Effect of different amino acid solutions on the oxidative stability of three different lipid emulsions in all-in-one admixtures.
Lipid peroxidation in parenteral nutrition mixtures is still a challenge. We aimed to evaluate the effect of two different amino acid solutions used in different clinical situations on lipid peroxidation of three different lipid emulsions (Intralipid, ClinOleic, and SMOFlipid) in all-in-one admixtures during 24 h of simulated infusion. The selected amino acid solutions included one used in stable patients and one used in renal insufficiency (Aminomel10E and Nephrotect, respectively). Eighteen all-in-one admixtures were prepared. The simulated infusion with light protection was conducted straight after the preparation for 24 h at room temperature. The lipid peroxidation process was evaluated in all-in-one admixtures and the original lipid emulsion by determining the malondialdehyde levels (high-performance liquid chromatography) and conjugated dienes and trienes (ultraviolet-visible spectrophotometry). Malondialdehyde in the original packaging was lower in SMOFlipid (9 µM) compared with Intralipid (27 µM, P = 0.0003) and ClinOleic (25 µM, P = 0.0001). During simulated infusion, ClinOleic showed a significantly lower rate of lipid peroxidation (26% decrease in aldehyde levels) in comparison with Intralipid and SMOFlipid (up to 39% and 31% increase in aldehyde levels, respectively) when the admixture was based on Aminomel10E. In admixtures based on Nephrotect, ClinOleic, and SMOFlipid showed better oxidative stability in comparison with Intralipid. Admixtures based on Nephrotect and Intralipid had higher levels of primary lipid peroxidation products than those based on ClinOleic (P = 0.030) or SMOFlipid (P = 0.071, not significant). Amino acid solutions influence the rate of lipid peroxidation. The observation should be confirmed in larger studies with different amino acid solutions.


Influence of heparin on interactions between C-reactive protein and polycations.
C-reactive protein (CRP) is a trace serum protein which elevates up to 1000-fold in concentration in association with inflammation and tissue necrosis. CRP binds with phosphocholine and phosphate esters; initiates reactions of agglutination, opsonization and complement consumption; and precipitates with protamine and synthetic polymers of lysine and arginine, and these reactivities are modulated by calcium and phosphocholine. We now report on the interactions of heparin with these polycations in the absence and presence of CRP, which show marked similarities to reactions between antigen and antibody. Heparin optimally precipitated with the polycations over a narrow range of reactant ratios, peaking at slight anion charge excess. The complexes formed did not dissociate in excess heparin: however, complex formation was significantly depressed when heparin was added in a single dose in excess of the amount required for optimal precipitation. Calcium did not affect the precipitation of heparin with polycation, and heparin did not precipitate with CRP. However, heparin did induce a rapid and efficient dissociation of CRP-polycation precipitates preformed at equivalence, with total release of CRP. Small amounts of heparin augmented precipitation under conditions of polycation excess of CRP, but as heparin levels were increased to amounts needed to reach equivalence with polycation, CRP was resolubilized in favor of the preferred heparin-polycation complexes. Chondroitin sulfate was similar to heparin in its effects upon the CRP-poly-L-arginine (PLA) interaction, while hyaluronic acid enhanced CRP-PLA precipitation at all concentrations tested and DNA had neither augmenting nor solubilizing effects. These data indicate that CRP-polycation interactions are significantly and selectively influenced in the presence of small amounts of heparin and certain other polyanions. This modulatory reactivity may be of importance in the biological reactivities of CRP during episodes of acute inflammation.


Readmissions at 30 days after inguinal hernia repair: A series of 5126 patients.
The evaluation of the re-admission rate within 30 days of inguinal hernia repair represents a patient management quality indicator. The goal of our study was to evaluate the re-admission rate at 30 days after inguinal hernia repair and identify the risk factors for re-admission. Based on a prospective national registry, patient data were collected during two years. The number of and reasons for re-admissions were compiled. A total of 5126 patients, mean age 61 years, underwent inguinal hernia repair. Ambulatory surgery was performed in 4013 (78%) patients. Failed ambulatory surgery was recorded for 100 (2%) patients. Thirty-three (0.64%) patients were re-admitted within 30 days following surgery for 34 various reasons. The re-admission rate after ambulatory surgery was 0.5%. Half of patients re-admitted presented with a severe complication that required re-intervention. In multivariable analysis, emergency hernia repair (OR 4.899 [1.309-18.327]; P=0.01) and prolonged duration of operation (OR 1.023 [1.009-1.037]; P=0.001) were identified as independent risk factors for re-admission within 30 days after surgery. Within this prospective national cohort, the overall re-admission rate after inguinal hernia repair was 0.64%, slightly less among the patients undergoing ambulatory surgery. Half of re-admitted patients required surgical re-operation. Emergency hernia repair and prolonged duration of operation were risk factors for re-admission.


Ventilation and cardiovascular studies during mechanical control of ventilation in horses.
Eleven out of 12 horses were underventilating while breathing spontaneously during halothane anaesthesia with high arterial carbon dioxide tensions. In addition, large alveolar to arterial oxygen tension gradients were found to be present. Mechanically, controlled ventilation with an intermittent positive pressure of 20-30 cm H2O reduced arterial carbon dioxide levels to normal. The alveolar to arterial oxygen gradients did not increase and in some cases decreased. These (A - a) Po2 gradients were due mainly to true shunt of the order of 30 per cent and not to ventilation perfusion inequality.


The Ideal Insertion Site for the Flexor Digitorum Profundus Tendon in Jersey Finger Repair: A Biomechanical Analysis.
Most jersey finger repair techniques involve reattaching the tendon to an approximate location corresponding to the tendon's native attachment. This study aimed to determine the biomechanical effect on the distal interphalangeal joint flexion forces and range of motion when the flexor digitorum profundus (FDP) tendon attachment site on the distal phalanx is altered within its broad footprint. We fixed 14 fresh-frozen cadaveric fingers to a wooden block with an attached pulley and weights system. A pressure mapping sensor placed under the fingertip measured the contact force and area in response to FDP tendon loading for the intact tendon and 3 repair sites along the FDP footprint. Two-way repeated-measures analysis of variance test using mixed-effect model was performed to test the influences of attachment location (intact, proximal, central, and distal) and digit (index, middle, and ring) on the outcomes. Mean ± SD contact force under 45 N tendon loading force was 43.5 ± 7.2 N for the intact tendon, 34.6 ± 7.4 N for the proximal insertion, 38.0 ± 7.1 N for the central insertion, and 43.1 ± 6.3 N for the distal insertion. Compared with the intact tendon, the proximal group generated notably less contact force. No significant difference was detected between the intact tendon and the central or distal repairs. Comparisons among the 3 repair groups show that the distal group generated significantly higher force than the proximal group. There was no difference between contact areas across all groups. The FDP tendon inserted at the distal edge of its footprint conferred significantly greater distal interphalangeal joint flexion force compared with the proximal insertion site and most closely resembled the intact FDP tendon. Biomechanically, distal reattachment of the FDP most closely approximates the contact force of the native anatomy and may help guide intraoperative placement of the repair footprint.


NMR measurement of the off rate from the first calcium-binding site of the synaptotagmin I C2A domain.
The off rate from the first calcium-binding site of the C2A domain of synaptotagmin I, a putative calcium receptor in neurotransmitter release, has been determined by 15N-nuclear magnetic resonance relaxation dispersion measurements. The exchange rate was obtained by fitting the dependence of the transverse relaxation rates on the interval between 180 degrees pulses in relaxation-compensated CPMG experiments at 3.2 microM calcium concentration. The measured k(ex) is 2.0x10(3) x s(-1). The calcium on rate of 3.5+/-1x10(7) x s(-1), determined from the measured off rate and the dissociation constant (5.3x10(-5) M), is close to the diffusion limit. These results are consistent with the proposed role of synaptotagmin I as a calcium sensor in release, but suggest that additional factors may help to accelerate the diffusion of Ca2+ to the sensor.


Selective TNF-α inhibitor-induced injection site reactions.
During the last decade, many new biological immune modulators entered the market as new therapeutic principles. TNF-α is a pro-inflammatory cytokine known to a have a key role in the pathogenic mechanisms of various immune-mediated or inflammatory diseases. TNF-α blockers have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs. Although generally well tolerated and safe, potential adverse events may be associated with TNF-α inhibitor treatment. The authors will briefly review the potential adverse drug reactions and the immunological mechanisms of injection site reactions (ISRs) in patients treated with etanercept and adalimumab. Patients treated with TNF-α inhibitors can develop ISR around the sites of injections. 'Type IV delayed type reaction' or 'recall ISRs'. Eosinophilic cellulitis or 'Wells syndrome', 'type III' and 'type I' reactions are reported. Long-term studies are necessary to determine the durability of response and the real risk of ISRs with golimumab and certolizumab pegol. Further studies are also necessary to evaluate the immunogenicity of these drugs.


Seasonal variations of air pollutant concentrations within Krasnoyarsk City.
This paper examines the significant differences in seasonal variations of criteria pollutant concentrations in various parts of a large urban area. These differences are caused by the microclimatic heterogeneity of the city and show the influence of breeze and orographic-type circulations on urban air pollution. The temperature heterogeneity of Krasnoyarsk territory during the winter leads to an increase of 150% in CO air pollution levels in the central part of city. During the summer the orographical heterogeneity of Krasnoyarsk City leads to increases of up to 400% in air pollution for different areas.


Aspiration of bile as a cause of respiratory distress in the newborn infant.
Early-onset respiratory distress and a radiographic appearance of an aspiration syndrome occurred in two neonates with gastroschisis who had evidence of inhalation of bile. Hypoxemic respiratory failure developed in both infants, contributing to death or prolonged respiratory morbidity. Bile aspiration syndrome should be considered whenever there is early-onset respiratory distress in a neonate with high intestinal obstruction.


Experimental analysis of EMG feedback in treating cerebral palsy.
Three subjects diagnosed as having severe choreoathetoid cerebral palsy were trained in the use of EMG feedback procedures. Both between- and within-session controls, including reversals of baseline, attempted muscle control with feedback, and muscle control without feedback, were employed to analyze the contribution of feedback procedures to improvements in muscle control. The data (1) indicate that feedback enhanced muscle control and (2) provide evidence of generalization of feedback effects to no-feedback conditions and untrained muscles.


Decellularized tilapia fish skin: A novel candidate for tendon tissue engineering.
The poor regenerative ability of injured tendon tissues remains a clinical challenge. However, decellularized extracellular matrix (ECM) combined with stem cells shows promise. In contrast to bovine and porcine ECM, marine-derived decellularized ECM has several advantages; it is easily obtained, poses less biological risk, and is not contraindicated on religious grounds. This study successfully fabricated decellularized tilapia fish skin (DTFS) with copious preserved collagen fibers and natural pore structures. The outer layer is smooth and dense, while the inner layer has a soft structure with a rough surface. After crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS), crosslinked DTFS (C-DTFS) showed improved mechanics in dry and wet conditions. In vitro, the leach liquor of crosslinked DTFS showed no cytotoxicity and promoted migration and tenonic differentiation of tendon-derived stem cells (TDSCs). Meanwhile, TDSCs seeded in the inner surface of DTFS maintained viability, differentiated, and exhibited spreading. Furthermore, cell-seeded scaffolds guided the regeneration of tendon tissue in a rat Achilles tendon defect model. Our results suggest that DTFS combined with TDSCs is a novel and promising therapeutic option for tendon tissue engineering.


Does application of moderately concentrated platelet-rich plasma improve clinical and structural outcome after arthroscopic repair of medium-sized to large rotator cuff tear? A randomized controlled trial.
Platelet-rich plasma (PRP) has the potential to improve tendon-bone healing. The evidence is still controversial as to whether PRP application after repair of medium-sized to large cuff tears leads to superior structural and clinical outcome, especially after single-row repair. In a randomized study, 102 patients (PRP group, 52 patients; control group, 50 patients) with medium-sized and large degenerative posterosuperior tears were included for arthroscopic repair with a minimum follow-up of 2 years. Patients were evaluated with clinical scores (visual analog scale score, Constant-Murley score, University of California-Los Angeles score, and American Shoulder and Elbow Surgeons score) and ultrasound to assess retear and vascularity pattern of the cuff. Visual analog scale scores were significantly lower in the PRP group than in controls at 1 month, 3 months, and 6 months but not later. Constant-Murley scores were significantly better in the PRP group compared with controls at 12 and 24 months, whereas University of California-Los Angeles scores were significantly higher in the PRP group at 6 and 12 months (P < .05). The American Shoulder and Elbow Surgeons score in both groups was comparable at all the times. At 24 months, retear in the PRP group (n = 2; 3.8%) was significantly lower than in the control group (n = 10; 20%; P = .01). The retear difference was significant only for large tears (PRP:control group, 1:6; P = .03). Doppler ultrasound examination showed significant vascularity in the PRP group repair site at 3 months postoperatively (P < .05) and in peribursal tissue until 12 months. Application of moderately concentrated PRP improves clinical and structural outcome in large cuff tears. PRP also enhances vascularity around the repair site in the early phase.


Dioscin Ameliorates Experimental Autoimmune Thyroiditis via the mTOR and TLR4/NF-κB Signaling.
Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear. The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively. Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group. Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.


Gas in the temporomandibular joint: computed tomography findings. Report of 3 cases.
In each of 3 patients referred for computed tomographic examinations of the temporomandibular joint, a gas collection was observed in the inferior space of the joint. The gas was observed on the posterosuperior surface of the mandibular condyle in the open mouth position in each patient. Each of 2 patients had saucer-shaped bone resorption of the mandibular condyle adjacent to the gas; 1 patient had no remarkable bone abnormality. A history of temporomandibular joint puncture or facial trauma was denied by all 3 patients.


Comparative study on key odorants of Jiujiang Fenggang Huangjiu and their succession regularities during aging using sensory-directed flavor analysis.
Huangjiu was a Chinese national alcohol with a unique flavor. The key odorants in Jiujiang Fenggang Huangjiu (JJFG) and their succession regularities during aging were systematically researched by a sensomics analysis approach. The volatiles of JJFG were isolated by solvent-assisted flavor evaporation, 77 odorants were identified using gas chromatography-olfactometry-mass spectrometry combined with odor-specific magnitude estimation. Three aroma recombinants, prepared using odorants with odor activity values ≥ 1, all showed good similarities with their corresponding samples (92.1%∼97.5%). After omission/addition tests, 7 new key aroma compounds were found in JJFG, including 1-octen-3-one, 1-pentanol, guaiacol, ethyl 2-hydroxy-4-methylpentanoate, 2-phenethyl acetate, ethyl butanoate, and (E,Z)-2,6-nonadienal. Using orthogonal partial least squares-discriminant analysis, 20 compounds with VIP ≥ 1 were found to be important indicators during aging of JJFG. Among them, sotolon, 3-methylsulfanylpropanal, et al. increased with aging. The improved solid-phase extraction can effectively quantify sotolon, with a recovery rate of 80.96%∼91.75%.


Relationships within the Proteobacteria of plant pathogenic Acidovorax species and subspecies, Burkholderia species, and Herbaspirillum rubrisubalbicans by sequence analysis of 16S rDNA, numerical analysis and determinative tests.
Sequence data for 16S rDNA of the type strains of Acidovorax avenae subsp. avenae, A. avenae subsp. cattleyae, A. avenae subsp. citrulli, A. konjaci and Herbaspirillum rubrisubalbicans were compared with GenBank library accessions of Burkholderia spp., Comamonas sp., Ralstonia solanacearum and Variovorax sp. Maximum Parsimony analysis produced two clusters: 1. Acidovorax spp., Comamonas sp., and Variovorax sp. (all in the Comamonadaceae), and 2. Burkholderia spp., Ralstonia solanacearum, and Herbaspirillum rubrisubalbicans. Maximum Likelihood analysis produced only one cluster (of the Comamonadaceae). Using nutritional and laboratory tests, all Acidovorax spp., Burkholderia spp., and Herbaspirillum rubrisubalbicans were discriminated in distinct clusters at the species level, and could be identified by selected determinative tests. There were no phenotypic tests constituted as a circumscription of the genera and which permitted the allocation of strains to genera. Strain identification as species allowed allocation to genera only by inference. The nomenclatural implications of these data are discussed.


Topical application of dopaminergic compounds can inhibit deprivation myopia in chicks.
Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the development of experimental myopia (short-sightedness). However, pharmacological investigations of dopamine in animal models rely heavily on intravitreal or systemic administration, which have several limitations for longer-term experiments. We therefore investigated whether administration of dopamine as a topical eye drop can inhibit the development of form-deprivation myopia (FDM) in chicks. We also examined whether chemical modification of dopamine through deuterium substitution, which might enhance stability and bioavailability, can increase dopamine's effectiveness against FDM when given topically. Dopamine or deuterated dopamine (Dopamine-1,1,2,2-d4 hydrochloride) was administered as a daily intravitreal injection or as daily topical eye drops to chicks developing FDM over an ascending dose range (min. n = 6 per group). Axial length and refraction were measured following 4 days of treatment. Both intravitreal (ED50 = 0.002μmoles) and topical application (ED50 = 6.10μmoles) of dopamine inhibited the development of FDM in a dose-dependent manner. Intravitreal injections, however, elicited a significantly higher level of protection relative to topical eye drops (p < 0.01). Deuterated dopamine inhibited FDM to a similar extent as unmodified dopamine when administered as intravitreal injections (p = 0.897) or topical eye drops (p = 0.921). Both intravitreal and topical application of dopamine inhibit the development of FDM in a dose-dependent manner, indicating that topical administration may be an effective avenue for longer-term dopamine experiments. Deuterium substitution does not alter the protection afforded by dopamine against FDM when given as either an intravitreal injection or topical eye drop.


Dynamic obstacle detection method based on U-V disparity and residual optical flow for autonomous driving.
As a core step of obstacle avoidance and path planning, dynamic obstacle detection is critical for autonomous driving. This study aimed to propose a dynamic obstacle detection method based on U-V disparity and residual optical flow for autonomous driving. First, a drivable area of an unmanned vehicle was detected using U-V disparity images. Then, obstacles in the drivable area were detected using U-V disparity images and the geometric relationship between obstacle size and its disparity. Finally, the motion likelihood of each obstacle was estimated by compensating the camera ego-motion. The innovation of the proposed method was that the searching range of the moving obstacles was greatly narrowed by detecting the obstacles in the drivable area, which greatly improved not only the moving obstacle detection efficiency but also the detection accuracy. Datasets from the KITTI benchmark and our self-acquired campus scene data were chosen as testing samples. The experimental results showed that our method could achieve high detection precision, low missed detection rate and less time consumption.


Comprehensive determination of the processing level of rhizome of Polygonatum sibiricum by macroscopic, micromorphological, and microscopic characterizations.
The rhizome of Polygonatum sibiricum Red. (PR, Huangjing in Chinese) has served as traditional medicine and foodstuff in China for over 2000 years. However, due to its irritating effect on the throat, Huangjing must be processed before clinical use. People have been exploring to determine the processing level of traditional Chinese medicine in an accurate tool. The evaluation of PR processing levels based on macroscopic and microscopic characteristics has not yet been performed. This study aimed to provide a convenient method to determine the level of PR processing by monitoring the changes in color and crystal inclusion. According to the Chinese Pharmacopeia (2020 edition), macroscopic, micromorphological, and microscopic observations were performed with a polarized light microscope. Color quantization based on the CIE L* a* b* color system using a CM-2300d colorimeter. Color parameters h° , L* , and ΔE* had a significant influence on the differentiation ability. The inner transverse section of PR samples gradually turned into moist black with specular luster, which was consistent with the traditional identification of "brightness like oil and color like black lacquer." The change rate of the needle crystal morphology increased with the processing level, and the change rate of the needle crystal of the fifth product was over 90%. Combined with the correlation analysis, needle-like crystals were related to color parameters and could be used as an alternative marker to discriminate PR samples from different processing levels. The results confirmed the potential applicability of macroscopic and microscopic features for the classification of PR samples with different processing levels. RESEARCH HIGHLIGHTS: Color parameters h° , L* , and ΔE* had a significant influence on the differentiation ability. Micromorphological results were consistent with the traditional identification. High correlations were found between color parameters and needle-like crystals.


Heterogeneity of glucose-6-phosphate dehydrogenase enzymopathies in the GDR.
G6PD variants of 13 patients from 12 German families with different clinical symptoms have been characterized kinetically. Vmax G6PD was nearly zero in red blood cells of all carriers. Therefore G6PD variants were isolated from leucocytes, which proved to be a suitable source for analysis of instable G6PD variants. The testing program included KmG6P, KmNADP, Ki values of NADPH, ATP and 2,3 P2G, rate of utilization of dG6P, Gal6P, dNADP, NAD, and pH dependence. From the results obtained one can conclude that all analyzed G6PD variants represent individual mutations. The degree of metabolic dysregulation can be explained by the different kinetic and physico-chemical properties of these G6PD variants.


Management of simple renal cyst in children: French multicenter experience of 36 cases and review of the literature.
The widespread use of renal ultrasonography has resulted in simple renal cysts (SRC) being discovered with increasing frequency in routine pediatric urological practice. Management of SRC, however, remains controversial. Most SRC are asymptomatic, are diagnosed incidentally, and have no clinical consequence. Our goal was to focus on management strategies for SRC in children with the support of our experience and a review of the literature. A literature review was made of SRC in children since 1950, analyzing epidemiologic data, diagnosis, and management. In addition, a retrospective multicenter study was conducted from 1998 to 2009. Patients included presented with a unique SRC. Data recorded were patient characteristics (age, gender), symptoms, imaging features of the cyst (size, side, pole, and location), type of management, and long-term outcomes. To focus on management, two groups of patients were defined: primary surgical management and primary conservative management consisting of clinical and US follow-up. Our results were compared with the literature. Thirty-six cases were included. Fifteen patients were symptomatic. Comparing the two groups, long-term outcomes were similar. The only significant factors were preoperative (age of the patient, diameter and location of the cyst): the bigger the cyst, the more likely it was to be exorenal, and the greater the likelihood that surgery would be performed (p = 0.006). Symptoms were not a significant indicator for surgery. According to the literature and our experience, and considering the benign natural history of SRC and the similar outcomes whatever the treatment, primary conservative management is recommended for all cases. Surgery should be restricted to symptomatic large compressive cysts, increase in cyst size on follow-up, and uncertain diagnosis. Percutaneous cyst aspiration with sclerotherapy has not yet been used enough to ascertain its safety, and requires prospective evaluation.


Oncolytic Newcastle disease virus expressing a checkpoint inhibitor as a radioenhancing agent for murine melanoma.
Monoclonal antibodies (mAbs) targeting negative regulators, or checkpoint molecules (e.g. PD1/PD-L1 & CTLA4), of anti-tumoural T cells have demonstrated clinical efficacy in treating several neoplastic diseases. While many patients enjoy remarkable responses to checkpoint inhibitors, a majority show adverse effects. Understanding how checkpoint inhibitors may augment established chemotherapy or radiotherapy regimens or other immunotherapies like oncolytic viruses may lead to better clinical outcomes measured by improved efficacy with reduced toxicity. Here, we assess how Newcastle disease virus (NDV), an oncolytic virus in clinical testing, may interact with radiotherapy to enhance checkpoint inhibitor blockade. An immunocompetent B16-F10 murine melanoma model, generally considered to be a poorly immunogenic or "cold" tumour, was utilised to query whether combining localised radiotherapy with NDV may be more effective than either therapy alone in controlling tumours in mice treated with anti-PD1 or anti-CTLA4 monoclonal antibodies. We also investigated whether localised administration of a checkpoint inhibitor through an intratumoural injection of NDV that expresses anti-CTLA4 single-chain variable fragment (scFv) is comparable to systemic administration of anti-CTLA4 when combined with radiation in mediating its anti-tumour efficacy. Response rates were characterised by measuring tumour size over time, observation of complete tumour regression, and overall survival. Our results show that combining NDV plus radiotherapy with checkpoint inhibitors (PD1 or CTLA4 targeted mAbs) results in significantly better complete tumour regression rates with an abscopal effect in a murine model of melanoma than either single therapy combined with checkpoint inhibitors. Finally, we also show that localised administration of a recombinant NDV expressing anti-CTLA4 plus radiation is comparable to systemic anti-CTLA4 plus radiation in mediating its anti-tumour effect as assayed by survival benefit. Our results show that oncolytic NDV plus radiotherapy work together with checkpoint inhibitors to enhance tumour clearance of murine melanoma. NDV is an effective radiotherapy dose-sparing and immunotherapeutic agent capable of transgenic, in vivo expression of an anti-CTLA4 targeted scFv antibody with the potential to spare systemic exposure. The National Institutes of Health grant HHSN272201400008C supported the work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Delayed diagnosis of anomalous origin of the left coronary artery 16 years after mitral valve replacement.
Mitral insufficiency caused by ischemia is frequently found in anomalous origin of the left coronary artery from the pulmonary artery. We report a case of a 25-year-old woman who was diagnosed to have anomalous origin of the left coronary artery from the pulmonary artery and had successful left internal mammary artery bypass grafting 16 years after mitral valve replacement for mitral insufficiency of an unknown cause in her childhood.


Applying dissemination and implementation research methods to translate a school-based asthma program.
Our school-based asthma program has reduced asthma exacerbations for youth with health disparities in the Denver metropolitan area, due partly to addressing social determinants of health, such as access to health care and medications. Dissemination and implementation (D&I) science approaches accelerate the translation of evidence-based programs into routine practice. D&I methods are being applied more commonly to improve health equity. The purpose of this publication was to give an overview of D&I research methods, using our school-based asthma program as an example. To successfully scale out our program across the state of Colorado, we are applying a D&I framework that guides the adaptation of our existing implementation approach to better meet our stakeholders' local context-the Exploration, Preparation, Implementation, Sustainment framework. In a pragmatic trial design, we will evaluate the outcomes of implementing the program across 5 Colorado regions, with attention to health equity, using a second commonly used D&I framework-Reach, Effectiveness, Adoption, Implementation, and Maintenance. Our central hypothesis is that our program will have broad and equitable reach to eligible students (primary outcome) and will reduce asthma attacks and symptoms. This D&I approach accelerates dissemination of our program and is an applicable process for translating other effective allergy/asthma programs to address asthma and allergy-related disparities.


Acute intermittent porphyria after right hemi-colectomy.
Acute intermittent porphyria is a rare autosomal dominant metabolic disease. It is caused by a genetic mutation that results in deficiency of porphobilinogen deaminase enzyme, the third enzyme in heme biosynthesis. Acute intermittent porphyria precipitated by surgery is very rare. We present a 24 year-old woman who developed acute intermittent porphyria five days after right hemi-colectomy. Her presentation included neuro-visceral and psychiatric manifestations, and severe hyponatremia. She received critical care symptomatic management including mechanical ventilation. The diagnosis was based on a positive urine test for porphobilinogen and confirmed by the presence of a heterozygous mutation in the hydroxyrmethylbilane synthase (HMBS) gene (c.760delC p Leu254). Acute intermittent porphyria is the most common and life threatining type of acute porphyrias. It is more common in women and usually presents after puberty with acute abdominal pain and diverse neuro-psychiatric manifestations that can be confused with several surgical and medical diseases. Acute intermittent porphyria after surgery is most likely due to postoperative pain and low-calorie intake. Once suspected, prompt ICU management including high calorie intake are necessary to avoid serious complications and mortality before starting definitive treatment with hematin. Acute intermittent porphyria should be suspected in any patient, particularly young women, who develop diverse neuro-visceral and psychiatric manifestations and hyponatremia after surgery.


DUSP4 promotes esophageal squamous cell carcinoma progression by dephosphorylating HSP90β.
The molecular and pathogenic mechanisms of esophageal squamous cell carcinoma (ESCC) development are still unclear, which hinders the development of effective treatments. In this study, we report that DUSP4 is highly expressed in human ESCC and is negatively correlated with patient prognosis. Knockdown of DUSP4 suppresses cell proliferation and patient-derived xenograft (PDX)-derived organoid (PDXO) growth and inhibits cell-derived xenograft (CDX) development. Mechanistically, DUSP4 directly binds to heat shock protein isoform β (HSP90β) and promotes the ATPase activity of HSP90β by dephosphorylating HSP90β on T214 and Y216. These dephosphorylation sites are critical for the stability of JAK1/2-STAT3 signaling and p-STAT3 (Y705) nucleus translocation. In vivo, Dusp4 knockout in mice significantly inhibits 4-nitrochinoline-oxide-induced esophageal tumorigenesis. Moreover, DUSP4 lentivirus or treatment with HSP90β inhibitor (NVP-BEP800) significantly impedes PDX tumor growth and inactivates the JAK1/2-STAT3 signaling pathway. These data provide insight into the role of the DUSP4-HSP90β-JAK1/2-STAT3 axis in ESCC progression and describe a strategy for ESCC treatment.


Ischemic preconditioning reduces the severity of ischemia/reperfusion-induced pancreatitis.
In various organs, including heart, kidneys, brain, liver and stomach, preconditioning by brief exposure to ischemia protects the organ against damage evoked by subsequent severe ischemia. This study has been undertaken to check whether two brief ischemic periods protect the pancreas against severe ischemia/reperfusion-induced pancreatitis and, if so, what is the role of sensory and vagal nerves in this phenomenon. In male Wistar rats, the ischemic preconditioning of the pancreas was performed by clamping of celiac artery (2 x 5 min with 5 min interval). Thirty minutes after preconditioning or sham operation, the ischemia/reperfusion-induced pancreatitis was evoked by clamping of inferior splenic artery for 30 min using microvascular clips, followed by 1 h reperfusion. Sensory nerves ablation was induced 10 days before final experiments by capsaicin. Truncal vagotomy was performed 1 week before the experiment. Exposure to regular 30-min pancreatic ischemia followed by 1 h reperfusion led to the development of acute hemorrhagic pancreatitis. Ischemic preconditioning, applied prior to induction of pancreatitis, caused the reduction in plasma lipase, plasma interleukin-1beta and histological signs of pancreatic damage, as well as attenuated the reduction in pancreatic blood flow and DNA synthesis. Ablation of sensory nerves by capsaicin caused an aggravation of ischemia/reperfusion-induced pancreatic damage and attenuated a protective effect of ischemic preconditioning. Noxious effect of sensory nerves ablation on the pancreas was accompanied by the reduction in pancreatic blood flow and an increase in plasma interleukin-1beta. Similar but less pronounced deleterious effect on the pancreas was observed after vagotomy. We conclude that: (1) pancreatic ischemic preconditioning reduces the severity of ischemia/reperfusion-induced pancreatitis; (2) this effect seems to be related, at least in part, to the improvement of pancreatic blood flow and the reduction in the release of proinflammatory interleukin-1beta; (3) sensory and vagal nerves are involved in protective effect of ischemic preconditioning against pancreatic damage.


A conservative approach in a child with haematuria after accidental rectal impalement trauma.
We present a case of an 11-year-old boy with haematuria after traumatic rectal insertion of a sharp metal stick. It demonstrates that an expectative management with close observation can be considered in patients with rectal impalement trauma presenting with haematuria and stable vital parameters without significant injury on abdominal ultrasound.


Synthesis Strategies towards Tagged Homogeneous Catalysts To Improve Their Separation.
The recycling of homogeneous catalysts while keeping them in the homogeneous matrix is an ongoing challenge many reactions face if they are to find industrial applications. While a plethora of different synthetic approaches towards better, recyclable homogeneous catalysts exist, the literature shows a gap when one searches for a concise overview of the different catalyst modifications. This Review is designed to close that gap by summarising the existing synthesis pathways towards polar, non-polar, fluorous, and molecular-weight-enlarged catalysts and by examining their respective synthesis routes with a focus on modular and late-stage approaches. Furthermore, we map out the potential for a generally applicable tag library that allows straightforward catalyst modifications to tune them for each desired recycling strategy.


Visual cognition: rats compare shapes among the crowd.
Rats can discriminate simple shapes visually, even if they are moved around, made smaller, or partially covered up; the strategy they use may help shed light on human brain mechanisms for discriminating complex features, such as faces.


Digital dentistry: an overview of recent developments for CAD/CAM generated restorations.
As in many other industries, production stages are increasingly becoming automated in dental technology. As the price of dental laboratory work has become a major factor in treatment planning and therapy, automation could enable more competitive production in high-wage areas like Western Europe and the USA. Advances in computer technology now enable cost-effective production of individual pieces. Dental restorations produced with computer assistance have become more common in recent years. Most dental companies have access to CAD/CAM procedures, either in the dental practice, the dental laboratory or in the form of production centres. The many benefits associated with CAD/CAM generated dental restorations include: the access to new, almost defect-free, industrially prefabricated and controlled materials; an increase in quality and reproducibility and also data storage commensurate with a standardised chain of production; an improvement in precision and planning, as well as an increase in efficiency. As a result of continual developments in computer hardware and software, new methods of production and new treatment concepts are to be expected, which will enable an additional reduction in costs. Dentists, who will be confronted with these techniques in the future, require certain basic knowledge if they are to benefit from these new procedures. This article gives an overview of CAD/CAM-technologies and systems available for dentistry today.


Rate-limiting factors for lymphocyte protein synthesis. Ribosome commitment and the capacity of lymphocyte cell-free systems to translate exogenous mRNAs.
The properties of the protein synthesising systems of different lymphocyte preparations have been compared with those of non-lymphoid tissues. Polysome profiles from rat thymocytes, sheep mesenteric lymphocytes, rat liver and mouse ascites tumours showed that the commitment of ribosomes to protein synthesis in lymphocytes was relatively low. Initiation factor activities, assessed on the abilities of post-mitochondrial fractions to support exogenous mRNA translation, were limited or undetectable in lymphoid tissues. While the thymocyte system translated globin mRNA, the response was enhanced by ascites extracts rich in initiation factors. The mesenteric lymphocyte system responded only marginally to globin mRNA and poly(U) but the responses were not enhanced by ascites extracts. The activity of isolated mesenteric ribosomes was comparable with ribosomes from other tissues, indicating that extraribosomal factors were responsible for the poor overall activity of the mesenteric system. Finally, the effects of cycloheximide on the recruitment of polysomes in lymphocytes indicated that the commitment of ribosomes to protein synthesis might be restricted by both limited mRNA availability and limited capacity for initiation of mRNA translation.


DNA packaging: a new class of molecular motors.
DNA is packaged into preformed bacteriophage capsids to liquid crystalline density by the action of a portal protein complex. Single molecule packaging studies indicate that this is a new and extremely powerful class of molecular motors.


Extrapulmonary manifestations of sarcoidosis.
Sarcoidosis is a systemic disease characterized by the development of epithelioid granulomas in various organs. Although the lungs are involved in most patients with sarcoidosis, virtually any organ can be affected. Recognition of extrapulmonary sarcoidosis requires awareness of the organs most commonly affected, such as the skin and the eyes, and vigilance for the most dangerous manifestations, such as cardiac and neurologic involvement. In this article, the common extrapulmonary manifestations of sarcoidosis are reviewed and organ-specific therapeutic considerations are discussed.


An interim report of flurbiprofen for the control of idiopathic hypercalciuria.
Twenty patients with idiopathic hypercalciuria were entered into an 8 week open study to examine the effects of flurbiprofen 50 mg three times a day on urinary calcium excretion. Five patients had to be withdrawn because of side-effects. A statistically significant reduction in urinary calcium excretion was seen after 2 (p = 0.01) and 6 (p = 0.008) weeks treatment. The results suggest that flurbiprofen may be a useful alternative for the treatment of this disorder. The 25% of patients withdrawn due to side-effects may be a limiting factor.


Crowding induces differences in the diffusion of thermophilic and mesophilic proteins: a new look at neutron scattering results.
The dynamical basis underlying the increased thermal stability of thermophilic proteins remains uncertain. Here, we challenge the new paradigm established by neutron scattering experiments in solution, in which the adaptation of thermophilic proteins to high temperatures lies in the lower sensitivity of their flexibility to temperature changes. By means of a combination of molecular dynamics and Brownian dynamics simulations, we report a reinterpretation of those experiments and show evidence that under crowding conditions, such as in vivo, thermophilic and homolog mesophilic proteins have diffusional properties with different thermal behavior.


Insights into the statistical physics modeling and fractal like kinetic approach for the adsorption of As(III) on coordination polymer gel based on zirconium(IV) and 2-thiobarbituric acid.
A novel coordination polymer gel based on zirconium(IV) and 2-thiobarbituric (ZrTBA) was synthesized and explored its potential to remediate As(III) from water. Box-Behnken design with desirability function and genetic algorithm yielded the optimized conditions (initial concentration=194 mg L-1, dosage = 42.2 mg, time= 95 min and pH = 4.9) for maximum removal efficiency (99.19 %). The experimental saturation capacity for As(III) was 178.30 mg g-1. The steric parameter n > 1 of the best fitted statistical physics model: monolayer with two energies (R2 = 0.987-0.992) suggested multimolecular mechanism with vertical orientation of As(III) molecules onto the two active sites. XPS and FTIR confirmed the two active sites being zirconium and oxygen. The adsorption energies (E1 = 35.81-37.63 kJ/mol; E2 = 29.50-36.49 kJ/mol) and isosteric heat of adsorption indicated that physical forces governed the As(III) uptake. DFT calculations implied that the weak electrostatic interaction and hydrogen bonding were involved. The best fitted (R2>0.99) fractal like pseudo first order model established energetic heterogeneity. ZrTBA showed excellent removal efficiency in the presence of potential interfering ions and could be used up to 5 cycles of adsorption-desorption with < 8 % loss in the efficiency. ZrTBA removed ≥96.06 % As(III) from real water samples spiked at different levels of As(III).


SS-31 Improves Cognitive Function in Sepsis-Associated Encephalopathy by Inhibiting the Drp1-NLRP3 Inflammasome Activation.
Neuroinflammation and microglial activation are involved in the pathogenesis of sepsis-associated encephalopathy (SAE). Mitochondrial dynamics emerged as a new player in the regulation of immunological processes. In this study, we aimed at exploring the effects of mitochondrial-targeted antioxidant peptide SS-31 on cognitive function in mice with SAE. In mice, SS-31 was intraperitoneally administered for seven consecutive days after cecal ligation and puncture surgery. SS-31 improved cognitive performance and survival rate of mice and alleviated hippocampal inflammation, reactive oxygen species production, and excessive mitochondrial fission. The increase of nucleotide-binding oligomerization domain 3 (NLRP3) and phosphorylated dynamin-related protein 1 (Drp1) ser616 in microglia was attenuated by SS-31. In vitro, the microglial cell line BV-2 was pre-treated with SS-31, followed by lipopolysaccharide/adenosine triphosphate induction. SS-31 effectively decreased the activation of NLRP3 inflammasome, mitochondrial translocation of Drp1, excessive mitochondrial fission, and mitochondrial membrane recruitment of gasdermin-D N-terminal (GSDMD-N). Similarly, knockdown of Drp1 inhibited the activation of NLRP3 inflammasome. SS-31 improved survival rate and cognitive functions of mice with SAE, related to mitochondrial fission protein Drp1 to inhibiting activation of NLRP3 inflammasome.


Silencing of lncRNA SNHG17 inhibits the tumorigenesis of epithelial ovarian cancer through regulation of miR-485-5p/AKT1 axis.
Epithelial ovarian cancer (EOC) stands up for about 90% of ovarian cancer cases, which is the frequent cause of death among women. LncRNAs are involved in progression of EOC. Meanwhile, lncRNA SNHG17 was upregulated in EOC, while the detailed function of SNHG17 in EOC remains unclear. Protein and mRNA levels were assessed by western blot and RT-qPCR, respectively. The function of SNHG17 in EOC cells was tested by CCK-8, Ki-67 staining, flow cytometry and transwell assay. Dual luciferase was applied for assessing the relation among SNHG17, miR-485-5p and AKT1. Furthermore, in vivo experiments were applied to test the impact of SNHG17 in EOC. SNHG17 knockdown reduced the proliferation and promoted the apoptosis of EOC cells. Consistently, si-SNHG17 obviously reduced the invasion and epithelial-to-mesenchymal transition (EMT) process of EOC cells. MiR-485-5p was proved to be the target miRNA of SNHG17, and SNHG17 negatively regulated the level of miR-485-5p. MiR-485-5p inhibitor significantly abolished the anti-tumor impact of si-SNHG17 on EOC. AKT1 was identified to be targeted by miR-485-5p, and miR-485-5p negatively modulated AKT1 and p-mTOR levels. Moreover, miR-485-5p mimics reduced the proliferation, migration and promoted the apoptosis of EOC cells via targeting AKT1. Furthermore, si-SNHG17 markedly suppressed EOC growth in vivo. SNHG17 silencing inhibits the development of EOC via regulation of miR-485-5p/AKT1 axis. Thus, our study might supply a novel strategy against EOC.


[Thyroid effect on brain activity in adolescents during heart rhythm biofeedback session].
Types of neurophysiologic and thyroid condition in 15-17-year old adolescents were studied for the purpose of heart rhythm biofeedback session effect by heart rhythm variability parameters. Changes of heart rhythm vegetative regulation activity modulate functional capacities of central vegetative regulation structures. The biofeedback training with heart rhythm variability parameters increases brain bioelectrical activity in different frequency ranges. The thyroid system modulates functional activity of vegetative regulation central structures uppermost at sympathotonic and thyreotropin increasing leads to increase of rhythm maker structure reactivity in brain.


Comparison of the beta-adrenoceptors in the myocardium and coronary vasculature of the kitten heart.
The relative potencies of (minus) noradrenaline, (minus)-adrenaline, (plus or minus)-isoprenaline and (plus or minus)-salbutamol have been assessed for their positive inotropic and chronotropic actions on kitten isolated atria. These relative potencies have been compared with those obtained for the relative coronary dilator potencies in two preparations. These were intact hearts perfused by Langendorff's method and isolated perfused coronary arteries from the kitten. The relative molar potencies for inotropic effects were noradrenaline 1: adrenaline1: iso-prenaline 7: salbutamol 0.6. The observed ratios for chronotropic effects were not significantly different from those for inotropic effects. The relative potencies of noradrenaline, adrenaline and isoprenaline as myocardial stimulants were similar to their relative potencies as coronary dilators in the intact heart. Similar relative potencies for noradrenaline and isoprenaline were also found in the isolated coronary artery but adrenaline was only one third as active as noradrenaline on this preparation. In both the intact heart and in the isolated coronary artery salbutamol was about one tenth as active as noradrenaline. It was therefore less active relative to noradrenaline as a coronary dilator than as a myocardial stimulant. In spite of these differences in relative potency ratios for myocardial and coronary dilator effects, similar dissociation constants (Kb values) for practolol against isoprenaline were found in driven atria and in isolated coronary arteries. Myocardial and coronary vascular beta-adrenoceptors thus can both be placed in the general classification of beta1-adrenoceptors.


DNA fingerprinting of single colonies of Helicobacter pylori from gastric cancer patients suggests infection with a single predominant strain.
In each of six gastric cancer patients, repetitive extragenic palindromic PCR DNA fingerprints of 18 single colonies of Helicobacter pylori from the gastric antrum, corpus, and cardia were identical and matched that of the parental isolate. In three additional gastric cancer patients, 17 of 18 single-colony DNA fingerprints were identical to each other and to the DNA fingerprint of the corresponding parental isolate.


The future of pyrogenicity testing: Phasing out the rabbit pyrogen test. A meeting report.
The rabbit pyrogen test (RPT) was the benchmark for pyrogenicity testing, but scientific advancements have provided innovative and humane methods, such as the in vitro monocyte-activation test (MAT). However, transitioning from the RPT to the MAT has been challenging. The European Directorate for the Quality of Medicines & HealthCare, the Council of Europe, and the European Partnership for Alternative Approaches to Animal Testing jointly hosted an international conference entitled "The future of pyrogenicity testing: phasing out the rabbit pyrogen test". The conference aimed to show how the European Pharmacopoeia intends to remove the RPT from its texts by 2026, facilitate the use of MAT, and identify gaps in the suppression of RPT. The events contributed to a better understanding of the barriers to RPT replacement and acceptance of in vitro alternatives. Participants comprised stakeholders from Asia, Europe, and North America, including vaccine developers, contract laboratories, and regulators. Participants shared their replacement strategies and experiences with MAT implementation. They emphasised the need for continued cooperation between stakeholders and stressed the importance of international harmonisation of regulatory requirements to help accelerate MAT acceptance outside Europe. Despite the challenges, the willingness to eliminate the unnecessary use of RPT was common across all participants.


Safety and effectiveness of switching to Abacavir/Lamivudine plus rilpivirine for maintenance therapy in virologically suppressed HIV-1 individuals in Singapore (SEALS).
The efficacy and tolerability of an antiretroviral regimen are important considerations for selection of HIV-1 infection maintenance therapy. Abacavir/lamivudine plus rilpivirine (ABC/3TC + RPV) has been shown in international studies to be effective and well-tolerated in virologically suppressed individuals. This study evaluated the effectiveness and safety of switching to ABC/3TC + RPV as maintenance therapy in virologically suppressed HIV-1 infected individuals in Singapore. In this retrospective, single-centre study, we included individuals who were prescribed ABC/3TC + RPV, had HIV-1 viral load (VL) < 50 copies/ml immediately pre-switch, and had no documented history of resistance mutations or virologic failure to any of the components. The follow-up period was 48 ± 12 weeks. The primary outcome was the proportion of individuals who maintained virologic suppression of HIV-1 VL < 50 copies/ml at the end of follow-up period based on on-treatment analysis. The secondary outcomes were the resistance profiles associated with virologic failure, changes in immunologic and metabolic parameters, and the safety profile of ABC/3TC + RPV. A total of 222 individuals were included in the study. The primary outcome was achieved in 197 individuals [88.8%, 95% confidence interval: 83.7-92.4%]. There were 21 individuals (9.5%) who discontinued treatment for non-virologic reasons. The remaining 4 individuals experienced virologic failure, of whom, 3 of these individuals had developed emergent antiretroviral resistance and had HIV-1 VL > 500 copies/ml at the end of the 48 ± 12 weeks follow-up period. The remaining individual experienced sustained low level viremia and subsequently achieved viral suppression without undergoing resistance testing. A total of 49 adverse events were observed in 31 out of 222 individuals (14.0%), which led to 13 individuals discontinuing therapy. Neuropsychiatric adverse events were most commonly observed (53.1%). A statistically significant increase in CD4 was observed (p < 0.01), with a median absolute change of 31 cells/uL (interquartile range: - 31.50 to 140.75). No significant changes in lipid profiles were detected. ABC/3TC + RPV is a safe and effective switch option for maintenance therapy in virologically suppressed HIV-1 individuals with in Singapore.


The relationship between growth fractions and oestrogen receptors in human breast carcinoma, as determined by immunohistochemical staining.
Measurements of the growth fraction (GF) and oestrogen receptor (OR) status were performed by immunohistochemical staining, using the monoclonal antibodies Ki-67 and anti-OR, in consecutive cryostat sections of biopsies from 74 women with primary breast cancer, and 12 women with benign breast disease. A significant inverse correlation was identified between the GF and OR status (r = -0.452, P less than 0.0001), but a group of OR-positive tumours with high GFs was also observed. There was a strong positive correlation between immunocytochemically determined OR percentages and values obtained with a cytosolic OR biochemical assay for the 70 cases in which both techniques were performed (r = 0.801, P less than 0.0001). A significant relationship was also revealed between the histological grade of infiltrating ductal carcinomas and their associated GFs (r = 0.622, P less than 0.0001). No correlation was found between the GF and the number of positive axillary nodes. Our findings suggest that GF and OR status are useful independent prognostic parameters in breast cancer, but the former probably has an overriding influence. Both parameters may be useful guides for selection of appropriate endocrine and/or adjuvant chemotherapy.


Calcium binding sites in the vesicles of the carotid and aortic body chief cells.
Chief cells of the carotid and aortic body chemoreceptors possess numerous cytoplasmic dense-core vesicles which are known to contain primarily dopamine. Following fixation in solutions containing 50 mM CaCl2, a 20--30 nm electron-dense particle (EDP) is often observed eccentrically located in many of the vesicles. Approximately 44% of the carotid body and 16% of the aortic body vesicles contain an EDP. The EDP probably represents the Ca++ binding site critical to the stimulus-secretion coupling events culminating in exocytosis of these vesicles. The presence of Ca++ in the cytoplasmic vesicles was verified by electron probe X-ray microanalysis.


Developmental changes of calretinin immunoreactivity in the lamprey spinal cord.
We studied the distribution of calretinin immunoreactivity (CR-ir) in the rostral and intermediate levels of the spinal cord of lampreys from embryonic to adult periods. CR-ir was first observed at hatching in motoneurons and primary sensory neurons of the spinal cord, the dorsal cells. During the prolarval period two new cell types showed CR-ir: ganglion cells and interneurons. Motoneurons, dorsal cells, and ganglion cells were strongly positive, whereas interneurons were weakly stained in late prolarvae. The intensity of CR-ir in these four types of cells changed during the larval period. Increase of CR-expression was found in interneurons but a decrease in dorsal cells and in ganglion cells. These changes were more evident in premetamorphic larvae. Postmetamorphic lampreys showed almost no CR-ir in dorsal cells. In adult lampreys, the interneurons showed the highest CR-ir, whereas motoneurons were more weakly stained than in earlier stages of development. Moreover, in adults the dorsal cells and the ganglion cells showed no CR-ir. The present study shows that CR-ir changes during lamprey spinal cord development in different types of neurons, sometimes in opposite ways. This plasticity of CR-expression may indicate different needs from subsets of lamprey spinal cord cells involved in the different locomotor behaviors along its life cycle.


Vertical one-and-a-half syndrome in a patient with pecheron artery ischemia: A case report.
Vertical one-and-a-half syndrome (VOHS) is an uncommon presentation resulting from a unilateral thalamomesencephalic stroke with involvement of the rostral interstitial nucleus of the medial longitudinal fasciculus and posterior commissure. The artery of Percheron (aPe) is a branch of the posterior cerebral artery (PCA) and it is a variant that arises as a solitary trunk supplying both medial thalami and upper midbrain. A 78-year-old female patient, presented at the hospital emergency with approximately 12 hours of sudden onset of diplopia, associated with dizziness. Neurological exam revealed torsional nystagmus associated with bilateral upgaze palsy with limitation of infraduction on the left. We describe a rare case of VOHS associated with ischemic alterations at the MRI suggesting an aPe impairment. The conjugate gaze control lies anatomically at the midbrain at the central nervous system (CNS). This report describes a rare type of VOHS and brings a new insight on a possible aPe topography possibly causing this clinical presentation.


Adhesive interactions of neutrophils and leukotriene synthesis.
Cell-substrate and cell-cell adhesion of neutrophils has been found to slow down the calcium ionophore A23187-induced synthesis of 5-lipoxygenase (5-LO) metabolites of arachidonic acid. Addition of the exogenous substrate, arachidonic acid (AA), together with A23187, resulted in the enhanced production of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) by adherent neutrophils in comparison with those by the cells in suspension. We observed also the enhanced production of 5-LO metabolites in attached cells when we stimulated the cells by the combined action of phorbol 12-myristate 13-acetate (PMA) and A23187. Thus, the adhesion to solid substrate and to other cells, an important regulatory factor for the activity of many cells, is a powerful regulator of leukotriene production by neutrophils.


Neuroprotective Effects of Tetrahydroxystilbene Glucoside against Rotenone-Induced Toxicity in PC12 Cells.
To investigate the mechanism of the protective effect of tetrahydroxystilbene glucoside (TSG) on nerve cells, an injury model induced by rotenone in PC12 cells was constructed. Cell viability was detected by using cell counting kit-8 (CCK8) assay. Apoptosis was detected by using flow cytometry. The mitochondrial membrane potential (MMP) was detected by using the fluorescent probe JC-1. Generation of reactive oxygen species (ROS) in PC12 cells was determined using the 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester (CM-H2DCFDA) probe. Protein expression in PC12 cells was detected using Western blotting. The results showed that TSG (20-100 µM) attenuated the cytotoxic effects of rotenone on PC12 cells. TSG pretreatment attenuated the apoptosis rate, the degradation of poly(ADP-ribose)polymerase (PARP) and the activation of cleaved caspase 3, which was induced by rotenone. TSG can significantly reduce the effect of rotenone on the reduction of MMP and the expression of cytoC in the cytosolic fraction. TSG attenuated rotenone-induced de-phosphorylation and mitochondrial translocation of cofilin, as well as rotenone-induced accumulation of ROS. The Western blot results showed that ROT could decrease the expression level of phosphorylated (p)-Glycogen synthase kinase-3β (GSK)-3β and p-AKT, and TSG could weaken these effects of rotenone. In addition, TSG increased the expression level of nuclear factor-E2-related factor 2 (Nrf2) in the nuclear fraction. These results suggest that TSG could protect PC12 cells against rotenone through multiple pathways. Thus, TSG has the potential to become a novel neuroprotective agent.


Transforming growth factors type beta 1 and beta 2 suppress rat astrocyte autoantigen presentation and antagonize hyperinduction of class II major histocompatibility complex antigen expression by interferon-gamma and tumor necrosis factor-alpha.
The transforming growth factors (TGF) type beta 1 and beta 2 are regulatory cytokines strongly affecting rat astrocyte immune functions. Both cytokines suppressed presentation of autoantigen by astrocytes: highly encephalitogenic T cells cocultured with TGF-beta-treated astrocytes in the presence of myelin basic protein did not become activated to transfer experimental allergic encephalomyelitis, a central nervous system (CNS) autoimmune disease. Furthermore, TGF-beta 1 and -beta 2 antagonized hyperinduction of astrocyte major histocompatibility complex (MHC) class II antigen expression by interferon-gamma and tumor necrosis factor-alpha. Thus, TGF-beta might be a potential regulator of CNS inflammation.


Ameliorative potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) on the relative tissue weights of streptozotocin-induced diabetic rats.
To investigate the ameliorating potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) incorporated feeds on the renal and liver growths of diabetic rats, induced with 55 and 65 mg/kg body weight of Streptozotocin. The blood glucose level of the rats was measured with a glucometer, the protein and glucose and specific gravity (SPGR) in the urine samples of the rats were measured using urine assay strips and urinometer respectively. The chemical composition and antioxidant screening of the test feeds were carried out using standard techniques. Administration of the test feeds for 21 days to the diabetic rats of groups 4 and 5, resulted in 58.75% and 38.13% decreases in hyperglycemia and amelioration of their elevated urinary protein, glucose, SPGR, and relative kidney weights. The diabetic rats administered cocoyam incorporated feeds, had 2.71% and 19.52% increases in weight and growth rates, the diabetic rats administered unripe plantain incorporated feeds had 5.12% and 29.52% decreases in weight and growth rates while the diabetic control rats had 28.69%, 29.46%, 248.9% and 250.14% decreases in weights and growth rates. The cocoyam incorporated feeds contained higher antioxidants, minerals and phytochemicals except alkaloids than unripe plantain feed. Cocoyam and unripe plantain could be useful in the management of diabetic nephropathy.


Allogeneic bone marrow transplantation in children: single institution experience from 1974 to 1992.
At the Children's Hospital, University of Helsinki, Finland, bone marrow transplantations have been performed since 1974. Between 1974 and 1992, 62 children received allogeneic bone marrow grafts. Median patient age was 9.3 years. Thirty-two patients had ALL, 13 AML and 11 had severe aplastic anemia (SAA). Graft failure occurred in 4 of the 62 patients. The overall long-term survival rate was 47%. Relapse of leukemia was the most common cause of death, especially in patients with ALL transplanted in second or later remission. Deaths during the first 2 months after transplant have decreased with time. In a small country such as Finland, it is important to centralize the experience of allogeneic BMTs, particularly for pediatric patients.


Emotional intelligence as a predictor of self-efficacy among students with different levels of academic achievement at Kermanshah University of Medical Sciences.
studies have indicated that emotional intelligence is positively related to self-efficacy and can predict the academic achievement. The present study aimed to investigate the role of emotional intelligence in identifying self-efficacy among the students of Public Health School with different levels of academic achievement. This correlational study was conducted on all the students of Public Health School. 129 students were included in the study through census method. Data were collected using Emotional Intelligence and self-efficacy questionnaires and analyzed using descriptive statistics and regression analysis by SPSS 14. The average score of students with high academic achievement was higher in self-efficacy (39.78±5.82) and emotional intelligence (117.07±10.33) variables and their components than that of students with low academic achievement (39.17±5.91, 112.07±13.23). The overall emotional intelligence score to predict self-efficacy explanation was different among students with different levels of academic achievement (p<0.001). Self-efficacy structure was explained through self-awareness and self-motivation components in students with low academic achievement (r=0.571). In students with high academic achievement, self-awareness, self-motivation and social consciousness played an effective role in explaining self-efficacy (r=0.677, p<0.001). Emotional intelligence and self-efficacy play an important role in achieving academic success and emotional intelligence can explain self-efficacy. Therefore, it is recommended to teach emotional intelligence skills to students with low academic achievement through training workshops.


An innovative role for tenoxicam as a quorum sensing inhibitor in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is an opportunistic pathogen exhibiting higher resistance to commonly used antibiotics. Microbial resistance to antibiotics is a major problem that hinders attempts to control microbial infections. Quorum sensing inhibitors could help us solve such problem by repressing quorum sensing that controls the production of virulence factors in many pathogens including P. aeruginosa. In this study, the influence of tenoxicam, a non-steroidal anti-inflammatory drug, on quorum sensing in P. aeruginosa was characterized. Treatment of P. aeruginosa with tenoxicam decreased production of many virulence factors such as pyoverdin, rhamnolipids, pyocyanin, elastase, proteases, and hemolysins. Moreover, qRT-PCR revealed a significant reduction in expression of quorum sensing genes in tenoxicam-treated P. aeruginosa in comparison with untreated bacteria. Tenoxicam markedly reduced the capacity of P. aeruginosa to kill mice infection model. Mice injected with tenoxicam-treated P. aeruginosa exhibited higher survival rate as compared with those inoculated with untreated bacteria. Current data clearly demonstrate that tenoxicam has quorum sensing inhibitory effect on P. aeruginosa. Tenoxicam could play a role in reduction of Pseudomonas quorum sensing-dependant virulence factors production, and therefore affect its pathogenesis in the host. In summary, the current study suggests that tenoxicam could be used as adjuvant to antibiotics in the management of diseases caused by P. aeruginosa.


Evaluating a Targeted Bedside Measure of Cerebral Perfusion in a Nonhuman Primate Model of Neonatal Hypoxic-Ischemic Encephalopathy.
To compare ultrasound-derived resistive indices (RIs) obtained at the level of the thalamus via fast Doppler ultrasound with traditional anterior cerebral artery measures in a model of neonatal hypoxic-ischemic encephalopathy and to correlate each with clinical outcomes. Nine nonhuman primate neonates underwent no umbilical cord occlusion (n = 3), umbilical cord occlusion without hypothermia (n = 3), or umbilical cord occlusion with hypothermia (n = 3). The RI was measured in the anterior cerebral artery and thalamus on days 0, 1, and 4 of life. Magnetic resonance imaging with spectroscopy was performed on day 4. Mean thalamus and anterior cerebral artery RI values in the first 36 hours of life were statistically different in neonates who died (+0.13; P = .019) or developed cerebral palsy (-0.08; P = .003). Thalamic RI values showed stronger associations with serum and spectroscopic lactate values than those in the anterior cerebral artery. The umbilical cord occlusion-with-hypothermia group showed a significant increase in the RI in the thalamus but not the anterior cerebral artery. Resistive index measurements in the thalamus may eventually supplement other bedside measures for predicting outcomes in the HIE population, but further studies need to differentiate the effect of hypothermia from illness severity on thalamic perfusion.


Simulation in elemental mapping using aberration-corrected electron microscopy.
Elemental mapping at the atomic scale in aberration-corrected electron microscopes is becoming increasingly widely used. In this paper we describe the essential role of simulation in understanding the underlying physics and thus in correctly interpreting these maps, both qualitatively and quantitatively.


The covalent structure of calf skin type III collagen. V. The amino acid sequence of the cyanogen bromide peptide alpha 1(III)CB9A (position 789 to 927).
The cyanogen bromide peptide alpha 1(III)CB9A is 139 amino acid residues in length and occupies positions 789--927 along the alpha 1(III) chain. Peptides necessary for the complete sequence analysis were obtained after fragmentation of alpha 1(III)CB9B with trypsin, protease from Staphylococcus aureus V8, hydroxylamine and chymotrypsin. They were separated mainly by chromatography on Sephadex G-50 and phosphocellulose and subsequently sequenced using the automated Edman degradation procedure.


Human epithelial teratocarcinoma cells (P3): radiobiological characterization, DNA damage, and comparison with other rodent and human cell lines.
Survival parameters and immediate DNA damage induced by 60Co gamma rays, 50-kVp X rays, and Janus fission-spectrum neutrons in human epithelial P3 cells (derived from an embryonic teratocarcinoma) are compared with those for Chinese hamster lung V79 cells. DNA damage caused by X and gamma irradiation, measured by alkaline elution methods, is the same in both cell types, whereas the P3 cells are about two times more sensitive (as measured by Do ratios of the final survival curve slope) to the lethal effects of these radiations than are the V79 cells. Human P3 cells are also more sensitive to the lethal effects of fission-spectrum neutrons than V79 cells. Survival experiments with split radiation doses and hypertonic salt treatment indicate that both P3 cells and V79 cells can recover from radiation-induced damage efficiently.


Approximately half of patients with coronary spastic angina had pathologic exercise tests.
We examined the clinical usefulness of treadmill exercise tests (TETs) in diagnosing coronary spastic angina (CSA). We performed the TETs and 24-h Holter monitoring in 300 CSA patients consisting of 152 patients with rest angina, 77 patients with effort angina, and 71 patients with rest and effort angina. Organic stenosis (>75%) was observed in 44 patients. Multiple spasms were recognized in 204 patients (68%). Positive TETs were recognized in 113 patients (38%) and borderline was observed in 30 patients (10%). Positive response was significantly higher in patients with organic stenosis than those without fixed stenosis (63.6% vs. 33.2%, p<0.001). Moreover, ST elevation was more frequent in patients with organic stenosis than those without fixed stenosis (27.3% vs. 1.2%, p<0.001). Positive response in patients with effort angina (46.8%) was higher than those in patients with rest angina (33.6%) and rest and effort angina (36.6%), but not significant. Positive response was not different between single spasm and multiple spasms. In all 300 patients, ST segment elevation was observed in only four patients (1.3%) on the 24-h Holter monitoring. TET was useful in documenting ischemia in patients with CSA. More than a third of patients with CSA had positive TETs. Moreover, we obtained the pathologic TET response in approximately half of patients with CSA.


A novel SMARCAL1 missense mutation that affects splicing in a severely affected Schimke immunoosseous dysplasia patient.
Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive disease characterized by skeletal dysplasia, focal segmental glomerulosclerosis, renal failure and immunodeficiency. In this work, we report the molecular studies undertaken in a severely affected SIOD patient that died at six years old due to nephropathy. The patient was screened for mutations using a targeted skeletal dysplasias panel. A homozygous novel missense mutation was identified, c.1615C > G (p.[Leu539Val]) that was predicted as mildly pathogenic by in silico pathogenicity prediction tools. However, splicing prediction software suggested that this variant may create a new splicing donor site in exon 9, which was subsequently confirmed using a minigene assay in HEK293 cells. Thus, the splicing alteration, c.1615C > G; r.1615c > g, 1615_1644del; (p.[Leu539_Ile548del]), results in the loss of 10 amino acids of the HARP-ATPase catalytic domain and the RPA-binding domain. Several studies have demonstrated a weak genotype-phenotype correlation among such patients. Thus, the molecular characterization has helped us to understand why a predicted weakly pathogenic missense mutation results in severe SIOD and should be considered in similar scenarios.


Neurofascin is a glial receptor for the paranodin/Caspr-contactin axonal complex at the axoglial junction.
In myelinated fibers of the vertebrate nervous system, glial-ensheathing cells interact with axons at specialized adhesive junctions, the paranodal septate-like junctions. The axonal proteins paranodin/Caspr and contactin form a cis complex in the axolemma at the axoglial adhesion zone, and both are required to stabilize the junction. There has been intense speculation that an oligodendroglial isoform of the cell adhesion molecule neurofascin, NF155, expressed at the paranodal loop might be the glial receptor for the paranodin/Caspr-contactin complex, particularly since paranodin/Caspr and NF155 colocalize to ectopic sites in the CNS of the dysmyelinated mouse Shiverer mutant. We report that the extracellular domain of NF155 binds specifically to transfected cells expressing the paranodin/Caspr-contactin complex at the cell surface. This region of NF155 also binds the paranodin/Caspr-contactin complex from brain lysates in vitro. In support of the functional significance of this interaction, NF155 antibodies and the extracellular domain of NF155 inhibit myelination in myelinating cocultures, presumably by blocking the adhesive relationship between the axon and glial cell. These results demonstrate that the paranodin/Caspr-contactin complex interacts biochemically with NF155 and that this interaction is likely to be biologically relevant at the axoglial junction.


Development of Colorimetric and Ratiometric Fluorescence Membranes for Detection of Nitrate in the Presence of Aluminum-Containing Compounds.
In this study, a quantitative analysis of nitrate in aqueous solution was performed through the combination of an oxazine170 perchlorate⁻ethyl cellulose (O17-EC) membrane with aluminum-containing compounds. Aluminum of Devarda's alloy (DA) or a clay hydrotalcite (HT) was employed for the reduction of nitrate to produce ammonia, and the produced ammonia was detected by the O17-EC membrane. The method of combining the O17-EC membrane with aluminum compounds has showed a broad detection range of nitrate. That is, the DA was combined with the O17-EC membrane and showed the linear nitrate detection ranges of 1⁻10 mM and 10⁻100 mM, while the O17-EC membrane immobilized with the clay HT showed a linear detection range of 0.1⁻1 mM nitrate. The visual color transition of the nitrate-sensing membranes at different nitrate concentrations was clearly observed under sunlight or irradiation of a light-emitting diode (LED) at an excitation wavelength of 470 nm (LED470).


Modeling Alzheimer's Disease Using Human Brain Organoids.
Alzheimer's disease (AD) is the primary cause of dementia, to date. The urgent need to understand the biological and biochemical processes related to this condition, as well as the demand for reliable in vitro models for drug screening, has led to the development of novel techniques, among which stem cell methods are of utmost relevance for AD research, particularly the development of human brain organoids. Brain organoids are three-dimensional cellular aggregates derived from induced pluripotent stem cells (iPSCs) that recreate different neural cell interactions and tissue characteristics in culture. Here, we describe the protocol for the generation of brain organoids derived from AD patients and for the analysis of AD-derived pathology. AD organoids can recapitulate beta-amyloid and tau pathological features, making them a promising model for studying the molecular mechanisms underlying disease and for in vitro drug testing.


Temperature effect on nanometer-scale physical properties of mixed phospholipid monolayers.
Mixed dipalmitoylphosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC) monolayers have been deposited on mica using Langmuir-Blodgett technique, as a model system for biomembranes. Nanometer-scale surface physical properties were quantitatively characterized with the gradual temperature change using the atomic force microscope. At 25 degrees C, tapping mode imaging revealed the clear phase-separation in the form of microscopic DPPC domain embedded in a DOPC matrix and the obvious step height between the higher DPPC phase and the lower DOPC phase. Surface force measurement made at 25 degrees C in contact mode showed significant contrasts in deformation elasticity, adhesion, and jump-to-surface. These physical property differences were kept below 40 degrees C, while they almost disappeared over 40 degrees C. In addition, the reversibility of the properties for the temperature change was also found.


Import and processing of precursor to mitochondrial aspartate aminotransferase. Structure-function relationships of the presequence.
The precursor protein of pig mitochondrial aspartate aminotransferase (pre-mAspAT) contains a 29-residue presequence (Joh, T., Nomiyama, H., Maeda, S., Shimada, K., and Morino, Y. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 1-5). Pre-mAspAT produced in an in vitro transcription and translation system was avidly imported into pig and rat liver mitochondria to be processed to the mature form of the enzyme. The pre-mAspAT was also processed to the mature form upon incubation with mitochondrial extracts. We synthesized precursor proteins with alterations within the presequence and compared quantitatively the effects of these mutations on the rates of both import and processing. Single and multiple substitutions of four basic residues with neutral amino acids at positions 5, 8, 18, and 28 showed that each residue contributes differentially to import and processing. Substitutions of His5 and Arg8 with glycines abolished the import activity but did not appreciably affect the rate of processing. Substitution of Arg28 with leucine at the position adjacent to the cleavage site seriously impaired the processing without appreciably affecting the rate of import. Analysis of deletions revealed that the amino-terminal region from position 2 to 8 was essential for both the import and processing. Thus the positive charges in the amino-terminal region are critical for import while the amino-terminal peptide segment and the cleavage site region appear to be requisite for recognition by a processing protease.


Treatment of macular edema due to branch retinal vein occlusion with single or multiple intravitreal injections of bevacizumab.
We examined the predictive factors for final visual acuity (VA) with macular edema of branch retinal vein occlusion (BRVO) treated by intravitreal injection of bevacizumab (IVB) and examined the differences between patients without recurrent macular edema due to BRVO after a single IVB and patients treated with multiple IVB because of recurrent macular edema. In this retrospective study, 37 eyes of 37 patients with BRVO were treated with IVB and followed up for more than 24 weeks. Eighteen eyes showed no recurrence of macular edema after a single IVB (single IVB group). The remaining 19 eyes showed recurrent macular edema and underwent multiple IVB (multiple IVB group). VA and morphologic parameters of optical coherence tomography were examined. Mean VA, central retinal thickness, and mean retinal thickness in a circular region of 1-mm diameter at the fovea improved significantly with IVB treatment in both groups. Final VA was correlated with baseline VA and integrity grade of the photoreceptor inner and outer segment (IS/OS) line beneath the fovea. Baseline VA and IS/OS line grade at 4 weeks may be predictive factors for final VA.


Impact of call center work in subjective voice symptoms and complaints--an analytic study.
To estimate the prevalence of vocal symptoms, occupational risk factors, associated symptoms and their impact on the professional activity of the telemarketers. Cross-section analytical study with 124 telemarketers and 109 administrative workers (control group) selected from a random sample stratified by gender. The subjects answered an anonymous self-administered questionnaire involving issues related to the presence of vocal symptoms, potential risk factors for dysphonia, and vocal impact of symptoms in professional activity. The presence of one or more voice symptoms that occurred daily or weekly was considered positive for the presence of vocal symptoms. The prevalence of vocal symptoms was found in 33% of telemarketers and in 21% of the control group, indicating an association between vocal symptoms and the activity of the telemarketer. When adjusted for confounders, this association remained in the sense of risk. In telemarketers, the sensation of dry air, ambient noise, and lack of vocal rest were the most frequently reported complaints reported by those presenting vocal symptoms. Almost 70% of telemarketers with vocal symptoms reported that these symptoms interfere with their professional activity. The rate of absenteeism by vocal symptoms in this group was 29%. Vocal symptoms are common in most telemarketers when compared to their peer controls, and significantly affect their job performance.


Effect of training based on health belief model and behavioral intention on improving dental and oral self-care behavior in 9-12-year-old Iranian female students.
Training dental and oral health behaviors by using appropriate training models and theories is an important issue in preventing dental and oral diseases. the present study aimed to investigate the effect of training based on the health belief model and behavioral intention on dental and oral health behaviors in female students aged 9-12 years old in the city of Rudsar, Guilan, Iran. This research is an interventional study conducted on 84 female students aged 9-12 years old, who lived in the city of Rudsar (n = 42 in the control group and n = 42 in the interventional group) in 2019. The data collection tools included questions on demographic variables, structures of the health belief model (perceived sensitivity, perceived severity, perceived barriers and benefits, self-efficiency), behavioral intention, and performance. The questionnaire was completed before the intervention and 3 months after it by both groups. The intervention group received four 45-min sessions. The data were analyzed using SPSS 24, descriptive tests, independent sample t-test, pair sample t-test, and regression (P < 0.05). The mean age of the intervention and control groups was 10.88 ± 1.01 and 10.80 ± 1.01, respectively. The results showed that the average scores of all structures of the health belief model and behavioral intention in the intervention group significantly changed compared to the average scores obtained before the intervention (P < 0.05). Moreover, the average scores of perceived sensitivity (p < 0.009), perceived barriers (p < 0.007), self-efficiency (p < 0.001), and behavioral intention (p < 0.001) significantly changed after the intervention in both groups (p < 0.05). According to the results, the health belief model and the behavioral intention were effective in improving dental and oral health so that they can be applied to improving people's dental and oral health. It can also be used as a model to design, implement, and monitor medical health programs.


Tissue distribution and transmission routes for the tsetse fly endosymbionts.
The tsetse fly Glossina is the vector of the protozoan Trypanosoma brucei spp., which causes Human and Animal African Trypanosomiasis in sub-Saharan African countries. To supplement their unbalanced vertebrate bloodmeal diet, flies permanently harbor the obligate bacterium Wigglesworthia glossinidia, which resides in bacteriocytes in the midgut bacteriome organ as well as in milk gland organ. Tsetse flies also harbor the secondary facultative endosymbionts (S-symbiont) Sodalis glossinidius that infects various tissues and Wolbachia that infects germ cells. Tsetse flies display viviparous reproductive biology where a single embryo hatches and completes its entire larval development in utero and receives nourishments in the form of milk secreted by mother's accessory glands (milk glands). To analyze the precise tissue distribution of the three endosymbiotic bacteria and to infer the way by which each symbiotic partner is transmitted from parent to progeny, we conducted a Fluorescence In situ Hybridization (FISH) study to survey bacterial spatial distribution across the fly tissues. We show that bacteriocytes are mono-infected with Wigglesworthia, while both Wigglesworthia and Sodalis are present in the milk gland lumen. Sodalis was further seen in the uterus, spermathecae, fat body, milk and intracellular in the milk gland cells. Contrary to Wigglesworthia and Sodalis, Wolbachia were the only bacteria infecting oocytes, trophocytes, and embryos at early embryonic stages. Furthermore, Wolbachia were not seen in the milk gland and in the fat body. This work further highlights the diversity of symbiont interactions in multipartner associations and supports two maternal routes of symbiont inheritance in the tsetse fly: Wolbachia through oocytes, and, Wigglesworthia and Sodalis by means of milk gland bacterial infection at early post-embryonic stages.


Crystal structures of beta-neurexin 1 and beta-neurexin 2 ectodomains and dynamics of splice insertion sequence 4.
Presynaptic neurexins (NRXs) bind to postsynaptic neuroligins (NLs) to form Ca(2+)-dependent complexes that bridge neural synapses. beta-NRXs bind NLs through their LNS domains, which contain a single site of alternative splicing (splice site 4) giving rise to two isoforms: +4 and Delta. We present crystal structures of the Delta isoforms of the LNS domains from beta-NRX1 and beta-NRX2, crystallized in the presence of Ca(2+) ions. The Ca(2+)-binding site is disordered in the beta-NRX2 structure, but the 1.7 A beta-NRX1 structure reveals a single Ca(2+) ion, approximately 12 A from the splice insertion site, with one coordinating ligand donated by a glutamic acid from an adjacent beta-NRX1 molecule. NMR studies of beta-NRX1+4 show that the insertion sequence is unstructured, and remains at least partially disordered in complex with NL. These results raise the possibility that beta-NRX insertion sequence 4 may function in roles independent of neuroligin binding.


[Dynamics of neurophysiological indices in experimental animals with chronic circulatory vertebrobasillar disorders and chronic lumbosacral myeloid ischemia in response to magnetic fields and electric stimulation].
Three series of experiments were made on mature non-inbred male and females rats with body mass 160-200 g. Chronic circulatory vertebrobasilar disorder (CCVD) in the rats was provoked by ligation of subclavian arteries. The animals showed longer latent periods of evoked total motor potentials reflecting impairment of the central motoneuron. Inhibition of impulse conduction along the peripheral nerves and decreased M-response amplitudes in the experimental animals with CCVD and myeloid ischemia in the lumbosacral area points to a significant affection of the segmental system of the spinal cord and other parts of the autonomic nervous system.


HPLC analysis and pharmacokinetics of the enantiomers of R,S-oxazepam and R,S-temazepam with their corresponding glucuronide conjugates in urine and plasma of man.
R,S-Oxazepam and R,S-temazepam can be separated in their enantiomers by means of a chiral AGP column. The corresponding R- and S-glucuronide conjugates can be separated on a normal reversed-phase C18 column. Man conjugates the S-enantiomer of oxazepam and temazepam both better than the R-enantiomer. The urinary recovery of the glucuronides following either R,S,-oxazepam or R,S-temazepam almost amounts to 100% of the dose administered.


Comparison of the sensitivity to ultraviolet irradiation of reovirus 3 and some viruses of the Kemerovo group.
The kinetics of UV inactivation of the tick-borne Kemerovo (strain R-10) and Lipovnik (strain Lip-91) viruses which have been preliminarily classified as possible members of the Reovirus group was examined. Reovirus 3 and Sindbis virus served as reference double-stranded RNA and single-stranded RNA viruses, respectively. The parameters of UV inresembled those of Reovirus 3. This is consistent with their tentative classification as reovirus-like viruses.


The Shunt of It.
Pulmonary arteriovenous malformations (PAVMs) are rare and most often identified in patients with hereditary hemorrhagic telangiectasia (HHT). We describe a patient with severe hypoxemia and orthodeoxia with imaging findings consistent with PAVMs. Resected lung pathologic findings confirmed the presence of numerous microscopic vascular abnormalities within the right lower lobe that was consistent with diffuse pulmonary arteriovenous shunts. Family history was negative for HHT but was positive for pulmonary arterial hypertension (PAH) in two second-degree relatives. A vascular malformation gene panel was negative for genes that commonly are associated with HHT but identified a pathogenic variant in the gene encoding bone morphogenetic protein receptor-2 (BMPR2 p.Cys123∗). Pathogenic variants in BMPR2 are a well-known cause of hereditary PAH; there have been several reports to date of patients with PAVMs and PAH. However, this is the first patient to be reported with a pathogenic variant in BMPR2 to have PAVMs in isolation.


Correction: Using time series analysis approaches for improved prediction of pain outcomes in subgroups of patients with painful diabetic peripheral neuropathy.
[This corrects the article DOI: 10.1371/journal.pone.0207120.].


Comparison of outcomes after everolimus-eluting stent implantation in diabetic versus non-diabetic patients in the Tokyo-MD PCI study.
Diabetes mellitus (DM), especially in those requiring insulin for treatment, is known to be a risk factor for adverse events after percutaneous coronary intervention using first-generation drug-eluting stents. However, the role of DM in patients treated with everolimus-eluting stents (EES) is less known. The purpose of the present analysis was to evaluate the outcomes of treatment with EES for DM patients both requiring and not requiring insulin, and to compare them with non-DM patients. Of patients treated with EES in the Tokyo-MD PCI study, an all-comer, multicenter, observational cohort study, we identified 199 insulin-requiring diabetics (IRDM), 575 non-insulin requiring diabetics (NIRDM), and 1092 non-diabetics (non-DM). The main outcomes were major adverse cardiovascular events (MACE) defined as a composite of all-cause death, myocardial infarction, and stroke, and target lesion revascularization (TLR). The cumulative incidence of MACE and TLR was significantly greater in patients with IRDM than non-DM [MACE: hazard ratio 1.97, 95% confidence interval (CI) 1.31-2.90, p<0.01; TLR: hazard ratio 3.43, 2.07-5.55, p<0.0001] according to univariate Cox proportional hazards model. After adjusting for confounders using the multivariate Cox proportional hazard model, the risk of IRDM versus non-DM for TLR remained significant (hazard ratio 1.92, 1.10-3.29, p=0.02). The incidence of TLR in NIRDM was slightly greater than that in non-DM according to univariate analysis (hazard ratio 1.65, 1.07-2.54, p=0.02). However, the risk was not statistically different in the multivariate analysis (hazard ratio 1.52, 0.97-2.35, p=0.06). In this all-comer, observational study, the risk of TLR was greater in IRDM compared with non-DM after EES implantation, while the increased risk for TLR from NIRDM did not reach statistical significance.


Mechanisms of illegitimate recombination.
Illegitimate recombination, which is one of the major causes of genome rearrangements, can occur in a number of ways. These might involve enzymes which cut and join DNA or enzymes which replicate DNA, as illustrated by two examples: (i) formation of deletions at the replication origin (ori) of an Escherichia coli bacteriophage, M13; and (ii) excision of E. coli transposon Tn10. It is proposed that a common theme to various ways by which illegitimate recombination can occur might be the capacity to create ends in the DNA molecule and to make the ends meet.


7-Deoxy-13-dihydrodaunomycinone in cultures of Streptomyces coeruleorubidus.
7-Deoxy-13-dihydrodaunomycinone was isolated from three strains of Streptomyces coeruleorubidus. Its production was found to rise at the end of cultivation and to be stimulated by lowered aeration intensity.