Generalized Licen Planus Treated With Narrowband UV-B Phototherapy: Results From 10 Patients and a Review of the Literature.
Generalized lichen planus can be difficult to treat. One alternative for patients who do not respond to common topical and systemic treatments, such as corticosteroids and oral antihistamines, is phototherapy. Narrowband UV-B phototherapy offers several advantages and is currently the main treatment modality. In this study, we present the results corresponding to 10 patients with generalized lichen planus treated with narrowband UV-B phototherapy. We performed a prospective study of adult patients with generalized lichen planus affecting more than 20% of their body surface area. A complete response was observed in 8 patients (80%) and the disease recurred in 2 of these (recurrence rate, 25%). These rates are similar to those reported in the literature reviewed. Narrowband UV-B phototherapy is a widely used alternative to systemic treatments in GLP, but there are very few reports of its results in the literature.


Alteration of chondroitin sulfate composition on proteoglycan produced by knock-in mouse embryonic fibroblasts whose versican lacks the A subdomain.
Versican/proteoglycan-mesenchymal (PG-M) is a large chondroitin sulfate (CS) proteoglycan of the extracellular matrix (ECM) that is constitutively expressed in adult tissues such as dermis and blood vessels. It serves as a structural macromolecule of the ECM, while in embryonic tissue it is transiently expressed at high levels and regulates cell adhesion, migration, proliferation, and differentiation. Knock-in mouse embryonic (Cspg2(Delta3/Delta3)) fibroblasts whose versican lack the A subdomain of the G1 domain exhibit low proliferation rates and acquire senescence. It was suspected that chondroitin sulfate on versican core protein would be altered when the A subdomain was disrupted, so fibroblasts were made from homozygous Cspg2(Delta3/Delta3) mouse embryos to investigate the hypothesis. Analysis of the resulting versican deposition demonstrated that the total versican deposited in the Cspg2(Delta3/Delta3) fibroblasts culture was approximately 50% of that of the wild type (WT), while the versican deposited in the ECM of Cspg2(Delta3/Delta3) fibroblasts culture was 35% of that of the WT, demonstrating the lower capacity of mutant (Cspg2(Delta3/Delta3)) versican deposited in the ECM. The analysis of CS expression in the Cspg2(Delta3/Delta3) fibroblasts culture compared with wild-type fibroblasts showed that the composition of the non-sulfate chondroitin sulfate isomer on the versican core protein increased in the cell layer but decreased in the culture medium. Interestingly, chondroitin sulfate E isomer was found in the culture medium. The amount of CS in the Cspg2(Delta3/Delta3) cell layer of fibroblasts with mutant versican was dramatically decreased, contrasted to the amount in the culture medium, which increased. It was concluded that the disruption of the A subdomain of the versican molecule leads to lowering of the amount of versican deposited in the ECM and the alteration of the composition and content of CS on the versican molecule.


Movement-Pattern Training to Improve Function in People With Chronic Hip Joint Pain: A Feasibility Randomized Clinical Trial.
Study Design Feasibility randomized clinical trial. Background Rehabilitation may be an appropriate treatment strategy for patients with chronic hip joint pain; however, the evidence related to the effectiveness of rehabilitation is limited. Objectives To assess feasibility of performing a randomized clinical trial to investigate the effectiveness of movement-pattern training (MPT) to improve function in people with chronic hip joint pain. Methods Thirty-five patients with chronic hip joint pain were randomized into a treatment (MPT) group or a control (wait-list) group. The MPT program included 6 one-hour supervised sessions and incorporated (1) task-specific training for basic functional tasks and symptom-provoking tasks, and (2) strengthening of hip musculature. The wait-list group received no treatment. Primary outcomes for feasibility were patient retention and adherence. Secondary outcomes to assess treatment effects were patient-reported function (Hip disability and Osteoarthritis Outcome Score), lower extremity kinematics, and hip muscle strength. Results Retention rates did not differ between the MPT (89%) and wait-list groups (94%, P = 1.0). Sixteen of the 18 patients (89%) in the MPT group attended at least 80% of the treatment sessions. For the home exercise program, 89% of patients reported performing their home program at least once per day. Secondary outcomes support the rationale for conduct of a superiority randomized clinical trial. Conclusion Based on retention and adherence rates, a larger randomized clinical trial appears feasible and warranted to assess treatment effects more precisely. Data from this feasibility study will inform our future clinical trial. Level of Evidence Therapy, level 2b-. J Orthop Sports Phys Ther 2016;46(6):452-461. Epub 26 Apr 2016. doi:10.2519/jospt.2016.6279.


Prognostic value of variables derived from heart rate variability in patients with traumatic brain injury after decompressive surgery.
Measurement of heart rate variability can reveal autonomic nervous system function. Changes in heart rate variability can be associated with disease severity, risk of complications, and prognosis. We aimed to investigate the prognostic value of heart rate variability measurements in patients with moderate-to-severe traumatic brain injury after decompression surgery. We conducted a prospective study of 80 patients with traumatic brain injury after decompression surgery using a noninvasive electrocardiography device for data collection. Assessment of heart rate variability parameters included the time and frequency domains. The correlations between heart rate variability parameters and one-year mortality and functional outcomes were analyzed. Time domain measures of heart rate variability, using the standard deviation of the RR intervals and the square root of the mean squared differences of successive RR intervals, were statistically significantly lower in the group of patients with unfavorable outcomes and those that died. In frequency domain analysis, very low-frequency and total power were significantly higher in patients with favorable functional outcomes. High-frequency, low-frequency, and total power were statistically significantly higher in patients who survived for more than one year. Multivariate analysis using a model combining age and the Glasgow Coma Scale score with variables derived from heart rate variability substantially improved the prognostic value for predicting long-term outcome. These findings reinforced the concept that traumatic brain injury impacts the brain-heart axis and cardiac autonomic modulation even after decompression surgery, and variables derived from heart rate variability may be useful predictors of outcome.


Fuji Intelligent Chromo Endoscopy and staining technique for the diagnosis of colon tumor.
Colon cancer is a common malignant tumor in the clinic with an incidence rate that is increasing in recent years. The key point for improving the survival rate is the diagnosis and treatment at an early stage. The purpose of this study was to compare the difference of the Fuji Intelligent Chromo Endoscopy (FICE) and staining technique for the diagnosis of colon tumors and non-tumor lesions. From March to November 2007, 654 patients were examined with ordinary colonoscopy. Among them 223 patients with colon neoplasm or polypoid lesion were included. The patients were examined with a magnifying ordinary colonoscopy, a magnifying FICE technique and magnifying staining technique. The pit pattern and blood capillary form of the lesion were examined, an endoscopic diagnosis was made and it was compared with the pathologic diagnosis. Four hundred and fifty-one neoplasms were detected in the 223 patients, among those 91.1% (411/451) were detected with the magnifying ordinary endoscopy while 99.1% (447/451) were detected with the FICE technique; there was a significant difference between the two methods. FICE could clearly show the structure and form of mucosal blood capillaries (P < 0.01) but there was no significant difference between the two methods for showing the pit pattern. The coincident rate of FICE for the diagnosis of tumor and non-tumor lesions was 91.6% (413/451), that of the magnifying staining technique was 82.0% (370/451) (P < 0.05). Magnifying FICE could show the mucosal microstructure and blood capillary form and it had a superiority of high coincident rate, high sensitivity and specificity when compared with ordinary magnifying colonoscopy and magnifying staining endoscopy. In addition, it was easy to operate and a biopsy could be taken from the target, so it has a satisfactory clinical practical value.


3D Printed Gene-activated Octacalcium Phosphate Implants for Large Bone Defects Engineering.
The aim of the study was the development of three-dimensional (3D) printed gene-activated implants based on octacalcium phosphate (OCP) and plasmid DNA encoding VEGFA. The first objective of the present work involved design and fabrication of gene-activated bone substitutes based on the OCP and plasmid DNA with VEGFA gene using 3D printing approach of ceramic constructs, providing the control of its architectonics compliance to the initial digital models. X-ray diffraction, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and compressive strength analyses were applied to investigate the chemical composition, microstructure, and mechanical properties of the experimental samples. The biodegradation rate and the efficacy of plasmid DNA delivery in vivo were assessed during standard tests with subcutaneous implantation to rodents in the next stage. The final part of the study involved substitution of segmental tibia and mandibular defects in adult pigs with 3D printed gene-activated implants. Biodegradation, osteointegration, and effectiveness of a reparative osteogenesis were evaluated with computerized tomography, SEM, and a histological examination. The combination of gene therapy and 3D printed implants manifested the significant clinical potential for effective bone regeneration in large/critical size defect cases.


Abnormal Dielectric Constant of Nanoconfined Water between Graphene Layers in the Presence of Salt.
Ultra-low dielectric constant of nanoconfined water between two flat slabs is a subject of recent experimental and theoretical research. The impact of dissolution of sodium chloride (NaCl) with various concentrations on the dielectric properties of nanoconfined water between graphene layers are investigated using molecular dynamics simulations. We found that, with increasing salt concentration, (i) the out-of-plane dielectric constant increases and (ii) the in-plane dielectric constant decreases non-linearly. Surprisingly, for channels with heights 6.8Å < h < 8 Å, we found an abnormal increase in the in-plane dielectric constant versus salt concentration, which can be linked to the formation of 2D-ice-like structure. This study sheds light on the variation of dielectric properties of nanoconfined water between graphene layers in the presence of salt, which is of importance in ion transport and electrochemical energy storage.


Ceramide synthase 2 deletion decreases the infectivity of HIV-1.
The lipid composition of HIV-1 virions is enriched in sphingomyelin (SM), but the roles that SM or other sphingolipids (SLs) might play in the HIV-1 replication pathway have not been elucidated. In human cells, SL levels are regulated by ceramide synthase (CerS) enzymes that produce ceramides, which can be converted to SMs, hexosylceramides, and other SLs. In many cell types, CerS2, which catalyzes the synthesis of very long chain ceramides, is the major CerS. We have examined how CerS2 deficiency affects the assembly and infectivity of HIV-1. As expected, we observed that very long chain ceramide, hexosylceramide, and SM were reduced in CerS2 knockout cells. CerS2 deficiency did not affect HIV-1 assembly or the incorporation of the HIV-1 envelope (Env) protein into virus particles, but it reduced the infectivites of viruses produced in the CerS2-deficient cells. The reduced viral infection levels were dependent on HIV-1 Env, since HIV-1 particles that were pseudotyped with the vesicular stomatitis virus glycoprotein did not exhibit reductions in infectivity. Moreover, cell-cell fusion assays demonstrated that the functional defect of HIV-1 Env in CerS2-deficient cells was independent of other viral proteins. Overall, our results indicate that the altered lipid composition of CerS2-deficient cells specifically inhibit the HIV-1 Env receptor binding and/or fusion processes.


Enhancement of the foaming properties of protein dried in the presence of trehalose.
Surface tension, foamability, and foam stability kinetics have been measured for the pure proteins bovine serum albumin (BSA) and beta-lactoglobulin, before and after aqueous solutions of the proteins had been subjected to different drying conditions, and also for whey protein concentrate (WPC). Pure proteins were air-dried, at 78 or 88 degrees C, in the presence and absence of sucrose or trehalose, at a mass ratio of 5:1 sugar/protein. WPC was spray-dried in the presence of various sugars: trehalose, sucrose, lactose, and lactitol. Spray-drying WPC without sugars resulted in a dramatic decrease in the foam stability, whereas drying in the presence of sugars gave better retention of the original foaming properties. Trehalose in particular resulted in almost complete retention of the foam stability observed for the nondried WPC. Pure beta-lactoglobulin showed similar behavior, but trehalose did not seem to afford the same protection to BSA.


Evaluation of the efficacy and safety of favipiravir and interferon compared to lopinavir/ritonavir and interferon in moderately ill patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial.
We will evaluate the efficacy and safety of favipiravir and interferon beta-1a compared to lopinavir/ritonavir and interferon beta-1a in patients with confirmed COVID-19, who are moderately ill. This is a phase 3, single-center, randomized, open-label, controlled trial with a parallel-group design carried out at Shahid Mohammadi Hospital, Bandar Abbas, Iran. All patients with age ≥ 20 years admitted at the Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. 1. Confirmed diagnosis of infection with SARS-CoV-2 using polymerase chain reaction and/or antibody tests. 2. Moderate COVID-19 pneumonia (via computed tomography and/or X-ray imaging), requiring hospitalization. 3. Hospitalized ≤ 48 h. 4. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. 1. Underlying conditions, including chronic hepatitis, cirrhosis, cholestatic liver diseases, cholecystitis, peptic ulcers, acute and chronic renal failure, and peptic ulcers. 2. Severe and critical COVID-19 pneumonia. 3. History of allergy to favipiravir, lopinavir/ritonavir, and interferon beta-1a. 4. Pregnancy and breastfeeding. Intervention group: favipiravir (Zhejiang Hisun, China) with interferon beta-1a (CinnaGen, Iran). This group will receive 1600 mg favipiravir twice a day for the first day and 600 mg twice a day for the following 4 days with five doses of 44 mcg interferon beta-1a every other day. lopinavir/ritonavir (Heterd Company, India) with interferon beta-1a (CinnaGen, Iran). This group will receive 200/50 mg lopinavir/ritonavir twice a day for 7 days with five doses of 44 mcg interferon beta-1a every other day. Other supportive and routine care will be the same in both groups. The primary outcome of the trial is the viral load of SARS-CoV-2 in the nasopharyngeal samples assessed by RT-PCR after 7 days of randomization as well as clinical improvement of fever and O2 saturation within 7 days of randomization. The secondary outcomes are the length of hospital stay and the incidence of serious adverse drug reactions within 7 days of randomization. Eligible patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). A web-based system will be used to generate random numbers for the allocation sequence. Each number relates to one of the study arms. This is an open-label trial without blinding and placebo control. A total of 60 patients will be randomized into two groups (30 patients in the intervention group and 30 patients in the control group). The trial protocol is version 1.0, 22 July 2020. Recruitment began on 25 July 2020 and is anticipated to be completed by 25 September 2020. Iranian Registry of Clinical Trials (IRCT) IRCT20200506047323N3 . Registered on 22 July 2020. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Risk factors, comorbiditiEs and Atherogenic dysLipidaemia in Indian YOUNG patients with dyslipidaemia attending hospital/clinic: REAL YOUNG (dyslipidaemia) study.
To evaluate the pattern of dyslipidaemia, risk factors, and comorbidities in young Indian adults with dyslipidaemia. A retrospective, multi-centric real-world study included individuals with dyslipidaemia, aged 18 - 45 years, attending to 623 hospitals/clinics across India. Data were collected retrospectively from medical records to note demographics, risk factors (smoking, alcohol consumption, sedentary lifestyle, family history of dyslipidaemia, diabetes mellitus, and hypertension), and clinical details (height, weight, waist circumference, body mass index (BMI), blood pressure, blood sugar, glycated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL-C), and high-density lipoprotein (HDL-C)).A descriptive analysis and comparative analysis (Mann-Whitney U test and Chi-square test) were done. Of the total 8135 patients, the majority were men (65.0%). Overall, 87.1% of population had one or multiple comorbidities which included the presence of dyslipidaemia alone (12.9%), dyslipidaemia with diabetes and hypertension (39.1%), dyslipidaemia with diabetes (33.6%), and dyslipidaemia with hypertension (14.4%). Sedentary lifestyle was prevalent observation in >50% of the population. Youngest age (18 - 25) group had higher prevalence of hypertriglyceridemia (63.2%), high LDL-C levels (56.8%), and low HDL-C levels (64.6%), while patients from the age group >25 to ≤35 years had the highest incidence of hypercholesterolemia (66.6%). Atherogenic dyslipidaemia was observed in 41.9%, 25.5%, and 23.2% of patients from age groups of ≥18 to ≤25, >25 to ≤35, and >35 to ≤45 years, respectively. Patients with HbA1c ≥6.5% had significantly higher levels of TG, TC, LDL-C, and lower HDL-C compared to those with HbA1c <6.5%. Hypertriglyceridemia, high LDL-C, low HDL-C, and atherogenic dyslipidaemia were prevalent in the young Indian cohort and sedentary lifestyle, and HbA1c ≥ 6.5% were the predominant risk factors of dyslipidaemia.


Alpha-Helical Fragaceatoxin C Nanopore Engineered for Double-Stranded and Single-Stranded Nucleic Acid Analysis.
Nanopores are used in single-molecule DNA analysis and sequencing. Herein, we show that Fragaceatoxin C (FraC), an α-helical pore-forming toxin from an actinoporin protein family, can be reconstituted in sphingomyelin-free standard planar lipid bilayers. We engineered FraC for DNA analysis and show that the funnel-shaped geometry allows tight wrapping around single-stranded DNA (ssDNA), resolving between homopolymeric C, T, and A polynucleotide stretches. Remarkably, despite the 1.2 nm internal constriction of FraC, double-stranded DNA (dsDNA) can translocate through the nanopore at high applied potentials, presumably through the deformation of the α-helical transmembrane region of the pore. Therefore, FraC nanopores might be used in DNA sequencing and dsDNA analysis.


Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier.
Epidermal TNF expression increases in response to cutaneous permeability barrier disruption and wound healing. TNF signaling is mediated by acid and neutral sphingomyelinases (A- and N-SMase), which generate ceramide, an important regulator of proliferation, differentiation, and apoptosis. In the epidermis, ceramide is known to be an integral part of the extracellular stratum corneum (SC) lipid bilayers that constitute the permeability barrier of the skin. We show here that topical application of TNF after experimental injury to the SC of hairless mice (hr(-/-)) enhances barrier repair. In TNF receptor p55-deficient (TNF-R55-deficient) mice (hr(+/+)), cutaneous barrier repair was delayed compared with wild-type (hr(+/+)) or TNF-R75-deficient (hr(+/+)) animals. After barrier disruption in hairless (hr(-/-)) and wild-type (hr(+/+)), but not in TNF-R55-deficient (hr(+/+)) mice, the enzymatic activities of both A-SMase and N-SMase were significantly enhanced. Stimulation of SMase activities was accompanied by an increase in C(24)-ceramide levels. Most A-SMase activity in hairless mice (hr(-/-)) was found in the outer epidermal cell layers and colocalized in the lamellar bodies with A-SMase and sphingomyelin. Reduction of epidermal A-SMase activity by the inhibitor imipramine resulted in delayed permeability barrier repair after SC injury. Together, these results suggest that TNF-R55 signaling pathways contribute to cutaneous permeability barrier repair through SMase-mediated generation of ceramide.


Geographic analysis of host use, development, and habitat use of an acanthocephalan species, Leptorhynchoides thecatus.
Leptorhynchoides thecatus (Linton, 1891), an acanthocephalan parasite of freshwater fishes, varies in host use, development, and habitat use throughout North America. Spatial structure of these characteristics was examined from data extracted from the literature. Geographic patterns were inferred from point comparisons using correllograms and then tested with Moran's I statistic for global and local significance, and visually from regional means within major river drainages. Species of Micropterus Lacepède, 1802 (black basses) were common hosts in most regions, except the Lower Mississippi and South Atlantic regions where species of Lepomis Rafinesque, 1819 (sunfishes) were common hosts. Development, described as the proportions of adults relative to cystacanths (extraintestinal juveniles), decreased with latitude. Habitat use of L. thecatus showed marked geographic patterns. Leptorhynchoides thecatus occurred in the intestine of sunfishes in the South Atlantic and Lower Mississippi regions, in the ceca in fish of all species included in the study in the Missouri and Texas-Gulf regions, and both in ceca and intestines in fish of all species in northern regions. Leptorhynchoides thecatus showed geographic patterning within the variable traits across the range of the species. These patterns may be the result of ecological factors or of genetic differences that might indicate L. thecatus comprises multiple cryptic species.


Targeting Chemosensory Ion Channels in Peripheral Swallowing-Related Regions for the Management of Oropharyngeal Dysphagia.
Oropharyngeal dysphagia, or difficulty in swallowing, is a major health problem that can lead to serious complications, such as pulmonary aspiration, malnutrition, dehydration, and pneumonia. The current clinical management of oropharyngeal dysphagia mainly focuses on compensatory strategies and swallowing exercises/maneuvers; however, studies have suggested their limited effectiveness for recovering swallowing physiology and for promoting neuroplasticity in swallowing-related neuronal networks. Several new and innovative strategies based on neurostimulation in peripheral and cortical swallowing-related regions have been investigated, and appear promising for the management of oropharyngeal dysphagia. The peripheral chemical neurostimulation strategy is one of the innovative strategies, and targets chemosensory ion channels expressed in peripheral swallowing-related regions. A considerable number of animal and human studies, including randomized clinical trials in patients with oropharyngeal dysphagia, have reported improvements in the efficacy, safety, and physiology of swallowing using this strategy. There is also evidence that neuroplasticity is promoted in swallowing-related neuronal networks with this strategy. The targeting of chemosensory ion channels in peripheral swallowing-related regions may therefore be a promising pharmacological treatment strategy for the management of oropharyngeal dysphagia. In this review, we focus on this strategy, including its possible neurophysiological and molecular mechanisms.


Future directions in the European union for veterinary education as related to food-producing animals, with special reference to Greece.
During the past 50 years, procedures for raising food-producing animals have changed. Intensification of food production was necessary to keep prices low and to fulfill market demands for the continuously increasing worldwide population. Intensification of farming procedures produced many new problems, some of which had a considerable impact on public opinion about how animals are raised and how food of animal origin is produced and preserved. "Man made diseases" of animals such as bovine spongiform encephalopathy (BSE); contamination of foods with dioxins either through contamination of animal feeds or from the environment; and increased microbial resistance to drugs used for treatment, for prophylaxis of animals from infectious agents, and for growth promotion are some well-known hazards of intensified farming. Veterinarians working on food-producing animals are faced with an increased demand for foods of high quality and safety in developed countries, and higher quantities in the rest of the world. These qualitative and quantitative changes indicate that they must adjust to these new conditions. They will be most successful if their education is adjusted to meet the challenges that the public has created for them through new concepts of the production of food of animal origin. One such concept is the production of foods under fully certified procedures from the farm to the consumer's table. Food safety measures protecting public health will better be achieved if the education of the future veterinarian includes the principles of Hazard Analysis Critical Control Points (HACCP) starting at farm level. This article provides some market-driven ideas in this direction for European Union (EU) countries, including Greece.


[Analysis of parents' compliance in non-hospital settings during operation of expressed breast milk bank].
To investigate the parents' compliance in non-hospital settings during the operation of expressed breast milk bank. In September 2014, a questionnaire survey was carried out to investigate the parents' willingness about feeding the inpatient neonates with maternal expressed breast milk, to evaluate the effectiveness of the breast milk feeding supporting system, and to monitor the compliance in non-hospital settings during the delivery of maternal expressed breast milk. Improvements in education were made according to the results. A second survey was done in September 2015. A total of 340 questionnaires were sent out, and 338 usable questionnaires were returned. According to the time when the questionnaires were sent out, they were divided into two groups: 2014 group (n=229) and 2015 group (n=109). The age of most mothers was 20-30 years in the 2014 group and 30-40 years in the 2015 group. Most mothers delivered at the West China Second Hospital of Sichuan University in both groups, but the 2015 group had a significantly higher proportion than the 2014 group (74.3% vs 61.6%; P<0.05). Guidance was given to mothers in the presence of insufficient breast milk production in both groups, but the 2015 group had a significantly higher proportion than the 2014 group (91.7% vs 79.9%; P<0.05). Both groups had good family compliance in the collection, storage, and transport of breast milk. There were no significant differences in their compliance with washing hands, sterilizing instruments, and using a clean special refrigerator between the two groups. The expressed breast milk was transported strictly according to the procedure in both groups, but the 2015 group had a significantly higher proportion than the 2014 group (100% vs 87.1%; P<0.05). Before and after improvements in the health education, most parents have good compliance in the collection, storage, and transport of breast milk.


Combined megaloblastic and immunohemolytic anemia associated--a case report.
A 55-year-old female with a history of psychosis and rheumatoid arthritis was admitted to the hospital for fatigue and dizziness. At admission, macrocytic anemia, high serum lactic acid dehydrogenase (LDH) and gastrin concentrations, decreased serum vitamin B12 concentration, with macroovalocytes and poikilocytes in peripheral blood smear suggested the diagnosis of pernicious anemia. Indirect antiglobulin test (IAT) was negative. Surprisingly, treatment by vitamin B12 and folic acid administered for two weeks was ineffective and followed by transitory worsening of hemoglobin concentration on day 8. Repeat direct antiglobulin test (DAT) and IAT were positive. This immunotransfusion conversion, suggesting the presence of autoimmune hemolytic anemia, could be explained by change in the macroblastic erythrocyte population, i.e. emerging red cells with completely exposed membrane antigens due to vitamin B12 treatment and/or higher degree of dysregulation of the lymphocyte clone secreting erythrocyte autoantibodies. We proposed the coexistence of pernicious and autoimmune hemolytic anemia; therefore, methylprednisolone was added to vitamin B12 treatment. This therapy successfully improved hemoglobin and erythrocyte concentration. Although megaloblastic-pernicious anemia is a common disease, association of pernicious and autoimmune hemolytic anemia with two mechanisms of hemolysis (ineffective erythropoiesis and immune mechanism) is a rare condition, with only several dozens of cases described so far.


Enhanced Surface Properties of Branched Poly(ether sulfone) from Semifluorinated Polyhedral Oligomeric Silsequioxanes.
Hybrid systems in which poly(ether sulfone) (PESU) chains are grafted to semifluorinated polyhedral oligomeric silsesquioxane (POSS) cores are expected to integrate the advantages of both fluoropolymers and POSS into the polymer system to yield excellent surface properties. For that purpose, we synthesized a novel octa-functional perfluorocyclopentenyl-POSS (PFCP-POSS), which was used as a "core" grafting point. Commercial PESU was successfully grafted to PFCP-POSS via the nucleophilic addition-elimination reaction between the phenolic chain ends and reactive PFCP moieties to yield a hybrid branched polymer possessing a semifluorinated POSS core. X-ray photoelectron spectroscopy, neutron reflectivity, and atomic force microscopy indicated that the preparation of nanostructured polymer surfaces occurs by migration of the low surface energy components (PFCP-POSS molecules), while POSS aggregation is suppressed by covalent attachment to the long PESU chains. The resulting PFCP-POSS modified PESU films were highly transparent and yielded hydrophobic surfaces with low surface energy and high modulus for potential applications in high performance coatings and composites.


Decreased plasticity of glucoregulatory responses in aged rats: effects of chronic stress.
These experiments were conducted to determine the effects of age and chronic stress on the ability of rats to attenuate stimulus-induced glucose and insulin responses during repeated exposure to a mild stressor. Young (5-month) and old (21-month) Fischer 344 male rats were either exposed to intermittent sessions of an escapable footshock stress for 3 months, or to no chronic stress. Afterwards, blood samples were obtained from each rat before, during, and after the first and fourth exposure to a novel motion stimulus. Between the first and the fourth exposure to the motion stimulus a pronounced attenuation of glucose and insulin responses was seen in both groups of young rats, and in old chronically stressed rats, but not in old control animals. Thus, it appears that the adverse effects of aging on plasticity of glucoregulatory response processes were significantly diminished by exposure of the animals to periodic challenges from their external environment.


Autologous Haematopoietic Stem Cell Transplantation and Systemic Sclerosis: Focus on Interstitial Lung Disease.
Autologous hematopoietic stem cells transplantation (AHSCT) has been employed as treatment for severe systemic sclerosis (SSc) with high risk of organ failure. In the last 25 years overall survival and treatment-related mortality have improved, in accordance with a better patient selection and mobilization and conditioning protocols. This review analyzes the evidence from the last 5 years for AHSCT-treated SSc patients, considering in particular the outcomes related to interstitial lung disease. There are increasing data supporting the use of AHSCT in selected patients with rapidly progressive SSc. However, some unmet needs remain, such as an accurate patient selection, pre-transplantation analysis to identify subclinical conditions precluding the transplantation, and the alternatives for post-transplant ILD recurrence.


Systematic literature review of humanistic and economic burdens of chronic rhinosinusitis with nasal polyposis.
We conducted a systematic literature review (SLR) of randomized controlled trials and real-world evidence (RWE) studies to determine the humanistic (e.g. health-related/disease-specific quality of life [QOL]) and economic (e.g. direct and indirect costs) burdens of chronic rhinosinusitis with nasal polyposis (CRSwNP). The SLR adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase, MEDLINE and Evidence-Based Medicine Reviews databases were searched using OVID. Relevant studies involving adult patients with CRSwNP published between 1 January 2008 and 16 February 2019 were included, with relevant conference abstracts from 1 January 2017, onward. Sino-Nasal Outcomes Test (SNOT)-22 was the most frequently used disease-specific health-related QOL/patient-reported outcomes instrument for patients with CRSwNP. Baseline SNOT-22 scores ranged from 25 to 73 for surgical candidates and from 14 to 56 for medically managed patients with CRSwNP. Mean baseline EuroQol-5 Dimensions (EQ-5D) index for patients with CRSwNP ranged from 0.81 to 0.86, and mean baseline Short Form-6 Dimensions (SF-6D) ranged from 0.67 to 0.75. Three months (EQ-5D) and 5 years (SF-6D) post-endoscopic sinus surgery (ESS), rates increased from 0.81 to 0.89 and from 0.69 to 0.80, respectively. One year post-diagnosis, patients with CRSwNP had significantly more systemic prescriptions, underwent significantly more medical procedures, demonstrated greater health care resource utilization and had significantly greater mean health care costs compared with matched controls (all p < .001). Overall, for patients with initial ESS, CRSwNP was associated with higher disease-related expenditures compared with CRS without nasal polyposis (NP), even for patients who did not undergo revision surgery. This SLR identified substantial humanistic burden among surgery candidates. RWE shows that surgeries were used to treat relatively more severe CRSwNP patients as recommended by guidelines. Patient QOL is improved significantly after surgery; however, there is a lack of evidence on patients with revision surgery. Surgery is also associated with higher costs, and the presence of NP was a predictor of revision surgery. Patients with CRSwNP demonstrate greater health care resource utilization and costs compared to those with CRS without NP. Costs associated with different severity of CRSwNP and revision surgery need to be assessed further.


Inner Ear Anomalies in Children With Apert Syndrome: A Radiological and Audiological Analysis.
Apert syndrome is a multisystem genetic disorder typically characterized by craniosynostosis and syndactyly. Studies also report an increased incidence of hearing loss in children with Apert syndrome in comparison to the general population. The aim of this study was to gain an understanding of the inner ear radiological anatomical variations seen in children with Apert syndrome and correlate these with audiological outcomes. This was a retrospective review of computed tomography imaging of patients with Apert syndrome. Radiological images were examined for anatomical variations in inner ear structures. These were correlated with audiological testing. Nineteen patients were included in the study. The most commonly observed anomaly was an absent bony window of the lateral semi-circular canal (SCC) in 11 patients (58%), followed by an enlarged lateral SCC in 12 patients (63%). This combination of anomalies was seen collectively in 42% of patients and together these give the appearance of a 'rectangular vestibular cavity'. Audiological results were available in 11 patients and 9 of these patients had a conductive hearing loss. To the authors' knowledge, this is the first study that reports radiological findings alongside audiological testing in Apert syndrome and describes the appearance of a 'rectangular vestibular cavity'.


Changes in Plasma von Willebrand Factor and Cellular Fibronectin in MRI-Defined Traumatic Microvascular Injury.
The neuropathology of traumatic brain injury (TB) is diverse, including primary injury to neurons, axons, glial cells, vascular structures, and secondary processes, such as edema and inflammation that vary between individual patients. Traumatic microvascular injury is an important endophenotype of TBI-related injury. We studied patients who sustained a TBI requiring ER evaluation and had an MRI performed within 48 h of injury. We classified patients into 3 groups based on their MRI findings: (1) those that had evidence of traumatic microvascular injury on susceptibility or diffusion weighted MRI sequences without frank hemorrhage [Traumatic Vascular Injury (TVI) group; 20 subjects]. (2) those who had evidence of intraparenchymal, subdural, epidural, or subarachnoid hemorrhage [Traumatic Hemorrhage (TH) group; 26 subjects], and (3) those who had no traumatic injuries detected by MRI [MRI-negative group; 30 subjects]. We then measured plasma protein biomarkers of vascular injury [von Willebrand Factor (vWF) or cellular fibronectin (cFn)] and axonal injury (phosphorylated neurofilament heavy chain; pNF-H). We found that the TVI group was characterized by decreased expression of plasma vWF (p < 0.05 compared to MRI-negative group; p < 0.00001 compared to TH group) ≤48 h after injury. cFN was no different between groups ≤48 h after injury, but was increased in the TVI group compared to the MRI-negative (p < 0.00001) and TH (p < 0.00001) groups when measured >48 h from injury. pNF-H was increased in both the TH and TVI groups compared to the MRI-negative group ≤48 h from injury. When we used the MRI grouping and molecular biomarkers in a model to predict Glasgow Outcome Scale-Extended (GOS-E) score at 30-90 days, we found that inclusion of the imaging data and biomarkers substantially improved the ability to predict a good outcome over clinical information alone. These data indicate that there is a distinct, vascular-predominant endophenotype in a subset of patients who sustain a TBI and that these injuries are characterized by a specific biomarker profile. Further work to will be needed to determine whether these biomarkers can be useful as predictive and pharmacodynamic biomarkers for vascular-directed therapies after TBI.


Effects of SQ 31,765, a new calcium channel blocker, on stress and myosin light chain phosphorylation in swine carotid media.
The vasorelaxant activity of SQ 31,765 and diltiazem was studied in intact and Triton X-100 detergent-skinned fibers of the swine carotid media. Both calcium channel blockers were used to relax or prevent contractions induced by depolarization with 110 mM KCl. The potencies of SQ 31,765 and diltiazem were similar for relaxing or preventing the tonic component of KCl-induced contractions of intact vascular smooth muscle strips. A significantly higher concentration of either compound was required to prevent the phasic component of the contraction. The possible direct effects of these calcium channel blockers on contractile function were examined in the detergent-skinned carotid medial fiber contracted with 3 microM Ca2+. Both stress and myosin light chain (MLC) phosphorylation levels were determined in detergent-skinned fibers in the presence and absence of the channel blockers. Neither compound affected stress or MLC phosphorylation in Ca2(+)-contracted detergent-skinned fibers, indicating a lack of direct effect on the contractile proteins. Thus, SQ 31,765 appears to act selectively at the level of the sarcolemma.


Serum osteoprotegerin correlates with age and bone mass in postmenopausal, but not in fertile age women.
Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) are bone turnover modulators expressed by osteoblasts. The aim of this study was to assess the relationship between the circulating OPG/RANKL system, age and bone mass, in fertile age and postmenopausal women. In this cross-sectional observational study on 48 patients (fertile age, n = 22; postmenopause, n = 26), we investigated the correlation between serum OPG and RANKL, age and bone mineral density (BMD). Serum concentrations of OPG and RANKL were determined by enzyme-linked immunosorbent assay (ELISA); estimate BMD evaluation was performed with heel quantitative ultrasonometry (QUS). Serum OPG significantly increased (p = 0.003) and serum RANKL significantly decreased (p = 0.002), in the postmenopausal group compared to fertile age women. A significant correlation of serum OPG with age (r(s) = 0.39, p = 0.047) and BMD (r(s) = 0.45, p = 0.023) in postmenopausal women, and between RANKL and BMD (r(s) = 0.48, p = 0.024) in fertile age was found. These data demonstrate in vivo that the OPG/RANKL system is significantly associated with menopausal status and could play a role in postmenopausal osteoporosis.


Sublethal effects of triclosan and triclocarban at environmental concentrations in silver catfish (Rhamdia quelen) embryos.
Although banished in some countries, triclosan (TCS) and triclocarban (TCC) have been detected in surface waters in concentrations ranging from ng L-1 to μg L-1 and have shown to affect non-target organisms posing risk to aquatic ecosystems. However, the majority of the studies consider higher levels of these chemicals and single exposure effects to investigate their potential risks, rather than using environmentally relevant concentrations and their binary mixture. In this study, the toxicity of TCS and TCC, and their binary mixture was assessed in catfish embryos (Rhamdia quelen, a south American native species) exposed to environmental concentrations during 96 h. Organisms were evaluated through the endpoints of developmental abnormalities (spine, fin, facial/cranial and thorax), biochemical biomarkers related to oxidative stress responses: catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) activities, protein carbonylation (PCO) and neurotoxicity by acetylcholinesterase activity (AChE). The data showed that TCS caused fin abnormalities, decrease of SOD activity and increase of AChE activity in the catfish embryos of 96hpf. On the other hand, TCC and the binary mixture showed a higher abnormality index for the 96hpf embryos, and an induction of CAT and GST activities for the mixture treatment. The results obtained were able to show potential, but not severe, toxicity of TCS and TCC even in low concentrations and a short period of exposure. The relevance of studies approaching real scenarios of exposure should be reinforced, considering environmental concentrations of chemicals, interactions of contaminants in complex mixtures and the use of a native species such as R. quelen exposed during initial stages of development.


Equilibrium and kinetic measurements reveal rapidly reversible binding of Ras to Raf.
Raf is a serine/threonine kinase that binds through its amino-terminal regulatory domain to the GTP form of Ras and thereby activates the mitogen-activated protein kinase pathway. In this study, we have characterized the interaction of the Ras-binding domain of Raf with Ras using equilibrium binding methods (scintillation proximity assay and fluorescence anisotropy), rather than with more widely used nonequilibrium procedures (such as enzyme-linked immunosorbent assay and affinity precipitation). Initial studies using glutathione S-transferase fusion proteins with either residues 1-257 or 1-190 of Raf showed that although it was possible to detect Ras binding using an enzyme-linked immunosorbent assay or affinity precipitation, it was substoichiometric; under equilibrium conditions with only a small excess of Raf almost no binding was detected. This difference was probably due to the presence of a high percentage of inactive Raf protein. Further studies used protein containing residues 51-131 of Raf, which expressed in Escherichia coli as a stable glutathione S-transferase fusion. With this protein, binding with Ras could readily be measured under equilibrium conditions. The catalytic domain of neurofibromin inhibited binding of Ras to Raf, and Raf inhibited the binding of Ras to neurofibromin showing that Raf and neurofibromin cannot be bound simultaneously to Ras. The affinities of interaction of neurofibromin and Raf with Harvey-RasLeu-61 were similar. The rate constant for dissociation of Raf from Ras was estimated to be >1 min-1, suggesting that Ras, Raf, and neurofibromin may be in rapid equilibrium in the cell. In contrast to previous reports, under equilibrium conditions there was no evidence for a difference in affinity between the minimal Ras binding domain of Raf (residues 51-131) and a region containing an additional 16 carboxyl-terminal amino acids, suggesting that residues 132-147 do not form a critical binding determinant.


Human testing of pesticides: ethical and scientific considerations.
I reviewed ethical and scientific aspects of 6 human pesticide-dosing studies submitted to the Environmental Protection Agency (EPA) for consideration during the pesticide reregistration process. All had serious ethical or scientific deficiencies-or both-including unacceptable informed consent procedures, unmanaged financial conflicts of interest, inadequate statistical power, inappropriate test methods and endpoints, and distorted results. Given today's knowledge of the effects of pesticides, there is no assurance that any such study can be completely free of short-term risks, long-term risks, or both. Therefore, there is no basis for allowing pesticide studies to continue or for using them during the pesticide reregistration process. An EPA committee that is free from political and financial conflicts of interest should review this practice.


Love, money, or flexibility: what motivates people to work in consumer-directed home care?
The purpose of this study was to investigate the impact of wages and benefits (relative to other jobs available to workers), controlling for personal characteristics, on the recruitment and retention of providers working in a consumer-directed home care program. I used the results of focus groups to design a survey that was administered to 2,260 workers stratified by ethnicity and working in eight California counties that represented the range of wage and benefit packages available. I used logistic regression to measure the effect of wage and benefit levels, controlling for covariates, on home care workers' stated reason for entering and remaining in the job. Two thirds of respondents reported that commitment to their consumer was the most important reason why they took the job and flexibility was the second most important reason, regardless of wages and benefits and personal characteristics. However, in the county in which very part-time workers were eligible, health insurance was the most important reason for retention. Wage levels above $9 an hour mattered somewhat, especially where the increase was recent. Family providers responded to wage and benefit incentives similarly to non-family providers. To improve recruitment and retention of consumer-directed home care workers, jobs should be flexible and provide affordable health insurance for part-time workers. The effect of wages suggests that recruitment might be improved with higher wages, but only when they reach the $9 to $10 range (in 2004 dollars). Finally, policy must recognize that family caregivers have financial needs similar to non-family caregivers.


4-Hydroxy-2-nonenal induces apoptosis by activating ERK1/2 signaling and depleting intracellular glutathione in intestinal epithelial cells.
Excessive reactive oxygen species (ROS) induces oxidative damage to cellular constituents, ultimately leading to induction of apoptotic cell death and the pathogenesis of various diseases. The molecular mechanisms for the action of ROS in intestinal diseases remain poorly defined. Here, we reported that 4-hydroxy-2-nonenal (4-HNE) treatment led to capses-3-dependent apoptosis accompanied by increased intracellular ROS level and reduced glutathione concentration in intestinal epithelial cells. These effects of 4-HNE were markedly abolished by the antioxidant L-cysteine derivative N-acetylcysteine (NAC). Further studies demonstrated that the protective effect of NAC was associated with restoration of intracellular redox state by Nrf2-related regulation of expression of genes involved in intracellular glutathione (GSH) biosynthesis and inactivation of 4-HNE-induced phosphorylation of extracellular signal-regulated protein kinases (ERK1/2). The 4-HNE-induced ERK1/2 activation was mediated by repressing mitogen-activated protein kinase phosphatase-1 (MKP-1), a negative regulator of ERK1/2, through a proteasome-dependent degradation mechanism. Importantly, either overexpression of MKP-1 or NAC treatment blocked 4-HNE-induced MKP-1 degradation, thereby protecting cell from apoptosis. These novel findings provide new insights into a functional role of MKP-1 in oxidative stress-induced cell death by regulating ERK1/2 MAP kinase in intestinal epithelial cells.


Movement of ions through fixed pores in the neural membrane.
A simple configuration is first proposed for the pores used by sodium and potassium ions in moving through the neural membrane. The voltage dependence of the ion current through a system of such pores is then derived from diffusion theory and shown not to agree well with experimental observation. Good agreement is obtained, however, when the end segments of the pores are modified to include constrictions and ion-specific trapping centers.


Effects of Cold Stimulation on Mitochondrial Activity and VEGF Expression in vitro.
We aimed to clarify the effects of cold stimulation at various temperatures on mitochondrial activity and vascular endothelial growth factor (VEGF) expression in vitro. Human fibroblast, human mesenchymal stem cell, and rat skeletal muscle myoblast cell lines were used. For each cell type, cells were divided into 4 groups and stimulated in various cold temperatures (0, 4, 17 and 25°C) 3 times for 15 min each by placement on crushed ice or floating on cold water set at each temperature. Control cells were subjected to warm water at 37°C. Factors related to mitochondrial activity, mitochondrial DNA copy numbers, and VEGF expression were analyzed 24 h after the last cold stimulation. In all cell types, significant increases of factors related to mitochondrial activity and mitochondrial DNA copy numbers were seen in the 4°C and 17°C-stimulated cells compared with control cells. In rat skeletal muscle cells stimulated at 4°C, VEGF expression significantly increased compared to the control cells. Our data suggest that cold stimulation at certain temperatures promotes mitochondrial activity, biogenesis and VEGF expression.


Do preparatory behaviours predict alcohol consumption among UK university students?
This study explored whether the frequency and habitual nature of engagement in three behaviours that may serve as preparation for alcohol consumption on a night out with friends - that is, contacting friends to arrange a night out, buying alcohol, drinking alone at home before going out - predicted consumption on such nights. Prospective correlational design. One hundred and twenty UK university students (68 female, 50 male, two non-binary, mean age = 20.78 years, SD = 1.52) completed a survey comprising intentions, habits, and frequency and habit for the three preparatory behaviours. One week later, a second survey measured the number of nights out with friends on which alcohol was drunk (i.e., drinking frequency) and the number on which four or more alcoholic drinks were consumed (i.e, excessive drinking). Regression models were run to predict drinking frequency and excessive drinking. Drinking frequency was predicted only by frequency of contacting friends (B = .28, SE = .12, p = .02), and habitually drinking alone before going out (B = .20, SE = .09, p = .03). Excessive drinking was only predicted by alcohol consumption habit (B = .67, SE = .23, p = .003). Preceding actions may influence the frequency of alcohol consumption on nights out, independently of intentions and habits relating to alcohol consumption. While interventions to reduce consumption quantity in a single session might focus on disrupting the habits that sustain drinking episodes, efforts to reduce alcohol consumption frequency on nights out might focus on disrupting behaviours that precede alcohol consumption.


Tumor suppressive maspin and epithelial homeostasis.
Maspin is a 42-kDa novel serine protease inhibitor (serpin) with multifaceted tumor suppressive activities. To date, the consensus that maspin expression predicts a better prognosis still largely holds for breast, prostate, colon, and oral squamous cancers. Interestingly, however, more detailed analyses revealed a biphasic expression pattern of maspin in early steps of tumorigenicity and re-expression of maspin in dormant cancer metastatic revertants. These data suggest a sensitivity of maspin expression to changes of epithelial microenvironments, and a role of maspin in epithelial homeostasis. Experimental evidence consistently showed that maspin suppresses tumor growth, invasion and metastasis, induces tumor redifferentiation, and enhances tumor cell sensitivity to apoptosis. Maspin protein isolated from biological sources is a monomer, which is present as a secreted, a cytoplasmic, a nuclear, as well as a cell surface-associated protein. Nuclear maspin is associated with better prognoses of cancer. It is further noted that extracellular maspin is sufficient to block tumor induced extracellular matrix degradation, tumor cell motility and invasion, whereas intracellular maspin is responsible for the increased cellular sensitivity to apoptosis. Despite these exciting developments, the mechanistic studies of maspin have proven challenging primarily due to the lack of a prototype molecular model. Although the maspin sequence has overall homologies with other members in the serpin superfamily, it does not behave like a typical serpin, that is, non-inhibitory toward active serine proteases in solution. This novel feature is in line with the X-ray crystallographic evidence. Several recent studies dedicated to finding the maspin partners support a paradigm shift. The current review is intended to summarize these recent findings and discuss a new perspective of maspin in epithelial homeostasis.


Comparison of the Effectiveness of Nonablative Fractional Laser versus Pulsed-Dye Laser in Thyroidectomy Scar Prevention.
The anterior neck is the site of open thyroidectomy and where postoperative scarring can cause distress to patients. Both fractional and pulsed-dye lasers are effective and safe methods for preventing and improving surgical scars. This study evaluated the improvement in scar appearance with laser intervention during the wound healing process. We evaluated the effect of nonablative fractional and pulsed-dye lasers on fresh thyroidectomy scars. Patients were treated 3 times at 4-week interval with a follow-up visit at the 6(th) month. Scars were divided into 2 halves for each optional treatment. At every visit, a questionnaire evaluating the scar and patient satisfaction was completed. Thirty patients completed the 6-month process. The mean Vancouver Scar Scale scores improved significantly from 8.0 to 4.6 and 8.2 to 4.7 with nonablative fractional and pulsed-dye lasers, respectively (p<0.001). However, there was no significant difference between the 2 methods (p=0.840). There remains no consensus on the optimal treatment of scars. The present study indicates nonablative fractional and pulsed-dye lasers significantly improve scars. Nonablative fractional lasers are non-inferior to pulsed-dye lasers. Further studies are required to corroborate this finding.


Yam storage protein dioscorins from Dioscorea alata and Dioscorea japonica exhibit distinct immunomodulatory activities in mice.
The aim of this study was to elucidate the effect of the major storage protein dioscorin isolated from two different yam species, Tainong No. 1 (TN1-dioscorins) and Japanese yam (Dj-dioscorins), on the immune activities of mice. Dj-dioscorins, like TN1-dioscorins, could induce expression of the pro-inflammatory cytokines and stimulate phagocytosis of RAW 264.7. Intraperitoneal injection of the TN1-dioscorins into mice stimulated phagocytosis of bone marrow, spleen, and thymic cells. In contrast, the T and B cells in bone marrow, spleen, and thymus isolated from mice injected with Dj-dioscorins had higher proliferative responses to mitogens. Furthermore, Dj-dioscorins enhanced proliferation of CD4(+), CD8(+), and Tim3(+) (Th1) cells in spleen and CD19(+) cells in both spleen and thymus. Supplement of Dj-dioscorins in the lymphoid cells isolated from Dj-dioscorins primed mice induced cell proliferation of both spleen and thymic cells. These findings indicated that TN1-dioscorins have a higher ability to stimulate the phagocytic activity of the lymphoid cells than Dj-dioscorins, whereas Dj-dioscorins possess more abilities than TN1-dioscorins to enhance the proliferation of the lymphoid cells.


Universal Triboelectric Nanogenerator Simulation Based on Dynamic Finite Element Method Model.
The lack of a universal simulation method for triboelectric nanogenerator (TENG) makes the device design and optimization difficult before experiment, which protracts the research and development process and hinders the landing of practical TENG applications. The existing electrostatic induction models for TENGs have limitations in simulating TENGs with complex geometries and their dynamic behaviors under practical movements due to the topology change issues. Here, a dynamic finite element method (FEM) model is proposed. The introduction of air buffer layers and the moving mesh method eliminates the topology change issues during practical movement and allows simulation of dynamic and time-varying behaviors of TENGs with complex 2D/3D geometries. Systematic investigations are carried out to optimize the air buffer thickness and mesh densities, and the optimized results show excellent consistency with the experimental data and results based on other existing methods. It also shows that a 3D disk-type rotating TENG can be simulated using the model, clearly demonstrating the capability and superiority of the dynamic FEM model. Moreover, the dynamic FEM model is used to optimize the shape of the tribo-material, which is used as a preliminary example to demonstrate the possibility of designing a TENG-based sensor.


Discrimination and its relation to psychosocial well-being among diverse youth in Sweden.
Experiences of discrimination and links to well-being have been examined extensively, but several gaps remain. The current study addresses four of those gaps by (1) examining both aggregated and source-specific forms of discrimination, (2) comparing the experiences of minority and majority group members, (3) expanding the range of outcomes to include socially and developmentally appropriate measures, and (4) conducting the study in Sweden, a context in which discrimination and well-being are not well understood. The sample consisted of 573 adolescents and emerging adults (71% women, Mage = 19.21 years) who completed survey measures of discrimination and psychosocial well-being (self-esteem, life satisfaction, school adjustment, and identity distress). Findings indicated that minority groups reported more frequent discrimination, and more often cited ethnicity as the source of discrimination, whereas majority groups most often cited gender. Experiencing discrimination was related to poorer psychosocial well-being similarly for all groups. Youth experiencing ethnic discrimination were more often subjected to multiple forms of discrimination compared with those subjected to other forms of discrimination. Taken together, this study brings important information on the complexity of discrimination among youth in the multicultural context of migration in Sweden.


Photosystem Stoichiometry and Excitation Distribution in Chloroplasts from Surface and Minus 20 Meter Blades of Macrocystis pyrifera, the Giant Kelp.
The photochemical apparatus organization in the thylakoid membrane of Macrocystis pyrifera, the giant kelp, was investigated. Chloroplasts were isolated from surface and minus 20 meter blades. Photosynthetic electron-transport complex quantitation revealed ratios of photosystem (PS) II/cytochrome b(6)-f/PSI = 1.8:3.3:1.0 in surface and 2.2:2.3:1.0 in minus 20 meter blades. The apparent photosynthetic unit size of chloroplasts from minus 20 meter blades (chlorophyll/P700 = 1485:1) was about 45% larger than that of surface blades (chlorophyll/P700 = 1025:1). The larger photosynthetic unit size of minus 20 meter blades is attributed to the substantially lower intensity of sunlight reaching the minus 20 meter habitat. In different chloroplast preparations, the effective absorption cross section of PSI and PSII to 670 nanometer light (chlorophyll a) and 481 nanometer light (chlorophyll c and fucoxanthin) was investigated. The results showed larger functional antenna size for PSII (about 90%) and for PSI (about 50%) in minus 20 meter than in surface blades. Moreover, the efficiency of utilization of 481 nanometer light by Macrocystis chloroplasts was equal to that of 670 nanometer light. It is concluded that the chlorophyll c-fucoxanthin complex in brown algae enables the highly efficient utilization of blue-green wavelengths of the nearshore marine environment and contributes to the dominance of M. pyrifera in this habitat.


E pluribus unum: A phylogenetic and phylogeographic reassessment of Laevapex (Pulmonata: Ancylidae), a North American genus of freshwater limpets.
The North American freshwater limpet genus Laevapex (Walker, 1903) is a ubiquitous inhabitant of lentic and slow-moving lotic habitats east of the Rocky Mountains, but uncertainty clouds its systematic affinities, the phylogenetic validity of its constituent nominal species, and its degree of genetic connectivity among drainages. We addressed these issues by sampling the genus throughout much of its collective range and constructing representative nuclear and mitochondrial (mt) gene trees, in addition to performing morphometric analyses of shell shape variation. Our results identify neotropical Gundlachia and South American Uncancylus as sister lineages for Laevapex and reveal a pronounced sub-familial dichotomy within the Ancylidae, separating these three New World genera from a Holarctic (Ferrissia (Ancylus, Rhodacmea)) sister clade. Five nominal taxa (L. fuscus, L. diaphanus, L. peninsulae, L. sp., and "F."arkansasensis), indistinguishable in our morphometric analyses, were polyphyletic in the mt gene trees, exhibited modest levels (< 3.9%) of genetic divergence in the primary (103 of 109 individuals) mt clade and, with one minor exception, they appeared fixed for a single nuclear ITS-2 genotype. Although complicated by the presence of rare, highly divergent mt lineages (of either introgressive or persistent ancestral polymorphic origin) in some populations, the molecular data were consistent with a taxonomic conclusion that these five nominal taxa represent a single polymorphic lineage of the type species L. fuscus. AMOVA analyses indicated that 56% of the observed mt variation could be attributed to among population differences, only two of 36 haplotypes were detected in more than one sampling location, and estimates of among-population mt gene flow were generally low at both regional and continental scales. Unrooted network analyses revealed a number of mt tip clades, one restricted to the southwestern part of the range, the remainder having overlapping distributions in eastern North America. All of the eastern tip clades occurred in the Mid-Atlantic region, and these samples displayed by far the highest levels of collective mt diversity. However, directional gene flow estimates indicated that this region has been a recipient (especially from Alabama populations), rather than a source of haplotypic diversity, implying that it likely represents a center of overlap, not a primary ice age refugium, for this limpet species.


Immunoregulatory role of nitric oxide in Legionella pneumophila-infected macrophages.
Nitric oxide (NO) is an intercellular messenger molecule produced by a variety of cells, including macrophages. However, the role of NO in infection, especially its immunological role, is poorly understood. In the present study, the role of NO in Legionella pneumophila-infected macrophages was examined. Whereas infection of mouse macrophages in vitro with L. pneumophila did not induce detectable NO, when the macrophages were primed with interferon-gamma (IFN-gamma), the treated macrophages markedly inhibited bacterial replication and produced a large amount of NO. Treatment with NO inhibitors, such as NG-monomethyl-L-arginine (L-MMA) or aminoguanidine, as well as culture in arginine-free medium, significantly inhibited NO production; however, the anti-L. pneumophila activity induced by IFN-gamma was not diminished. Examination of cytokine levels in L. pneumophila-infected macrophages primed with IFN-gamma revealed a moderate increase of interleukin-6 (IL-6) production; however, inhibition of NO by L-MMA markedly increased IL-6 production. Reconstitution of NO in the L. pneumophila-infected macrophages primed with IFN-gamma and treated with L-MMA to inhibit endogenous NO production following addition of sodium nitroprusside reduced IL-6 production to normal levels. The levels of IL-6 mRNA in L-MMA-treated macrophages were the same as in nontreated macrophages, as demonstrated by quantitative RT-PCR. Thus, these results indicate that NO may regulate IL-6 production independently of its role in antimicrobial function in L. pneumophila-infected macrophages and their immunoregulation on IL-6 production may be due to a post-transcriptional mechanism.


[Assessment of conformation changes of immunoglobulin G molecules using a fluorescent probe].
A proximate method for conformational changes detection in immunoglobulin G preparations used in research and medical practice is introduced. This method is based on the measurement of IgG-connected 1,8-anilinenaphtalenesulphonate fluorescent probe (ANS) time of damping. When the protein structure is broken fluorescence damping time of IgG-connected ANS rises up.


Mucinous cystic neoplasm of the liver: A case report.
Mucinous cystic neoplasm of the liver (MCN-L) is a cyst-forming epithelial neoplasm. The most distinguishing feature is the ovarian-type subepithelial stroma on pathological examination. An abdominal ultrasound incidentally revealed a liver tumor in a 32-year-old woman. Physical and laboratory examination results did not reveal any abnormalities. Enhanced abdominal computed tomography (CT) revealed a cystic space measuring 7.2 cm × 5.4 cm in the liver. Subsequent CT showed an increase in tumor size. Thus, we performed surgical resection of the tumor and gallbladder. Postoperative histopathological examination confirmed the diagnosis of MCN-L. At the 6-mo of follow-up, no recurrence was observed on ultrasound or CT. Since preoperative diagnosis of MCN-L is difficult, active surgery is recommended and helpful for the diagnosis and treatment of MCN-L.


The effects of uncontrollable, unpredictable aversive and appetitive events: similar effects warrant similar, but not identical, explanations?
Exposure to uncontrollable, unpredictable appetitive events produces a variety of cognitive debilitations and vegetative changes, as does exposure to uncontrollable, unpredictable aversive events. Similarities include impaired escape from aversive events, impaired discrimination, finicky consumption, analgesia, and body weight loss. However, in stark contrast, uncontrollable aversive stress causes reduced motor activity where as similar appetitive treatment does not; aversively induced debilitation is causally related to energy regulation, whereas the appetitively induced effects are not. Parallel mechanisms are suggested to explain these effects in terms of a revised anxiety account of the aversive effects, and a frustration account of the appetitive effects. Finally, factors likely to limit important research to resolve the many remaining issues are identified: negative presentation of animal research, political decision making, and ignorance and fear in committees which review the ethics of research.


Infection-related hospitalization following ureteroscopic stone treatment: results from a surgical collaborative.
Unplanned hospitalization following ureteroscopy (URS) for urinary stone disease is associated with patient morbidity and increased healthcare costs. To this effect, AUA guidelines recommend at least a urinalysis in patients prior to URS. We examined risk factors for infection-related hospitalization following URS for urinary stones in a surgical collaborative. Reducing Operative Complications from Kidney Stones (ROCKS) is a quality improvement (QI) initiative from the Michigan Urological Surgery Improvement Collaborative (MUSIC) consisting of academic and community practices in the State of Michigan. Trained abstractors prospectively record standardized data elements from the health record in a web-based registry including patient characteristics, surgical details and complications. Using the ROCKS registry, we identified all patients undergoing primary URS for urinary stones between June 2016 and October 2017, and determined the proportion hospitalized within 30 days with an infection-related complication. These patients underwent chart review to obtain clinical data related to the hospitalization. Multivariable logistic regression analysis was performed to determine risk factors for hospitalization. 1817 URS procedures from 11 practices were analyzed. 43 (2.4%) patients were hospitalized with an infection-related complication, and the mortality rate was 0.2%. Median time to admission and length of stay was 4 and 3 days, respectively. Nine (20.9%) patients did not have a pre-procedure urinalysis or urine culture, which was not different in the non-hospitalized cohort (20.5%). In hospitalized patients, pathogens included gram-negative (61.5%), gram-positive (19.2%), yeast (15.4%), and mixed (3.8%) organisms. Significant factors associated with infection-related hospitalization included higher Charlson comorbidity index, history of recurrent UTI, stone size, intra-operative complication, and procedures where fragments were left in-situ. One in 40 patients are hospitalized with an infection-related complication following URS. Awareness of risk factors may allow for individualized counselling and management to reduce these events. Approximately 20% of patients did not have a pre-operative urine analysis or culture, and these findings demonstrate the need for further study to improve urine testing and compliance.


On the electronic character of localized singlet 2,2-dimethoxycyclopentane-1,3-diyl diradicals: substituent effects on the lifetime.
Photodenitrogenation of the diazenes 4 affords exclusively the housanes 5 through intramolecular cyclization of the spectrally detected and characterized singlet diradicals 3. The lifetime of singlet diradical 3, determined by transient absorption measurements, depends on the Y and Z substituents at the para position of the phenyl ring and has the following order: Y, Z = OMe, OMe > OMe, CN > CN, CN > OMe, H > Cl, Cl approximately CN, H approximately Me, Me > H, H. This unprecedented substituent effect reveals stabilization of the singlet 2,2-dimethoxycyclopentane-1,3-diyl diradicals 3 through radical, zwitterionic, pi-bonding, and hyperconjugative structures.


Tailoring Spin Textures in Complex Oxide Micromagnets.
Engineered topological spin textures with submicron dimensions in magnetic materials have emerged in recent years as the building blocks for various spin-based memory devices. Examples of these magnetic configurations include magnetic skyrmions, vortices, and domain walls. Here, we show the ability to control and characterize the evolution of spin textures in complex oxide micromagnets as a function of temperature through the delicate balance of fundamental materials parameters, micromagnet geometries, and epitaxial strain. These results demonstrate that in order to fully describe the observed spin textures, it is necessary to account for the spatial variation of the magnetic parameters within the micromagnet. This study provides the framework to accurately characterize such structures, leading to efficient design of spin-based memory devices based on complex oxide thin films.


Iridium-Catalyzed Regioselective B(4)-Alkenylation and B(3,5)-Dialkenylation of o-Carboranes.
Iridium(I)-catalyzed regioselective B(4)-alkenylation has been developed from o-carboranyl sulfoxonium ylides and alkynes through B(4)-H activation. The sequential B(4)- and B(6)-alkenylation afforded B(3,5)-dialkenylated o-carboranyl sulfoxonium ylides in one pot. Eventually, two alkenyl groups, the same or different, were introduced at positions 3 and 5 of the carborane. Sulfoxonium ylide used as a directing group remains available for further functionalization and is converted to B-alkenylated o-carboranyl trichloromethyl ketones.


Study of human adult parotid duct in the area of penetration through buccinator muscle and their functional relationship as a sphincter.
The adult human parotid duct is roughly 6-8 cm long. From the parotid gland, parotid duct traverses through masseter muscle, penetrates through buccinator muscle, and opens into the oral cavity. This unique form of the parotid duct is likely correlated with the function of the duct, directly affected by the movement of the buccinator muscle during mastication and swallowing. Histological structure of the duct is known to be different in each region, and details of smooth muscle present in the parotid duct are mostly unclear. In this study, we conducted SEM and histological observations of the area where the parotid duct penetrates the buccinator muscle, and an observation of smooth muscle to investigate its existence using alpha-smooth muscle antibody. We confirmed the presence of an abundance of skeletal muscle bundles likely originating from the buccinator muscle under the epithelium of the parotid duct wall in the region where it penetrates the buccinator muscle. We also observed that some of the muscle fibers were completely attached to the epithelium. We observed a lack of smooth muscle in this region of the duct wall. From these results, we suggest that the area of the duct penetrating buccinator muscle plays a role in regulating the salivary passage through the contraction of the surrounding buccinator muscle fibers.


Morphology-Based Deep Learning Approach for Predicting Osteogenic Differentiation.
Early, high-throughput, and accurate recognition of osteogenic differentiation of stem cells is urgently required in stem cell therapy, tissue engineering, and regenerative medicine. In this study, we established an automatic deep learning algorithm, i.e., osteogenic convolutional neural network (OCNN), to quantitatively measure the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs). rBMSCs stained with F-actin and DAPI during early differentiation (day 0, 1, 4, and 7) were captured using laser confocal scanning microscopy to train OCNN. As a result, OCNN successfully distinguished differentiated cells at a very early stage (24 h) with a high area under the curve (AUC) (0.94 ± 0.04) and correlated with conventional biochemical markers. Meanwhile, OCNN exhibited better prediction performance compared with the single morphological parameters and support vector machine. Furthermore, OCNN successfully predicted the dose-dependent effects of small-molecule osteogenic drugs and a cytokine. OCNN-based online learning models can further recognize the osteogenic differentiation of rBMSCs cultured on several material surfaces. Hence, this study initially demonstrated the foreground of OCNN in osteogenic drug and biomaterial screening for next-generation tissue engineering and stem cell research.


Comparison of 20 nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages.
Widespread use of silver nanoparticles raises questions of environmental and biological impact. Many synthesis approaches are used to produce pure silver and silver-shell gold-core particles optimized for specific applications. Since both nanoparticles and silver dissolved from the particles may impact the biological response, it is important to understand the physicochemical characteristics along with the biological impact of nanoparticles produced by different processes. The authors have examined the structure, dissolution, and impact of particle exposure to macrophage cells of two 20 nm silver particles synthesized in different ways, which have different internal structures. The structures were examined by electron microscopy and dissolution measured in Rosewell Park Memorial Institute media with 10% fetal bovine serum. Cytotoxicity and oxidative stress were used to measure biological impact on RAW 264.7 macrophage cells. The particles were polycrystalline, but 20 nm particles grown on gold seed particles had smaller crystallite size with many high-energy grain boundaries and defects, and an apparent higher solubility than 20 nm pure silver particles. Greater oxidative stress and cytotoxicity were observed for 20 nm particles containing the Au core than for 20 nm pure silver particles. A simple dissolution model described the time variation of particle size and dissolved silver for particle loadings larger than 9 μg/ml for the 24-h period characteristic of many in-vitro studies.


RNA transcription and translation in the hearts of normal and cardiomyopathic Syrian hamsters.
The cardiomyopathic Syrian hamster has an autosomal recessive defect that results in the development of an early onset cardiac myopathy leading to cardiac dysfunction and, eventually, complete heart failure. To assess the regulatory mechanisms modulating gene expression in the normal and myopathic myocardium, we investigated both RNA transcription and translation. Our results indicated that the incorporation of [3H]UMP into myocardial cell nuclear RNA decreased 10-fold from 7 to 210 days of age in the normal Syrian hamster. The incorporation of [3H]UMP was approximately 50% lower in the cardiomyopathic as compared with the normal Syrian hamster. RNA translation, as assessed by rabbit reticulocyte lysate in vitro translation, indicated that a coordinated 50% decrease in RNA translation occurred in normal Syrian hamster from 7 to 210 days of age. A further reduction of 20% in translation was found in cardiomyopathic Syrian hamster ventricular RNA translation as compared with matched random bred control groups. Two-dimensional polyacrylamide gel analysis of cell-free translated protein products demonstrated two myocardial peptides that were found to be consistently altered when the normal and cardiomyopathic Syrian hamsters were compared. These results indicate that transcription and translation decrease with age and that these processes are further downregulated, in an additive manner, with the genesis of the disease process.


Age, gender and reactivity to allergens independently influence skin reactivity to histamine.
The ability to mount an IgE response to allergens is a prerequisite for the development of positive allergen skin tests. Histamine is commonly used as a positive control in skin prick testing and provides a measure of nonspecific skin reactivity, similar to bronchial hyper-responsiveness. To determine whether allergen responsiveness, age, gender and season of the year contribute to histamine sensitivity, 620 subjects (502 of them with at least one known sensitizing allergen and the remaining 118 non-allergic controls) were prick-tested with a panel of allergens common in the Northern Italy semi-rural area where the patients lived, and with 10 mg/ml histamine dihydrochloride. We found higher histamine reactivity in allergic versus control individuals (median value 23.7 versus 19.8 mm2; p=0.0497). Likewise, we found in allergic subjects a correlation between allergen responsiveness in terms of number of positive allergens at skin prick test and sensitivity to histamine (mono- sensitized versus poly-sensitized subjects: p=0.0015). Moreover older age and male sex were associated with a higher response to histamine, also when separately considering allergic subjects (p<0.0001 in both cases: correlation coefficient for age versus histamine reactivity: r=0.3408). The correlation between allergen responsiveness and sensitivity to histamine was maintained also when statistically balanced for age and sex. Allergen responsiveness, gender and age allow more accurate prediction of histamine sensitivity than either parameter alone.


Sucrose uptake and compartmentation in sugar beet taproot tissue.
Active sucrose uptake by discs of mature sugar beet (Beta vulgaris L. cv GW-D2 and USH-20) root tissue shows a biphasic dependence on external sucrose. At concentrations up to 20 millimolar sucrose, the active uptake mechanism appears to approach saturation, with an apparent K(m) of 3.6 millimolar. At higher external sucrose concentrations, a linear dependence becomes obvious indicating the probable presence of a nonsaturable, metabolically dependent uptake component. Active transport was not observed at external sucrose concentrations that caused tissue plasmolysis. Passive sucrose uptake in unplasmolyzed tissue showed a linear dependence on external sucrose concentration. The mitochondrial and/or suspected vacuolar ATPase inhibitors oligomycin, diethylstilbestrol, and N,N-dicyclohexylcarbodiimide strongly inhibited active sucrose uptake, whereas the putative plasmalemma-specific ATPase inhibitor orthovanadate was without effect.Sucrose efflux patterns from root discs indicated three distinct sucrose compartments having efflux kinetics consistent with those for cell wall, cytoplasm, and vacuole with the vacuole being the slowest releasing compartment. The sucrose contents and volumes of the compartments indicated that sucrose uptake into the vacuole was against a concentration gradient. Combined sucrose uptake/efflux analyses indicated that sucrose uptake into the vacuole is primarily an active transport process while transport into the cytoplasm is apparently passive, at least at external sucrose concentrations above 20 millimolar. We discuss the possibility that active sucrose uptake into the vacuoles of sugar beet storage cells is rate limited by passive sucrose transport to the active uptake site.


Fine-needle biopsy: should this be the first choice in endoscopic ultrasound-guided tissue acquisition?
Endoscopic ultrasound (EUS)-guided tissue acquisition is an indispensable technique for the diagnosis of many diseases of the gastrointestinal tract and adjacent structures. EUS-guided fine-needle aspiration (EUS-FNA) is known for its high accuracy and low complication rate. However, the outcome of EUS-FNA highly depends on several factors such as the location and characteristics of the lesion, endosonographer's experience, technique of sampling and sample preparation, type and size of the needle used, and presence of a cytopathologist for rapid on-site examination. EUS-guided fine-needle biopsy is useful to obtain core tissue samples with relatively fewer passes. Aspiration of core tissue with preserved architecture is beneficial for the diagnosis of certain diseases and the performance of ancillary testing such as tumor molecular profiling. Issues related to needle size, type, and their acquired samples for cytologic and histologic evaluation are discussed here.


[Acute adrenocortical insufficiency].
Severe acute adrenocortical insufficiency or adrenal crisis are often elusive diagnoses that may result in severe morbidity and mortality when undiagnosed or ineffectively treated. Although more than 50 steroids are produced within the adrenal cortex, cortisol and aldosterone are far the most abundant and physiologically active. In primary adrenocortical insufficiency, glucocorticoid and mineral-corticoid properties are lost; however, in secondary adrenocortical insufficiency (i.e., secondary to disease or suppression of the hypothalamic-pituitary axis), mineralocorticoid function is preserved. Every emergency physician should be familiar with adrenocortical insufficiency--a potentially life-threatening entity. The initial diagnosis and decision to treat are presumptive and are based on history, physical examination, and, occasionally, laboratory findings. Delay in treatment while attempting to confirm this diagnosis can result in poor patient outcomes. This article review data about physiology, pathophysiology of the adrenal cortex, physiologic effects of glucocorticoids, aldosterone, causes of primary and secondary adrenal insufficiency, frequency, clinical picture, laboratory and imaging studies of adrenal crisis, laboratory evaluation of adrenal function and emergency therapy, replacement therapy, mortality/morbidity of this pathology.


The Genotoxicity of Priority Polycyclic Aromatic Hydrocarbons (PAHs) Containing Sludge Samples.
ABSTRACT In this research work we developed in vitro tests utilizing mammalian cell cultures, which can rapidly assess effect of exposure of oily sludge-derived chemicals on human and ecological health. Many of these are hazardous to health and environment due to their toxicity and/or accumulation potential in sediments as well as in organisms. Petroleum refinery and petrochemical industry-derived oily sludges contain toxic polycyclic aromatic hydrocarbons (PAHs), some of which are lipophilic in nature. Risk assessment of environmental samples suffers from inadequate availability of toxicity data, lack of knowledge about behavior of genotoxic substances in complex matrices, paucity of information on synergistic and antagonistic interactions of mixture of components, etc.; the literature describing the behavior of genotoxic substances in complex mixtures is sparse and sometimes contradictory. The present study aims at assessing the genotoxic potential of oily sludges collected from an integrated petroleum refinery and petrochemical industry located in the southwestern part of India and a petrochemical industry located in the western part of India using a battery of genotoxicity assays such as DNA damage/strand break, chromosomal aberration, p(53) protein induction, and apoptosis in CHO-K1 cell culture system. Exposure with different dose levels of sludge extracts (25, 50, 100 muL) in CHO-K1 cells could cause statistically significant level of (P < 0.001) DNA damage, chromosomal aberration, p(53) protein induction, and apoptosis in comparison to negative control treatment groups, and the genotoxicity was attributed to PAHs present in the sludge as identified by GC-MS. This implies that the sludges are genotoxic in nature in mammalian cells tested, and the exposure to these may pose a potential genotoxic risk to human beings.


Ear canal and middle-ear tumors: a single-institution series of 87 patients.
Ear canal and middle ear tumors are rare and exhibit variability in histology and clinical manifestation. Surgical resection remains the treatment of choice, but individualized approach is needed to preserve function when possible. To review the management and outcome of ear canal and middle ear tumors at an academic referral center. Helsinki University Hospital (HUS) patient files were searched for clinically and histologically confirmed ear canal and middle ear tumors over a 14-year period. The minimum follow-up time was 2 years. Eighty-seven patients with 88 tumors were identified. There were 20 (23%) benign external auditory canal (EAC), 36 (41%) benign middle ear space (MES), 29 (33%) malignant EAC, and 3 (3%) malignant MES tumors. Most (92%) tumors were managed with primary resection. Thirty-five percent of the operatively managed patients had a residual or a recurrent tumor. EAC and MES tumors show great diagnostic and histologic heterogeneity with need for individualized investigative and treatment approaches. In benign tumors, we advocate aggressive local surgical control without sacrificing vital structures. In malignant tumors, we recommend local surgical control with or without adjunct RT.


Demographic profile of blood donors at three major Brazilian blood centers: results from the International REDS-II study, 2007 to 2008.
The profile of blood donors changed dramatically in Brazil over the past 20 years, from remunerated to nonremunerated and then from replacement to community donors. Donor demographic data from three major blood centers establish current donation profiles in Brazil, serving as baseline for future analyses and tracking longitudinal changes in donor characteristics. Data were extracted from the blood center, compiled in a data warehouse, and analyzed. Population data were obtained from the Brazilian census. During 2007 to 2008, there were 615,379 blood donations from 410,423 donors. A total of 426,142 (69.2%) were from repeat (Rpt) donors and 189,237 (30.8%) were from first-time (FT) donors. Twenty percent of FT donors returned to donate in the period. FT donors were more likely to be younger, and Rpt donors were more likely to be community donors. All were predominantly male. Replacement donors still represent 50% of FT and 30% of Rpt donors. The mean percentage of the potentially general population who were donors was approximately 1.2% for the three centers (0.7, 1.5, and 3.1%). Adjusting for the catchment's area, the first two were 2.1 and 1.6%. Donors in the three Brazilian centers tended to be younger with a higher proportion of males than in the general population. Donation rates were lower than desirable. There were substantial differences in sex, age, and community/replacement status by center. Studies on the safety, donation frequencies, and motivations of donors are in progress to orient efforts to enhance the availability of blood.


Why are rhizobial symbiosis genes mobile?
Rhizobia are one of the most important and best studied groups of bacterial symbionts. They are defined by their ability to establish nitrogen-fixing intracellular infections within plant hosts. One surprising feature of this symbiosis is that the bacterial genes required for this complex trait are not fixed within the chromosome, but are encoded on mobile genetic elements (MGEs), namely plasmids or integrative and conjugative elements. Evidence suggests that many of these elements are actively mobilizing within rhizobial populations, suggesting that regular symbiosis gene transfer is part of the ecology of rhizobial symbionts. At first glance, this is counterintuitive. The symbiosis trait is highly complex, multipartite and tightly coevolved with the legume hosts, while transfer of genes can be costly and disrupt coadaptation between the chromosome and the symbiosis genes. However, horizontal gene transfer is a process driven not only by the interests of the host bacterium, but also, and perhaps predominantly, by the interests of the MGEs that facilitate it. Thus understanding the role of horizontal gene transfer in the rhizobium-legume symbiosis requires a 'mobile genetic element's-eye view' on the ecology and evolution of this important symbiosis. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.


Characterization of Leishmania infection in rodents from endemic areas of the Islamic Republic of Iran.
Between 1991-2000, Leishmania species were isolated and characterized by isoenzyme and molecular analysis from rodents caught in various parts of the Islamic Republic of Iran. In areas endemic for cutaneous leishmaniasis, parasites were observed by direct microscopy in smears from 18.6% of 566 specimens. L. major was isolated from 4 species: Rhombomys opimus, Meriones libycus, Tatera indica and Mer. hurrianae. L. turanica was isolated from R. opimus for the first time in this country. In endemic areas of visceral leishmaniasis, parasites were observed in liver and spleen from 13.7% of 504 rodents. Two species were positive on culture; promastigotes isolated from Mer. persicus were characterized as L. donovani zymodeme LON50 and from Mesocricetus auratus as L. infantum LON49.


Why do they engage in such hard programs? The search for excellence in youth basketball.
Excellent performance in sport has a strong positive relationship with the accumulated hours of practice. The specialization years are seen as a decisive moment to lift the skill level, athletic readiness and commitment but the selection and orientation of talent has been strongly dependent of biological and motor variables. The purpose of this study is to describe the achievement and motivation variables that can explain the belonging to an elite competitive level of young basketball players. Eighty-two basketball players under 16 years fulfilled the WOFO Questionnaire (Spence and Helmreich, 1983), and an adapted version of the DPMQ (De Bruin, Rikers and Schmidt, 2007). Forty players (mean age 15. 8 ± 0.96) were engaged in high performance centres and forty-two (mean age 15.6 ± 1.01) played in national level clubs. A decision tree and a random forest analysis between elite and national level players were performed. The most discriminant variable was Will to Excel, with 85,2% true positives in elite or national level. Mastery and competitiveness did not enter the final model. The will to reach excellence in performance can be considered as a condition to engage in more specialized and demanding practice. The assessment of the path to expertise only through motor variables or through the accumulated hours of deliberate practice is limited and can lead to mistaken identification or orientation of young sport talents. The use of a more comprehensive model is needed. Key pointsExcellent performance in sport has a strong positive relationship with the accumulated hours of practice.It seems reasonable that if the young athletes are better selected, have better training conditions and practice and compete more time with better teammates and opponents, the chance of becoming competent adult athletes is greater.A self orientation to excellence may play a crucial role in persistence in practice, in order to achieve higher standards in competition.The specific motivation that underpins participation at different levels and help the coaches to be sensitive to non-biological or non-functional variables, leading to a better knowledge and caring of the adolescents they teach.The assessment of the path to expertise only through motor variables or through the accumulated hours of deliberate practice is limited and can lead to mistaken identification or orientation of young sport talents.


Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation.
Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing.