[Variance analysis of Cd2+, Zn2+, and Mn2+ effect on membrane Na+,K(+)-ATPase activity of loach embryos].
The evaluation of influences Cd2+, Zn2+, Mn2+ in concentrations 10(-6), 10(-5), 10(-4) M (factor of dose) on the Na+, K(+)-ATP-ase activity in the early period of development (60-330 min.) of loach embryos (time factor) using one- and two-factor analysis of variance has been performed. It has been detected, that the changes of enzyme activity are mainly caused by action of the explored cations and do not depend on time of embryos development. The most influence on activity in the indicated period of embryos development of loach renders Cd2+ in concentration 10(-4) M, relative value of its influence being 95.7% (p = 0.01). Substantial concentration dependence of the Na+, K(+)-ATP-ase activity is exposed to the action of each of cations. The values of the influence of their concentration changes during the studied period of development differ insignificantly for all cations and make 76.2-77.5% (p < 0.01).


[Published effects of screening in parental and child health care].
A summary of research data on the evaluation of eight screening activities in Child Health Care in the Netherlands. Literature review. Department of Public Health, Erasmus University Rotterdam, the Netherlands. The literature was reviewed regarding screening effects on congenital hip pathology, congenital heart disease, retained testis, hydrocephalus, hearing loss, psychomotor retardation, visual disabilities, and phenylketonuria (PKU) and congenital hypothyroidism (CHT). For 8 types of screenings 17 targets could be established. Targets were defined in terms of a decrease of the adverse outcome of the diseases as a result of the screening. The efficacy of the screening for 3 of these targets (decrease of the adverse outcomes of PKU and CHT and needless orchidopexy) was convincingly established. For the other targets the available data were insufficient. Data on undesirable effects of screening were scarce. For 6 of the 8 screening activities some data on test properties were available. Research data on the effects of screening in Child Health Care in the Netherlands are incomplete. It is important to improve the scientific basis of these prevention activities.


Myoclonic movements of the elbow and wrist as a rare complication of supracondylar humerus fracture in a child.
Supracondylar humerus fractures are associated with neurological complications. This report describes a child who suffered from persistent myoclonus-like movements of the elbow and wrist as a consequence of a previous displaced fracture. Symptoms were progressive. Seven years later, sensation was decreased in the ulnar nerve distribution. Palpation of the ulnar nerve exacerbated the myoclonic jerks. As symptoms progressed, electoneuromyography became abnormal. Cubital tunnel release and anterior transposition of the ulnar nerve were required to reach full recovery. Long-term outcome was excellent. In conclusion, myoclonus-like movements are a rare complication of supracondylar humerus fractures, resulting from ulnar nerve injury.


Biogeo-optics: particle optical properties and the partitioning of the spectral scattering coefficient of ocean waters.
We propose a direct method of partitioning the particulate spectral scattering coefficient of the marine hydrosol based on the concurrent determination of the concentrations of particulate mineral and organic matter (the total mass of optically active scattering material exclusive of water) with the particulate spectral scattering coefficient. For this we derive a Model II multiple linear regression model. The multiple linear regression of the particulate spectral scattering coefficient against the independent variables, the concentrations of particulate inorganic matter and particulate organic matter, yields their mass-specific spectral scattering cross sections. The mass-specific spectral scattering cross section is simply the particle scattering cross section normalized to the particle mass, a fundamental optical efficiency parameter for the attenuation of electromagnetic radiation [Absorption and Scattering of Light by Small Particles, (Wiley-Interscience, 1983), pp. 80-81, 289]. It is possible to infer the optical properties of the suspended matter from the mass-specific spectral scattering cross sections. From these cross sections we partition the particulate spectral scattering coefficient into its major components.


Nitrous oxide scavenging in dental surgery. II. An evaluation of a local exhaust system.
A deleterious effect on physical and mental health of chronic exposure to trace concentrations of nitrous oxide has been reported. Despite careful handling and sedation technique, gas-tight equipment and breathing circuits, a non-recirculation ventilation system and efficient expired and excess gas scavenging equipment, high local nitrous oxide concentrations may occur e.g. with the use of poorly fitting nose masks and/or the administration of nitrous oxide to uncooperative patients. Local exhaust systems have proved valuable in such situations. The aim of this study was to determine the optimal location of a local exhaust system in relation to leakage in an experimental situation with high local nitrous oxide contamination in a dental surgery and to establish the necessary evacuation capacity of such a local exhaust system. Four different evacuation capacities, 140, 200, 260 and 300m3/h, and three different distances from the patient to the nozzle of the local exhaust system, 10, 20, 30 cm, were tested. With the local exhaust system used in this study, an optimal capacity of about 200 m3/h and a position 20 cm or less in front of the patient seem to meet requirements of occupational exposure to nitrous oxide set by national boards of safety and health.


Echolocating bats cry out loud to detect their prey.
Echolocating bats have successfully exploited a broad range of habitats and prey. Much research has demonstrated how time-frequency structure of echolocation calls of different species is adapted to acoustic constraints of habitats and foraging behaviors. However, the intensity of bat calls has been largely neglected although intensity is a key factor determining echolocation range and interactions with other bats and prey. Differences in detection range, in turn, are thought to constitute a mechanism promoting resource partitioning among bats, which might be particularly important for the species-rich bat assemblages in the tropics. Here we present data on emitted intensities for 11 species from 5 families of insectivorous bats from Panamá hunting in open or background cluttered space or over water. We recorded all bats in their natural habitat in the field using a multi-microphone array coupled with photographic methods to assess the bats' position in space to estimate emitted call intensities. All species emitted intense search signals. Output intensity was reduced when closing in on background by 4-7 dB per halving of distance. Source levels of open space and edge space foragers (Emballonuridae, Mormoopidae, Molossidae, and Vespertilionidae) ranged between 122-134 dB SPL. The two Noctilionidae species hunting over water emitted the loudest signals recorded so far for any bat with average source levels of ca. 137 dB SPL and maximum levels above 140 dB SPL. In spite of this ten-fold variation in emitted intensity, estimates indicated, surprisingly, that detection distances for prey varied far less; bats emitting the highest intensities also emitted the highest frequencies, which are severely attenuated in air. Thus, our results suggest that bats within a local assemblage compensate for frequency dependent attenuation by adjusting the emitted intensity to achieve comparable detection distances for prey across species. We conclude that for bats with similar hunting habits, prey detection range represents a unifying constraint on the emitted intensity largely independent of call shape, body size, and close phylogenetic relationships.


Protein-RNA interactions in belladonna mottle virus investigated by laser Raman spectroscopy.
Raman difference spectroscopy of the belladonna mottle virus (BDMV) and its separated RNA and protein components indicates that molecular interaction occurs between the single-stranded RNA genome and capsid subunits. The molecular interactions that stabilize the virion at pH 5.0 are altered or eliminated at pH 8.0, even though release of the RNA from the capsid is prevented by the addition of divalent metal cations (Ca2+). From the perturbations that occur to Raman lines of cytosine and adenine rings of the encapsidated RNA molecule between pH values of 5.0 and 8.0, it is concluded that cytosines are protonated in significant numbers at the conditions which maintain the native virus structure and that the stacking of adenines is altered by changes in pH. The degree of protonation of RNA bases can be reduced by elevation of the pH to 8.0 for encapsidated RNA or by release of the RNA from the capsid at pH 5.0. Although the protein groups that interact with the viral RNA cannot be identified unambiguously from the Raman spectra, it is apparent that the molecular environments of aromatic amino acid side chains are altered with the same changes in pH (from 5.0 to 8.0) that perturb the cytosine and adenine ring structures. No significant change in secondary structures of the capsid subunit can be detected with changes in pH or with RNA release. On the other hand, the characteristic Raman lines of the phosphate groups of packaged RNA differ from those of naked RNA at all pH values examined, most likely as a result of specific electrostatic binding of divalent cations to RNA phosphates within the virus shell.


Low rate of subsequent surgery and serious complications following intra-articular steroid injection for base of thumb osteoarthritis: national cohort analysis.
Intra-articular steroid injection is commonly used to treat base of thumb osteoarthritis (BTOA), despite a lack of large-scale data on safety and effectiveness. We estimate the incidence of serious complications and further procedures following BTOA injection, including the risk of post-operative serious surgical site infection for subsequent operative intervention. Hospital Episode Statistics data linked to mortality records from 1 April 1998 to 31 March 2017 were used to identify all BTOA injections undertaken in adults in the National Health Service secondary care in England. Patients were followed up longitudinally until death or 31 March 2017. A multivariable regression with a Fine and Gray model adjusting for the competing risk of mortality in addition to age, sex and socioeconomic deprivation was used to identify factors associated with progression to further procedure. Secondary outcomes included serious complications after injection and subsequent surgical site infection. A total of 19 120 primary injections were performed during the 19-year period in 18 356 patients. Of these 76.5% were female; mean age 62 years (s.d. 10.6); 50.48% underwent further procedure; 22.40% underwent surgery. Median time to further intervention was 412 days (IQR 110-1945). Female sex was associated with increased risk of proceeding to surgery. Serious complication rate following injection was 0.04% (0.01-0.08) within 90 days. Of those proceeding to surgery 0.16% (0.06-0.34) presented with a wound infection within 30 days and 90 days, compared with an overall post-operative wound infection rate of 0.03% (0.02-0.05). Very low rates of serious complications were identified following BTOA injections performed in secondary care; only one in five patients proceeded to subsequent surgery. clinicaltrials.gov, https://www.clinicaltrials.gov, NCT03573765.


[Health care process in neurology].
The clinical assistance to patients with neurological disorders is composed of different clinical procedures performed in a sequential order. It has many similarities to the industrial procedures. The patient with a neurological problem will receive clinical assistance as outpatient, in-patient or in the emergency department. Through out all theses events we can identify different aspects of the health care management. It is important to take into account several distinctive aspects of the neurological disorders such as its high prevalence, chronicity and important morbidity, the complexity of the diagnostic techniques and treatment, as well as the active participation of the patient in the illness. The management of the clinical procedures involves the development of clinical pathways and guidelines as essential tools to improve the quality of clinical assistance and to reduce the variability within clinical practice.


Heat treatment of pre-hydrolyzed silane increases adhesion of phosphate monomer-based resin cement to glass ceramic.
This study evaluated the influence of different forms of heat treatment on a pre-hydrolyzed silane to improve the adhesion of phosphate monomer-based (MDP) resin cement to glass ceramic. Resin and feldspathic ceramic blocks (n=48, n=6 for bond test, n=2 for microscopy) were randomly divided into 6 groups and subject to surface treatments: G1: Hydrofluoric acid (HF) 9.6% for 20 s + Silane + MDP resin cement (Panavia F); G2: HF 9.6% for 20 s + Silane + Heat Treatment (oven) + Panavia F; G3: Silane + Heat Treatment (oven) + Panavia F; G4: HF 9.6% for 20 s + Silane + Heat Treatment (hot air) + Panavia F; G5: Silane + Heat Treatment (hot air) + Panavia F; G6: Silane + Panavia F. Microtensile bond strength (MTBS) test was performed using a universal testing machine (1 mm/min). After debonding, the substrate and adherent surfaces were analyzed using stereomicroscope and scanning electron microscope (SEM) to categorize the failure types. Data were analyzed statistically using two-way test ANOVA and Tukey's test (=0.05). Heat treatment of the silane containing MDP, with prior etching with HF (G2: 13.15 ± 0.89a; G4: 12.58 ± 1.03a) presented significantly higher bond strength values than the control group (G1: 9.16 ± 0.64b). The groups without prior etching (G3: 10.47 ± 0.70b; G5: 9.47 ± 0.32b) showed statistically similar bond strength values between them and the control group (G1). The silane application without prior etching and heat treatment resulted in the lowest mean bond strength (G6: 8.05 ± 0.37c). SEM analysis showed predominantly adhesive failures and EDS analysis showed common elements of spectra (Si, Na, Al, K, O, C) characterizing the microstructure of the glass-ceramic studied. Heat treatment of the pre-hydrolyzed silane containing MDP in an oven at 100 °C for 2 min or with hot air application at 50 ± 5 ºC for 1 min, was effective in increasing the bond strength values between the ceramic and resin cement containing MDP.


Evaluation of Gentamicin and Lidocaine Release Profile from Gum Acacia-crosslinked-poly(2-hydroxyethylmethacrylate)-carbopol Based Hydrogels.
No doubt, the prevention of infection is an indispensable aspect of the wound management, but, simultaneous wound pain relief is also required. Therefore, herein this article, incorporation of antibiotic agent 'gentamicin' and pain relieving agent 'lidocaine' into hydrogel wound dressings, prepared by using acacia gum, carbopol and poly(2-hydroxyethylmethacrylate) polymers, has been carried out. The hydrogels were evaluated as a drug carrier for model drugs gentamicin and lidocaine. Synthesis of hydrogel wound dressing was carried out by free radical polymerization technique. The drug loading was carried out by swelling equilibrium method and gel strength of hydrogels was measured by a texture analyzer. Porous microstructure of the hydrogel was observed in cryo-SEM images. The hydrogel showed mesh size 37.29 nm, cross-link density 2.19× 10-5 mol/cm3, molecular weight between two cross-links 60.25× 10-3 g/mol and gel strength 0.625±0.112 N in simulated wound fluid. It is concluded that the pH of swelling medium has influenced the network structure of hydrogel i.e., molecular weight of the polymer chain between two neighboring cross links, crosslink density and the corresponding mesh size. A good correlation was established between gel strength and network parameters. Cryo-SEM images showed porous morphology of hydrogels. These hydrogels were found to be biodegradable and antimicrobial in nature. Drug release occurred through Fickian diffusion mechanism and release profile was best fitted in first order model. Overall it is concluded that modification in GA has led to formation of a porous hydrogels for wound dressing applications.


Pressure dependent aerosol formation from the cyclohexene gas-phase ozonolysis in the presence and absence of sulfur dioxide: a new perspective on the stabilisation of the initial clusters.
The ozonolysis of cyclohexene is studied with respect to the pressure dependent formation of stable gas-phase products and secondary organic aerosol (SOA) as well as the influence of the presence of SO(2). In addition the rate coefficient for the initial reaction cyclohexene + O(3) was determined at 295 K. The observed increase in CO and ethene yields at low pressures and the absence of ketene in the product spectrum confirm previously proposed reaction pathways forming these decomposition products. An enhanced ethene formation at pressures below 300 mbar coincides with drastically decreased aerosol yields pointing to a high influence on SOA formation of chemical activation driven dynamics in the vinylhydroperoxide channel. The static reactor experiments at 450 mbar in the presence of SO(2) in the present study showed a similar sensitivity of additional particle formation to H(2)SO(4) number densities as found in near-atmospheric flow reactor experiments [Sipiläet al., Science, 2010, 327, 1243], a surprising result with regard to the very different experimental approaches. At low pressures (around 40 mbar) no significant new particle formation is observed even at high H(2)SO(4) concentrations. These findings indicate that the collisional stabilisation of initial clusters is an important aspect for SOA formation processes involving sulfuric acid and organic compounds. The results may have implications for geo-engineering strategies based on stratospheric sulfur injection, but caution is mandatory when room temperature laboratory results are extrapolated to stratospheric conditions.


Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1.
Multiple myeloma (MM) is characterized by the malignant expansion of differentiated plasma cells. Although many chemotherapeutic agents display cytotoxic activity toward MM cells, patients inevitably succumb to their disease because the tumor cells become resistant to the anticancer drugs. The cancer stem cell hypothesis postulates that a small subpopulation of chemotherapy-resistant cancer cells is responsible for propagation of the tumor. Herein we report that efflux of the pluripotent stem cell dye CDy1 identifies a subpopulation in MM cell lines characterized by increased expression of P-glycoprotein, a member of the ABC (ATP-binding cassette) superfamily of transporters encoded by ABCB1. We also demonstrate that ABCB1-overexpressing MM cells are resistant to the second-generation proteasome inhibitor carfilzomib that recently received accelerated approval for the treatment of therapy-refractive MM by the U.S. Food and Drug Administration. Moreover, increased resistance to carfilzomib in sensitive MM cells following drug selection was associated with upregulation of ABCB1 cell-surface expression which correlated with increased transporter activity as measured by CDy1 efflux. We further show that chemosensitization of MM cells to carfilzomib could be achieved in vitro by cotreatment with vismodegib, a hedgehog pathway antagonist which is currently in MM clinical trials. CDy1 efflux may therefore be a useful assay to determine whether high expression of ABCB1 is predictive of poor clinical responses in MM patients treated with carfilzomib. Our data also suggest that inclusion of vismodegib might be a potential strategy to reverse ABCB1-mediated drug resistance should it occur.


Relationship of Two-Hour Plasma Glucose and Abdominal Visceral Fat with Bone Mineral Density and Bone Mineral Content in Women with Different Glucose Metabolism Status.
Several studies have reported the relationship of diabetes mellitus (DM) and obesity with bone mineral density (BMD), but the conclusions remain unclear. This study aimed to provide more information for the relationship of plasma glucose and abdominal visceral fat (AVF) with BMD and bone mineral content (BMC) in women with different glucose metabolism status. Patients were screened by oral glucose tolerance test (OGTT) and were divided into three groups: normal glucose tolerance (NGT, n=132), pre-diabetes mellitus (pre-DM, n=28) and newly diagnosed type 2 DM (T2DM, n=27) groups. Plasma glucose concentrations, anthropometric measurements, body composition, and BMD were measured. Analysis of variance (ANOVA), pearson correlation, and multiple linear regression models were used to evaluate the relationship between BMD, plasma glucose, AVF, and other variables. The percentage of subjects with osteoporosis or low BMD was 29.9%, and 66.7% subjects in T2DM group were significantly higher than that in the pre-DM (28.6%) and NGT (22.7%) groups (p=0.005 and p<0.001, respectively). Both BMD at femoral neck (FN) and lumbar spine (LS) of T2DM group were lower than those in NGT group (p=0.009 and p=0.003, respectively), and BMC of T2DM group was lower than those of NGT and pre-DM groups (p<0.001). The results of statistical analysis revealed that both two-hour plasma glucose (2-h PG) and age showed negative correlation with BMC, FN BMD, and LS BMD. AVF showed positive correlation with BMC and LS BMD. Furthermore, the lean mass (LM) showed independent positive effects on BMC. Our findings suggest that 1) Age is a strong negative predictor of bone mass. 2) A direct negative effect of increasing 2-h PG might be more prominent at bone mass in women. 3) A moderate increase in AVF is beneficial to bone mass, while excessive increase might be harmful. 4) LM is a positive predictor of BMC.


Adsorption of organic contaminants by graphene nanosheets, carbon nanotubes and granular activated carbons under natural organic matter preloading conditions.
The effect of NOM preloading on the adsorption of phenanthrene (PNT) and trichloroethylene (TCE) by pristine graphene nanosheets (GNS) and graphene oxide nanosheet (GO) was investigated and compared with those of a single-walled carbon nanotube (SWCNT), a multi-walled carbon nanotube (MWCNT), and two coal based granular activated carbons (GACs). PNT uptake was higher than TCE by all adsorbents on both mass and surface area bases. This was attributed to the hydrophobicity of PNT. The adsorption capacities of PNT and TCE depend on the accessibility of the organic molecules to the inner regions of the adsorbent which was influenced from the molecular size of OCs. The adsorption capacities of all adsorbents decreased as a result of NOM preloading due to site competition and/or pore/interstice blockage. However, among all adsorbents, GO was generally effected least from the NOM preloading for PNT, whereas there was not observed any trend of NOM competition with a specific adsorbent for TCE. In addition, SWCNT was generally affected most from the NOM preloading for TCE and there was not any trend for PNT. The overall results indicated that the fate and transport of organic contaminants by GNSs and CNTs type of nanoadsorbents and GACs in different natural systems will be affected by water quality parameters, characteristics of adsorbent, and properties of adsorbate.


Persistent Behavioral Deficits in Rats after Parasagittal Fluid Percussion Injury.
Although traumatic brain injury (TBI) is now considered a chronic disease, few studies have investigated the long-term behavioral deficits elicited by a well-established rodent model of injury. Here we evaluate behavioral measures, commonly used in TBI research, to determine which tests are useful for studying long-term effects of brain injury in rats. Male Sprague-Dawley rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid-percussion injury (FPI), sham injury, or maintenance as naïve cohorts. Rats underwent neuroscore, beam-balance, and beam-walk tests for 3 days after injury. Subsequently, in separate groups at 3, 6, or 12 months, they were re-tested on the same tasks followed by a working memory version of the Morris water maze. On post-injury days (PIDs) 1-3, significant effects of injury on neuroscore, beam-balance, and beam-walk were observed. Differences in the beam-walk task were not detectable at any of the later time-points. However, deficits persisted in beam-balance out to 3 months and neuroscore out to 6 months. Working memory deficits persisted out to 12 months, at which time a reference memory deficit was also evident. These data suggest that balance and motor coordination recovered more quickly than neurological deficits. Furthermore, while deficits in working memory remained stable over the 12-month period, the late onset of the reference memory deficit points to the progressive nature of the injury, or an age/TBI interaction. In conclusion, standard behavioral tests are useful measures of persistent behavioral deficits after parasagittal FPI and provide evidence that TBI is a chronic condition that can change over time and worsen with age.


Type-A influenza viruses in the feces of migratory waterfowl.
Type-A influenza viruses were commonly recovered from cloacal swab specimens from migratory waterfowl. Experiments indicated that the the virus replicated in various cells of the digestive tract.


Improving processes to capture present-on-admission pressure ulcers.
To enhance the learner's competence with information geared toward improving processes to capture present-on-admission pressure ulcers. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Analyze the research study presented and its effects regarding identification of present-on-admission pressure ulcers (PrUs) and reduction of healthcare-acquired conditions.2. Identify implications of proper admission skin assessment and documentation on reimbursement by the Centers for Medicare & Medicaid Services.3. Implement recommendations from the research study for ways to improve PrU documentation on admission assessment. This study was designed to determine if a process could be built to accurately capture present-on-admission (POA) pressure ulcers (PrUs). Will a formalized electronic process designed to identify, communicate, and document assessment findings of POA PrUs from clinical nurses to admitting physicians reduce missed identification of POA PrUs, improve communication processes, improve physicians' documentation, and improve reimbursement for the hospital? A before-and-after study design in a single site over a 4-month period compared with the same period during the previous 2 years. An acute-care, 333-bed hospital in the Midwestern United States.Nurses were the primary study population. The wound assessment screen in the electronic medical record (EMR) was revised to include a new prompt for POA documentation and communication to the admitting physician of the assessment findings. An increase in POA PrU reporting and reduction in hospital-acquired condition (HAC) reported PrUs. A statistically significant change (2010: P < .01, z = 2.507; 2011: P < .01, z = 2.632) was found for POA; HAC also had a statistically significant change (2010: P = .02, z = 2.411; 2011: P < .01, z = 2.781). The implementation of the electronic prompt did not contribute to the improvement in the POA and HAC rates because the reduction occurred before the EMR prompt intervention. Changing processes such as EMR upgrades, shared governance, Magnet journey, participation in the National Database of Nursing Quality Indicators, and unit-based nursing councils and skin care champions may have exerted positive forces and contributed to improvement in the communication process between the admitting physicians and the clinical nurses.


Magnetic resonance imaging analysis of the upper cervical spine extensor musculature in an asymptomatic cohort: an index of fat within muscle.
To establish a simple method to quantify muscle/fat constituents in cervical muscles of asymptomatic women using magnetic resonance imaging (MRI), and to determine whether there is an age effect within a defined age range. MRI of the upper cervical spine was performed for 42 asymptomatic women aged 18-45 years. The muscle and fat signal intensities on axial spin echo T1-weighted images were quantitatively classified by taking a ratio of the pixel intensity profiles of muscle against those of intermuscular fat for the rectus capitis posterior major and minor and inferior obliquus capitis muscles bilaterally. Inter- and intra-examiner agreement was scrutinized. The average relative values of fat within the upper cervical musculature compared with intermuscular fat indicated that there were only slight variations in indices between the three sets of muscles. There was no significant correlation between age and fat indices. There were significant differences for the relative fat within the muscle compared with intermuscular fat and body mass index for the right rectus capitis posterior major and right and left inferior obliquus capitis muscles (p=0.032). Intraclass correlation coefficients for intraobserver agreement ranged from 0.94 to 0.98. Inter-rater agreement of the measurements ranged from 0.75 to 0.97. A quantitative measure of muscle/fat constituents has been developed, and results of this study indicate that relative fatty infiltration is not a feature of age in the upper cervical extensor muscles of women aged 18-45 years.


Adult Aging Moderates the Relationship Between Trait Cognitive Anxiety and Subjective Everyday Cognitive Difficulties.
The present aim was to determine, across the adult lifespan, the extent to which different dimensions of trait anxiety might affect subjective cognitive difficulties in everyday life. Following Attentional Control Theory (ACT; Eysenck et al., 2007), we predicted that trait anxiety would have a greater effect on attention and verbal abilities than on visual abilities. We also expected trait cognitive anxiety to exhibit more robust relationships with cognition than trait somatic anxiety. Importantly, we predicted that effects of anxiety would be greater in older adults, in line with the Strength and Vulnerability Integration model (SAVI; Charles, 2010). The sample comprised 286 United Kingdom-based adults aged 18-93 years. Participants completed self-report measures of trait cognitive and somatic anxiety (the State-Trait Inventory for Cognitive and Somatic Anxiety; STICSA, Ree et al., 2008) and everyday cognitive difficulties (the Multiple Abilities Self-Report Questionnaire; MASQ, Seidenberg et al., 1994). Moderated regression models were constructed, including trait cognitive or somatic anxiety as a predictor of cognitive difficulties, and age as the moderator variable. Covariates included depression, stress (the Depression Anxiety Stress Scales-short form; DASS-21, Lovibond and Lovibond, 1995), gender, current mental health treatment status, and physical health status. When cognitive anxiety was the predictor variable, somatic anxiety was also included as a covariate, and vice-versa. Trait cognitive anxiety and age interacted to predict all MASQ subscales other than visual-perceptual ability. Difficulties with attention, verbal memory, and language abilities were significantly greater at higher levels of anxiety for all age groups, with the effect greatest in older adults. Difficulties with visual-spatial memory were significantly greater at higher levels of anxiety in middle-aged and older adults only. Higher trait somatic anxiety predicted difficulties with verbal memory and language ability independently of age, and interacted with age to predict language difficulties. Interestingly, age also significantly predicted less subjective difficulty with attention, independently of anxiety level. The results show that trait cognitive and somatic anxiety are both related to subjective, everyday cognitive difficulties. However, effects of trait cognitive anxiety are more robust across cognitive domains and tend to increase, or first appear, over the course of the adult lifespan.


Docetaxel (Taxotere) administered in weekly schedules.
The administration of a weekly low-dose taxane markedly reduces the severity of myelosuppression compared with a once-every-3-week schedule and allows the dose intensity (mg/m2/wk) of treatment to be increased. The dose-limiting toxicity observed in a weekly phase I trial was fatigue/asthenia. The maximum tolerated dose of a weekly docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) phase I study was 43 mg/m2; 36 mg/m2 was recommended for further study. This finding was similar to that in another phase I/II trial of weekly docetaxel in previously treated patients with metastatic breast cancer in which the recommended dose for the phase II study was 35 mg/m2. In this latter study, an objective response rate of 50% and a 0% incidence of febrile neutropenia have been reported. Other studies have been conducted to evaluate the efficacy and safety of the weekly schedule. One such study is an ongoing phase II trial in elderly or medically unfit patients with previously untreated advanced non-small cell lung cancer in whom weekly docetaxel appears active and well tolerated. Further investigation of weekly docetaxel alone or in combination is warranted.


[The experience with the supervision and treatment of the patients presenting with external otitis].
This clinical study was designed to estimate the efficacy and tolerability of the locally applied Pimafucort preparation for the treatment of diffuse otitis of bacterial and mycotic origin. The results of dynamic bacteriological investigation in conjunction with clinical observations give reason to recommend the local therapy as the sole treatment of uncomplicated forms of diffuse external otitis.


COMIDA: a radionuclide food chain model for acute fallout deposition.
A dynamic food chain model and computer code, named "COMIDA," has been developed to estimate radionuclide concentrations in agricultural food products following an acute fallout event. COMIDA estimates yearly harvest concentrations for five human crop types (Bq kg-1 crop per Bq m-2 deposited) and integrated concentrations for four animal products (Bq d kg-1 animal product per Bq m-2) for a unit deposition that occurs on any user-specified day of the year. COMIDA is structurally very similar to the PATHWAY model and includes the same seasonal transport processes and discrete events for soil and vegetation compartments. Animal product assimilation is modeled using simpler equilibrium models. Differential transport and ingrowth of up to three radioactive progeny are also evaluated. Benchmark results between COMIDA and PATHWAY for monthly fallout events show very similar seasonal agreement for integrated concentrations in milk and beef. Benchmark results between COMIDA and four international steady-state models show good agreement for deposition events that occur during the middle of the growing season. COMIDA will be implemented in the new Department of Energy version of the MELCOR Accident Consequence Code System for evaluation of accidental releases from nuclear power plants.


Arterio-venous shunting in renal transplant rejection.
The angiographic appearance of arterio-venous shunting has been reported in one previous case of a patient with acute severe transplant rejection. Two additional cases are presented here. In the first the arteriovenous shunting is massive, and the venous filling is within the first second of the study. In the second the shunting is less severe, and the venous filling occurs later in the arterial phase. Shunting is probably caused by multiple microscopic arterio-venous fistulae secondary to the vasculitis of rejection. We propose that the presence of arterio-venous shunting suggests renal transplant rejection and may indicate a poor prognosis for reversal of this rejection.


Hierarchical peroxiredoxin assembly through orthogonal pH-response and electrostatic interactions.
Morpheeins are proteins that adapt their morphology and function to the environment. Therefore, their use in nanotechnology opens up the bottom-up preparation of anisotropic metamaterials, based on the sequential use of different stimuli. A prominent member of this family of proteins is peroxiredoxins (Prx), with dual peroxidase and chaperone function, depending on the pH of the media. At high pH, they show a toroidal morphology that turns into tubular stacks upon acidification. While the toroidal conformers have been explored as building blocks to yield 1D and 2D structures, the obtention of higher ordered materials remain unexplored. In this research, the morpheein behaviour of Prx is exploited to yield columnar aggregates, that are subsequently self-assembled into 3D anisotropic bundles. This is achieved by electrostatic recognition between the negatively charged protein rim and a positively charged porphyrin acting as molecular glue. The subsequent and orthogonal input lead to the alignment of the monodimensional stacks side-by-side, leading to the precise assembly of this anisotropic materials.


Differences and similarities in the diagnosis and treatment of Graves' disease in Europe, Japan, and the United States.
In three separate studies, members of the American Thyroid Association (ATA), the European Thyroid Association (ETA), and the Japan Thyroid Association (JTA) were surveyed by questionnaire on their management of Graves' disease. The aim was to determine how expert clinical thyroidologists employ diagnostic procedures and the three different therapies that are available for this disorder. In this report, we identify, summarize, compare, and contrast similarities and differences in the results of these surveys in these three different regions of the world. In general, ATA members used fewer diagnostic tests than did their European or Japanese colleagues. For the index patient, radioiodine was the therapy of choice for 69% of ATA respondents but only 22% and 11% of ETA and JTA respondents, respectively. In contrast, only 30.5% of ATA respondents chose antithyroid drugs as first-line therapy compared to 77% of ETA and 88% of JTA respondents. There was consensus on the relative lack of a role for thyroidectomy except for narrow indications. The implications of these differing approaches for the diagnosis and treatment of hyperthyroidism due to Graves' disease are discussed.


Short- to Long-Term Effects of Virtual Reality on Motor Skill Learning in Children With Cerebral Palsy: Systematic Review and Meta-Analysis.
Many studies have started integrating virtual reality (VR) into neurorehabilitation for children with cerebral palsy (CP). The results of the effects of VR on motor skill learning, including the short- to long-term results of relevant studies, must be pooled in a generic framework. This systematic review and meta-analysis aimed to investigate the short- to long-term effects of therapies including VR on motor skill learning in children with CP. Two examiners followed the inclusion and exclusion criteria of the "Participant, Intervention, Control, and Outcome" framework. Randomized controlled trials (RCTs) and non-RCTs were considered if they compared VR-included interventions with control groups on motor functions and daily life activities in children with CP. PubMed, ScienceDirect, Embase, and IEEE Xplore databases were searched. The modified Downs and Black assessment was used to assess the methodological quality of the included studies. Meta-analyses and subgroup analyses for RCTs were conducted whenever possible. A total of 7 RCTs, 2 non-RCTs, and 258 children with CP were included. The priority focus of 78% (7/9) of the studies was upper limb functions. There was a significant short-term effect of adding VR to conventional therapies on upper limb functions when compared with conventional therapies (P=.04; standardized mean difference [SMD]=0.39, 95% CI 0.01-0.76). The overall medium- to long-term effects showed a trend toward favoring the VR group, although the difference was not statistically significant (P=.06; SMD=0.37, 95% CI -0.02 to 0.77). For balance (P=.06; SMD=1.04, 95% CI -0.04 to 2.12), gross motor functions (P=.30; SMD=2.85, 95% CI -2.57 to 8.28), and daily life activities outcomes (P=.21; SMD=0.29, 95% CI -0.16 to 0.74), the overall effect in the short term also showed a trend toward favoring the VR group, but these results were not statistically significant. VR seems to have additional benefits for motor skill learning in children with CP. Studies with follow-up outcomes of VR training focusing on balance and gross motor functions in patients with CP were quite limited. Future research on balance and gross motor function outcomes should target particularly long-term results of therapies including VR on motor skill learning. PROSPERO International Prospective Register of Systematic Reviews CRD42021227734; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021227734.


Nonlinear theory of nonparaxial laser pulse propagation in plasma channels
Nonparaxial propagation of ultrashort, high-power laser pulses in plasma channels is examined. In the adiabatic limit, pulse energy conservation, nonlinear group velocity, damped betatron oscillations, self-steepening, self-phase modulation, and shock formation are analyzed. In the nonadiabatic limit, the coupling of forward Raman scattering (FRS) and the self-modulation instability (SMI) is analyzed and growth rates are derived, including regimes of reduced growth. The SMI is found to dominate FRS in most regimes of interest.


Fitness costs of insecticide resistance in natural breeding sites of the mosquito Culex pipiens.
Genetic changes conferring adaptation to a new environment may induce a fitness cost in the previous environment. Although this prediction has been verified in laboratory conditions, few studies have tried to document this cost directly in natural populations. Here, we evaluated the pleiotropic effects of insecticide resistance on putative fitness components of the mosquito Culex pipiens. Experiments using different larval densities were performed during the summer in two natural breeding sites. Two loci that possess alleles conferring organophosphate (OP) resistance were considered: ace-1 coding for an acetylcholinesterase (AChE1, the OP target) and Ester, a ''super locus" including two closely linked loci coding for esterases A and B. Resistance ace-1 alleles coding for a modified AChE1 were associated with a longer development time and shorter wing length. The pleiotropic effects of two resistance alleles Ester1 and Ester4 coding for the overproduced esterases A1 and A4-B4, respectively, were more variable. Both A1 and A4-B4 reduced wing length, although only A1 was associated with a longer preimaginal stage. The fluctuating asymmetry (FA) of the wing did not respond to the presence or to the interaction of resistance alleles at the two loci at any of the density levels tested. Conversely, the FA of one wing section decreased when larval density increased. This may be the consequence of selection against less developmentally stable individuals. The results are discussed in relation to the local evolution of insecticide resistance genes.


Sentinel node biopsy in patients with cutaneous melanoma of the head and neck.
Biopsy of head and neck sentinel nodes (SNs) can be technically problematic due to the unpredictable and variable drainage patterns of this anatomic region. The aim of the present study was to evaluate the feasibility of SN biopsy for cutaneous melanoma of the head and neck. We performed SN biopsy in 17 patients affected by stage I cutaneous melanoma of the head and neck on the basis of lymphoscintigraphy, blue dye and gamma probe. A total of 24 procedures were performed. Drainage to more than one lymphatic basin was observed in five patients (two basins in three cases and three basins in two cases) and in all cases SN biopsy was performed in all basins. The biopsy distribution by site was: six cervical nodes, five parotid nodes, four supraclavicular and submandibular nodes, three auricular and axillary nodes. The SN identification rate was 87.5% (21/24); metastases were discovered in four cases, with a positivity rate of 23.6%. At the time of writing, 1 patient is alive with local disease, 3 patients are dead and 13 are alive and free of disease with a follow-up ranging from 1 to 40 months (median, 21 months) following SN biopsy. In our opinion preoperative lymphoscintigraphy and the intraoperative use of a gamma probe are useful for the identification of lymphatic drainage of cutaneous melanoma of the head and neck.


Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas.
MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs. From 44 MAP patients who developed > or = 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. KRAS2, the mutation cluster region (MCR) of APC, p53, and SMAD4 were analyzed for somatic mutations. MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic APC MCR mutations occurred in 14% (5/36) while 64% (23/36) had KRAS2 mutations (22/23 c.34G>T). G>T transversions were found in p53 and SMAD4, although the relative frequency compared to other mutations was low. MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development) but not in P53 and SMAD4 (implicated in tumour progression) might indicate a predominant MUTYH effect in early carcinogenesis.


Life and Death of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficient Erythrocytes - Role of Redox Stress and Band 3 Modifications.
G6PD catalyzes the first, pace-making reaction of pentosephosphate cycle (PPC) which produces NADPH. NADPH maintains glutathione and thiol groups of proteins and enzymes in the reduced state which is essential for protection against oxidative stress. Individuals affected by G6PD deficiency are unable to regenerate reduced glutathione (GSH) and are undefended against oxidative stress. G6PD deficiency accelerates normal senescence and enhances the precocious removal of chronologically young, yet biologically old cells. The term hemolytic anemia is misleading because RBCs do not lyse but are removed by phagocytosis. Acute hemolysis by fava bean ingestion in G6PD deficient individuals (favism) is described being the best-studied natural model of oxidant damage. It bears strong analogies to hemolysis by oxidant drugs or chemicals. Membrane alterations observed in vivo during favism are superimposable to changes in senescent RBCs. In summary, RBC membranes isolated from favic patients contained elevated amounts of complexes between IgG and the complement fragment C3b/C3c and were prone to vesiculation. Anti-band 3 IgG reacted to aggregated band 3-complement complexes. In favism extensive clustering of band 3 and membrane deposition of hemichromes were also observed. Severely damaged RBCs isolated from early crises had extensive membrane cross-bonding and very low GSH levels and were phagocytosed 10-fold more intensely compared to normal RBCs.


Roles of temperature and ventilation in oxygen consumption: A chemical kinetics view from the van't Hoff-based formulation.
In this study, we successfully estimated the apparent activation energy of a microbially driven oxygen-consuming reaction (microbial-driven) based on tracer data. The concept of the apparent chemical reaction rate constant was employed to estimate various thermodynamic parameters associated with the oxygen consumption rate in conjunction with Arrhenius/Eyring equations. Normal Ea values of 80-90 kJ mol-1 were found in the upper layers of the South China Sea and Sulu Sea, while higher Ea values (300-1000 kJ mol-1) were observed in the rapidly ventilated Mediterranean Sea, the Sea of Japan, and the Bering Sea with lower temperatures. We classified the characteristics of typical sea basins into four categories. The temperature-dependent oxygen consumption rate relationship in each marine region was systematically calculated to derive the respective thermodynamic characteristic values. This allowed us to parameterize the rate-temperature relationship into thermodynamic quantities, enabling more effective integration of distinct basin characteristics within different sea areas into the marine biochemical model. Parameterization facilitates relatively accurate prediction of changes such as temperature, oxygen consumption rate.


An optimal spatial configuration of sample sites for air pollution monitoring.
A novel sampling design is proposed that optimizes the spatial configuration of sampling sites and captures maximum intraurban variability in ambient air pollution with a minimum sample size. Unlike the classical sampling design, a deterministic approach is adopted and the redundancy in the site selection is minimized by controlling for spatial autocorrelation. The proposed design was tested and implemented in a medium-sized midwestern city. The analysis suggested that 32 sites were adequate to capture more than 95% of the total variance in airborne particulate 10 microm or less in aerodynamic diameter (PM10). A list of 20 households was prepared around each of the 32 sites. Households were approached in order of their distance from these sites until one was recruited for intensive indoor and outdoor air pollution monitoring from spring through fall of 2008. Finally, 30 households located around the optimal sites participated in the study. One set of four photometric and gravimetric samplers was deployed for each indoor and outdoor environment. The average ambient PM10 concentration (monitored from April to September 2008) at the selected locations was lower but statistically insignificant as compared with the PM10 (computed using the data from mobile sampling in 2006) at the optimal sites.


Lyme borreliosis: current issues in diagnosis and management.
Lyme borreliosis is the most common vector-borne bacterial infection in temperate areas of the northern hemisphere. It has been perceived as difficult to diagnose and treat, but much is now known about its clinical presentations, which largely fall into well defined categories in both adults and children. This review features recent publications on clinical diagnosis and management. The reported incidence of Lyme borreliosis has increased markedly in many countries. Many recent publications have focused on clinical and laboratory aspects of paediatric and adult neuroborreliosis, and there is now strong evidence for the efficacy of oral doxycycline for most presentations of neuroborreliosis. Serological tests have improved significantly. Several studies have confirmed that patients treated for early Lyme borreliosis have good overall long-term outcomes. Studies of patients with persistent symptoms following treatment have not shown evidence for active infection or for sustained benefit from prolonged antibiotic treatment. Greater efforts are needed to provide education for prevention and early diagnosis to avoid late complications. Further improvements in diagnostic tests would be welcomed. More research is required to assess the causes and management of post-Lyme symptoms.


Putative chromaffin cell survival and enhanced host-derived TH-fiber innervation following a functional adrenal medulla autograft for Parkinson's disease.
We report heretofore undescribed clinical and histological features of a patient with idiopathic Parkinson's disease who showed marked and persistent motoric benefit from an adrenal medulla autograft for 18 months following grafting. The patient returned to the preoperative level of disability prior to his death 30 months after implantation, the longest survival to date for an adrenal transplant. The graft site was primarily necrotic and large numbers of macrophages were still present at the time of death. A few tyrosine hydroxylase-immunoreactive cells were found within the graft, providing the first evidence that adrenal medullary cells may be viable and produce catecholamines following human transplantation. A dense network of tyrosine hydroxylase-immunoreactive terminals and processes was also seen ventral to the implant site and on both of its lateral borders. This response may represent sprouting by residual host dopaminergic neurons mediated by the vigorous response to injury displayed by the host striatum. The relative paucity of surviving chromaffin cells, however, provides further evidence that adrenal medulla grafts survive poorly following intracerebral implantation, and factors other than dopamine replacement may be responsible for most of the functional effects observed following chromaffin cell transplantation.


Bacterial toxins in musculoskeletal infections.
Musculoskeletal infections (MSKIs) remain a major health burden in orthopaedics. Bacterial toxins are foundational to pathogenesis in MSKI, but poorly understood by the community of providers that care for patients with MSKI, inducing an international group of microbiologists, infectious diseases specialists, orthopaedic surgeons and biofilm scientists to review the literature in this field to identify key topics and compile the current knowledge on the role of toxins in MSKI, with the goal of illuminating potential impact on biofilm formation and dispersal as well as therapeutic strategies. The group concluded that further research is needed to maximize our understanding of the effect of toxins on MSKIs, including: (i) further research to identify the roles of bacterial toxins in MSKIs, (ii) establish the understanding of the importance of environmental and host factors and in vivo expression of toxins throughout the course of an infection, (iii) establish the principles of drug-ability of antitoxins as antimicrobial agents in MSKIs, (iv) have well-defined metrics of success for antitoxins as antiinfective drugs, (v) design a cocktail of antitoxins against specific pathogens to (a) inhibit biofilm formation and (b) inhibit toxin release. The applicability of antitoxins as potential antimicrobials in the era of rising antibiotic resistance could meet the needs of day-to-day clinicians.


Bias associated with failing to incorporate dependence on event history in Markov models.
When using state-transition Markov models to simulate risk of recurrent events over time, incorporating dependence on higher numbers of prior episodes can increase model complexity, yet failing to capture this event history may bias model outcomes. This analysis assessed the tradeoffs between model bias and complexity when evaluating risks of recurrent events in Markov models. The authors developed a generic episode/relapse Markov cohort model, defining bias as the percentage change in events prevented with 2 hypothetical interventions (prevention and treatment) when incorporating 0 to 9 prior episodes in relapse risk versus a model with 10 such episodes. Magnitude and sign of bias were evaluated as a function of event and recovery risks, disease-specific mortality, and risk function. Bias was positive in the base case for a prevention strategy, indicating that failing to fully incorporate dependence on event history overestimated the prevention's predicted impact. For treatment, the bias was negative, indicating an underestimated benefit. Bias approached zero as the number of tracked prior episodes increased, and the average bias over 10 tracked episodes was greater with the exponential compared with linear functions of relapse risk and with treatment compared with prevention strategies. With linear and exponential risk functions, absolute bias reached 33% and 78%, respectively, in prevention and 52% and 85% in treatment. Failing to incorporate dependence on prior event history in subsequent relapse risk in Markov models can greatly affect model outcomes, overestimating the impact of prevention and treatment strategies by up to 85% and underestimating the impact in some treatment models by up to 20%. When at least 4 prior episodes are incorporated, bias does not exceed 26% in prevention or 11% in treatment.


A Practical Guide to Molecular Dynamics Simulations of DNA Origami Systems.
The DNA origami method exploits the self-assembly property of nucleic acids to build diverse nanoscale systems. The all-atom molecular dynamics (MD) method has emerged as a powerful computational tool for atomic-resolution characterization of the in situ structure and physical properties of DNA origami objects. This chapter provides step-by-step instructions for building atomic-scale models of DNA origami systems, using the MD method to simulate the models, and performing basic analyses of the resulting MD trajectories.


Detachment of Descemet's membrane from grafts following wound separation: light and scanning electron microscopic study.
Examination of 4 specimens of failed grafts following wound rupture shows that separation of Descement's membrane from the periphery of the graft in the area of dehiscence is followed by morphological changes in endotelial cells and by the development of fibrous membranes. Defective wound healing after repair is probably caused by persistent edema of graft stroma. With sudden decompression of the globe, rupture and total detachment of Descemet's membrane may occur. Changes in Descemet's membrane and eventual failure of the graft may occur mostly on the basis of anatomical changes in the endothelium of the graft and not necessarily by inflammation which was not present in these 4 specimens.


Enhancement of the efficiency of phosphoproteomic identification by removing phosphates after phosphopeptide enrichment.
Immobilized metal affinity chromatography (IMAC) and titanium oxide (TiO2) chromatography are simple, widely used, and cost-effective methods to enrich phosphopeptides, but the sample loading buffer composition, desalting procedure, and control of loading amount are critical to avoid nonspecific interactions and to achieve efficient phosphopeptide enrichment. Although the combination of MS3 analysis and high-resolution mass spectrometry (MS) is helpful to identify phosphopeptides, the quality of many MS/MS spectra having a neutral loss peak of phosphate is still too poor to allow sequence identification, and this results in many false-negative as well as false-positive identifications. Here, we present a novel strategy, which is based on the use of alkaline phosphatase to remove phosphates and analysis of phospho/dephosphopeptide retention times to increase the reliability of identification. The use of phospho/dephosphopeptide retention time ratios allows the identification of phosphopeptides with high confidence with the aid of a focused database of dephosphopeptides. This approach was very effective to identify multiple phophorylations in tryptic peptides. A 'true' phosphorylation data set should contain about 90% phospho-Ser and a few percent phospho-Tyr, and this ratio can be used as a quality criterion for evaluation of data sets. By applying this efficient approach, we were able to identify more than one thousand phosphopeptides.


Physisorption of hydroxide ions from aqueous solution to a hydrophobic surface.
We present results from detailed molecular dynamics simulations revealing a counterintuitive spontaneous physical adsorption of hydroxide ions at a water/hydrophobic interface. The driving force for the migration of the hydroxide ions from the aqueous phase is the preferential orientation of the water molecules in the first two water layers away from the hydrophobic surface. This ordering of the water molecules generates an electrical potential gradient that strongly and favorably interacts with the dipole moment of the hydroxide ion. These findings offer a physical mechanism that explains intriguing experimental reports indicating that the interface between water and a nonionic surface is negatively charged.


Research on coordination of the NEV battery closed-loop supply chain considering CSR and fairness concerns in third-party recycling models.
Due to the pressure of the ecological environment and government, it is incumbent for enterprises to undertake corporate social responsibility (CSR). However, during the recycling process, awareness of equity concerns due to the distribution of benefits among members has intensified, and it is crucial to resolve channel conflicts and design a reasonable cooperation model to recycle used power batteries. Therefore, this paper constructs a closed-loop supply chain composed of power battery manufacturer, retailer and third-party collector based on the consideration of cascade utilization, in order to study the impact of the level of CSR and the degree of fairness concern on the decision-making of channel participants. Our research shows that: (1) Fairness concern behavior adversely affects the supply chain, which raises the sales price and reduces the collecting rate and the utility of the supply chain as a whole. (2) Undertaking CSR is beneficial to the development of the power battery market, and also helps to reduce the sense of unfairness among third-party recycling companies. (3) The cost-sharing contract effectively coordinates the distribution of supply chain benefits and improves the recycling rate. Finally, we further verify the correctness of the conclusions through numerical studies.


Evidence that inositol 1-phosphate in brain of lithium-treated rats results mainly from phosphatidylinositol metabolism.
In cerebral cortex of rats treated with increasing doses of LiCl, the relative concentrations of Ins(1)P, Ins(4)P and Ins(5)P (when InsP is a myo-inositol phosphate) are approx. 10:1:0.2 at all doses. In rats treated with LiCl followed by increasing doses of pilocarpine a similar relationship occurs. myo-Inositol-1-phosphatase (InsP1ase) from bovine brain hydrolyses Ins(1)P, Ins(4)P and Ins(5)P at comparable rates, and these substrates have similar Km values. The hydrolysis of Ins(4)P is inhibited by Li+ to a greater degree than is hydrolysis of Ins(1)P and Ins(5)P. D-Ins(1,4,5)P3 and D-Ins(1,4)P2 are neither substrates nor inhibitors of InsP1ase. A dialysed high-speed supernatant of rat brain showed a greater rate of hydrolysis of Ins(1)P than of D-Ins(1,4)P2 and a lower sensitivity of the bisphosphate hydrolysis to LiCl, as compared with the monophosphate. That enzyme preparation produced Ins(4)P at a greater rate than Ins(1)P when D-Ins(1,4)P2 was the substrate. The amount of D-Ins(3)P [i.e. L-Ins(1)P, possibly from D-Ins(1,3,4)P3] is only 11% of that of D-Ins(1)P on stimulation with pilocarpine in the presence of Li+. DL-Ins(1,4)P2 was hydrolysed by InsP1ase to the extent of about 50%; both Ins(4)P and Ins(1)P are products, the former being produced more rapidly than the latter; apparently L-Ins(1,4)P2 is a substrate for InsP1ase. Li+, but not Ins(2)P, inhibited the hydrolysis of L-Ins(1,4)P2. The following were neither substrates nor inhibitors of InsP1ase; Ins(1,6)P2, Ins(1,2)P2, Ins(1,2,5,6)P4, Ins(1,2,4,5,6)P5, Ins(1,3,4,5,6)P5 and phytic acid. myo-Inositol 1,2-cyclic phosphate was neither substrate nor inhibitor of InsP1ase. We conclude that the 10-fold greater tissue contents of Ins(1)P relative to Ins(4)P in both stimulated and non-stimulated rat brain in vivo are the consequence of a much larger amount of PtdIns metabolism than polyphosphoinositide metabolism under these conditions.


Accuracy of a digital removable partial denture fabricated by casting a rapid prototyped pattern: A clinical study.
A limited number of clinical studies have evaluated the accuracy of a digitally generated removable partial denture (RPD) intraorally. An analysis of the accuracy of the digital RPD on a larger number of participants was needed. The purpose of this clinical study was to analyze the accuracy of digital RPDs by using the replica technique. The fit accuracy of digital RPDs fabricated using electronic surveying was analyzed by fabricating replicas with silicone registration material and measuring with a stereomicroscope and image program. A total of 348 measurements in 10 participants were analyzed. The internal discrepancy of the metal framework was evaluated among participants using different Kennedy classifications. The accuracy of fittings in the cingulum and occlusal rest areas were compared according to the denture support type and the measured position below the rest. A 2-way and 1-way ANOVA and an independent 2-sample t test were used for statistical analysis (α=.05). Statistically significant differences were found in the internal discrepancy of the various framework components (P<.05), but no differences were found among participants with different Kennedy classifications (P>.05). The discrepancy under the periphery of the rest was determined to be smaller than that of the center, especially for the cingulum rest (P<.01). Digital RPDs fabricated using electronic surveying varied in accuracy of fit. According to the rest contact positions, the accuracy observed at the periphery was better than at the center.


Longterm outcomes and quality of life after Z-shaped anastomosis for Hirschsprung's disease.
Z-shaped anastomosis is one of the modifications of Duhamel's procedure that was designed to eliminate the blind rectal pouch and to achieve complete resection of the colorectal septum. It has been the most widely performed operation in Japan for many years. The longterm postoperative function of evacuation and quality of life of the patients are considered important to evaluate this procedure. At Kyushu University Hospital, from 1963 to 1997, 127 patients with Hirschsprung's disease underwent Z-shaped anastomosis. As a result, 122 out of 127 patients (96%) survived. The present status and symptoms, and anorectal functions, including a manometric study and barium enema, were evaluated during the clinical followup. A total of 99 of the 122 surviving patients (81%) were available for this study, and the mean postoperative period was 16 years. Evacuation scores in all patients were as follows; excellent, 62.2%; good, 28.6%; fair, 8.2%; and poor, 1.0%. The percentage of the patients who showed severe symptoms was 4.1% for diarrhea, 3.1% for constipation, 5.1% for incontinence, and 7.1% for soiling. The evacuation score improved chronologically and tended to reach a plateau at 10 to 15 years after operation, at which time 73% of the patients showed excellent outcomes and 95% were satisfactory (good or excellent). The appearance of a sense of defecation and an increase in the pressure difference between the anal canal and the rectum substantially contributed to the improvement in the defecation score. The appearance of the rectosphincteric reflex, including the atypical one, was seen in 40.5% of patients, but the appearance of a reflex did not seem to be related to the clinical status of defecation. Twenty-two of 30 patients older than 20 years were married, and 8 patients had children. The evacuation scores of in-patients undergoing Z-shaped anastomosis improved with age and were satisfactory (good or excellent) in most patients at least 10 years after operation. Most of the patients adapted to a normal social life.


Health benefits of dietary fat reduction by a novel fat replacer: Mimix.
The primary goals of this study were to identify any health benefits of the replacement of dietary fat with a novel fat replacer, Mimix, and to assure that the consumption of this fat replacer did not convey any deleterious health effects. Male, weanling, Fischer 344 rats were fed one of six diets containing between 5 and 20% w/w as fat for 8 weeks. These diets included two high fat diets (safflower oil or lard), a low fat diet and three diets where 15% of the fat in the high fat diets was replaced with various amounts of Mimix. When animals were fed a diet rich in saturated fat they consumed significantly more energy than other diet groups. When 15% saturated fat (lard) was replaced with safflower oil animals adjusted their food intake so that no difference in energy intake was observed between the high safflower diet and the low fat and Mimix diets. When the various Mimix fat replacements were compared to animals fed a high fat lard diet there was incomplete compensation of energy intake. Animals fed the high fat lard diet also had higher glucose and total serum cholesterol than their low fat and fat replacement counterparts. Feeding a high fat safflower oil diet to rats resulted in a significantly lower total serum cholesterol and serum triglyceride than all other diets. Replacement of dietary fat with Mimix demonstrated no deleterious effects on the heart, liver and intestinal tract that were all of normal weight, morphology and colour compared to other diet groups. Body composition analysis demonstrated that animals fed high fat diets had higher body fat mass at the expense of lean body mass. This was most obvious for animals fed high fat lard diets who had heavier epididymal fat pads. These data demonstrate that the replacement of dietary fat with the novel fat replacer Mimix can convey a number of health benefits in the absence of any deleterious effects.


The Knowledge and Attitude about New Generation Tobacco Products among Physicians.
Health hazards of e-cigarettes including "e-cigarette or vaping product use-associated lung injury" are better understood today. Just as e-cigarettes, heated tobacco products release toxic emissions. We aimed to determine the knowledge and attitude about new generation tobacco products among physicians who were the members of an organization for health care professionals, the majority of whom are pulmonologists. In this cross-sectional study, a self-administered online questionnaire-based survey was conducted among the physicians from April to October 2019. The survey included questions about demographics (gender, age, graduation date from medical institution, and academic title), their smoking status, their knowledge and attitudes toward new generation tobacco products, and additionally about whether new generation tobacco products can be used to aid in smoking cessation. Among the 506 members who responded to the survey, 56.7 % were female; the mean age was 42.4 ± 10.9 years (20-74). About 74.5% were pulmonologists, 5.5% were thoracic surgeons, and 20% were other physicians. Among the responders, the frequency of those who have not heard of new generation tobacco products before was determined as 9.5%, 24.5%, and 41.3%. At least 58.9% of participants lacked the knowledge necessary to discuss these products with their patients and the rate reached 76.7% for the heated tobacco product. To the question of whether new generation tobacco products can be used in smoking cessation, 68.4% responded "I never agree that they can be used." Non-current smokers (P = .003), elders (P = .001), those who had training on smoking cessation assistance (P = .001), and those who had experience in smoking cessation assistance (P = .009) were significantly more prevalent in the group who answered: "I never agree that they can be used." Physicians must become considerably more knowledgeable about the new generation tobacco products and hazards. Otherwise, these new tobacco products may pose new threats to national and global tobacco control efforts.


Clinical assessment of the St. Jude medical cardiac prosthesis. A 5-year experience.
Mechanical prosthetic valves have established their long-term durability, but the incidence of thromboembolism has been less satisfying. Therefore, the search for the perfect valve continues. The choice of replacing a cardiac valve with a prosthetic valve is based upon its hemodynamics, durability, thromboembolic and hemolytic characteristics. The hemodynamic assessment of the St. Jude Valve demonstrates that it performs well in the aortic, mitral, and tricuspid positions. The central bileaflet flow design leads to minimal gradients, even in the small valves which make it ideal for its use in children. The purpose of its all-pyrolite construction is to decrease the incidence of thromboembolism. Replacement of heart valves with the St. Jude Medical prosthesis was initiated in April, 1979. An analysis of all patients undergoing valve replacement between April 1, 1979, and June 1, 1984, was carried out to assess the durability, incidence of thrombosis, and thromboembolic as well as other complications.


[Reorganization of services: challenges of the psychiatric reform].
This qualitative study, based on social survey, aimed at understanding actions carried out in mental health in nine cities of the 10th Health District of the Health Care Module of Cascavel, Paraná, Brazil. Nine municipal health secretaries participated in a semi-structured interview carried out between July and September, 2004. Collective Subject Discourse (CSD) was used to analyze the data. Five CSD and three meaning-generating themes (service reorganization, home visits, and prevention) were identified. The present article discusses theme 1--service reorganization, which should include diverse mental health care modes integrated to the regional basic health care network.


[Zenker's diverticulum].
An experience with treatment of 14 women and 15 men aged from 41 to 83 years with Zenker's diverticulum was analyzed. Most liable to the disease were people at the age from 50 to 70 years. The average duration of the disease was 3-4 years. All the patients were subjected to improved surgical interventions: resection of the diverticulum (11 patients), operations under the control of the endoscopic technique (18 patients). Resections of the diverticulum were combined with cryopharyngeal myotomy. No complications were noted. There were no lethal outcomes. So, wider indications to operative treatment in patients with Zenker's diverticulum, endoscopic methods used at all stages of treatment as well as improved methods of performing the operation enabled the authors to obtain good immediate and long-term results.


Fiber-optic multiphoton flow cytometry in whole blood and in vivo.
Circulating tumor cells in the bloodstream are sensitive indicators for metastasis and disease prognosis. Circulating cells have usually been monitored via extraction from blood, and more recently in vivo using free-space optics; however, long-term intravital monitoring of rare circulating cells remains a major challenge. We demonstrate the application of a two-photon-fluorescence optical fiber probe for the detection of cells in whole blood and in vivo. A double-clad fiber was used to enhance the detection sensitivity. Two-channel detection was employed to enable simultaneous measurement of multiple fluorescent markers. Because the fiber probe circumvents scattering and absorption from whole blood, the detected signal strength from fluorescent cells was found to be similar in phosphate-buffered saline (PBS) and in whole blood. The detection efficiency of cells labeled with the membrane-binding dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindoldicarbocyanine, 4-chlorobenzenesulfonate (DiD) was demonstrated to be the same in PBS and in whole blood. A high detection efficiency of green fluorescent protein (GFP)-expressing cells in whole blood was also demonstrated. To characterize in vivo detection, DiD-labeled untransfected and GFP-transfected cells were injected into live mice, and the cell circulation dynamics was monitored in real time. The detection efficiency of GFP-expressing cells in vivo was consistent with that observed ex vivo in whole blood.


Long-term results of the phase II dose and volume de-escalation trial for locoregionally advanced nasopharyngeal carcinoma.
Patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) were assigned to dose and volume de-escalated intensity-modulated radiation therapy (IMRT) based on response to induction chemotherapy (IC) to limit treatment related toxicity while preserving efficacy. A single-arm de-escalated phase II trial was performed in this study. Patients with LANPC received two cycles of IC with docetaxel 60 mg/m2 d1, cisplatin 25 mg/m2/day d1-3 and 5-fluorouracil 500 mg/m2/day d1-5 q21d, followed by IMRT. The gross tumor volume of the primary intracavity nasopharyngeal tumor and involved lymph nodes were delineated based on the post-IC tumor extension. Part of the prescribed doses were reduced from 70.4 Gy to 66 Gy for T3-4 diseases. The primary end point was 5-year progression-free survival (PFS) in stage III and IVA-B NPC compared with historical controls of 50% and 35%. Between January 2010 and November 2013, 48 and 83 eligible patients with stage III and IVA-B NPC were accrued to this trial. With a median follow-up of 92 months, the 5-year and 8-year estimated PFS were 89.6% and 76.0%, 63.9% and 58.0% for patients with stage III and IVA-B disease, which were all improved in comparison with historical controls. Grade 3 acute mucositis were developed in 27.5% patients. Cranial neuropathy and asymptomatic temporal lobe necrosis were found in 2.3% and 1.5% patients. Dose and volume de-escalated IMRT was associated with high PFS and mild late neurological toxicities for IC responders. Further exploration of de-escalation strategies in appropriate patients is needed. Clinical trials.gov identifier: NCT03389295.


Ventriculocoronary artery connections with the hypoplastic left heart: a 4-year prospective study: incidence, echocardiographic and clinical features.
Ventriculocoronary connections (VCCs), also called sinusoids, occur with hypoplastic left heart (HLH). Previous reports are limited to case reports, pathologic series, and surgical series with limited detail, which may underestimate the incidence and overestimate the severity of VCCs in HLH. A study was conducted to determine the incidence VCCs in HLH, their effect on survival, and their echocardiographic and clinical features. The echocardiograms and medical records of 100 consecutive neonatal HLH cases were analyzed. All had an aortic and a mitral valve diameter and a left ventricular (LV) volume less than Z-3. For palliation, Norwood, Sano, or hybrid procedures were used, and if the patient was alive, subsequent bidirectional Glenn and extracardiac Fontan procedures were applied. Cases were classified as manifesting mitral and aortic atresia (MAAA), mitral and aortic stenosis (MSAS), or mitral stenosis and aortic atresia (MSAA). All other diagnoses or any case with additional cardiac anomalies were excluded from the study. Overall, VCCs were found in 15% of the cases. They occurred in 56% of the MSAA subtype cases and were not statistically associated with a high mortality rate. However, in one case, large and multiple VCCs definitely caused or contributed to early death. All VCCs had a transmyocardial course, a turbulent color-Doppler flow, and a dominant usually retrograde systolic coronary artery flow pattern. The VCCs were associated (p < 0.05) with MSAA, endocardial fibroelastosis, and ascending aortic size less than 2 mm. As shown by the findings, 15% of the HLH patients had MSAA with VCCs. Unless the VCCs were large or extensive, they did not contribute to mortality. Detailed echocardiographic analysis of VCCs in HLH was feasible. Recent reports emphasize more severe cases.


The effects of drug market regulation on pharmaceutical prices in Europe: overview and evidence from the market of ACE inhibitors.
This study provides an overview of policy measures targeting pharmaceutical expenditure in Europe and analyses their impact on originator pharmaceutical prices. Panel data methods are used to examine the market of ACE Inhibitors in six European countries (Denmark, France, Germany, Netherlands, Sweden, United Kingdom) over period 1991-2006. We find that although some measures are effective in reducing originator prices, others appear to have an insignificant effect. Results suggest that supply side measures such as mandatory generic substitution, regressive pharmacy mark-ups and claw-backs are effective in reducing pharmaceuticals prices. Results are not as strong for demand side measures. Profit controls and the use of cost-effectiveness analysis appear to have a negative effect on prices, while results on reference pricing are inconclusive. Findings also indicate that, although originator prices are not immediately affected by generic entry, they may be influenced by changes in generic prices post patent expiry.


Neuromolecular Regulation of Aggression Differs by Social Role during Joint Territory Defense.
In response to a territory intrusion, neighboring males of the African cichlid fish Astatotilapia burtoni engage in aggressive joint territory defense in a manner that depends on their social role. Here, we examine the possible function of several neuroendocrine and neuromodulator pathways previously implicated in the regulation of complex social behavior. We find that the neuromolecular regulation of aggression during joint territory defense is very much dependent on an individual's role in this context. In neighbors but not in residents, aggression is correlated to gene expression in the medial part of the dorsal telencephalon (area Dm), the putative homolog to the mammalian basolateral amygdala. This correlation is strikingly high for expression of the serotonin receptor 5-HT2c, suggesting the serotonin system is important in regulating context-dependent behavior. Furthermore, by examining candidate gene expression co-variance patterns in area Dm and in the lateral part of the dorsal telencephalon (area Dl), the putative homolog to the mammalian hippocampus, we identify two main patterns: gene expression is co-regulated within, but not across, brain regions, and co-regulation is synergistic rather than antagonistic. Our results highlight the critical effect of social context on both behavior and its neuromolecular basis.


Contemporary hernia smartphone applications (apps).
Smartphone technology and downloadable applications (apps) have created an unprecedented opportunity for access to medical information and healthcare-related tools by clinicians and their patients. Here, we review the current smartphone apps in relation to hernias, one of the most common operations worldwide. This article presents an overview of apps relating to hernias and discusses content, the presence of medical professional involvement and commercial interests. The most widely used smartphone app online stores (Google Play, Apple, Nokia, Blackberry, Samsung and Windows) were searched for the following hernia-related terms: hernia, inguinal, femoral, umbilical, incisional and totally extraperitoneal. Those with no reference to hernia or hernia surgery were excluded. 26 smartphone apps were identified. Only 9 (35 %) had named medical professional involvement in their design/content and only 10 (38 %) were reviewed by consumers. Commercial interests/links were evident in 96 % of the apps. One app used a validated mathematical algorithm to help counsel patients about post-operative pain. There were a relatively small number of apps related to hernias in view of the worldwide frequency of hernia repair. This search identified many opportunities for the development of informative and validated evidence-based patient apps which can be recommended to patients by physicians. Greater regulation, transparency of commercial interests and involvement of medical professionals in the content and peer-review of healthcare-related apps is required.


Comparison of passively transferred antibodies in bighorn and domestic lambs reveals one factor in differential susceptibility of these species to Mannheimia haemolytica-induced pneumonia.
Mannheimia haemolytica consistently causes fatal bronchopneumonia in bighorn sheep (BHS; Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related species Ovis aries (domestic sheep [DS]). In BHS herds affected by pneumonia, lamb recruitment is severely impaired for years subsequent to an outbreak. We hypothesized that a lack of maternally derived antibodies (Abs) against M. haemolytica provides an immunologic basis for enhanced susceptibility of BH lambs to population-limiting pneumonia. Therefore, the objective of this study was to determine the titers of Abs directed against M. haemolytica in the sera of BH and domestic lambs at birth through 12 weeks of age. Results revealed that BH lambs had approximately 18-fold lower titers of Ab against surface antigens of M. haemolytica and approximately 20-fold lower titers of leukotoxin-neutralizing Abs than domestic lambs. The titers of leukotoxin-neutralizing Abs in the serum and colostrum samples of BH ewes were approximately 157- and 50-fold lower than those for domestic ewes, respectively. Comparatively, the higher titers of parainfluenza 3 virus-neutralizing Abs in the BH lambs ruled out the possibility that these BHS had an impaired ability to passively transfer Abs to their lambs. These results suggest that lower levels of leukotoxin-neutralizing Abs in the sera of BH ewes, and resultant low Ab titers in their lambs, may be a critical factor in the poor lamb recruitment in herds affected by pneumonia.


A new multivalent B cell activation model--anti-IgD bound to Fc gamma RI: properties and comparison with CD40L-mediated activation.
CHO cells permanently transfected with mouse Fc gamma RI alpha chain were prepared and used as a model to polyclonally activate murine B cells. The transfected CHO cells were treated with mitomycin C and placed into culture with varying quantities of anti-IgD. Using this model, murine splenic B cells (from BALB/c or C57Bl/6) were activated by mouse IgG2a-anti-IgD (10.4.22 or AF3.33) in a manner that is analogous to the activation of B cells seen with highly polyvalent anti-IgD (H delta(a)/1) prepared by chemical cross-linking to dextran. Efficient B cell activation was seen with nanogram quantities of anti-IgD. In the presence of IL-4 and IL-5, IgG1 production levels were equivalent to or better than seen when stimulation was with H delta(a)/1-dextran; however, IgE induction was not seen in either situation. The Ig production capacity was compared to that seen when B cells were activated with CD40L, using either CD40L-transfected CHO or a soluble CD40L construct. In the presence of IL-4 and IL-5, once a critical threshold of B cells was present, IgE and to a lesser extent IgG1 production was inversely proportional to B cell number when CD40L was the activating agent. In contrast, with Fc gamma RI-anti-IgD, IgM and IgG1 production was directly proportional to B cell number, while IgE production was never seen. Finally, when B cells were co-activated with immobilized anti-IgD and CD40L simultaneously, the IgE production from B cells induced by CD40L was strongly inhibited, while IgG1 and IgM production were not affected. Since B cell co-activation via sIg and CD40L would be a common scenario in secondary follicles, this inhibition of IgE production may be one of the reasons why serum IgE levels are much below IgG in normal immune situations.


Use of genetically modified mouse models to assess pathways of benzene-induced bone marrow cytotoxicity and genotoxicity.
Benzene induces bone marrow cytotoxicity and chromosomal breaks as a primary mode of action for the induction of bone marrow toxicity. Our research group has used genetically modified mouse models to examine metabolic and genomic response pathways involved in benzene induced cytotoxicity and genotoxicity in bone marrow and in hematopoietic stem cells (HSC). We review our studies using NQO1-/- mice and mEH-/- mice to examine the roles of these enzymes, NAD(P)H:quinone oxidoreductase-1 (NQO1) and microsomal epoxide hydrolase (mEH) in mediating benzene-induced toxicity. NQO1 catalyzes the detoxication of benzene quinone metabolites and mEH catalyzes the hydrolysis of benzene oxide. Our studies using gene expression profiling of bone marrow and enriched HSC populations isolated from the bone marrow of benzene-exposed mice demonstrate differential gene expression responses of key genes induced by inhaled benzene. These studies show that benzene toxicity is regulated by a number of genetic pathways that affect the production of reactive metabolites and DNA damage response pathways in a target tissue.


Increasing chronic disease preventive care in community mental health services: clinician-generated strategies.
People with a mental health condition experience a high prevalence of chronic disease risk behaviours e.g., tobacco smoking and physical inactivity. Recommended 'preventive care' to address these risks is infrequently provided by community mental health services. This study aimed to elucidate, among community mental health managers and clinicians, suggestions for strategies to support provision of preventive care. Three qualitative focus groups (n = 14 clinicians) were undertaken in one regional community mental health service to gather perspectives of barriers to preventive care provision, deductively coded against the domains of the Theoretical Domains Framework (TDF). Drawing on the learnings from the focus groups, individual interviews (n = 15 managers and clinicians) were conducted in two services to identify suggestions for strategies to increase preventive care. Strategies were inductively coded and mapped into TDF domains. Barriers were identified across a wide range of TDF domains, most notably knowledge and environmental context and resources. Nine strategies were identified across three themes: training, resources and systems changes; mapping to all 14 TDF domains. Future research seeking to increase implementation of preventive care may be guided by these findings. There is need for greater recognition and resourcing of preventive care as a priority and integral component of mental health treatment.


Expression of double-stranded RNA-activated protein kinase in keratinocytes and keratinocytic neoplasia.
Double-stranded RNA-activated protein kinase (PKR) is a interferon-induced protein initially known for its inhibitory effects on cellular and viral protein synthesis. In recent studies, PKR has been shown to be an important participant in a broad array of cellular processes, including signal transduction, differentiation, apoptosis, cell growth, and tumorigenesis. The expression of PKR in normal human keratinocytes (NHEK) was examined, and its expression in several skin lesions was compared immunohistochemically with that of proliferating cell nuclear antigen (PCNA). Expression of PKR mRNA was detected in NHEK without IFNgamma treatment; the level of PKR mRNA increased with IFNgamma treatment for two hours. Immunoblot analysis revealed that the monoclonal anti-PKR antibody reacted specifically with a 68kDa PKR protein in extracts from NHEK. Immunohistochemistry revealed that PKR protein was expressed in normal epidermis and mucosa. PKR expression was not restricted only to suprabasal cells but was also observed in basal cells positive for PCNA. In psoriatic plaques, PKR expression was lower in basal and parabasal keratinocytes and comparable in suprabasal keratinocytes to the levels in normal skin. PKR was partially detected in atypical cells in non-invasive keratinocytic neoplasia but was completely absent from undifferentiated tumor cells of squamous cell carcinoma. The present study demonstrated that PKR protein is constitutively expressed in epidermal and epithelial keratinocytes of normal skin and mucosa and indicated that a loss of PKR is not associated with the malignant transformation itself but with the increased cell proliferative activity and the altered differentiation of keratinocytes.


Children with autism spectrum disorder are skilled at reading emotion body language.
Autism is commonly believed to impair the ability to perceive emotions, yet empirical evidence is mixed. Because face processing may be difficult for those with autism spectrum disorder (ASD), we developed a novel test of recognizing emotion via static body postures (Body-Emotion test) and evaluated it with children aged 5 to 12 years in two studies. In Study 1, 34 children with ASD and 41 typically developing (TD) controls matched for age and verbal intelligence (VIQ [verbal IQ]) were tested on (a) our new Body-Emotion test, (b) a widely used test of emotion recognition using photos of eyes as stimuli (Baron-Cohen et al.'s "Reading Mind in the Eyes: Child" or RMEC [Journal of Developmental and Learning Disorders, 2001, Vol. 5, pp. 47-78]), (c) a well-validated theory of mind (ToM) battery, and (d) a teacher-rated empathy scale. In Study 2 (33 children with ASD and 31 TD controls), the RMEC test was simplified to the six basic human emotions. Results of both studies showed that children with ASD performed as well as their TD peers on the Body-Emotion test. Yet TD children outperformed the ASD group on ToM and on both the standard RMEC test and the simplified version. VIQ was not related to perceiving emotions via either body posture or eyes for either group. However, recognizing emotions from body posture was correlated with ToM, especially for children with ASD. Finally, reading emotions from body posture was easier than reading emotions from eyes for both groups.


Expression of Doublecortin, Glial Fibrillar Acidic Protein, and Vimentin in the Intact Subpallium and after Traumatic Injury to the Pallium in Juvenile Salmon, Oncorhynchus masou.
Fetalization associated with a delay in development and the preservation of the features of the embryonic structure of the brain dominates the ontogeny of salmonids. The aim of the present study was to comparatively analyze the distribution of the glial-type aNSC markers such as vimentin and glial fibrillar acidic protein (GFAP) and the migratory neuronal precursors such as doublecortin in the telencephalon subpallium of juvenile masu salmon, Oncorhynchus masou, in normal conditions and at 1 week after an injury to the dorsal pallium. Immunohistochemical labeling of vimentin, GFAP, and doublecortin in the pallium of intact juvenile masu salmon revealed single cells with similar morphologies corresponding to a persistent pool of neuronal and/or glial progenitors. The study of the posttraumatic process showed the presence of intensely GFAP-labeled cells of the neuroepithelial type that form reactive neurogenic zones in all areas of the subpallial zone of juvenile masu salmon. A comparative analysis of the distribution of radial glia in the dorsal, ventral, and lateral zones of the subpallium showed a maximum concentration of cells in the dorsal part of subpallium (VD) and a minimum concentration in the lateral part of subpallium VL. An essential feature of posttraumatic immunolabeling in the masu salmon subpallium is the GFAP distribution patterns that are granular intracellular in the apical periventricular zone (PVZ) and fibrillar extracellular in the subventricular (SVZ) and parenchymal zones (PZ). In contrast to those in intact animals, most of the GFAP+ granules and constitutive neurogenic niches in injured fish were localized in the basal part of the PVZ. With the traumatic injury to the subpallium, the number of Vim+ cells in the lateral and ventral regions significantly increased. At 1 week post-injury, the total immunolabeling of vimentin cells in the PVZ was replaced by the granular pattern of Vim immunodistribution spreading from the PVZ to the SVZ and deeper parenchymal layers of the brain in all areas of the subpallium. A significant increase in the number of DC+ cells was observed also in all areas of the subpallium. The number of cells increased both in the PVZ and in the SVZ, as well as in the deeper PZ. Thus, at 1 week after the injury to the dorsal pallium, the number of DC, Vim, and GFAP expressing cells of the neuroepithelial type in the subpallium of juvenile masu salmon increased, and additionally GFAP+ radial glia appeared in VD, which was absent from intact animals.


Physiology of na+/h+ exchangers in the male reproductive tract: relevance for male fertility.
The maintenance of pH homeostasis in the male reproductive tract is kept through the involvement of several mechanisms, among which is included the transmembranous movement of H(+) ions. Na(+)-H(+) exchangers (SLC9, solute carrier 9 family members) are among the membrane transporters known to participate in intracellular and extracellular pH regulation but also have important roles in salt and water absorption across epithelia and in the regulation of cell volume. The presence of several Na(+)-H(+) exchangers has been reported in the male reproductive tract. Their involvement in the processes that ensure the correct pursuance of the spermatogenetic event and spermatozoa maturation has been suggested. Indeed, the formation of mature spermatozoa is highly dependent on the maintenance of adequate ductal luminal milieu pH and ionic balance. Perturbations in these processes result in reduced male reproductive potential and consequently male subfertility and/or infertility. Thus, it is imperative to understand H(+) transport dynamics in order to identify and counteract possible alterations associated with reduced male fertility caused by pathological conditions. Herein, we will discuss the expression pattern and physiological roles of SLC9 family members in the cells of the male reproductive tract as well as the molecular basis of H(+) transport and its involvement in male reproductive potential.