Observation of degenerate one-dimensional sub-bands in cylindrical InAs nanowires.
One-dimensional (1D) sub-bands in cylindrical InAs nanowires (NWs) are electrically mapped as a function of NW diameter in the range of 15-35 nm. At low temperatures, stepwise current increases with the gate voltage are clearly observed and attributed to the electron transport through individual 1D sub-bands. The 2-fold degeneracy in certain sub-band energies predicted by simulation due to structural symmetry is experimentally observed for the first time. The experimentally obtained sub-band energies match the simulated results, shedding light on both the energies of the sub-bands as well as the number of sub-bands populated per given gate voltage and diameter. This work serves to provide better insight into the electrical transport behavior of 1D semiconductors.


Characterization of micronutrient supplements use by Brazilian children 6-59 months of age: Brazilian National Survey on Child Nutrition (ENANI-2019).
This study aimed to characterize micronutrient supplements use among Brazilian children 6-59 months of age included in the Brazilian National Survey on Child Nutrition (ENANI-2019; n = 12,598). Micronutrient supplements use at the time of the interview and the 6 months prior to it was evaluated using a structured questionnaire. The following indicators were included: micronutrient supplement use; supplements containing a single micronutrient; supplements of the Brazilian National Iron Supplementation Program (PNSF); multivitamin supplements with or without minerals; multivitamin supplements with minerals; multivitamin supplements without minerals. The estimates and their respective 95% confidence intervals (95%CI) were calculated for Brazil and according to macroregion, educational level of the mother or caregiver, and type of health care service used, considering the sampling plan, weights, and calibration. In Brazil, the prevalence of micronutrient supplements use was 54.2% (95%CI: 50.5; 57.8), with the highest prevalence in the North Region (80.2%; 95%CI: 74.9; 85.6) and among children 6-23 months of age (69.5%; 95%CI: 65.7; 73.3). The prevalence of the use of supplements containing exclusively iron and exclusively vitamin A in Brazil was 14.6% (95%CI: 13.1; 16.1) and 23.3% (95%CI: 19.4; 27.1), respectively. The prevalence of the use of multivitamin with or without minerals in Brazilian children 6-59 months of age was 24.3% (95%CI: 21.4; 27.2). These results may help to understand the practice of supplements use among Brazilian children and support the proposal of national public policies for the prevention and control of micronutrient deficiencies.


Design, sythesis and evaluation of a series of 3- or 4-alkoxy substituted phenoxy derivatives as PPARs agonists.
Peroxisome proliferators-activated receptors (PPARα, γ and δ) are potentially effective targets for Type 2 diabetes mellitus therapy. The severe effects of known glitazones and the successfully approved agents (saroglitazar and lobeglitazone) motivated us to study novelly potent PPARs drugs with improved safety profile. In this work, we received 15 carboxylic acids based on the combination principle to integrate the polar head of bezafibrate with the hydrophobic tail of pioglitazone. Another 12 tetrazoles based on the bioisosterism principle were obtained accordingly. Furthermore, in vitro PPARs transactivation assays on these 3- or 4-alkoxy substituted phenoxy derivatives afforded six compounds. Interactions and binding stability from the docking analysis and 20 ns molecular dynamic simulations confirmed the representative compounds to be suitable and plausible for PPARs pockets. The above-mentioned results demonstrated that the compounds may be used as reference for further optimization for enhanced PPARs activities and wide safety range.


Organocatalytic Transformation of Aldehydes to Thioesters with Visible Light.
A metal- and oxidant-free catalytic method for accessing structurally diverse thioesters from readily accessible, widespread aldehydes, is described. A strategy of a simple organic 9,10-phenanthrenequinone-promoted hydrogen atom transfer (HAT) with visible light was successfully implemented to selectively generate acyl radicals without inducing crossover reactivity of thioester products. The preparative power of the method was demonstrated by broad substrate scope and wide functional group tolerance, and enabled the late-stage modification of complex structures, which are difficult to achieve with the existing protocols.


Ternary complex of plasmid DNA with NLS-Mu-Mu protein and cationic niosome for biocompatible and efficient gene delivery: a comparative study with protamine and lipofectamine.
Non-viral gene delivery methods are considered due to safety and simplicity in human gene therapy. Since the use of cationic peptide and niosome represent a promising approach for gene delivery purposes we used recombinant fusion protein and cationic niosome as a gene carrier. A multi-domain fusion protein including nuclear localization motif (NLS) and two DNA-binding (Mu) domains, namely NLS-Mu-Mu (NMM) has been designed, cloned and expressed in E. coli DE3 strain. Afterward, the interested protein was purified by affinity chromatography. Binary vectors based on protein/DNA and ternary vectors based on protein/DNA/niosome were prepared. Protamine was used as a control. DNA condensing properties of NMM and protamine were evaluated by various experiments. Furthermore, we examined cytotoxicity, hemolysis and transfection potential of the binary and ternary complexes in HEK293T and MCF-7 cell lines. Protamine and Lipofectamine™2000 were used as positive controls, correspondingly. The recombinant NMM was expressed and purified successfully and DNA was condensed efficiently at charge ratios that were not harmful to cells. Peptidoplexes showed transfection efficiency (TE) but ternary complexes had higher TE. Additionally, NMM ternary complex was more efficient compared to protamine ternary vectors. Our results showed that niosomal ternary vector of NMM is a promising non-viral gene carrier to achieve an effective and safe carrier system for gene therapy.


Evolution of photonic structure on deformation of cholesteric elastomers.
We subject a monodomain cholesteric liquid crystal elastomer to uniaxial strain perpendicular to its helical axis and study the response of its texture to deformation. A combination of mechanical, optical, and x-ray scattering measurements confirms the prediction for the director rotation, coarsening, and then unwinding the cholesteric helix. The study of optical absorption of circularly polarized light quantifies the complex dependence of the photonic band-gap structure on strain and directly relates to the microscopic deformation of elastomer. Agreement is found with the recently proposed theoretical prediction of the photonic structure of cholesteric elastomers.


Antidiabetic Drugs: Mechanisms of Action and Potential Outcomes on Cellular Metabolism.
Diabetes mellitus (DM) is one of the most prevalent chronic diseases and has been a leading cause of death in the last decades. Thus, methods to detect, prevent or delay this disease and its co-morbidities have long been a matter of discussion. Nowadays, DM patients, particularly those suffering with type 2 DM, are advised to alter their diet and physical exercise regimens and then proceed progressively from monotherapy, dual therapy, and multi-agent therapy to insulin administration, as the disease becomes more severe. Although progresses have been made, the pursuit for the "perfect" antidiabetic drug still continues. The complexity of DM and its impact on whole body homeodynamics are two of the main reasons why there is not yet such a drug. Moreover, the molecular mechanisms by which DM can be controlled are still under an intense debate. As the associated risks, disadvantages, side effects and mechanisms of action vary from drug to drug, the choice of the most suitable therapy needs to be thoroughly investigated. Herein we propose to discuss the different classes of antidiabetic drugs available, their applications and mechanisms of action, particularly those of the newer and/or most widely prescribed classes. A special emphasis will be made on their effects on cellular metabolism, since these drugs affect those pathways in several cellular systems and organs, promoting metabolic alterations responsible for either deleterious or beneficial effects. This is a crucial property that needs to be carefully investigated when prescribing an antidiabetic.


Humeral head surface arthroplasty: a case report.
Shoulder osteoarthritis is one of the common causes of the shoulder pain. The shoulder arthroplasty is an effective treatment alternative for the patients at advanced disease stage. We presented the first incident case in Thailand who had been diagnosed with primary glenohumeral osteoarthritis and was surgically treated by the humeral head surface arthroplasty. Efficacy and clinical outcomes of this treatment were described.


[Pulmonary rehabilitation in patients with chronic obstructive pulmonary disease].
Chronic obstructive pulmonary disease (COPD) irreversibly damages pulmonary function leading to disorder of arterial bloodgases, arterialpartial prescure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), appearance of dyspnea, and decrease of physical condition. The aim of this study was to establish if medical treatment and respiratory rehabilitation in COPD used simultaneously lead to the greater improvement of PaO2, PaCO2 and physical condition and decreaseing dyspnea than medical treatment alone. A total of 60 patients divided into three groups according to the severity of obstruction (mild--I, severe--II, very severe--III) weretested. Each group had the two subgroups of patients--first one with those treated both with medical treatment and respiratory rehabilitation (A) and the second one with the patients treated only with medical treatment (B). The treatment took 21 days. The measurements of PaO2 and PaCO2) intensity of dyspnea at rest and exercise (10--point Borg Category Scale), and physical capacity (Six-Minute Walk Test--6MWT) were done on the first and on the last day of testing. The results showed that all of the patients who were treated with the combination of medical treatment and respiratory rehabilitation had significantly higher increase in the values of PaO2 (I--p < 0.01; II--p < 0.05; III--p < 0.01), score of Borg's scale (I--p < 0.05, p < 0.001; II--p < 0.05, p < 0.001; III--p < 0.001, p < 0.001) and 6MWT (I--p < 0.001; II--p < 0.001; III--p < 0.001), and that statistically significant increase of the values of PaCO2 (p < 0.05) had only the patients with very severe COPD treated with the combination of drugs and respiratory rehabilitation. Based on the obtained results we conclude that using respiratory rehabilitation in combination with pharmacological treatment of COPD gives statistically higher improvement of values of PaO2 and PaCO2, and physical condition, and also leads to decrease of intensity of dyspnea than using just drug therapy.


Mitochondrial-driven ubiquinone enhances extracellular calcium-dependent nitric oxide production and reduces glycochenodeoxycholic acid-induced cell death in hepatocytes.
Ca(2+) mobilization, nitric oxide (NO), and oxidative stress have been involved in cell death induced by hydrophobic bile acid in hepatocytes. The aim of the study was the elucidation of the effect of the antioxidant mitochondrial-driven ubiquinone (Mito Q) on the intracellular Ca(2+) concentration, NO production, and cell death in glycochenodeoxycholic acid (GCDCA)-treated HepG2 cells. The role of the regulation of the intracellular Ca(2+) concentration by Ca(2+) chelators (EGTA or BAPTA-AM), agonist of Ca(2+) entrance (A23187) or NO (L-NAME or NO donor), was assessed during Mito Q cytoprotection in GCDCA-treated HepG2 cells. Cell death, NO synthase (NOS)-1, -2, and -3 expression, Ca(2+) mobilization, and NO production were evaluated. GCDCA reduced the intracellular Ca(2+) concentration and NOS-3 expression and enhanced cell death in HepG2. NO donor prevented and L-NAME enhanced GCDCA-induced cell death. The reduction of Ca(2+) entry by EGTA, but not its release from intracellular stores by BAPTA-AM, reduced the expression of NOS-3 and enhanced cell death in control and GCDCA-treated cells. Mito Q prevented the reduction of intracellular Ca(2+) concentration, NOS-3 expression, NO production, and cell death in GCDCA-treated HepG2 cells. The conclusion is that the recovery of Ca(2+)-dependent NOS-3 expression by Mito Q may be considered an additional cytoprotective property of an antioxidant.


Holographic interferogram analysis from a single view.
Quantitative analysis of a holographic interferogram requires either multiple interferograms and hence a great deal of data or strict a priori assumptions. This work presents a class of assumptions that reduces to one the number of views necessary for three-dimensional motion. The method involves relating points on the body via rigid-body theory and calculating deviations from this ideal deformation. It requires knowledge of the expected deformation. An example is given using internally pressurized spherical shells.


Cancer: a "stem-cell" disease?
Nowadays, we believe that cancer is a genetic disease. We focus on the genetic targets and epigenetic changes in a tumor. Remarkably, many crucial signal pathways in a malignant cell involve "stem-ness" genes. The prevalence of stem-ness in cancer suggests that cancer has a stem-cell origin and is a stem-cell disease. The observation that many innate stem-ness properties are easily interchangeable with malignant hallmarks needs to be further elucidated. There appears to be a malignant potential in every stem cell and a stem cell potential in every malignant cell. I hypothesize that cancer is a stem-cell disease rather than a genetic disease. We will use homeobox genes to endow a certain progenitor cell with specific stem-ness properties and confer different stem-cell phenotypes to the particular cell type in a hierarchical manner. We will demonstrate that an earlier homeobox gene plus a genetic defect (such as Pten loss) tend to form a more virulent tumor, while a later homeobox gene plus the same genetic defect tend to express a more indolent phenotype. Importantly, we will show that in clinically relevant cancer subtypes, those with worse clinical outcomes may paradoxically harbor fewer genetic mutations than those with better outcomes do. The recognition that cancer is a stem-cell disease will instigate major paradigm shifts in our basic understanding of cancer. Many fundamental principles of oncology, such as multistep carcinogenesis, need to be reconciled. The realization that cancer is a stem-cell disease will also have profound clinical implications on personalized care. Many aspects of our current clinical trials need to be reevaluated.


Lipoxins are potential endogenous antiinflammatory mediators in asthma.
Lipoxins, endogenous eicosanoids biosynthetized in vivo at inflammation sites, are potential antiinflammatory mediators. Subjects with severe asthma present chronic inflammation of the airways despite long-term treatment with oral glucocorticoids. Therefore it is of interest to investigate the potential antiinflammatory effects of lipoxin A4 (LXA4) and lipoxin B4 (LXB4) that could attenuate chronic inflammation. In a first time, we detected interleukin (IL)-8 and LXA4 in supernatants of induced sputum. IL-8 was heightened in severe asthma (p = 0.001), whereas high concentrations of lipoxin A4 were present in mild asthma (p = 0.001). We then studied the effects of LXA4 on IL-8 released in vitro. Nanomolar concentrations of LXA4 and LXB4 inhibited the IL-8 released by peripheral blood mononuclear cells from the two groups of patients with asthma: a maximal inhibition of 29.4% (p < 0.01) was observed for patients with mild asthma, and 41.5% inhibition (p < 0.001) for patients with severe asthma at 1 nM and 100 nM LXA4 concentrations, respectively. Polymerase chain reaction analysis indicated that peripheral blood mononuclear cells from patients with asthma expressed the LXA4 receptor mRNA. Moreover, pertussis toxin reversed LXA4- and LXB4-inhibited IL-8 release. These findings suggest that lipoxins have potential antiinflammatory action in asthma.


Impact of the COVID-19 Pandemic on Physical and Mental Health in Lower and Upper Middle-Income Asian Countries: A Comparison Between the Philippines and China.
Objective: The differences between the physical and mental health of people living in a lower-middle-income country (LMIC) and upper-middle-income country (UMIC) during the COVID-19 pandemic was unknown. This study aimed to compare the levels of psychological impact and mental health between people from the Philippines (LMIC) and China (UMIC) and correlate mental health parameters with variables relating to physical symptoms and knowledge about COVID-19. Methods: The survey collected information on demographic data, physical symptoms, contact history, and knowledge about COVID-19. The psychological impact was assessed using the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety, and Stress Scale (DASS-21). Findings: The study population included 849 participants from 71 cities in the Philippines and 861 participants from 159 cities in China. Filipino (LMIC) respondents reported significantly higher levels of depression, anxiety, and stress than Chinese (UMIC) during the COVID-19 (p < 0.01) while only Chinese respondents' IES-R scores were above the cut-off for PTSD symptoms. Filipino respondents were more likely to report physical symptoms resembling COVID-19 infection (p < 0.05), recent use of but with lower confidence on medical services (p < 0.01), recent direct and indirect contact with COVID (p < 0.01), concerns about family members contracting COVID-19 (p < 0.001), dissatisfaction with health information (p < 0.001). In contrast, Chinese respondents requested more health information about COVID-19. For the Philippines, student status, low confidence in doctors, dissatisfaction with health information, long daily duration spent on health information, worries about family members contracting COVID-19, ostracization, and unnecessary worries about COVID-19 were associated with adverse mental health. Physical symptoms and poor self-rated health were associated with adverse mental health in both countries (p < 0.05). Conclusion: The findings of this study suggest the need for widely available COVID-19 testing in MIC to alleviate the adverse mental health in people who present with symptoms. A health education and literacy campaign is required in the Philippines to enhance the satisfaction of health information.


Respiratory infections during SARS outbreak, Hong Kong, 2003.
The effect of community hygienic measures during the outbreak of severe acute respiratory syndrome in Hong Kong was studied by comparing the proportion of positive specimens of various respiratory viruses in 2003 with those from 1998 to 2002. Community hygienic measures significantly reduced the incidence of various respiratory viral infections.


Multicenter comparative study of three "non-destructive" methods of detecting the cleanliness of the da Vinci surgical robotic instrument.
The robotic instrument of the da Vinci surgical system determines the accuracy of robotic-assisted surgery, However, the most effective cleaning method of robotic equipment is a challenge for healthcare professionals. This study compared three da Vinci robot-assisted surgery manipulators to detect the effect of "non-destructive" testing of the cleaning effect by two different methods. The post-surgical cleaning of the da Vinci robotic instruments in the Sun Yat-sen University Cancer Center, The First Affiliated Hospital of Guangzhou Medical University and the Shenzhen Second People's Hospital was performed using two different processes from January 2019 to January 2020: manual joint automatic ultrasonic cleaning and automatic mechanical cleaning. The efficacy of visual estimation, the residual protein assay (quantitative) and adenosine triphosphate (ATP) biological biofluorescence detection of the cleanliness of the mechanical instrument's work (distal working end) surface and the shaft's inner chamber was compared. If the cleaning effect of any position on the surface or inner cavity of the manipulator did not qualify, the entire robotic instrument was judged as disqualified. A total of 198 cases of da Vinci robotic instrument postoperative cleanliness data were collected. The qualifying rates of automatic ultrasonic cleaning were 96.97% by visual estimation, 93.94% by residual protein assay and 60.61% by ATP biological fluorescence detection. The respective rates for automatic mechanical cleaning were 100% by visual estimation, 90.91% by residual protein assay and 66.67% by ATP biological fluorescence detection. The cleaning of the da Vinci robotic instrument detected by "non-destructive" residual protein assay or ATP biological fluorescence detection is more accurate than visual estimation.


Feasibility of tri-weekly docetaxel-based chemotherapy for elderly patients (age 75 and older) with castration-resistant prostate cancer.
To evaluate the efficacy and safety of docetaxel-based chemotherapy for elderly metastatic castration-resistant prostate cancer (CRPC) patients aged 75 or higher. Twenty CRPC patients aged 75 or higher (older group) and 31 CRPC patients younger than 75 years (younger group) were treated by a regimen of docetaxel (70 mg/m(2)) once every 3 weeks. Adjustment for docetaxel dosage and period per cycle was subject to investigator's judgment. The median relative dose intensity of both groups was 0.84, while the median dose intensity and the number of treatment cycles of the younger and older groups were 14.6 versus 12.3 mg/m(2)/week (p = 0.021), and 9 versus 8 cycles (p = 0.15), respectively. In the older group, PSA response rate was 50%, median time to biochemical progression was 7.5 months, and median survival time was 15.5 months, without any significant difference compared to those of the younger group. No significant difference in the incidence of grade 3-4 adverse events was noted between both groups. All these parameters for efficacy are comparable to those reported for tri-weekly docetaxel regimen. Tri-weekly treatment by docetaxel (70 mg/m(2)) with proper adjustment might contribute to maintaining efficacy and safety of the treatment for elderly CRPC patients.


Toxicity identification evaluation of five metals performed with two organisms (Daphnia magna and Lactuca sativa).
When trying to identify the main toxicants in effluents, natural waters, sediments, soil leachates, and leachates from products, the Toxicity Identification Evaluation (TIE) procedure has proven useful. To enhance the use of this procedure for soil, sewage, and sediment samples, we wanted to evaluate this TIE procedure, regarding metal toxicity, for the 96-h root elongation test performed with Lactuca sativa (lettuce) seeds. We also wanted to evaluate the effect of TIE treatment on the toxicity of Mn and Fe to Daphnia magna. Bioassays were performed with Daphnia magna (48-h immobility) and lettuce seeds (96-h root elongation) to determine the effect concentrations for both organisms of Ag, Cu, Fe, Mn, and Zn. The TIE was then performed at the determined Daphnia 48-h EC(84) and Lactuca 96-h EC(50) for each metal. Our results showed that the order of the metal toxicity was Ag>Cu>Zn>Fe>Mn, for Daphnia and Ag = Zn = Fe = Cu > Mn for lettuce seeds. We also found that toxicity of the metals for Daphnia magna was reduced according to the prevailing knowledge regarding Cu, Zn, and Ag. However, the toxicity of Ag and Cu for Daphnia was also reduced by filtration through a C18 resin. Toxicity of Mn and Fe was reduced by filtration through a CM resin and increase of pH. For lettuce seeds, toxicity of the metals was reduced by the same treatments as for Daphnia magna with the exception of EDTA addition, which did not affect Cu toxicity to lettuce seeds. No effects were found for filtration through a C18 resin. We suggest that the TIE procedure using lettuce seeds can be used in toxicity identification of metals. However, the effects of pH manipulations were often stronger with lettuce and should be interpreted with care.


[Breast adenocarcinoma: critical analysis of sentinel lymph node histopathological results of 542 procedures].
Between February 2001 and March 2003, 542 sentinel lymph node procedures were performed for localised breast carcinoma (T0-T1, N0, M0) without any previous treatment. Frozen sections were performed in 515 cases and they did not reveal metastases in 446 cases. Fifty-two micrometastases < 2 mm and 18 macrometastases were reported by definitive histopathological exam. Axillary clearance was performed in 50/70 patients (38 with micrometastases and 12 for macrometastases). Modalities of histopathological procedure are discussed and particularly number and interval of serial slides with or without immunochemistry ; 81.8% (36/44) of micrometastases were detected on the two first serial sections. Decisional value of axillary clearance performed in case of micrometastases is also evaluated.


A flexible loop in yeast ribosomal protein L11 coordinates P-site tRNA binding.
High-resolution structures reveal that yeast ribosomal protein L11 and its bacterial/archael homologs called L5 contain a highly conserved, basically charged internal loop that interacts with the peptidyl-transfer RNA (tRNA) T-loop. We call this the L11 'P-site loop'. Chemical protection of wild-type ribosome shows that that the P-site loop is inherently flexible, i.e. it is extended into the ribosomal P-site when this is unoccupied by tRNA, while it is retracted into the terminal loop of 25S rRNA Helix 84 when the P-site is occupied. To further analyze the function of this structure, a series of mutants within the P-site loop were created and analyzed. A mutant that favors interaction of the P-site loop with the terminal loop of Helix 84 promoted increased affinity for peptidyl-tRNA, while another that favors its extension into the ribosomal P-site had the opposite effect. The two mutants also had opposing effects on binding of aa-tRNA to the ribosomal A-site, and downstream functional effects were observed on translational fidelity, drug resistance/hypersensitivity, virus maintenance and overall cell growth. These analyses suggest that the L11 P-site loop normally helps to optimize ribosome function by monitoring the occupancy status of the ribosomal P-site.


Antimicrobial resistance of Staphylococcus spp. isolated from organic and conventional Minas Frescal cheese producers in São Paulo, Brazil.
The genus Staphylococcus is recognized worldwide as a cause of bacterial infections in humans and animals. Antibiotics used in dairy cattle combined with ineffective control can increase antimicrobial resistance. The objective of this study was to characterize 95 Staphylococcus strains isolated from organic and conventional Minas Frescal cheese production regarding antibiotic resistance (phenotype and genotype), presence of sanitizer-resistant genes and biofilm-formation genes, and SCCmec typing. Most strains (25.3%) showed higher resistance to penicillin, followed by oxacillin (21.1%) and clindamycin (11.6%). Among antibiotic resistance genes, the most prevalent were blaZ (25.3%), mecA (13.7%), lsaB (6.3%), msrA (4.2%), ant4 (3.2%), and tetM (2.1%); among sanitizer-resistance genes they were qacA/B (5.3%) and qacC (6.3%); and among biofilm, bap (4.2%), icaA (29.5%), icaD (41.1%). However, there was no statistically significant difference between organic and conventional dairy products, possibly due to the lack of synthetic antibiotic use on conventional farms during the sample collection period. Methicillin-resistant Staphylococcus aureus (MRSA) had their SCCmec identified as types I and IVc, and the methicillin-resistant coagulase-negative staphylococci had nontypeable SCCmec. These results suggest that there are antibiotic-resistant strains in both organic and conventional Minas Frescal cheese production in the state of São Paulo, Brazil. This supports the idea that improved quality control is needed from the milking stage up to the final product.


Scientific basis of organ preservation.
To review the basic mechanisms involved during hypothermia and reperfusion, with special attention paid to efforts being made in refining solutions and the molecular characterization of cells during preservation. Several graft-related molecules have been identified as correlating with early graft dysfunction and/or poor outcome in the immediate posttransplant period. Also, different inhibitors have been utilized to ameliorate the preservation-induced injury, alone or in combination with different preservation solutions. Preservation-induced injury is a major contributing factor to early graft dysfunction in organ recipients. The success of organ transplantation is critically dependent on the quality of the donor organ. Donor-organ quality, in turn, is determined by a variety of factors, including donor age, donor management prior to organ procurement, the duration of hypothermic storage, and perfusion techniques utilized to protect organs from ischemia/reperfusion injury, which in turn cause a dramatic reprogramming of cell metabolism during organ transplantation. The expression of a number of inflammatory genes has been associated with early graft dysfunction and/or poor outcome in the immediate postoperative period. Some therapeutic manipulations have been demonstrated to be of significance in attaining near-normal organ function after transplantation.


[Potassium ion transport in the erythrocytes of the frog Rana ridibunda].
The K+ transport in isolated erythrocytes from the frog Rana ridibunda has been studied using 86Rb as a tracer at the temperature of 18-20 degrees C. At physiological K+ concentration (3 mM) in C1- medium ouabain and furosemide inhibited K+ influx by approximately 42 and 47%, respectively. Furosemide had no effect on the Na+ (22Na) transport under the same conditions. The replacement of C1- by NO-3 in medium resulted in significant decrease of total K+ influx, which was not inhibited by furosemide. The ouabain- and furosemide-sensitive components of K+ influx hyperbolically increased as a function of external K+e concentration (1-90 mM) in C1- medium and calculated values of Vmax were 2.2 +/- 0.14 and 5.8 +/- 1.2 mmol/1 cells/h, respectively. K+ influx into frog erythrocytes in the presence of both ouabain and furosemide in NO-3 medium was significantly lower compared with C1- medium. C1--dependent, furosemide-insensitive component of K+ influx increased in a saturable fashion in the range of K+e concentration from 1 to 90 mM. Residual component of K+ transport in NO3 medium in the presence of the blockers was a linear function of K+e concentration and is characterized by the constant of K+ influx rate equal to 0.028 +/- 0.002 h-1. The data obtained indicate that in parallel with the Na, K-pump specific K, C1-transporter participates in K+-transport in the frog erythrocyte membrane. The latter mechanism was only partially blocked by 1 mM furosemide.


Primary and secondary CoQ(10) deficiencies in humans.
CoQ(10) deficiencies are clinically and genetically heterogeneous. This syndrome has been associated with five major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) cerebellar ataxia, (4) isolated myopathy, and (5) nephrotic syndrome. In a few patients, pathogenic mutations have been identified in genes involved in the biosynthesis of CoQ(10) (primary CoQ(10) deficiencies) or in genes not directly related to CoQ(10) biosynthesis (secondary CoQ(10) deficiencies). Respiratory chain defects, ROS production, and apoptosis variably contribute to the pathogenesis of primary CoQ(10) deficiencies.


The significance of shape and orientation in single-particle weak-scatterer models.
Particles that have a density and compressibility comparable to those of the surrounding medium (weak scatterers) are often modeled as spherical scatterers of equivalent volume. The simplicity and symmetry of the spherical model does not however account for the effect of the angle of incidence of the incident field onto the particle. By performing a comparative study of scattering models for the case of a fluid sphere, it is shown that models derived using the Born approximation closely match the exact solution for weak scatterers. This approximation is therefore applied to produce a model for the fluid disk, which is used to investigate the significance of particle shape and orientation. Scattering by a red blood cell of given volume modeled as a sphere is compared to the result obtained by approximating its shape as a disk of varying aspect ratio and orientation. The spherical model is shown to provide a good description for frequencies up to 20 MHz, beyond which particle shape becomes significant. This effect could go undetected if the scattered field is only observed at 90 degrees relative to the direction of the incident field. Nevertheless, the significance of particle shape and orientation might form the basis of a novel detection technique.


Doctors' decisions and prognostications for infants with Down syndrome.
Random samples of pediatricians, family practitioners and pediatric surgeons were surveyed with a questionnaire, which included three questions regarding their decisions about treatment of duodenal atresia in two hypothetical infants with Down syndrome, one with complete trisomy 21 and one with mosaicism. Results showed that doctors are more likely now to advocate surgery than in the past. Pediatricians and family practitioners had similar views, but pediatricians were more assertive about treatment if parents refused. Pediatric surgeons had the most pessimistic outlook and a greater number would not encourage surgery. There was a relationship between the doctors' prognostications and their decisions about treatment. These results emphasize the importance of ensuring that doctors have accurate perceptions about the capabilities of individuals born with Down syndrome.


Soluble tumor necrosis factor (sTNF) receptors: a possible prognostic marker for bone marrow transplantation-related complications.
Involvement of tumor necrosis factor (TNF) in bone marrow transplantation (BMT)-associated complications has been documented. Biological response to TNF requires interaction with specific cell membrane receptors. Extracellular domains of these receptors are released into body fluids as soluble molecules, and participate in the bioactivity of TNF. Serum levels of p55 and p75 soluble tumor necrosis factor receptors (sTNFR) were determined in 34 patients with different diseases who underwent BMT. Sequential studies initiated 10 days before BMT and continued up to 110 days post-transplantation showed that p55 and p75 sTNFR levels were elevated significantly in patients who subsequently developed major transplant-related complications (TRC). Moreover, both sTNFR levels were increased 2- to 3-fold over control values during post-BMT febrile periods in those patients who at a later stage suffered major TRC. These results indicate that the serum level of sTNFR may be used as a prognostic marker for major TRC in BMT.


Predictive factors of clinical outcomes in patients with COVID-19 treated with tocilizumab: A monocentric retrospective analysis.
The aim of this retrospective observational study is to analyse clinical, serological and radiological predictors of outcome in patients with COVID-19 pneumonia treated with tocilizumab, providing clinical guidance to its use in real-life. This is a retrospective, monocentric observational cohort study. All consecutive patients hospitalized between February the 11th and April 14th 2020 for severe COVID-19 pneumonia at Reggio Emilia AUSL and treated with tocilizumab were enrolled. The patient's clinical status was recorded every day using the WHO ordinal scale for clinical improvement. Response to treatment was defined as an improvement of one point (from the status at the beginning of tocilizumab treatment) during the follow-up on this scale. Bivariate association of main patients' characteristics with outcomes was explored by descriptive statistics and Fisher or Kruskal Wallis tests (respectively for qualitative or quantitative variables). Each clinically significant predictor was checked by a loglikelihood ratio test (in univariate logistic models for each of the considered outcomes) against the null model. A total of 173 patients were included. Only hypertension, the use of angiotensin-converting enzyme inhibitors, PaO2/FiO2, respiratory rate and C-reactive protein were selected for the multivariate analysis. In the multivariable model, none of them was significantly associated with response. Evaluating a large number of clinical variables, our study did not find new predictors of outcome in COVID19 patients treated with tocilizumab. Further studies are needed to investigate the use of tocilizumab in COVID-19 and to better identify clinical phenotypes which could benefit from this treatment.


Animal Models of Adenomyosis.
Adenomyosis is a nonmalignant uterine disorder in which endometrial tissue exists within and grows into the myometrium. Animal models have generated limited insight into the still-unclear pathogenesis of adenomyosis, provided a platform for preclinical screening of many drugs and compounds with potential as therapeutics, and elucidated mechanisms underlying the pain and fertility issues that occur in many women with the disease. Spontaneous adenomyosis has been studied in nonhuman primates, primarily in the form of case reports. Adenomyosis is routinely experimentally induced in mice through methods such as neonatal tamoxifen exposure, pituitary engraftment, and human tissue xenotransplantation. Several studies have also reported hormonal or environmental toxicant exposures that give rise to murine adenomyosis, and genetically engineered models have been created that recapitulate the human-like condition, most notably involving alteration of β-catenin expression. This review describes the animal models for adenomyosis and their contributions to our understanding of the factors underpinning the development of symptoms. Animal models represent a unique opportunity for understanding the molecular basis of adenomyosis and developing efficacious treatment options for affected women. Herein, we assess their different potentials and limitations with regard to identification of new therapeutic interventions and reflect on future directions for research and drug validation.


Trends in opiate and opioid poisonings in addicts in north-east Paris and suburbs, 1995-99.
(1). To assess the trends in the number, mortality and the nature of severe opiate/opioid poisonings from 1995 to 1999 in north-east Paris and adjacent suburbs and (2). to examine the effects of the introduction of high-dose buprenorphine on these parameters. Retrospective, 5-year study with review of pre-hospital, hospital and post-mortem data. Eighty patients from the toxicological intensive care unit (TICU) in north-east Paris, 421 patients from the pre-hospital emergency medical service in a north-east suburb of Paris (SAMU 93) and 40 deaths from the coroner's office in Paris. We found that the number of pre-hospital opiate/opioid poisonings and deaths decreased over 5 years. During the same time frame, opiate/opioid poisoning admissions to our TICU remained steady, but the number of deaths declined. From 1995 to 1999, the detection of buprenorphine among opiate/opioid-poisoned TICU patients increased from two to eight occurrences per year while detection of opiates diminished from 17 to 10 occurrences per year. Increased buprenorphine detection correlated directly with increasing sales over this time period. In spite of the increased use of buprenorphine, the mortality associated with opiate/opioid poisonings has diminished in the pre-hospital environment from 9% in 1995 to 0% in 1999, and in the TICU from 12% in 1995 to 0% in 1997 and thereafter. We found a high frequency of multiple opiate/opioid use in severe poisonings, as well as the frequent association of other psychoactive drugs including ethanol. The number and the mortality of opiate/opioid poisonings appear to be stable or decreasing in our region. The association of multiple opiates/ opioids appears nearly as common as the association with other psychoactive drugs. The introduction of high-dose buprenorphine coincides with a decrease in opiate/opioid poisoning mortality. Further study will be necessary to clarify this observation.


Recent advances in computational predictions of NMR parameters for the structure elucidation of carbohydrates: methods and limitations.
All living systems are comprised of four fundamental classes of macromolecules--nucleic acids, proteins, lipids, and carbohydrates (glycans). Glycans play a unique role of joining three principal hierarchical levels of the living world: (1) the molecular level (pathogenic agents and vaccine recognition by the immune system, metabolic pathways involving saccharides that provide cells with energy, and energy accumulation via photosynthesis); (2) the nanoscale level (cell membrane mechanics, structural support of biomolecules, and the glycosylation of macromolecules); (3) the microscale and macroscale levels (polymeric materials, such as cellulose, starch, glycogen, and biomass). NMR spectroscopy is the most powerful research approach for getting insight into the solution structure and function of carbohydrates at all hierarchical levels, from monosaccharides to oligo- and polysaccharides. Recent progress in computational procedures has opened up novel opportunities to reveal the structural information available in the NMR spectra of saccharides and to advance our understanding of the corresponding biochemical processes. The ability to predict the molecular geometry and NMR parameters is crucial for the elucidation of carbohydrate structures. In the present paper, we review the major NMR spectrum simulation techniques with regard to chemical shifts, coupling constants, relaxation rates and nuclear Overhauser effect prediction applied to the three levels of glycomics. Outstanding development in the related fields of genomics and proteomics has clearly shown that it is the advancement of research tools (automated spectrum analysis, structure elucidation, synthesis, sequencing and amplification) that drives the large challenges in modern science. Combining NMR spectroscopy and the computational analysis of structural information encoded in the NMR spectra reveals a way to the automated elucidation of the structure of carbohydrates.


Design of a brightness-enhancement-film-adaptive freeform lens to enhance overall performance in direct-lit light-emitting diode backlighting.
In this study, a brightness-enhancement-film- (BEF) adaptive method is proposed to design freeform lenses for enhancing brightness performance in a direct-lit light-emitting diode (LED) backlight system. A detailed design algorithm is presented based on the analysis of the output optical properties of the BEF. By introducing a constriction factor, we can control the light intensity distribution curve at will to adapt to the characteristics of the BEF and make more light transmit through the BEF. Compared with an LED backlight system without a freeform lens, the BEF-adaptive lens method can improve axial luminance by 20.67% and output efficiency by 6.02%.


Neuropeptide Y phase shifts circadian rhythms in vivo via a Y2 receptor.
Neuropeptide Y (NPY) injected into the suprachiasmatic region 6 h before the onset of locomotor activity produces phase advances in circadian rhythms. The present study investigated whether the phase advances produced by NPY in Syrian hamsters are mediated by a Y1- or Y2-like NPY receptor by comparing the phase advancing effects of the Y1 agonist, [Leu31, Pro34]NPY, and the Y2 agonist, NPY(3-36), following their injection into the suprachiasmatic region. Microinjection of the Y2 agonist produced phase advances that were significantly greater than those produced by the microinjection of the Y1 agonist. These data support the hypothesis that the phase advancing effects of NPY in the suprachiasmatic region are mediated by a Y2-like NPY receptor, similar to results found in vitro.


Use of avidity enzyme-linked immunosorbent assay and avidity Western blot to discriminate between acute and chronic Neospora caninum infection in cattle.
Avidity serological tests (avidity enzyme-linked immunosorbent assay [ELISA] and avidity Western blot) were developed and used to differentiate between acute (primary infection, reinfection, and recrudescence) and chronic Neospora caninum infection in cattle. In addition, the pattern of immunoglobulin G (IgG) avidity maturation against different specific antigens of N. caninum tachyzoites was studied. Sequential serum samples were collected from cattle naturally and experimentally infected with N. caninum. Four groups of experimentally infected cattle were included in the study and were representative of primary infection, reinfection, chronic infection, and noninfection. Serum samples were also collected from naturally infected cattle classified into nonaborting and aborting cows on the basis of clinical findings and serological profiles, and a third group composed of seronegative cows that seroconverted during the course of the experiment. All samples were tested by avidity ELISA and avidity Western blot. The IgG avidity ELISA allowed the discrimination between primary and chronic infection because all experimentally primary-infection cows showed low avidity indexes at week 4 postinfection (p.i.) compared with the high avidity values found at week 20 postinfection. However, this test did not allow the discrimination of reinfection or recrudescence from chronic infection. Regarding IgG avidity Western blot results, no antigenic markers correlating with acute (primary infection, recrudescence, and reinfection) or chronic infection were recognized. However, the 17-kD immunodominant antigen was mostly responsible for high avidity values obtained by avidity ELISA because it was intensively recognized by high-avidity antibodies in all chronically infected animals after urea treatment.


LIF and BMP signaling generate separate and discrete types of GFAP-expressing cells.
Bone morphogenetic protein (BMP) and leukemia inhibitory factor (LIF) signaling both promote the differentiation of neural stem/progenitor cells into glial fibrillary acidic protein (GFAP) immunoreactive cells. This study compares the cellular and molecular characteristics, and the potentiality, of GFAP(+) cells generated by these different signaling pathways. Treatment of cultured embryonic subventricular zone (SVZ) progenitor cells with LIF generates GFAP(+) cells that have a bipolar/tripolar morphology, remain in cell cycle, contain progenitor cell markers and demonstrate self-renewal with enhanced neurogenesis - characteristics that are typical of adult SVZ and subgranular zone (SGZ) stem cells/astrocytes. By contrast, BMP-induced GFAP(+) cells are stellate, exit the cell cycle, and lack progenitor traits and self-renewal--characteristics that are typical of astrocytes in the non-neurogenic adult cortex. In vivo, transgenic overexpression of BMP4 increases the number of GFAP(+) astrocytes but depletes the GFAP(+) progenitor cell pool, whereas transgenic inhibition of BMP signaling increases the size of the GFAP(+) progenitor cell pool but reduces the overall numbers of astrocytes. We conclude that LIF and BMP signaling generate different astrocytic cell types, and propose that these cells are, respectively, adult progenitor cells and mature astrocytes.


Plasma Membrane Alterations in Callus Tissues of Tuber-bearing Solanum Species during Cold Acclimation.
Plasma membrane alterations in two tuber-bearing potato species during a 20-day cold acclimation period were investigated. Leaf-callus tissues of the frost-resistant Solanum acaule Hawkes ;Oka 3878' and the frost-susceptible, commonly grown Solanum tuberosum ;Red Pontiac,' were used. The former is a species that can be hardened after subjecting to the low temperature, and the latter does not harden. Samples for the electron microscopy were prepared from callus cultures after hardening at 2 C in the dark for 0, 5, 10, 15, and 20 days. After 20 days acclimation, S. acaule increased in frost hardiness from -6 to - 9 C (killing temperature), whereas frost hardiness of S. tuberosum remained unchanged (killed at -3 C). Actually, after 15 days acclimation, a -9 C frost hardiness level in S. acaule callus cultures had been achieved.Membrane protein particle aggregation was monitored using freeze-fracture electron microscopy. Protein particles were aggregated in S. acaule up to 10 days after the initiation of acclimation treatment and then redistributed almost to the level of control after 15 days. No such changes were observed for S. tuberosum under similar experimental conditions. The change in protein particle aggregation pattern in S. acaule is interpreted as indicating the presence of an adaptive fluidity control mechanism in that species.


UV-Curable Urethane Acrylate Resin from Palm Fatty Acid Distillate.
Palm fatty acid distillate (PFAD), is a by-product of the crude palm oil refining process. It comprises mainly of free fatty acids-around 45% palmitic and 33% oleic acids-as the major components. Ultra-violet (UV) curable urethane acrylate (UA) oligomers could be synthesized from PFAD, by the following procedure. A hydroxyl terminated macromer was first prepared by reacting PFAD with a mixture of isophthalic acid, phthalic anhydride, neopentagylcol (NPG), and pentaerythritol. The macromer was then reacted with 2-hydroxylethylacrylate (2HEA) and toluene diisocynate (TDI) to generate a resin, containing acrylate side chains for UV curable application. A series of UA resins were prepared by using 15, 25, 45, 55, and 70% of PFAD, respectively. The UA resin has Mw in the range of 3,200 to 27,000. They could be cured by UV irradiation at an intensity of 225 mW/cm². Glass transition temperature (Tg) of the cured film was measured by differential scanning calorimeter (DSC), and hardness of the film was determined by a pendulum hardness tester, according to American Society for Testing and Materials (ASTM)4366. The resins were used in a wood-coating application. All of the cured films showed good adhesion, hardness, and chemical resistance except for the one using the 70% PFAD, which did not cure properly.


Sudden death associated with lipoma of the cerebellopontine angle.
Intracranial lipomas are rare benign tumors considered exceptional when localized in the cerebellopontine angle (CPA), with an incidence of 0.1% of the total number of expansive processes located in this area. We present a case of the sudden death of a 26-year-old young woman in which an unencapsulated neoformation of 0.8 cm was documented at the right cerebellopontine angle and was histologically characterized as intracranial lipoma. The cause of death was then identified as a cardiocirculatory failure secondary to supratentorial (uncal right) herniation caused by the lipoma of the pontocerebellar angle with high-grade diffuse cerebral edema.


Inconsistencies in the correlates of blood pressure and heart rate.
Various correlates of blood pressure (BP) and resting heart rate (HR) were compared in a study population of 1667 male and 520 female factory employees in Israel. The strong positive association between HR and both diastolic and systolic BP described in other epidemiologic studies was again evident. However, the correlates of HR and BP did not coincide. In multiple regression analyses age was found to be positively associated with BP in both sexes, whereas it was only moderately associated with HR in males and inversely associated with HR in females. Relative weight was positively associated with BP in both sexes but its association with HR was linear in young males and older females and U- or J-shaped in the other sub-groups. Cigarette smoking was inversely associated with diastolic BP in several subgroups but was positively associated with HR in most sub-groups. Ethnic-related variations in blood pressure, where found, did not parallel any differences in HR and in one group they were contradictory. The inconsistencies in the correlates of HR and blood pressure may reflect different mechanisms by which certain factors influence BP with varying effects on the HR.


Detection of anti-ovalbumin IgG in serum by immune complex transfer enzyme immunoassay.
An immune complex transfer enzyme immunoassay for anti-ovalbumin IgG in serum is described. Serum-specific antibody was reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-ovalbumin conjugate and ovalbumin-peroxidase conjugate. The complex formed by the three components was trapped onto polystyrene balls coated with anti-2,4-dinitrophenyl group IgG, eluted with epsilonN-2,4-dinitrophenyl-L-lysine and transferred to polystyrene balls coated with anti-human IgG-gamma-chain. Bound peroxidase activity was determined by fluorometry. This enzyme immunoassay was 300- to 1,000-fold more sensitive and more reliable than the enzyme-linked immunosorbent assay (ELISA). Anti-ovalbumin IgG was detected in 100% of healthy subjects using this method while only 14% were detected by ELISA.


Color, Music, and Emotion: Bach to the Blues.
When people make cross-modal matches from classical music to colors, they choose colors whose emotional associations fit the emotional associations of the music, supporting the emotional mediation hypothesis. We further explored this result with a large, diverse sample of 34 musical excerpts from different genres, including Blues, Salsa, Heavy metal, and many others, a broad sample of 10 emotion-related rating scales, and a large range of 15 rated music-perceptual features. We found systematic music-to-color associations between perceptual features of the music and perceptual dimensions of the colors chosen as going best/worst with the music (e.g., loud, punchy, distorted music was generally associated with darker, redder, more saturated colors). However, these associations were also consistent with emotional mediation (e.g., agitated-sounding music was associated with agitated-looking colors). Indeed, partialling out the variance due to emotional content eliminated all significant cross-modal correlations between lower level perceptual features. Parallel factor analysis (Parafac, a type of factor analysis that encompasses individual differences) revealed two latent affective factors- arousal and valence -which mediated lower level correspondences in music-to-color associations. Participants thus appear to match music to colors primarily in terms of common, mediating emotional associations.


G, A and M immunoglobulin levels in parturient's blood serum, umbilical blood of their neonates and the amniotic fluid in physiological deliveries.
The present investigation is aimed at determination of G, A and M immunoglobulins concentration levels in the blood serum of parturients, umbilical blood of their neonates and in the amniotic fluid in 50 women with physiological pregnancy and delivery whose neonates were fully mature. In order to evaluate IgG, IgA and IgM concentration in the biological fluids, the method of inhibition of passive hemagglutination was applied. IgG and IgA were detected in all the three environments, while the presence of IgM was confirmed in all cases in the blood serum but only in 78% of the tested samples of the aminotic fluid. Mean values of IgG and IgM concentration both in the parturients' serum as well as in the umbilical blood of their neonates as compared with the values found in the amniotic fluid, revealed statistically significant differences. The statistically significant correlation noted between the values of IgG concentration in the parturients' serum and the umbilical blood of their neonates was not confirmed in the case of IgA and IgM.


[Kinetic features of ascites and solid Ehrlich tumors].
Such biological parameters as tumor volume, Ki-67 and p53, which characterize the development of ascites and solid tumor of Ehrlich were evaluated. The kinetic curve of growth of ascites tumor was S-shaped (Gomperts) while that of the solid one--cubic (Speer-Retsky). Ki-67 expression level was found to be in cyclic correlation with duration (3 and 6 day intervals) which might be worth considering when working out therapeutic procedure. Moreover, no increase in cell death was observed when tumor growth slowed down.


Effectiveness of Remdesivir, Lopinavir/Ritonavir, and Favipiravir for COVID-19 Treatment: A Systematic Review.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel strain that causes acute respiratory illnesses known as coronavirus disease 2019 (COVID-19). Currently, there is limited information regarding the therapeutic management for this disease. Several studies have stated that antivirals drugs such as remdesivir, favipiravir, and lopinavir/ritonavir may potentially inhibit the virus from spreading to the host. The aim of this systematic review was to summarize the clinical effectiveness and safety of remdesivir, favipiravir, and lopinavir/ritonavir on COVID-19. The PubMed and Cochrane Library databases were searched up to July 2021 to identify eligible experimental randomized controlled trials on remdesivir, favipiravir, and lopinavir/ritonavir for COVID-19 patients. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. From 158 references, 15 studies were included in the review. The results showed that remdesivir has some potential benefits for hospitalized COVID-19 patients, as seen from clinical improvements such as faster recovery time, less duration of hospitalization, and fewer respiratory side effects among COVID-19 patients. However, the impact of remdesivir in reducing mortality remains uncertain. Treatment with favipiravir has shown promising improvement in the clinical status of COVID-19 patients, although the results suggested no significant differences in some clinical parameters such as length of hospitalizations and clinical recovery. A combination of favipiravir with other supportive therapy showed more favorable outcomes for COVID-19 patients. Furthermore, the use of lopinavir/ritonavir in COVID-19 patients reported no significant clinical improvement compared to standard care with notable adverse effect reactions. This study provides an overview of the evidence-based role of remdesivir, favipiravir, and lopinavir/ritonavir in the management of COVID-19. A thorough assessment of the benefit-risk profile in COVID-19 patients is urgently needed. The current review was based on very limited available data; therefore, further well-designed clinical trials are required.


Promoting exercise behaviour: an integration of persuasion theories and the theory of planned behaviour.
The purpose of this study was to examine the effectiveness of a theoretical integrated persuasive message on exercise motivation in college students. Four hundred and fifty introductory psychology students (M age = 20.02 years; SD = 3.94) were randomly assigned to reading positively or negatively framed strong messages advocating exercise. The messages were attributed to a credible source, a non-credible source or to a no-source control condition. Theory of planned behaviour (TPB) constructs (i.e. attitude, subjective norm, perceived behavioural control) and cognitive responses (i.e. thought listing) were measured immediately and 2 weeks following the delivery of the intervention. Unfortunately, the results did not corroborate previous research, as we did not find any significant effects between experimental groups on any psychological or behavioural variable. There may be several potential explanations for the lack of effects, including the interaction between the type of persuasive information (TPB implications) and sources of persuasion and how these persuasive messages are processed (elaboration likelihood model/cognitive response implications). The theoretical implications of this research are discussed with a view towards future directions for exercise promotion initiatives using theoretically driven interventions.


[Neurology in the works of Lope de Vega].
The Madrilenian Félix Lope de Vega Carpio (1562 1635) was the first Spanish playwright. As a privileged witness to his time and with an exquisite knowledge of the human soul, he managed to portray all the social and human reality of the Golden Age in his more than 700 plays. Illnesses and those who suffer them are to be found throughout his works. Many neurological diseases, such as apoplexy, melancholy, headaches or epilepsy, appear quite often in his plays. His descriptions are accurate and the ideas about each disease reflect the knowledge that existed during his time (galenic, medieval or renaissance).


A Case of Autism with Ring Chromosome 14.
Autism is a complex neuropsychiatric disorder that manifests in early childhood. Although the etiology is unknown yet but, new hypothesis focused on identifying the key genes related to autism may elucidate its etiology. The main objective of the present study was to verify the value of karyotyping in autistic children and identifying association between chromosome abnormalities and autism. We examined the peripheral blood lymphocytes cell culture for cytogenetic alterations by GTG-banding technique. The investigation was carried out on 50 autistic patients referred by Pediatric neurologist to Cytogenetic Laboratory in Khorasan-e-razavi Province, Iran. Using GTG-banding technique, the chromosome analysis of patients identified an unbalanced male karyotype with a r (14) in all 50 metaphaseswere examined. Since structural abnormalities may have a critical role in the etiology of autism, according to the region where is affected and number of related genes, therefore an outcome with wide spectrum of clinical manifestations could be expected. Furthermore by considering of recent study, the results indicated that there is an association between chromosome 14 with brain development and neurological disorders, but, in conclusion, it could not be suggested that in order to postulate cytogenetic testing in idiopathic autism patients, specifically screening for chromosome 14 which might has diagnostic value.


Grape juice concentrate protects reproductive parameters of male rats against cadmium-induced damage: a chronic assay.
The aim of the present study was to investigate the effects of long-term grape juice concentrate (GJC) consumption, in two dosages, on the reproductive parameters of cadmium-exposed male rats. The effects of the concentrate on body mass gain, plasma testosterone levels, reproductive organ weights, daily sperm production, sperm morphology, testis histopathological and histomorphometrical parameters, and testicular antioxidant markers were investigated. Wistar rats (n 54) were distributed into six groups: CdCl2; cadmium and grape juice I (1·18 g/kg per d); cadmium and grape juice II (2·36 g/kg per d); grape juice I (1·18 g/kg per d); grape juice II (2·36 g/kg per d); control. A single dose of CdCl2 (1·2 mg/kg body weight (BW)) was injected intraperitoneally and the grape juice was administered orally for 56 d. The results indicated that cadmium changed all reproductive and antioxidant parameters. At dosage I (1·18 g/kg BW), GJC consumption did not show the effects against cadmium-induced damages. In contrast, at dosage II (2·36 g/kg BW), the GJC improved the gonadosomatic index (P= 0·003), serum testosterone levels (P= 0·001), the relative weight of epididymis (P= 0·013) and ventral prostate (P= 0·052), the percentage of normal sperm (P= 0·001), and histopathological and histomorphometrical parameters. In addition, at this dosage, normalisation of the enzymatic activity of superoxide dismutase (P= 0·001) and of testicular levels of glutathione (P= 0·03) were observed. The parameters of the non-exposed rats did not depict significant alterations. In conclusion, the product was able to act as a protector of reproductive function against cadmium-induced damage. Such a property was expressed in a dose-dependent manner as the more effective dose was dosage II. The GJC acted possibly by antioxidant mechanisms.


[Circadian rhythm of the heart rate and autonomic nervous system stimulation tests in patients with systemic lupus erythematosus].
We studied 19 women (mean age 35 +/- 13 years) with systemic lupus erythematosus (SLE), in order to evaluate whether or not alterations in the circadian rhythm of heart rate (HR) occur in patients with pathologic responses to stimulation tests of the autonomic nervous system (ST-ANS). The duration of SLE was 5.3 +/- 5 years. None of the patients had clinical signs of cardiopathy or dysautonomy, nor were any of them taking drugs with known effects on the heart or ANS. Nine patients (47%, group A) had normal ST-ANS and 10 (53%, group B) had an abnormal response to at least 1 ST-ANS (5 to sympathetic ANS, 3 to parasympathetic and 2 to both ST-ANS). Age, duration of disease and therapy were not different between the 2 groups. All patients underwent 24-hour ambulatory ECG monitoring, and chronobiologic analysis of hourly HR was carried out by single and mean cosinor methods. A significant circadian rhythm was found both in the total sample (mesor 80 b/min, acrophase h 13:12; p less than 0.01), and, separately, in group A (mesor 82 b/min, acrophase h 13:11; p less than 0.01) and group B (mesor 78 b/min, acrophase h 13:12; p less than 0.01). No difference existed between the HR circadian rhythms of the 2 groups. Thus, our data show the possibility of ANS involvement in SLE patients without clinical signs of dysautonomy; the analysis of the HR circadian rhythm does not appear to be a sensitive method to identify early involvement of the ANS in these patients.


Control of the actin cytoskeleton in plant cell growth.
Plant cells grow through increases in volume and cell wall surface area. The mature morphology of a plant cell is a product of the differential rates of expansion between neighboring zones of the cell wall during this process. Filamentous actin arrays are associated with plant cell growth, and the activity of actin-binding proteins is proving to be essential for proper cell morphogenesis. Actin-nucleating proteins participate in cell expansion and cell plate formation whereas the recycling of actin monomers is required to maintain actin dynamics and controlled growth. Coordination of actin-binding protein activity and other aspects of cytoskeletal behavior during cell development maintains cohesive cell expansion. Emerging plant signaling networks are proving to be powerful regulators of morphology-shaping cytoskeletal activity, and in this review we highlight current research in actin network regulation.


High-order DBR semiconductor lasers: effect of grating parameters on grating performance.
In this paper, a high-order distributed Bragg reflector (DBR) semiconductor laser operating at 1064 nm is demonstrated based on simulation analysis. To get optimal Bragg grating characteristics, four parameters of the Bragg grating were analyzed in detail. Forty-nine-order Bragg gratings were designed with a reflectivity of 6% and a FWHM of 3 nm, which can realize mode selection while lasing. The Bragg gratings were designed to maximize the use of light. Transmission of the rear laser facet is theoretically 0. This simulation result provides a simple and efficient DBR semiconductor laser scheme without cavity surface coating.


Fecal incontinence: three steps to successful management.
Fecal incontinence is a socially disruptive problem that occurs with increased frequency in older individuals. The causes of incontinence in this age group include abnormalities of rectal storage capacity, fecal impaction with overflow incontinence and disorders of rectosphincteric continence mechanisms. Evaluation consists of a careful history and physical examination, followed by studies of anorectal structure and function in selected patients. Therapeutic approaches include disimpaction and colonic cleansing, dietary modifications, pharmacologic agents, biofeedback techniques, and surgery. Most patients can be treated successfully with nonsurgical measures, with improvement in their quality of life.


Coexistence of Essential Thrombocythemia, Iron-Refractory Iron Deficiency Anemia and Renal Cell Carcinoma.
Essential thrombocythemia (ET) is a Philadelphia chromosome (Ph)-negative myeloproliferative neoplasm. It is characterized by thrombocytosis and megakaryocytic hyperplasia of the bone marrow with JAK2V617F mutation. Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder, which is mainly characterized by iron deficiency anemia not responding to oral iron intake, but partially responding to parenteral iron therapy. Recently, it has been shown that IRIDA has stemmed from mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (matriptase-2) expressed by the liver. Renal cell carcinoma (RCC) accounts for 2-3% of all cancers. As the most common solid lesion in the kidneys, it represents approximately 90% of all renal malignancies. Approximately 30% of patients with symptomatic RCCs seem to display paraneoplastic syndromes. The symptom that may result from erythrocytosis is the most well-known paraneoplastic hematological event. Here, we report a patient who presents with coexistence of RCC and thrombocytosis, which hasn't been caused by hormonal factors that are produced in tumor cells. This patient has been therefore diagnosed with ET. The patient who was expected to display RCC with polycythemia, conversely present with IRIDA.


Broadly reactive antibody-dependent cellular cytotoxic response to HIV-1 envelope glycoproteins precedes broad neutralizing response in human infection.
To determine if and when the antibody-dependent cell-mediated cytotoxic (ADCC) response of human serum exhibits broad reactivity across HIV-1 strains, multiple sera were tested for their ability to mediate ADCC against target cells infected with recombinant vaccinia vectors expressing envelope genes of HTLV-IIIB or HTLV-IIIRF. These vectors were found to express the envelope glycoproteins of the two HIV-1 strains and so were appropriate targets for ADCC assays. All the HIV-1-positive sera were able to mediate ADCC against both HTLV-IIIB and HTLV-IIIRF envelope-expressing targets at similar titer. In sera from early seroconverters, the ADCC response was again broadly reactive, even in those sera that exhibited strain-specific neutralizing antibody responses. The ADCC response to natural infection with HIV-1 is therefore broadly reactive and precedes the development of a broad neutralizing antibody response. The broad reactivity of HIV-1-specific ADCC responses may be important for protection against cell-associated virus in vaccine development.


Carotid intervention: stent or surgery? A prospective audit.
This study represents a prospective audit comparing carotid artery stenting (CAS) with carotid endarterectomy (CEA), performed by a single surgical team. Between January 2005 and December 2008, 440 patients were referred; 177 had CAS and 263 CEA. Selection of procedure was individualised and contra-indications for CAS included internal carotid artery (ICA) stenosis > 85-90%, intraluminal thrombus, ICA tortuosity, gross surface ulceration of plaque and excessive calcification. Type III aortic arch and arch calcification also precluded CAS. Standard techniques were used for both procedures with a protection device routinely used for CAS. Most CEAs were performed under general anaesthesia, with selective intraluminal shunting. One hundred and eighty-six patients were selected for CAS; nine (48% ) were converted to CEA for technical reasons. The operative risk profile was similar, but significantly more in the CAS group were hypertensive. Almost half (49% ) in the CAS group were asymptomatic vs 26% in the CEA group. All asymptomatics had 70+ % stenosis on Duplex Doppler. Results were reported within one month of the procedure. The stroke rate was 2.3% for CAS vs 1.9% for CEA (p > 0.05). Stroke and death plus one M1 was 4.5% after CAS vs 3.4% after CEA (p > 0.05). Disabling stroke occurred in 1.1% of CAS patients vs 0.4% of CEA patients. These results are satisfactory and compare favourably with other similar series.


Extracellular vesicles degradation pathway based autophagy lysosome pathway.
As an ancient intracellular degradation pathway, the autophagy lysosome pathway exists in various cells continuously and stably and maintains cellular homeostasis by degrading damaged organelles and misfolded proteins that are prejudicial to cells. Extracellular vesicles (EVs) including microparticles and exosomes, are derived from varieties of mammalian tissue cells such as platelets, endothelial cells, cardiomyocytes. Through large quantity of active substances carried by EVs, EVs exert momentous biological functions. Recent researches have revealed the molecular mechanism of the interaction between extracellular vesicles and autophagy. In this review, we first elaborate that extracellular vesicles are identified and internalized by target cells by means of receptor-ligand. Since extracellular vesicles contain multiple functional molecules, we subsequently describe the process of intracellular autophagy pathway induced by extracellular vesicles, which activates autophagy-related pathways or delivers autophagy-associated molecules. Finally, we introduced the effects of extracellular vesicle-induced autophagy on extracellular vesicles and target cells respectively. In conclusion, this article integrates relevant theoretical knowledge of autophagy caused by extracellular vesicles and provides a new direction for the study of extracellular vesicles in the future.


Blood flow distribution within the rib cage muscles.
We used 15-microns radiolabeled microspheres to study the regional distribution of blood flow (Q) among parasternal (PS), transversus thoracis, and external (EI) and internal intercostal muscles (II) in nine anesthetized supine mongrel dogs. We measured Q (ml.min-1.100 g-1) in each intercostal space (ICS) during spontaneous breathing, inspiratory resistive loading, and mechanical ventilation following paralysis. At necropsy the EI, II, and PS were excised and sampled separately for each ICS. During paralysis there was no consistent gradient in Q among the PS, II, and EI muscles. During spontaneous breathing, Q to PS increased linearly by 125% between the first and fourth to sixth ICS, Q to EI decreased progressively from the first/second ICS to the fifth/sixth ICS, whereas Q to the II was uniform. During inspiratory resistive loading, in which mouth pressures of -16 +/- 4 cmH2O were generated, the PS gradient was similar to that during spontaneous breathing. Also, Q to the EI increased in the cranial interspaces (P less than 0.02), whereas Q to the II of the seventh/eighth ICS was greater than that of the first/second ICS (P less than 0.001). Furthermore, with loading, ventrodorsal gradients in Q appeared within both EI and II interspaces. There was no consistent gradient in Q within the transversus thoracis muscle during any of the interventions. Our results demonstrate nonuniform Q within PS, EI, and II during both spontaneous and inspiratory resistive loaded breathing. On the assumption that changes in Q reflect changes in activation, our results suggest systematic topographical patterns of recruitment of rib cage respiratory muscles.


Molecular screening of XY SRY-negative sex reversal cases in horses revealed anomalies in amelogenin testing.
Male-to-female sex reversal in horses is a developmental disorder in which phenotypic females have a male genetic constitution. Male-to-female sex reversal is the second most common genetic sex abnormality, after X chromosome monosomy. All male-to-female sex reversal cases studied to date have been found to be infertile. Therefore, a screening test is particularly useful in laboratories doing DNA genotyping in horses. Our laboratory has tested > 209,000 horses for parentage using a panel of microsatellite markers and the sex marker gene amelogenin (AMEL). Suspect XY sex reversal cases are reported females with a male profile by AMEL testing. After routine genotyping, 49 cases were detected and further tested using the sex-determining region Y (SRY) gene, confirming the XY SRY-negative genotype of suspect sex reversal cases. When some inconsistencies arose in the initial result, a molecular panel of X- and Y-linked markers was analyzed for these samples. Of the 49 cases, 33 were confirmed as XY SRY-negative. The remaining 16 cases were identified as false-positives as a result of anomalies of AMEL testing in horses.


Cancer Stem Cells in Glioblastoma Multiforme.
To identify and characterize cancer stem cells (CSC) in glioblastoma multiforme (GBM). Four-micrometer thick formalin-fixed paraffin-embedded GBM samples from six patients underwent 3,3-diaminobenzidine (DAB) and immunofluorescent (IF) immunohistochemical (IHC) staining for the embryonic stem cell (ESC) markers NANOG, OCT4, SALL4, SOX2, and pSTAT3. IF IHC staining was performed to demonstrate co-expression of these markers with GFAP. The protein expression and the transcriptional activities of the genes encoding NANOG, OCT4, SOX2, SALL4, and STAT3 were investigated using Western blotting (WB) and NanoString gene expression analysis, respectively. DAB and IF IHC staining demonstrated the presence of a CSC population expressing NANOG, OCT4, SOX2, SALL4, and pSTAT3 with the almost ubiquitous presence of SOX2 and a relatively low abundance of OCT4, within GBM. The expression of NANOG, SOX2 and, pSTAT3 but, not OCT and SALL4, was confirmed by WB. NanoString gene analysis demonstrated transcriptional activation of NANOG, OCT4, SALL4, STAT3, and SOX2 in GBM. This study demonstrated a population of CSCs within GBM characterized by the expression of the CSC markers NANOG, SALL4, SOX2, pSTAT3 and OCT4 at the protein and mRNA levels. The almost ubiquitous presence of SOX2 and a relatively low abundance of OCT4 would support the putative existence of a stem cell hierarchy within GBM.


Outer retinal tubulation: a novel optical coherence tomography finding.
To describe tubular structures found in the outer retina seen in a variety of retinal disorders. Sixty-nine eyes of 63 patients were examined with spectral-domain optical coherence tomography. Optical coherence tomography C-scans were correlated with their corresponding B-scans. The prevalence, number, size, and shape of the tubular structures were determined. Branching tubules were identified in the outer retina of 54 patients with age-related macular degeneration and in 9 patients with other diagnoses. The tubules appeared as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans, measuring 40 to 140 microm high and 40 to 2260 microm wide. Morphologic features ranged from single straight or branching tubules to complex cavitary networks, usually overlying areas of pigment epithelial alteration or subretinal fibrosis. The tubules generally remained stable over time. In a retinal practice specializing in advanced age-related macular degeneration, these structures were identified in 60 of 248 patients (24.2%) seen during a 3-month period. Degenerating photoreceptors may become arranged in a circular or ovoid fashion during a process we propose to term outer retinal tubulation. These changes are apparently common in advanced diseases affecting the outer retina and retinal pigment epithelium. This observation has practical implications because these findings can be misinterpreted as intraretinal or subretinal fluid, possibly prompting unnecessary interventions.


Plant Dermatitis: More Than Just Poison Ivy.
Plants can cause allergic contact dermatitis (ACD), mechanical irritant contact dermatitis, chemical irritant contact dermatitis, light-mediated dermatitis, and pseudophytodermatitis. Allergic contact dermatitis to chemicals in the Toxicodendron genus, which includes poison ivy, poison oak, and poison sumac, is the most common cause of plant ACD; however, many other plants, such as Compositae, Alstroemeriaceae, and Rutaceae plants also are important causes of dermatitis. In individuals with recurrent ACD from plants other than Toxicodendron, patch testing can be used to identify the source of allergic reactions to plant species. This article provides an overview of the various plant dermatoses, common culprits of plant dermatitis, and diagnostic and therapeutic options for plant dermatoses.


Methods for multiple-marker mapping of quantitative trait loci in half-sib populations.
In this paper we consider the detection of individual loci controlling quantitative traits of interest (quantitative trait loci or QTLs) in the large half-sib family structure found in some species. Two simple approaches using multiple markers are proposed, one using least squares and the other maximum likelihood. These methods are intended to provide a relatively fast screening of the entire genome to pinpoint regions of interest for further investigation. They are compared with a more traditional single-marker least-squares approach. The use of multiple markers is shown to increase power and has the advantage of providing an estimate for the location of the QTL. The maximum-likelihood and the least-squares approaches using multiple markers give similar power and estimates for the QTL location, although the likelihood approach also provides estimates of the QTL effect and sire heterozygote frequency. A number of assumptions have been made in order to make the likelihood calculations feasible, however, and computationally it is still more demanding than the least-squares approach. The least-squares approach using multiple markers provides a fast method that can easily be extended to include additional effects.


Carcinogenesis of renal cell carcinoma reflected in HLA ligands: A novel approach for synergistic peptide vaccination design.
Despite recent advances in immunotherapy of renal cell carcinoma (RCC), peptide vaccination strategies still lack an approach for personalized peptide vaccination that takes intra- and inter-tumoral heterogeneity and biological characteristics into account. In this study, we use an immunoprecipitation and mass spectrometry-based approach supplemented by network analysis of HLA ligands to target this goal. By analyzing HLA-presented peptides for HLA class I and II of 11 malignant and 6 non-malignant kidney tissue samples, more than 2,700 peptides and 1,600 corresponding source proteins were identified. A high overlap with HLA ligands derived from peripheral blood mononuclear cells (PBMCs) was detected most likely due to tumor-infiltrating inflammatory cells and therefore excluded from network analysis. Subsequent biological function analysis of HLA ligands by the GeneMANIA online platform showed enrichment for well established, but also novel, pathways and biological processes involved in carcinogenesis of RCC almost exclusively in malignant tissue samples. By exploring source proteins involved in these overrepresented pathways, we verified various known tumor-associated antigens (TAAs) for RCC (e.g., CA9, EGLN3, IGFBP3, MMP7, PAX2, VEGFA, or EGFR) but could also detect novel TAAs for RCC (e.g., PLOD2, LOX, ENPEP, or TGFBI). Some of these new TAAs had already been shown to elicit a T cell response in cancer patients. Thus, network analysis of HLA ligands provided a new platform for implementing personalized, multipeptide vaccines with potentially synergistic antitumor effects.


[Chronic kidney disease: do generalists and nephrologists differ in their care?].
Chronic kidney disease (CKD) is a major public health problem. We report an evaluation of the CKD perception from a French family physician's (FP) point of view. A questionnaire was sent to a representative and independently selected sample of 497 FP, i.e. 20% of the FP working in the administrative region Lorraine. There were 214 completed surveys, i.e. response rate: 43%. Age of FP was: < 40 years of age: 13%, 40-50: 40%, > 50: 47%. The geographic working place was urban: 41%, rural: 22%, urban and rural: 37%. Ninety-nine per cent of FP has a nephrologist, devoted to CKD referral. Twenty-one per cent of FP has a comprehensive picture of CKD and 75% thinks that CKD diagnostic is difficult Thirty per cent of FP were aware of CKD guidelines. For FP, risk-factors for CKD were: hypertension: 93%, diabetes: 99%, age over 65: 64%, urinary infection: 34%, hematuria/proteinuria: 78%, anaemia: 43%, therapeutics associated with risk of renal injury: 79%, all of these circumstances: 20%. The referral decision to a nephrologist was done at a mean creatinine clearance of 41+/-12 ml/min. Age over 80, dementia, and cancer were considered to be a contra-indication of renal replacement therapy, for respectively 30%, 69%, and 63% of FP. CME was associated with better awareness of guidelines, and use of clearance rather than serum creatinin. From FP point of view, overall awareness of CKD guidelines is low. In the context of the current nephrology services, greater sharing of CKD care with FP is needed.


Perspectives of sex therapy outcome: a survey of AASECT providers.
Randomly selected AASECT members who reported that they conduct sex therapy (N = 289) responded to a questionnaire about their sex therapy caseloads. Desire discrepancies between partners was the most common problem (31%). Least commonly reported problems were vaginismus (5%), ejaculatory inhibition (5%), and primary erectile dysfunction (2%). Highest success rates (client satisfaction with sexual functioning) were for premature ejaculation (62%), secondary orgasmic dysfunction (56%), and desire discrepancies (53%). Primary erectile dysfunctions had the lowest success rate (25%). The most commonly used treatment methods were a focus on communication skills, general sex education, homework assignments, and a focus on the sexual interaction; sensate focus, and the discussion of nonsexual individual and/or relationship issues also were quite commonly used. From a discriminant function analysis, the combined Therapists and Multiple-certified provider groups reported focusing on sexual interactions more than the combined Counselors and Educators; the Educators were the least likely providers to use a focus either on sexual interactions or on homework assignments. The Counselors were the most likely, and the Educators the least likely, to use communication skills. Therapists and the Multiple-certified providers estimated higher treatment success rates than Counselors and Educators for premature ejaculation, secondary erectile dysfunction, vaginismus, primary orgasmic dysfunction, sexual avoidance, ejaculatory inhibition, and sexual arousal problems. The Educators were the least successful with dyspareunia. Educators and Counselors were similar in reporting the fewest clients with sexual arousal problems. Therapists and Multiple-certified providers reported spending more treatment hours with desire discrepancies and desire problems. The implications of the findings for clinical practitioners and researchers are discussed.


Persistent pain produces stress-like alterations in hippocampal neurogenesis and gene expression.
Clinical observations have shown that patients with chronic pain are often depressed, suggesting the importance of the affective or emotional component of pain and its impact on cognition. In this study we investigated pain-induced activation of the hippocampus to address possible molecular and cellular events that may underlie the comorbidity of chronic pain and depression. Rats received either an acute (formalin) or chronic (complete Freund's adjuvant) inflammatory stimulus to the hind paw or an acute or chronic immobilization. Results demonstrated that pain can alter hippocampal morphology and gene expression. Bromodeoxyuridine (BrdU) staining indicated that neurogenesis in the hippocampal dentate gyrus was significantly reduced after long-term inflammatory nociception, similar to previous observations after various stress models. Important activators of nociception-induced spinal central sensitization, the neurokinin-1 (NK-1) receptor and brain-derived neurotrophic factor (BDNF), have also been intimately associated with depressive processes in the limbic system. In situ hybridization assay results demonstrated that either pain or stress (acute or chronic treatments) reduced the levels of both NK-1 receptor and BDNF mRNAs in the cornu ammonis 1-3 sublayers of the hippocampus, suggesting a possible role of these neuromediators in processing of pain in higher brain centers. The findings in this study demonstrate that persistent pain induces stress-like damaging modulatory effects in the hippocampus, which is one of the limbic regions involved in the pathophysiology of depression. Targeting these mechanisms (which are potential contributors to the emotional impact of pain) may provide novel therapeutic approaches for relieving depression-like aspects of chronic pain.


Effects of Mechanical Stimulation on Avena Coleoptile Segment Elongation in a High Resolution, Continuous Growth-recording System.
The effects of an abrasive mechanical stimulation of the inner epidermal surfaces of excised Avena coleoptile segments were examined in relation to growth in the presence and absence of exogenously supplied indole-3-acetic acid. Mechanical stimulation of this nature, provided immediately following excision, was found to elicit a small, transient increase in endogenous growth rate which contributed to a larger initial rapid growth response (previously referred to as a tactile response). These results, contrary to the earlier reports, suggest that the inner epidermal mechanical or tactile stimulation does not account for the entire initial rapid growth response. Preliminary experiments indicate that an alternative form of mechanical stimulation (segment excision) may contribute to that portion of initial rapid growth which is not attributable to inner epidermal abrasion.Following its initial growth-enhancing effect, inner epidermal stimulation had either no effect or in some cases appeared inhibitory to endogenous growth. Growth in response to exogenous auxin was appreciably inhibited by this form of mechanical stimulation.


Arthroscopic removal of improvised explosive device (IED) debris from the wrist: a case report.
We present a case in which arthroscopy was used to remove foreign body debris secondary to an improvised explosive device (IED) from the wrist. The patient had noted pain for 6 months after sustaining multiple injuries after an IED detonation near the armored car in which he was traveling. He had pain on examination at the ulnar fovea with palpation and palpable clunking with forced ulnar deviation. Radiographs showed multiple small metallic objects scattered throughout the soft tissues, with one larger intra-articular object in the wrist. Metallic objects in joints can cause lead toxicity, chondral injury, and inflammatory reaction or abscess. Minimally invasive surgical treatment was proposed with the goals of further joint evaluation and excision of the metallic debris. Arthroscopic removal of the foreign body and repair of the triangular fibrocartilage complex resolved the patient's symptoms, and he had improved function at final follow-up at 22 months.


Corticotropin-releasing hormone induces vascular endothelial growth factor release from human mast cells via the cAMP/protein kinase A/p38 mitogen-activated protein kinase pathway.
Mast cells are involved in allergic reactions but also in innate immunity and inflammation. Corticotropin-releasing hormone (CRH), the key regulator of the hypothalamic-pituitary-adrenal axis, also has proinflammatory effects, apparently through mast cells. We showed recently that CRH selectively stimulates human leukemic mast cells and human umbilical cord blood-derived mast cells to release newly synthesized vascular endothelial growth factor (VEGF) without release of either preformed mediators or cytokines. This effect was mediated through the activation of CRH receptor-1 and adenylate cyclase with increased intracellular cAMP. However, the precise mechanism by which CRH induces VEGF secretion has not yet been defined. Here, we show that CRH-induced VEGF release was dose-dependently inhibited by the specific protein kinase A inhibitor N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89) or the p38 mitogen-activated protein kinase (MAPK) inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) but not by the specific inhibitor 2'-amino-3'-methoxyflavone (PD98059) of mitogen-activated protein kinase kinase, the upstream kinase of the extracellular signal-regulated protein kinase (ERK) or the c-Jun N-terminal kinase (JNK) inhibitor 1,9-pyrazoloanthrone anthra-(1,9-cd)pyrazol-6(2H)-one (SP600125). Furthermore, CRH significantly increased protein kinase A activity, which could be mimicked by the cell-permeable cAMP analog 8-bromo-cAMP, and was blocked by H89 or the adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536). CRH also induced rapid phosphorylation of p38 MAPK, which was mimicked by 8-bromo-cAMP and was inhibited by H89 or SB203580. CRH did not stimulate ERK or JNK phosphorylation and did not increase intracellular calcium levels. These results indicate that CRH induces VEGF release in human mast cells via selective activation of the cAMP/protein kinase A/p38 MAPK signaling pathway, thereby providing further insight into the molecular mechanism of how CRH affects the release of a key proinflammatory mediator.


A multi-biomarker study on Atlantic salmon (Salmo salar L.) affected by the emerging Red Skin Disease in the Baltic Sea.
For half a decade, the Atlantic salmon in the Baltic Sea has been facing severe health issues. Clinical signs like haemorrhage, erosions and ulcerative/necrotic skin conditions in returning adults have been reported from different Swedish rivers. These primary disease signs precede a secondary, terminal fungal infection. As initial investigations of the disease did not provide conclusive answers regarding the pathogenesis, this study was initiated to gain insight into a possible link between this so-called Red Skin Disease and anthropogenic influences. Therefore, returning salmon were caught in rivers along the Swedish coast and different tissues were sampled. The focus was put on the measurements of a battery of biomarkers as well as biochemical and haematological parameters, which were analysed using multivariate statistics. The main findings were a severe osmotic haemodilution, an immune response and an alteration of the carbohydrate metabolism in diseased fish. Furthermore, oxidative stress does not seem to be a likely factor in the pathogenesis. Concluding, certain changes in physiological parameters were shown to be indicative for the disease patterns, while others were ruled out as significant factors. Thus, this study contributes to the understanding of the Red Skin Disease and may act as a hypothesis generator for future studies.


Evoked spinal reflexes and force development in elite athletes with middle-portion Achilles tendinopathy.
Controlled laboratory study. To compare the neuromuscular function of the triceps surae muscle bilaterally in elite athletes with unilateral chronic Achilles tendinopathy. Previous studies suggest that tendinopathies or chronic pain may lead to a spinal/supraspinal level modulation of the excitability or voluntary activation of ipsilateral motor units. However, this has not been studied in Achilles tendinopathy. Fourteen college athletes (mean ± SD age, 24.2 ± 1.7 years) who had unilateral chronic middle-portion tendinopathy in their Achilles tendons were recruited. Bilateral measurements of soleus reflex tests, including H-reflex and V wave, and rate of force development (RFD), as well as corresponding electromyography of the tibialis anterior and triceps surae muscles, were performed. Statistical within-subject and between-leg comparisons were made. In the leg with tendinopathy, the V wave of the soleus muscle was significantly increased (P<.001). The side with tendinopathy also had a reduced normalized RFD (0-30, 0-50, and 0-100 ms) in plantar flexion, and concomitant higher electromyography ratios between the tibialis anterior and soleus (0-30 and 0-50 milliseconds) during the early stage of explosive contractions (P<.05). No significant differences were found for H-reflex, maximal plantar flexion and dorsiflexion torque, and absolute RFD. Higher volitional supraspinal reflexes and lower maximal-strength independent force development occur in the triceps surae of elite athletes with unilateral middle-portion Achilles tendinopathy. These changes potentially indicate an acquired compensatory mechanism for maximal force production and deficits in explosive strength. The RFD is also suggested as a sensitive parameter to depict neuromuscular changes during treatment of chronic tendinopathies.


The electrochemical basis of odor transduction in vertebrate olfactory cilia.
Most vertebrate olfactory receptor neurons share a common G-protein-coupled pathway for transducing the binding of odorant into depolarization. The depolarization involves 2 currents: an influx of cations (including Ca2+) through cyclic nucleotide-gated channels and a secondary efflux of Cl- through Ca2+-gated Cl- channels. The relation between stimulus strength and receptor current shows positive cooperativity that is attributed to the channel properties. This cooperativity amplifies the responses to sufficiently strong stimuli but reduces sensitivity and dynamic range. The odor response is transient, and prolonged or repeated stimulation causes adaptation and desensitization. At least 10 mechanisms may contribute to termination of the response; several of these result from an increase in intraciliary Ca2+. It is not known to what extent regulation of ionic concentrations in the cilium depends on the dendrite and soma. Although many of the major mechanisms have been identified, odor transduction is not well understood at a quantitative level.