Functional imaging: PET.
Among various neuroimaging techniques used for the evaluation of children with intractable epilepsy, positron emission tomography (PET) employing various PET tracers plays a very important role, especially in localizing areas of focal cortical dysplasia. This is particularly important in infants, where incomplete myelination may limit the structural information provided by MRI. In children with tuberous sclerosis, PET can differentiate between epileptogenic and nonepileptogenic tubers, previously not thought to be possible with neuroimaging. PET may reveal cortical or subcortical abnormalities in various epilepsy syndromes, such as infantile spasms and Landau-Kleffner syndrome. Various other applications of PET have included the investigation of epileptic networks, secondary epileptic foci, dual pathology, and neuroinflammation. Finally, PET can also be used to evaluate various cognitive processes and their underlying neurological substrates and can help in addressing the issue of brain plasticity and reorganization, related to epilepsy.


Enhanced adsorptive removal of sulfamethoxazole from water using biochar derived from hydrothermal carbonization of sugarcane bagasse.
This research work primarily focussed on the production of biochar from sugarcane bagasse through HTC followed by NaOH activation at inert atmosphere for removing SMX from water. The biochar was characterized for structural morphology and presence of functional groups. XRD and FTIR analysis confirmed that presence of aromatized graphitic structure accumulated with oxygenated functional groups are responsible for the elimination of SMX. SEM analysis portrayed the sphere-shaped structure of biochar with hydrophobic groups interior and hydrophilic groups exterior. BET isotherm revealed the active surface area equal to 1099 m2/g with high coverage of mesopores structure. Pzpc of adsorbent is evaluated to 6.5 stating that effective removal of SMX depends on ionization effects induced due to reaction medium. Kinetics study revealed the sorption of SMX followed chemical interaction pertaining to Elovich model. Isotherm studies revealed that Freundlich model fitted well stating heterogeneous mode of interaction. Immobilization of SMX on surface of ABC is due to charge assisted hydrogen bonding and π-π interaction with graphitized carbon, showing maximum sorption capacity of 400 mg/g through spontaneous reaction. The results suggested that HTC derived biochar had great adsorption affinity with respect to pH towards SMX and could be employed as an effective sorbent in cleaning water contaminants.


[Accessibility of deaf women to the public health system of the Basque Country (Spain)].
To explore what are the perceptions and experiences of deaf women in relation to accessibility to the Basque Public Health System (Osakidetza). As a secondary objective, explore the experience of these women about gender violence. A qualitative study with exploratory design is developed. The selection of the informants was carried out through intentional sampling. Deaf women were invited to participate through the Federation of Deaf People of the Basque Country. Four discussion groups were developed between October 2013 and July 2014, with duration of 90-120minutes. The discussion groups were recorded in video for their later literal transcription in which the service of interpreters of sign language of Euskadi participated. Thematic analyses carried out. Three main categories arise: 1) feelings of discrimination and limitation of the principle of autonomy; 2) barriers and facilitators in the accessibility to the health system; and 3) vulnerability of deaf women as a result of the lack of communication. Nowadays, deaf women continue having difficulties in accessing to the health system in our context. The results of this study can be the starting point for the development of health policies and institutional protocols.


Superior Capsular Reconstruction: Proposed Biomechanical Advantages.
The intact rotator cuff provides dynamic stability for the glenohumeral joint through range of motion by compressing the humeral head to the center of the glenoid. Maintenance of articular congruity provides a stable fulcrum for the more forceful muscles of the shoulder girdle. Massive rotator cuff tears disrupt the concavity-compression mechanism and lead to unopposed superior pull of the deltoid. As a result, superior migration of the humerus, abutment of the acromion, and, in some cases, progression to cuff tear arthropathy occur. Arthroscopic superior capsular reconstruction has emerged as an effective treatment in select indications. Several potential biomechanical advantages to SCR have been described on the basis of cadaver studies. By tethering the greater tuberosity to the glenoid, superior migration is resisted, and the center of rotation is stabilized. The interpositional spacer effect describes reduced subacromial contact pressure, and the reduction is greater with thicker grafts. Side-to-side suturing of the graft to residual tendon and capsule achieves capsular continuity and may further improve the stabilizing function of the residual capsule and prevent medial-lateral elongation of the graft. Although these biomechanical principles overlap to some degree, their summation offers an explanation for the improved pain and function seen in patients who undergo superior capsular reconstruction.


Efficacy of botulinum toxin in severe Tourette syndrome with dystonic tics involving the neck.
Severe dystonic tics involving the neck may lead to the development of serious spine disease. The pharmacological treatment of tics offers symptomatic relief, but clinically relevant improvement of severe tics is not frequently achieved and serious adverse events may result. Botulinum toxin (BnT) appears to be a safe and effective treatment for tics, but some concern exists about which group of patients may benefit from treatment. We report a patient affected by Tourette syndrome with tetraparesis and cervical myelopathy secondary to violent dystonic tics involving the neck, in which a more aggressive course of treatment with BnT in addition to neuroleptic medication resulted in complete resolution of cervical tics after 12 months of follow-up.


Diversity within the species Clostridium butyricum: pan-genome, phylogeny, prophage, carbohydrate utilization, and antibiotic resistance.
Clostridium butyricum has been recognized as a strong candidate for the "next generation of probiotics" due to its beneficial roles on humans. Owing to our current understanding of this species is limited, it is imperative to unveil the genetic variety and biological properties of C. butyricum on sufficient strains. We isolated 53 C. butyricum strains and collected 25 publicly available genomes to comprehensively assess the genomic and phenotypic diversity of this species. Average nucleotide identity and phylogeny suggested that multiple C. butyricum strains might share the same niche. Clostridium butyricum genomes were replete with prophage elements, but the CRISPR-positive strain efficiently inhibited prophage integration. Clostridium butyricum utilizes cellulose, alginate, and soluble starch universally, and shows general resistance to aminoglycoside antibiotics. Clostridium butyricum exhibited a broad genetic diversity from the extraordinarily open pan-genome, extremely convergent core genome, and ubiquitous prophages. In carbohydrate utilization and antibiotic resistance, partial genotypes have a certain guiding significance for phenotypes.


Medical examiners and Crimean-Congo hemorrhagic fever contamination risk.
Crimean-Congo Hemorrhagic Fever (CCHF) is an acute zoonotic infection caused by the CCHF virus. The viruses' activity peaks during April and May with a mortality rate of 3-30%. Transmission of the virus to human occurs through tick bites or exposure to infected animals' tissues or blood. The major at-risk group includes farmers living in endemic areas. Health-care workers are the second most affected group. Virus has shown up in a diverse geographic area which includes Middle East, Asia, Africa and Eastern Europe and is considered one of the most wide-spread tick borne infections. The most recent cases are from Iran and Turkey. This article represents autopsy results of four CCHF infected cases in 2011 and 2012, in Ankara, Turkey.


Correction of juxtaarticular deformities in children using the Ilizarov apparatus.
Deformity correction using external fixation was performed for various disorders in children. We reviewed 18 children who underwent juxtaarticular deformity correction using the Ilizarov apparatus with either a transverse or focal dome osteotomy. The amount of deformity correction, external fixation time, external fixation index, length gained, and incidence of complications were examined. A series of 27 operations were performed in lower limb segments on 10 femurs and 17 tibias in 10 boys and 8 girls. The mean age at operation was 12 years (5-18 years). Deformity corrections were performed using a transverse osteotomy in 16 segments and a focal dome osteotomy in 11. The average deformity corrected was 19 degrees (6 degrees-31 degrees). Acute correction was done in 14 segments and gradual correction in 13 segments. The mean lengthening was 4.2 cm in 12 segments (2-8 cm). The mean external fixation time was 161 days (78-352 days). In acute corrections, the external fixation time with a focal dome osteotomy (101 days) tended to be shorter than with a transverse osteotomy (142 days). Accurate limb alignment was obtained for all cases. A focal dome osteotomy by maximizing the area of bony contact was more effective than a transverse osteotomy for acute deformity correction.


The phenotypic and mutational spectrum of Thai female patients with ornithine transcarbamylase deficiency.
Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder affecting both males and females. Hemizygous males commonly present with severe hyperammonemic encephalopathy during the neonatal period. Heterozygous females have great phenotypic variability. The majority of female patients can manifest later in life or have unrecognized symptoms, making the diagnosis of OTCD in females very challenging. Here we report on three unrelated Thai female cases with OTCD presenting with different manifestations including aggressive behavior, acute liver failure and severe encephalopathy. Whole exome sequencing successfully identified disease-causing mutations in all three cases including two novel ones: the c.209_210delAA (p.Lys70Argfs*17) and the c.850T>A (p.Tyr284Asn). This study affirms variable symptoms in female patients with OTCD and emphasizes the importance of early recognition and prompt management for favorable outcomes. In addition, identification of two novel causative variants expands the genotypic spectrum of OTC.


Rehabilitation of the injured knee.
The basis of rehabilitation is to return the patient to the preinjury status. The physician must recognize that muscle is made up of both Type I and Type II fibers, Type I having endurance and Type II having speed capabilities. Immobilization for long periods of time is destructive to the ligaments, muscles, and cartilage of the affected area. Some immobilization is required, however, for the healing of tissues. The basis of any postinjury rehabilitation program should take into account that controlled motion can decrease the deleterious effect of immobilization. At the same time, it allows for healing. The ranges of motion that are allowed must be determined for each specific injury. An approach to determining the losses in the psychological and physiologic states of the patient is identified and recommendations for rehabilitation are given.


Supratentorial ependymomas: prognostic factors and outcome analysis in a retrospective series of 46 adult patients.
Ependymomas account for 2% of all intracranial tumors in adults. Supratentorial ependymomas are less common than their infratentorial counterparts. To the authors' knowledge to date, the predictive values of surgery, histology, and patient-related prognostic factors for these tumors remain unresolved. The authors report a series of adult patients with supratentorial ependymomas to characterize the roles of surgery and histology in tumor control. The authors retrospectively studied a homogenous population of 46 adult patients who had supratentorial ependymomas from 24 French neurosurgical centers between 1990 and 2004. All clinicoradiologic and follow-up data were analyzed, and a central pathologic review was performed by 2 certified neuropathologists. The mean (+/-standard error) 5- and 10-year overall survival rates for the entire population were 57.1% +/- 8.7% and 41.8% +/- 9.9%, respectively. The 5- and 10-year progression-free survival rates for the entire cohort were of 33.8% +/- 8.1% and 25.4 +/- 8%, respectively. On both univariate and multivariate analysis, age <55 years, greater extent of surgery, and lower histologic grade were associated with longer overall and progression-free survival. However, longer progression-free survival but was not considered a candidate variable for the multivariate model, because data were available for only 34 of 46 patients. In association with age and extent of surgery, histologic grade was identified as a major prognostic factor in adult supratentorial ependymomas. The application of a simple and reproducible grading scheme using objective anaplastic criteria appeared to be both useful practically and clinically applicable. The role of adjuvant radiotherapy for patients with incompletely resected, low-grade ependymomas needs to be investigated further.


A molecular dynamics study on the diffusion and imprint ability of spectinomycin under different sizes of aniline oligomers.
Molecularly imprinted polymers (MIP) are the polymers created by molecular imprinting techniques that leave cavities for the specific interactions with a template molecule and have been applied in molecular selectivity tasks. In this study, the molecular dynamics (MD) simulation technique was used to demonstrate that aniline oligomer could be developed as a potential MIP for detection and separation of the spectinomycin drug molecule for gonorrhea treatment. MD simulations were performed for the systems of a spectinomycin within aniline oligomers of different sizes. The mean square displacement (MSD) and the diffusivity calculated from MD simulations showed that the diffusion coefficient was significantly dropped when the length of aniline oligomer was greater than two. The diffusion coefficient of spectinomycin became the lowest within aniline trimers, corresponded to the highest atomic distribution of MIP around the template. Then, the specific cavity in MIP systems with and without spectinomycin was calculated to assess the stability of the cavity created by the template. The volume of a cavity created within the trimer system was closest to the spectinomycin volume and therefore became the optimal oligomer size for further development of MIP.


Real-time MR tracking of AAV gene therapy with βgal-responsive MR probe in a murine model of GM1-gangliosidosis.
Transformative results of adeno-associated virus (AAV) gene therapy in patients with spinal muscular atrophy and Leber's congenital amaurosis led to approval of the first two AAV products in the United States to treat these diseases. These extraordinary results led to a dramatic increase in the number and type of AAV gene-therapy programs. However, the field lacks non-invasive means to assess levels and duration of therapeutic protein function in patients. Here, we describe a new magnetic resonance imaging (MRI) technology for real-time reporting of gene-therapy products in the living animal in the form of an MRI probe that is activated in the presence of therapeutic protein expression. For the first time, we show reliable tracking of enzyme expression after a now in-human clinical trial AAV gene therapy (ClinicalTrials.gov: NTC03952637) encoding lysosomal acid beta-galactosidase (βgal) using a self-immolative βgal-responsive MRI probe. MRI enhancement in AAV-treated enzyme-deficient mice (GLB-1-/-) correlates with βgal activity in central nervous system and peripheral organs after intracranial or intravenous AAV gene therapy, respectively. With >1,800 gene therapies in phase I/II clinical trials (ClinicalTrials.gov), development of a non-invasive method to track gene expression over time in patients is crucial to the future of the gene-therapy field.


Bilateral adrenal hemorrhage in a total knee patient associated with enoxaparin usage.
Bilateral adrenal hemorrhage is a rare but potentially catastrophic complication of chemoprophylaxis. We report a patient who underwent a total knee arthroplasty and subsequently developed bilateral adrenal hemorrhage from enoxaparin. Once the patient was diagnosed with acute adrenal insufficiency, corticosteroids were promptly started, and the patient made a dramatic recovery and did not suffer further complications.


Spectroscopic properties of gallium arsenide tetramers: Ga2As2, Ga2As2+ and Ga2As2-.
Spectroscopic properties of the low-lying electronic states of Ga2As2 and its ions are studied using the complete active-space self-consistent field (CASSCF) and density function theory (DFT) followed by the coupled-cluster single and double substitutions (including triple excitations) (CCSD(T)) calculations. The stability of low-lying electronic states is examined by computing vibrational frequency. The energies of the ground states and a number of excited electronic states have been computed to predict the spectra of Ga2As2 and its ions. The ionization energy, electronic affinity, and atomization energy are estimated at the CCSD(T)/6-311+G(d) level and compared with the available experimental results.


Fusarium Poae (Peck) Wollenw. - Occurrence in maize ears, nivalenol production and mycotoxin accumulation in cobs.
Fusarium poae (Peck) Wollenw. occurred In maize ears with "pink rot" during 1985-1993 up to 18% of Fusarium isolates, with maximum frequency in 1990. Nivalenol and fusarenone X were produced under laboratory conditions by 13 out of 14 isolates up to 115 μg/g and 13.3 μg/g respectively. The same isolates produced diacetoxyscirpenol (DAS) up to 21.7 μg/g and 15-monoacetoxyscirpenol (MAS) up to 12.3 μg/g. However, In none of the strain cultures were T-2 toxin and HT-2 toxin detected. In samples of naturally Infected maize grain nivalenol was detected at levels of 1.8-32.5 μg/g and fusarenone X was not present. In corresponding axial stems were present both nivalenol (up to 13.5 μg/g) and fusarenone X (up to 2.4 μg/g).


Occurrence and transfection of a Giardia virus.
The presence of virus-derived RNA was investigated in 38 axenically growing Giardia isolates from different geographic areas. The RNA virus was demonstrated in Giardia strains from humans in the U.S.A., England and the majority of strains from Poland. Two strains isolated respectively from a cat and a cavia also contained it. Giardia strains from humans in Belgium and Israel did not contain this RNA virus. Transfection of the RNA virus was accomplished from English and Polish strains, as well as from the cat isolate to isolates lacking it. Differences were observed both in sensitivity of Giardia strains to transfection and in infectivity of the RNA virus from different Giardia strains. Transfection could be carried out with sonicated Giardia extract as well as with filter sterilized medium in which Giardia strains containing RNA virus had grown. The RNA virus did not replicate in Giardia-free medium. No correlation could be demonstrated between the presence of the RNA virus in Giardia isolates and their in vitro resistance to some antiprotozoal drugs, nor with the fact that the strain originated from symptomatic or asymptomatic carriers. The presence of the RNA virus in Giardia trophozoites did not influence the isoenzyme patterns or restriction endonuclease patterns of repetitive DNA. A correlation may exist with the length of time since the isolation in axenic culture of the strain.


Antiulcer drugs and gastric cancer.
Inhibitors of gastric acid secretion are efficient drugs in the treatment of acid-related diseases. However, by reducing gastric acidity, hypergastrinemia develops. Gastrin regulates its target cell, the enterochromaffin (ECL) cell, both functionally and tropicaly. Long-term hypergastrinemia in whatever species studied, has been shown to induce tumors originating from the ECL cell. In man, at least 10 years of hypergastrinemia, accompanied by high or reduced gastric acidity is necessary to induce ECL cell carcinoids. There are reports indicating development of ECL cell carcinoids after long-term treatment with proton pump inhibitors. Moreover, the ECL cell may give rise to gastric carcinomas of diffuse type, which have increased during the last decades. Furthermore, most of the carcinomas developing in patients with long-lasting hypergastrinemia are of ECL cell origin. Therefore, long-lasting iatrogenic hypergastrinemia induced by potent inhibitors of acid secretion may be expected to increase the occurrence of gastric carcinomas in the future.


Use of RNAi technology to develop a PRSV-resistant transgenic papaya.
Papaya ringspot virus (PRSV) seriously limits papaya (Carica papaya L.) production in tropical and subtropical areas throughout the world. Coat protein (CP)- transgenic papaya lines resistant to PRSV isolates in the sequence-homology-dependent manner have been developed in the U.S.A. and Taiwan. A previous investigation revealed that genetic divergence among Hainan isolates of PRSV has allowed the virus to overcome the CP-mediated transgenic resistance. In this study, we designed a comprehensive RNAi strategy targeting the conserved domain of the PRSV CP gene to develop a broader-spectrum transgenic resistance to the Hainan PRSV isolates. We used an optimized particle-bombardment transformation system to produce RNAi-CP-transgenic papaya lines. Southern blot analysis and Droplet Digital PCR revealed that line 474 contained a single transgene insert. Challenging this line with different viruses (PRSV I, II and III subgroup) under greenhouse conditions validated the transgenic resistance of line 474 to the Hainan isolates. Northern blot analysis detected the siRNAs products in virus-free transgenic papaya tissue culture seedlings. The siRNAs also accumulated in PRSV infected transgenic papaya lines. Our results indicated that this transgenic papaya line has a useful application against PRSV in the major growing area of Hainan, China.


Bioavailability and short-term tolerability of alendronate in glucocorticoid-treated children.
Children receiving glucocorticoids (GCs) are at an increased risk of fragility fractures. Conservative measures may be inadequate in treating low bone mass, giving rise to fractures in this population; as such, attention has turned to the use of bisphosphonates. The goal of this study was to evaluate the bioavailability and single-dose tolerability of alendronate (ALN) in children receiving a stable dose of GCs. Children (ages 4-17 years) receiving GC treatment for their chronic illnesses received intravenous (125 μg) and oral (35 mg) ALN in a 2-period, randomized crossover study, with doses separated by at least a 7-day washout period. Urine was collected for either 8 or 24 hours after drug administration to determine urinary excretion of ALN and bioavailability. Tolerability was assessed by continuous collection of adverse events reported during the study. The main outcome measures were total urinary excretion rates, oral bioavailability of ALN, and adverse events. There were 12 patients in the 4- to 11-year-old group (mean age, 8.1 years; 5 girls) and 12 patients in the 12- to 17-year-old group (mean age, 14.3 years; 5 girls). The least-squares mean bioavailability (90% CI) for children aged 4 to 11 years (n = 12) was 0.43% (0.27-0.67) and for children aged 12 to 17 years (n = 12) it was 0.39% (0.26-0.60). The least-squares mean bioavailability for all ages combined was 0.41% (0.30-0.56), with no statistical difference between the 2 age groups. The total urinary excretion of ALN after the intravenous dose was similar between groups. Fifteen patients reported a total of 36 transient clinical nonserious adverse events, all of which were mild or moderate in intensity; the most common were headache (n = 13), abdominal pain (n = 3), limb, neck, or facial pain (n = 6), and ankle or knee swelling (n = 3). The mean oral bioavailability of ALN was similar to previous pharmacokinetic studies in children with osteogenesis imperfecta and slightly lower than that observed in historical adult controls. Alendronate was generally well tolerated, with minor adverse events that resolved uneventfully. Elucidation of the full adverse-effect profile of this agent was limited by the single-dose nature of this study, and robust comparisons of the pharmacokinetics of ALN in different age groups may need a larger number of patients.


Catecholamines increase nerve growth factor mRNA content in both mouse astroglial cells and fibroblast cells.
Previous studies have shown that catecholamines increase the nerve growth factor (NGF) content in medium conditioned by mouse L-M fibroblast cells and mouse astroglial cells. In this study, the NGF mRNA levels in these cells were measured by Northern blot analysis. In astroglial cells treated with epinephrine (EN), the cellular NGF mRNA level increased prior to accumulation of NGF in the culture medium. 3-Hydroxytyramine (DA) and norepinephrine (NE) also increased the cellular NGF mRNA content. An increased level of NGF mRNA elicited by EN was also observed in mouse L-M cells. These results indicate that catecholamines enhance NGF synthesis of L-M fibroblast cells and astroglial cells by increasing the cellular content of NGF mRNA. The present results also indicate that the effects of catecholamines are not mediated by adrenergic receptors.


Enhanced production of gamma-aminobutyrate (GABA) in recombinant Corynebacterium glutamicum strains from empty fruit bunch biosugar solution.
Recent interest has been focused on the production of platform chemicals from renewable biomass due to increasing concerns on global warming and depletion of fossil fuel reserves. Microbial production of platform chemicals in biorefineries has been suggested to be a promising solution for these problems. Gamma-aminobutyrate (GABA), a versatile bulk chemical used in food and pharmaceutical industry, is also used as a key monomer for nylon 4. GABA can be biologically produced by decarboxylation of glutamate. In this study, we examined high glutamate-producing Corynebacterium glutamicum strains as hosts for enhanced production of GABA from glucose and xylose as carbon sources. An Escherichia coli gadB mutant with a broad pH range of activity and E. coli xylAB genes were expressed under the control of a synthetic H36 promoter. When empty fruit bunch (EFB) solution was used as carbon source (45 g/L glucose and 5 g/L xylose), 12.54 ± 0.07 g/L GABA was produced by recombinant C. glutamicum H36GD1852 expressing E. coli gadB mutant gene and xylAB genes. Batch fermentation of the same strain resulted in the production of 35.47 g/L of GABA when EFB solution was added to support 90 g/L glucose and 10 g/L xylose. This is the first report of GABA production by recombinant C. glutamicum strains from co-utilization of glucose and xylose from EFB solution. Recombinant C. glutamicum strains developed in this study should be useful for an efficient and sustainable production of GABA from lignocellulosic biomasses.


Prehospital Trauma Life Support (PHTLS) training of ambulance caregivers and impact on survival of trauma victims.
The Prehospital Trauma Life Support (PHTLS) course has been widely implemented and approximately half a million prehospital caregivers in over 50 countries have taken this course. Still, the effect on injury outcome remains to be established. The objective of this study was to investigate the association between PHTLS training of ambulance crew members and the mortality in trauma patients. A population-based observational study of 2830 injured patients, who either died or were hospitalized for more than 24 h, was performed during gradual implementation of PHTLS in Uppsala County in Sweden between 1998 and 2004. Prehospital patient records were linked to hospital-discharge records, cause-of-death records, and information on PHTLS training and the educational level of ambulance crews. The main outcome measure was death, on scene or in hospital. Adjusting for multiple potential confounders, PHTLS training appeared to be associated with a reduction in mortality, but the precision of this estimate was poor (odds ratio, 0.71; 95% confidence interval, 0.42-1.19). The mortality risk was 4.7% (36/763) without PHTLS training and 4.5% (94/2067) with PHTLS training. The predicted absolute risk reduction is estimated to correspond to 0.5 lives saved annually per 100,000 population with PHTLS fully implemented. PHTLS training of ambulance crew members may be associated with reduced mortality in trauma patients, but the precision in this estimate was low due to the overall low mortality. While there may be a relative risk reduction, the predicted absolute risk reduction in this population was low.


Structure-permeation relationships for the non-invasive transdermal delivery of cationic peptides by iontophoresis.
Transdermal iontophoresis enables the controlled, non-invasive administration of peptide therapeutics. The aims of this study were (i) to evaluate the effect of amino acid sequence and the spatial distribution of peptide physicochemical properties on electrotransport, and (ii) to develop a quantitative model to predict peptide transport rates. Experimental results showed that the distribution of molecular properties over the peptide surface significantly affected iontophoretic delivery: different arrangements of the same residues resulted in different transport behavior. Computational studies generated three-dimensional quantitative structure-permeation relationships (3D-QSPR) based on 3D descriptors. The model predicted that iontophoresis was favored by peptide hydrophilicity but hindered by voluminous, localized hydrophobicity. Molecular characteristics that favor electrotransport are the converse of those required for passive diffusion across biological membranes. The data represent the first analysis of peptide electrotransport in terms of the spatial distribution of molecular properties and provide insight into the ab initio prediction of transdermal iontophoretic peptide delivery.


Local Spectroscopic Characterization of Spin and Layer Polarization in WSe_{2}.
We report scanning tunneling microscopy and scanning tunneling spectroscopy (STS) measurements of monolayer and bilayer WSe_{2}. We measure a band gap of 2.21±0.08 eV in monolayer WSe_{2}, which is much larger than the energy of the photoluminescence peak, indicating a large excitonic binding energy. We additionally observe significant electronic scattering arising from atomic-scale defects. Using Fourier transform STS, we map the energy versus momentum dispersion relations for monolayer and bilayer WSe_{2}. Further, by tracking allowed and forbidden scattering channels as a function of energy we infer the spin texture of both the conduction and valence bands. We observe a large spin-splitting of the valence band due to strong spin-orbit coupling, and additionally observe spin-valley-layer coupling in the conduction band of bilayer WSe_{2}.


Differences in the sorption kinetics of various non-ionisable pesticides in a limited number of agricultural soils from the Mediterranean basin.
Adsorption in soil of organic contaminants, such as pesticides, is a time-dependent process, which can be relevant for understanding and predicting the potential pollution risk of different water sources. The adsorption behavior of six different pesticides with a wide range of physicochemical properties (log KOW 1.26-5.8) was evaluated in up to three different soils with low organic carbon (OC) content (≤1.2%). Pesticide sorbed amounts were fitted to several mathematical models to unravel the mechanisms involved in the adsorption process. The linear distribution constants revealed that pendimethalin and the pyrethroid insecticides were strongly retained in soil, whereas the other three compounds were moderately or weakly adsorbed. In the three soils, the pseudo second order model described more accurately the sorption kinetics of all the contaminants. The more hydrophobic pesticides (log KOW ≥ 4.6) presented lower kinetic rates as compared with the other compounds under study. Both Elovich and intraparticle diffusion models reflected a strong contribution of a rapid initial adsorption on soil surface for thiacloprid, dimethenamid and fenarimol. For the hydrophobic pesticides this contribution was moderate according to the intraparticle diffusion model. Therefore, slower diffusion into the soil micropores was more relevant for the more hydrophobic compounds and for the bigger molecules, and less significant for the more polar pesticides because almost 90% of the total amount adsorbed was achieved in the rapid initial stage.


Establishment of a modified Kyoto classification scoring model and its significance in the diagnosis of Helicobacter pylori current infection.
We aimed to establish a modified model of the Kyoto classification score and verify its accuracy for predicting Helicobacter pylori (HP) infection during endoscopy. Patients who underwent gastroscopy from June 2020 to March 2021 were included in this study. Atrophy, intestinal metaplasia, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, spotty redness, xanthoma, map-like redness, fundic gland polyp, and regular arrangement of collecting venules (RAC) were recorded according to the Kyoto classification of gastritis. The HP infection status of participants was determined by a 13C breath test, anti-HP antibody, and histopathologic hematoxylin and eosin staining. The modified Kyoto classification scoring model was established based on univariate analysis and logistic regression analysis. The modified scoring model was used to judge the status of HP infection in patients undergoing gastroscopy from July to September 2021 and to evaluate the accuracy of the prediction. Of 667 participants in the derivation dataset, 326 cases had HP infection and 341 cases did not. Atrophy, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, and spotty redness were associated with HP current infection. Thus, a new scoring model, termed the modified Kyoto classification scoring model, was constructed that included atrophy, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, spotty redness, fundic gland polyp, and RAC as indicators. To test the model, 808 subjects, including 251 HP-positive patients, comprised the validation dataset. The modified Kyoto classification scoring model improved the accuracy of endoscopic determination of HP current infection and has clinical application potential in the Chinese population.


Antibody-catalyzed cleavage of the D-Ala-D-Lac depsipeptide: an immunological approach to the problem of vancomycin resistance.
Vancomycin resistance is currently a major healthcare problem. The development of a catalytic monoclonal antibody (mAb) that hydrolyzes the D-Ala-D-Lac depsipeptide provides a potentially novel antibiotic strategy. A phosphonate hapten design was used to program antibody catalysis. The characteristics of the hapten were shown to be important for obtaining a viable immune response and several catalytic mAbs that cleave a peptidoglycan model substrate. The best mAb afforded a >500-fold rate enhancement over background.


Effects of ketamine on prepubertal Wistar rats: Implications on behavioral parameters for Childhood-Onset Schizophrenia.
Early childhood schizophrenia (COS) is a rare condition and has no established animal model to test new treatments. Previous studies have shown that repeated doses of 25 mg/kg ketamine produce schizophrenia-like changes in adult male Wistar rats, but adequate doses of ketamine in animal COS studies are not yet known. Male and female Wistar rats, 23 days old, received an injection of ketamine or intraperitoneal saline (i.p.) for 8 days. The animals underwent different behavioral tests: open field, social interaction, pre-pulse startle inhibition (PPI). Female rats showed behavioral changes at all ketamine doses (5, 15, 25 and 50 mg/kg), in contrast to males that only at 50 mg/kg dose had interrupted PPI and higher stereotypy in the open field test. The present study demonstrated that ketamine at a dose of 50 mg/kg once daily from 23 to 31 days postnatal reproduced changes similar to schizophrenia in pre-pubertal male and female Wistar rats and could be used, with other interventions, in future studies with animals in COS.


Dynamics of phosphodiesterase-induced cAMP dissociation from protein kinase A: capturing transient ternary complexes by HDXMS.
cAMP signaling is a fundamental cellular process necessary for mediating responses to hormonal stimuli. In contrast to cAMP-dependent activation of protein kinase A (PKA), an important cellular target, far less is known on termination in cAMP signaling, specifically how phosphodiesterases (PDEs) facilitate dissociation and hydrolysis of bound cAMP. In this study, we have probed the dynamics of a ternary complex of PKA and a PDE-RegA with an excess of a PDE-nonhydrolyzable cAMP analog, Sp-cAMPS by amide hydrogen/deuterium exchange mass spectrometry (HDXMS). Our results highlight how HDXMS can be used to monitor reactions together with mapping conformational dynamics of transient signaling complexes. Our results confirm a two-state model for active RegA-mediated dissociation of bound cAMP. Further, our results reveal that Sp-cAMPS and RegA mediate mutually exclusive interactions with the same region of PKA and at specific concentrations of Sp-cAMPS, RegA is capable of blocking Sp-cAMPS reassociation to PKA. This provides a molecular basis for how PDEs modulate levels of intracellular cAMP so that PKA is better suited to responding to fluxes rather than constant levels of cAMP. This study underscores how HDXMS can be a powerful tool for monitoring reactions together with mapping conformational dynamics in signaling proteins. This article is part of a Special Issue entitled: Mass spectrometry in structural biology.


METTL3 regulates N6-methyladenosine modification of ANGPTL3 mRNA and potentiates malignant progression of stomach adenocarcinoma.
N6-methyladenosine (m6A) is associated with mammalian mRNA biogenesis, decay, translation and metabolism, and also contributes greatly to gastrointestinal tumor formation and development. Therefore, the specific mechanisms and signaling pathways mediated by methyltransferase-like 3 (METTL3), which catalyzes the formation of m6A chemical labeling in stomach adenocarcinoma (STAD), are still worth exploring. Quantitative real-time PCR (qRT-PCR) was constructed to detect the expression of METTL3 in gastric cancer cell lines and patient tissues. The biological function of METTL3 was investigated in vitro/in vivo by Cell Counting Kit-8, colony formation assay, Transwell assay and nude mouse tumorigenesis assay. Based on the LinkedOmics database, the genes co-expressed with METTL3 in the TCGA STAD cohort were analyzed to clarify the downstream targets of METTL3. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA stability analysis were employed to explore the mechanism of METTL3 in gastric cancer progression. We analyzed TCGA data and found that METTL3 was frequently elevated in STAD, and demonstrated that METTL3 was present at high levels in clinical STAD tissues and cells. High METTL3 expression was more likely to have advanced TNM tumors and distant metastasis. On the other hand, METTL3 silencing effectively impeded the higher oncogenic capacity of AGS and HGC27 cells in vivo and in vitro, as reflected by slowed cell growth and diminished migration and invasion capacities. Continued mining of the TCGA dataset identified the co-expression of angiopoietin-like 3 (ANGPTL3) and METTL3 in STAD. Lower level of ANGPTL3 was related to increased level of METTL3 in STAD samples and shorter survival times in STAD patients. ANGPTL3 enrichment limited the growth and metastasis of STAD cells. Besides, ANGPTL3 mRNA levels could be decreased by METTL3-dominated m6A modifications, a result derived from a combination of MeRIP-qPCR and RNA half-life experiments. Importantly, the inhibitory effect of METTL3 silencing on cancer could be reversed to some extent by ANGPTL3 inhibition. Overall, our findings suggested that METTL3 functioned an oncogenic role in STAD by reducing ANGPTL3 expression in an m6A-dependent manner. The discovery of the METTL3-ANGPTL3 axis and its effect on STAD tumor growth will contribute to further studies on the mechanisms of gastric adenocarcinoma development.


Is a repressive-defensive coping style really so bad? Comment on DeNeve and Cooper (1998).
This comment refers to the meta-analysis of K. M. DeNeve and H. Cooper showing that repressive defensiveness compared with 136 other personality traits was most strongly, but negatively, related to subjective well-being. It is shown that for theoretical and empirical reasons the relationship cannot be negative.


Intraindividual comparison of capsule behavior of 2 hydrophobic acrylic intraocular lenses during a 5-year follow-up.
To evaluate and compare the 5-year postoperative anterior (ACO) and posterior capsule opacification (PCO), the occurrence of glistenings, and the level of anterior capsule retraction after implantation of 2 designs of 1-piece hydrophobic acrylic IOLs. Hospital St. John, Vienna, Austria. Randomized controlled prospective case series. Patients had an Acrysof SA60AT IOL (Group A) implanted in 1 eye and a Tecnis ZCB00 IOL (Group B) implanted in the fellow eye. At 1, 3, and 5 years, the PCO level was evaluated with the Evaluation of Posterior Capsule Opacification software. The level of ACO and capsule retraction was graded subjectively. Glistenings were scored as present or not present. Fifty eyes of 25 patients were evaluated after 5 years. No significant differences in PCO scores were found between the 2 groups at all follow-up visits (1 year: 0.06 ± 0.12 [SD] versus 0.07 ± 0.13, P = .35; 3 years: 0.23 ± 0.36 versus 0.22 ± 0.32, P = .66; 5 years: 0.36 ± 0.41 versus 0.36 ± 0.54, P = .98). A significant increase in PCO score was found between 3 and 5 years (P < .01). Anterior capsule opacification was present in Group A and Group B in 18.0% and 2.7% of eyes (P = .03), in 92.0% and 24.0% of eyes, and in 100% and 52% of eyes (P < .01) at 1, 3, and 5 years, respectively. Glistenings (5 years 100%) were observed in Group A. Both IOLs had a comparable PCO rate 5 years after surgery, although more ACO and retraction as well as glistenings were observed in Group A.


The influence of the pericellular microenvironment on the chondrocyte response to osmotic challenge.
To examine whether differences in the pericellular microenvironment of different chondron preparations influence the chondrocyte volume regulatory response to experimental osmotic challenge. Mechanically extracted chondrons (MC), enzymatically extracted chondrons (EC) and isolated chondrocytes (IC) were seeded into agarose and sampled at 1, 3 and 7 days. Samples mounted in a perfusion chamber were subjected to osmotic challenge. The cross-sectional areas of the chondrocyte and pericellular microenvironment were measured under isotonic, hypertonic and hypotonic conditions, and percentage change calculated. Separate samples were immunolabeled for type VI collagen and keratan sulfate. Initially, the microenvironment of MC represented 60% of the chondron area and was occupied by type VI collagen and keratan sulfate. In EC, the microenvironment comprised 18% of the chondron area with narrow bands of type VI collagen and keratan sulfate. IC had no visible microenvironment, with small amounts of type VI collagen and keratan sulfate present. All preparations sequestered additional pericellular macromolecules during culture. Under isotonic conditions, the EC and IC chondrocytes were larger than those of MC. All chondrocytes shrank under hypertonic conditions and swelled under hypotonic conditions. MC were the least responsive, displaying the most efficient volume regulation. IC showed the largest response initially but this decreased with time. EC exhibited intermediate responses that decreased as the microenvironment increased in size. The composition and structural integrity of the pericellular microenvironment do influence the cellular response to experimental osmotic challenge. This suggests that the microenvironment functions in situ to mediate the chondrocyte response to physicochemical changes associated with joint loading.


Endoscopic submucosal dissection for gastric cancer.
Endoscopic submucosal dissection (ESD) is a novel endoscopic treatment that enables a clinician to resect an early-stage gastric cancer in en bloc fashion. ESD is indicated for those cancers in which there is a high probability of en bloc resection and low probability of lymph node metastasis. The latter may be the limiting factor at institutions skilled at ESD. Several ESD techniques are available with similar outcomes. Thus, selection depends on operator preference and expertise. Gastrectomy with lymphadenectomy should be applied initially to those early gastric cancers with high probability of positive lymph nodes or as an additional treatment after ESD. Endoscopic mucosal resection (EMR) should be reserved for small, nonulcerated, intramucosal, differentiated cancers. Disadvantages of ESD in comparison with EMR are longer operation times and higher incidences of intraoperative bleeding and perforation, but the indication for ESD includes larger and ulcerative lesions not amenable to EMR.


Negative symptom dimensions in first episode psychosis: Is there a difference between schizophrenia and non-schizophrenia spectrum disorders?
Identifying discrete dimensions that underline negative symptoms in First Episode Psychosis (FEP) could improve the understanding and the treatment of such invalidating symptomatology. The aim of this study is to examine the negative symptom structure in FEP individuals and to compare the resulting factor configurations between FEP subjects with and without Schizophrenia Spectrum Disorders (SSD vs non-SSD). One hundred and seventy participants (88 SSD and 82 non-SSD), aged 13-35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Positive and Negative Syndrome Scale (PANSS). A principal component analysis was then performed to investigate PANSS negative symptom structure in both non-SSD and SSD groups. Whereas in the SSD sample a 3-factor model solution (i.e., "Socio-Emotional Disengagement", "Motor/Thought Poverty", and "Avolition/Apathy" dimensions) was identified, a 2-factor model solution (with a mixed alogia/avolition domain in addition to a mixed socio-emotional disengagement/expressive deficits dimension) appeared more appropriate in the non-SSD group. Our results show a relevant difference in the negative symptom factor structure between SSD and non-SSD individuals. In particular, a different specificity and significance of negative symptom models in FEP populations with diagnoses other than schizophrenia (compared to those with SSD) must be realistically considered. Notably, a "Motor/Thought Poverty" domain, which specifically includes alogia and motor retardation separately from the other PANSS negative items, appears to specifically characterize FEP young patients with the schizophrenia spectrum.


Early activation or a more protective regime after arthroscopic subacromial decompression--a description of clinical changes with two different physiotherapy treatment protocols--a prospective, randomized pilot study with a two-year follow-up.
To describe clinical changes with two protocols of physiotherapy following arthroscopic subacromial decompression (ASD) over two years. Reliability of Functional Index of the Shoulder was performed. A prospective, randomized pilot study, within-subject design. Thirty-four shoulders (13 women), mean age 46 (SD 7) years with primary shoulder impingement, listed for arthroscopic subacromial decompression. The traditional group (n = 20) started with active assisted range of motion exercises on the day of surgery, dynamic exercises for the rotator cuff after six weeks and strengthening exercises after eight weeks. The progressive group (n = 14) started active assisted range of motion and dynamic exercises for the rotator cuff on the day of surgery. Strengthening exercises started after six weeks. A clinical evaluation was made preoperatively, six weeks, three, six, 12 and 24 months after surgery. Pain, patient satisfaction, active range of motion and muscular strength were evaluated. Shoulder function was evaluated using Constant score, Hand in neck, Pour out of a pot and Functional Index of the Shoulder. Both groups showed significant improvements in pain during activity and at rest, in range of motion in extension and abduction, in strength of external rotation and in function. There were no clinical differences in changes between groups. Most patients were pain-free from six months. After two years, the majority of patients achieved > or = 160 degrees in flexion, > or = 175 degrees in abduction and 80 degrees in external rotation, the traditional achieved 67 and the progressive group 87 with Constant score. Early activation using a comprehensive, well-defined and controlled physiotherapy protocol can be used safely after arthroscopic subacromial decompression.


Cervical epidural abscess presenting as giant cell arteritis.
Maxillofacial surgeons may be involved in the initial investigation and management of temporal arteritis. We present a case of a cervical epidural abscess with clinical features of temporal arteritis.


Development of the Canadian Marginalization Index: a new tool for the study of inequality.
Area-based measures of socio-economic status are increasingly used in population health research. Based on previous research and theory, the Canadian Marginalization Index (CAN-Marg) was created to reflect four dimensions of marginalization: residential instability, material deprivation, dependency and ethnic concentration. The objective of this paper was threefold: to describe CAN-Marg; to illustrate its stability across geographic area and time; and to describe its association with health and behavioural problems. CAN-Marg was created at the dissemination area (DA) and census tract level for census years 2001 and 2006, using factor analysis. Descriptions of 18 health and behavioural problems were selected using individual-level data from the Canadian Community Health Survey (CCHS) 3.1 and 2007/08. CAN-Marg quintiles created at the DA level (2006) were assigned to individual CCHS records. Multilevel logistic regression modeling was conducted to examine associations between marginalization and CCHS health and behavioural problems. The index demonstrated marked stability across time and geographic area. Each of the four dimensions showed strong and significant associations with the selected health and behavioural problems, and these associations differed depending on which of the dimensions of marginalization was examined. CAN-Marg is a census-based, empirically derived and theoretically informed tool designed to reflect a broader conceptualization of Canadian marginalization.


Processing of spent platinum-based catalysts via fusion with potassium hydrogenosulfate.
This work describes a route for processing spent platinum-based commercial catalysts (Pt and PtSnIn/Al(2)O(3)) via fusion with potassium hydrogenosulfate (KHSO(4)). Samples were previously ground. The optimized experimental parameters were: temperature, 450°C; time, 3h; sample/flux mass ratio, 1/10. The fused mass was dissolved in water and the elements present were isolated by a multi-step separation procedure. Platinum was recovered as the only water-insoluble residue. About 45 wt% of aluminium was recovered as KAl(SO(4))(2)·12H(2)O (alum), whereas the remaining element was recovered as Al(OH)(3). Tin and indium were recovered together as sulfides at pH 1. About 72 wt% of potassium was recovered as K(2)SO(4) when the final effluent was treated with sulfuric acid (pH 1) and slowly evaporated. Generation of final wastes was greatly reduced. More than 98 wt% of the elements present in the catalysts examined was recovered.


Integration of exosomal miR-106a and mesothelial cells facilitates gastric cancer peritoneal dissemination.
Metastatic organotropism is considered the end stage of malignancy with the mechanism still have some mysteries that have not been disclosed. Although the role of miR-106a is well studied, its involvement in the formation of peritoneal metastasis transported by exosomes is less discussed. Gastric cancer (GC)-derived exosomes were identified by transmission electron microscopy and the integration with peritoneal mesothelial cells (PMC) was confirmed by PKH-26 staining. Cell phenotype was assessed by EdU and flow cytometry. MiR-106a and its targets were authenticated by luciferase reporter assay. The mesothelial-to-mesenchymal transition (MMT) and extracellular matrix (ECM) degeneration were determined and morphological transformation was measured by transwell assay. Immunodeficient mouse was conducted to investigate the tumorigenesis and tumor growth. The final was tissue analysis. MiR-106a enrichment in GC-exosomes can be delivered and integrated into PMC to establish a proper pre-metastatic niche (PMN). We found that PMC could internalize exosomal-miR-106a and lead to increased apoptotic rate and decreased proliferative vitality. The direct target Smad7 and TIMP2 were proved to be effectively reduced by translocation of exosomal miR-106a. We confirmed that exosomal miR-106a was able to induce MMT and accelerate ECM through targeting Smad7 and TIMP2 to activate TGF-β pathway. Animal model investigated that the tumorigenesis and tumor growth could be influenced by exosomes, and exosomal-miR-106a could promote the formation of xenograft tumor. Tissue analysis verified the ectopic miR-106a expression in gastric cancer metastasis. Our data suggest that exosomal miR-106a facilitates gastric cancer peritoneal dissemination by integrating PMC to destroy mesothelial barrier.


Drugs and the liver.
The authors discuss the liver's influence on drug disposition in the body and the influence of drugs on the liver. Drug-induced hepatotoxicity with regard to mechanisms and causative agents is discussed, as well as administration of drugs to patients with existing liver disease.


Isoform-selective thiazolo[5,4-b]pyridine S1P1 agonists possessing acyclic amino carboxylate head-groups.
Replacement of the azetidine carboxylate of an S1P(1) agonist development candidate, AMG 369, with a range of acyclic head-groups led to the identification of a novel, S1P(3)-sparing S1P(1) agonist, (-)-2-amino-4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)-2-methylbutanoic acid (8c), which possessed good in vivo efficacy and pharmacokinetic properties. A 0.3mg/kg oral dose of 8c produced a statistically significant reduction in blood lymphocyte counts 24h post-dosing in female Lewis rats.


The ambiguous meanings of the racial/ethnic categories routinely used in human genetics research.
Many researchers are currently studying the distribution of genetic variations among diverse groups, with particular interest in explaining racial/ethnic health disparities. However, the use of racial/ethnic categories as variables in biological research is controversial. Just how racial/ethnic categories are conceptualized, operationalized, and interpreted is a key consideration in determining the legitimacy of their use, but has received little attention. We conducted semi-structured, open-ended interviews with 30 human genetics scientists from the US and Canada who use racial/ethnic variables in their research. They discussed the types of classifications they use, the criteria upon which they are based, and their methods for classifying individual samples and subjects. We found definitions of racial/ethnic variables were often lacking or unclear, the specific categories they used were inconsistent and context specific, and classification practices were often implicit and unexamined. We conclude that such conceptual and practical problems are inherent to routinely used racial/ethnic categories themselves, and that they lack sufficient rigor to be used as key variables in biological research. It is our position that it is unacceptable to persist in the constructing of scientific arguments based on these highly ambiguous variables.


Dynamics of colorectal cancer.
Colorectal cancer results from an accumulation of mutations in tumor suppressor genes and oncogenes. An additional defining characteristic of colorectal cancer is its genetic instability. Two main types of genetic instability have been identified. Microsatellite instability leads to an increased point mutation rate, whereas chromosomal instability refers to an enhanced rate of accumulating gross chromosomal aberrations. All colon cancer cell lines are genetically unstable. An interesting question is whether genetic instability arises early in tumorigenesis. An early emergence of genetic instability could drive most of the somatic evolution of cancer. Here, we review mathematical models of colorectal tumorigenesis and discuss the role of genetic instability.


Molecular mechanisms of anthracycline activity.
On the basis of evidence that anthracyclines are DNA intercalating agents and DNA is the primary target,a large number of analogs and related intercalators have been developed. However, doxorubicin andclosely related anthracyclines still remain among the most effective antitumor agents. Multiple mechanismshave been proposed to explain their efficacy. They include inhibition of DNA-dependent functions, freeradical formation, and membrane interactions. The primary mechanism of action is now ascribed to drug interferencewith the function of DNA topoisomerase II. The stabilization of the topoisomerase-mediated cleavablecomplex results in a specific type of DNA damage (i.e., double-strand protein-associated DNA breaks).The drug-stabilized cleavable complex is a potentially reversible molecular event and its persistence,as a consequence of strong DNA binding, may be recognized as an apoptotic stimulus. Indirect evidencesupports the notion that the bioreductive processes of the quinone moiety generating the semiquinone radicalwith concomitant production of reactive oxygen species may contribute to the drug effects. The cellulardefense mechanisms and response to genotoxic/cytotoxic stress appear to be critical determinants of thetumor sensitivity to anthracyclines.


Frequency of disagreements between producers and veterinarians about pain management in cattle.
Pain management is a key element of ensuring animal welfare. Although the opinions of both producers and veterinarians affect decisions about the use of pain mitigation on cattle operations, little is known about how they communicate about this topic. Given the importance of a veterinary-client-patient relationship for developing pain mitigation protocols, understanding the communication between veterinarians and producers is key to the implementation of robust, industry-wide pain management protocols. The objectives of this survey were to understand how producers and veterinarians may respond to disagreements about pain mitigation and to determine where respondents obtain their knowledge about pain recognition and treatment. Results presented herein are part of a larger study previously described. An online survey was distributed to 6 cattle industry groups. Surveys that were >80% complete were included for analysis (n = 1,066). Approximately half of the respondents identified as producers (497, 46.6%) and half as veterinarians (569, 53.4%). The majority of producers believed that disagreements about the use of pain management in cattle never affected their relationship with their veterinarians (349, 70.2%). The veterinarian respondents indicated more disagreements, although the frequency was relatively low, with 43.9% (250) indicated having a disagreement less than once a year. Most producers and veterinarians indicated they were either "extremely unlikely" or "somewhat unlikely" to dissolve the relationship completely if disagreements about pain management arose (veterinarians: 398/569, 70%; producers: 294/497, 59.1%). Veterinarians and producers reported gaining their knowledge about pain recognition from a variety of sources including personal experience and continuing education opportunities. Disagreements about pain mitigation occurred infrequently; however, this could be due to few discussions about pain management in general. These results indicated that there is opportunity for veterinarians to engage with their producers in more discussions about pain management.


Effectiveness and safety of novel motorized spiral enteroscopy: a systematic review and meta-analysis.
Motorized spiral enteroscopy (MSE) is a novel advance in small bowel examination that is characterized as fast with a deep insertion. The aim of this study was to elucidate the effectiveness and safety of MSE. Relevant articles that were published before November 1, 2022 were identified by searching PubMed, EMBASE, Cochrane, and the Web of Science. The technical success rate (TSR), total (pan)-enteroscopy rate (TER), depth of maximum insertion (DMI), diagnostic yield, and adverse events were extracted and analyzed. Forest plots were graphed based on random effects models. A total of 876 patients from 8 studies were eligible for analysis. The pooled results of the TSR were 95.0% [95% confidence interval (CI) 91.0-98.0%, I2 = 78%, p < 0.01] and the pooled outcome of the TER was 43.1% (95% CI 24.7-62.5%, I2 = 95%, p < 0.01). The pooled results of the diagnostic and therapeutic yields were 77.2% (95% CI 69.0-84.5%, I2 = 84%, p < 0.01) and 49.0% (95% CI 38.0-60.1%, I2 = 89%, p < 0.01), respectively. The pooled estimates of adverse and severe adverse events were 17.2% (95% CI 11.9-23.2%, I2 = 75%, p < 0.01) and 0.7% (95% CI 0.0-2.1%, I2 = 37%, p = 0.13), respectively. MSE is a novel alternative approach for small bowel examination that can achieve high TER and diagnostic and therapeutic yields, and relatively low rates of severe adverse events. Head-to-head studies comparing MSE and other device-assisted enteroscopies are warranted.


Preservation of redox, polyamine, and glycine modulatory domains of the N-methyl-D-aspartate receptor in Alzheimer's disease.
This study used [3H]dizocilpine ([3H]MK-801) binding to the N-methyl-D-aspartate (NMDA) receptor to examine redox, polyamine, and glycine modulatory sites in membranes derived from the superior frontal and the superior temporal cortex of patients with Alzheimer's disease. In control subjects the competitive polyamine site antagonist arcaine inhibited [3H]dizocilpine binding in a dose-dependent fashion and this curve was shifted to the right by the addition of 50 microM spermidine. Arcaine inhibition of binding was more potent in the temporal cortex than in the frontal cortex, in both the absence and presence of 50 microM spermidine. In Alzheimer's disease, arcaine inhibition of [3H]dizocilpine binding (in both the absence and the presence of spermidine) was not different from control in either of the two brain areas examined. The sulfhydryl redox site of the NMDA receptor was assessed using the oxidizing agent 5,5'-dithio-bis(2-nitrobenzoic acid), which inhibited binding in a dose-dependent fashion. This inhibition was similar in patients with Alzheimer's disease and control subjects. Glycine-stimulated [3H]dizocilpine binding was also unaffected in patients with Alzheimer's disease. However, in the temporal cortex there was a significant age-associated decline in [3H]dizocilpine binding in the presence of 100 microM glutamate (Rs = -0.71) and 100 microM glutamate plus 30 microM glycine (Rs = -0.90). There was also an age-related increase in arcaine IC50 (which reflects an age-related decrease in arcaine affinity) in the frontal cortex, determined both in the absence (Rs = 0.83) and the presence (Rs = 0.79) of spermidine. These data indicate that the NMDA receptor and its modulatory redox, polyamine, and glycine subsites are intact in patients with Alzheimer's disease and that the modulatory activity of polyamine and glycine sites decline with aging.


[A comparative study on the acupoints of specialty of Baihui, Shuigou and Shenmen in treating vascular dementia].
To study the relative specialty of the acupoints of Baihui (DU20), Shuigou (DU26) and Shenmen (HT7) in treating vascular dementia (VD). Fifty patients suffering from VD were divided into 5 groups randomly and treated by conventional acupuncture for hemiplegia, or conventional acupuncture plus needling in DU20, DU26, HT7 respectively or simultaneously. Clinical symptoms were observed, and the scales such as Hasegawa's dementia scale-recension (HDS-R), activities of daily living (ADL) and functional activities questionnaire (FAQ) were used for assessment before and after acupuncture treatment. The scores were processed statistically. DU20 and HT7 could improve the abilities of memory, orientation, reaction and reduce adamancy and trance. Besides, DU 20 was helpful in improving the abilities of understanding, calculating and social adapting. While DU26 is helpful in treating retardation, failure in daily activities, trance and poor memory. The combination of the 3 acupoints could improve the intelligence and social adapting ability of VD patients. DU20, DU26 and HT7 had its own effect in treating VD, but the effect of three points used in combination was the best.


Understanding of the drug resistance mechanism of hepatitis C virus NS3/4A to paritaprevir due to D168N/Y mutations: A molecular dynamics simulation perspective.
Hepatitis C virus (HCV) NS3/4A protease is an attractive target for the development of antiviral therapy. However, the evolution of antiviral drug resistance is a major problem for treatment of HCV infected patients. Understanding of drug-resistance mechanisms at molecular level is therefore very important for the guidance of further design of antiviral drugs with high efficiency and specificity. Paritaprevir is a potent inhibitor against HCV NS3/4A protease genotype 1a. Unfortunately, this compound is highly susceptible to the substitution at D168 in the protease. In this work, molecular dynamics simulations of paritaprevir complexed with wild-type (WT) and two mutated strains (D168 N and D168Y) were carried out. Due to such mutations, the inhibitor-protein hydrogen bonding between them was weakened and the salt-bridge network among residues R123, R155 and D168 responsible for inhibitor binding was disrupted. Moreover, the per-residue free energy decomposition suggested that the main contributions from key residues such as Q80, V132, K136, G137 and R155 were lost in the D168 N/Y mutations. These lead to a lower binding affinity of paritaprevir for D168 N/Y variants of the HCV NS3/4A protease, consistent with the experimental data. This detailed information could be useful for further design of high potency anti-HCV NS3/4A inhibitors.


Influence of viscous Rhodella grisea (Rhodophyceae) proteoglycan on chemically induced cough reflex.
An algal extracellular biopolymer (over 8.5 × 10(5)Da) composed of carbohydrates (52%) and protein (∼13%) has been isolated from a red alga Rhodella grisea growing in natural conditions by concentration of water medium, alcohol precipitation, dialysis and freeze-drying. This mucilagineous biopolymer contained xylose and its 3-O- and 4-O-methyl derivatives (∼63%), galactose (∼12%), glucuronic acid (11-12%), glucose (∼5%), rhamnose (∼4%), fucose (∼3-4%) and low content of others accompaning sugars. When tested on the citric acid-induced cough and reactivity of airways smooth muscle in vivo in the test system guinea pigs, this biopolymer assigned a significant cough suppressing effect. The reactivity of airways smooth muscle was not affected indicating that expectoration effect was not suppressed by biopolymer application, which is important from the pharmacological point of view.


Heterogeneity in tissue oxygenation: from physiological variability in normal tissues to pathophysiological chaos in malignant tumours.
Heterogeneity is a feature of both normal oxygen supply to tissue and of a supply that is disturbed due to a wide range of different pathologies. Here, the physiological importance of heterogeneity of tissue oxygenation is revisited. The anatomical and functional basis for heterogeneity of blood flow, local and regional regulatory mechanisms in normal tissues and the pathophysiology of the failure of regulation will be examined.Under physiological conditions, regulation of blood flow distributions at global, regional and microregional levels play coordinated roles in ensuring adequate O2 supply to all tissue cells. How this is achieved may be organ-/organ layer-specific, depending on its function and priorities to match local O2 delivery to consumption. Examples where these regulatory mechanisms break down under conditions of ischaemia and shock will also be given.In contrast, pathologic heterogeneity in tissue oxygenation resulting from uncontrolled, chaotic growth as seen in malignant tumours represents a pathophysiological status that is not predictable which, in general, is associated with chronic and acute hypoxia. This can have fatal consequences due to hypoxia- induced (mal-)adaptive processes, malignant tumour progression and treatment resistance.


[From one epidemic to the next: how can the learned experience serve to alleviate the psychosocial impact of Covid-19 confinement?]
The confinement of the population for an indefinite period within the framework of the national French prevention strategy of Covid-19 has a negative psychosocial impact already documented in other countries. In the past, several epidemics have built different strategies of prevention. It is urgent to consider how strategies used in other epidemics might be useful and helpful to manage the quarantine used to prevent the epidemics of COVID-19.


Crystal structure of trans-(1,8-dibutyl-1,3,6,8,10,13-hexa-aza-cyclo-tetra-decane-κ(4) N (3),N (6),N (10),N (13))bis-(isonicotinato-κO)nickel(II) determined from synchrotron data.
The title compound, [Ni(C6H4NO2)2(C16H38N6)], was prepared through self-assembly of a nickel(II) aza-macrocyclic complex with isonicotinic acid. The Ni(II) atom is located on an inversion center and exhibits a distorted octa-hedral N4O2 coordination environment, with the four secondary N atoms of the aza-macrocyclic ligand in the equatorial plane [average Ni-Neq = 2.064 (11) Å] and two O atoms of monodentate isonicotinate anions in axial positions [Ni-Oax = 2.137 (1) Å]. Intra-molecular N-H⋯O hydrogen bonds between one of the secondary amine N atoms of the aza-macrocyclic ligand and the non-coordinating carboxyl-ate O atom of the anion stabilize the mol-ecular structure. Inter-molecular N-H⋯N hydrogen bonds, as well as π-π inter-actions between neighbouring pyridine rings, give rise to the formations of supra-molecular ribbons extending parallel to [001].


Antimicrobial chlorhexidine/silver sulfadiazine-coated central venous catheters versus those uncoated in patients undergoing allogeneic stem cell transplantation.
Only a minimum is known about clinical effect of antimicrobial-coated central venous catheters (CVC) in stem cell transplantation settings, where CVC-related infections impose major threat to severely immunocompromised patients. In this prospective, non-sponsored and nonrandomized study, there were 49 uncoated multi-lumen and non-tunneled CVCs and 58 antimicrobial chlorhexidine/silver sulfadiazine-coated CVCs inserted in allogeneic stem cell transplanted patients to facilitate treatment during conditioning and pre-engraftment phase (<30days after transplantation). No significant differences were found between the two groups with respect to gender, age, intensity of pretransplant chemotherapy conditioning, duration of leucopenia, number of days with inserted CVC, number of CVC occlusive dressing changes performed per patient, and number of non-CVC-related infections. In the antimicrobial coated CVC group, there were observed less median days with fever [2 (0-18) vs. 4 (0-16), p = 0,17], fever incidence (67% vs. 77.5%, p = 0.28), and less days with fever per 1,000 catheter-days (108 vs. 147, p = 0.001), less patients with positive CVC blood cultures (36% vs. 45%, p = 0.05), repeatedly positive CVC blood cultures (8.6% vs. 26%, p = 0,018), less positive CVC blood cultures per 1,000 catheter-days (14 vs. 29, p = 0.005), and less positive CVC tip cultures (17.3% vs. 34.6%, p = 0.065) observed. Lower number of patients with fever, days with fever, and lower number of patients with positive and repeatedly positive CVC blood cultures indicates less intensive antibiotic and antipyretic treatment probably needed in neutropenic allo-transplanted patients with indwelling antimicrobial-coated CVCs. Real impact on antibiotic consumption should be verified in large randomized study.


Direct label-free measurement of the distribution of small molecular weight compound inside thick biological tissue using coherent Raman microspectroscopy.
Distributions of small molecular weight (less than 300 Da) compounds inside biological tissue have been obscure because of the lack of appropriate methods to measure them. Although fluorescence techniques are widely used to characterise the localisation of large biomolecules, they cannot be easily applied to the cases with small molecule compounds. We used CARS spectroscopy to detect and identify a label-free small molecule compound. To facilitate detection in aqueous environment, we utilised time-resolved and phase-sensitive techniques to reduce non-resonant background generated from water. We applied this technique to detect small molecular weight compound, taurine, inside mouse cornea tissue immersed in taurine solution as an initial model experiment. We detected a Raman peak of taurine near wavenumber 1033 cm(-1) inside cornea and successfully characterised its depth profile in the tissue. Our CARS spectra measurement can be a promising method to measure and visualise the distribution of small bio-related compounds in biological background without using any labeling, paving the way for new cell biological analysis in various disciplines.


Comparisons of the effects of vacuum-uv and far-uv synchrotron radiation on dry yeast cells of different uv sensitivities.
Far-uv-sensitive (rad l/rad l) and wild-type cells of diploid Saccharomyces cerevisiae were irradiated in vacuum at 155, 170, 220, and 250 nm using synchrotron radiation (SR). Inactivation, gene conversion at leu l, and membrane damage as judged by methylene blue penetration were measured. Radiations of all these wavelengths killed dry yeast cells. In the vacuum uv, radiation at 155 and 170 nm induced membrane damage but not gene conversion, whereas far-uv radiation at 220 and 250 nm induced gene conversion but not membrane damage. The far-uv-sensitive strain showed no enhanced sensitivity to vacuum-uv radiation. These results indicate that damage to the cell membrane is considerably more important than to nuclear DNA for yeast cell inactivation by vacuum-uv radiation.


Direct transatrial transcatheter SAPIEN valve implantation through right minithoracotomy in a degenerated mitral bioprosthetic valve.
Transcatheter valve implantation into failing surgical mitral bioprosthetic valves have been reported. This strategy avoids performing high-risk repeat cardiac surgery in elderly patients with multiple comorbidities. All these patients have been treated by a transapical approach. We report a case of failing bioprosthetic mitral valve in an 82-year-old woman successfully treated with a 29-mm Edwards SAPIEN balloon expandable bioprosthesis (Edwards Lifesciences, Irvine, CA) with direct left atrial approach through a right anterior thoracotomy. Our experience demonstrates the technical feasibility and safety of this approach. Therefore, mitral valve-in-surgical valve implantation may be a viable treatment alternative in carefully selected patients.


ID2 promotes the expansion and survival of growth-arrested pancreatic beta cells.
Inhibitors of DNA binding proteins (Ids) are implicated in the control of proliferation and differentiation. Herein, we tested the hypothesis that Id2 could stimulate proliferation and survival in differentiated pancreatic beta cells. We showed that Id2-enhanced proliferation of a growth-arrested pancreatic beta cell line (BTC-tet). This was mediated by the Rb pathway, as shown by an E2F1-driven reporter assay and Western immunoblot of phosphorylated Rb protein. Id2 also induced expression of Bcl-2, accompanied by a significant reduction of critical mediators of cytokine stimulation, including p38 MAPK and NFkappaB, as well as apoptosis markers, caspase-3 and Annexin-V. Overall, our data suggest that Id2 enhances proliferation and survival of growth-arrested BTC-tet cells.


Biliary elimination and pharmacokinetics of vinorelbine in micropigs.
The biliary elimination and pharmacokinetics of vinorelbine (NVB) were investigated in five conscious micropigs provided with a double-terminal choledocal fistula allowing the collection and reinstillation of bile. After the i.v. administration of NVB (0.5 mg/kg), serum and bile samples were collected over a 48-h period. The concentrations of NVB were measured by high-performance liquid chromatography. The serum concentrations decreased rapidly from a maximal value of 208.6 ng/ml (SD, 111.7 ng/ml). The mean half-life was 10.9 h (SD, 8.6 h) and the mean AUC0-48 h was 292.8 ng ml-1 h (SD, 79.4 ng ml-1 h). The bile concentrations were high, amounting to 16.0 micrograms/ml (range, 5.4-27.7 micrograms/ml). The 0- to 48-h biliary excretion of unchanged NVB accounted for 25.8% (SD, 5.7%) of the injected dose, with 21.5% (SD, 4.0%) being eliminated during the 0- to 8-h period. Desacetyl-NVB was found in an inconstant manner and in very low amounts in bile samples. In addition, no glucuronide of NVB could be detected. Thus, in the micropig, biliary excretion represents an important route of elimination for NVB.


A decision-directed approach for prioritizing research into the impact of nanomaterials on the environment and human health.
The emergence of nanotechnology has coincided with an increased recognition of the need for new approaches to understand and manage the impact of emerging technologies on the environment and human health. Important elements in these new approaches include life-cycle thinking, public participation and adaptive management of the risks associated with emerging technologies and new materials. However, there is a clear need to develop a framework for linking research on the risks associated with nanotechnology to the decision-making needs of manufacturers, regulators, consumers and other stakeholder groups. Given the very high uncertainties associated with nanomaterials and their impact on the environment and human health, research resources should be directed towards creating the knowledge that is most meaningful to these groups. Here, we present a model (based on multi-criteria decision analysis and a value of information approach) for prioritizing research strategies in a way that is responsive to the recommendations of recent reports on the management of the risk and impact of nanomaterials on the environment and human health.


Nociceptive and inflammatory responses induced by formalin in the orofacial region of rats: effect of anti-TNFalpha strategies.
This study evaluated the effects of different anti-TNFalpha strategies on the nociceptive and inflammatory responses triggered by formalin in the rat orofacial region. Formalin injection (2.5%) into the right upper lip caused a nociceptive response that was biphasic, with the first phase observed between 0 and 3 min and the second phase between 12 and 30 min. Plasma extravasation induced by formalin was time-related and reached the peak at 360 min. The monoclonal antibody anti-TNFalpha (25 and 50 pg/lip) significantly inhibited the second phase of formalin-induced nociceptive behavior, while the first phase remained unaltered. The systemic treatment with the chimeric anti-TNFalpha antibody infliximab also caused a significant inhibition of the second phase. Interestingly, the local administration of infliximab (50 pg/lip) produced a significant reduction of both phases of formalin-induced nociception. In addition, the systemic pretreatment with the preferential inhibitor of TNFalpha synthesis thalidomide (25 and 50 mg/kg, p.o) promoted a marked reduction of the first and second phases of formalin-evoked nociception. The local administration of the monoclonal antibody anti-TNFalpha (25 and 50 pg/lip) or infliximab (50 pg/lip) markedly reduced the plasma extravasation induced by formalin. Otherwise, formalin-elicited plasma extravasation was not significantly affected by the systemic administration of either infliximab (1 mg/kg; s.c) or thalidomide (50 mg/kg, p.o). Present data suggest that blocking TNFalpha effects, through different pharmacological tools, could represent a good alternative to control orofacial inflammatory pain that is refractory to other drugs.


Does Dosage or Duration of Concurrent Oral Corticosteroid Influence Elevated Risk of Postoperative Complications After Total Joint Arthroplasty?
This report seeks to clarify whether the dosage and duration of preoperative concurrent corticosteroid use influence postoperative complications after primary total joint arthroplasty (TJA). This retrospective single institutional study enrolled 1128 primary TJA cases, including 905 total hip arthroplasties and 223 total knee arthroplasties at a minimum 6 months of follow-up. Mean follow-up period was 51.9 ± 34.1 months (range 6-146). Of all joints, 120 joints (10.6%) were associated with chronic concurrent oral corticosteroid use. Multivariate analysis was performed to identify whether chronic concurrent oral corticosteroid use elevated the risk of postoperative complications including surgical site infection/periprosthetic joint infection, delayed wound healing, periprosthetic fracture, and implant loosening. For chronic concurrent oral corticosteroid user, we determined whether the dosage and duration of preoperative concurrent corticosteroid use influenced postoperative complications and have an effective threshold for postoperative complications using receiver operating characteristic curve analysis. The multivariate analysis revealed that American Society of Anesthesiologist Physical Status 3 was an independent risk factor for postoperative complications, while concurrent oral corticosteroid use was not an independent risk factor. When we compared joints with (n = 13) and without (n = 107) postoperative complications in chronic concurrent oral corticosteroid user, there was no statistical difference in the dosage (P = .97) and duration (P = .69) between the 2 groups. Area under the curve values for the oral corticosteroid dosages and duration were 0.482 and 0.549, respectively. This study revealed that neither dosage nor duration of concurrent oral corticosteroid use was predictive of postoperative complications after TJA. American Society of Anesthesiologist Physical Status 3 is a major factor in postoperative complications after TJA.


Folate metabolism in the superior cervical ganglion histochemical study.
By means of histochemical methods, folic acid, dihydrofolate reductase and NADH2-cytochrome-C-reductase were studied in the bovine superior cervical ganglion, in parallel with quantitative estimations of dihydrofolate reductase activity and in connection with the process of ageing. Various levels of folate metabolism were present in nerve cells and glial cells, as well as in pre or postganglionic nerves. In the process of ageing the activity of dihydrofolate reductase gradually decreased and the folic acid concentration in the nerve cells increased. Thus the enzyme --- substrate ratio appeared to favour the enzyme in young animals but the substrate in old animals.


[Hydrocyanic acid content in cerals and cereal products].
In the above paper for the first time a systematic study of the amount of hydrocyanic acid in grains and cereal products is reported. Among 24 analysed wheat, rye, maize and oats types, the presence of hydrocyanic acid could be identified in 19 cases in their Karyopses. Similar is the result with 28 among 31 analysed cereal products. The content of hydrocyanic acid lies between 0.1 and 45 microgram/100 gr dried mass.


Sparteine increases insulin release by decreasing the K+ permeability of the B-cell membrane.
The effects of sparteine on the pancreatic B-cell function have been studied with mouse islets. In the presence of a non-stimulatory concentration of glucose (3 mM), sparteine (0.2-1 mM) decreased the rate of 86Rb+ efflux from islet cells, depolarized the B-cell membrane, induced a glucose-like electrical activity and stimulated insulin release. This increase in release was observed over a large range of glucose concentrations (3-20 mM), and was most marked in the presence of 10 mM glucose. At this concentration of glucose, the effect of sparteine was already detected with 0.02 mM and was maximal with 0.5 mM. Higher concentrations of sparteine only had a transient effect on insulin release. In the presence of 10 mM glucose, 0.2 mM sparteine decreased 86Rb+ efflux and increased 45Ca2+ efflux from islet cells. The effect on 86Rb+ efflux was only transient in the presence of extracellular calcium, whereas the effect on 45Ca2+ efflux required the presence of extracellular calcium. The electrical activity induced by glucose in B-cells was augmented by sparteine which, at a concentration of 0.5 mM, produced a persistent depolarization with continuous spike activity. The potentiation of insulin release by sparteine was not reversible, but was inhibited by adrenaline and completely blocked by omission of extracellular calcium. Sparteine reversed the increase in 86Rb+ efflux and the decrease in insulin release caused by diazoxide. These results show that sparteine increases insulin release by reducing the K+-permeability of the B-cell membrane.


Tensions between work and home: job quality and working conditions in the institutional contexts of Germany and Spain.
Good jobs can generate capabilities that allow employees to avoid tensions between work and family/home. Following the conceptual framework of Amartya Sen, we examine how job-related demands and resources are related to the level of interference, as well as satisfaction with managing work and home in Spanish and German employees, using three different large-scale European surveys: European Quality of Life Survey and two waves of the European Social Survey. We find that long working hours systematically increase tensions between work and home, as do time pressure, job-related stress, and working hard. Job control or autonomy at work, which is hypothesized to expand individuals' capabilities and agency, tends to increase work–home interference rather than alleviate it. Family responsibilities and household demands do not seem relevant to the tensions employees experience at the work–home interface. This also holds true for women, which is a surprising result in view of the "double burden" hypothesis. Employed mothers in Germany and Spain are a select group of women, as combining employment with raising children in conservative–corporatist and conservative–familialist states may be particularly problematic. Thus while the institutional contexts of Germany and Spain curtail women's ability to reconcile employment and parenthood, the mothers (and fathers) who are employed do not experience significantly higher levels of work–family/home tensions than nonparents.


Stage progression of congenital cholesteatoma in children.
This study aimed to investigate the most prevalent stage in each age-group of children with congenital cholesteatoma (CC) and verify the correlation between the stage and the age of the patients for the type of CC ("closed" keratotic cyst and "open" infiltrative types). Patients diagnosed with CC between 2004 and 2009 (n = 156; 116 boys and 40 girls; mean age, 5 years and 5 months; range, 12 months-16 years and 7 months) were enrolled retrospectively. Assessment of stage and type of CC was performed with preoperative high-resolution temporal bone computed tomography and intraoperative findings. The stage of CC was determined using Potsic's staging system classified into four stages according to ossicular involvement and mastoid extension. The patients consisted of groups divided on the basis of a 2-year interval. The prevalence of stage I began to decline from the age-group of 1-2 years. In contrast, the prevalence of stages III increased from the age-group of 3-4 years and that of stage IV from the age-group 5-6 years. The prevalence of "open" infiltrative type CC increased from approximately the age of 7 years, thus showing some correlation with age but not with stage. The prevalence of CC with the advanced stage increased since the age of 2 years. Therefore, the importance of early diagnosis and treatment of CC should be more emphasized.


Clinical implications of serum autotoxin in regular follow up after pediatric living donor liver transplantation for biliary atresia.
Pediatric patients sometimes develop graft fibrosis after living donor liver transplant (LDLT). Autotaxin is a recently developed serum marker for hepatic fibrosis. We studied the relationship between serum autotaxin levels and histological findings in patients after LDLT for biliary atresia (BA). Information on patients aged <19 years who received LDLT for BA and were followed for at least 1 year after LDLT was gathered. Autotaxin levels were compared with pathological fibrosis scores. The study included 52 patients, of whom 4 patients had no fibrosis (F0), 36 patients had F1 fibrosis, and 12 patients had F2. The median serum autotaxin level was 0.89 mg/L. In patients with portal vein (PV) complications such as stenosis or thrombosis (n = 7), the mean autotoxin level was 1.25 mg/L compared with 0.95 mg/L in patients without PV complications (p = 0.004). Among patients without PV complications, the mean autotaxin level was 0.90, 0.88, and 1.18 mg/L in F0, F1, and F2 fibrosis, respectively. The mean autotaxin was higher in F2 fibrosis than in F0 or F1 fibrosis (p<0.05). Autotoxin had a high area under the curve (0.86) with the cut-off level of 0.897 mg/L. Serum autotaxin is a novel marker for liver fibrosis in patients after pediatric LDLT for BA. Study of Diagnostic Test. Level II.


Stabilization clamp for insertion of deep brain stimulation electrodes: technical note.
Deep brain stimulation (DBS) electrodes are being implanted with increasing frequency for the management of movement disorders and chronic pain. Success with this neuro-augmentative technique requires accurate electrode lead placement. In order to enhance accuracy of final lead placement and ease of insertion, we describe a useful and reliable DBS electrode lead stabilization device developed and used at our centre. The DBS electrode stabilization device consists of a 2-clamp system designed to fit the Leksell stereotactic frame. The clamps work in series to secure the stereotactic lead at the time of its final positioning in the desired subcortical target without the need of fluoroscopic control. The DBS electrode stabilization device has been used in 30 patients for 54 electrode implantations at our institution since 2000. Postoperative magnetic resonance imaging was performed in all cases and confirmed accurate placement of the electrodes. Accurate electrode lead placement is critical for the clinical efficacy of DBS systems. The simple and reliable stabilization device described here is easy to operate and enhances the final placement accuracy of DBS electrode leads.


Sleep Disturbance Trajectories in Osteoarthritis.
Sleep disturbance is common among adults with osteoarthritis (OA), but little is known about patterns over time. In this cohort study, we identified restless sleep trajectories and associated factors in adults with or at high risk for knee OA. Longitudinal (2004-2014) restless sleep (≥3 nights/week) annual reports over 8 years from 4359 Osteoarthritis Initiative participants were analyzed. Group-based trajectory modeling identified heterogeneous temporal patterns. Logistic regression identified baseline health and behavioral predictors of trajectory membership. Four restless sleep trajectory groups were identified: good (69.7%, persistently low restless sleep probabilities), worsening (9.1%), improving (11.7%), and poor (9.5%, persistently high). Among 2 groups initially having low restless sleep prevalence, the worsening trajectory group had an increased likelihood of baseline cardiovascular disease (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.01-2.33), pulmonary disease (OR, 1.48; 95% CI, 1.07-2.05), lower physical activity (OR, 1.29; 95% CI, 1.03-1.61), knee pain (OR, 1.04; 95% CI, 1.00-1.07), depressive symptoms (OR, 1.03; 95% CI, 1.01-1.06), and a decreased likelihood of better mental health (OR, 0.97; 95% CI, 0.95-0.98) at baseline. Among 2 groups initially having high restless sleep prevalence, the poor group had an increased likelihood of baseline depressive symptoms (OR, 1.03; 95% CI, 1.00-1.05). Four trajectories of restless sleep over 8 years were identified using data collected from over 4000 older adults aged 45 to 79 years with or at higher risk for knee OA. The presence of depressive symptoms, less physical activity, knee pain, poor mental health, cardiovascular disease, or pulmonary disease was each associated with unfavorable trajectories.


Diversity and the bottom line. Interview by Richard Haugh.
Fred Hobby, new head of the Institute for Diversity in Health Management, explains why cultural diversity is an organizational imperative in today's heterogenetic landscape.


Hexavalent chromium elimination from wastewater by integrated micro-electrolysis composites synthesized from red mud and rice straw via a facile one-pot method.
The widely spread chromium (Cr) contamination is rising environmental concerns, while the reutilization of agro-industrial by-products are also urgently demanded due to their potential risks. In this study, we prepared the integrated micro-electrolysis composites (IMC) through a facile one-pot method with red mud and rice straw. The effects of components relatively mass ratios as well as pyrolysis temperature were analyzed. The XRD, XPS, SEM, FTIR, and various techniques proved the IMC was successfully synthesized, which was also used to analyze the reaction mechanisms. In this study, the dosage of IMC, pH, adsorption time, and temperature of adsorption processes were explored, in the adsorption experiment of Cr(VI), dosage of IMC was 2 g/L (pH 6, 25 °C, and 200 rpm) for isothermal, while the concentration and contact time were also varied. According to the batch experiments, IMC exhibited acceptable removal capacity (190.6 mg/g) on Cr(VI) and the efficiency reached 97.74%. The removal mechanisms of adsorbed Cr(VI) were mainly elaborated as chemical reduction, complexation, co-precipitation, and physical adherence. All these results shed light on the facile preparation and agro-industrial by-products recycled as engineering materials for the heavy metals decontamination in wastewater.


Cranial isotopic section scanning.
Some results of isotopic cranial section scanning are presented from a busy neurosurgical practice. Isotopes have been used for parenchymal lesions and also CSF pathway imaging. Comparisons with information yielded by other neuroradiological techniques have indicated that tomographic sections are a worthwhile addition to rectilinear isotope scans. In particular comparison with X-ray transmission (EMI) scans has confirmed the anatomical accuracy of the method and the two techniques have proved complementary in patient management.


Stimulus-Dependent Inhibitor of Apoptosis Protein Expression Prolongs the Duration of B Cell Signalling.
Different dynamic behaviours of signalling activity can induce distinct biological responses in a variety of cells. However, the molecular mechanisms that determine the dynamics of kinase activities in immune cells are not well understood. In this study, we showed that the duration of both IκB kinase (IKK) and extracellular signal-regulated kinase (ERK) activities in B cell receptor (BCR)- and CD40-signalling pathways in B cells were regulated by transcriptional feedback loops. We conducted a time-course transcriptome analysis after BCR or CD40 stimulation and identified the following four candidate genes as feedback regulators for IKK and ERK: inhibitor of apoptosis protein (IAP), TNF alpha-induced protein 3, dual-specificity phosphatase 5, and sprouty homolog 2. Quantitative experiments and mathematical modelling suggested that IAP inhibition shortened the duration of IKK and ERK activity following both BCR and CD40 pathway stimulation, indicating a positive role for IAP in B cell signalling. Furthermore, transient kinase activities induced by IAP blockage reduced the levels of delayed expression genes. Together, our findings suggest that IKK and ERK activity durations can be fine-tuned by the coordinated regulation of positive and negative transcriptional feedback and that these network properties determine the biological output of B cells.


Energy metabolism in different human skeletal muscles during voluntary isometric contractions.
The energy turnover in contracting skeletal muscle was studied by measuring the rate of temperature rise during voluntary, isometric contractions and circulatory arrest in M. soleus, M. sacrospinalis and M. biceps brachii in 14 males, by thermoelements inserted in the muscles. A linear relationship between rate of temperature rise and force intensity given as per cent of maximal voluntary contraction (MVC) was demonstrated in biceps (r = 0.95), but not so clearly confirmed in soleus (r = 0.73). Muscle biopsies were taken from the same muscles and fibre type distribution was determined histochemically by staining for ATPase. The rate of heat production at MVC showed positive correlation to the percentage of fast twitch (FT) fibres in the muscles (r = 0.90). Linear extrapolation indicates that the maximal energy turnover in human FT fibres is approximately six times that of slow twitch (ST) fibres during voluntary isometric contractions.