Deviant lysosomal Ca2+ signalling in neurodegeneration. An introduction.
Lysosomes are key acidic Ca2+ stores. The principle Ca2+-permeable channels of the lysosome are TRP mucolipins (TRPMLs) and NAADP-regulated two-pore channels (TPCs). Recent studies, reviewed in this collection, have linked numerous neurodegenerative diseases to both gain and loss of function of TRPMLs/TPCs, as well as to defects in acidic Ca2+ store content. These diseases span rare lysosomal storage disorders such as Mucolipidosis Type IV and Niemann-Pick disease, type C, through to more common ones such as Alzheimer and Parkinson disease. Cellular phenotypes, underpinned by endo-lysosomal trafficking defects, are reversed by chemical or molecular targeting of TRPMLs and TPCs. Lysosomal Ca2+ channels therefore emerge as potential druggable targets in combatting neurodegeneration.


Protective effects of kojic acid on the periphery blood and survival of beagle dogs after exposure to a lethal dose of gamma radiation.
In previous studies, it has been shown that pretreatment with kojic acid (KA) not only increased the 30 day survival rate of mice after exposed to a lethal dose of gamma radiation but also had significant radioprotective effects on the hematopoietic system, the immune system and DNA of mice exposed to a 4 Gy sublethal dose of radiation. Furthermore, pretreatment with KA has also been shown to protect Chinese hamster ovary (CHO) cells against ionizing radiation-induced damage. In this investigation, beagle dogs were used to evaluate whether KA could also be radioprotective in a large animal model. Dogs in the group pretreated with kojic acid after whole-body exposure to a lethal dose of 3 Gy gamma radiation had a 51 day survival rate of 66.7% versus the dogs in the 3 Gy irradiation only group, which all died within 16 days of postirradiation. General vital signs (body weight or temperature) of animals in the kojic acid pretreated group reduced and increased maximally at day 14 postirradiation and then reverted to normal levels gradually. The hematopoiesis studies indicated that the white blood cells/red blood cells, hemoglobin content and hematocrit of dogs pretreated with kojic acid decreased sharply at day 23/day 21 postirradiation, and then gradually elevated. In addition, the DNA content of dogs pretreated with KA were significantly increased compared with that of dogs in the irradiation group at day 4 postirradiation and the number of micronuclei in the group pretreated with kojic acid declined sharply compared with that of the irradiation only group. KA appears to possess marked protective effects from radiation-induced damage and therefore, may be a promising novel radioprotective agent.


Immune landscape and biomarkers for immuno-oncology in colorectal cancers.
Recent advances in immuno-oncology have increased understanding of the tumor immune microenvironment (TIME), and clinical trials for immune checkpoint inhibitor treatment have shown remission and/or durable response in certain proportions of patients stratified by predictive biomarkers. The TIME in colorectal cancer (CRC) was initially evaluated several decades ago. The prognostic value of the immune response to tumors, including tumor-infiltrating lymphocytes, peritumoral lymphoid reaction, and Crohn's-like lymphoid reaction, has been well demonstrated. In this review, we describe the chronology of TIME research and review the up-to-date high-dimensional TIME landscape of CRC. We also summarize the clinical relevance of several biomarkers associated with immunotherapy in CRC, such as microsatellite instability, tumor mutational burden, POLE/POLD mutation, consensus molecular subtype, and programmed death-ligand 1 expression.


Mathematical modeling of surface roughness in magnetic abrasive finishing of BK7 optical glass.
Magnetic abrasive finishing (MAF) is one of the advanced machining processes efficiently used to finish hard-to-machine materials. Simulation and modeling of the process is of particular importance to understand the mechanics of material removal and consequently achieve a high-quality surface with a minimum of surface defects. Hence, in this paper, we performed a numerical-experimental study to mathematically model the surface roughness during the MAF of BK7 optical glass. For this purpose, the initial roughness profile was estimated using fast Fourier transform (FFT) and a Gaussian filter. We obtained the final surface profile based on the material removal mechanisms and the corresponding chipping depth values evaluated by finite element analysis. We then validated experimentally the simulation results in terms of the arithmetic average surface roughness (R(a ). The comparison between the obtained results demonstrates that the theoretical and experimental findings are in good agreement when predicting the parameters' effect on surface roughness behavior.


Interaction between cytochrome c and cytochrome c peroxidase: excited-state reactions of zinc- and tin-substituted derivatives.
The effect of cytochrome c peroxidase (CCP) and apoCCP on the fluorescence and phosphorescence of Zn and Sn cytochrome c (cyt c) and the effect of cyt c on the fluorescence and phosphorescence of Zn CCP were examined. We found the following: The fluorescence yields of Zn and Sn cyt c were quenched by about 20% by CCP, consistent with energy transfer between the two chromophores with a separation of about 1.8 nm. The phosphorescence spectrum of Zn cyt c (but not Sn cyt c) shifts by 20 nm to the blue upon complexation with either CCP or apoCCP; at the same time the phosphorescence lifetime of Zn cyt c decreases from 12 +/- 2 to 6 ms with apoCCP addition. Zn CCP phosphorescence decay increases from 8.3 to 9.1 ms upon addition of poly(L-lysine) used to mimic cyt c. It is concluded from these results that binding of the redox partner or an analogue to Zn CCP and Zn cyt c results in a conformational change. The respective phosphorescence lifetimes of Zn and Sn cyt c were 13 and 3 ms in the absence of CCP and 1.6 and 1.1 ms in the presence of CCP; this corresponds to a quenching rate due to CCP of 519 and 570 s-1, for Zn and Sn cyt c, respectively. The phosphorescence of Zn CCP is also affected by native cyt c but is dramatically less than the complementary pair; the quenching rate constant is 17 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of continuous positive airway pressure on leptin levels in patients with obstructive sleep apnea: a meta-analysis.
Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea hypopnea syndrome (OSAHS), but previous studies assessing the effect of CPAP on leptin in patients with OSAHS yielded conflicting results. In this study, we conducted a meta-analysis to determine whether CPAP therapy could reduce serum leptin levels. Databases of PubMed, Elsevier, and SCI were thoroughly searched by 2 independent reviewers. RevMan (version 5.2) was used for data synthesis. Weighted mean difference (WMD) before and after CPAP therapy was calculated to estimate the effects of CPAP therapy. A total of 11 studies involving 413 participants were included. Meta-analysis showed that the total WMD for leptin levels was 1.44 units (95% confidence interval: 1.11-1.77, P < .01) before and after CPAP therapy. Subgroup analysis exhibited that leptin was decreased within 3 days after the therapy, and it was further reduced within 1 to 3 months and beyond. The results of our meta-analysis showed that CPAP could significantly reduce leptin levels in OSAHS patients without concomitant weight loss.


[Health care models for patients with multiple chronic conditions and the role of the hospital pharmacy/the hospital pharmacist].
Managing care for patients with chronic conditions currently represents one of the greatest challenges to health care systems. As a subgroup of these patients, those with multiple chronic conditions are at greater risk for death or disability, and they consume more resources. They are characterized by the coexistence of two or more chronic illnesses lasting a year or longer which require ongoing medical attention and/or interfere with their daily activities. For these polypathological patients pharmaceutical care would be of special benefit, thus, their needs should be a priority objective for hospital pharmacy. To increase awareness of this type of patients and the characteristics of the principal approaches and health care models proposed to improve chronic disease management, as well as to emphasize the urgency for hospital pharmacists to join these models, and to present various activities that pharmacists might carry out as an integral part of these approaches. Numerous models exist internationally, including the Chronic Care Model and the Kaiser Permanente pyramid of risks. In our country a growing number of initiatives has culminated in the recent Seville Declaration. For the hospital pharmacy, caring for the chronically ill patient following a model that is multi-professional, cooperative, integral, and patient centered, is an enormous task. Pharmacy departments and the Spanish Society of Hospital Pharmacy should reorient their strategies for pharmaceutical care, training, and research. Of special interest are those activities designed to improve adherence, adequacy, and continuity in treatments, all the while emphasizing active patient participation.


Effects of strength, endurance and combined training on myosin heavy chain content and fibre-type distribution in humans.
This study investigated the effect of strength training, endurance training, and combined strength plus endurance training on fibre-type transitions, fibre cross-sectional area (CSA) and MHC isoform content of the vastus lateralis muscle. Forty volunteers (24 males and 16 females) were randomly assigned to one of four groups: control (C), endurance training (E), strength training (S), or concurrent strength and endurance training (SE). The S and E groups each trained three times a week for 12 weeks; the SE group performed the same S and E training on alternate days. The development of knee extensor muscle strength was S>SE>E ( P<0.05) and has been reported elsewhere. The reduction in knee extensor strength development in SE as compared to S corresponded to a 6% increase in MHCIIa content ( P<0.05) in SE at the expense of the faster MHCIId(x) isoform ( P<0.05), as determined by electrophoretic analyses; reductions in MHCIId/x content after S or E training were attenuated by comparison. Both S and SE induced three- to fourfold reductions ( P<0.05) in the proportion of type IIA/IID(X) hybrid fibres. S also induced fourfold increases in the proportion of type I/IIA hybrid fibres within both genders, and in a population of fibres expressing a type I/IID(X) hybrid phenotype within the male subjects. Type I/IIA hybrid fibres were not detected after SE. Both S and SE training paradigms induced similar increases (16-19%, P<0.05) in the CSA of type IIA fibres. In contrast, the increase in CSA of type I fibres was 2.9-fold greater ( P<0.05) in S as compared to SE after 12 weeks. We conclude that the interference of knee extensor strength development in SE versus S was related to greater fast-to-slow fibre-type transitions and attenuated hypertrophy of type I fibres. Data are given as mean (SEM) unless otherwise stated.


Fishes from the Itapecuru River basin, state of Maranhão, northeast Brazil.
The Itapecuru is a relatively large river in the northeastern Brazilian state of Maranhão. During several expeditions to this basin, we collected 69 fish species belonging to 65 genera, 29 families and 10 orders. Characiformes and Siluriformes were the orders with the largest number of species and Characidae, Loricariidae, Cichlidae, Auchenipteridae and Pimelodidae were the richest families. About 30% of the fish fauna of the Itapecuru basin is endemic or restricted to northeastern Brazil. Just over a fifth (22%) of the species is also known to occur in the Amazon basin and only a few are more widely distributed in South American.


Down-regulation of miRNA-451a and miRNA-486-5p involved in benzene-induced inhibition on erythroid cell differentiation in vitro and in vivo.
Exposure to high-dose benzene leads to the inhibition of erythroid differentiation. However, whether lower doses of benzene exposure resemble high-dose effects in erythroid differentiation, as well as the underlying mechanisms, remains largely unknown. To identify the microRNAs (miRNAs) specifically responsible for benzene exposure and their regulatory role in erythroid differentiation, we performed miRNA microarray in CD34+ hematopoietic progenitor cells isolated from human umbilical cord blood after treatment with hydroquinone (HQ), a metabolite of benzene at concentrations of 0, 1.0, 2.5, and 5.0 μM. As a result, HQ treatment inhibited erythroid differentiation in a dose-response manner. miRNA microarray analysis revealed that miRNA-451a, miRNA-486-5p and miRNA-126-3p expression were significantly lower in HQ-treated CD34+ hematopoietic progenitor cells. In vitro studies showed that miRNA-451a and miRNA-486-5p were up-regulated during erythroid differentiation both in CD34+ hematopoietic progenitor cells and K562 cells. The increase in the percentage of benzidine-positive cells and the expression of γ-globin in K562 cells transfected with either miRNA-451a or miRNA-486-5p mimic indicated that both miRNAs played a role in the promotion of erythroid cell differentiation. Overexpression of either miRNA-451a or miRNA-486-5p attenuated the inhibitory effects on erythroid differentiation in HQ-treated K562 cells. In vivo study showed a decreasing count of peripheral red blood cell (RBC) in C57BL/6J male mice treated with aerosol benzene at concentrations of 0, 1, 5, 25 ppm (time weight average, TWA). In addition, the expression of miRNA-451a or miRNA-486-5p was negatively correlated with the concentration of benzene inhalation on erythroid toxicity of C57BL/6J mice. Particularly, the decline in miRNA-451a and miRNA-486-5p expression appeared in male chronic benzene poisoning patients, and was correlated with a constant decrease in their RBC counts over the first 3 months after being diagnosed. These findings indicate that the suppression of miRNA-451a or miRNA-486-5p might be associated with the benzene-induced perturbation of erythroid cell differentiation.


Laparoscopy-assisted management of jejunal bezoar obstruction.
Treatment of intestinal bezoar causing obstruction is usually straightforward by an open approach, with either digital fragmentation or removal of the bezoar via an enterotomy. Herein, we report a case of small bowel bezoar obstruction treated successfully by laparoscopic technique. The bezoar was fragmented manually via a minilaparotomy and then pushed into the cecum with laparoscopic forceps. Laparoscopic management is an alternative to conventional surgery for intestinal bezoar that provides shorter hospital stay and less postoperative pain and may be recommended as the treatment of choice of such patients.


Combined modality approach in breast cancer with isolated or multiple metastases.
One hundred thirty-six patients with isolated recurrence of breast cancer received regional therapy (surgery and/or irradiation) followed by combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC). The disease-free survival of the group receiving FAC was compared to that of a historical control group treated with only regional therapy. The median disease-free interval between the first and second recurrence for the control group was 9 months and for the patients receiving FAC, 38 months (p less than 0.01). The median survivals from first recurrence for the control and the FAC groups were 40 months and 60 months, respectively (p less than 0.02). In addition, 20 selected patients with multiple sites of metastasis or bulky isolated recurrence were initially treated with FAC chemotherapy; following complete or partial response with chemotherapy, these patients had regional therapy at the known sites of metastases. At a median follow-up time of 54 months, 9/20 patients (45%) have remained in complete remission. Combined modality approach significantly prolongs the disease-free survival of patients with isolated recurrences of breast cancer, and in selected patients with multiple metastases, this approach results in extended complete remissions.


Long-acting methylphenidate has an effect on aggressive behavior in children with attention-deficit/hyperactivity disorder.
Aggression is frequently observed in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to assess the efficacy with regard to oppositional and aggressive behavior of a new long-acting methylphenidate preparation (Medikinet retard, MPH-MR), with equal portions of the immediate-release and the sustained-release active substance, and especially to look at correlations between either teacher or parent assessment of aggression and ADHD sub-symptomatology. Eighty five children and adolescents (6-16 years) were investigated in a double-blind, randomized, clinical trial over 5 weeks under a treatment with MPH-MR using symptom checklists for ADHD, oppositional-defiant and conduct disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). A total of 64.9% of the children showed oppositional defiant disorder/conduct disorder (ODD/CD) symptoms. A statistically significant effect was found in the group treated with MPH (verum-group). On the basis of Cohen's criteria, high effects were found for aggressive symptoms in school (d = 1.0), but not in the afternoon (d = 0.4). There were also lower effect sizes for more severe aggressive symptoms. We found characteristic correlations between ODD/CD symptoms and the ADHD subscale hyperactivity/impulsivity compared to the subscale inattention. Long-acting MPH is effective in the treatment of oppositional-defiant and aggressive behavior, especially concerning milder symptoms. The expected correlation between impulsivity and aggressiveness could be confirmed.


Performance of the molecular Alere I influenza A&B test compared to that of the xpert flu A/B assay.
Data on the performance of rapid molecular point-of-care use platforms for diagnosis of influenza are lacking. We validated nasopharyngeal (NP) flocked specimens in universal transport medium (UTM) and evaluated the clinical sensitivity and specificity of the Alere i influenza A&B test compared to those of the Xpert flu A/B assay. The Alere i influenza A&B test had an overall sensitivity and specificity of 93.8% and 62.5% for influenza A, respectively, and of 91.8% and 53.6% for influenza B, respectively. The poor specificity was due to influenza virus samples determined positive for both type A and B.


Analytical and preparative applications of magnetic split-flow thin fractionation on several ion-labeled red blood cells.
Magnetic Split-flow thin (SPLITT) fractionation is a newly developed technique for separating magnetically susceptible particles. Particles with different field-induced velocities can be separated into two fractions by adjusting applied magnetic forces and flow-rates at inlets and outlets. Magnetic particles, Dynabeads, were used to test this new approach of field-induced velocity for susceptibility determination using magnetic SF at different magnetic field intensities. Reference measurements of magnetic susceptibility were made using a superconducting quantum interference device (SQUID) magnetometer. Various ion-labeled red blood cells (RBC) were used to study susceptibility determination and throughput parameters for analytical and preparative applications of magnetic SPLITT fractionation (SF), respectively. Throughputs were studied at different sample concentrations, magnetic field intensities, and channel flow-rates. The susceptibilities of Dynabeads determined by SPLITT fractionation (SF) were consistent with those of reference measurement using a superconducting quantum interference device (SQUID) magnetometer. Determined susceptibilities of ion-labeled RBC were consistent within 9.6% variations at two magnetic intensities and different flow-rates. The determined susceptibilities differed by 10% from referenced measurements. The minimum difference in magnetic susceptibility required for complete separation was about 5.0 x 10(-6) [cgs]. Sample recoveries were higher than 92%. The throughput of magnetic SF was approximately 1.8 g/h using our experimental setup. Magnetic SF can provide simple and economical determination of particle susceptibility. This technique also has great potential for cell separation and related analysis. Continuous separations of ion-labeled RBC using magnetic SF were successful over 4 hours. The throughput was increased by 18 folds versus early study. Sample recoveries were 93.1 +/- 1.8% in triplicate experiments.


The relevance of asymptomatic endometriosis.
Asymptomatic endometriosis is likely to be a physiological phenomenon of very limited relevance to both the physician and the patient. The evolution of our understanding of this phenomenon is a parable for modern medicine. It is likely that access to a new diagnostic technique, a powerful armoury of medical and surgical treatments and the necessity for doctors to feel they are doing something positive for the patient, have created an incorrect disease model for asymptomatic endometriosis. As responsible clinicians and medical scientists it behoves us to honestly re-examine our approach to this phenomenon.


Mesh reinforcement increases bursting strength of intestinal anastomoses in steroid-treated rabbits.
We tested the hypothesis that reinforcement of small bowel anastomoses with polyglycolic acid mesh (PGAM) would increase bursting strength in steroid-treated subjects. Twenty-two New Zealand white rabbits weighing 3-4 kg received methylprednisolone 0.2 mg/kg/day IM for 7-13 days preoperatively and until killed 4-5 days postoperatively. Steroid effect was confirmed by a 58.3 per cent decrease in absolute lymphocyte count and a histologic reduction in anastomotic fibroblast proliferation and collagen deposition. Two small bowel anastomoses were performed in each animal using standard two-layer suture technique. One of the two anastomoses, randomly assigned, was circumferentially reinforced with PGAM such that each animal served as its own control. Anastomotic bursting pressures, determined on postoperative Day 4-5, were significantly higher in mesh-reinforced anastomoses (P = 0.003). Histologic examination of the reinforced anastomoses revealed a well-developed layer of fibroblasts and collagen between the PGAM and bowel wall serosa. These results demonstrate that polyglycolic acid mesh reinforcement significantly increases the bursting strength of small bowel anastomoses in steroid-treated rabbits.


Combination chemotherapy for advanced squamous cell carcinoma of the head and neck.
Fifteen patients with advanced squamous cell carcinoma of the head and neck were treated with the six-drug Price-Hill regimen (vincristine, bleomycin, methotrexate, hydrocortisone, 5-fluorouracil, and leucovorin). Only two partial remissions were obtained, and the regimen produced moderate toxicity. Our results are not as favorable as those of Price and Hill.


Overexpression of TMAC2, a novel negative regulator of abscisic acid and salinity responses, has pleiotropic effects in Arabidopsis thaliana.
Phytohormone abscisic acid (ABA) regulates many aspects of plant development and growth. To explore the molecular mechanism of ABA, we identified the novel ABA-regulated genes in Arabidopsis thaliana by searching for genes possessing two or more ABREs (ABA-responsive elements). One of these genes, two or more ABREs-containing gene 2 (TMAC2) is highly induced by ABA and NaC1. Database searches revealed that TMAC2 encodes a protein with no domains of known function. Expression of TMAC2-GFP fusion protein in Arabidopsis mesophyll protoplasts indicated that TMAC2 is targeted to the nucleus. Although the gene has a basal level of expression in various Arabidopsis organs/tissues except for adult leaves, a high expression level was detected in roots. Constitutive overexpression of TMAC2 in plants resulted in the insensitivity to ABA and NaCl, suggesting that TMAC2 plays a negative role in ABA and salt stress responses. Furthermore, TMAC2-overexpressing plants exhibited the short roots, late flowering and starch-excess phenotypes. RT-PCR analysis showed that decreased expression of two floral- and one starch degradation-related genes, SOC1/AGL20 and SEP3/AGL9, and SEX1, respectively, may lead to altered phenotypes of TMAC2-overexpressing plants. Taken together, our data reveal that TMAC2 acts in the nucleus and is an important negative regulator of ABA and salt stress responses, and could play a critical role in controlling root elongation, floral initiation and starch degradation.


Directional adaptation of reactive saccades and hand pointing movements is not independent.
It is a matter of debate whether reactive saccades and hand pointing movements share common adaptive mechanism. To find out, the authors used a double-step paradigm in which the direction either of eye or of hand movements was adaptively modified in a first block of 300 trials, and the direction of the other motor system was then modified with opposite polarity in a second block of 300 trials. In a third block, single-step stimuli were used to test for after effects. The authors found that subjects adapted in the second block less well than in the first, and that aftereffects were adequate for the first rather than the second block. When the second block was extended to 500 trials, adaptation was still poor but aftereffects were now adequate for the second block. From this the authors concluded that double-step adaptation of the first motor system interferes with the subsequent adaptation of the other motor system (i.e., the adaptive mechanisms for eyes and hand are not independent).


Analysis of risk allele frequencies of single nucleotide polymorphisms related to open-angle glaucoma in different ethnic groups.
The prevalence of open-angle glaucoma (OAG) varies from 0.5% to 7.0% among populations of diverse ancestry, suggesting the existence of genetic differences. The purposes of this study were to provide insights into genetic causes of OAG, which can result in prevalence and phenotype differences among populations of diverse ancestry for OAG, and to compare allele frequencies of intraocular pressure (IOP) elevation-related SNPs in OAG among Koreans and other ethnic groups. We collected the data on a total of 135 OAG-associated single nucleotide polymorphisms (SNPs) from a genome-wide association studies (GWAS) catalog. The population-level allele frequencies of these SNPs were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact test to assess whether the effect allele at a given SNP was significantly enriched or depleted. European, American, and South Asian populations showed similar heatmap patterns, while African, East Asian, and Korean populations had distinct patterns. Korean population presented different profiles compared to other groups; rs1579050 (FMNL2 gene), rs2024211 (CAV2;CAV1), and rs8141433 (GNB1L;TXNRD2 gene), which are known to be associated with IOP variation, were enriched in Americans, Europeans, and Africans, and depleted in Koreans. These can be the candidates for the causative genes of differences in the prevalence of IOP variation in OAG according to ethnic groups. Differences in allele frequencies associated with IOP related SNPs between Koreans and other ethnicities were observed, which may explain the high prevalence of OAG with normal IOP predominantly in Koreans and East Asians.


Spatial variability of the characteristics of combined wet weather pollutant loads in Paris.
An on-site observatory of urban pollutant loads in combined sewers has been created in Paris in order to investigate wet weather pollutant loads at different spatial scales. This observatory is composed of six urban catchments, covering areas from 41 to 2581ha. For a wide range of parameters including suspended solids (SS), volatile suspended solids (VSS), chemical oxygen demand (COD), biochemical oxygen demand (BOD5), total organic carbon (TOC), total Kjeldahl nitrogen (TKN), metals (Cd, Cu, Pb, Zn), aliphatic hydrocarbons and polycyclic aromatic hydrocarbons (AHs and PAHs), this article serves to evaluate the potential scale effect on wet weather flow (WWF) quality. Although the extensive data set compiled herein has emphasized the high variability in WWF quality from one rain event to the next, no scale effect could be observed for a given rain event on pollutant concentrations, distributions between dissolved and particulate phases, pollutant contents and loads. Such results are of prime importance since they suggest (i) no spatial scale influence on WWF quality for the considered catchments and (ii) similar dominant sources and transfer processes at the various spatial scales.


Imparting the unique properties of DNA into complex material architectures and functions.
While the remarkable chemical and biological properties of DNA have been known for decades, these properties have only been imparted into materials with unprecedented function much more recently. The inimitable ability of DNA to form programmable, complex assemblies through stable, specific, and reversible molecular recognition has allowed the creation of new materials through DNA's ability to control a material's architecture and properties. In this review we discuss recent progress in how DNA has brought unmatched function to materials, focusing specifically on new advances in delivery agents, devices, and sensors.


A new modeling method in feature construction for the HSQC spectra screening problem.
Large-scale biological analyses produce huge amounts of data. As a consequence, automation in the data analysis process is needed. Sample screening problems in NMR high-throughput protein structure analysis are the typical examples. Especially, screening by protein (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra must be done quantitatively by a human expert. One popular solution for this problem is data mining. Machine learning methods can automatically extract rules and achieve high accuracy in prediction when a good quality training dataset is prepared. However, they tend to be a black box and the learned machines suffer the risk of overfitting to the dataset. We propose a model which evaluates HSQC spectra for feature construction. The model calculates similarity between the measured chemical shifts and those of a random coil peak model. We applied our feature construction method for the machine learning discrimination of folded protein HSQC spectra from unfolded ones, and compared our model-based features with those of conventional sequence-based features and image recognition features. The results revealed that our method has sufficient discrimination power and less overfits on training data, as compared to the other methods. In addition, our method succeeded reduction of input data complexity towards further investigation. Supplementary data are available at Bioinformatics online.


[Headache--differential diagnosis and therapy].
Only few guidelines exist for the therapy of chronic pain syndromes but are available for headache. It is important to know the therapeutic principles and apply them to the patients. The education of a patient suffering from headache is a main factor for a successful therapy. Physician and psychologist together in cooperation with the patient can achieve a better quality of life for the patient. New developments of the medication used for the therapy of chronic headache will result in a better symptom control in the next years.


The Risk Assessment and Clinical Research of Bile Duct Injury After Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma.
To retrospectively evaluate the risk factors and the clinical outcomes of bile duct injury after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) and to evaluate factors that aid clinical detection and subsequent treatment of the injured bile duct. All patients undergoing TACE for HCC were retrospectively reviewed for identification of bile duct injury. The clinical spectrum of all the patients analyzed including patients' demographics, laboratory data, radiologic imaging and mode of treatment. From January 2015 to December 2017, a total of 21 patients (4.3%) out of 483 patients with 693 TACE procedures were identified to have bile duct injury at our single institution. There were 17 males and 4 females, with a mean age of 59.8±11.6 years (range 34-84). About 14.3% (3/21) patients show the high-density shadow around the bile duct wall in one week non-enhanced CT, and 76.2% (16/21) cases ALP>200 U/L, all these patients showed bile duct injury on the subsequent follow-up CT. Post-TACE follow-up blood biochemistry showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) increased significantly compared with pre-TACE level. The incidence of various types of bile duct injuries on CT was intrahepatic bile duct dilatation (57.1%), biloma (25.7%) and hepatic hilar biliary strictures (17.1%), respectively. Patients with prior hepatectomy as well as proximal arterial chemoembolization carried a higher risk of post-TACE bile duct injury in terms of microvascular damage to the peribiliary capillary plexus. Bile duct injury complicating TACE is not caused by a single factor, but by a variety of factors, and is closely related to the microvascular compromise of the bile ducts and subsequent chronic biliary infection. Lipiodol deposited along the bile duct wall and the sharp rise of ALP>200 U/L in one week after TACE can predict bile duct injury and early intervention may prevent the occurrence of serious complications. The probability of bile duct injury in patients with prior hepatectomy and proximal arterial chemoembolization increases significantly.


The effect of K+ concentration on the energy metabolism in perfused rat heart.
From experiments at various perfusion pressures in hemoglobin-free perfused rat hearts, oxygen consumption and redox shift of pyridine nucleotide were found to vary linearly with cardiac work. This relation was used for analysis of the energy metabolism associated with ion pumps. Mechanical activities such as left ventricular pressure and heart rate varied with the extracellular K+ concentration. Ion-pump dependent changes in oxygen consumption and redox state of pyridine nucleotide, estimated as the difference of the values at normal (4.7 mM) and various other extracellular K+ concentrations with corrections for the change due to mechanical work, were found to vary linearly with the K+ concentration. The slope for oxygen consumption was about 0.1 mumol/min/g X wet wt per mM K+. Lactate release changed markedly but transiently, about 1 min after changing the extracellular K+ concentration, and its amount varied linearly with the K+ concentration. In the steady state, however, lactate release was almost independent of the extracellular K+ concentration, although oxidized pyridine nucleotide increased with increasing K+ concentration. Coronary flow increased with the extracellular K+ concentration. Heart rate changed little between 1 and 12 mM K+, but decreased sharply above 12 mM K+. At 20 mM K+, heart beat was arrested and approximately 40% of myoglobin was deoxygenated. The intracellular oxygen concentration was estimated to be about 10 microM even during aerobic perfusion. Similarly, Ca2+-free arrested heart was found to be in a hypoxic state. The results showed that oxygen entry into cardiac tissue is facilitated by the cardiac cycle.


Effect of exhaustive exercise stress on the cytokine response.
Fifteen athletes were investigated 24 h before, 1 h after, and 20 h after an exhaustive exercise stress test (mean duration 68 min). Testing for cytokines was done in serum, urine, and the supernatants of whole blood cell cultures, which were stimulated with lipopolysaccharide (LPS), concanavalin A (Con A), or phythaemagglutinin (PHA). Elevated levels of interleukin 6 (IL-6) and soluble IL-2 receptor (sIL-2R) were found 1 h after the run in both serum and urine samples. TNF-alpha in serum was also increased, whereas IL-2 in urine was decreased after the exercise. All other testings in serum and urine (including IFN-gamma) gave borderline or negative results. In cell cultures, the LPS-induced release of the inflammatory cytokines TNF-alpha, IL-1, and IL-6 was suppressed 1 h after exercise. Also, the Con-A-induced and LPS-induced release of IFN-gamma, and the PHA-induced release of IL-2 were suppressed 1 h after exercise. In contrast, Con-A-induced release of IL-2 was mildly increased after the run. We conclude that exercise of the intensity and duration described here causes an activation of the immune system, which is immediately counter-regulated. Twenty hours after the exercise, most of the observed changes were back to pre-exercise levels, indicating only a short duration for this suppressive counter-regulation.


Severe neurological abnormalities associated with a mutation in the zinc-finger domain in a group A xeroderma pigmentosum patient.
All the reported Japanese patients with group A xeroderma pigmentosum (XP) have two or three mutations at codon 116 in exon 3, codon 228 in exon 6, and the splicing acceptor site of intron 3 of XP group A complementing (XPAC) gene. A homozygote (XP39OS) with a nonsense mutation at codon 228 has less severe neurological abnormalities than patients with the splicing mutation at the acceptor site of intron 3. As homozygotes for the nonsense mutation at codon 116, which truncates a carboxyl-terminal site of XPAC protein at an early part of its zinc-finger domain, have not been reported previously, the possible severity of associated neurological abnormalities was not known. We report a group A XP patient, XP18OS, who had neurological abnormalities which were more severe than those in patients homozygous for the splicing mutation. The polymerase chain reaction product from exon 3 of the patient's XPAC gene was digested completely into three fragments by MseI restriction endonuclease. Thus, the patient was homozygous for the mutation at codon 116.


The asymmetric facial skin perfusion distribution of Bell's palsy discovered by laser speckle imaging technology.
Bell's palsy is a kind of peripheral neural disease that cause abrupt onset of unilateral facial weakness. In the pathologic study, it was evidenced that ischemia of facial nerve at the affected side of face existed in Bell's palsy patients. Since the direction of facial nerve blood flow is primarily proximal to distal, facial skin microcirculation would also be affected after the onset of Bell's palsy. Therefore, monitoring the full area of facial skin microcirculation would help to identify the condition of Bell's palsy patients. In this study, a non-invasive, real time and full field imaging technology - laser speckle imaging (LSI) technology was applied for measuring facial skin blood perfusion distribution of Bell's palsy patients. 85 participants with different stage of Bell's palsy were included. Results showed that Bell's palsy patients' facial skin perfusion of affected side was lower than that of the normal side at the region of eyelid, and that the asymmetric distribution of the facial skin perfusion between two sides of eyelid is positively related to the stage of the disease (P < 0.001). During the recovery, the perfusion of affected side of eyelid was increasing to nearly the same with the normal side. This study was a novel application of LSI in evaluating the facial skin perfusion of Bell's palsy patients, and we discovered that the facial skin blood perfusion could reflect the stage of Bell's palsy, which suggested that microcirculation should be investigated in patients with this neurological deficit. It was also suggested LSI as potential diagnostic tool for Bell's palsy.


Identification of a cis-element that mediates multiple pathways of the endoplasmic reticulum stress response in rice.
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress. Intracellular signalling pathways are activated to alleviate the stress. The ER stress sensor IRE1 induces the active form of key transcription factors, such as XBP1 in mammals and bZIP50 in Oryza sativa (rice), by mediating the unconventional splicing of their mRNAs. Although the characterization of cis-elements that are recognized by these transcription factors is essential for understanding ER stress responses, such cis-elements remain unidentified in plants. Here, a cis-element named pUPRE-II was identified from promoters of bZIP50-dependent genes using chromatin immunoprecipitation assays and electrophoretic mobility shift assays. The sequence of pUPRE-II (e.g., 5'-GATGACGCGTAC-3' in the OsSAR1 promoter) was found to be flexible and not identical with that of mUPRE, a cis-element that preferentially interacts with mammalian XBP1. Unexpectedly, the transcription factor bZIP60, another ER stress sensor in rice, and a counterpart of mammalian ATF6, also showed strong binding affinity for pUPRE-II without assistance from co-factors. Reporter assays indicated that pUPRE-II significantly contributes to gene expression mediated by bZIP50 or bZIP60 in rice. Although both bZIP50 and bZIP60 bound to pUPRE-II, these transcription factors showed distinct requirements for transcriptional activation. This study provides a missing link between ER stress sensors and stress-responsive genes in rice. Furthermore, the characteristics of pUPRE-II highlight the uniqueness of ER stress-responsive transcription in plants.


Comparison of force-time parameters and EMG in static explosive gripping by various exertion conditions: muscle fatigue state and submaximal exertion.
The purpose of this study was to compare the exertion and electromyography (EMG) properties during the developmental phase (DFmax) in static explosive grip (SEG), rapid submaximal exertion grip, namely fake SEG exertion (FAKE), and SEG in a muscle fatigue state. Thirty healthy males and females performed the SEG and FAKE exertions (50% and 75% of peak value as a target value). Then, they performed sustained repeated rhythmic grip for 6 min (30 times x min(-1)), and SEG after 1-min, 4-min, and 7-min (SEG after the exertion). EMG was measured concurrently to compare with the muscle activation property during each grip exertion. Eight force-time parameters evaluating the DFmax in addition to the peak value were selected. The peak value significantly decreased, and the mean power spectrum density shifted to the low-wave in SEG after the exertion as compared with before. Therefore, SEG after the exertion was judged to be a muscle fatigue state. In addition, because the frequency properties in each exertion differed, the muscle activation properties during their DFmaxs were considered to differ. From the comparison between SEG before and after the exertion and FAKE, it is suggested that the time of reaching the peak value and the relative muscle strength when reaching an inflection point are not useful as parameters to evaluate the explosive muscle function during SEG. The maximal increasing volume during the DFmax and integrated area until 0.25 and 0.5 s could discriminate a difference of the DFmaxs according to each exertion and they are useful parameters.


[Pollen monitoring in Poland].
The author presents the history of aerobiological studies in Poland. The first scientist to undertake research regarding this problem in Poland was Mieczysław Obtułowicz. The research on this topic was resumed again in Krakow and Rabka in the 1960s. since 1989, constant measurements of plant pollen and fungal spore concentrations have been conducted by volumetric methods in over ten sites in Poland, in a network created by P. Rapiejko. In 1989 the first pollen report, worked out by the Allergen Research Centre appeared in daily newspapers. Pollen information (current data reports and forecast) is available to the public through radio broadcasts, television and newspapers. Pollen calendar for Poland is presented. Pollen sampling methods employed in these studies are also briefly described.


Effects of Salinity on Sperm Motility, Fertilization, and Development in the Pacific Herring, Clupea pallasi.
We investigated the effects of salinity on fertilization and early development in a population of Pacific herring, Clupea pallasi, that migrate from oceanic waters into the San Francisco Bay estuary to spawn. The salinity range for fertilization fell between 8 and 28 ppt, with an optimal range of about 12 to 24 ppt. In comparison, the range for a population of C. harengus membras (Airisto Sound, Finland) that reside year-round in the Baltic Sea was 4 to 24 ppt. Roles for both Na+ and K+ were indicated in C. pallasi fertilization since increasing Na+ in the presence of 10 mM K+ (concentration of seawater) mimicked the effects of increased overall salinity, whereas reduced effects were obtained if [K+] was held at 5 mM (that of half-strength seawater). The initiation of C. pallasi sperm motility by components of the egg chorion, a prerequisite for fertilization, was inhibited at both elevated (28 and 32 ppt) and reduced (4 and 8 ppt) salinities. Embryonic development through larval hatching in C. pallasi exhibited a salinity tolerance similar to that of fertilization; optimum development was obtained at salinities between 8 and 24 ppt. A comparison of developmental progression in 3.5, 14, and 28 ppt seawater revealed that salinity effects became evident during the post-gastrulation stages of development and that progression to hatching was delayed in both the lower and higher salinities for those embryos that completed development.


Human bocaviruses: Possible etiologic role in respiratory infection.
Four species of human bocaviruses (HBoV) are currently included in the Bocavirus genus. There is satisfactory evidence demonstrating an association between HBoV1 and respiratory disease in children, and there is evidence that HBoV2 (and possibly the HBoV3 and HBoV4 species) are associated with gastroenteritis. In particular, HBoV1 has been associated with a prolonged period of persistence in the mucosa of the respiratory tract. Virus persistence does play a role in the high frequency of co-infections with proper pathogens of the upper and lower respiratory tracts. The high detection rate of multiple respiratory viruses in up to 83% of respiratory specimens and the presence of asymptomatic HBoV1 infections complicate the elucidation of the pathogenic role of the agent. Overall, a large amount of data are available concerning HBoV1, whereas little information is available about other bocavirus species. High viral loads are often associated with symptoms, and viremia may be associated with systemic manifestations such as encephalopathy. The effects and mechanisms of latency, persistence, reactivation, and reinfection are poorly understood. Thus, particularly in co-infections, the pathogenic contribution of the detected bocavirus species cannot be accurately stated. This review summarizes the current knowledge of HBoV species and provides perspectives for future clinical studies.


Highly efficient one-step scarless protein tagging by type IIS restriction endonuclease-mediated precision cloning.
Protein tagging with a wide variety of epitopes and/or fusion partners is used routinely to dissect protein function molecularly. Frequently, the required DNA subcloning is inefficient, especially in cases where multiple constructs are desired for a given protein with unique tags. Additionally, the generated clones have unwanted junction sequences introduced. To add versatile tags into the extracellular domain of the transmembrane protein THSD1, we developed a protein tagging technique that utilizes non-classical type IIS restriction enzymes that recognize non-palindromic DNA sequences and cleave outside of their recognition sites. Our results demonstrate that this method is highly efficient and can precisely fuse any tag into any position of a protein in a scarless manner. Moreover, this method is cost-efficient and adaptable because it uses commercially available type IIS restriction enzymes and is compatible with the traditional cloning system used by many labs. Therefore, precision tagging technology will benefit a number of researchers by providing an alternate method to integrate an array of tags into protein expression constructs.


Action of granulocyte-macrophage colony-stimulating factors: studies using a human leukemia cell line.
Granulocyte-macrophage colony-stimulating factors (CSFs) have previously been shown to stimulate colony formation in soft agar culture by a human myelogenous leukemia cell line known as KG-1. We have used KG-1 cells as a model system to investigate the interaction of CSF with myeloid cells. We now report that exposure of KG-1 cells to human CSFs in liquid culture results in a rapid (within 3 hr) burst of RNA synthesis and, after a lag of about 10 hr, a stimulation of DNA and protein synthesis. RNA and protein synthesis were maximally stimulated about 2-fold and DNA synthesis was stimulated about 2.5-fold. The stimulation was specific; various growth factors, hormones, and mouse CSFs had no effect on KG-1 macromolecular synthesis. Treatment with CSF did not discernibly alter the morphological appearance of the KG-1 cells (primarily myeloblasts) nor did it qualitatively affect the pattern of newly synthesized proteins separable by one- and two-dimensional electrophoresis. Several myeloid leukemia cell lines that were not responsive to CSF in agar culture, including a dedifferentiated variant of KG-1, showed little or no stimulation of macromolecular synthesis upon exposure to CSF. We have used the CSF-dependent stimulation of macromolecular synthesis of KG-1 to develop a rapid, sensitive microassay for human CSFs. The assay, involving thymidine incorporation by the cells, should be useful for characterization and purification of human CSFs.


COL11A2 as a candidate gene for vertebral malformations and congenital scoliosis.
Human vertebral malformations (VMs) have an estimated incidence of 1/2000 and are associated with significant health problems including congenital scoliosis (CS) and recurrent organ system malformation syndromes such as VACTERL (vertebral anomalies; anal abnormalities; cardiac abnormalities; tracheo-esophageal fistula; renal anomalies; limb anomalies). The genetic cause for the vast majority of VMs are unknown. In a CS/VM patient cohort, three COL11A2 variants (R130W, R1407L and R1413H) were identified in two patients with cervical VM. A third patient with a T9 hemivertebra and the R130W variant was identified from a separate study. These substitutions are predicted to be damaging to protein function, and R130 and R1407 residues are conserved in zebrafish Col11a2. To determine the role for COL11A2 in vertebral development, CRISPR/Cas9 was used to create a nonsense mutation (col11a2L642*) as well as a full gene locus deletion (col11a2del) in zebrafish. Both col11a2L642*/L642* and col11a2del/del mutant zebrafish exhibit vertebral fusions in the caudal spine, which form due to mineralization across intervertebral segments. To determine the functional consequence of VM-associated variants, we assayed their ability to suppress col11a2del VM phenotypes following transgenic expression within the developing spine. While wildtype col11a2 expression suppresses fusions in col11a2del/+ and col11a2del/del backgrounds, patient missense variant-bearing col11a2 failed to rescue the loss-of-function phenotype in these animals. These results highlight an essential role for COL11A2 in vertebral development and support a pathogenic role for two missense variants in CS.


Dural invasion by craniofacial and calvarial neoplasms: MR imaging and histopathologic evaluation.
The authors prospectively correlated results of magnetic resonance (MR) imaging and histologic examination of the dura in 17 patients with craniofacial and calvarial neoplasms and possible intracranial extension. Contrast material-enhanced MR imaging revealed dural enhancement in 14 patients and no enhancement in three. In four cases, the dura deep to the tumor appeared as a continuous band of enhancement and there was a thin unbroken hypointense zone between the dura and the tumor. Histologic examination in these four patients revealed only dural inflammation without neoplastic spread. In 10 patients, there was a break in the continuity of the enhancement of the underlying dura or a portion of the dura and overlying enhancing tumor could not be separated on MR images. The hypointense zone was focally absent in nine of these cases, and in all 10 there was invasion of the dura by adjacent tumor. Among the other three patients, in whom dural enhancement was not discernible, one had dural invasion by tumor while the other two did not.


Awake Prone Positioning in Non-Intubated Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19.
Awake prone positioning (APP) has been advocated to improve oxygenation and prevent intubation of patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). This paper aims to synthesize the available evidence on the efficacy of APP. We performed a systematic review of proportional outcomes from observational studies to compare intubation rate in patients treated with APP or with standard care. A total of 46 published and 4 unpublished observational studies that included 2,994 subjects were included, of which 921 were managed with APP and 870 were managed with usual care. APP was associated with significant improvement of oxygenation parameters in 381 cases of 19 studies that reported this outcome. Among the 41 studies assessing intubation rates (870 subjects treated with APP and 852 subjects treated with usual care), the intubation rate was 27% (95% CI 19-37%) as compared to 30% (95% CI 20-42%) (P = .71), even when duration of application, use of adjunctive respiratory assist device (high-flow nasal cannula or noninvasive ventilation), and severity of oxygenation deficit were taken into account. There appeared to be a trend toward improved mortality when APP was compared with usual care (11% vs 22%), which was not statistically significant. APP was associated with improvement of oxygenation but did not reduce the intubation rate in subjects with acute respiratory failure due to COVID-19. This finding is limited by the high heterogeneity and the observational nature of included studies. Randomized controlled clinical studies are needed to definitively assess whether APP could improve key outcome such as intubation rate and mortality in these patients.


Cloning of a human cancer cell line (NSCLC-N6) and comparative study of the clones in vitro.
Non-small-cell lung carcinoma (NSCLC) is a particularly serious disease because of its chemoresistance to current treatments. To investigate the nature of his generally innate resistance, we cloned an established cell line (NSCLC-N6) derived from a non-small cell bronchopulmonary carcinoma. Four cell subpopulations (C15, C65, C92 and C98) were isolated from the mother line. These four clones were studied in comparison with each other for cell doubling time in vitro, ploidy, chemosensitivity in vitro, cytogenetic, expression of the oncogene erb-B2 and other tumor markers (Kr, CEA and Chr A). Each clone shows a distinct biologic pattern for various biological parameters. Our results indicated hat cell doubling time (in vitro) increased when the hyperploid population was prevailing. The clones differ in their chemosensitivity to therapeutic agents. This cellular diversity might help to explain why these tumors are chemoresistant. This heterogeneity within NSCLC tumors should be taken into consideration in the choice of treatment.


Triple extraction method enables high quality mass spectrometry-based proteomics and phospho-proteomics for eventual multi-omics integration studies.
Large-scale multi-omic analysis allows a thorough understanding of different physiological or pathological conditions, particularly cancer. Here, an extraction method simultaneously yielding DNA, RNA and protein (thereby referred to as "triple extraction", TEx) was tested for its suitability to unbiased, system-wide proteomic investigation. Largely proven efficient for transcriptomic and genomic studies, we aimed at exploring TEx compatibility with mass spectrometry-based proteomics and phospho-proteomics, as compared to a standard urea extraction. TEx is suitable for the shotgun investigation of proteomes, providing similar results as urea-based protocol both at the qualitative and quantitative levels. TEx is likewise compatible with the exploration of phosphorylation events, actually providing a higher number of correctly localized sites than urea, although the nature of extracted modifications appears somewhat distinct between both techniques. These results highlight that the presented protocol is well suited for the examination of the proteome and modified proteome of this bladder cancer cell model, as efficiently as other more widely used workflows for mass spectrometry-based analysis. Potentially applicable to other mammalian cell types and tissues, TEx represents an advantageous strategy for multi-omics on scarce and/or heterogenous samples.


[Pick's disease in senescence].
We report two patients with Pick's disease in senescence. Patient 1 is a 78-year-old woman. She developed abnormal behavior at the age of 76 years. Neurological examination at age 76 revealed poor rapport, easy angriness, "Denkfaulheit", oral tendency, and slight dementia [WAIS (Wechsler Adult intelligence Scale) total IQ 62]. Cranial CT scan and MRI showed bilateral atrophy of the frontal and temporal lobe, especially of the temporal lobe. Patient 2 is a 73-year-old man. He developped sexual abnormal behavior and "triebhafte Hemmungslossigkeit" at the age of 71 years. Neurological examination at age 72 revealed poor rapport, lack of spontaneity, easy angriness, "Denkfaulheit", and slight dementia [WAIS total IQ 91]. Transient "stehende Redensarten" was noticed. Cranial CT scan and MRI showed bilateral atrophy of the frontal and temporal lobe, especially of the frontal lobe. To our knowledge, Pick's disease with an onset in the senescence is very rare. Pick's disease should be included in the differential diagnosis of abnormal behavior in the senescence.


Revisiting the Derivation of Batterer Subtypes: Towards Profiling the Abuser.
Research directed toward profiling an abuser to develop effective treatment modalities should consider the framework for how batterer subtypes were developed. This article evaluates a seminal work in batterer typology for a review of its method and findings. Findings indicate that the formation of batterer subtypes rely on unstable theory and methods: (a) Variables were not held constant, (b) Theoretical constructs lack clarity, (c) There were unclear boundaries for subtypes. A re-evaluation of this particular line of typology research should address the utility and relevance of these batterer subtypes in an effort to address methodological implications that may help profile and treat abusers.


Applicability of American Joint Committee on Cancer and College of American Pathologists Regression Grading System in Rectal Cancer.
Different tumor grading systems have been proposed to predict the association between tumor response and clinical outcome after preoperative chemoradiotherapy in patients with rectal cancer. The American Joint Committee on Cancer and College of American Pathologists regression grading system was recommended as the standard tumor regression grading system for rectal adenocarcinoma. This study evaluated the clinical applicability of the American Joint Committee on Cancer and College of American Pathologists regression grading system in neoadjuvant-treated patients with rectal cancer. This is a retrospective cohort study based on clinical data from a prospectively maintained colorectal cancer database. This study was performed at a single tertiary referral center. A total of 144 patients with primary locally advanced mid-to-low rectal adenocarcinoma who underwent preoperative long-course chemoradiotherapy and total mesorectal excision between 2003 and 2012 were included. The primary outcome measures were the 5-year overall survival rate, the relapse-free survival rate, the cancer-specific survival rate, and cumulative recurrence rates. Of the 144 patients, 16 (11%) were diagnosed as American Joint Committee on Cancer and College of American Pathologists regression grade 0, 43 patients (30%) as grade 1, 61 patients (42%) as grade 2, and 25 patients (17%) as grade 3.After a median follow-up time of 83 months (range, 3 to 147 mo), 5-year survival estimates for grades 0, 1, 2, and 3, were 93%, 77%, 81%, and 54% for overall survival (p = 0.006); 93%, 82%, 75%, and 55% for relapse-free survival (p = 0.03); and 100%, 86%, 89%, and 63% for cancer-specific survival (p = 0.006). The multivariate Cox regression analyses confirmed the American Joint Committee on Cancer and College of American Pathologists regression grading system as a prognostic factor for overall (p = 0.04), relapse-free (p = 0.02), and cancer-specific survival (p = 0.04). This was a retrospective study. Our study findings confirm the clinical relevance and applicability of the American Joint Committee on Cancer and College of American Pathologists regression grade system as a predictive factor for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/A320.


Prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats.
The objective of the study was to find out the prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats. Male SD rats received different doses of quercetin @ 25mg, 50mg, 100mg and 200mg/Kg BW, 1h prior to hypobaric hypoxia exposure (7,620m, for 6h). Quercetin 50 mg/kg BW supplemented orally 1h prior to hypoxia exposure was considered to be the optimum dose, due to significant reduction (p<0.001) in lung water content and lung transvascular leakage compared to control (hypoxia, 6h). Further, biochemical analysis (ROS, MDA, GSH, GPx, LDH, and albumin) and differential expressions of proteins (IKK-α/β, NFĸB, Nrf-2,TNF-α, ICAM-1, VCAM, P-selectin, Hif-1α, VEGF, TNF-α, TGF-β, INF-γ and IL-4) were determined by western blotting and ELISA. Changes in lung parenchyma were assessed by histopathology. Quercetin (50 mg/kg BW) prophylaxis under hypoxia showed significant reduction in oxidative stress (ROS and MDA), concomitant increase in antioxidants (GSH, GPx and SOD) followed by decreased LDH and albumin extravasation in BAL fluid over hypoxia. Quercetin prophylaxis significantly down regulated hypoxia induced increase in IKKα/β and NFĸB expressions leading to reduction in the levels of pro-inflammatory cytokines (TNF-α and INF-γ) followed by up regulation of anti-inflammatory cytokines (IL-4 and INF-γ) in lungs. Further, hypoxia mediated increase in HIF-1α was stabilized and VEGF levels in lungs were significantly down regulated by quercetin supplementation, leading to reduction in vascular leakage in lungs of rats under hypoxia. However, Quercetin has also enacted as Nrf-2 activator which significantly boosted up the synthesis of GSH under hypoxic condition compared to hypoxia. Histopathological observations further confirmed that quercetin preconditioning has an inhibitory effect on progression of oxidative stress and inflammation via attenuation of NFκB and stabilization HIF-1α in lungs of rats under hypoxia.These studies indicated that quercetin prophylaxis abrogates the possibility of hypobaric hypoxia induced pulmonary edema in rats.


Does intratesticular testosterone administration modify the evolution of transitory testicular ischemia in pre-pubertal rats?
Testicular torsion followed by ischemia results in variable degrees of infertility and until now there appears to be no effective way to recover it. Testosterone participation in the maintenance of male sexual organs and spermatogenesis led us to hypothesize that intratesticular administration could recover ischemic injury. We divided 40 Wistar rats in 2 groups, of 20 each. One group was control and the other underwent a 120-minute testicular ischemia by means of a vascular clamp on the left spermatic cord. Each group was further subdivided in 2 subgroups. The first one was observed and the second received intratesticular testosterone 25 mg. starting on the third day after injury and during the next 7 consecutive days. Half the animals were sacrificed 30 days after injury and the remaining ones after 60 days. Weight, volume, number of seminiferous tubules, histology and spermatogenesis of the same side and contralateral testes were examined. For statistical analysis ANOVA and Fisher's tests were applied. It was found that testosterone was capable of acting upon volume and weight of the left testis (p=0.0001). The animals receiving intratesticular testosterone showed lower testicular weight and volume after 30 and 60 days, respectively. This subgroup also showed a higher number of seminiferous tubules, modified histology and absent spermatogenesis suggesting testicular atrophy. We concluded that intratesticular injection of testosterone 25 mg. once a day during 7 consecutive days after transitory testicular ischemia causes ipsilateral testis atrophy. The animals in control group showed testicular histological recovery 60 days after injury. There were no significant histological differences in the contralateral testes.


Metabolic and hormonal factors controlling food intake.
Food intake is controlled by stimuli acting at the pre- and postabsorptive levels. Preabsorptively, nutrients present in the stomach and intestine elicit signals contributing to meal-ending satiety. Neurally mediated signals and hormonal signals both seem instrumental in the production of this gastrointestinal satiety. Postabsorptively, metabolic receptors in the liver that sense the oxidation of metabolic fuels seem to play an important role in the control of post-meal satiety and meal initiation. These receptors are apparently connected with the brain by vagal afferents, because hepatic vagotomy eliminates the effects of various metabolites and metabolic inhibitors on food intake. Glucoreceptors in the hindbrain that sense the utilization of glucose are probably also involved in control of meal initiation. Finally, humoral factors reflecting the size of the fat depots may also function as feedback signals in the control of feeding.


The role of migration barriers for dispersion of Proliferative Kidney Disease-Balance between disease emergence and habitat connectivity.
Natural and uninterrupted water courses are important for biodiversity and fish population stability. Nowadays, many streams and rivers are obstructed by artificial migration barriers, often preventing the migration of fish. On the other hand, distribution of pathogens by migrating fishes is still a point of concern. Pathogen transport and transmission is a driving force in the dynamics of many infectious diseases. The aim of the study was to investigate the possible consequences of the removal of an artificial migration barrier for the upstream transport of Tetracapsuloides bryosalmonae, the causative agent of Proliferative Kidney Disease (PKD) in brown trout, by migrating fish. To test this question, a river system was selected with a migration barrier separating a PKD positive river from a PKD negative tributary. After removal of the barrier, PKD prevalence and pathology was examined during five years after elimination of the barrier. In the tributary, no PKD was recorded at any time of the survey. By means of unidirectional PIT (passive integrated transponder)-tagging, we confirmed upstream migration of adult brown trout into the tributary during the cold season, presumably for spawning. By eDNA, we confirmed presence of T. bryoalmonae and Fredericella sp., the definitive host, DNA in water from the PKD positive river stretch, but not in the PKD negative tributary. Our study illustrates the importance of the connectivity of streams for habitat maintenance. Although migration of brown trout from a PKD-positive river into a PKD-negative tributary, mainly for spawning, was confirmed, upstream spreading of PKD was not observed.


[Effects of wide band frequency noise on NMDAR1(zeta 1), NMDAR2A(epsilon 1) subunit and ABR threshold in the different area of brain of AD rats poisoned by glutamic acid].
To investigate the change of NMDAR1 (zeta 1) subunit expression in temple cortex, frontal lobe, hippocampus and cerebellum of three different group rat after 98 dB wide frequency noise exposure. Western Blot and RT-PCR technique, combined with auditory brainstem response (ABR) measurement. (1) Expressions of NMDAR1 (zeta 1) subunit in frontal cortex, temple cortex, hippocampus and cerebellum have no difference, but AD model rat is much weaker than the control group. (2) Expression of NMDAR2A (epsilon 1) in temple cortex for physiological saline groups rat have a mostly increase (plus noise), moreover, those are weakest expression in hippocampus. NMDAR1 (zeta 1) subunit in cerebellum have highest expression, moreover, it is weakest in temple cortex. (3) NMDAR1 (zeta1), NMDAR2A (epsilon 1) subunit expression in hippocampus for three groups rat have a down-regulation after adding noise. (4) NMDAR1 (zeta 1), NMDAR2A (epsilon 1) subunit mRNA expression in control group have no remarkable difference in different cortex. (5) Expressions of NMDAR2A (epsilon 1) in frontal temple cortex, hippocampus for AD model rat are less than that of other groups, weakest in cerebellum, weaker in frontal. Wide band frequency noise can reduce the expression of NMDAR1 (zeta 1) subunit in hippocampus and cerebellum of AD model rat, however, the way of regulation is not in the mRNA level. Wide band frequency noise can inhibit the expression of NMDAR2A (epsilon 1) in hippocampus, temple cortex of AD model rat, which has been regulated by mRNA level and have cortex area difference.


The supraorbital keyhole approach via an eyebrow incision applied to obtain the olfactory bulb as a source of olfactory ensheathing cells--radiological feasibility study.
BACKGROUND. The purpose of the study was to test the suitability of supraorbital keyhole craniotomy with an eyebrow incision for obtaining olfactory bulb for therapeutic purposes. METHODS. Fifty three high-resolution axial head computed tomography images of patients with a mean age of 55 ± 15 years were used. The exclusion criterion was a pathology of the anterior skull base. The virtual keyhole supraorbital craniotomy was placed on each side of a three-dimensional skull model with respect to the anatomical landmarks. Trajectories of neurosurgical instrument transitions to the anterior and posterior aspects of olfactory grooves (OGs) were subsequently designed with the use of a neuronavigation planning station and measured with correction allowing the avoidance of collisions with skull base structures. Three types of anatomical configuration were divided, reflecting the extent of the correction needed to reach the bottom of OG. RESULTS. Simulation of the surgical access and consequent metrological analysis was performed on 97 skull sides - 9 (8.5%) sides were excluded due to the large frontal sinus. The mean length of the craniotomy basis was 30.71 mm, lengths of the anterior and posterior trajectories were 53.25 and 58.24 mm, respectively (p < 0.0001). In 37% of cases the value of the corrections exceeded the depth of OG. CONCLUSIONS. The supraorbital keyhole approach via an eyebrow incision may be applied to obtain the olfactory bulb as a source of olfactory ensheathing cells in over 60% of cases. Further verification and evaluation of the surgical handiness based on cadaver specimens is justifiable.


Phenotypic Responses to and Genetic Architecture of Sterility Following Exposure to Sub-Lethal Temperature During Development.
Thermal tolerance range, based on temperatures that result in incapacitating effects, influences species' distributions and has been used to predict species' response to increasing temperature. Reproductive performance may also be negatively affected at less extreme temperatures, but such sublethal heat-induced sterility has been relatively ignored in studies addressing the potential effects of, and ability of species' to respond to, predicted climate warming. The few studies examining the link between increased temperature and reproductive performance typically focus on adults, although effects can vary between life history stages. Here we assessed how sublethal heat stress during development impacted subsequent adult fertility and its plasticity, both of which can provide the raw material for evolutionary responses to increased temperature. We quantified phenotypic and genetic variation in fertility of Drosophila melanogaster reared at standardized densities in three temperatures (25, 27, and 29°C) from a set of lines of the Drosophila Genetic Reference Panel (DGRP). We found little phenotypic variation at the two lower temperatures with more variation at the highest temperature and for plasticity. Males were more affected than females. Despite reasonably large broad-sense heritabilities, a genome-wide association study found little evidence for additive genetic variance and no genetic variants were robustly linked with reproductive performance at specific temperatures or for phenotypic plasticity. We compared results on heat-induced male sterility with other DGRP results on relevant fitness traits measured after abiotic stress and found an association between male susceptibility to sterility and male lifespan reduction following oxidative stress. Our results suggest that sublethal stress during development has profound negative consequences on male adult reproduction, but despite phenotypic variation in a population for this response, there is limited evolutionary potential, either through adaptation to a specific developmental temperature or plasticity in response to developmental heat-induced sterility.


The effects of solutes on the freezing properties of and hydration forces in lipid lamellar phases.
Quantitative deuterium nuclear magnetic resonance is used to study the freezing behavior of the water in phosphatidylcholine lamellar phases, and the effect upon it of dimethylsulfoxide (DMSO), sorbitol, sucrose, and trehalose. When sufficient solute is present, an isotropic phase of concentrated aqueous solution may coexist with the lamellar phase at freezing temperatures. We determine the composition of both unfrozen phases as a function of temperature by using the intensity of the calibrated free induction decay signal (FID). The presence of DMSO or sorbitol increases the hydration of the lamellar phase at all freezing temperatures studied, and the size of the increase in hydration is comparable to that expected from their purely osmotic effect. Sucrose and trehalose increase the hydration of the lamellar phase, but, at concentrations of several molal, the increase is less than that which their purely osmotic effect would be expected to produce. A possible explanation is that very high volume fractions of sucrose and trehalose disrupt the water structure and thus reduce the repulsive hydration interaction between membranes. Because of their osmotic effect, all of the solutes studied reduced the intramembrane mechanical stresses produced in lamellar phases by freezing. Sucrose and trehalose at high concentrations produce a greater reduction than do the other solutes.


Order-disorder character and twinning in the structure of a new synthetic titanosilicate: (Ba,Sr)4Ti6Si4O24 x H2O.
Prismatic crystals of the title compound, up to 100 microm long and {001} twinned by metric merohedry, were obtained as a side-product of a hydrothermal run devoted to synthesizing the heterophyllosilicate lamprophyllite. Single-crystal X-ray diffraction data were collected on a Bruker-AXS Smart Apex diffractometer from a crystal with approximate composition (Ba(0.80)Sr(0.20))(4)Ti6Si4O24 x H2O. The structure was solved and refined as a disordered structure in the space group Cmmm [a(o) = 5.906 (2), b(o) = 20.618 (8), c(o) = 16.719 (6) A, R = 0.089 for 682 reflections with I(o) > 2sigma(I(o))], and then deciphered by the order-disorder (OD) theory as an ordered structure and refined in the space group P2/c [a = 5.906, b = 16.719, c = 10.724 A, beta = 105.99 degrees , R = 0.083 for 1090 reflections with I(o) > 2sigma(I(o))]. The discussion based on the OD theory shows that the refined ordered structure corresponds to one (2M) of two maximum degree of order (MDO) polytypes. The structure of the second MDO polytype (4O) was modelled but not refined because it does not substantially occur in our sample. In the structure, infinite (001) ribbons of Ti octahedra elongated along the [100] direction are connected by (SiO3)4 four-membered rings, thus realising a new type of heteropolyhedral framework. The ribbons are three-octahedra wide and one-octahedron thick; they are formed by linking, via edge-sharing, rutile-type edge-sharing rows of octahedra. This ribbon represents a slice of the octahedral sheet that occurs in perrierite-(Ce), Ce4MgFe2Ti2O8(Si2O7)2. The (Ba,Sr) ions are hosted within two independent [100] narrow channels both delimited by four Ti octahedra and four Si tetrahedra. The disorder of H2O is discussed on the basis of a Raman spectrum.


Stacking as a Key Property for Creating Nanoparticles with Tunable Shape: The Case of Squalenoyl-Doxorubicin.
The development of elongated nanoparticles for drug delivery is of growing interest in recent years, due to longer blood circulation and improved efficacy compared to spherical counterparts. Squalenoyl-doxorubicin (SQ-Dox) conjugate was previously shown to form elongated nanoparticles with improved therapeutic efficacy and decreased toxicity compared to free doxorubicin. By using experimental and computational techniques, we demonstrate here that the specific physical properties of SQ-Dox, which include stacking and electrostatic interactions of doxorubicin as well as hydrophobic interactions of squalene, are involved in the formation of nanoassemblies with diverse elongated structures. We show that SQ-Dox bioconjugate concentration, ionic strength, and anion nature can be used to modulate the shape and stiffness of SQ-Dox nanoparticles. As those parameters are involved in nanoparticle behavior in biological media, these findings could bring interesting opportunities for drug delivery and serve as an example for the design of original nanodrugs with stacking properties tuned for particular clinical purposes.


Technique for serial right and left ventricular endocardial biopsy in dogs.
A method is described for obtaining left and right ventricular endocardial biopsies repeatedly over a period of 3-6 mo in the dog. The left ventricular endocardial biopsy technique consists of the placement of a catheter via the venous route across the atrial septum and into the left ventricle. The biopsy catheter is in turn placed within this transseptal catheter. Tissues obtained by this method were satisfactory for both light and electron microscopic examination. At postmortem examination, only minimal and insignificant damage existed at the biopsy site. Consequently, we recommend this technique for the study of progressive pathologic changes in the endocardium that occur during the course of an experiment which can be identified and quantified in comparison to the control state.


A Prospective, Randomized Study of Surgical Positioning Software Shows Improved Cup Placement in Total Hip Arthroplasty.
Several technologies are available to assist surgeons with acetabular component positioning in total hip arthroplasty. The purpose of this study was to determine whether surgical positioning software would improve cup position compared with fluoroscopy. This prospective, randomized study compared 200 primary total hip arthroplasty cups placed with and without surgical positioning software. All cases were performed by a single surgeon using the direct anterior approach with fluoroscopy. The target abduction and anteversion angles were set at 40° and 20°, respectively, and measured postoperatively. Cup placement time, total fluoroscopy time, and cup position were compared between groups. Mean abduction was 40.4° (range, 32.7°-49.0°) in the software group compared with 42.3° (range, 33.7°-51.1°) in the control group. The cups placed using software were significantly closer to the target abduction angle (P<.001) with fewer outliers. Mean anteversion was 20.8° (range, 11.2°-31.7°) in the software group compared with 21.8° (range, 11.3°-34.3°) in the control group (P=.063). Eighty-seven percent of cups in the software group fell within 5° of the abduction target, compared with only 68% in the control group (P<.01). Cup placement took longer in the software group (7:04 minutes vs 4:58 minutes, P<.001), and 2 seconds more total fluoroscopy time was used in that group as well (12.9 seconds vs 11.1 seconds, P<.001). The software improved both the accuracy and the precision of cup placement, with only modest increases in surgical time and fluoroscopy time. [Orthopedics. 2019; 42(1):42-47.].


The Association between Non-Medical Prescription Drug Use and Suicidal Behavior among United States Adolescents.
Adolescence represents a vulnerable time for the development of both drug use/abuse and mental illness. Although previous research has substantiated a relationship between drug use and suicidal behavior, little research has examined this relationship with non-medical prescription drug use. Given the growing prevalence of non-medical prescription drug use (NMPDU) among adolescents, this study explored the association between NMPDU and suicidal behavior. Nationally representative data were derived from 16, 410 adolescents who completed the 2009 National Youth Risk Behavior Survey. Approximately 19.8% of participants reported lifetime NMPDU. NMPDU was associated with significantly increased odds of suicidal behavior (P < 0.01), with seriously considering attempting suicide and making a plan about attempting suicide representing the strongest correlates for males and females. Results suggest the importance of 1) continued reinforcement of drug education programs in high school begun at earlier ages and 2) mental health care and screenings among adolescents.


[Fresh injuries of the tractus intermedius of the extensor aponeurosis. Diagnosis, classification and therapy].
A test for early diagnosis of closed isolated ruptures of the central slip of the extensor hood is described. Five different lesions are described. Conservative treatment is adequate for ruptures with undislocated bone fragments. Operative treatment is required when the central slip has been avulsed with a dislocated bone fragment, in cases of combined lesions of the PIP joint (including central slip, collateral ligaments and/or the palmar plate) and finally open lesions. An isolated closed rupture of the central slip is a relative indication for surgery and is treated conservatively under specified circumstances.


MAPKDB: A MAP kinase database for signal transduction element identification.
The mitogen activated protein kinase (MAPK) cascade is a central signal transduction platform, ubiquitous within the eukaryotes. MAPKs function prominently in different essential cellular processes such as proliferation, differentiation, survival and defense to pathogen attack. The 32 MAPKs of Glycine max (soybean) have been examined functionally to determine if they have any defense role, focusing in on infection by the plant-parasitic nematode Heterodera glycines. Of these 32 MAPKs, 9 have been shown to have a defense function. Hence, the Mitogen Activated Protein Kinase database (MAPKDB) has been developed to assist in such research. The MAPKDB allows users to search the annotations with sequence data for G. max transgenic lines undergoing overexpression (OE) or RNA interference (RNAi) of its defense map kinases. These defense MAPKs include map kinase 2 (MPK2), MPK3, MPK4, MPK5, MPK6, MPK13, MPK16, and MPK20. The database also contains data analysis information for each sample that helps to detect the differential expression of the genes identified within these samples. The database also contains data for each sample that helps to detect the differential expression of the genes identified within these samples. The database has been developed to manage G. max MAPK sequences with sequence alignment for 18 different samples along with two additional OE and RNAi control experiments for a total of 20.


Characteristic and mercury adsorption of activated carbon produced by CO2 of chicken waste.
Preparation of activated carbon from chicken waste is a promising way to produce a useful adsorbent for Hg removal. A three-stage activation process (drying at 200 degrees C, pyrolysis in N2 atmosphere, followed by CO2 activation) was used for the production of activated samples. The effects of carbonization temperature (400-600 degrees C), activation temperature (700-900 degrees C), and activation time (1-2.5 h) on the physicochemical properties (weight-loss and BET surface) of the prepared carbon were investigated. Adsorptive removal of mercury from real flue gas onto activated carbon has been studied. The activated carbon from chicken waste has the same mercury capacity as commercial activated carbon (Darco LH) (Hg(v): 38.7% vs. 53.5%, Hg(0): 50.5% vs. 68.8%), although its surface area is around 10 times smaller, 89.5 m2/g vs. 862 m2/g. The low cost activated carbon can be produced from chicken waste, and the procedure is suitable.


Life Science Majors' Math-Biology Task Values Relate to Student Characteristics and Predict the Likelihood of Taking Quantitative Biology Courses.
Expectancy-value theory of achievement motivation predicts that students' task values, which include their interest in and enjoyment of a task, their perceptions of the usefulness of a task (utility value), and their perceptions of the costs of engaging in the task (e.g., extra effort, anxiety), influence their achievement and academic-related choices. Further, these task values are theorized to be informed by students' sociocultural background. Although biology students are often considered to be math-averse, there is little empirical evidence of students' values of mathematics in the context of biology (math-biology task values). To fill this gap in knowledge, we sought to determine 1) life science majors' math-biology task values, 2) how math-biology task values differ according to students' sociocultural background, and 3) whether math-biology task values predict students' likelihood of taking quantitative biology courses. We surveyed life science majors about their likelihood of choosing to take quantitative biology courses and their interest in using mathematics to understand biology, the utility value of mathematics for their life science career, and the cost of doing mathematics in biology courses. Students on average reported some cost associated with doing mathematics in biology; however, they also reported high utility value and were more interested in using mathematics to understand biology than previously believed. Women and first-generation students reported more negative math-biology task values than men and continuing-generation students. Finally, students' math-biology task values predicted their likelihood of taking biomodeling and biostatistics courses. Instructional strategies promoting positive math-biology task values could be particularly beneficial for women and first-generation students, increasing the likelihood that students would choose to take advanced quantitative biology courses.


Chronotype and personality factors of predisposition to seasonal affective disorder.
The study aimed to recognize the personality factors of a predisposition to seasonal mood fluctuations in a non-clinical sample. A group of 101 subjects (57 women, 44 men; mean age 26.4 ± 6.5 years) completed a battery of tests comprising a Seasonal Pattern Assessment Questionnaire (SPAQ), Chronotype Questionnaire (ChQ), a NEO-Five Factor Inventory and a Coping Inventory for Stressful Situations (CISS). A smaller sample (n = 44) completed a Winter Blues Scale (WBS). Women scored significantly higher than men in seasonality (p = 0.014), neuroticism (p = 0.049), agreeableness (p = 0.010), and avoidance-oriented coping style (p = 0.041). Subjects with seasonal affective disorder (SAD) (n = 41) or sub-SAD (n = 33), as diagnosed with SPAQ, exhibited higher levels of neuroticism (p = 0.017) and openness (p = 0.016) in comparison to non-SAD individuals. The latter declared a less frequent avoidance coping style. Both measures of seasonality, i.e. the SPAQ Global Seasonality Score and WBS, correlated significantly (r = 0.28 and 0.44, respectively) with the subjective amplitude of the circadian rhythm, as described with the "distinctness" scale of ChQ. Female gender, neuroticism and openness were confirmed as factors linked to seasonal mood variability. Additionally, the study revealed an association between susceptibility to mild winter depression and an avoidance-oriented coping style. The avoidance coping style was correlated positively with all the aspects of seasonality described by SPAQ (correlation coefficients from 0.21 to 0.34). Both sub-types of avoidance-oriented style, i.e. distraction and social diversion, were associated with marked subjective seasonal changes in sleep length, mood and the energy level. While the subjective amplitude of circadian rhythm proved to be connected with seasonality, the subjective acrophase of the rhythm (morningness-eveningness preference) did not. It may be hypothesized that sensitivity to natural environmental conditions/synchronizers is a separate individual trait shaping the subject's proneness to energy and mood changes both in diurnal and year scale, i.e. circadian and seasonal mood variations.


Enhanced Efficiency and Stability of an Aqueous Lead-Nitrate-Based Organometallic Perovskite Solar Cell.
We investigate the stability of an active organometallic perovskite layer prepared from a two-step solution procedure, including spin coating of aqueous lead nitrate (Pb(NO3)2) as a Pb2+ source and sequential dipping into a methylammonium iodide (CH3NH3I) solution. The conversion of CH3NH3PbI3 from a uniform Pb(NO3)2 layer generates PbI2-free and large-grain perovskite crystallites owing to an intermediate ion-exchange reaction step, resulting in improved humidity resistance and, thereby, improved long-term stability with 93% of the initial power conversion efficiency (PCE) after a period of 20 days. The conventional fast-converted PbI2-dimethylformamide solution system leaves small amounts of intrinsic PbI2 residue on the resulting perovskite and MAPbI3 crystallites with uncontrollable sizes. This accelerates the generation of PbI2 and the decomposition of the perovskite layer, resulting in poor stability with less than 60% of the initial PCE after a period of 20 days.


Persistence of epoxy-based sealer residues in dentin treated with different chemical removal protocols.
The presence of residual endodontic sealer in the pulp chamber may cause discoloration of the dental crown and interfere with the adhesion of restorative materials. The aim of this study was to compare the efficacy of different solvents in removing residues of an epoxy resin-based sealer (AH Plus) from the dentin walls of the pulp chamber, by scanning electron microscopy (SEM). Forty-four bovine incisor dental crown fragments were treated with 17% EDTA and 2.5% NaOCl. Specimens received a coating of AH Plus and were left undisturbed for 5 min. Then, specimens were divided in four groups (n = 10) and cleaned with one of the following solutions: isopropyl alcohol, 95% ethanol, acetone solution, or amyl acetate solution. Negative controls (n = 2) did not receive AH Plus, while in positive controls (n = 2) the sealer was not removed. AH Plus removal was evaluated by SEM, and a score system was applied. Data were analyzed by Kruskal-Wallis and Dunn tests. None of the solutions tested was able to completely remove AH Plus from the dentin of the pulp chamber. Amyl acetate performed better than 95% ethanol and isopropyl alcohol (p < 0.05), but not better than acetone (p > 0.05) in removing the sealer from dentin. No significant differences were observed between acetone, 95% ethanol, and isopropyl alcohol (p > 0.05). It was concluded that amyl acetate and acetone may be good options for cleaning the pulp chamber after obturation with AH Plus.


Sleep deprivation induces structural changes in the adult rat testis: The protective effects of olive oil.
Sleep deprivation (SD) is a common problem in today's stressful lifestyle and have physiological consequences, including reproductive dysfunction and infertility. As an antioxidant, olive oil may be effective in reducing testicular and spermatological damage by decreasing the production of free radicals. This study investigated the effects of olive oil on sperm quality and testicular structure using stereological methods to assess rats with SD. When comparing SD group to grid floor+distilled water (GR) group, we found that the sperm count and motility, as well as the percentage of slow progressive sperm was significantly lower in SD group (p<0.05), but the percentage of immotile sperm was higher (p<0.01). However, no improvement was observed in sperm count or motility after concomitant treatment of SD group with olive oil. Stereological examinations revealed no significant change in the total volumes of the seminiferous tubules, interstitial tissue, and germinal epithelium in the study groups. Conversely, the total number of testicular cell types was significantly lower in SD group than in GR group. Although the total number of Sertoli and Leydig cells was significantly higher in the SD+olive oil group than in the untreated SD group, no significant difference in the total number of other testicular cell types was observed between the two groups. SD potentially induced structural changes in testis that affected sperm count and motility. However, olive oil only improved the total number of Sertoli and Leydig cells in the animals with SD and did not improve sperm count and motility.


[Medicine, physicians and medical ethics in Jewish tradition through the ages].
Medicine has always had a place of honor in the Jewish heritage. Since Biblical times, the sources of Judaism have valued the physician's activities and seen them as a partnership with God's deeds. Later, in the times of the Mishna and the Talmud, a model of scholars evolved who were not only learned sages but also had extensive medical and scientific knowledge. Their dealings with various issues in medical ethics were the basis for deliberation on questions that appeared throughout history on the advancement of medical science. The various sources from this period show the sages' sensitivity regarding the subject of human life, saving lives and the importance of the availability of medicine for all segments of the population. During the years following the completion of the Talmud, the medical profession was common among the Jews and they excelled in this field. Jewish doctors left behind a Legacy of values in medicine. Hebrew was considered a significant Language in the medical field and was cited in various medical texts such as in the book written by Vesalius, the "father" of modern anatomy. The rapid progress of medicine poses new challenges in bioethics. There is a need for physicians with extensive medical knowledge along with an understanding of ethical issues in order to offer solutions to new situations. Knowledge of the Jewish literature throughout the ages on a variety of subjects and the essential values which are their foundation can contribute to the modern discussion on biomedical questions. This is even more important in Israeli society where many of the laws are formed based on Jewish values. Engagement with Jewish medical ethics can help in educating physicians to have the ability to contribute to public debate and legislation in a way that would balance between the values and needs which an ethical issue raises.


Attitudinal, Experiential, and Situational Predictors of Sexual Assault Perpetration.
Past research demonstrates that sexual assault perpetration is caused by multiple factors including attitudes, early experiences, and situational factors. In this study, 343 college men described either a sexual assault they had committed or their worst date. Discriminant function analysis indicated that attitudes about gender roles and alcohol, number of consensual sex partners, how well the man knew the woman, how isolated the setting was, alcohol consumption during the event, the man's misperception of the woman's cues during the event, and prior consensual sexual activity between the man and the woman discriminated between sexual assaults and worst dates. Additionally, tactics used to obtain sex, self attributions, the perceived seriousness of the assault, and the extent to which it disrupted relationships with others significantly discriminated between men who committed forced sexual contact, sexual coercion, and rape. These results demonstrate the importance of considering both individual characteristics and situational factors in theories and prevention activities.