimental allergic encephalomyelitis (EAE) is an autoimmune syndrome that can be induced in Lewis rats by myelin basic protein (BP) in complete Freund's adjuvant (CFA). Rats that have recovered from a primary episode of EAE display paradoxical long-term resistance to EAE reinduction by BP-CFA. Previous observations indicated, however, that clinical disease could be reinduced in convalescent rats by a concomitant secondary challenge with BP-CFA + Bordetella pertussis extract (PERT). Vascular permeability changes in the central nervous system (CNS) paralleled disease reinduction. To further probe the relationship between disease reinduction and vascular permeability, convalescent rats were treated with the vasoactive amine antagonist cyproheptadine (CYP) prior to a secondary challenge with BP-CFA + PERT. Data presented here indicate that CYP treatment results in substantial protection of convalescent rats from clinical disease reinduction by BP-CFA + PERT. CYP did not, however, prevent the development of new CNS lesions. CYP therapy also altered the clinical course of EAE induced by a primary injection of BP-CFA + PERT. In these rats, there was a delay in the onset of clinical signs as well as in the appearance of CNS lesions. Nevertheless, both CYP-treated and untreated naive rats challenged with BP-CFA + PERT eventually developed severe and usually lethal EAE. The effect of CYP on EAE induced in naive rats without including PERT in the sensitization protocol was also evaluated. In contrast to the mitigating effect of CYP on EAE induced or reinduced by BP-CFA + PERT, CYP treatment did not affect the clinical course or the development of CNS lesions in rats challenged with BP-CFA alone. Likewise, the passive transfer of EAE, mediated by mitogen-stimulated cells obtained from BP-CFA-sensitized donors, was not affected by CYP treatment. Collectively, these data indicate that CYP therapy altered the expression of EAE induced by regimens that included PERT, but did not affect EAE induced without PERT. In view of the opposing effects of PERT and CYP on vascular permeability, these data are consistent with the hypothesis that alterations in vascular permeability may play a crucial role in controlling the expression of autoimmune neurological diseases.


Hormone signaling in plant development.
Hormone signaling plays diverse and critical roles during plant development. In particular, hormone interactions regulate meristem function and therefore control formation of all organs in the plant. Recent advances have dissected commonalities and differences in the interaction of auxin and cytokinin in the regulation of shoot and root apical meristem function. In addition, brassinosteroid hormones have recently been discovered to regulate root apical meristem size. Further insights have also been made into our understanding of the mechanism of crosstalk among auxin, cytokinin, and strigolactone in axillary meristems.


Movers and shakers: maize transposons as tools for analyzing other plant genomes.
Transposons have been successfully exploited as insertional mutagens for the efficient identification and isolation of genes (transposon tagging) in many organisms. Plants are no exception. The maize Activator and Suppressor-mutator transposons function when transferred into heterologous plant species, and many different gene tagging systems have been developed. These systems have recently been used to clone novel and important genes, including disease resistance loci from Nicotiana tabacum, tomato and flax.


[Clinical evaluation of pulpotomy in the treatment of deciduous teeth with deep dentine caries].
To study the curative effect of pulpotomy in the treatment of deciduous teeth with deep caries. 45 deciduous molars with deep caries from 3 8 years old children were selected at random. Pulpotomy was performed on these treated teeth. Clinical examination and X-ray films for the treated teeth were taken to follow up all the teeth at 6 months, one year and two years respectively after treatment. At one year after treatment, 45 cases were followed up, the rate of success in clinical examination and in X-ray photographs both were 100%. While at two years after treatment, 42 cases were followed up and 3 cases were lost, the rate of success in clinical examination was 95% and the rate of success in X-ray photographs was 88%. The reasons of the failure were internal absorption and pulpitis followed by fracture and exfoliation of the obturators in the treated teeth. Pulpotomy in deciduous teeth with deep caries was a reliable and effective method. It is necessary to follow up the treated teeth by X-ray at regular intervals after treatment.


Relationship of herpes simplex virus type-2 antibodies and squamous dysplasia to cervical carcinoma in situ.
Serum specimens from 75 women with cervical carcinoma in situ, 84 with squamous dysplasia, and 132 controls, who had previously been interviewed and tested for complement fixing antibodies against a number of organisms, were analyzed for HSV-2 antibodies. Carcinoma in situ and severe dysplasia were associated with HSV-2 antibodies. Mild dysplasia was related to evidence of prior infection by Trichomonas vaginalis, adenoviruses, and Mycoplasma pneumoniae, plus a history of vaginal discharge. Severe dysplasia was less strongly related to these variables. The relative risk of dysplasia increased with the number of different pathogens by which a woman had been infected. It is concluded that HSV-2 may be a cause of carcinoma in situ; that much dysplasia is a nonspecific reaction of the cervical epithelium to chronic inflammation; and that dysplastic lesions that are caused by HSV-2, and hence may be a precursor to carcinoma in situ, tend to be distinguished by their severity.


Surgical treatment of esophageal varices caused by an arteriovenous fistula between an artery of the thyroid gland and the submucosal venous network of the esophageal wall.
We report a case of esophageal varices caused by an arteriovenous fistula between an artery of the thyroid gland and the submucosal venous network of the esophageal wall. The fistula developed in a 51-year-old woman 24 years after she received subtotal thyroidectomy to treat Graves' disease. At the same time, gastrointestinal endoscopy revealed the presence of uncommon esophageal varices that were limited to the cervical and upper thoracic esophagus. Angiography confirmed the presence of both an arteriovenous fistula of the peripheral residual thyroid gland and the esophageal varices, after which we successfully treated the varices by surgical resection of the fistula.


Ultrasound-triggered biomimetic ultrashort peptide nanofiber hydrogels promote bone regeneration by modulating macrophage and the osteogenic immune microenvironment.
The immune microenvironment plays a vital role in bone defect repair. To create an immune microenvironment that promotes osteogenesis, researchers are exploring ways to enhance the differentiation of M2-type macrophages. Functional peptides have been discovered to effectively improve this process, but they are limited by low efficiency and rapid degradation in vivo. To overcome these issues, peptide with both M2 regulatory and self-assembly modules was designed as a building block to construct an ultrasound-responsive nanofiber hydrogel. These nanofibers can be released from hydrogel in a time-dependent manner upon ultrasound stimulation, activating mitochondrial glycolytic metabolism and the tricarboxylic acid cycle, inhibiting reactive oxygen species production and enhancing M2 macrophage polarization. The hydrogel exhibits advanced therapeutic potential for bone regeneration by triggering M2 macrophages to secrete BMP-2 and IGF-I, accelerating the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts. Thus, modularly designed biomimetic ultrashort peptide nanofiber hydrogels provide a novel strategy to rebuild osteogenic immune microenvironments for bone repair.


Identification of candidate sequences that determine virulence in Coxsackievirus B4.
We have previously shown that a major determinant of virulence for coxsackievirus B4 mapped to the 5' end of the viral genome. Comparison of the corresponding cDNA sequences of a virulent and a non-virulent virus has allowed the identification of candidate determinants of virulence in the 5' untranslated region and the capsid proteins VP1, VP2 and VP4. Thirteen nucleotide substitutions were observed in a region spanning 3298 nucleotides. Four mutations were detected in the non-coding region. Of the remaining nine mutations, four were silent while five resulted in amino acid substitutions in VP1, VP2 and VP4. The amino acid substitutions in the virulent virus were analyzed in relation to the three-dimensional structures of the capsid proteins of poliovirus. Two substitutions mapped to the amino termini of VP1 and VP4. Of the two substitutions observed in VP2, one mapped to the large loop that connects beta strand E with the radial helix on the back surface of the eight-stranded antiparallel beta barrel while the other mapped to beta strand G. One amino acid substitution in VP1 mapped to the loop connecting beta strands D and E at a site close to a major determinant of attenuation in poliovirus type 2.


Frequency Range Measures in Carnatic Singers.
Frequency range measures in singers reflect their physiological capacity, vocal flexibility, training effects, strengths, and limitations in singing. Since this information is vital for pedagogic and clinical purposes, this study aimed to measure the frequency range in Carnatic singers while singing different aspects of the vocal music. Practice task (gliding from lowest to highest note) and performance task (singing a song with vocal ornaments) were recorded from 55 trained Carnatic singers (40 females and 15 males). The auditorily verified portions of various vocal ornaments in Carnatic singing (such as aalapanai, pallavi, anupallavi, charanam, and niraval) were coded as separate tokens. A total of 385 tokens were analyzed using PRAAT software for estimating frequency range in semitones during practice task (SFRprac) and performance task (SFRperf). Descriptive, ANOVA, Tukey HSD, independent t, and Mann-Whitney U were used for statistical analysis. SFRprac was higher than SFRperf in Carnatic singers. During practice, singers explored their physiological range to improve their vocal ability. However, during performance they tend to maintain a comfortable singing range to have a flawless rendition. Aalapanai (most creative portion) had the highest frequency range (females: 22.96 ST, males: 24.57 ST) than other types of vocal ornaments in performance signing. Practice frequency range (SFRprac) and performance frequency range (SFRperf) were not statistically different across male and female singers. This study described the frequency range measures in various aspects and nuances of Carnatic singing. Its clinical and pedagogic importance are discussed.


Calcium-activated chloride channels in müller cells acutely isolated from tiger salamander retina.
Ca(2+)-activated chloride channels were identified with whole-cell patch-clamp recording techniques in salamander retinal Müller cells. Cl(Ca) channels were activated by membrane depolarizations that elicited Ca2+ influx or the application of the Ca2+ ionophore, ionomycin. The Ca channel blocker, Cd2+, abolished the Cl(Ca) channel tail currents. Increasing the duration of the depolarizing pulse resulted in enhancement of the Cl(Ca) channel tail current. Repetitive depolarizations with rapid pulses to +20 mV produced a buildup of I(Cl(Ca)), which reversed at 0 mV in symmetrical [Cl-] and at -40 mV when intracellular [Cl-] was reduced to 10% of the external concentration. I(Cl(Ca)) was blocked by the Cl channel blocker niflumic acid, while niflumic acid had no effect on voltage-gated Ca channels. These results offer the first demonstration of Cl(Ca) channels in a nonastrocytic glial cell and expand our understanding of the functional capacities of retinal glial cells.


Comparative studies on lipid metabolism in various salt transporting organs of the European eel (Anguilla anguilla). Mono-unsaturated phosphatidylethanolamine as a key substance.
1. Incorporation in vivo into tissue lipids of (1-14C)acetate added to the water in the incubation tank showed the same relative distribution pattern of 14C-activity among various phospholipids in the gills, the esophagus and the intestine, when the eel was incubated in sea-water; in fresh water this pattern was found only in the intestine, while both the gills and the esophagus showed a relative excess of 14C-label in phosphatidylethanolamine (PE). 2. Similar studies with (32P)phosphate also showed a relative excess of (32P)PE in both the gills and esophagus in fresh water compared to sea-water, and no such difference in the intestine. 3. As long as the labelled precursors were added to the water in the incubation tank both (14C)PE and (32P)PE were not identical to unlabelled PE on thin-layer chromatograms, and the 14C-labelled lipids contained predominantly C16:1 and C18:1 fatty acids. 4. However, when the two precursors were injected directly into the eel there was no longer any marked difference between the distribution patterns of radioactivity among gill phospholipids in fresh water and sea-water; there was no longer any difference between labelled and unlabelled PE on thin-layer chromatograms, and the 14C-labelled gill lipids contained predominantly C16:0 and C18:0 fatty acids. 5. The corresponding liver lipids were affected neither by a change in environmental salinity nor in precursor application.


Gender Dysphoria in a 62-Year-Old Genetic Female With Congenital Adrenal Hyperplasia.
We report a case of gender dysphoria (GD) in a 62-year-old genetic female patient, raising the pros and cons of performing corrective surgery later in life. This 46,XX DSD patient was registered and reared as a girl; CAH was diagnosed late in childhood. Poor adherence to treatment and lack of proper psychological management contributed to evident GD. Living for years as a male, the patient applied for a legitimate male identification document in his late 50s; thereafter, he requested a sex-reassignment surgery "to disguise his female body upon his death." We informed the patient and family about surgery hazards, while analytical therapy allowed the group to evaluate the actual wish for surgery. When the wish was brought up, the role of death urged the group to rethink the course of treatment. During the process, it became clear that the patient's desire for surgery, more than a wish for changing the genitalia, expressed an impulse related to issues of endorsement and acceptance of his male identity. This report raises interesting questions about sexuality in a social context and prompts the idea that sexuality is broader than sex itself, raising new questions on the psychological risks faced when considering a body change after years of living with a disorder of sex development.


From genetic associations to functional studies in multiple sclerosis.
Genetic screens steadily reveal more loci that show robust associations to complex human diseases, including multiple sclerosis (MS). Although some of the identified genetic variants are easily interpreted into a biological function, most of the genetic associations are frequently challenging to interpret. Underlying these difficulties is the fact that chip-based assays typically detect single nucleotide polymorphisms (SNPs) representative of a stretch of DNA containing many genomic variants in linkage disequilibrium. Furthermore, a large proportion of the SNPs with strongest association to MS are located in regions of the DNA that do not directly code for proteins. Here we discuss challenges faced by MS researchers to follow up the large-scale genetic screens that have been published over the past years in search of functional consequences of the identified MS-associated SNPs. We discuss experimental design, tools and methods that may provide the much-needed biological insights in both disease etiology and disease manifestations.


Activity patterns of the common vole, Microtus arvalis - Automatic recording of behaviour in an enclosure.
The activity behaviour of the common vole, Microtus arvalis was studied in an enclosure during a one-year cycle. The number of voles varied between 2 and 25 specimens. Emergence from burrows, running through pathways and visits at a feeding site were automatically recorded by passage counters which we developed for use in the field. The results can be summarized as follows: 1. The voles were day-active throughout the year - no change of the activity phase was observed. A significant proportion of activity at daytime was due to foraging trips to the feeding site, but the voles were active in the pathway-system, too. At night only a few short visits to the feeding site were recorded and almost no activity in the pathways was detectable. 2. In addition to the day-activity recorded by the passage counters we observed other activities like burrowing and storage almost exclusively at daytime, especially at dawn and dusk. 3. During daylight hours the voles were active on the surface in a synchronized short-term activity rhythm of about two hours. 4. This clear-cut activity pattern was changed for two reasons only: by juveniles beginning to venture from their burrows and by wet and cold weather conditions. 5. The activity pattern of voles kept in a cage within the enclosure was in accordance with previous investigations - the caged voles exhibited a distinct short-term rhythm of feeding bouts during daylight hours and showed extensive wheel-running activity at night. Thus they had maximum locomotor activity at a time, during which the voles in the enclosure were only occasionally active on the surface. Including previous results we assume from our investigations that voles are primarily day-active organisms. Although the short-term rhythm is closely related to metabolic demands there is evidence that its basic function is not to forage but to emerge for regular control of the territory. The hypothesis is put forward that short-term activity on the surface, which is synchronized with the activity of the population, might be advantageous to maintain territories. In continuation it is suggested that specimen which defend their territories effectively are most likely to survive at high densities in population cycles. Therefore the complex temporal structure of the voles' activity pattern might be favoured by selection.


Vertigo and dizziness in children: When to consider a neurological cause.
Vertigo is common in childhood and adolescence. Although children and adults share common causes of vertigo, epidemiology changes with aging. For instance, ischemic stroke is less frequent in childhood, whereas audiovestibular disorders, such as vestibular neuritis and the migraine equivalent, are the leading causes of vertigo. However, even if severe causes of vertigo are rare, clinicians must not miss them. In this review, we discuss the neurological causes of central vertigo in children. The diagnostic approaches reviewed here are focused on the search for signs of severity, such as an abrupt onset, infectious context, or intracranial hypertension, which may subsequently require brain imaging.


[Guidelines on the appropriate use of animal models for developing therapies in multiple sclerosis].
The advance in the achievement of effective therapies for multiple sclerosis (MS), the definition of appropriate therapeutic windows and to establish better diagnostic and prognostic biomarkers have become a challenging task for both researchers and clinicians. Some pitfalls in clinical trials might be related to lack of adequacy of the preclinical studies in MS experimental animal models. To standardize the methodological protocols of experimental models by developing a set of guidelines for preclinical studies by groups of experts from REEM (Spanish Network for MS). A guide with recommendations for the application of MS models including a detailed assessment of appropriate experimental models taking into account the objective of the study that has been presented. Standards and quality criteria necessary in a preclinical study have been included. Standardized animal models of MS are essential to increase the success of the preclinical findings in order to transfer them to the clinical practice.


Retarded Onchocerca volvulus L1 to L3 larval development in the Simulium damnosum vector after anti-wolbachial treatment of the human host.
The human parasite Onchocerca volvulus harbours Wolbachia endosymbionts essential for worm embryogenesis, larval development and adult survival. In this study, the development of Wolbachia-depleted microfilariae (first stage larvae) to infective third stage larvae (L3) in the insect vector Simulium damnosum was analysed. Infected volunteers in Cameroon were randomly and blindly allocated into doxycycline (200 mg/day for 6 weeks) or placebo treatment groups. After treatment, blackflies were allowed to take a blood meal on the volunteers, captured and dissected for larval counting and DNA extraction for quantitative real-time PCR analysis. PCR results showed a clear reduction in Wolbachia DNA after doxycycline treatment in microfilariae from human skin biopsies with > 50% reduction at one month post-treatment, eventually reaching a reduction of > 80%. Larval stages recovered from the insect vector had similar levels of reduction of endosymbiotic bacteria. Larval recoveries were analysed longitudinally after treatment to follow the kinetics of larval development. Beginning at three months post-treatment, significantly fewer L3 were seen in the blackflies that had fed on doxycycline treated volunteers. Concomitant with this, the proportion of second stage larvae (L2) was significantly increased in this group. Doxycycline treatment and the resulting decline of Wolbachia endobacteria from the microfilaria resulted in retarded development of larvae in the insect vector. Thus, anti-wolbachial treatment could have an additive effect for interrupting transmission by reducing the number of L3 that can be transmitted by blackflies.


A New Sustainable Multistep Catalytic Process from Benzene to Caprolactam: Amination, Hydroximation and Beckmann Rearrangement Promoted and Catalyzed by Trifluoroacetic Acid.
Here we report some results on a 3 steps benzene caprolactam process via amination, aniline Hydroxymation and Beckmann rearrangement. The amination proceeds with hydroxylamine trifluoroacetate, with 97% of conversion and selectivity of 90%, catalyzed by V compounds. We achieve 98% of conversion and 95% of selectivity in the hydroxymation of aniline in the presence of hydroxylamine trifluoroacetate, sulfonic resin and Pd/C. While in the absence of the resin, hydrogenation of hydroxylamine trifluoroacetate occurs readily to the ammonium salt. The reaction occurs likely by the exchanged hydroxylamine and the aniline reduction intermediate. The use of hydroxylamine trifluoroacetate, instead of the chloride, favors the sustainability of the process by avoiding the ammonium chloride formation. The absence of salt except those derived from the trifluoroacetic acid allows a complete reuse of the trifluoroacetic acid and the only byproduct is ammonium nitrate obtained by resin regeneration. Beckmann rearrangement of the so produced cyclohexanone oxime occurs easily after diethyl ether evaporation and additions of a solution trifluoroacetic acid acetonitrile in high yield and selectivity. New three steps caprolactam process via benzene amination and aniline hydrogenation. The online version contains supplementary material available at 10.1007/s10562-022-04207-9.


Cilastatin does not alter superoxide dismutase activity.
Cilastatin inhibits dehydropeptidase-I, a zinc metaloenzyme that metabolizes imipenem. Because zinc stabilizes the mammalian superoxide dismutase, we postulated that cilastatin would also inhibit the dismutase. Cilastatin concentrations at levels threefold higher than those expected in urine, however, did not inhibit the superoxide dismutase activity.


Recipe for health: impacting diabetes in African Americans through faith-based edcuation.
The Recipe For Health educational initiative was designed to increase knowledge of diabetes prevention and management for African Americans (AAs) in rural Alabama. By providing culturally competent information, training, and skill-building activities to lay leaders in faith-based settings who teach church members, Recipe For Health can create a ripple effect of diabetes knowledge that could lower disease complications in the AA population.


Functional avoidance of lung in plan optimization with an aperture-based inverse planning system.
To implement SPECT-based optimization in an anatomy-based aperture inverse planning system for the functional avoidance of lung in thoracic irradiation. SPECT information has been introduced as a voxel-by-voxel modulation of lung importance factors proportionally to the local perfusion count. Fifteen cases of lung cancer have been retrospectively analyzed by generating angle-optimized non-coplanar plans, comparing a purely anatomical approach and our functional approach. Planning target volume coverage and lung sparing have been compared. Statistical significance was assessed by a Wilcoxon matched pairs test. For similar target coverage, perfusion-weighted volume receiving 10 Gy was reduced by a median of 2.2% (p=0.022) and mean perfusion-weighted lung dose, by a median of 0.9 Gy (p=0.001). A separate analysis of patients with localized or non-uniform hypoperfusion could not show which would benefit more from SPECT-based treatment planning. Redirection of dose sometimes created overdosage regions in the target volume. Plans consisted of a similar number of segments and monitor units. Angle optimization and SPECT-based modulation of importance factors allowed for functional avoidance of the lung while preserving target coverage. The technique could be also applied to implement PET-based modulation inside the target volume, leading to a safer dose escalation.


CPD of the future: a partnership between quality improvement and competency-based education.
Many of those involved in continuing professional development (CPD) over the past 10 years have engaged in discussions about its goals and activities. Whereas in the past CPD was viewed as an education intervention directed towards the medical expert role, recent research highlights the need to expand the scope of CPD and to promote its more explicit role in improving patient care and health outcomes. Recent developments in quality improvement (QI) and competency-based medical education (CBME), guided by appropriate theories of learning and change, can shed light on how the field might best advance. This paper describes principles of QI and CBME and how they might contribute to CPD, explores theoretical perspectives that inform such an integration and suggests a future model of CPD. Continuing professional development seeks to improve patient outcomes by increasing physician knowledge and skills and changing behaviours, whereas QI takes the approach of system and process change. Combining the strengths of a CPD approach with strategies known to be effective from the field of QI has the potential to harmonise the contributions of each, and thereby to lead to better patient outcomes. Similarly, competency-based CPD is envisioned to place health needs and patient outcomes at the centre of a CPD system that will be guided by a set of competencies to enhance the quality of practice and the safety of the health system. We propose that the future CPD system should adhere to the following principles: it should be grounded in the everyday workplace, integrated into the health care system, oriented to patient outcomes, guided by multiple sources of performance and outcome data, and team-based; it should employ the principles and strategies of QI, and should be taken on as a collective responsibility by physicians, CPD provider organisations, regulators and the health system.


Spectral properties and reactivity towards azide of Dicrocoelium dendriticum met-hemoglobin.
The spectroscopic properties of Dicrocoelium dendriticum met-hemoglobin, investigated between pH 3.8 and 10.5, display two proton-induced transitions with apparent pK values of 8.1 and 4.7. The spectral changes, over the pH region 6.5 to 10.5, correspond to the high to low spin transition usually observed in ferric hemoproteins. The relaxation time (tau = 3.2 ms at the pK) associated with this transition is closely similar to that observed in Aplysia limacina met-myoglobin, but approximately 1000-fold slower than that of sperm whale met-myoglobin. The spectral changes associated with the more acid transition are in the opposite direction and have not been resolved by the temperature jump method. The rate constants for the reaction of azide with Dicrocoelium dendriticum met-hemoglobin were measured between pH 3.8 and 6.7 by the temperature jump method. Two kinetic schemes, both consistent with the pH dependence of the apparent rate constant for binding of azide, were identified. No objective way of discriminating between the two models is available. However, one of them is amenable to a physical interpretation based on a comparison with the structural, kinetic and spectral properties of other monomeric hemoproteins.


Production of oyster mushroom (Pleurotus ostreatus) from some waste lignocellulosic materials and FTIR characterization of structural changes.
In this study, oyster (Pleurotus ostreatus) mushroom was cultivated from hazelnut branches (HB) (Corylus avellana L.), hazelnut husk (HH), wheat straw (WS), rice husk (RH) and spent coffee grounds (CG). Hazelnut branch waste was used for the first time in oyster mushroom cultivation. In the study, mushrooms were grown by preparing composts from 100 to 50% mixtures of each waste type. Yield, biological activity, spawn run time, total harvesting time and mushroom quality characteristics were determined from harvested mushroom caps. In addition, chemical analysis of lignocellulosic materials (extractive contents, holocellulose, α-cellulose, lignin and ash contents) were carried out as a result of mushroom production and their changes according to their initial amounts were examined. In addition, the changes in the structure of waste lignocellulosic materials were characterized by FTIR analysis. As a result of the study, 172 g/kg yield was found in wheat straw used as a control sample, while it was found as 255 g/kg in hazelnut branch pruning waste. The highest spawn run time (45 days) was determined in the compost prepared from the mixture of hazelnut husk and spent coffee ground wastes. This study showed that HB wastes can be used for the cultivation of oyster mushroom (P. ostreatus). After mushroom cultivation processes, holocelulose and α-cellulose content rates decreased while ash contents increased. FTIR spectroscopy indicated that significant changes occurred in the wavelengths regarding cellulose, hemicellulose and lignin components. Most significant changes occurred in 1735, 1625, 1510, 1322 and 1230 wavelengths.


Harnessing the Microbiome for Pancreatic Cancer Immunotherapy.
Late-stage pancreatic cancer harbors a fibrotic and immune-excluded tumor microenvironment that impedes immunotherapy success. A key to unlocking pancreatic cancer immunotherapy may be treating early-stage pancreatic cancer, when peripancreatic inflammation promoted by the microbiome potentiates oncogenic signaling and suppresses innate and adaptive immunity. Hence, understanding the role of microbiota in pancreatic cancer initiation, progression, and immunosuppression is crucial. We propose that not only are microbiota targets for immunomodulation in this disease, but also that microbiome profiling has a potential role in pancreatic cancer screening. Furthermore, combining microbiome profiling with liquid and tissue biopsy may validate the early pancreatic cancer treatment approach of microbiome modulation and immunotherapy.


Laparoscopic simultaneous resection of bilateral giant primary mature retroperitoneal teratoma of the adrenal region: A case report.
Giant mature retroperitoneal teratoma of the adrenal region is quite rare in adults. In most cases, open adrenalectomy is required to ensure complete resection. We describe a case of bilateral giant primary mature cystic teratoma in the region of both adrenal glands in a 22-year-old female patient. A 22-year-old female patient was admitted to our hospital with no complain after detecting to have 2 giant well circumscribed masses in a routine investigation. She was diagnosed with bilateral giant primary mature retroperitoneal teratoma of the adrenal region. The patient underwent en bloc excision of the mass through laparoscopic simultaneous resection. We carefully separated and retained most of the adrenal tissue on both sides during surgery. Pathology reported mature teratomas. Eleven days after operation, the patient made uneventful recovery and left the hospital without any complication. Preoperative imaging and histologic analysis confirmed mature retroperitoneal teratomas. It is feasible to treat such giant benign tumors by laparoscopic simultaneous resection.


Nonconcomitant metachronous triple mesenchymal benign tumors in a child: Report of a case.
Two or more primary neoplastic lesions are very rare in children. We report a child who is first of its kind in English literature who presented with noncontiguous metachronous lipoma, chondroma, and fibrolipoma.


Corticofugal feedback influences the generation of length tuning in the visual pathway.
In the feline visual system, neurons exhibiting sensitivity to the length of a moving contour were first observed in the cortex and described as 'hypercomplex cells'. In these cells an increase in stimulus length beyond an optimal value leads to a rapid decline in response. This decline has been attributed to an intracortical inhibitory input which may be driven by layer VI cells with very long receptive fields. It is now clear, however, that cells in the dorsal lateral geniculate nucleus (dLGN), exhibit a degree of length tuning similar to that of cortical 'hypercomplex cells', suggesting that this response property could be generated subcortically. Alternatively, as the dLGN receives a massive corticofugal projection from layer VI cells in the visual cortex, it is possible that this input has a function in generating length tuning in the dLGN. We have investigated this issue by comparing the length tuning of dLGN cells with and without corticofugal feedback. The data show that corticofugal feedback makes a highly significant contribution to the length tuning of dLGN cells. This raises the possibility that length tuning is an emergent property of the geniculo-cortical loop.


The role of ubiquitin-specific peptidases in glioma progression.
The balance between ubiquitination and deubiquitination is crucial for protein stability, function and location under physiological conditions. Dysregulation of E1/E2/E3 ligases or deubiquitinases (DUBs) results in malfunction of the ubiquitin system and is involved in many diseases. Increasing reports have indicated that ubiquitin-specific peptidases (USPs) play a part in the progression of many kinds of cancers and could be good targets for anticancer treatment. Glioma is the most common malignant tumor in the central nervous system. Clinical treatment for high-grade glioma is unsatisfactory thus far. Multiple USPs are dysregulated in glioma and have the potential to be therapeutic targets. In this review, we collected studies on the roles of USPs in glioma progression and summarized the mechanisms of USPs in glioma tumorigenesis, malignancy and chemoradiotherapy resistance.


The influence of a false-positive mammogram on a woman's subsequent behaviour for detecting breast cancer.
The aim was to investigate the influence of undergoing further examinations due to a false-positive mammogram on women's re-attendance at the next scheduled screening and their frequency of breast self-examination (BSE). Study participants included 517 women (62% response) recalled due to findings on screening mammograms indicating possible malignancies, and a matched control group of 285 women (68% response) with normal mammograms. Participants completed five and three questionnaires, respectively, during the 2 years following screening participation. While the groups did not differ significantly in screening re-attendance, women recalled due to false-positive mammograms reported significantly higher levels of anxiety related to the next screening than did women with normal mammograms. At the 1-year assessment, women with false-positive mammograms reported a significantly higher frequency of BSE than did women with normal mammograms. The present results indicate that being recalled due to a false-positive mammogram does not seem to negatively affect screening re-attendance, and may have a positive impact on BSE.


Class Anxiety in Secondary Education: Exploring Structural Relations with Perceived Control, Engagement, Disaffection, and Performance.
The aim of this study was to assess the relationships between class-related anxiety with perceived control, teacher-reported behavioral engagement, behavioral disaffection, and academic performance. Participants were 355 compulsory secondary students (9th and 10th grades; Mean age = 15.2 years; SD = 1.8 years). Structural equation models revealed performance was predicted by perceived control, anxiety, disaffection, and engagement. Perceived control predicted anxiety, disaffection, and engagement. Anxiety predicted disaffection and engagement, and partially mediated the effects from control on disaffection (β = -.277, p < .005; CI = -.378, -.197) and engagement (β = .170, p < .002; CI = .103 .258). The negative association between anxiety and performance was mediated by engagement and disaffection (β = -.295, p < .002; CI = -.439, -.182). Anxiety, engagement, and disaffection mediated the effects of control on performance (β = .352, p < .003; CI = .279, .440). The implications of these results are discussed in the light of current theory and educational interventions.


Association of regular use of ibuprofen and paracetamol, genetic susceptibility, and new-onset dementia in the older population.
Although the possible efficacy and adverse effects of paracetamol and ibuprofen on dementia are of global clinical and public health importance, to date, the relationship of the use of paracetamol and ibuprofen with incident dementia remains uncertain. We aimed to assess the prospective association of regular use of ibuprofen and paracetamol with new-onset dementia in an older population. This study included 212,968 participants from the UK Biobank, aged ≥60 years, with available data of ibuprofen, paracetamol use and without dementia at baseline. The primary outcome was new-onset all-cause dementia. The secondary outcomes included new-onset Alzheimer's disease and new-onset vascular dementia. During a median follow-up of 12.3 years, 6407 (3.0%) participants developed new-onset all-cause dementia. Participants who regularly used paracetamol had a significantly higher risk of new-onset all-cause dementia (adjusted HR, 1.18; 95%CI: 1.10-1.26), compared with non-users. However, there was no significant association between regular use of ibuprofen and new-onset all-cause dementia (users vs. non-users; adjusted HR, 1.06; 95%CI: 0.97-1.16). Furthermore, APOE ε4 dosage and genetic risk scores (GRS) of Alzheimer's disease calculated by 25 single nucleotide polymorphisms did not significantly modify the relationship of regular use of paracetamol and ibuprofen with new-onset all-cause dementia (Both P-interactions >0.05). Similar results were found in the propensity score analysis. Similar findings were also observed for new-onset Alzheimer's disease and new-onset vascular dementia. Regular use of paracetamol, but not ibuprofen, was associated with a significantly higher risk of new-onset dementia in the old population, regardless of genetic risks of dementia.


Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers.
Rotator cuff (RC) attaches to humerus across a triphasic yet continuous tissue zones (bone-fibrocartilage-tendon), termed "enthesis". Regrettably, rapid and functional enthesis regeneration is challenging after RC tear. The existing grafts bioengineered for RC repair are insufficient, as they were engineered by a scaffold that did not mimic normal enthesis in morphology, composition, and tensile property, meanwhile cannot simultaneously stimulate the formation of bone-fibrocartilage-tendon tissues. Herein, an optimized decellularization approach based on a vacuum aspiration device (VAD) was developed to fabricate a book-shaped decellularized enthesis matrix (O-BDEM). Then, three recombinant growth factors (CBP-GFs) capable of binding collagen were synthesized by fusing a collagen-binding peptide (CBP) into the N-terminal of BMP-2, TGF-β3, or GDF-7, and zone-specifically tethered to the collagen of O-BDEM to fabricate a novel scaffold (CBP-GFs/O-BDEM) satisfying the above-mentioned requirements. After ensuring the low immunogenicity of CBP-GFs/O-BDEM by a novel single-cell mass cytometry in a mouse model, we interleaved urine-derived stem cell-sheets into this CBP-GFs/O-BDEM to bioengineer an enthesis-like graft. Its high-performance on regenerating enthesis was determined in a canine model. These findings indicate this CBP-GFs/O-BDEM may be an excellent scaffold for constructing enthesis-like graft to patch large/massive RC tears, and provide breakthroughs in fabricating graded interfacial tissue.


Botanicals as medicinal food and their effects on drug metabolizing enzymes.
Botanicals fall under different regulations in different countries and are mostly consumed without the consultation of the healthcare professional. Over the last decade, utilization of herbal therapies has been extensively documented. The findings indicate the possibility of potential herb-drug interactions due to the concomitant administration of herbal extracts and prescription/over-the-counter drugs. Simultaneously, with the increasing public awareness and search for safer herbal remedies, the study on herbal-drug interactions has gained momentum through the study of drug metabolizing enzymes. Cytochrome P450 (CYP) inhibition or induction is probably the most common mechanism for the pharmacokinetic interactions of herbs and drugs. Any inhibition of CYP enzymes by herbal extracts may result in enhanced plasma and tissue concentration of drugs, leading to toxicity, while induction results in reduced drug concentration leading to decreased drug efficacy and treatment failure. Considering the rapidly growing herbal markets, these types of clinical interactions remain under-reported and unclear. With the increasing consumption of herbal extracts along with prescription medicines, the safety of herbs has become a concern. This article reviews the potential for drug interactions by herbal extracts through drug metabolizing enzymes.


Epidermal growth factor receptors in the canine antrum.
In this study we localized receptor binding sites for 125I-human epidermal growth factor (hEGF) in the antrum of the adult canine stomach. High levels of specific 125I-hEGF binding sites were observed over the mucosa and muscularis mucosa, whereas specific binding sites were not detectable over the submucosa, external circular and longitudinal muscle or myenteric neurons. These results are in agreement with previous studies which indicated that EGF stimulates the proliferation of cultured epithelial cells and inhibits gastric acid secretion. This suggests that EGF may be a useful therapeutic agent in the healing of gastric ulcers.


Nephropathy in the mature pig after the irradiation of a single kidney: a comparison with the immature pig.
The right kidney of 11 mature 10-month-old Large White female pigs was irradiated with single doses of 9.8-14.0 Gy of 60Co gamma rays. Individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured using 99mTc-DTPA and 131I-hippuran renography for periods up to 24 weeks after irradiation. Renal function was assessed either as a functional index, FI (FI = irradiated/unirradiated kidney function), or as the individual kidney GFR and ERPF. The radiation-induced changes after the irradiation of a single kidney (unilaterally irradiated--UI) of mature pigs were compared with those previously observed in 14-week-old immature pigs. Irradiation resulted in a dose-dependent reduction in the FI for both GFR and ERPF. However, these reductions were significantly less than those previously seen in immature pigs. Within 2 weeks of irradiation GFR increased in both the irradiated and the unirradiated kidneys in each animal, compared with unirradiated age-matched control kidneys. No marked changes in renal hemodynamics were seen in mature animals after a single dose of 9.8 Gy. This was in marked contrast to the pronounced reduction in the GFR and ERPF in the irradiated kidney previously observed in immature animals irradiated with an equivalent single dose of X rays. After higher doses, the irradiated kidney in mature pigs showed a dose-dependent reduction in GFR and ERPF. However, the extent of this reduction was significantly less than that seen in immature animals. There was no apparent difference in the response of the unirradiated kidneys in mature or immature pigs. The ED50 values, based on a probit fit to the data for the proportion of functional tests in which the irradiated kidney showed a greater than or equal to 50% reduction in GFR or ERPF, were higher in the mature animals; for example for ERPF the ED50 values were 11.76 +/- 0.28 Gy and 7.67 +/- 0.34 Gy for mature and immature animals, respectively. Thus, the UI kidney in mature pigs appears to be less radiosensitive than the UI kidney in immature animals.


The biogeography of polyphenolic compounds in marine macroalgae: temperate brown algal defenses deter feeding by tropical herbivorous fishes.
Many tropical brown algae have low levels of polyphenolic compounds and are readily consumed by herbivorous fish. In contrast, temperate brown algae often produce large quantities of phenolic compounds causing them to be distasteful to herbivorous gastropods and sea urchins. We hypothesized that tropical brown algae do not use phenolic compounds as antiherbivore defenses because these compounds are not effective deterrents against tropical fish. To test our hypothesis, we assessed the ability of extracts from 8 tropical and 13 temperate algae with a broad range of phenolic levels to deter feeding by herbivorous fishes on Guam. Extracts of the high-phenolic (>2% d.w.) temperate brown algae consistently deterred feeding by herbivorous fishes, whereas extracts from low phenolic (<2% d.w.) temperate and 6 of 8 low-phenolic tropical brown algae did not. Thus, phenolic compounds could be effective feeding deterrents towards herbivorous fishes on Guam, but for unknown reasons they are not used by Guamanian brown algae.


Alcohol, smoking and pregnancy: some observations on ethnic minorities in the United Kingdom.
This paper describes drinking and smoking patterns before and during pregnancy in 363 women from ethnic minorities living in West London. Drinking and smoking were less common and levels of consumption were lower amongst women of Afro-Caribbean, Asian or Oriental origin than amongst Europeans. However, 75% of the Afro-Caribbeans, 56% of the Orientals and 47% of the Asians did drink alcohol before pregnancy. Twenty-one per cent of the Europeans, 5% of the Afro-Caribbeans, 3% of the Orientals drank more than 100 g alcohol per week (the level at which fetal harm may result). Drinking and smoking decreased in pregnancy in all ethnic groups, but 31% of Afro-Caribbeans, 29% of Orientals and 18% of Asians continued drinking. It is important to take alcohol and smoking histories from all pregnant women whatever their racial origin as part of good antenatal care.


Specificity of paediatric jawbone lesions: tumours and pseudotumours.
Characteristics and epidemiology of jaw tumours have been described mostly in adults. Compared with their adult counterparts, childhood jaw tumours show considerable differences. The aim of this study was to describe the different jaw tumours in children, define diagnostic tools to determine their specificity and describe optimal treatment. All children patients with jaw lesions, excluding cysts, apical granuloma and osteitis were included in our study between 1999 and 2009. The medical records were analyzed for clinical, radiological, and pathological findings, treatments and recurrences. Mean patient age was 10.9 years old, ranging from 2 months to 18 years old. Of the 63 lesions, 18 were odontogenic and 45 non-odontogenic lesions. 6% of all cases were malignant tumours; the mean age of presentation was 7.25 years old, [ranging from 0.2 to 18 years old]. Approximately 80% of the tumours developed after 6 years of age. Odontogenic tumours occurred more often after the age of 6. Compared with their adult counterpart, childhood jaw tumours show considerable differences in their clinical behaviour and radiological and pathological characteristics. Clinical features of some tumours can be specific to children. Tumourigenesis is related to dental development and facial growth. Conservative treatment should be considered.


Synergistic effects of lectins in the interaction of thrombin with human platelets.
Several lectins have been studied for their effects on the interaction of thrombin with human platelets. Wheat germ agglutinin, concanavalin A and Ricinus communis lectin increased the number of high affinity sites for diisopropylphosphothrombin on washed platelets from 3000 to about 12 000 but the binding affinities were unchanged (Kd approx 4 nM). Two other lectins, Lens culinaris and Bandieria simplicifolia, were without effect. (2) Using formalinized platelets to avoid possible complications of the platelet release reaction, wheat germ agglutinin showed a marked increase (5-fold) in the binding of active thrombin, peanut agglutinin had no effect while Ricinus communis and :Bandieria simplicifolia showed marginal increases (2-fold). Thrombin binding was decreased to about one quarter with Lens culinaris, Phaseolus vulgaris and concanavalin A. (3) Wheat germ agglutinin caused a synergistic increase of platelet aggregation at low concentrations of thrombin (12.5 mU/ml) and ADP (1 microM), both in the absence and presence of added fibrinogen, but had no effect on ristocetin-induced aggregation.


Acetyl-11-keto-beta boswellic acid(AKBA) modulates CSTC-pathway by activating SIRT-1/Nrf2-HO-1 signalling in experimental rat model of obsessive-compulsive disorder: Evidenced by CSF, blood plasma and histopathological alterations.
Obsessive-Compulsive disorder (OCD) is a long-term and persistent mental illness characterised by obsessive thoughts and compulsive behaviours. Numerous factors can contribute to the development or progression of OCD. These factors may result from the dysregulation of multiple intrinsic cellular pathways, including SIRT-1, Nrf2, and HO-1. Inhibitors of selective serotonin reuptake (SSRIs) are effective first-line treatments for OCD. In our ongoing research, we have investigated the role of SIRT-1, Nrf2, and HO-1, as well as the neuroprotective potential of Acetyl-11-keto-beta boswellic acid (AKBA) against behavioural and neurochemical changes in rodents treated with 8-OH-DPAT. In addition, the effects of AKBA were compared to those of fluvoxamine (FLX), a standard OCD medication. Injections of 8-OH-DPAT into the intra-dorso raphe nuclei (IDRN) of rats for seven days induced repetitive and compulsive behaviour accompanied by elevated oxidative stress, inflammatory processes, apoptosis, and neurotransmitter imbalances in CSF, blood plasma, and brain samples. Chronic administration of AKBA at 50 mg/kg and 100 mg/kg p.o. restored histopathological alterations in the cortico-striatal-thalamo-cortical (CSTC) pathway, including the cerebral cortex, striatum, and hippocampal regions. Our investigation revealed that when AKBA and fluvoxamine were administered together, the alterations were restored to a greater degree than when administered separately. These findings demonstrate that the neuroprotective effect of AKBA can serve as an effective basis for developing a novel OCD treatment.


Brain Plasticity Induced by Musical Expertise on Proactive and Reactive Cognitive Functions.
Proactive and reactive brain activities usually refer to processes occurring in anticipation or in response to perceptual and/or cognitive events. Previous studies found that, in auditory tasks, musical expertise improves performance mainly at the reactive stage of processing. In the present work, we aimed at acknowledging the effects of musical practice on proactive brain activities as a result of neuroplasticity processes occurring at the level of anticipatory motor/cognitive functions. Accordingly, performance and electroencephalographic recordings were compared between professional musicians and non-musicians during an auditory go/no-go task. Both proactive (pre-stimulus) and reactive (post-stimulus) event-related potentials (ERPs) were analyzed. Behavioral findings showed improved performance in musicians compared to non-musicians in terms of accuracy. For what concerns electrophysiological results, different ERP patterns of activity both before and after the presentation of the auditory stimulus emerged between groups. Specifically, musicians showed increased proactive cognitive activity in prefrontal scalp areas, previously localized in the prefrontal cortex, and reduced anticipatory excitability in frontal scalp areas, previously localized in the associative auditory cortices (reflected by the pN and aP components, respectively). In the reactive stage of processing (i.e., following stimulus presentation), musicians showed enhanced early (N1) and late (P3) components, in line with longstanding literature of enhanced auditory processing in this group. Crucially, we also found a significant correlation between the N1 component and years of musical practice. We interpreted these findings in terms of neural plasticity processes resulting from musical training, which lead musicians to high efficiency in auditory sensorial anticipation and more intense cognitive control and sound analysis.


Effect of muscimol on ethanol-induced central nervous system depression.
In male Sprague-Dawley rats acute ethanol (1.0 and 2.0 g/kg) produced impairment of motor coordination and induced hypnosis (4.0 g/kg). Muscimol (1.25 mg/kg, IP) prior to ethanol administration enhanced motor impairment as measured by the aerial righting reflex. The rate of ethanol disappearance from the blood was unaltered by muscimol. Functional tolerance to the effect of ethanol on sleep time was produced by a 24 hr ethanol inhalation procedure. Animals tested 48 hr after ethanol inhalation exhibited a reduced sleep time from ethanol (4.0 g/kg). Muscimol (1.75 mg/kg) was administered along with ethanol 48 hr following 1 day of ethanol inhalation. Although the animals exhibited tolerance to ethanol-induced hypnosis, they did not manifest tolerance to the effect of muscimol.


Endoscopic Sphincterotomy for Cholecysto-Choledocholithiasis Complicates Subsequent Laparoscopic Cholecystectomy: A Retrospective Report From Sri Lanka.
Published literature so far has supported the fact that patients who underwent endoscopic retrograde cholangio-pancreatography and sphincterotomy (ERCPS) had a difficult perioperative course after subsequent laparoscopic cholecystectomy. Through a retrospective study, this original report mentions statistics in a Southeast Asian population comparing the effect on conversion to open surgery in patients undergoing laparoscopic cholecystectomy after ERCPS in a university hospital in Sri Lanka. The results of 205 patients who underwent laparoscopic cholecystectomy and 85 patients who were converted to open surgery between 2016 and 2018 were analyzed to find out whether ERCPS is a risk factor for conversion or subsequent perioperative morbidity. Demographics like age, gender and previous abdominal surgeries were comparable between the two groups. Cholecysto-choledocholithiasis and undergoing ERCPS for it were significant factors associated with conversion to open cholecystectomy. Performing laparoscopic cholecystectomy after ERCPS for cholecysto-choledocholithiasis is a significant challenge and preferably should be often handled by a more experienced surgeon.


Isolation and characterization of a proteolytic enzyme from the adult hookworm Ancylostoma caninum.
The adult hookworm Ancylostoma caninum releases a proteolytic enzyme which is thought to be essential for its adaption to parasitism. The protease was purified from parasite extracts by ion-exchange chromatography followed by gel filtration and hydrophobic interaction chromatography. The purified enzyme exhibited a molecular weight of 37,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and had an NH2-terminal sequence of Arg-His-His-Gln-Pro-Lys-Val-Ala-Leu-Leu-Gly-Ala-His-Gly-Gly-Ile. Using 125I-fibrin as substrate, the enzyme displayed optimal activity at pH 9-11 and was inactivated by dialysis against EDTA. The enzyme degraded [3H]elastin and both elastin and trypsin-labile glycoproteins in a rat vascular smooth muscle extracellular matrix. Antiserum raised to the protease in rabbits cross-reacted with extracts from the infective larval stage of A. caninum, suggesting that the production of the enzyme begins in an earlier developmental stage of the parasite life cycle. The role of the protease in the histolytic and anticlotting processes of the hookworm and its importance in immunity to ancylostomiasis is discussed.


Sensitive detection of microRNAs using polyadenine-mediated fluorescent spherical nucleic acids and a microfluidic electrokinetic signal amplification chip.
The identification of tumor-related microRNAs (miRNAs) exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications. Therefore, we developed a sensitive and efficient biosensor using polyadenine (polyA)-mediated fluorescent spherical nucleic acid (FSNA) for miRNA analysis based on strand displacement reactions on gold nanoparticle (AuNP) surfaces and electrokinetic signal amplification (ESA) on a microfluidic chip. In this FSNA, polyA-DNA biosensor was anchored on AuNP surfaces via intrinsic affinity between adenine and Au. The upright conformational polyA-DNA recognition block hybridized with 6-carboxyfluorescein-labeled reporter-DNA, resulting in fluorescence quenching of FSNA probes induced by AuNP-based resonance energy transfer. Reporter DNA was replaced in the presence of target miRNA, leading to the recovery of reporter-DNA fluorescence. Subsequently, reporter-DNAs were accumulated and detected in the front of with Nafion membrane in the microchannel by ESA. Our method showed high selectivity and sensitivity with a limit of detection of 1.3 pM. This method could also be used to detect miRNA-21 in human serum and urine samples, with recoveries of 104.0%-113.3% and 104.9%-108.0%, respectively. Furthermore, we constructed a chip with three parallel channels for the simultaneous detection of multiple tumor-related miRNAs (miRNA-21, miRNA-141, and miRNA-375), which increased the detection efficiency. Our universal method can be applied to other DNA/RNA analyses by altering recognition sequences.


Sensitive determination of bisoprolol enantiomers in plasma and urine by high-performance liquid chromatography using fluorescence detection, and application to preliminary study in humans.
A sensitive, stereoselective high-performance liquid chromatographic method with fluorescence detection for the measurement of bisoprolol enantiomers in human plasma and urine has been developed. Bisoprolol was extracted at alkaline pH with chloroform, followed by solid-phase extraction. The effluent was evaporated, and the reconstituted residue was chromatographed on a Chiralcel OD column with a mobile phase of hexane-2-propanol (10:0.9, v/v) containing 0.01% (v/v) diethylamine. Within the plasma and urine enantiomeric concentration ranges of 5-100 ng/ml and 25-1250 ng/ml, respectively, a linear relationship was obtained between the peak-height ratios and the corresponding concentrations. The limit of quantitation, defined as three times the baseline noise, was 2 ng/ml for each enantiomer in plasma. A preliminary pharmacokinetic study was undertaken in three healthy male volunteers following an oral dose of 5 mg of racemic bisoprolol. The results confirm that this assay is suitable for pharmacokinetic studies of bisoprolol enantiomers in humans following oral administration of the therapeutic dose.


Postoperative nutritional effects of early enteral feeding compared with total parental nutrition in pancreaticoduodectomy patients: a prosepective, randomized study.
The benefits of early enteral feeding (EEN) have been demonstrated in gastrointestinal surgery. But, the impact of EEN has not been elucidated yet. We assessed the postoperative nutritional status of patients who had undergone pancreaticoduodenectomy (PD) according to the postoperative nutritional method and compared the clinical outcomes of two methods. A prospective randomized trial was undertaken following PD. Patients were randomly divided into two groups; the EEN group received the postoperative enteral feed and the control group received the postoperative total parenteral nutrition (TPN) management. Thirty-eight patients were included in our analyses. The first day of bowel movement and time to take a normal soft diet was significantly shorter in EEN group than in TPN group. Prealbumin and transferrin were significantly reduced on post-operative day (POD) 7 and were slowly recovered until POD 90 in the TPN group than in the EEN group. EEN group rapidly recovered weight after POD 21 whereas it was gradually decreased in TPN group until POD 90. EEN after PD is associated with preservation of weight compared with TPN and impact on recovery of digestive function after PD.


Evolution: Adapting to a Warming World.
To be able to cope with climate change, species need to evolve. Demonstrating such evolution in wild populations is notoriously difficult. Replication of a 21-year-old experiment demonstrates that a long-distance migratory songbird has genetically adapted to climate change.


HLA-DRB1 gene polymorphisms and its associations with rheumatoid arthritis in Chinese Han women of Shaanxi province, northwest of China.
Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by symmetric polyarthritis. This study was designed to investigate the associations between HLA-DRB1 gene polymorphisms and RA in the Chinese Han population of Shaanxi province, northwest of China. In total, we identified 31 high-resolution HLA-DRB1 alleles in 109 patients with RA. Compared with the controls, the AF of HLA-DRB1*04:05 (P = 0.000, Pc = 0.007, OR = 3.462, 95%CI: 1.749-6.852) was significantly higher in patients with RA. In addition, the patients with RA had higher allele frequency (AF) of the HLA-DRB1*04:03 (P = 0.030, Pc = NS, OR = 4.737, 95%CI: 1.012-22.180); DRB1*04:06 (P = 0.018, Pc = NS, OR = 5.288, 95%CI: 1.145-24.422) and the shared epitope (SE) alleles (P = 0.004, Pc = NS, OR = 2.166, 95%CI: 1.279-3.667), respectively. Moreover, positive possibilities of RF and anti-CCP were significant higher in SE-positive patients compared to SR-negative patients (OR = 4.787, 95%CI: 1.101-20.824; OR = 3.775, 95%CI: 1.106-12.876, respectively). Our results indicated that HLA-DRB1*04:05, *04:03, *04:06 and SE alleles might be susceptibility allele for RA in Chinese Han population of Shaanxi province, northwest of China.


Vision and eating behavior.
Eating behavior is influenced by internal and external factors. Vision is one part of the complex pattern of factors influencing the amount of food consumed during a meal. The aim of this study was to explore the impact of vision on the microstructure of eating behavior and the subjective motivation to eat. Nine blind subjects and nine matched seeing control subjects consumed a standardized meal registered by VIKTOR, an eating monitor, measuring the microstructure of the eating behavior. The eating behavior of the control subjects was registered twice, with and without blindfold. The eating behavior of the blind subjects did not differ from that of seeing control subjects. However, the eating behavior of seeing subjects eating with blindfold demonstrated a clear impact of vision on eating behavior. When blindfolded, subjects ate 22% less food (p < 0.05), had shorter meal durations (p < 0.05), and had less decelerated eating curves (p < 0.05). Despite a smaller amount of food consumed when blindfolded, the reported feeling of fullness was identical to that reported after the larger meal consumed without blindfold. The importance of vision in regulating our eating behavior is further stressed in this study. Eating with a blindfold decreased the intake of food, without making subjects feel less full. Eating blindfolded, therefore, may force subjects to rely more on internal signals. These results might be used as an aid in the development of new treatment strategies for obese subjects.


Effects of straw returning and feeding on greenhouse gas emissions from integrated rice-crayfish farming in Jianghan Plain, China.
Great efforts have been devoted to assessing the effects of straw managements on greenhouse gas (GHG) emissions, global warming potential (GWP), and net economic budget in rice monoculture (RM). However, few studies have evaluated the effects of straw managements on GHG emissions and net ecosystem economic budget (NEEB) in integrated rice-crayfish farming (RC). Here, a randomized block field experiment was performed to comprehensively evaluate the effects of aquatic breeding practices (feeding or no feeding of forage) and straw managements (rice straw returning or removal) on soil NH4+-N and NO-3-N contents, redox potential (Eh), CH4 and N2O emissions, GWP, and NEEB of fluvo-aquic paddy soil in a rice-crayfish co-culture system in Jianghan Plain of China. We also compared the differences in CH4 and N2O emissions, GWP, and NEEB between RM and RC. Straw returning significantly increased CH4 and N2O emissions by 34.9-46.1% and 6.2-23.1% respectively compared with straw removal. Feeding of forage decreased CH4 emissions by 13.9-18.7% but enhanced N2O emissions by 24.4-33.2% relative to no feeding. Compared with RM treatment, RC treatment decreased CH4 emissions by 18.1-19.6% but increased N2O emissions by 16.8-21.0%. Moreover, RC treatment decreased GWP by 16.8-22.0% while increased NEEB by 26.9-75.6% relative to RM treatment, suggesting that the RC model may be a promising option for mitigating GWP and increasing economic benefits of paddy fields. However, the RC model resulted in a lower grain yield compared with the RM model, indicating that more efforts are needed to simultaneously increase grain yield and NEEB and decrease GWP under RC model.


Toxicity of 3-nitronaphthalimides to V79 379A Chinese hamster cells.
The cellular uptake and toxicity of a number of substituted 3-nitronaphthalimides was investigated. Uptake of these compounds into cells was initially rapid and reached a plateau after several hours, where in some cases intracellular concentrations were much greater than the corresponding extracellular concentrations. Little uptake was obtained, however, with a compound carrying an acidic substituent. Toxicity studies divided the compounds into two main groups; those where survival curves were convex and those where survival curves were concave. The shapes of survival curves of the latter group did not appear to reflect depletion of extracellular drug. Uptake and toxicity of different drugs were not well correlated and bioreductive metabolism of the nitro-substituent did not appear to be a major contributor to toxicity. There was no consistent differential toxicity of these drugs in aerobic and hypoxic conditions. It was concluded that the nature of the ring substituent had more effect on toxicity than the absolute concentration of the naphthalimide ring or bioreductive metabolism of the nitro-group.


A 60-Year-Old Swiss Woman Presenting with Migratory Radicular Pain Diagnosed with Lyme Disease by Western Blot.
BACKGROUND Many diagnostic guidelines have been established to support the diagnosis of Lyme disease, but a recent meta-analysis did not find that 2-tier tests were better than individual tests. Here, we present the case of a patient who was diagnosed by immunoblot only, a second-line test that is usually not performed if the first-line test is negative. CASE REPORT A 60-year-old Swiss woman, without relevant comorbidities, presented to our clinic with 1-week symptoms of migratory radiculitis in the L1, L2, and L5-S1 right dermatomes. Blood analysis and lumbar and brain MRI did not show any significant abnormalities. However, unexpected results were obtained after testing Lyme serologies. They were performed first with LIAISON® test (Diasorin, Italy) then with Borrelia VIRAstripe® immunoblot (Viramed, Germany) and a positive IgM result was only obtained with the latter. Consequently, doxycycline 100 mg 2×/day was initiated and the symptoms completely resolved after 6 weeks of treatment. Ever since, and more than 1 year after the initial presentation, the patient remains symptom-free. CONCLUSIONS As shown, it was possible to diagnose this patient and treat her successfully by testing all the available serologies. Furthermore, we were surprised to find out after a review of the literature that the IgM sensitivity in neuroborreliosis with the LIAISON® test is only 43.9-46% versus 90-100% with VIRAstripe®. Hence, clinicians need to understand the pitfalls of these tests before excluding Lyme disease.


Errors.
Errors are outcomes or patterns of outcomes you don't want to see. They are basically of two types: those that occur naturally as rare outcomes of effective processes and those that signal that the process is not working. The error rate in American medicine is known to be alarmingly large; it has not been looked at in dentistry. A topology of error is presented and it is shown how understanding the conditions that cause error, and thus the prevention of error, can only be developed by recognizing and analyzing error itself.


Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation.
Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk. Show paricalcitol regulation overinflammatory, fibrotic and mineral disorder parameters in CKD. Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol. We evaluated classic and newest mineral and bone metabolism serum parameters (calcium, phosphorus, parathormone, fibroblast growth factor-23 [FGF-23], Klotho, calcidiol), inflammatory-fibrosis and anticalcifying parameters (interleukin-6 and 10, tumor necrosis factor-a [TNF- α], transforming growth factor-b [TGF-β],bone morphogenic protein-7 [BMP-7] and fetuin-A) for four months. At the end of study soluble Klotho increased (p=.001), FGF-23 remained stable, calcium and phosphorus levels were not increased, calcidiol increased (p=.010) and PTH decreased (p=.002). Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment: interleukin-6 decreased significantly (p=.001) and also TNF-α did (p=.005), on the contrary, interleukin-10 and fetuin-A increased (p=.001 for both). Anti-fibrosis marker BMP-7 increased (p=.001) and TGF-b decreased (p=.001). We did not find significant changes in renal function. Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters, unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis. Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease.


Spanish translation of the ABC taxonomy for medication adherence.
The Ascertaining Barriers to Compliance (ABC) taxonomy was developed aiming at systematizing definitions and operationalizations of medication adherence. Its translation is crucial to improve the generalizability, application and comparison of study findings. To provide a consensus translation of the ABC taxonomy from English to Spanish. A two-phased approach was used, according to the Preferred Methods for the Translation of the ABC Taxonomy for Medication Adherence. Two literature reviews were conducted: to identify Spanish synonyms and definitions of the ABC taxonomy, and to identify a panel of Spanish-speaking experts in medication adherence. A Delphi survey was designed based on the synonyms and definitions found. The experts previously identified were invited to participate in the Delphi. A consensus of ≥85% was established for the first round. A moderate consensus (50-75%), a consensus (75-95%) or a strong consensus (>95%) were considered to be necessary in the second round. Forty potential synonyms of the ABC taxonomy terms were identified from a total of 270 papers. The response rate during the first Delphi round was 32% (63/197) and in the second round 86% (54/63). A strong consensus was reached for the term "inicio del tratamiento" (96%) and consensus for the term "implementación" (83%). A moderate consensus was obtained for "adherencia a la medicación" (70%), "interrupción del tratamiento" (52%), "manejo de la adherencia" (54%) and "disciplinas relacionadas con la adherencia" (74%). No consensus was reached for the term persistence. Five out of the seven definitions reached a consensus in the first round, and two definitions a moderate consensus after the second round. The adoption of the Spanish taxonomy will increase transparency, comparability and transferability of results in the field of medication adherence. This may facilitate benchmarking of adherence strategies between Spanish-speaking researchers and practitioners, and other language speakers.


Pancreatic solid serous cystadenoma treated by laparoscopy: Presentation of a new case report and review of the literature.
Solid serous cystadenoma is an uncommon benign pancreatic tumor, with only, including this case, 21 cases published so far. It is often misdiagnosis with other malignant pancreatic tumors. Below we report a new case of a solid serous cystadenoma of the pancreas treated by laparoscopic distal pancreatectomy in 53-year-old female who presented with epigastric pain. Histological and immunohistochemical examination revealed a solid serous cystadenoma of the pancreas. Preoperative diagnosis of this subtype of serous cystadenoma is difficult, and, due to its benign nature, conservative resection of the tumor is the recommended treatment. After analyzing the literature, including this case from our department, we discuss clinical presentation, imaging characteristics and histopathological findings, considering in particular difficulties in preoperative diagnosis, feasibility of laparoscopic resection.


Fragmentation and transferability in Hirshfeld atom refinement.
Hirshfeld atom refinement (HAR) is one of the most effective methods for obtaining accurate structural parameters for hydrogen atoms from X-ray diffraction data. Unfortunately, it is also relatively computationally expensive, especially for larger molecules due to wavefunction calculations. Here, a fragmentation approach has been tested as a remedy for this problem. It gives an order of magnitude improvement in computation time for larger organic systems and is a few times faster for metal-organic systems at the cost of only minor differences in the calculated structural parameters when compared with the original HAR calculations. Fragmentation was also applied to polymeric and disordered systems where it provides a natural solution to problems that arise when HAR is applied. The concept of fragmentation is closely related to the transferable aspherical atom model (TAAM) and allows insight into possible ways to improve TAAM. Hybrid approaches combining fragmentation with the transfer of atomic densities between chemically similar atoms have been tested. An efficient handling of intermolecular interactions was also introduced for calculations involving fragmentation. When applied in fragHAR (a fragmentation approach for polypeptides) as a replacement for the original approach, it allowed for more efficient calculations. All of the calculations were performed with a locally modified version of Olex2 combined with a development version of discamb2tsc and ORCA. Care was taken to efficiently use the power of multicore processors by simple implementation of load-balancing, which was found to be very important for lowering computational time.


Design and synthesis of small semi-mimetic peptides with immunomodulatory activity based on myelin basic protein (MBP).
Experimental allergic encephalomyelitis (EAE) is induced in susceptible animals by immunodominant determinants of myelin basic protein (MBP). Analogs of these disease-associated peptides have been identified with disease progression upon coimmunization. Usage of peptides, with disease-specific immunomodulatory capacity in vivo is limited, however, due to their sensitivity to proteolytic enzymes. Alternative approaches include the development of mimetic molecules which maintain the biological function of an original peptide, yet are stable and able to elicit their response in pharmacological quantities. A novel technique was employed to design a series of semi-mimetic peptides, based on the guinea pig MBP72-85 peptide used to induce EAE in Lewis rats. We used isonipecotic (iNip) and aminocaproic (Acp) acids as templates. Acp-MBP72-85 peptide derived analogues were effective in inducing EAE compared to iNip-peptide analogues which were ineffective at 350 micrograms. These findings suggest that the design and synthesis of semi-mimetic peptide molecules with immunomodulatory potential is possible and that eventually these molecules may form the basis for the development of novel and more effective disease-specific therapeutic agents.


Stereoselective renal effects of the loop diuretic ozolinone in the anesthetized dog.
The renal effects of i.v. injections of (+/-)-ozolinone, its enantiomers (-)-ozolinone and (+)-ozolinone and its prodrug (+/-)-etozoline, were compared with those of furosemide, in pentobarbital anesthetized dogs. Renal blood flow (electromagnetic flow-meter) and glomerular filtration rate (polyfructosan clearance) were assessed on the left denervated kidney together with renin secretion and urinary electrolyte excretion. (-)-Ozolinone (15.5 mg/kg i.v.) behaves as a stereoselective loop diuretic equipotent to 20 mg/kg of furosemide and 45 mg/kg of (+/-)-ozolinone; (+)-ozolinone induced only minor salidiuretic effects. Both ozolinone enantiomers markedly increased the renal blood flow and decreased the filtration fraction, suggesting that the vosodilating effect predominates on the efferent glomerular arterioles. (-)-Ozolinone also induced an acute rise in renin secretion. The inhibition of prostaglandin synthesis (indomethacin or meclofenamate) prevented renin hypersecretion in response to (-)-ozolinone and modified its salidiuretic effects but had no effect on the vascular response. The inhibition of the kallikrein-kinin system by aprotinin had no effect on the overall renal response to (-)-ozolinone. The inhibition of the renin-angiotensin system by captopril decreased blood pressure, prolonged the (-)-ozolinone-induced decrease in renal vascular resistance and increased renin secretion. Our results demonstrate that the loop diuretic, ozolinone, induces stereoselective and prostaglandin-dependent renin secretion, which is involved in the regulation of intra-renal hemodynamics.