Feasibility and effect of adding a concurrent parental component to a school-based wellness program using two modes of mobile-based technology - mixed methods evaluation of RCT.
This study assessed the feasibility and effect of two mobile modes (WhatsApp vs. a specially designed app) in their delivery of updates and assignments to parents. Two three-armed, randomized, controlled feasibility studies were conducted. In each trial, four schools with a total of 418 students in grade 5th, mean age 10.1 years, were randomly allocated to the control arm, youth-only arm, or youth & parental component arm. Only the data of those that completed all three assessments (pre, post and 3 months post program) were analyzed: 133 in the first trial and 137 in the second. In the youth-only arm, students participated in an interactive age-tailored prevention program delivered in 10 weekly, 90-min sessions on self-care behaviors, media literacy, self-esteem, and positive body image. The control groups in both studies received three health- and nutrition-related sessions. In the parental arm, in addition to the 'Favoring-Myself-Young's ten sessions program, parents received updates and were requested to complete shared assignments with their children. In the first year, the assignments were sent via WhatsApp, and in the following year via "Favoring Myself" smartphone application. Facilitators were third year undergraduate students. They used a detailed semi-structured guide and received 4-weekly hours of didactic and group dynamic supervision. Mixed-methods assessments were performed using semi-structured interviews with ten parents and five school staff members each year, as well as a computerized self-report questionnaire. Feasibility of parent-adolescent shared assignments in both digital modes was lower than expected. The use of WhatsApp had higher feasibility and uptake than the use of the special application. The addition of the concurrent parental component via WhatsApp was associated with superior improvement in self-esteem and identification of advertisement strategies, compared with the youth-only program. However, adolescents in the youth-only program delivered via the smartphone application demonstrated superior improvement compared to those in the youth and parental component arm. Although the addition of the concurrent parenting component was praised by the actively participating parents, overall, under the chosen structure and population, it did not prove to add statistically significant value to the youth-only arm. NCT03216018 (12.7.2017) and NCT03540277 (26.4.2018).


Single-molecule studies of SNARE complex assembly reveal parallel and antiparallel configurations.
Vesicle fusion in eukaryotes is thought to involve the assembly of a highly conserved family of proteins termed soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) into a highly stable parallel four-helix bundle. We have used intermolecular single-molecule fluorescence resonance energy transfer to characterize preassembled neuronal SNARE complexes consisting of syntaxin, synaptobrevin, and synaptosome-associated protein of 25 kDa on deposited lipid bilayers. Surprisingly, we found a mixture of parallel as well as antiparallel configurations involving the SNARE motifs of syntaxin and synaptobrevin as well as those of syntaxin and synaptosome-associated protein of 25 kDa. The subpopulation with the parallel four-helix bundle configuration could be greatly enriched by an additional purification step in the presence of denaturant, indicating that the parallel configuration is the energetically most favorable state. Interconversion between the configurations was not observed. From this observation, we infer the conversion rate to be <1.5 h-1. The existence of antiparallel configurations suggests a regulatory role of chaperones, such as N-ethylmaleimide-sensitive factor, or the membrane environment during SNARE complex assembly in vivo, and it could be a partial explanation for the relatively slow rates of vesicle fusion observed by reconstituted fusion experiments in vitro.


Oral host-microbe interactions investigated in 3D organotypic models.
The oral cavity is inhabited by abundant microbes which continuously interact with the host and influence the host's health. Such host-microbe interactions (HMI) are dynamic and complex processes involving e.g. oral tissues, microbial communities and saliva. Due to difficulties in mimicking the in vivo complexity, it is still unclear how exactly HMI influence the transition between healthy status and disease conditions in the oral cavity. As an advanced approach, three-dimensional (3D) organotypic oral tissues (epithelium and mucosa/gingiva) are being increasingly used to study underlying mechanisms. These in vitro models were designed with different complexity depending on the research questions to be answered. In this review, we summarised the existing 3D oral HMI models, comparing designs and readouts, discussing applications as well as future perspectives.


Role of fluctuations in membrane models: thermal versus nonthermal.
We study the comparative importance of thermal to nonthermal fluctuations for membrane-based models in the linear regime. Our results, both in 1+1 and 2+1 dimensions, suggest that nonthermal fluctuations dominate thermal ones only when the relaxation time τ is large. For moderate to small values of τ, the dynamics is defined by a competition between these two forces. The results are expected to act as a quantitative benchmark for biological modeling in systems involving cytoskeletal and other nonthermal fluctuations.


Interrelationship between metacarpal bone mass and bone mineral content in renal transplant recipients.
Metacarpal bone mass, bone mineral content in the forearm and bone mineral concentration were measured in 54 renal transplant recipients with a well functioning renal transplant a mean of 67 months after transplantation. Significantly decreased values of metacarpal bone mass, bone mineral content and bone mineral concentration were found. A highly significant correlation between metacarpal bone mass and bone mineral concentration was found in renal transplant recipients, probably indicating that changes in the amount of cortical bone and bone mineral occur simultaneously after renal transplantation.


Psychometric properties of a color-shape version of the switch task.
The current study aims to examine the psychometric properties of a color-shape version of the switch task. In Study 1, 128 participants completed a battery of standardized measures of executive functions (EFs) as well as the switch task to determine the construct validity of three traditionally computed costs (global, switch, and mixing) and primary variables (accuracy [ACC], reaction time [RT], and inverse efficiency score [IES] of the heterogeneous condition). In Study 2, 48 participants completed the task twice, seven days apart, to evaluate its short-term test-retest reliability. Results do not support the construct validity and the test-retest reliability of switch and mixing costs. The overall higher psychometric properties of the global costs (RT and IES), and primary variables (Hetero RT and IES) suggest that they may be useful measures for clinicians to assess EFs. The latter variables show evidence of convergent validity with standardized measures of EFs and good test-rest reliability (ICC ≥ .68).


Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains.
Parkinson's disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa - LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio.


Prior authorization for topical psoriasis treatments: is it cost-beneficial for managed care?
The introduction of novel therapeutic options for psoriasis has raised managed care's interest in controlling costs associated with dermatological treatments. Prior authorization (PA) can be a successful way of managing costs. However, experience with topical treatments for acne suggests that PA may not be cost-effective. The role of managed care in dermatology and the potential impact of PA requirements for novel topical therapies for psoriasis are considered. Using a model based on recent survey data, total annual cost estimates for a managed care organization to cover psoriasis treatment with a topical agent with or without PA requirements were calculated and compared. Costs for treatment and administrative costs associated with PA processes were included. The model assumed 68 000 insured patients required treatment (with an additional 1% to account for abuse/misuse), an average wholesale price of $100 per prescription (each prescription filled 4x/year), and a cost of $20 to process each PA request. The total annual costs were $28 573 600 when PA was required and $27 472 000 when PA was not required. Thus, there was a total annual loss to the managed care organization of $1 101 600 associated with PA requirements. Requiring PA for novel topical treatments for psoriasis, such as the new two-compound product containing calcipotriene and betamethasone dipropionate (Taclonex((R)); Warner Chilcott (US), Inc.; marketed as Daivobet((R))/Dovobet((R)) outside US by LEO Pharma), is not likely to be cost-effective for a managed care organization.


Bulevirtide for patients with compensated chronic hepatitis delta: A review.
Chronic hepatitis delta (CHD) affects approximately 10-20 million people worldwide and represents the most severe form of chronic viral hepatitis, as it is characterized by high rates of progression to cirrhosis and its complications (end-stage liver disease, hepatocellular carcinoma). In the last 30 years, the only treatment option for CHD has been represented by the off-label administration of Interferon (or Pegylated Interferon)-alpha: antiviral treatment, however, resulted in suboptimal (20-30%) virological response and was burdened by several side effects, de facto contraindicating Interferon (IFN) administration in patients with more advanced liver disease. Recently, Bulevirtide (BLV), a first-in-class HBV-HDV entry inhibitor blocking Na+ -taurocholate co-transporting polypeptide (NTCP), has provided very promising efficacy data in Phase II and Phase III (interim analysis) trials as well as in preliminary real-life reports. In July 2020, BLV has granted conditional approval by EMA for treatment of compensated CHD, at the dose of 2 mg/day by self-administered subcutaneous injections. In Phase II and Phase III trials, BLV was evaluated at different doses (2 vs. 10 mg/day) for 24 or 48 weeks, either in monotherapy or in combination with PegIFN. Administration of BLV monotherapy for 24 or 48 weeks resulted in 50%-83% virological response (HDV RNA ≥ 2 Log decline) rates and 45%-78% ALT normalization. Combination therapy with PegIFN provided synergistic effects. These results were replicated in real-life studies and confirmed also in patients with advanced cirrhosis and clinically significant portal hypertension. BLV treatment was optimally tolerated, resulting only in an asymptomatic increase of bile acids.


N-Aryltrifluoromethanesulfonimides as new trifluoromethylating agents for the (photo)catalyst-free functionalization of (hetero)aromatics.
The photoinduced (by UV or sunlight) catalyst-free radical trifluoromethylation of (hetero)aromatics (up to 87% yield) has been successfully achieved by using N-aryltrifluoromethanesulfonimides as the trifluoromethylating agents. The process likewise occurred under continuous flow conditions.


[Mastodynia. Premenstrual syndrome].
Mastodynia is defined as breast tenderness and pain, also called mastalgia. There are several types of cyclic, noncyclic and extramammary. The cyclic mastodynia is the most common one, and represents a clinical symptom of the premenstrual syndrome and of the more severe premenstrual dysphoric disorder. The article outlines different types of mastalgia with their typical clinical features, including the relatively rear Tietze's syndrome and MONDOR'S disease, as well as the PMS and the PMDD. The authors also offer a diagnostic algorithm and specific diagnostic criteria. There is also a discussion on the main treatment alternatives being symptomatic treatment of the most troublesome symptoms or alteration of the menstrual cycle and a brief discussion on the pharmaceutical preparations used for treatment including the administration of selective serotonin reuptake inhibitors (SSRI).


Inherited cortical HCN1 channel loss amplifies dendritic calcium electrogenesis and burst firing in a rat absence epilepsy model.
While idiopathic generalized epilepsies are thought to evolve from temporal highly synchronized oscillations between thalamic and cortical networks, their cellular basis remains poorly understood. Here we show in a genetic rat model of absence epilepsy (WAG/Rij) that a rapid decline in expression of hyperpolarization-activated cyclic-nucleotide gated (HCN1) channels (I(h)) precedes the onset of seizures, suggesting that the loss of HCN1 channel expression is inherited rather than acquired. Loss of HCN1 occurs primarily in the apical dendrites of layer 5 pyramidal neurons in the cortex, leading to a spatially uniform 2-fold reduction in dendritic HCN current throughout the entire somato-dendritic axis. Dual whole-cell recordings from the soma and apical dendrites demonstrate that loss of HCN1 increases somato-dendritic coupling and significantly reduces the frequency threshold for generation of dendritic Ca2+ spikes by backpropagating action potentials. As a result of increased dendritic Ca2+ electrogenesis a large population of WAG/Rij layer 5 neurons showed intrinsic high-frequency burst firing. Using morphologically realistic models of layer 5 pyramidal neurons from control Wistar and WAG/Rij animals we show that the experimentally observed loss of dendritic I(h) recruits dendritic Ca2+ channels to amplify action potential-triggered dendritic Ca2+ spikes and increase burst firing. Thus, loss of function of dendritic HCN1 channels in layer 5 pyramidal neurons provides a somato-dendritic mechanism for increasing the synchronization of cortical output, and is therefore likely to play an important role in the generation of absence seizures.


Predictive role of molecular subtypes in response to neoadjuvant chemotherapy in breast cancer patients in Northeast China.
Breast cancer is increasingly regarded as a heterogeneous disease which can be classified into distinct molecular subtypes with prognostic significance. ER, PR, HER2 and ki-67 were used to divided 102 breast cancers treated with neoadjuvant chemotherapy (NCT) into 4 subtypes: luminal A (ER+, PR+, HER2-, and ki-67≤14%), luminal B (ER+, PR+, HER2- and ki-67>14% ; ER+ and/or PR+, HER2+), HER2-overexpression (ER-, PR- and HER2+) and triple-negative (ER-, PR-, and HER2-). Among 102 patients, a pCR was seen in 16 (15.7%) patients. The pathologic complete remission (pC) rates according to different subtypes are as follows: luminal A, 0 of 20 (0.0%), luminal B, 2 of 23 (8.7%), HER2-overexpression 4 of 18 (22.2%), and triple-negative, 10 of 41 (24.4%) (p=0.041). In triple-negative subtype patients, the rates of pCR differed significantly among the 3 chemotherapy regimens with 5.6% (1/18) for CEF (cyclophosphamide, epirubicin and flurouracil), 20.0% (1/5) for TE (docetaxel and epirubicin) and 44.4% (8/18) for TCb (docetaxel and carboplatin) (p=0.024). In locally advanced breast cancer patients, the rates of pCR seem to differ among the 3 chemotherapy regimens with 6.7% (2/30) for CEF, 0.0% (0/8) for TE and 23.1% (6/26) for TCb, but this did not attain statistical significance (p>0.05). Molecular subtypes are good predictors for response to NCT in breast cancer patients in Northeast China. Compared with luminal A tumors, HER2-overexpression and triple-negative subtypes are more sensitive to NCT. For triple-negative breast cancer, we concluded that the TCb combination is a promising NCT regimen. Our results also indicated that the TCb combination is promising for the treatment of locally advanced breast cancer.


Immunohistochemical Analysis of Mismatch Repair Gene Proteins in Early Gastric Cancer Based on Microsatellite Status.
Microsatellite instability (MSI) is a major pathway involved in gastric carcinogenesis and is observed in 10-20% of early gastric cancers (EGCs). Early detection of EGCs with an MSI-high phenotype would be useful for elucidating the mechanisms of gastric carcinogenesis and improving outcomes in patients with GC. We explored the usefulness of immunohistochemical expression of mismatch repair (MMR) proteins, including MLH1, PMS2, MSH2, and MSH6 in EGC. We examined the expression of 4 MMR proteins using immunohistochemistry in 119 patients with EGC based on MS status, as determined by polymerase chain reaction-microsatellite analysis. In addition, methylation of the MLH1 gene was quantified by pyrosequencing. EGCs were classified into 46 MSI-high phenotypes and 73 microsatellite stable (MSS) phenotypes. Although loss of MLH1 expression was associated with loss of PMS2 expression in the MSI-high phenotype, discordant cases of loss of expression between MLH1 and PMS2 were found (MLH1 [-]/PMS2 [+], 3 cases). Loss of MLH1/PMS2 expression was observed in 2 of 73 MSS phenotypes. Loss of MSH2/MSH6 expression was found in 4 of 46 MSI-high phenotypes, whereas loss of MSH2/MSH6 expression was not detected in the MSS phenotype. In addition, loss of MLH1 expression was correlated with methylation of MLH1. However, there were discordant cases in which loss of MLH1 expression was not accompanied by methylation of MLH1. Although immunostaining of MMR proteins could help predict MSI in EGCs, immunostaining did not have the same value as genetic testing for determination of MSI.


The impact of cell phone texting on superficial blood flow, touch threshold, and symptoms for individuals with carpal tunnel syndrome.
It is unclear how individuals with carpal tunnel syndrome (CTS) are affected by texting, or how the texting performance of those with CTS might be impaired or different from individuals without CTS. The primary purpose of this case-control study was to determine the immediate effects of texting on superficial blood flow, sensory threshold, and symptoms of fatigue, numbness, and pain for individuals with CTS compared to asymptomatic age-matched controls. Another objective was to detect differences in texting performance between the two groups. Superficial blood flow, pain, fatigue, numbness, and touch threshold were measured before, and at three time points following a standardized 15-minute texting task. Overall texting speed was compared between groups. Changes in red blood cell concentration after the texting task was not significantly different for either the CTS group or controls for any of the measurement time points. Mean touch thresholds at baseline were 4.0 g/mm2 for the CTS group versus 2.6 g/mm2 for healthy controls; a 53%greater touch threshold. Following the texting task, touch threshold did not change for normal controls, but increased to 6.7 g/mm2 for the CTS group, representing a significant increase in touch threshold from baseline. Texting performance was compromised in people with CTS, and symptoms worsened with a short-term controlled texting task. Our results suggest that texting performance is limited in individuals with CTS and that texting results in a short term increase in touch threshold values for individuals with CTS. Further study is needed to determine the effect of long term texting on carpal tunnel pressures.


Depth in box spaces.
Human observers adjust the frontal view of a wireframe box on a computer screen so as to look equally deep and wide, so that in the intended setting the box looks like a cube. Perspective cues are limited to the size-distance effect, since all angles are fixed. Both the size on the screen, and the viewing distance from the observer to the screen were varied. All observers prefer a template view of a cube over a veridical rendering, independent of picture size and viewing distance. If the rendering shows greater or lesser foreshortening than the template, the box appears like a long corridor or a shallow slab, that is, like a 'deformed' cube. Thus observers ignore 'veridicality'. This does not fit an 'inverse optics' model. We discuss a model of 'vision as optical user interface'.


Radiosensitizing effect of electrochemotherapy in a fractionated radiation regimen in radiosensitive murine sarcoma and radioresistant adenocarcinoma tumor model.
Electrochemotherapy can potentiate the radiosensitizing effect of bleomycin, as shown in our previous studies. To bring this treatment closer to use in clinical practice, we evaluated the interaction between electrochemotherapy with bleomycin and single-dose or fractionated radiation in two murine tumor models with different histology and radiosensitivity. Radiosensitive sarcoma SA-1 and radioresistant adenocarcinoma CaNT subcutaneous tumors grown in A/J and CBA mice, respectively, were used. The anti-tumor effect and skin damage around the treated tumors were evaluated after electrochemotherapy with bleomycin alone or combined with single-dose radiation or a fractionated radiation regimen. The anti-tumor effectiveness of electrochemotherapy was more pronounced in SA-1 than CaNT tumors. In both tumor models, the tumor response to radiation was not significantly influenced by bleomycin alone or by electroporation alone. However, electrochemotherapy before the first tumor irradiation potentiated the response to a single-dose or fractionated radiation regimen in both tumors. For the fractionated radiation regimen, normal skin around the treated tumors was damaged fourfold less than for the single-dose regimen. Electrochemotherapy prior to single-dose irradiation induced more damage to the skin around the treated tumors and greater loss of body weight compared to other irradiated groups, whereas electrochemotherapy combined with the fractionated radiation regimen did not. Electrochemotherapy with low doses of bleomycin can also be used safely for radiosensitization of different types of tumors in a fractionated radiation regimen, resulting in a good anti-tumor effect and no major potentiating effect on radiation-induced skin damage.


Preparation of Thin-Film Composite Nanofiltration Membranes Doped with N- and Cl-Functionalized Graphene Oxide for Water Desalination.
In the present work, chemically modified graphene oxide (GO) was incorporated as a crosslinking agent into thin-film composite (TFC) nanofiltration (NF) membranes for water desalination applications, which were prepared by the interfacial polymerization (IP) method, where the monomers were piperazine (PIP) and trimesoyl chloride (TMC). GO was functionalized with monomer-containing groups to promote covalent interactions with the polymeric film. The composite GO/polyamide (PA) was prepared by incorporating amine and acyl chloride groups into the structure of GO and then adding these chemical modified nanomaterial during IP. The effect of functionalized GO on membrane properties and performance was investigated. Chemical composition and surface morphology of the prepared GO and membranes were analyzed by thermogravimetric analysis (TGA), Raman spectroscopy, FTIR spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM). The fabricated composite membranes exhibited a significant increase in permeance (from 1.12 to 1.93 L m-2 h-1 bar-1) and salt rejection for Na2SO4 (from 95.9 to 98.9%) and NaCl (from 46.2 to 61.7%) at 2000 ppm, when compared to non-modified membranes. The amine- and acyl chloride-functionalized GO showed improved dispersibility in the respective phase.


Effects of growth parameters on the structural and optical properties of InP/InGaP quantum structures for 808-nm-wavelength emissions.
InP/InGaP quantum structures with 808-nm-wavelength emissions were grown on semi-insulating GaAs (100) substrates via migration-enhanced molecular beam epitaxy. The effects of the growth conditions on the structural and optical properties of the InP/InGaP quantum structures were investigated. The scanning electron microscopy and atomic force microscopy images showed that the two-dimensional InP/InGaP quantum structures were transited to one-dimensional structures with an increasing repetition cycle. The photoluminescence spectra showed that the optical properties of the InP/InGaP quantum structures were significantly affected by various migration-enhanced epitaxy repetition numbers and growth temperatures. These results can help improve understanding of the effects of growth parameters on the structural and optical properties of InP/InGaP quantum structures for 808-nm-wavelength emissions.


Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men.
With increasing evidence for faulty paternal contribution to reproduction, there has been a steady increase in studies highlighting an association between sperm DNA damage, failed/delayed fertilisation and aberrant embryo development. Owing to prevailing ambiguity, the aims of the study were to analyse the genetic integrity of the male gamete and then to understand its association with age, standard semen parameters, lifestyle and occupational factors. The study included 504 subjects, attending university infertility clinic for fertility evaluation and treatment. Semen characteristics were analysed by standard criteria; terminal deoxynucelotidyl transferase-mediated nick end-labelling assay was employed for DNA damage assessment. The average incidence of sperm DNA damage in patients with normozoospermic semen parameters was <10%. Patients with oligozoospermia, severe oligozoospermia, oligoasthenoteratospermia, asthenoteratozoospermia and necrozoospermia had significantly higher level of sperm DNA damage (P < 0.001). Patients above 40 years of age had significantly high levels of DNA damage (P < 0.001) compared with their counterparts. Patients with varicocele and a history of alcohol consumption had higher incidence of spermatozoa with DNA damage (P < 0.01). Poor sperm characteristics in the ejaculate are associated with increased sperm DNA damage. Age-related increase in sperm DNA damage and association of the same with varicocele and alcohol consumption are also demonstrated.


Stem stiffness functionality in a submerged canopy patch under oscillatory flow.
Seagrass canopies are coastal ecosystems that are able to modify the abiotic environment through their architectural structure. They have different structural parameters, such as plant stem stiffness, patch length and canopy density, all of which determine their overall functionality in modifying the seafloor hydrodynamics within coastal areas. To determine the interaction between hydrodynamics and the canopy structure, a set of laboratory experiments were carried out with both rigid and flexible stems for different canopy densities, patch lengths and wave frequencies. In the upper part of the canopy, flexible plants move with the flow without generating drag or producing turbulent kinetic energy, while rigid plants generate drag and produce turbulent kinetic energy. In the inner canopy layer, both types of plants behave like rigid stems and produce turbulent kinetic energy. A non-dimensional model based on the turbulent kinetic energy, the wave velocity and the plant characteristics is presented to describe the behaviour of flexible and rigid plants under an oscillating flow. Flexible plants behave in a stiffer manner under high wave frequencies than under low wave frequencies, thus making their behaviour closer to that of rigid plant stems. This difference between both canopy structures can explain their distribution in the environment, with rigid canopies being more extended in more sheltered regions while flexible plants are characteristic of more exposed regions with high flow energy.


Steroidal alkaloids from the leaves of Sarcococca coriacea of Nepalese origin.
Two new steroidal alkaloids, (-)-vaganine D (1) [(20S)-20-(N,N-dimethylamino)-3 beta-(senecioylamino)-5 alpha-pregn-16-en-4 beta-yl acetate], and (+)-nepapakistamine A (2) [(20S)-20-(N-methylamino)-3 beta-(tigloylamino)-5 alpha-pregn-16-en-2 beta,4 beta-diacetate], were isolated from the leaves of Sarcococca coriacea. Their structures were elucidated on the basis of their spectral properties. Compounds 1 and 2 were found to be cholinesterase inhibitors.


Pharmacokinetics and brain uptake of a genetically engineered bifunctional fusion antibody targeting the mouse transferrin receptor.
Monoclonal antibodies (MAbs) are potential new therapeutics for brain diseases. However, MAbs do not cross the blood-brain barrier (BBB). The present work describes the genetic engineering of a fusion protein composed of a therapeutic single chain Fv (ScFv) antibody and a mouse/rat chimeric MAb against the mouse transferrin receptor (TfR). The TfRMAb acts as a molecular Trojan horse to ferry the therapeutic ScFv across the BBB in vivo in the mouse. The ScFv is fused to the carboxyl terminus of the heavy chain of the chimeric TfRMAb, and this fusion protein is designated cTfRMAb-ScFv. Chinese hamster ovary cells were permanently transfected, and a high secreting cell line in serum free medium was cloned. The cTfRMAb-ScFv fusion protein was purified to homogeneity on gels and Western blotting with protein G affinity chromatography. The cTfRMAb-ScFv fusion protein was bifunctional and bound both the target antigen, as determined by ELISA, and the mouse TfR, as determined with a radio-receptor assay. The cTfRMAb-ScFv fusion protein was radio-iodinated with the Bolton-Hunter reagent, and a pharmacokinetics study in mice showed that the fusion protein was rapidly cleared from blood with a median residence time of 175 +/- 32 min. The fusion protein was avidly taken up by brain with a % injected dose (ID)/g of 3.5 +/- 0.7, as compared to an MAb with no receptor specificity, which was 0.06 +/- 0.01% ID/g. These studies demonstrate that therapeutic MAbs may be re-engineered as fusion proteins with BBB molecular Trojan horses for targeted delivery across the BBB in vivo.


Psychogenic urinary retention in children: a case report.
Psychogenic urinary retention occurs relatively infrequently in children and is less common than in adults. The influence of psychogenic factors on voiding generally results in an irritative syndrome, but rarely in urinary retention. A definitive diagnosis is established by excluding other pathological conditions. Evaluation includes urine culture, renal echography, spine magnetic resonance imaging, voiding cysto-urethrography, intravenous pyelography, and uroflowmetry. Here, we report on a 6-year-old girl with a 1-month history of voiding difficulty. Urology studies, including urine culture, revealed Escherichia coli, which was not present in preadmission urine cultures. Renal ultrasound and radiological images showed no gross abnormalities or vesicoureteral reflux, but uroflowmetry showed a low flow rate with residual urine. The results of imaging studies and pediatric psychiatric consultation led to a diagnosis of psychogenic urinary retention combined with urinary tract infection. Urinary rehabilitation included intermittent catheterization, bladder training, and supportive psychotherapy, after which the patient recovered and was discharged.


Fundamental calculations on the surface area determination of supported gold nanoparticles by alkanethiol adsorption.
Surface area determination is a crucial step for the characterization of the activity of noble metal catalysts. Not only the development of useful determination methods but foremost the understanding of surface properties and their conversion into mathematical expressions are essential to obtain reliable results. A selective method to gain access to the specific surface area of gold on oxidic supports is the chemisorption of alkanethiol from suspensions. Therefore, the concentration of a 1-dodecanthiol solution before and after immersion of supported gold catalysts was determined by gas chromatography. To convert the concentration information into a specific surface area, the surface coverage, the surface atom concentration, the interatomic Au-Au distance, and the particle morphology were considered. Further calculations afforded the determination of a mean particle diameter. A good agreement was found between gold particle sizes obtained from transmission electron microscopy and thiol adsorption. The given mathematical expressions are highly valuable for a broad range of chemisorption methods and noble metal catalysts.


Microsurgical treatment of recurrent nasal polyposis.
Nasal polyposis has to be considered as an advanced form of chronic ethmoiditis requiring surgery. Its proliferation starts in the osteo-meatal complex of the lateral nasal wall, and follows typical routes. Depending on its extension endoscopical partial resections of the ethmoid may be carried out. For diffuse polyposis of all sinuses a complete endonasal ethmoidectomy together with the fenestration of the frontal, sphenoidal and maxillary sinuses (pansinus operation) is indicated. The importance of preoperative imaging by CT or polytomography, and of flanking measures, is stressed. Fair results concerning subjective relief and objective proof of lasting mucosal recovery are reported against the background of a low incidence of surgical complications.


LED-based indoor positioning system using novel optical pixelation technique.
At present, about 47 million people worldwide have Alzheimer's disease (AD), and because there is no treatment currently available to cure AD, people with AD (PWAD) are cared for. The estimated cost of care for PWAD in 2016 alone is about $236 billion, which puts a huge burden on relatives of PWAD. This work aims to reduce this burden by proposing an inexpensive indoor positioning system that can be used to monitor PWAD. For the positioning, freeform lenses are used to enable a novel optically pixeled LED luminaire (OPLL) that focuses beams from LEDs to various parts of a room, thereby creating uniquely identifiable regions which are used to improve positioning accuracy. Monte Carlo simulation with the designed OPLL in a room with dimensions 5 m × 5 m × 3 m is used to compute the positioning error and theoretical analysis and experiments are used to validate the time for positioning. Results show that by appropriate LED beam design, OPLL has a positioning error and time for positioning of 0.735 m and 187 ms which is 55.1% lower and 1.2 times faster than existing multiple LED estimation model proximity systems.


Intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation for preservation of facial nerve function in patients with large acoustic neuroma.
Although various monitoring techniques have been used routinely in the treatment of the lesions in the skull base, iatrogenic facial paresis or paralysis remains a significant clinical problem. The aim of this study was to investigate the effect of intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation on preservation of facial nerve function. From January to November 2005, 19 patients with large acoustic neuroma were treated using intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation (TCEMEP) for preservation of facial nerve function. The relationship between the decrease of MEP amplitude after tumor removal and the postoperative function of the facial nerve was analyzed. MEP amplitude decreased more than 75% in 11 patients, of which 6 presented significant facial paralysis (H-B grade 3), and 5 had mild facial paralysis (H-B grade 2). In the other 8 patients, whose MEP amplitude decreased less than 75%, 1 experienced significant facial paralysis, 5 had mild facial paralysis, and 2 were normal. Intraoperative TCEMEP can be used to predict postoperative function of the facial nerve. The decreased MEP amplitude above 75 % is an alarm point for possible severe facial paralysis.


[Amyloidosis. II. Current pathogenetic and clinico-nosographic aspects].
Amyloidosis is due to the overproduction of a precursor protein and its conversion into products capable of polymerisation into fibrils. The primary form, or that associated with multiple myeloma or Waldenström's macroglobulinaemia, marked by the presence of protein AL, includes the overproduction of Ig light chains followed by conversion on the part of lysosome enzymes. The forms can thus be classified as immunoproliferative diseases (plasma-cell dyscrasias). Secondary amyloidosis is primarily associated with neoplasia or chronic inflammation. Its biochemical label is the AA protein. Initially, there is overproduction of protein SAA, while the formation of AA-amyloid fibrils may theoretically be attributed to a variety of factors: changes in the amount of circulating SAA, the presence of amyloidogenetic SAA, variations in the activity of SAA catabolic systems, insufficient removal of acculated fibrils. The way in which the immunocompetent system intervenes is a controversial subject. Lesser froms of amyloidosis are known in which there are local deposits of amyloid: APUD-amyloidosis, amyloidomas. In some forms, the features of systemic accumulation are maintained, but only one organ is primarily involved. They are rarely of clinical significance (e.g. senile amyloidosis). Current biochemical techniques enable a clinical and nosographic distinction to be drawn between an Ig (AL)-amyloidosis and non-Ig (AA, APUD and AS) forms.


The relationship between the conflict management strategies and ethical leadership behaviours of nurse managers perceived by nurses.
The aims of this study were to determine nurse managers' level of ethical leadership perceived by nurses and to examine its relationship with conflict management strategies. Ethical leadership is about how managers use their power in their decisions and actions, and its source is based on moral and ethical authority. Therefore, it is important to understand the impact of ethical behaviours of nurse managers in the work environment on determining conflict management strategies. The data of this descriptive, correlational, and cross-sectional study were collected face-to-face from 285 nurses between April-June 2019. The data collection instruments included the introductory information form, the Ethical Leadership Scale, and The Rahim Organizational Conflict Inventory-II. Ethical leadership scores perceived by nurses in nurse managers were found 3.78, and the highest score was obtained from the behavioural ethics subscale (3.81 ± .91). In conflict management strategies perceived by nurses, it was determined that they got highest scores from collaborating style (3.76 ± .90) and lowest scores from competing style (2.90 ± .94). There was no significant relationship only between ethical leadership and its subscales and competing (r: -.038/-.041, p > .05). In other subscales, there were positive, moderate, and highly significant relationships (r: .466-.747, p < .001). The rate of explanatoriness of communicative ethics subscale in conflict management strategies ranged from 22.3% to 58.0%. The study shows that communicative ethics subscale significantly affects the conflict management strategies of nurse managers. Therefore, it is important for nurse managers to communicate bilaterally and be a role model for nurses. Ethical leaders value trust and respect in their interactions with employees and reflect what appropriate behaviour to the situation is. Nurses who perceive that their managers demonstrate ethical leadership behaviours will also evaluate their role in conflict resolution. On the other hand, the power-based, aggressive, noncompromising domination approach that the person imposes on others is not associated with the ethical leadership perception towards their managers by nurses and is a strategy that should not be preferred. Therefore, nurse managers who use appropriate conflict management strategies were seen as a role model by nurses.


Surveillance and management for serous cystic neoplasms of the pancreas based on total hazards-a multi-center retrospective study from China.
Serous cystic neoplasms (SCN) rarely have malignant potential, so accurate diagnosis of SCN is crucial for proper clinical management, especially to avoid unnecessary surgeries. However, the misdiagnosis of other pancreatic cystic neoplasm instead of SCN may highly increase the risk of malignancy in patients who receive no surgery. Data from a total of 678 patients with pathologically confirmed to have SCN at sixteen institutions in China from January 1st, 2006 to December 31st, 2016 were retrieved to evaluate the malignancy risk of SCN. Among the 678 patients confirmed to have SCN with postoperative pathologic analysis, 649 patients (95.7%) had only one lesion and the average maximum diameter was 3.8±2.47 cm. Four patients were pathologically verified as having serous cystadenocarcinoma, so the SCN actual malignancy rate was 0.6%, while the mortality due to pancreatic surgery in these high-volume centers was nearly 0.2-2%. However, among the 99 SCN patients based on preoperative radiology, three were confirmed to have intraductal papillary mucinous neoplasms (IPMN), nine as mucinous cystic neoplasms (MCN), and four as solid pseudopapillary tumors (SPT) after postoperative pathological analysis. Thus, the total theoretical malignancy rate resulting from preoperative misdiagnosis was elevated to approximately 2.9%, higher than the risk of perioperative mortality. When SCN can't be accurately distinguished from cystic tumors of pancreas, the malignant risk of cystic tumors may be higher than perioperative risk. However, if it can be diagnosed as SCN accurately, surgery can be avoided as well.


Self-referenced interferometry for single-shot detection of vector-vortex beams.
Vector-vortex (VV) beams are of significant interest for various applications. There have been substantial efforts toward developing a fast and efficient method for the characterization of generated VV beams which is crucial for their usage. Polarimetric approaches are commonly used to identify unknown VV beams but require multiple intensity recordings. This paper demonstrates a technique to detect VV beams and identify their parameters using the concept of self-referenced interferometry. The approach uses a single recorded interferogram to determine the beam parameters that allow rapid detection. The method even enables detection of VV beams having high-order optical vortices.


Volatile induction/maintenance of anaesthesia with sevoflurane increases jugular venous oxygen saturation and lumbar cerebrospinal fluid pressure in patients undergoing craniotomy.
Sevoflurane is a widely used volatile agent in neuroanaesthesia, and its nonirritant properties on the respiratory tract make sevoflurane suitable for volatile induction/maintenance of anaesthesia (VIMA). In the current trial, we investigate the effects of sevoflurane VIMA on lumbar cerebral fluid pressure (LCSFP) and jugular venous oxygen partial pressure in patients undergoing craniotomy for supratentorial intracranial surgery under bispectral index monitoring, determine jugular bulb venous oxygen saturation (SjvO2) and calculate cerebral perfusion pressure (CPP), arteriojugular venous oxygen content difference and cerebral oxygen extraction rate (COER) at different time points during the operation. Moreover, we compare these with total intravenous anaesthesia (TIVA) in patients receiving remifentanil and propofol continuous infusion. Twenty-six adult patients undergoing elective craniotomy were randomly allocated to either remifentanil-propofol (group TIVA) or sevoflurane (group VIMA). Mean arterial blood pressure, heart rate, LCSFP, CPP, SjvO2, arteriojugular venous oxygen content difference and COER were compared in the two groups at different time points under bispectral monitoring. Heart rate, mean arterial blood pressure, saturation of peripheral oxygen, BIS value and LCSFP were recorded at the time points including intubation (Tintub), 5 min (T5'int) and 15 min (T15'int) after intubation, the beginning of surgery (Tsurg), 5 min (T5m), 0.5 h (T0.5h), 1 h (T1h), 1.5 h (T1.5h), 2 h (T2h) and 2.5 h (T2.5h) after incision, the end of surgery (Tend), extubation (Textub) and 30 min (T30'end) after surgery. Arterial blood gas and jugular venous bulb blood gas analysis were performed at the time points of T0, T5'int, T5m, T1h, T2h, Tend, 15 min after operation (T15'end) and T30'end. LCSFP was increased above baseline levels in group VIMA and decreased in group TIVA from Tintub to T5m, and decreased to similar levels from T0.5h to T30'end in both groups. Mean arterial blood pressure was decreased to similar levels from T0.5h to Tend and returned to baseline levels at T30'end in both groups, and was significantly higher in group VIMA than in group TIVA at T5'int, T15'int, Tsurg and T5m. CPP was decreased to similar levels between the groups from T0.5h to Tend and returned to baseline levels at T30'end in both groups, and was significantly higher at Tintub, T5'int and T15'int in group VIMA than in group TIVA. Jugular venous oxygen partial pressure and SjvO2 were increased above baseline level from T5'int to T30'end in group VIMA, and decreased from T5'int to Tend, and returned to baseline level at T30'end in group TIVA. Arteriojugular venous oxygen content difference and COER were decreased from T5'int to T30'end in group VIMA, and increased above the baseline level from T5'int to Tend, and returned to the baseline level at T30'end in group TIVA. Sevoflurane VIMA increases SjvO2, lumbar CSF pressure and CPP, and decreases COER, which suggested that VIMA could be a better choice for patients with the risk of cerebral hypoperfusion or insufficient oxygen delivery. Propofol-based TIVA is associated with decreased SjvO2, LCSFP and CPP, and increased COER, and it might be suitable for patients with increased intracranial pressure.


Metastasis tumour suppressor-1 and the aggressiveness of prostate cancer cells.
Previous studies have suggested that metastasis tumour suppressor-1 (MTSS1) plays a key role in cancer metastasis. Firstly, in this study we assessed MTSS1 expression levels in prostate cancer cell lines to reveal any changes in cell properties. Secondly, we aimed to clarify the cellular function of MTSS1 in prostate cancer cells. MTSS1 expression levels were assessed in different types of cancer cell lines through the RT-PCR analysis technique. The influence of MTSS1 was further examined via biological overexpression and knockdown in the prostate cancer cell lines. Two prostate cell lines were chosen for either knockdown or overexpression of the MTSS1 gene. The overexpression of MTSS1 in PC-3 human prostate cancer cells significantly suppressed the migratory, growth and adherence properties of the cells (p<0.01). By contrast, the knockdown of MTSS1 in DU-145 human prostate cancer cells dramatically enhanced these properties (p<0.001). We concluded that MTSS1 demonstrates the ability to play a role in controlling the metastatic nature of prostate cancer cells.


Arsenic in cancer treatment: challenges for application of realgar nanoparticles (a minireview).
While intensive efforts have been made for the treatment of cancer, this disease is still the second leading cause of death in many countries. Metastatic breast cancer, late-stage colon cancer, malignant melanoma, multiple myeloma, and other forms of cancer are still essentially incurable in most cases. Recent advances in genomic technologies have permitted the simultaneous evaluation of DNA sequence-based alterations together with copy number gains and losses. The requirement for a multi-targeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biological and cytotoxic agents is currently under investigation in multimodal treatment regimens. Similarly, a combinational principle is applied in traditional Chinese medicine, as formulas consist of several types of medicinal herbs or minerals, in which one represents the principal component, and the others serve as adjuvant ones that assist the effects, or facilitate the delivery, of the principal component. In Western medicine, approximately 60 different arsenic preparations have been developed and used in pharmacological history. In traditional Chinese medicines, different forms of mineral arsenicals (orpiment-As(2)S(3), realgar-As(4)S(4), and arsenolite-arsenic trioxide, As(2)O(3)) are used, and realgar alone is included in 22 oral remedies that are recognized by the Chinese Pharmacopeia Committee (2005). It is known that a significant portion of some forms of mineral arsenicals is poorly absorbed into the body, and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulfide (realgar) for treatment of various forms of cancer in vitro and in vivo.


Strain related infectivity of Neisseria gonorrhoeae for the guinea-pig subcutaneous chamber and the variability of the immune resistance in different breeds of guinea-pig.
The ability of gonococci to infect the subcutaneous chamber in guinea-pigs is strictly strain related. This ability was usually present in prototrophic strains and auxotrophs requiring proline only which were obtained from patients with uncomplicated gonorrhoea, but it was invariably absent in Neisseria gonorrhoeae auxotypes requiring arginine, uracil, and hypoxanthine, or arginine only for growth. All the strains obtained from disseminated gonococcal infections (all dependent upon arginine, uracil, and hypoxanthine) were unable to infect the guinea-pig chamber. Hence, the high invasiveness of N. gonorrhoeae for man and its infectivity for guinea-pig chambers appear to be unrelated properties. Although guinea-pigs of the same origin (Dunkin-Hartley) were used throughout, the degree of immune resistance was found to differ between the lines supplied by various breeders--that is, after a standard immunisation schedule using whole cell gonococcal vaccines, the homologous immune resistance to challenge varied from weak or non-existent in some lines, to highly resistant in others.


Ochronotic Surprise during Total Knee Replacement! A Case Report.
Alkaptonuria is a rare autosomal recessive metabolic disorder characterized by accumulation of homogentisic acid (HGA) due to an inherited deficiency of the enzyme HGA oxidase. Unlike rheumatoid arthritis which affects the small joints of the hands and feet, ochronotic arthropathy predominantly involves the large weight-bearing joints such as hips, knees, and spine. The knee is the most common joint to be affected. Ochronotic arthropathy is usually managed conservatively, but for severely affected hip and knee joints, replacement is considered. This report describes a case of 57-year-old male who presented with bilateral knee osteoarthritis who was incidentally diagnosed with ochronosis intraoperatively during total knee arthroplasty, its challenges faced and post-operative functional outcome after 18 months follow-up. This case report highlights the need for high index of suspicion for preoperative diagnosis of ochronotic arthropathy. Difficult spinal anesthesia should be anticipated. Friable and stiff tendon due to ochronotic involvement can put the extensor tendon at risk of rupture during retraction of patella intraoperatively. Post-operative active quadriceps rehabilitation should be done with caution due to friable tendon.


Cyclic diaryliodonium salts: applications and overview.
Owing to the recent renewed interest and groundbreaking advances in hypervalent chemistry, cyclic diaryliodonium salts have had a myriad of unique applications in the past decade. Their numerous properties, such as an efficient dual arylation mechanism, straightforward one-pot synthesis compatibility, wide substrate scope, and functionalization tolerance, have made them appropriate starting materials for many bioactive compounds. Fluorenes, thiophenes, carbazoles, phenanthrenes, and many other useful cyclic bioactive molecules that are essential for pharmaceutical synthesis can be readily accessed from cyclic diaryliodonium salts. Particular focus has been given to the high optical activity and good enantiomeric excess of the products that facilitate the easy formation of many difficult-to-obtain optical isomers, such as atropisomers. This review aims to compile and summarize all the recent advances in synthesizing methodologies to prepare the important compounds where cyclic diaryliodonium salt is an integral part of the methodologies and would hopefully provide a good foundation for further research on this topic.


Severe traumatic brain injury: outcome in patients with diffuse axonal injury managed conservatively in Hospital Sultanah Aminah, Johor Bahru--an observational study.
Patients with isolated severe head injury with diffuse axonal injury and without any surgical lesion may be treated safely without cerebral resuscitation and intracranial pressure (ICP) monitoring. Seventy two patients were divided into three groups of patients receiving treatment based on ICP-CPP-targeted, or conservative methods either with or without ventilation support. The characteristics of these three groups were compared based on age, gender, Glasgow Coma Scale (GCS), pupillary reaction to light, computerized tomography scanning according to the Marshall classification, duration of intensive care unit (ICU) stays, Glasgow Outcome Score (GOS) and possible complications. There were higher risk of mortality (p < 0.001), worse GCS improvement upon discharge (p < 0.001) and longer ICU stays (p = 0.016) in ICP group compared to Intubation group. There were no significant statistical differences of GOS at 3rd and 6th months between all three groups.


Salt-induced phosphoproteomic changes in the subfornical organ in rats with chronic kidney disease.
Subfornical organ (SFO) is vital in chronic kidney disease (CKD) progression caused by high salt levels. The current study investigated the effects of high salt on phosphoproteomic changes in SFO in CKD rats. 5/6 nephrectomized rats were fed a normal-salt diet (0.4%) (NC group) or a high-salt diet (4%) (HC group) for three weeks, while sham-operated rats were fed a normal-salt diet (0.4%) (NS group). For phosphoproteomic analysis of SFO in different groups, TiO2 enrichment, isobaric tags for relative and absolute quantification (iTRAQ) labeling, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used. There were 6808 distinct phosphopeptides found, which corresponded to 2661 phosphoproteins. NC group had 168 upregulated and 250 downregulated phosphopeptides compared to NS group. Comparison to NC group, HC group had 154 upregulated and 124 downregulated phosphopeptides. Growth associated protein 43 (GAP43) and heat shock protein 27 (Hsp27) were significantly upregulated phosphoproteins and may protect against high-salt damage. Differential phosphoproteins with tight functional connection were synapse proteins and microtubule-associated proteins, implying that high-salt diet disrupted brain's structure and function. Furthermore, differential phosphoproteins in HC/NC comparison group were annotated to participate in GABAergic synapse signaling pathway and aldosterone synthesis and secretion, which attenuated inhibitory neurotransmitter effects and increased sympathetic nerve activity (SNA). This large scale phosphoproteomic profiling of SFO sheds light on how salt aggravates CKD via the central nervous system.


Replicon system for Lassa virus.
Lassa virus is endemic to West Africa and causes hemorrhagic fever in humans. To facilitate the functional analysis of this virus, a replicon system was developed based on Lassa virus strain AV. Genomic and antigenomic minigenomes (MG) were constructed consisting of the intergenic region of S RNA and a reporter gene (Renilla luciferase) in antisense orientation, flanked by the 5' and 3' untranslated regions of S RNA. MGs were expressed under the control of the T7 promoter. Nucleoprotein (NP), L protein, and Z protein were expressed from plasmids containing the T7 promoter and internal ribosomal entry site. Transfection of cells stably expressing T7 RNA polymerase (BSR T7/5) with MG in the form of DNA or RNA and plasmids for the expression of NP and L protein resulted in high levels of Renilla luciferase expression. The replicon system was optimized with respect to the ratio of the transfected constructs and by modifying the 5' end of the MG. Maximum activity was observed 24 to 36 h after transfection with a signal-to-noise ratio of 2 to 3 log units. Northern blot analysis provided evidence for replication and transcription of the MG. Z protein downregulated replicon activity close to background levels. Treatment with ribavirin and alpha interferon inhibited replicon activity, suggesting that both act on the level of RNA replication, transcription, or ribonucleoprotein assembly. In conclusion, this study describes the first replicon system for a highly pathogenic arenavirus. It is a tool for investigating the mechanisms of replication and transcription of Lassa virus and may facilitate the testing of antivirals outside a biosafety level 4 laboratory.


Efficacy of nicorandil on the prevention of contrast-induced nephropathy in patients with coronary heart disease undergoing percutaneous coronary intervention.
The purpose of this study was to explore the effect of nicorandil on the incidence of contrast-induced nephropathy in patients with coronary heart disease undergoing percutaneous coronary intervention. This study randomized 300 patients undergoing percutaneous coronary intervention to receive conventional treatment in the control group (hydration only; n = 150) vs. nicorandil therapy (nicorandil 10 mg three times daily plus hydration; n = 150). The primary endpoint was the incidence of contrast-induced nephropathy, defined as rise in serum creatinine ≥44.2 μmol/L or >25% above baseline within 72 hours after exposure to contrast administered during percutaneous coronary intervention. Secondary endpoints included differences in post-percutaneous coronary intervention serum creatinine, blood urea nitrogen, creatinine clearance rate, cystatin-C, and occurrence of major adverse events. Contrast-induced nephropathy incidence was 3.3% (5/150) in the nicorandil group vs. 10.7% (16/150) in the control group (P < 0.05). At 48 and 72 hours after contrast administration, cystatin-C levels were significantly lower and creatinine clearance rate were significantly higher with nicroandil therapy compared to conventional treatment (all P values <0.05). No statistical difference was observed in the incidence of major post-procedure side effect events in hospital and fourteen days of follow-up period between the nicorandil group and control group (3.3% vs. 4.0%, P > 0.05). Compared to conventional treatment, oral nicorandil therapy was associated with less contrast-induced nephropathy and improved renal function following contrast administration during percutaneous coronary intervention.


Synthesis and analysis of a methyl ether derivative of tetracycline which inhibits growth of Escherichia coli.
Tetracycline is a widely used broad spectrum antibiotic. A derivative of tetracycline was synthesized by methylation (-CH3) of the phenolic hydroxyl group, with the use of diazomethane (CH2N2). A methyl ether group is then formed from the reaction with diazomethane, which replaces the hydroxyl group. The newly formed derivative has reduced hydrogen bonding capability relative to the unmodified tetracycline. An infrared spectra shows the appearance of the ether group on the derivative and the Log P calculations indicate that the derivative has increased lipophilic tendency. The Lipophilic Substituent Constant calculated for the tetracycline derivative is 0.46, indicating a lipophilic substituent. The tetracycline derivative was soluble in aqueous solvents and was stable for more than five weeks when stored at < or = 0 degrees C. The derivative was placed in tissue culture utilizing Luria-Bertani (LB) media, at a concentration of 12.0 microg/mL and inhibited the growth of E. coli (XL-1 blue) from 15% to 20% within the initial sixteen hours.


Enhanced tolerance of transgenic poplar plants overexpressing gamma-glutamylcysteine synthetase towards chloroacetanilide herbicides.
A wild-type poplar hybrid and two transgenic clones overexpressing a bacterial gamma-glutamylcysteine synthetase in the cytosol or in the chloroplasts were exposed to the chloroacetanilide herbicides acetochlor and metolachlor dispersed in the soil. The transformed poplars contained higher gamma-glutamylcysteine and glutathione (GSH) levels than wild-type plants and therefore it was supposed that they would have an elevated tolerance towards these herbicides, which are detoxified in GSH-dependent reactions. Phenotypically, the transgenic and wild-type plants did not differ. The growth and the biomass of all poplar lines were markedly reduced by the two chloroacetanilide herbicides. However, the decrease of shoot and root fresh weights caused by the herbicides was significantly smaller in the transgenic than in wild-type plants. In addition, the growth rate of poplars transformed in the cytosol was reduced to a significantly lesser extent than that of wild-type plants following herbicide treatments. The effects of the two herbicides were similar. Herbicide exposures markedly increased the levels of gamma-glutamylcysteine and GSH in leaves of each poplar line. The increase in the foliar amounts of these thiols was stronger in the transgenic lines than in the wild type, particularly in the upper leaves. Considerable GST activities were detected in leaves of all poplar plants. Exposure of poplars to chloroacetanilide herbicides resulted in a marked induction of GST activity in upper leaf positions but not in middle and lower leaves. The extent of enzyme induction did not differ significantly between transgenic and wild-type poplars. Although the results show that the transgenic poplar lines are good candidates for phytoremediation purposes, the further improvement of their detoxification capacity, preferably by transformation using genes encoding herbicide-specific GST isoenzymes, seems to be the most promising way to obtain plants suitable for practical application.


A unified model for reconstruction and R2* mapping of accelerated 7T data using the quantitative recurrent inference machine.
Quantitative MRI (qMRI) acquired at the ultra-high field of 7 Tesla has been used in visualizing and analyzing subcortical structures. qMRI relies on the acquisition of multiple images with different scan settings, leading to extended scanning times. Data redundancy and prior information from the relaxometry model can be exploited by deep learning to accelerate the imaging process. We propose the quantitative Recurrent Inference Machine (qRIM), with a unified forward model for joint reconstruction and R2*-mapping from sparse data, embedded in a Recurrent Inference Machine (RIM), an iterative inverse problem-solving network. To study the dependency of the proposed extension of the unified forward model to network architecture, we implemented and compared a quantitative End-to-End Variational Network (qE2EVN). Experiments were performed with high-resolution multi-echo gradient echo data of the brain at 7T of a cohort study covering the entire adult life span. The error in reconstructed R2* from undersampled data relative to reference data significantly decreased for the unified model compared to sequential image reconstruction and parameter fitting using the RIM. With increasing acceleration factor, an increasing reduction in the reconstruction error was observed, pointing to a larger benefit for sparser data. Qualitatively, this was following an observed reduction of image blurriness in R2*-maps. In contrast, when using the U-Net as network architecture, a negative bias in R2* in selected regions of interest was observed. Compressed Sensing rendered accurate, but less precise estimates of R2*. The qE2EVN showed slightly inferior reconstruction quality compared to the qRIM but better quality than the U-Net and Compressed Sensing. Subcortical maturation over age measured by a linearly increasing interquartile range of R2* in the striatum was preserved up to an acceleration factor of 9. With the integrated prior of the unified forward model, the proposed qRIM can exploit the redundancy among repeated measurements and shared information between tasks, facilitating relaxometry in accelerated MRI.


Factors affecting stability of isozymes of creatine phosphokinase.
Human brain-type (BB) creatine phosphokinase (CPK) and skeletal muscle (MM) CPK were purified from autopsy tissues. The stability of each isozyme with and without the reducing agent mercaptoethanol in human plasma, saline solution, and saline solution with bovine serum albumin was studied. Human BB CPK, at 37 C, without added mercaptoethanol, lost 50% of its activity in 15 minutes during incubation in plasma. It was much more stable at both room temperature and 4 C. BB CPK was also unstable in saline solution plus bovine serum albumin in the absence of mercaptoethanol but was much more stable in the presence of mercaptoethanol. Plasma factors with molecular weights less than 1,000 were potent inhibitors of CPK activity. Electrophoresis following incubation of BB CPK in plasma without mercaptoethanol revealed a new band with CPK activity with the electrophoretic mobility close to that of cardiac muscle (MB) CPK, but no band with the electrophoretic mobility of MM CPK was noted. A new band whose electrophoretic mobility was intermediate between that of MM CPK and that of MB CPK appeared after 21 hours of incubation of MM CPK in human plasma. Modifications of methods for handling blood samples in order to increase the possibility of preserving CPK isozymes in human plasma are proposed. Immunologic methods for determining CPK isozymes may provide more definitive answers as to the nature of the isozyme species present in human sera in various diseases.


Supplementation of laying-hen feed with annatto tocotrienols and impact of α-tocopherol on tocotrienol transfer to egg yolk.
Hens can efficiently transfer nutrients from their feed to the eggs. Tocotrienols (T3s) have various health benefits including lowering cholesterol. Annatto is the only known source of T3s without the presence of α-tocopherol; hence it can be used to study T3 transfer without the interference of α-tocopherol. In this study, hens were fed diets for 7 weeks containing annatto at 100, 500, or 2000 ppm (by weight) and also 2000 ppm annatto with 200, 600, or 1000 ppm of added α-tocopherol to study the effect of α-tocopherol on transfer of T3s. No significant differences were found in egg production or properties. Significant differences (p < 0.05) were found in transfer efficiencies of tocopherol and T3s to the yolks. α-Tocopherol was transferred more efficiently (21.19-49.17%) than γ-T3 (0.50-0.96%) or δ-T3 (0.74-0.93%). Addition of 1000 ppm of α-tocopherol decreased the amount of γ-T3 but did not impact the transfer of δ-T3 to the egg. These feeding treatments did not impact the cholesterol content of the eggs.


Effect of prolactin replacement on the number of tyrosine hydroxylase expressing neurons in the arcuate nuclei of Ames dwarf and normal mice.
Ames dwarf mice do not synthesize or release growth hormone or prolactin (PRL) and have very poorly developed tuberoinfundibular dopaminergic (TIDA) neurons. An antibody to tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of dopamine, and immunohistochemical procedures were used in this study to compare the numbers of TH-immuno-positive neurons observed in the arcuate nuclei of Ames dwarf mice compared to phenotypically normal mice of the same strain. In female dwarfs, the number of TH-immunopositive neurons in the arcuate nuclei but not the pars compacta was markedly reduced when compared to normal females. The elevation of circulating PRL either by the implantation of a normal pituitary under the kidney capsule or by the daily administration of ovine PRL increased the numbers of arcuate neurons which expressed immunochemically detectable TH to a level comparable to that observed in untreated normal mice. The number of TH-expressing neurons was also reduced in the arcuate nuclei of dwarf males although the deficiency was not as great as in females. Ovine PRL seemed to have little effect on the numbers of TH-immunopositive neurons observed in either dwarf or normal male mice. These results suggest that the postnatal absence of PRL in mice does not result in a major reduction in the total population of TIDA neurons. Rather these neurons appear to be present in nearly normal numbers but are in a dormant state in the absence of circulating PRL.


Effectiveness of a rescue dose of antenatal betamethasone after an initial single course.
To evaluate the effects of a single rescue dose of antenatal betamethasone after an initial single course on the frequency of neonatal respiratory distress syndrome and perinatal infectious morbidity in pregnancies complicated with preterm labor and delivery. We performed a cohort analysis of singleton pregnancies for which delivery occurred between 28 and 34 weeks' gestation after a single course of betamethasone administered before 28 weeks' gestation. Patients were then segregated into the following 2 groups on the basis of betamethasone exposure at the delivery admission: (1) a single 12-mg injection (rescue group) and (2) observation only (observation group). Patients who delivered infants within 24 hours of the rescue dose were excluded, as were those who had ruptured membranes for longer than 24 hours before delivery, those with diabetes that required insulin, and those with exposure to repeated doses of betamethasone before admission. Data were analyzed by use of the Student t test, chi2 test, and Fisher exact test. Multiple logistic regression was performed to examine the effect of each steroid dosing regimen on respiratory distress syndrome. Two-tailed P values <.05 were considered to be significant. A total of 152 patients were included, with 89 in the rescue group and 63 in the observation group. Both groups were similar with respect to maternal demographics, mean gestational age at the initial single course and at delivery, mode of delivery, and mean birth weights. Rescue administration was significantly associated with a reduction in the frequency of respiratory distress syndrome (odds ratio, 0.44; 95% confidence interval, 0.2 to 0.9) and mean ventilator days (odds ratio, 0.44; 95% confidence interval, 0.2 to 0.8) compared with observation alone. All other studied perinatal outcomes analyzed were similar between the groups. Multiple logistic regression confirmed an independent association between a single rescue dose and a reduction in the frequency of respiratory distress syndrome (odds ratio, 0.40; 95% confidence interval, 0.2 to 0.9). A single rescue dose of betamethasone is associated with a reduction in the frequency of respiratory distress syndrome without an apparent increase in perinatal infectious disease.


[Blood sugar level in surgical patients].
Serum glucose levels of six different patient groups were investigated preoperatively, during operation, postoperatively and in the first postoperative days: Group A, 10 cholecystectomy patients with 5% glucose infusion 2000 ml/day at a constant infusion rate; group B, 10 cholecystectomy patients with 10% constant rate glucose infusion; group C, 20 cholecystectomy or hernia patients with saline infusion; group D, 34 patients with 5% free rate glucose infusion 2000 ml/day; group E, 15 atrial septal defect patients with 5% constant rate glucose infusion 1500 ml/day and group f, 14 valvular surgery patients with 5% constant rate glucose infusion. Serum glucose increased in all groups during the study, most in the group B and least in the group C. There were no significant differences between the groups A and D, so constant or "free" infusion rate are the same from this viewpoint. The differences between the saline group (C) and all other groups was per- and postoperatively and in the postoperative day significant (p less than 0.001). There were no significant differences between the open heart surgery groups (E and F) and general surgery groups (A and D).


Routes and mechanisms of post-endosomal cholesterol trafficking: A story that never ends.
Mammalian cells acquire most exogenous cholesterol through receptor-mediated endocytosis of low-density lipoproteins (LDLs). After internalization, LDL cholesteryl esters are hydrolyzed to release free cholesterol, which then translocates to late endosomes (LEs)/lysosomes (LYs) and incorporates into the membranes by co-ordinated actions of Niemann-Pick type C (NPC) 1 and NPC2 proteins. However, how cholesterol exits LEs/LYs and moves to other organelles remain largely unclear. Growing evidence has suggested that nonvesicular transport is critically involved in the post-endosomal cholesterol trafficking. Numerous sterol-transfer proteins (STPs) have been identified to mediate directional cholesterol transfer at membrane contact sites (MCSs) formed between 2 closely apposed organelles. In addition, a recent study reveals that lysosome-peroxisome membrane contact (LPMC) established by a non-STP synaptotagmin VII and a specific phospholipid phosphatidylinositol 4,5-bisphosphate also serves as a novel and important path for LDL-cholesterol trafficking. These findings highlight an essential role of MCSs in intracellular cholesterol transport, and further work is needed to unveil how various routes are regulated and integrated to maintain proper cholesterol distribution and homeostasis in eukaryotic cells.


Serum- and glucocorticoid-inducible kinase 1 sensitive NF-κB signaling in dendritic cells.
Dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity, are required for initiation of specific T cell-driven immune responses. Phosphoinositide-3-kinase (PI3K) suppresses proinflammatory cytokine production in DCs, which limits T helper (Th1) polarization. PI3K is in part effective by downregulation of transcription factor NF-κB. Downstream signaling elements of PI3K include serum- and glucocorticoid-inducible kinase 1 (SGK1) and its phosphorylation target N-myc downstream regulated gene 1 (NDRG1). The present study explored whether SGK1 and NDRG1 play a role in the regulation of NF-κB and DC-maturation. DCs were isolated from bone marrow (BMDCs) or spleen of mice lacking functional SGK1 (sgk1(-/-)) and corresponding wild type mice (sgk1(+/+)). Protein abundance was determined by Western blotting. Transcription was inhibited by siRNA. Abundance of maturation markers was quantified by flow cytometry. FITC-dextran uptake was determined to quantify phagocytosis. NDRG1 was similarly expressed in sgk1(+/+) and sgk1(-/-)BMDCs, but SGK1-dependent phosphorylation of NDRG-1 was decreased in sgk1(-/-)BMDCs. Silencing of NDRG1 in sgk1(+/+)BMDCs as compared to control empty vector-treated BMDCs enhanced nuclear abundance of NF-κB subunit p65. Moreover, the abundance of phosphorylated NF-κB inhibitor IκBα, of phosphorylated IκB kinase (IKKα/β) and of nuclear p65 were significantly higher in sgk1(-/-)BMDCs than in sgk1(+/+)BMDCs. Expression of maturation markers, MHC II, and CD86, was significantly larger and phagocytic capacity was significantly lower in sgk1(-/-) than in sgk1(+/+)BMDCs. Expression of CD86 and MHCII was also significantly higher in DCs isolated from the spleen of sgk1(-/-) mice than those from sgk1(+/+)mice. SGK1 and NDRG1 participate in the regulation of NF-κB signaling in and maturation of DCs.


Efficacy of four cleaning solutions for the decontamination of selected cytotoxic drugs on the different surfaces of an automated compounding system.
The automated aseptic preparation of ready-to-administer antineoplastic drug solutions with robotic systems reduces the risk of occupational exposure. However, the surfaces in the preparation area of the robot are to be cleaned by wiping with an appropriate cleaning solution. The aim of the study was to evaluate the cleaning efficacy of four cleaning solutions on four surface materials installed in the APOTECAchemo robot. Predefined amounts of cisplatin (Cis), 5-fluorouracil (5-FU), and cyclophosphamide (CP) were intentionally spread on test plates made of stainless steel, aluminium, polyoxymethylene, and polycarbonate just as installed in the robotic system APOTECAchemo. After drying, the plates were cleaned with 0.2% ethanolic NaOH, 0.23% isopropanolic sodium dodecylsulfate (SDS-2P), 0.5% sodium hypochlorite (NaOCl), and 0.1% benzalkonium chloride (BZK) solutions following a standardized wiping protocol. Residual contamination was recovered with wipe tests, Pt was quantified by voltammetry, and 5-FU and CP was quantified by gas chromatography-tandem mass spectrometry (GC-MSMS). The mean residual contamination after cleaning and the cleaning efficacy (CE) rates were calculated and aggregated on different levels. The CE rates varied between 81.5% and 100% and lay in the majority of cases above 90%. The lowest CE rates were registered for Pt contamination. Especially on aluminium surfaces the residual contamination was high. The overall CE rates of the three different drugs and four different surface types amounted to 98.3% for NaOCl, 97.9% for SDS-2P, 96.9% for ethanolic NaOH, and 96.5% for BZK. The tested cleaning solutions proved to be higher than 90% in most cases, but none of them was able to eliminate 100% of the intentional surface contamination of three antineoplastic drugs on the test plates. The cleaning efficacy varied according to the different surface types and antineoplastic drug. Results could be used in the daily clinical practice to develop and implement effective cleaning procedures.


Conditions for single-strand conformation polymorphism (SSCP) analysis of BRCA1 gene using an automated electrophoresis unit.
The single-strand conformation polymorphism procedure has been applied in routine testing for hereditary diseases and cancer. However, temperature, running time, gel composition, fragment length, etc. can influence its sensitivity. Mutation detection in the clinical setting depends on the development of automated technology, especially for large genes such as the breast cancer gene BRCA1. We analysed DNA samples with BRCA1 mutations in an automated system (GenePhor System; Amersham-Pharmacia Biotech, Uppsala, Sweden). The concentrations of DNA template and PCR primers, the effect of chilling after denaturation, and the temperature and time of the electrophoresis were investigated. All band-shifts were detected by electrophoresis at 5 degrees C for 2 h 15 min. Concentrations of DNA and samples used in the PCR did not affect the SSCP pattern, but chilling the PCR product in ice after denaturation was required. The type and position of mutation in the fragments did not influence the probability of a mobility shift, although SSCP analysis was more sensitive for fragments shorter than 350 bp. This automated SSCP method meets the requirements of fast turnaround and sensitivity and can be readily adapted to the screening of large genes such as BRCA1.


[Significances of COX-2, p21, Ki-67 expression and HPV infection in nasal inverted papilloma].
To investigate the significance of expression of COX-2, p21, Ki67 and HPV in nasal inverted papilloma. Detecting COX-2, p21, Ki-67 in 30 cases of nasal inverted papilloma (NIP), 20 cases of nasal polyps (NP) and 10 cases of normal nasal mucosa (NM) by two step immunohistochemical method, and HPV virus by flow-through hybridization method. The positive expression rate of COX-2 and Ki-67 in NIP, NP and NM group was decreased in turn, COX-2 had significant difference in the groups(χ2 = 30.00, P< 0. 05); the positive expression rate of Ki-67 had significant differences between NIP and NM group (χ2 = 8. 533, P<0. 05). The expression of COX-2 in NIP tissues was positively correlate with that of Ki-67 by using Spearman rank correlation analysis (r=0.78, P<0.05). Expression of p21 were not observed in NIP group. The positive rate of HPV was 26. 67% in 30 cases of NIP, all of HPV16 type. COX-2, Ki-67 and HPV infection have certain correlation with the occurrence of NIP. The occurrence of NIP has relationship with inflammatory reaction mediated by COX-2. Ki-67 can well reflect the proliferation activity of tumor cells, and can be used to measure the proliferation rate of nasal inverted papilloma. The COX-2 and Ki-67 have a synergistic role in the pathogenesis of NIP. p21 has no significant relationship with the incidence of NIP. HPV infection is related to the pathogenesis of NIP, but not as a;major factor in the pathogenesis of NIP.


Susceptibilities of Escherichia coli and Staphylococcus aureus to Aloe barbadensis.
The in vitro susceptibilities of Escherichia coli and Staphylococcus aureus were evaluated and the two organisms were susceptible to the inner gel of aloe barbadensis, though it was more effective against Staphylococcus aureus than Escherichia coli. The reduction for Aloe Vera (AV) needed to suppress the growth of the gram-positive bacterium was attributed to the structural differences between the two organisms.


Has society in the USA really given informed consent to managed health care?
It is the assertion of this paper that the current environment of applied managed care in the United States amounts in effect to bio-medical experimentation with humans as the subjects. The ethical dilemma of using humans as subjects of experimentation with unsure outcomes has been addressed historically. Perhaps the most famous attempt at delineating permissible behavior is the Nuremberg code of 1947. While stopping short of the logical extreme--accusing the managed care drivers of being war criminals--this text illustrates the unsatisfactory nature of the current health-care status quo, and proposes alternative means by which economic savings may be realized for the benefit of society, without violating the social obligation to provide health-care. Among the strongest proposals is that ethical or moral constraints may need the protection of regulation (legislation and possibly federal regulation) by and for the common good of the United States' society as a whole.


Coexpression of fractalkine and its receptor in normal human endometrium and in endometrium from users of progestin-only contraception supports a role for fractalkine in leukocyte recruitment and endometrial remodeling.
Leukocytes are critical mediators of endometrial remodeling, but the mechanisms by which leukocyte subpopulations enter the uterus are currently unknown. Endometrial leukocytes have no genomic progesterone receptors; thus, we hypothesized that leukocyte migration is induced indirectly by progesterone-regulated chemokines. Fractalkine (CX3CL1), a chemotactic membrane-bound adhesion factor, and its receptor (CX3CR1) were assessed by immunohistochemistry in endometrial samples across the menstrual cycle, in early pregnancy, and in women using progestin-only contraceptives. Fractalkine was localized predominantly to glandular epithelial and decidualized stromal cells, with the highest staining intensity in the secretory phase and early pregnancy. It was also detected in subpopulations of endometrial leukocytes (macrophages and uterine NK cells), with maximal numbers during the proliferative phase and early pregnancy. CX3CR1 was similarly colocalized to the glandular epithelium and decidualized stromal cells, with the highest expression in the secretory phase. CX3CR1-positive leukocytes (macrophages and neutrophils) were in greatest abundance during the menstrual phase. In the endometrium of women using progestin-only contraceptives, immunoreactive fractalkine was markedly reduced in the glandular epithelium, but was increased in decidualized stroma and infiltrating leukocytes. These findings support a number of roles for fractalkine in the endometrium, in the secretory phase, in early pregnancy, and when influenced by progestin-only contraceptives.


Influence of serum-free medium on the expression of glutamate transporters and the susceptibility to glutamate toxicity in cultured cortical neurons.
The presence of glia and glial glutamate transporters seems to modify glutamate-mediated toxicity in neuronal cultures. In this work we cultured cortical cells in serum-containing medium and in a serum-free medium (Neurobasal medium + B27 supplement) and studied the expression of the glutamate transporters GLAST, GLT, and EAAC by immunocytochemistry and RT-PCR. The proportion of glial cells was below 10% in the Neurobasal medium and 46% in the serum-containing medium. Semiquantitative evaluation of the mRNA for the glutamate transporters showed similar amounts in cells grown in serum-free and serum-containing media. We detected immunoreactivity for the three transporters in both media, but EAAC was coexpressed with the neuronal marker MAP2, whereas GLAST and GLT predominated in nonneuronal cells. When the cultures were treated with glutamate for 15 min, the cultures in serum-containing medium showed a clear concentration-dependent neuronal death, whereas cells primed in this medium and switched to Neurobasal medium, as well as cells grown only in the latter, were less sensitive to glutamate concentrations up to 1 mM. A similar difference in the sensitivity to excitotoxicity was observed when the glutamate uptake inhibitor L-trans-2,4-pyrrolidine-dicarboxylate was applied during 6 hr, although the accumulation of extracellular glutamate was similar in the two media. We conclude that glutamate transporters with the culture conditions studied are sensitive to glutamate uptake inhibition and that Neurobasal/B27 medium protects cells against excitotoxicity.


[The index and secondary patients in tuberculosis transmission--a retrospective epidemiological study of 3783 patients newly registered in recent 15 years in Aichi, Japan].
To elucidate the characteristics of the index and secondary patients in clusters containing multiple TB patients who were examined epidemiologically. The subjects of this retrospective study were 3783 TB patients registered in Aichi between 1989 and 2003. All recorded files were reviewed to identify multiple TB patients in the same transmission group. When multiple patients with a registration interval of less than 10 years were found in the same transmission group, the first patient was considered as the index case, and the other patients were regarded as secondary cases. A total of 106 index patients and 132 secondary patients were found. The index patients occupied 2.8% of the total 3783 registered patients, or 0.9 per 100,000 population. Secondary patients occupied 3.5% and 1.2 per 100,000. Of the 106 clusters, 77.4% consisted of two patients, 15.1% three patients, and 7.5% four or more patients. Smear-positive patients were found in 66.0% of the index patients, 27.3% of the secondary patients, and 30.3% of the 3783 overall patients, and the differences were highly significant between the index and secondary patients, as well as between the index and overall registered patients (p < 0.001). The proportion of the index patients to all registered patients was 6.1% for smear-positive patients, 1.8% for culture-positive patients, and 1.1% for bacilli-negative patients. The differences were highly significant between smear-positive and culture-positive patients, as well as between smear-positive and bacilli-negative patients (p < 0.001). The findings of this retrospective study suggest that 2.8% of the total registered patients, 6.1% of smear-positive patients, and 0.9 per 100,000 population was the index patients.


[Enzymatic and scintigraphic determined infarct size: significance for left ventricular function following infarct].
In a prospective study, the relationship between extent and location of myocardial infarction and the resulting left ventricular dysfunction was assessed and the question asked, how well these parameters may be assessed non-invasively a few weeks after the acute event. One hundred and fifty survivors of a first myocardial infarction were studied in the acute stage by serial ECG and CPK recordings and 5 weeks later by thallium201-(Tl)-scintigraphy and radionuclide angiocardiography. Myocardial damage was assessed enzymatically (maximal CPK; CPKmax) in the acute phase and scintigraphically in the subacute phase using a Tl-score considering extent (in percent of total myocardium in each projection) and severity (decrease in thallium-uptake) of scintigraphic infarct defects. There were significant correlations between Tl-score and max. CPK (r = .69) as well as between Tl-score and left ventricular ejection fraction (LVEF) (r = .65; p less than .001 each), but this correlation was better for subgroups with anterior vs. inferior infarctions (r = -.68 vs. r = -.59; p less than or equal to .001 for each). Furthermore, LVEF could be predicted based on the Tl-score: 88% of patients with values less than 7 had an LVEF of greater than 45%, whereas 77% of patients with a thallium-score of more than 12 had an LVEF less than 45%. Reproducibility of the Tl-score assessed in 30 patients over 3 months was excellent (r = .96) with low variability between the two analyses (+/- 1.5). Thus, after a first myocardial infarction, a direct relationship between enzymatically and scintigraphically, assessed infarct size and LVEF could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)


Shape-dependent antibacterial activities of Ag2O polyhedral particles.
Ag(2)O particles with different polyhedral shapes including octahedron, truncated octahedron, and cube were successfully synthesized by a simple wet-chemical method using silver nitrate, ammonia, and sodium hydroxide as raw materials at room temperature. Simply by tuning the concentration of starting materials, the shape of Ag(2)O particles evolved from octahedron to cube, and the size gradually decreased from 1-2 microm to 400-700 nm. As examples for promising applications, the antibacterial activities of the as-prepared Ag(2)O polyhedral particles were preliminarily studied. It has been found the antibacterial activity of Ag(2)O particles against E. coli depends on the shape of Ag(2)O particles, demonstrating that the surface structure of Ag(2)O particles affects the antibacterial activity.


Lack of measurable complement fixing antibodies against viral antigens.
A serological and clinical study was performed to find the common features of 130 patients without antibodies against 11 or more different antigens in the complement fixation (CF) test. These patients (=1.6%) were discovered during hte screening of 8,021 adult patients. Rheumatoid factor(s) (RF) were found in the sera of 113 of the patients. In the remaining 17 patients no common serological or clinical markers were found. Myeloma M-components were found in three cases. The lack of measurable CF antibodies in RF positive cases was apparently due to the inhibitory effect of RF(s) in the CF test. This was indicated by a positive reaction in CF after centrifugal separation of IgM and IgG fractions and also by the detection of antibodies using immunodiffusion method. Possible immune complexes were sought using the platelet aggregation test, which was positive for the sera of 47 (=37%) of the patients. The clinical diagnosis of the 130 CF-nonreactors was rheumatoid arthritis (RA) (ARA criteria) in 23 cases and pulmonary diseases in 65 cases. In a comparison group of equal size there were only 3 RA patients and 15 with pulmonary disease. RA was thus found in 20% of the RF positive CF-nonreacting patients. In the comparison group of 52 RA patients 8 CF-nonreactors were found (=15%). This suggests that the effect of RF(s) from RA patients in CF reaction varies greatly.


Empowering leadership, perceived organizational support, trust, and job burnout for nurses: a study in an Italian general hospital.
A strong nursing leadership that instills trust in the leader and in the organization is an important component for an effective leadership, particularly for health care organizations, because trust defines the heart of health care workplaces by promoting patient safety, excellence in care, recruitment, and retention of the nursing staff. This study aimed to test the impact of perceived empowerment leadership style expressed by the nurse supervisor, nurses' perceived organizational support, trust in the leader, and trust in the organization on nurses' job burnout. A group of 273 nurses from an Italian public general hospital took part in a cross-sectional study on a voluntary basis by filling out an anonymous questionnaire. Empowering leadership was an important predictor of trust in the leader. Trust in the organization was influenced by perceived organizational support and by the Informing dimension of the empowering leadership style. Trust in the leader and trust in the organization showed a negative impact on job burnout and also mediated the effects of some empowering leadership dimensions and perceived organizational support on job burnout. The central role of trust in health care organizations was corroborated, as well as the beneficial effects of adopting specific features of empowerment leadership behaviors toward the nursing staff. Empowering leadership could be successfully proposed in training programs directed to nurses' supervisors and health care managers.


Low growth temperatures modify the efficiency of light use by photosystem II for CO2 assimilation in leaves of two chilling-tolerant C4 species, Cyperus longus L. and Miscanthus x giganteus.
Two C4 plants, Miscanthus x giganteus and Cyperus longus L., were grown at suboptimal growth temperatures and the relationships between the quantum efficiencies of photosynthetic electron transport through photosystem II (PSII) (PSII operating efficiency; Fq'/Fm') and CO2 assimilation (phiCO2) in leaves were examined. When M. x giganteus was grown at 10 degrees C, the ratio of the PSII operating efficiency to phiCO2 increased relative to that found in leaves grown at 14 and 25 degrees C. Similar increases in the Fq'/Fm': phiCO2 occurred in the leaves of two C. longus ecotypes when the plants were grown at 17 degrees C, compared to 25 degrees C. These elevations of Fq'/Fm': phiCO2 at low growth temperatures were not attributable to the development of anthocyanins, as has been suggested for maize, and were indicative of the operation of an alternative sink to CO2 assimilation for photosynthetic reducing equivalents, possibly oxygen reduction via a Mehler reaction, which would act as a mechanism for protection of PSII from photoinactivation and damage. Furthermore, in M. x giganteus grown at 10 degrees C, further protection of PSII was effected by a 20-fold increase in zeaxanthin content in dark-adapted leaves, which was associated with much higher levels of non-photochemical quenching of excitation energy, compared to that observed in leaves grown at 14 and 25 degrees C. These differences may explain the long growing season and remarkable productivity of this C4 plant in cool climates, even in comparison to other C4 species such as C. longus, which occur naturally in such climates.


Treatment of behavioral/psychological symptoms in Alzheimer's disease.
This review examines the evidence for the use of drugs as part of the treatment of depressive/psychotic symptoms and behavioral disturbances in persons with Alzheimer's disease. Although conventional antidepressants appear to relieve depressive symptoms in Alzheimer's disease patients, placebo seems equally effective. The use of most medications used to control psychotic symptoms and disturbed/disturbing behaviors in Alzheimer's disease is off-label and not strongly supported by randomized, placebo-controlled trials, especially for so-called agitation. For these reasons, trials of psychotropic drugs in Alzheimer's disease need a placebo condition in addition to active comparators and in the case of nondrug treatments, a sham treatment condition. Cholinesterase inhibiting drugs may reduce behavioral symptoms in addition to slowing cognitive decline. Selective (for brain region) GABA agonists seem to offer the greatest theoretical promise for reducing agitated behaviors not driven by depression or psychosis.


An isotopic assay of dUTPase activity based on coupling with thymidylate synthase.
A new rapid, sensitive and convenient procedure is presented allowing determination of dUTPase activity. With [5-(3)H]dUTP used as the substrate, dUTPase, converts it to the corresponding monophosphate and is coupled with thymidylate synthase-catalyzed reaction, resulting in tritium release from [5-(3)H]dUMP. Following charcoal absorption of the labeled nuleotides, radioactivity of tritiated water is determined. The new assay was tested to show comparable results with a previously described assay, based on measuring dUTPase-catalyzed [5-(3)H]dUMP production.