The effect of in vivo grown corneal epithelium transplantation on persistent epithelial defects with limbal stem cell deficiency.
We report our experience with corneal epithelium, grown in vivo, transplantation in three patients with persistent epithelial defect (PED). The three patients had ocular surface disease unresponsive to standard treatments and were therefore chosen for transplantation. They underwent transplantation of epithelial sheets, grown in vivo, to the most affected eye. In vivo cultivation was carried out in the cornea of a living related donor. After epithelialization was completed, the epithelium grown on an amniotic membrane was harvested gently; it was then transplanted into the patient's eye after debridement of fibrovascular tissue. The cultivated epithelium was completely epithelialized by 2 weeks; it was well-differentiated with well-formed hemidesmosome. On immunohistochemical staining, p63, connexin 43, and Integrin beta4 were expressed in the cells on the epithelial sheet. The PED was covered completely and maintained for 4 weeks in all cases. However, corneal erosion recurred after 5 weeks in two cases. This novel technique demonstrates the corneal epithelial cells can be expanded in vivo successfully on denuded amniotic membrane of a healthy cornea and harvested safely. A corneal epithelial sheet, grown in vivo, can be transplanted to treat eye with a severe ocular surface disease, such as total limbal deficiency.


Scaling behaviors of α-zein in acetic acid solutions.
Whether the concentration scaling behavior of a protein solution is similar to that of neutral polymer solutions, polyelectrolyte solutions, or neither still remains unclear. In this paper, the structure and rheological properties of α-zein in acetic acid solutions have been investigated by small-angle X-ray scattering (SAXS), rheology, and circular dichroism (CD) measurements. Through the investigation of the radii of gyration, the secondary structure, and the solution viscosities of α-zein in acetic acid solutions as a function of α-zein concentration, we observed two distinct scaling regions with an identical threshold. This critical concentration is close to the bulk density of the α-zein in very dilute solution. The scaling relationships are close to the theoretical predictions for polyelectrolyte solutions, but obvious discrepancies still exist. The phenomena presented here may be widely present in other protein solutions, which can stimulate more attentions on the understanding of the scaling behaviors of protein solutions.


[Antimicrobial stewardship in primary care setting].
Antibiotic overuse in primary care setting is a major contributor to the development of resistant bacteria. Antibiotic consumption is low in Switzerland compared to neighbour countries, but improvement is possible and has to be pursued. Antibiotic stewardship helps physician to better recognize patients who need antibiotic (guidelines implementation, electronic decision support and laboratory testing) and educate patients about the uselessness of antibiotics in a given situation (delayed prescription and shared decision making). Clinical studies demonstrated the efficacy of these interventions in reducing antibiotic consumption, mainly in acute respiratory infections, without affecting patients' clinical outcome.


Regulation of aeroallergen immunity by the innate immune system: laboratory evidence for a new paradigm.
Over the last decade, it has become increasingly clear that innate responses to microbes are mediated largely by toll-like receptors (TLRs), which recognize a diverse family of molecules produced by viruses, bacteria and fungi. This article will present evidence that TLRs also play a dominant role in innate responses to non-infectious immunostimulatory materials present in house dust extracts (HDEs) and the living environments they represent. However, our investigations challenge the commonly held view that microbial products in ambient air protect against the allergic march by promoting protective Th1 biased responses to inspired aeroallergens. Instead, all HDEs studied to date have preferentially promoted the development of Th2 biased airway hypersensitivities when used as adjuvants for intranasal (i.n.) vaccination. In contrast, daily low dose i.n. HDE delivery was found to promote the development of aeroallergen tolerance. This article will review these experimental findings as evidence to propose a new paradigm by which airborne TLR ligands and other stimulants of innate immunity may influence aeroallergen specific immunity and the genesis of allergic respiratory diseases.


The effect of the aortic valve orientation on cavitation.
When implanting a mechanical aortic valve the annulus orientation is important with respect to turbulence. However, the effect on cavitation has not yet been investigated. The aim of this study was to investigate how cavitation is influenced hereof in vivo. Three pigs were included in the study. An Omnicarbon 21mm valve equipped with a rotating mechanism enabling controlled rotation of the valve was implanted in aortic position. Under stable hemodynamic conditions, measurements were performed using a hydrophone positioned at the aortic root. The valve was rotated from 0-360° in increments of 30°. From the pressure fluctuations recorded by the hydrophone the root mean square of the 50 kHz high pass filtered signal as well as the non-deterministic signal energy was calculated as indirect measures of cavitation. Various degrees of cavitation were measured but no relationship was found between either of the two cavitation measures and the valve orientation. Hemodynamics varied during the experiments for all pigs (3.9-5.7 l/min; 5.0-7.2 l/min; 3.1-7.5 l/min). Changes in cavitation quantities seemed to be caused by changes in hemodynamics rather than valve angular position. In conclusion, these results do not favor any position over another in terms of cavitation potential.


Evidence for additional FREM1 heterogeneity in Manitoba oculotrichoanal syndrome.
Manitoba Oculotrichoanal (MOTA) syndrome is an autosomal recessive disorder present in First Nations families that is characterized by ocular (cryptophthalmos), facial, and genital anomalies. At the commencement of this study, its genetic basis was undefined. Homozygosity analysis was employed to map the causative locus using DNA samples from four probands of Cree ancestry. After single nucleotide polymorphism (SNP) genotyping, data were analyzed and exported to PLINK to identify regions identical by descent (IBD) and common to the probands. Candidate genes within and adjacent to the IBD interval were sequenced to identify pathogenic variants, with analyses of potential deletions or duplications undertaken using the B-allele frequency and log(2) ratio of SNP signal intensity. Although no shared IBD region >1 Mb was evident on preliminary analysis, adjusting the criteria to permit the detection of smaller homozygous IBD regions revealed one 330 Kb segment on chromosome 9p22.3 present in all 4 probands. This interval comprising 152 SNPs, lies 16 Kb downstream of FRAS1-related extracellular matrix protein 1 (FREM1), and no copy number variations were detected either in the IBD region or FREM1. Subsequent sequencing of both genes in the IBD region, followed by FREM1, did not reveal any mutations. This study illustrates the utility of studying geographically isolated populations to identify genomic regions responsible for disease through analysis of small numbers of affected individuals. The location of the IBD region 16 kb from FREM1 suggests the phenotype in these patients is attributable to a variant outside of FREM1, potentially in a regulatory element, whose identification may prove tractable to next generation sequencing. In the context of recent identification of FREM1 coding mutations in a proportion of MOTA cases, characterization of such additional variants offers scope both to enhance understanding of FREM1's role in cranio-facial biology and may facilitate genetic counselling in populations with high prevalences of MOTA to reduce the incidence of this disorder.


EP1 receptor: Devil in emperors coat.
EP1 receptor belongs to prostanoid receptors and is activated by prostaglandin E2. The receptor performs contrasting functions in central nervous system (CNS) and other tissues. Although the receptor is neurotoxic and proapoptotic in CNS, it has also been reported to act in an antiapoptotic manner by modulating cell survival, proliferation, invasion, and migration in different types of cancers. The receptor mediates its neurotoxic effects by increasing cytosolic Ca2+ levels, leading to the activation of its downstream target, protein kinase C, in different neurological disorders including Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and epilepsy. Antagonists ONO-8713, SC51089, and SC51322 against EP1 receptor ameliorate the neurotoxic effect by attenuating the neuroinflammation. The receptor also shows increased expression in different types of cancers and has been found to activate different signaling pathways, which lead to the development, progression, and metastasis of different cancers. The receptor stimulates the cell survival pathway by phosphorylating the AKT and PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathways. Although there are limited studies about this receptor and not a single clinical trial has been targeting the EP1 receptor for different neurological disorders or cancer, the receptor is appearing as a potential candidate for therapeutic targets. The aim of this article is to review the recent progress in understanding the pathogenic roles of EP1 receptors in different pathological conditions.


Supranuclear ophthalmoplegia in olivopontocerebellar degeneration.
Autosomal dominant olivopontocerebellar degeneration was diagnosed in a family of Scottish ancestry by clinical examination and autopsy. In addition to having progressive cerebellar ataxia, head titubation, and severe dysarthria, the patients are unable to initiate saccadic eye movements. Slow pursuit movements are normal. Reflex movements of the eyes caused by passive rotation or caloric labyrinthine stimulation are not impaired but are not associated with nystagmus. The phenomenon can be classified as supranuclear pseudo-ophthalmoplegia. It differs from congenital ocular motor apraxia in age at onset and the absence of random eye movements. The anatomic lesion responsible for the defect of saccadic eye movements remains to be established.


Automatic segmentation of the female pelvic floor muscles on MRI for pelvic floor function assessment.
Pelvic organ prolapse (POP) is a pelvic floor dysfunction disease which affects females. The volume of pelvic floor muscle, especially the levator ani muscle (LAM), is an important indicator of pelvic floor function. However, muscle volume measurements depend on manual segmentation, which is clinically time-consuming. In this work, we present an efficient automatic segmentation model of pelvic floor muscles with magnetic resonance imaging (MRI) based on DenseUnet, to achieve muscle volume calculation and provide a reference for the assessment of pelvic floor function. A total of 49 female pelvic floor magnetic resonance (MR) series were retrospectively enrolled from the First Affiliated Hospital of Army Military Medical University between 2013 and 2021, including 21 normal participants and 28 patients with stage 1-4 POP. The LAM, internal obturator muscle (IOM), and external anal sphincter (EAS) were manually segmented. An improved DenseUnet was proposed for automatic segmentation of these 3 muscles. The Dice similarity coefficient (DSC), Hausdorff distance (HD), and average symmetrical surface distance (ASSD) were used to evaluate segmentation results. The segmentation performance of the improved DenseUnet was compared with those of standard DenseUnet, ResUnet, Unet++, and Unet. The improved DenseUnet showed a good performance. The average DSC and standard deviation of the LAM, IOM, and EAS was 0.758±0.151, 0.716±0.173, and 0.810±0.147, respectively. The average HD was 22.41, 19.00, and 36.01 mm, respectively; and the average ASSD was 3.66, 3.80, and 5.23 mm, respectively. The average DSC and standard deviation of the normal group and POP group was 0.779±0.166 and 0.757±0.154, respectively. There was no significant difference between the muscle volume of the improved DenseUnet and manual segmentation (all P values >0.05). The average total segmentation time for 1 case was 10.18 s on our setup, which is much lower than the manual segmentation time of 45 minutes. The improved DenseUnet segments the pelvic floor muscles in MRI quickly and efficiently, with good precision and faster speed than those of manual segmentation. This can assist doctors in quickly segmenting pelvic floor muscles, calculating muscle volume, and further evaluating pelvic floor function.


Plasma membrane perturbations of KB3 cells induced by the bleomycin-iron complex.
The effect of the anticancer drug bleomycin on acyl chain order of KB cell membranes was examined by electron paramagnetic resonance and fluorescence polarization spectroscopies using respectively, the 5-doxyl stearic acid spin probe and the 1,6-diphenyl-1,3,5-hexatriene and the 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene fluorescent probes. Measurements of the order parameter, S, by the two techniques showed a perturbation of the plasma membrane fluidity with bleomycin-iron, while no effect was observed with bleomycin or iron alone. A kinetic study of the location of the 1,6-diphenyl-1,3,5-hexatriene fluorescent probe into the cell was followed by fluorescence microscopy. Lipid peroxidation measurements were also performed using isolated unsaturated lipids, intact cells, or isolated plasma membranes whose purity was checked by electronic microscopy. These membrane perturbation effects not observed with bleomycin-iron in the presence of a hydroxyl radical scavenger, dimethyl thiourea, or a chelating agent, desferrioxamine, were correlated with the ability of the complex to generate highly reactive oxygen species.


Intermittent and arrhythmic "runaway" pacemaker.
An unusual case of intermittent and arrhythmic runaway pacemaker is described. The malfunction was detected during implantation, at which time it caused ventricular fibrillation in the patient in whom it was implanted. The authors wish to emphasize the necessity of accurate pacemaker testing in the factory and the operating room, and to stress the importance of manufacturing pacemakers unable to emit a high number of impulses, even in the presence of a faulty circuit component.


NMR and IR Investigations of Strong Intramolecular Hydrogen Bonds.
For the purpose of this review, strong hydrogen bonds have been defined on the basis of experimental data, such as OH stretching wavenumbers, νOH, and OH chemical shifts, δOH (in the latter case, after correction for ring current effects). Limits for O-H···Y systems are taken as 2800 > νOH > 1800 cm-1, and 19 ppm > δOH > 15 ppm. Recent results as well as an account of theoretical advances are presented for a series of important classes of compounds such as β-diketone enols, β-thioxoketone enols, Mannich bases, proton sponges, quinoline N-oxides and diacid anions. The O···O distance has long been used as a parameter for hydrogen bond strength in O-H···O systems. On a broad scale, a correlation between OH stretching wavenumbers and O···O distances is observed, as demonstrated experimentally as well as theoretically, but for substituted β-diketone enols this correlation is relatively weak.


Prediction of Nephrotoxicity Associated With Cisplatin-Based Chemotherapy in Testicular Cancer Patients.
Cisplatin-based chemotherapy may induce nephrotoxicity. This study presents a random forest predictive model that identifies testicular cancer patients at risk of nephrotoxicity before treatment. Clinical data and DNA from saliva samples were collected for 433 patients. These were genotyped on Illumina HumanOmniExpressExome-8 v1.2 (964 193 markers). Clinical and genomics-based random forest models generated a risk score for each individual to develop nephrotoxicity defined as a 20% drop in isotopic glomerular filtration rate during chemotherapy. The area under the receiver operating characteristic curve was the primary measure to evaluate models. Sensitivity, specificity, and positive and negative predictive values were used to discuss model clinical utility. Of 433 patients assessed in this study, 26.8% developed nephrotoxicity after bleomycin-etoposide-cisplatin treatment. Genomic markers found to be associated with nephrotoxicity were located at NAT1, NAT2, and the intergenic region of CNTN6 and CNTN4. These, in addition to previously associated markers located at ERCC1, ERCC2, and SLC22A2, were found to improve predictions in a clinical feature-trained random forest model. Using only clinical data for training the model, an area under the receiver operating characteristic curve of 0.635 (95% confidence interval [CI] = 0.629 to 0.640) was obtained. Retraining the classifier by adding genomics markers increased performance to 0.731 (95% CI = 0.726 to 0.736) and 0.692 (95% CI = 0.688 to 0.696) on the holdout set. A clinical and genomics-based machine learning algorithm improved the ability to identify patients at risk of nephrotoxicity compared with using clinical variables alone. Novel genetics associations with cisplatin-induced nephrotoxicity were found for NAT1, NAT2, CNTN6, and CNTN4 that require replication in larger studies before application to clinical practice.


Boundary conditions and defect lines in the Abelian sandpile model.
We add a defect line of dissipation, or crack, to the Abelian sandpile model. We find that the defect line renormalizes to separate the two-dimensional plane into two half planes with open boundary conditions. We also show that varying the amount of dissipation at a boundary of the Abelian sandpile model does not affect the universality class of the boundary condition. We demonstrate that a universal coefficient associated with height probabilities near the defect can be used to classify boundary conditions.


Efficacy Of Local Anaesthesia In Repair Of Inguinal Hernia.
Local anaesthesia has been identified as the most favourable anaesthesia for elective inguinal hernia repair with respect to complication rate, cost effectiveness and overall patients' satisfaction. This study was conducted to determine the efficacy of local anaesthesia in inguinal hernia in terms of pain relief, wound infection and hospital stay. In this randomized controlled trial (RCT), 60 patients with inguinal hernia were included at the General Surgical 'B' Unit, Ayub Teaching Hospital Abbottabad. The day-case rates were significantly higher when patients underwent surgery under LA compared to GA (82.6% versus 42.6%). The incidence of urinary retention was higher in the GA group (p<0.05). There were 17 (2.9%) re-admissions overall. The reasons for readmission included haematoma (n=6), severe pain (n=4), infection (n=3), fainting (n=2) and urinary retention (n=2). This study demonstrates that local anaesthesia for inguinal hernia repair has better efficacy as compared to general anaesthesia.


Form and function in the unique inner ear of a teleost: the silver perch (Bairdiella chrysoura).
Members of the teleost family Sciaenidae show significant variation in inner ear and swim bladder morphology as well as in the relationship between the swim bladder and the inner ear. In the silver perch (Bairdiella chrysoura), a Stellifer-group sciaenid, both the saccular and utricular otoliths are enlarged relative to those in other teleosts. Additionally, its swim bladder is two-chambered, and the anterior chamber surrounds the otic capsule and terminates lateral to the saccules. Structure and function of the auditory system of the silver perch were explored by using gross dissections, scanning electron microscopy, CT scan reconstruction, and auditory brainstem response approach. Several morphological specializations of the auditory system of the silver perch were found, including expansion of the utricular and lagenar otoliths, close proximity between the saccules and the utricles, deeply grooved sulci on the saccular otoliths, two-planar saccular sensory epithelia, and a unique orientation pattern of sensory hair cell ciliary bundles on the saccular sensory epithelium. It was determined that the silver perch can detect up to 4 kHz, with lowest auditory thresholds between 600 Hz and 1 kHz. Audition in the silver perch is comparable to that in the goldfish (Carassius auratus), a hearing "specialist." The morphological specializations of the inner ear and swim bladder of the silver perch may be linked to its enhanced hearing capabilities. The findings of this study support the proposal that sciaenids are excellent model species for investigating structure-function relations in the teleost auditory system.


'A'ole Drugs! Cultural Practices and Drug Resistance of Rural Hawaiian Youth.
This qualitative study examined how Native Hawaiian youth from rural communities utilized cultural practices to promote drug resistance and/or abstinence. Forty-seven students from 5 different middle schools participated in gender specific focus groups that focused on the cultural and environmental contexts of drug use for Native Hawaiian youth. The findings described culturally specific activities that participants used in drug related problem situations. The findings also suggested that those youth with higher levels of enculturation were able to resist drugs more effectively than those youth who were disconnected from their culture. The implications of these findings for social work practice are discussed.


Pharmacokinetic and clinical parameters of zopiclone and trimipramine when administered simultaneously to volunteers.
Zopiclone is a new sedative showing a rapid onset of hypnotic effect and a relatively short duration of action. The goal of this study was to assess the kinetic parameters of zopiclone and its interaction with trimipramine when administered concomitantly. Ten normal subjects each received doses of zopiclone (7.5 mg), trimipramine (50 mg), and zopiclone (7.5 mg) + trimipramine (50 mg) orally at 7-day intervals. The absorption of zopiclone was rapid, the observed plasma peak concentration and 95 per cent of all absorption occurring within one hour. The average elimination half-life was 3.8 +/- 0.2 h. The volunteers reported a bitter taste at an average of 24 min after zopiclone administration at which time concentrations in saliva were approximately 50 ng ml-1. Trimipramine decreased the relative bioavailability determined for zopiclone by 13.7 per cent, while zopiclone decreased the relative bioavailability of trimipramine by an average of 26.6 per cent, although neither of these changes was statistically significant (p greater than 0.05); there were no substantial changes in other kinetic parameters. It is concluded that zopiclone presents advantages over some other sedative drugs as it is rapidly absorbed and eliminated. When zopiclone is administered with trimipramine, the decrease in the relative bioavailability of trimipramine may be clinically significant.


On-chip cell culture on a microarray of extracellular matrix with surface modification of poly(dimethylsiloxane).
Microfluidic cell culture chips allow to perform assays of small-volume samples rapidly and reproducibly. Most of these chips are made of poly(dimethylsiloxane) (PDMS), which is a flexible, durable, transparent and inexpensive polymer that can be easily applied to fabrication of microstructures by photolithography and replica molding. However, not many cells are able to grow on unmodified PDMS because the cells need appropriate scaffolds on the surface. Here we report surface modification of a PDMS substrate with a microarray of extracellular matrix (ECM) for on-chip cell culture. The ECM proteins collagen and fibronectin were covalently immobilized on an 8 x 8 microarray format by micropatterned UV-induced graft polymerization through a photomask and dehydration-condensation reaction through a microfabricated stencil. Identical spots of ECMs were successfully formed and the geometry of the spots accurately corresponded to the micropattern of the photomask and stencil. We demonstrate the culture of CHO-K1 cells on the ECM microarray chip. Cells proliferated on the fibronectin spots during the 2-day culture.


Crystallographic Characterization of II-VI Semiconducting Nanostructures via Optical Second Harmonic Generation.
We demonstrate the utility of optical second harmonic generation (SHG) polarimetry to perform structural characterization of noncentrosymmetric, single-crystalline II-VI semiconducting nanowires, nanobelts, and nanoflakes. By analyzing anisotropic SHG polarimetric patterns, we distinguish between wurtzite and zincblende II-VI semiconducting crystal structures and determine their growth orientation. The crystallography of these nanostructures was then confirmed via transmission electron microscopy measurements performed on the same system. In addition, we show that some intrinsic material properties such as nonlinear coefficients and geometry-dependent optical in-coupling coefficients can also be determined from the SHG experiments in WZ nanobelts. The ability to perform SHG-based structural characterization and crystallographic study of II-VI semiconducting single-crystalline nanomaterials will be useful to correlate structure-property relationships of nanodevices on which transmission electron microscopy measurements cannot be typically performed.


Exploring Structural Determinants of Bias among D4 Subtype-Selective Dopamine Receptor Agonists.
The high affinity dopamine D4 receptor ligand APH199 and derivatives thereof exhibit bias toward the Gi signaling pathway over β-arrestin recruitment compared to quinpirole. Based on APH199, two novel groups of D4 subtype selective ligands were designed and evaluated, in which the original benzyl phenylsemicarbazide substructure was replaced by either a biphenylmethyl urea or a biphenyl urea moiety. Functional assays revealed a range of different bias profiles among the newly synthesized compounds, namely, with regard to efficacy, potency, and GRK2 dependency, in which bias factors range from 1 to over 300 and activation from 15% to over 98% compared to quinpirole. These observations demonstrate that within bias, an even more precise tuning toward a particular profile is possible, which─in a general sense─could become an important aspect in future drug development. Docking studies enabled further insight into the role of the ECL2 and the EPB in the emergence of bias, thereby taking advantage of the diversity of functionally selective D4 agonists now available.


Angiocardiography and exercise testing at one month after a first myocardial infarction.
The results of exercise testing (77 patients), left ventriculography and coronary arteriography (78 patients) are presented for men under the age of 60, one month after a first myocardial infarct. Cineangiocardiography revealed that patients with anterior infarction (n = 25) had both poorer left ventricular function and more totally occluded vessels than those with either inferior (n = 33) or subendocardial infarction (n = 20). In contrast, patients with inferior and subendocardial infarction had a greater proportion of myocardium supplied by sub-total lesions likely to be haemodynamically significant (75%-99% cross sectional area loss). Subendocardial infarction was also characterised by the best left ventricular function and the fewest number of total coronary occlusions. Stress testing showed that the combination of ischaemic ST segment changes and angina during exercise was 91% predictive of severe coronary disease (equivalent to triple vessel disease) while no angina in the presence of a negative test was 81% predictive of mild or moderate disease. Stenoses of 75%-99% cross sectional area loss were more common when angina occurred during exercise testing, and both angina and ischaemic ST segment changes occurred within ten minutes in all four patients with haemodynamically significant left main coronary artery lesions. Our data supports the usefulness of exercise testing after a first myocardial infarct and may provide valuable baseline information in the analysis of long term prognosis.


Phase 1 study of high-dose metronidazole: a specific in vivo and in vitro radiosensitizer of hypoxic cells.
Metronidazole was administered orally to 25 patients and its maximum concentration in blood and tumor tissues, its ability to cross the blood/brain barrier and concentrate in the cerebrospinal fluid and brain tumor tissue, its immediate and long-term toxicity, and its enhancement of irradiation in normal tissue were studied. Maximum blood concentrations of 700-1,200 muM (120-220 mug/ml) were obtained at four hours with doses of 6 g/m2. Moderate and transient nausea and vomiting were the only immediate signs of toxicity. No long-term toxicity was found up to 18 months after administration of the drug. These data indicate that metronidazole can feasibly be adminstered in clinical trials of fractionated radiotherapy using dosages ranging from 9.5 to 11 g three times a week for three to four weeks.


[Trait anxiety and type behavior pattern (A and B) as modifiers of immediate reaction towards violent behaviors].
Experience of violence at the work place leads to serious consequences for both an employee and the organization. That is why prevention programs are necessary to reduce the risk of violence at work as well as possible adverse consequences of violent acts that cannot be predicted and prevented. Some research studies suggest that the range and severity of individual consequences of experiencing violence at work depend on the personality of victims, including their typical reactions to violent acts. In this paper, such personal characteristics as trait-anxiety, type A/B behavior pattern (TABP/TBBP) are discussed as potential modifiers of individual reaction towards the violence experienced at work. A sample of 1163 nurses, representative of the Mazovian Voivodship was surveyed. The standardized "paper and pencil" questionnaires were employed in the survey. The relationship between direct reaction to violence and trait-anxiety and TABP/TBBP was analyzed. Tendency to express an aggressive reaction towards violent behavior of others was positively correlated with a high level of trait-anxiety and TABP and submissive reactions to violence with a high level of trait-anxiety and TBBP, whereas tendency to express assertive reaction when being attacked was related to a low level of trait-anxiety and TBBP. Statistically significant relationship between trait-anxiety and behavior pattern was observed. A high level of anxiety is correlated with ineffective coping with violent acts as submissive and aggressive reaction. The tendency to express these two kinds of behavior when facing violence is strengthen by behavior pattern. The tendency to aggressive reactions as a response to aggression of others is stronger when a high level of trait-anxiety is accompanied by TABP. The tendency to present submissive reactions as a response to aggression of others is stronger when a high level of anxiety and TBBP characterize the individual who faces a violent act. These individual characteristics are thought to be rather stable and difficult to change, but they should be taken into account in the process of designing the violence prevention programs for the organization. We believe that in our attempts to reduce the extent of the problem we should provide information on the role of individual characteristics in the process of coping with violence and recommend to employ positive effects of the repeated assertiveness training in the violence prevention programs as a useful tool for teaching people how to behave in the face of aggressiveness of others.


Synthesis of violet phosphorus with large lateral sizes to facilitate nano-device fabrications.
Violet phosphorus has been proven to be the most stable phosphorus allotrope and has attracted much attention recently. The growth of violet phosphorus with large lateral sizes is crucial to obtain good quality violet phosphorene for nanodevice fabrication. Herein, a large number of violet phosphorus plates have been produced from molten lead using an optimized method to achieve red bronze luster. The crystal structure of the as-produced violet phosphorus was determined by single-crystal X-ray diffraction to be monoclinic with the space group P2/n (13) (CSD-2160375), identical to the one from the chemical vapor transport method (CSD-1935087). The as-produced violet phosphorus plates were found to have lateral sizes of 1.30 ± 0.41 mm2. The violet phosphorus plates were easily exfoliated and directly transferred to silicon substrates to facilitate building of a back-gate field-effect transistor. A hole mobility of 2.308 cm2 V-1 s-1 was obtained from a violet phosphorus nanosheet with a thickness of 52 nm under ambient conditions. The absolute responsivity of 130 mA W-1 with a fast response time of 27 ms was also obtained under the irradiation of a 530 nm laser.


Hodgkin's disease in Indian children: outcome with chemotherapy alone.
To assess the efficacy of chemotherapy alone, using four cycles of COPP alternating with four cycles of ABVD in all stages of childhood Hodgkin's disease (HD). Between January 1991 and February 2001, 148 previously untreated patients were investigated, treated, and analyzed for remission and survival. There were 134 boys and 14 girls with a median age of 8 years, 75% were less than 10 years old. 63.5% had advanced stage disease (IIB-IV). B symptoms were present in 54.4% of cases; bulky mediastinal mass in 18 cases (12.2%); spleen and bone marrow involvement in 22 (14.9%) and four cases (2.7%), respectively. Mixed cellularity (MC) subtype was found in 86.0%. Response to treatment was evaluated in 133 patients: complete remission (CR) was achieved in 121 patients (91.0%), partial remission (PR) in seven (5.3%), progression occurred in two (1.5%), and three (2.3%) died on therapy. Four patients with mediastinal residual disease were given additional involved field radiotherapy. Out of 111 patients analyzable, five (4.5%) have relapsed 6-30 months after completing chemotherapy, and were treated with additional cycles of ABVD and low-dose involved field radiotherapy. The 5-year actuarial overall survival (OS) and event-free survival (EFS) are 91.5 and 87.9%, respectively. Advanced stage, B symptoms, anemia, spleen, and marrow involvement were adverse prognostic factors for survival. Chemotherapy alone with alternating COPP/ABVD, without additional radiotherapy, provides high rates of durable remission and is an effective therapy in childhood HD, even in case of large mediastinal mass and peripheral or abdominal bulky disease.


Smartphone use motivation and problematic smartphone use in a national representative sample of Chinese adolescents: The mediating roles of smartphone use time for various activities.
Previous studies on smartphone use motivation (SUM) and problematic smartphone use (PSU) have been limited in the utilization of regional samples of emerging adults (e.g., college students) and also in the foci on the direct association between SUM and PSU. To address such gaps, using data from a large, national representative sample of Chinese young adolescents and their parents this study examined the associations between adolescents' various types of SUM and their PSU, and also tested the potential mediating roles of smartphone use time (SUT) that adolescents spent on various activities in such associations. A nationwide representative sample of 8,261 Chinese adolescents (Mage = 12.86 years old, SD = 1.76; 42.6% females) and their parents (49% mothers) participated in this survey study. Instrumental SUM (i.e., to expand knowledge or acquire information) was associated negatively with PSU via longer SUT spent on learning and shorter SUT spent on entertainment and communication. Self-expression SUM (i.e., to gain acceptance and recognition of others by maintaining or improving self-images) was associated with longer SUT spent on both learning and entertainment, which, in turn, predicted lower and higher levels of PSU, respectively. Last, hedonic SUM (i.e., to gain pleasure) was associated positively with PSU via longer SUT spent on entertainment and communication. These findings contribute to the literature by adding greater specificity in our understanding of the implications of SUM and SUT in the etiology of PSU during the critical life stage of adolescence in a Chinese cultural context.


Spontaneous recovery from severe neurotoxic envenoming by a Malayan krait Bungarus candidus (Linnaeus) in Thailand.
A patient bitten by Bungarus candidus (Malayan krait) developed nausea, vomiting, weakness, and myalgia 30 minutes after being bitten. One hour later, ptosis and occulomotor palsies as well as tightness of his chest were noted. Respiratory failure requiring mechanical respiration appeared 8 hours after the bite and lasted for nearly 96 hours. The two bite sites were virtually painless and resulted in slight transient erythema and edema. No specific antivenin was available, and treatment consisted of respiratory support and management of aspiration pneumonitis. Recovery was complete.


[An unusual way of detecting Horton's disease: inflammatory abdominal aortitis].
We report an original case of giant cell arteritis, revealed by abdominal aortic arteritis on CT-scan, which was performed because the patient presented with a biological inflammatory syndrome. Course was favorable with steroid therapy. CT-scan, one month later, demonstrated a stable appearance of both regular and concentric thickening of the abdominal aortic wall. Aortic involvement is rare and occurs late in the course of giant cell arteritis. Usually clinical and biological manifestations of aortitis associated with giant cell arteritis either absent or non specific, leading to diagnostic difficulties. Furthermore, aortic giant cell arteritis is a major cause of morbidity and mortality. Gravity of aortic impairment is mainly linked to the risk of development of aneurysm and/or acute dissection. A search for aortic involvement should therefore routinely be carried out, once a year, in patients with giant cell arteritis, particularly a complete vascular clinical examination and a chest X-ray. Finally, our case report suggests that non invasive methods, notably CT-scan, may serve as a helpful test in diagnosis and follow-up of aortic giant cell arteritis.


Forme fruste of von Recklinghausen's disease: unilateral association of an orbital neurofibroma, a trigeminal neurinoma, and an acoustic neurinoma. Case Report.
A patient who presented with a tumor of the left ambient cistern, a left cerebellopontine angle tumor, and a left orbital tumor causing left hearing loss and left exophthalmos without café au lait spots or cutaneous neurofibromas is described. There was no family history of von Recklinghausen's disease. A cerebellopontine angle tumor removed by a suboccipital craniectomy was an acoustic neurinoma. An ambient cistern tumor was approached through a subtemporal route. A tumor arising from the trigeminal nerve was also a neurinoma. An orbital neurofibroma was excised by a frontal craniotomy with removal of the orbital roof. This rare unilateral association of neurinomas and a neurofibroma on the left side was thought to be a forme fruste of von Recklinghausen's disease, and it could be considered a presentation of a mosaic of von Recklinghausen's disease.


Cervical spine fracture patterns mandating screening to rule out blunt cerebrovascular injury.
Aggressive screening for blunt cerebrovascular injury (BCVI) and prompt anticoagulation for documented injuries has resulted in a significant reduction in ischemic neurologic events. An association between vertebral artery injuries (VAIs) and specific cervical spine fracture patterns has been suggested; however, current screening guidelines would subject all patients with cervical spine fractures to imaging because no distinction has been made for carotid artery injuries (CAIs). We hypothesized that specific cervical spine fracture patterns that warrant screening evaluation exist, hence limiting unwarranted diagnostic imaging. Patients undergoing screening for BCVI on the basis of injury patterns and mechanism have been prospectively followed at our regional trauma center since January 1996. During the study period from January 1996 to January 2005, there were 17,007 blunt trauma admissions. Twenty-three patients presented with symptoms of BCVI. Screening angiography was performed in 766 patients (4.5%), and diagnosed 258 (34%) patients with BCVI. One hundred twenty-five patients with BCVI had cervical spine fractures; 18 patients had isolated CAI; 84 had isolated VAI, and 23 had combined CAI and VAI. Eight patients with VAI had minor cervical fractures but underwent screening for other injury patterns. Fractures in the remaining patients with BCVI were 1 of 3 patterns. Subluxations in 56 (48%) patients, C1 to C3 cervical spine fractures in 42 (36%), or extension of the fracture through the foramen transversarium in 19 (16%). Cervical spine fractures were the sole indication for screening in 90% of the study population. Screening yield of all patients admitted with 1 of these 3 fracture patterns was 37%. Blunt cerebrovascular injury is associated with complex cervical spine fractures that include subluxation, extension into the foramen transversarium, or upper C1 to C3 fractures. Patients sustaining such cervical fractures should undergo prompt screening.


A cytogenetic and molecular study of a series of 45,X fetuses and their parents.
The parental origin of the single X chromosome in 10 45,X fetuses was studied using DNA restriction fragment length polymorphisms. In six the single X was maternal in origin, in one it was paternal, and in one the results were consistent with a paternal origin. Therefore the parental origin of the X in 45,X fetuses that survive to the second or third trimester of pregnancy is similar to that of spontaneous abortions and live births with a 45,X constitution. The mothers of two of the fetuses were themselves found to have an abnormal sex chromosome complement, but in neither case did it appear to be related to the chromosome abnormality in the fetus.


Expression of merosin in the thymus and its interaction with thymocytes.
Merosin is a 700 kDa multichain protein that has several properties in common with laminin, one of the major extracellular matrix proteins present in basement membranes. Both contain B1 and B2 light chains, but merosin has a distinct M-chain compared with the laminin A-chain. Merosin is present in the basement membrane of placenta, striated muscle, and peripheral nerve. Using the RT-PCR assay, we demonstrate that merosin, but not laminin, is also expressed in the thymus. A partial cDNA sequence of the mouse merosin M-chain was 88% identical to the human M-chain, and the deduced amino acid sequences were 95% identical. 18-24% of adult mouse thymocytes bound to human merosin in vitro. Mg2+, but not Ca2+, was essential for binding. Binding was inhibited by antibodies recognizing VLA alpha 6 or beta 1, suggesting that the VLA-6 integrin is a merosin receptor. An anti-beta 4 integrin subunit mAb failed to inhibit binding, suggesting that the alpha 6 beta 4 integrin was not involved. Thymocytes were fractionated into immature and mature populations based on their expression of the heat stable antigen, recognized by the J11d mAb. Virtually all thymocytes expressed VLA-6, but only immature thymocytes (J11d+) bound to meroson. PMA treatment did not significantly increase the binding of J11d+ thymocytes nor did induce binding in the mature J11d- population. In constrast, both splenic T cells and unseparated lymph node cells showed enhanced binding to merosin after PMA stimulation. The expression of merosin in the thymus and its selective interaction with immature thymocytes suggest that thymocyte-merosin interactions may play a role in T cell development.


Macrophage metabolism in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH), have emerged as significant contributors to hepatic morbidity worldwide. The pathophysiology of NAFLD/NASH is multifaceted, variable, and remains incompletely understood. The pivotal role of liver-resident and recruited macrophages in the pathogenesis of NAFLD and NASH is widely acknowledged as a crucial factor in innate immunity. The remarkable plasticity of macrophages enables them to assume diverse activation and polarization states, dictated by their immunometabolism microenvironment and functional requirements. Recent studies in the field of immunometabolism have elucidated that alterations in the metabolic profile of macrophages can profoundly influence their activation state and functionality, thereby influencing various pathological processes. This review primarily focuses on elucidating the polarization and activation states of macrophages, highlighting the correlation between their metabolic characteristics and the transition from pro-inflammatory to anti-inflammatory phenotypes. Additionally, we explore the potential of targeting macrophage metabolism as a promising therapeutic approach for the management of NAFLD/NASH.


Systematic review of social norms, attitudes, and factual beliefs linked to the sexual exploitation of children and adolescents.
Despite growing interest in the role of social norms in perpetuating the harmful practice of sexual exploitation of children and adolescents (SECA), little is known about the state of the literature on this issue. This systematic review aims to summarize what associated norms, attitudes and factual beliefs have been identified by the SECA literature worldwide. Multiple database searches were conducted using controlled vocabulary and keywords referring to SECA. Our searches identified 3690 unique references. After applying our exclusion criteria, 49 studies, including over 14,000 participants from 37 countries and most world regions, were included. Across studies we identified six injunctive norms perpetuating SECA: owning goods as a social status marker ; being sexually active; exchanging sex for favors; contributing financially to the household; stigma and discrimination against young people who experienced SECA; and lack of social sanctions for SECA perpetrators. These norms were supported by enhanced tolerance of SECA when it involved older or more physically developed adolescents and when it occurred in poverty-affected contexts. Beliefs around markers that denote adolescents' readiness for sex; men's entitlement to sex; and the perceived benefits of intergenerational relationships, also contributed to the maintenance and reproduction of SECA. Findings from all regions suggested that marginalized young people are particularly vulnerable to SECA. Interventions to reduce SECA must consider individual, social, and structural factors and how they interrelate. Context-specific social norms interventions are needed to address harmful norms, promote protective norms, and improve services for those who have experienced SECA.


Serotonin and 5-hydroxytryptophan on blood pressure and renal blood flow in anesthetized rats.
The effects of exogenous (injected) serotonin on mean blood pressure and renal blood flow in male Sprague-Dawley rats were compared with the effects of enhanced endogenous serotonin, accomplished by injections of 5-hydroxytryptophan (5-HTP). Responses were evaluated with and without carbidopa, which blocks peripheral conversion of 5-HTP to serotonin, and with and without indomethacin to assess the contribution of prostanoids. Both serotonin (0.25-1.0 micrograms) and 5-HTP (50-200 micrograms) decreased blood pressure and renal blood flow and increased renal vascular resistance in dose-dependent fashion. Hypotensive responses with both agents were greater after arterial injections into the aortic arch than after intravenous injections (into the jugular vein). Carbidopa had no significant effects on responses to serotonin but ablated the ability of 5-HTP to increase renal vascular resistance and decrease renal blood flow. Carbidopa did not alter the hypotensive action of 5-HTP. Indomethacin had no significant effect on responses to serotonin or 5-HTP. These results support a direct renal vasoconstrictor effect for exogenous and endogenously formed serotonin and a hypotensive effect probably arising in the central nervous system.


Concurrent immune thrombocytopenic purpura and Guillain-Barre syndrome in a patient with Hashimoto's thyroiditis.
Immune thrombocytopenic purpura (ITP), Guillain-Barre syndrome (GBS), and Hashimoto's thyroiditis (HT) are autoimmune disorders caused by impaired self-tolerance mechanisms triggered by interaction between genetic and environmental factors. ITP is an immune-mediated destruction of platelets resulting in mucocutaneous bleeding, GBS is an ascending motor paralysis caused by an inflammatory demyelination of peripheral nerves, and HT is characterized by autoimmune-mediated destruction of the thyroid gland. The concurrent development of ITP and GBS has only rarely been reported in the literature, and GBS itself rarely occurs with other autoimmune disorders. We present a 21 year-old patient with known Hashimoto's hypothyroidism that simultaneously developed GBS and ITP after an upper respiratory tract infection. To the best of our knowledge, this is the first reported case of these three autoimmune disorders in the same patient. This points to a possible common genetic predisposition to these disorders.


Chlorpropamide-induced cholestatic liver failure resulting in death.
To describe the first reported case of a death that occurred as a result of chlorpropamide-induced cholestatic liver disease. We review the clinical and laboratory details of an 81-year-old man with type II diabetes mellitus, who was hospitalized because of nausea, vomiting, and jaundice. The patient had been taking a sulfonylurea (chlorpropamide, 250 mg orally three times a day) for 2 months. On initial assessment, the patient was noted to have cutaneous and scleral icterus and an erythematous maculopapular rash on the torso. The alkaline phosphatase level was substantially increased, and the transaminases were mildly increased. Use of all medications was discontinued. In the hospital, the patient's status rapidly deteriorated, and death ensued after cardiopulmonary arrest on day 6. The findings were consistent with a hypersensitivity reaction to chlorpropamide that ultimately resulted in fulminant cholestatic liver disease and death.


Analytical, ultrastructural, autoradiographic and biochemical studies on [3H]dicarboxylic acid added to cultures of melanoma cells.
Lentigo maligna and malignant melanoma can be treated by dicarboxylic acids (C9 and C12), which are competitive inhibitors of tyrosinase. We therefore studied the intracellular location and possible sites of action of dodecanedioic acid (C12) in murine melanoma cells, using EM autoradiography and biochemical analysis of lipid extracts by HPLC. Significant levels of radioactivity were found in the mitochondria and in the nuclei but not in association with membranes of rough endoplasmic reticulum, Golgi-associated endoplasmic reticulum, or Golgi apparatus, and not in coated vesicles or melanosomes. Biochemical analysis revealed that the diacid underwent beta-oxidation, which occurs only in mitochondria. The results suggest that the toxicity of dicarboxylic acids in melanoma cells is not related to anti-tyrosinase activity but may be due to interference with oxidoreductase enzymes in the mitochondria and possibly to inhibition of DNA synthesis in the nucleus.


Keep on brushing: a longitudinal study of motivational text messaging in young adults aged 18-24 years receiving Work and Income Support.
Using text messaging, underpinned by the Health Belief Model, this study aimed to improve tooth brushing frequencies among unemployed young adults aged 18-24 years. Set within Work and Income's Linwood Community Link office (one Christchurch branch of the New Zealand Government's employment and beneficiary services), unemployed young adults aged 18-24 years with access to a mobile phone were recruited using either a purpose-built computer kiosk or Work and Income's Facebook site. Participants completed a baseline survey and then received and responded to a series of motivational text messages over 10 weeks. Self-reported tooth brushing frequency was the primary outcome variable. Important socio-demographic (age, gender, ethnicity, employment status) and method-specific (level of attrition, distribution of successful text messages deliveries, active withdrawal) variables were also collected. Longitudinal analyses of these responses employed generalized estimating equation (GEE) models. Four hundred and three registered for the trial, of whom 171 (42%) were eligible. Self-reported tooth brushing twice or more per day increased from 51% at baseline to 70% at week 3, 74% at week 6, and 73% at week 9 - an increase significant in crude (P<0.001) and adjusted (P<0.001) GEE analyses. No important differences were noted between age, gender, or ethnic groups, although attrition was relatively high with only 26% participating by week 9. However, no evidence of differential attrition was observed. Invention through motivational text messaging improved the measured oral health self-care behavior in a hard-to-reach group carrying a disproportionately heavy oral health burden. This intervention warrants further investigation.


Mast Cell Proteases Cleave Prion Proteins and a Recombinant Ig against PrP Can Activate Human Mast Cells.
IgE Abs, best known for their role in allergic reactions, have only rarely been used in immunotherapies. Nevertheless, they offer a potential alternative to the more commonly used IgGs. The affinity of IgE Ag binding influences the type of response from mast cells, so any immunotherapies using IgEs must balance Ag affinity with desired therapeutic effect. One potential way to harness differential binding affinities of IgE is in protein aggregation diseases, where low-affinity binding of endogenous proteins is preferred, but enhanced binding of clusters of disease-associated aggregated proteins could target responses to the sites of disease. For this reason, we sought to create a low-affinity IgE against the prion protein (PrP), which exists in an endogenous monomeric state but can misfold into aggregated states during the development of prion disease. First, we determined that mast cell proteases tryptase and cathepsin G were capable of degrading PrP. Then we engineered a recombinant IgE Ab directed against PrP from the V region of a PrP-specific IgG and tested its activation of the human mast cell line LAD2. The αPrP IgE bound LAD2 through Fc receptors. Crosslinking receptor-bound αPrP IgE activated SYK and ERK phosphorylation, caused Fc receptor internalization, and resulted in degranulation. This work shows that a recombinant αPrP IgE can activate LAD2 cells to release enzymes that can degrade PrP, suggesting that IgE may be useful in targeting diseases that involve protein aggregation.


[Informed consent in the terminal care].
One of the biggest problems to perform terminal care is how to communicate with patient's families. Mental stresses of patients who are expected to die and of their families are extremely serious. To release their stresses, kind and detailed explanation of patient condition should be given every day by the clinical team consisted of doctors and nurses. We should realize that mental support given by the clinical staff would be an important care point to alleviate the stresses of patients and to alleviate the stresses and the strains of their families. And we can say that performing terminal care is essential to promote informed consent.


Palladium/Silver Synergistic Catalysis in Direct Aerobic Carbonylation of C(sp(2))-H Bonds Using DMF as a Carbon Source: Synthesis of Pyrido-Fused Quinazolinones and Phenanthridinones.
An unprecedented Pd/Ag synergistic catalysis in the direct carbonylation of C(sp(2))-H bonds utilizing DMF as the carbon source under oxygen is described and demonstrated in the synthesis of pyrido-fused quinazolinone and phenanthridinone scaffolds. Control experiments indicated that the "C" of the carbonyl group is derived from the methyl group of DMF and "O" originates from oxygen as in the case of Ge's recent work. This transformation offers an alternative avenue for "CO-free" carbonylations.


Order out of chaos: the use of a matrix to validate curriculum integrity.
The rapid pace of change in the health care system now mandates that curriculum design be a dynamic, living process. A structural grid, or matrix, that lists the nursing courses and the major concepts identified in the philosophy and the theoretical framework was developed by the nursing faculty. The matrix is a visual representation of the curriculum concepts and how they are implemented in each course. The matrix serves as a reference point to validate that the essential knowledge for safe practice and new developments in nursing are being taught. The matrix is a living document, expected to evolve, that validates the integrity of the curriculum and confirms that faculty are "teaching what they say they are teaching."


Assessment of two venous drainage techniques in coronary artery bypass graft surgery.
We compared the influence on immediate postoperative cardiac performance, incidence of supraventricular tachyarrhythmia, fluid balance, and respiratory function of two methods of venous drainage during cardiopulmonary bypass (CPB). Two groups of 50 patients were studied. All 100 patients were operated electively for coronary artery bypass grafting. In group 1, cardiac drainage was achieved by using a two-stage cavo-atrial cannula, group 2 patients had drainage cannulae in the superior and inferior vena cava with caval tapes. There were no significant differences between both groups regarding postoperative hemodynamics. Right ventricular stroke work index in groups 1 and 2 differed insignificantly. The incidence of episodes of supraventricular tachyarrhythmia were 19 in group 1 and 23 in group 2 (p NS). Peroperative fluid balance was higher in group 1, but hematocrit during CPB was in the same range. Blood gas analysis values did not differ among the groups during the first 32 hours. The average duration of assisted ventilation was 30.3 +/- 5.4 hours in group 1 and 27.8 +/- 3.1 hours in group 2 (p NS). Thus, in patients undergoing coronary artery bypass grafting with standard techniques of intermittent cardioplegia, double caval cannulation is not superior to single atrio-caval drainage as far as postoperative left and right heart performance, and prevention of supraventricular tachyarrhythmia is concerned. Single cannulation did not increase the risk of undue hemodilution or respiratory dysfunction.


Broadband GaAsSb Nanowire Array Photodetectors for Filter-Free Multispectral Imaging.
Highly compact, filter-free multispectral photodetectors have important applications in biological imaging, face recognition, and remote sensing. In this work, we demonstrate room-temperature wavelength-selective multipixel photodetectors based on GaAs0.94Sb0.06 nanowire arrays grown by metalorganic vapor phase epitaxy, providing more than 10 light detection channels covering both visible and near-infrared ranges without using any optical filters. The nanowire array geometry-related tunable spectral photoresponse has been demonstrated both theoretically and experimentally and shown to be originated from the strong and tunable resonance modes that are supported in the GaAsSb array nanowires. High responsivity and detectivity (up to 44.9 A/W and 1.2 × 1012 cm √Hz/W at 1 V, respectively) were obtained from the array photodetectors, enabling high-resolution RGB color imaging by applying such a nanowire array based single pixel imager. The results indicate that our filter-free wavelength-selective GaAsSb nanowire array photodetectors are promising candidates for the development of future high-quality multispectral imagers.


Application of design of experiment for floating drug delivery of tapentadol hydrochloride.
The aim of the present study was to apply design of experiment (DOE) to optimize floating drug delivery of tapentadol hydrochloride. Tapentadol hydrochloride is a synthetic opioid used as a centrally acting analgesic and effective in both experimental and clinical pain. The half-life of the drug is about 4 hours and oral dose is 50 to 250 mg twice a day. For optimization 3(2) full factorial design was employed for formulation of tapentadol hydrochloride tablets. Sodium bicarbonate was incorporated as a gas-generating agent. Combination of polymers Xanthan gum and Locust bean gum was used to achieve controlled release effect. The concentration of polymers was considered as the independent variables and dependent variables were floating lag time and swelling index of the tablets. From the factorial batches, it was observed that formulation containing combination of 20% sodium bicarbonate and 10% citric acid shows optimum floating ability whereas the formulation containing 20% Xanthan gum and 28% Locust bean gum shows optimum sustained drug release pattern with adequate floating.


Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling.
Spermatogenesis is a continuous and productive process supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs), which arise from undifferentiated precursors known as gonocytes and are strictly controlled in a special 'niche' microenvironment in the seminiferous tubules. Sertoli cells, the only somatic cell type in the tubules, directly interact with SSCs to control their proliferation and differentiation through the secretion of specific factors. Spermatocyte meiosis is another key step of spermatogenesis, which is regulated by Sertoli cells on the luminal side of the blood-testis barrier through paracrine signaling. In this review, we mainly focus on the role of Sertoli cells in the regulation of SSC self-renewal and spermatocyte meiosis, with particular emphasis on paracrine and endocrine-mediated signaling pathways. Sertoli cell growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), as well as Sertoli cell transcription factors, such as ETS variant 5 (ERM; also known as ETV5), nociceptin, neuregulin 1 (NRG1), and androgen receptor (AR), have been identified as the most important upstream factors that regulate SSC self-renewal and spermatocyte meiosis. Other transcription factors and signaling pathways (GDNF-RET-GFRA1 signaling, FGF2-MAP2K1 signaling, CXCL12-CXCR4 signaling, CCL9-CCR1 signaling, FSH-nociceptin/OPRL1, retinoic acid/FSH-NRG/ERBB4, and AR/RB-ARID4A/ARID4B) are also addressed.


Synthesis and characterization of a polymeric network made of polyethylene glycol and chitosan as a treatment with antibacterial properties for skin wounds.
Polyethylene glycol has been widely investigated for wound healing and dressing applications. Despite its advantages (i.e. great biocompatibility), polyethylene glycol lacks antibacterial activity. For this reason, semi-interpenetrated polymeric networks were prepared by combining a chemically cross-linked polyethylene glycol network with chitosan. The aim of this work was to identify the best amount of chitosan able to improve the antibacterial properties against Staphylococcus aureus. Briefly, the networks were synthesized by a sequential method, adding chitosan in different proportion to the polyethylene glycol. The antibacterial activity was tested following the MGA 0100 of the Pharmacopeia of the United States of Mexico. Fourier-transform infrared with attenuated total reflection spectroscopy, scanning electron microscopy and swelling behavior PBS at 37° C and room temperature were also performed to characterize the polymeric networks. The results showed that PC-2% was able to inhibit the bacterial growth of Staphylococcus aureus even more than Fosfomycin antibiotic. The networks showed cylindrical pores of different sizes (50-100 µm). The maximum swelling of all the networks was achieved in PBS at 37°C (>315%). Free hemoglobin and hemolysis assays were also evaluated to know the compatibility with erythrocytes. Human dermal fibroblasts were used to evaluate direct cytotoxicity. Therefore, the produced gels exerted interesting antibacterial activity and showed good biocompatibility properties.


Aquaporins in Obesity.
Obesity is one of the most important metabolic disorders of this century and is associated with a cluster of the most dangerous cardiovascular disease risk factors, such as insulin resistance and diabetes , dyslipidemia and hypertension , collectively named Metabolic Syndrome. The role of aquaporins in glycerol metabolism facilitating glycerol release from the adipose tissue and distribution to various tissues and organs, unveils these membrane channels as important players in lipid balance and energy homeostasis and points to their involvement in a variety of pathophysiological mechanisms including insulin resistance, obesity and diabetes.This review summarizes the physiologic role of aquaglyceroporins in glycerol metabolism and lipid homeostasis, describing their specific tissue distribution, their involvement in glycerol balance and their implication in obesity and fat-related metabolic complications. The development of specify pharmacologic modulators able to regulate aquaglyceroporins expression and function , in particular AQP7 in adipose tissue, might constitute a novel approach for controlling obesity and other metabolic disorders.


Contribution of SLC30A8 variants to the risk of type 2 diabetes in a multi-ethnic population: a case control study.
Several studies have shown the association of solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 with type 2 diabetes (T2D). However, the association of alternative variants and haplotypes of SLC30A8 with T2D have not been studied in different populations. The aim of this study is to assess the association of the alternative SLC30A8 variants, rs7002176 and rs1995222 as well as the most common variant, rs13266634 and haplotypes with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian subjects. Single nucleotide polymorphisms (SNPs) of SLC30A8; rs7002176, rs1995222 and rs13266634 were genotyped in 1140 T2D and 973 non-diabetic control subjects. Of these, 33 GADA positive diabetic subjects and 353 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The recessive genetic model controlled for age, race, gender and BMI shows that the alternative SLC30A8 variant, rs1995222 is associated with GADA negative diabetes (OR = 1.29, P = 0.02) in Malaysian subjects. The most common variant, rs13266634 is also associated with GADA negative diabetes (OR = 1.45, P = 0.001). This association is more pronounced among Malaysian Indians (OR = 1.93, P = 0.001). Moreover, the CG haplotype and CG-CG diplotype have been equally associated with increased diabetic risk (OR = 1.67, P = 8.6 × 10-5). SLC30A8 SNPs and haplotypes are associated with GADA negative diabetes in Malaysian subjects, and this association is markedly higher among Malaysian Indian subjects.


Factors associated with good outcome using lateral mass plate fixation.
The immediate and long-term outcomes of 70 consecutive patients who underwent subaxial lateral mass fixation between June 1996 and June 2001 were reviewed. Intraoperative fluoroscopy and somatosensory evoked potential (SEP) monitoring were used in all patients. Immediate postoperative computed tomography (CT) was performed to determine screw trajectory and placement. Follow-up ranged from 2 to 7 years. Postoperative CT showed 206 (58%) of 356 screws had unicorticate and 42% bicorticate purchase. Furthermore, 96 (27%) screws had suboptimal trajectory, but only 5 of these screws minimally penetrated the foramen transversarium without resultant vascular or neurological sequelae. A sudden unilateral intraoperative SEP amplitude decrease during screw placement in 2 patients resolved with screw removal and alteration of screw trajectory. The overall fusion success rate was 91.5% and screw pull-out developed in 2 patients. The recommended drilling technique and trajectory (15 degrees - 25 degrees rostral in the sagittal plane, 20 degrees - 30 degrees lateral in the axial plane), supplemented bone grafting, and intraoperative SEP monitoring are all associated with good screw placement, fusion, and neurological outcome and are recommended for all lateral mass fusion procedures.


Anatomic features of the furcal nerve and its clinical significance.
Attention must be paid to the furcal nerve when analyzing lumbosacral radicular symptoms, especially when neurologic findings are atypical and the responsible level cannot be assessed. An anatomic and clinical study of the furcal nerve showed the following: the furcal nerve was found in all dissections, and it arises at the L4-root level in most dissections (93%); the furcal nerve has its own anterior and posterior root fibers and its own dorsal nerve root ganglion. This proves that the furcal nerve is an independent nerve root. Neurologic symptoms, suggestive of two roots being involved, are frequently due to furcal nerve compression.


Intra-urban patterns of neighborhood-level social capital: a pilot study.
Background: Social capital is a construct of interaction and social trust in one's fellow community members. These interactions can provide a safety net for individuals in terms of information, social support, and adherence to social norms. While a number of studies have previously examined the relationship between social capital and health outcomes, few have examined the theparallel relationship of social capital and geographic "place" with respect to health outcomes. Methods: Considering social capital as facilitated by specific structures, we evaluate the relationship between neighborhood-level social capital and disability rates in a major Southern US city. Disability rates were collected through neighborhood-level data via the AmericanCommunity Survey (ACS) and compared to a geocoded map of neighborhood-level social capital measures during spring, 2016. Results: Higher social capital within a neighborhood coincided with lower disability rates in that neighborhood (r=-0.14, P=0.016) when compared to random assortment models. Conclusion: Findings from this research add evidence to the value of the built environment, not only providing resources and shaping choices, but for facilitating important social relationships.


Modulation of vascular smooth muscle cell growth by magnesium-role of mitogen-activated protein kinases.
We tested the hypothesis that Mg(2+) influences growth of vascular smooth muscle cells (VSMCs) by modulating cell cycle activation through mitogen-activated protein (MAP) kinase-dependent pathways. Rat VSMCs were grown in culture medium containing normal Mg(2+) (1.02 mmol/L, control) and increasing concentrations of Mg(2+) (2-4 mmol/L) for 1-8 days. Effects of varying extracellular Mg(2+) concentration ([Mg(2+)](e)) on intracellular free Mg(2+) concentration ([Mg(2+)](i)) were assessed using mag-fura. Growth actions of Mg(2+) were evaluated by measuring cell cycle activation, DNA synthesis, and protein synthesis. Expression of cell cycle promoters, cyclin D1, cyclin E, Cdk2, and Cdk4 was assessed by immunoblotting. Phosphorylation of cell cycle inhibitors p21(cip1) and p27(kip1) and MAP kinases, ERK1/2, p38MAP kinase, and JNK was evaluated using phospho-specific antibodies. [Mg(2+)](i) increased in a dose-dependent manner in response to increasing [Mg(2+)](e). These effects were evident within 2 days and maximal responses were obtained after 6 days. High [Mg(2+)](e) induced cell cycle activation with a lower proportion of cells in G(1) phase (75 +/- 1.0%) and a higher fraction of cells in S phase (12 +/- 0.7%) versus control (G(1), 88.5 +/- 1.4%; S, 6.8 +/- 1.2%; P < 0.05). This was associated with increased protein content of cyclin D1 and Cdk4 and decreased activation of p21(cip1) and p27(kip1). In cells exposed to 2 mmol/L Mg(2+), DNA and protein synthesis was increased approximately threefold. Phosphorylation of MEK1/2 and ERK1/2 was enhanced two to threefold in cells grown in 2 mmol/L Mg(2+). These effects were rapid, occurring within 2 days. Phosphorylation of MEK3/6, p38 MAP kinase, and JNK was unaltered by increasing [Mg2](e). PD98059 (10(-5) mol/L), specific MEK1/2 inhibitor, but not SB202190 (10(-5) mol/L) (specific p38 MAP kinase inhibitor), attenuated Mg(2+)-induced growth actions. These data demonstrate the novel findings that cell cycle activation and growth regulation by Mg(2+) occurs via ERK1/2-dependent, p38 MAP kinase-independent pathways.


Xmn1 restriction polymorphism of apolipoprotein AI gene and lipoprotein levels in obesity.
The aim of this study was to assess any association between an Xmn1 restriction site polymorphism of the apo AI gene and lipoprotein levels in obesity. A cross sectional study was made of lipid variables in relation to genetic and anthropometric factors in obese people at the Nutrition Outpatient Clinic of Bichat Hospital in Paris, France. The subjects were 97 unrelated French Caucasian subjects (65 women and 32 men) selected on the basis of 20% over-weight. The following main outcome measures were recorded: body mass index (BMI) and waist to hip ratio (WHR), cholesterol (C) and triglyceride (TG) concentrations in serum and lipoproteins (including HDL subfractions), apolipoproteins AI and B, determination of apo AI Xmn1 genotypes. Three alleles, designated X1, X2, X3, could be detected with frequencies 0.84, 0.12, and 0.04 respectively. The X2 carriers had higher concentrations of LpA-I, A-II (HDL particles containing both Apo AI and Apo AII) in the whole group: 0.90 vs 0.77 and 0.72 g/l in X1X1 and X1X3 respectively (P < 0.01). The genotype X1X2 was also associated with higher HDL-C in obese men (0.47 vs 0.36 g/l in X1X1, P < 0.05). In X1X1 women, BMI was positively correlated with serum and VLDL-TG (P < 0.05) and negatively with HDL2-C (P < 0.05), WHR being positively correlated with serum TG (P < 0.05), VLDL-TG (P < 0.01) and negatively with HDL-(P < 0.05) and HDL2-C (P < 0.01). These correlations were not found in subjects carrying the X2 allele.(ABSTRACT TRUNCATED AT 250 WORDS)


Ocular Involvement in Systemic Lupus Erythematosus: The Experience of Two Tertiary Referral Centers.
To assess the prevalence of the ocular manifestations related to the disease and/or ascribable to the administration of potentially toxic drugs in a cohort of 98 patients with systemic lupus erythematosus (SLE). Retrospective, observational study reporting the experience of two tertiary referral centers. Overall, an ocular involvement was detected in 29 patients (29.6%), sometimes preceding of months the diagnosis of SLE, more often revealed at diagnosis or throughout its course. More than a single ocular manifestation was found in 20 of the 29 patients with ophthalmological findings (68.9%). The array of ocular morbidity included, in a decreasing order of frequency, cataracts, keratoconjunctivitis sicca, glaucoma, discoid lesions of eyelids, episcleritis, retinopathy, vortex keratopathy, choroidopathy and retinal detachment, central retinal vein occlusion, and hydroxychloroquine-induced toxic maculopathy. It is advised that a multidisciplinary team for the diagnosis and treatment of SLE should regularly include the presence of an ophthalmologist.


Detection of dendritic cell subsets in the tumor microenvironment by multiplex immunohistochemistry.
Dendritic cells (DCs) are essential in antitumor immunity. In humans, three main DC subsets are defined: two types of conventional DCs (cDC1s and cDC2s) and plasmacytoid DCs (pDCs). To study DC subsets in the tumor microenvironment (TME), it is important to correctly identify them in tumor tissues. Tumor-derived DCs are often analyzed in cell suspensions in which spatial information about DCs which can be important to determine their function within the TME is lost. Therefore, we developed the first standardized and optimized multiplex immunohistochemistry panel, simultaneously detecting cDC1s, cDC2s, and pDCs within their tissue context. We report on this panel's development, validation, and quantitative analysis. A multiplex immunohistochemistry panel consisting of CD1c, CD303, X-C motif chemokine receptor 1, CD14, CD19, a tumor marker, and DAPI was established. The ImmuNet machine learning pipeline was trained for the detection of DC subsets. The performance of ImmuNet was compared with conventional cell phenotyping software. Ultimately, frequencies of DC subsets within several tumors were defined. In conclusion, this panel provides a method to study cDC1s, cDC2s, and pDCs in the spatial context of the TME, which supports unraveling their specific roles in antitumor immunity.


Nanoparticle assisted solvent selective transdermal combination therapy of curcumin and 5-flurouracil for efficient cancer treatment.
Skin cancer is one among the many prominent diseases of the modern world and millions of people are suffering due to the lack of proper medication. Even though transdermal drug delivery systems (TDDS) provide an efficient route of drug administration, the advantages of combination chemotherapy have rarely been extended into TDDS. In the present work, a polymer capable of simultaneously encapsulating two anti-cancer drugs: 5-flurouracil (5-FU) and curcumin (CUR), and releasing them with varying kinetics as a function of the leaching solvent was developed. The prepared TDDS had two copolymers: alginate coated aminated nanodextran (ALG@AND) and chitosan coated folate decorated aminated β-CD nano particles (CS@FA-g-AβCD). After inducing surface charges, both copolymers were coupled together by electrostatic forces. All the synthetic procedures for the preparation of TDDS were monitored using FTIR, DLS, Zeta Potential, SEM and TEM. The final TDDS was then evaluated for its solvent selectivity. Sustained release of 5-FU and CUR was observed with ethanol (EtOH) and 1-butanol (BuOH) respectively. However, these solvents could also release a small amount of the second drug which led to combinatorial therapy. The in vitro solvent selective drug permeation profiles were evaluated using Franz diffusion cell on rat skin. In order to evaluate the economic feasibility of the prepared TDDS, in vivo skin adhesion tests, skin irritation analysis, water vapour permeability and average visible transmittance were performed. Results proved that solvents could not only elute the drugs in a sustained manner, but could also act as penetration enhancers. Biological and histological studies carried out on skin and cancer cell lines suggested the potential usefulness of the prepared material in combinatorial chemotherapy.


[Childhood linear psoriasis].
Linear distribution of psoriasis is rare. This presentation offers to physicians some diagnostic difficulty, especially in the absence of a history of pre-existing psoriasis or in the presence of any other linear dermatosis. In this study, we report cases of 3 girls, ages 4 yr, 5 yr and 10 yr, admitted to our dermatology department. The clinical features and differential diagnosis of this skin disease which, in children, can be easily mistaken for inflammatory verrucous epidermal nevus, are discussed.


Mode-dependent nonequilibrium temperature in aging systems.
We introduce an exactly solvable model for glassy dynamics with many relaxational modes, each one characterized by a different relaxational time scale. Analytical solution of the aging dynamics at low temperatures shows that a nonequilibrium or effective temperature can be associated to each time scale or mode. The spectrum of effective temperatures shows two regions that are separated by an age-dependent boundary threshold. Region I is characterized by partially equilibrated modes that relax faster than the modes at the threshold boundary. Thermal fluctuations and time correlations for modes in region I show that those modes are in mutual thermal equilibrium at a unique age-dependent effective temperature theta(s). In contrast, modes with relaxational time scales longer than that of modes at the threshold (region II) show diffusive properties and do not share the common temperature theta(s). The shift of the threshold toward lower energy modes as the system ages, and the progressive shrinking of region II, determines how the full spectrum of modes equilibrates. As is usually done in experiments, we have defined a frequency-dependent effective temperature and we have found that all modes in region I are mutually equilibrated at the temperature theta(s) independently of the probing frequency. The present model aims to explain transport anomalies observed in supercooled liquids in terms of a collection of structurally disordered and cooperative rearranging mesoscopic regions.


Functional characterization of the microtubule-binding and -destabilizing domains of CPAP and d-SAS-4.
We previously identified a novel centrosomal protein CPAP, which carries a 112-residue motif that is essential for microtubule destabilization. In this report, we define both the microtubule (MT) binding and destabilizing domains in human CPAP and analyze the mutations that affect its MT-destabilizing activity. Analysis of a series of CPAP truncated proteins showed that the MT-binding domain (MBD; residues 423-607) of CPAP is located next to its MT-destabilizing domain (MDD; residues 311-422). Site-specific mutagenesis revealed that the mutations that either disrupt the alpha-helical structure (Y341P, I346P, L348P, and triple-P) or alter the charge property (KR377EE) of the MDD significantly affect its MT-destabilizing ability. The activity for binding to a tubulin heterodimer was also significantly reduced in KR377EE mutant. Furthermore, we have analyzed the putative function of Drosophila d-SAS-4, a distant relative of human CPAP, which shares a conserved approximately 20-aa sequence with the MDD of CPAP. Our results show that mutations in this conserved sequence also eliminate d-SAS-4's MT-destabilizing activity, suggesting that d-SAS-4 and CPAP may play similar roles within cells.


The Ih Channel Gene Promotes Synaptic Transmission and Coordinated Movement in Drosophila melanogaster.
Hyperpolarization-activated cyclic nucleotide-gated "HCN" channels, which underlie the hyperpolarization-activated current (Ih), have been proposed to play diverse roles in neurons. The presynaptic HCN channel is thought to both promote and inhibit neurotransmitter release from synapses, depending upon its interactions with other presynaptic ion channels. In larvae of Drosophila melanogaster, inhibition of the presynaptic HCN channel by the drug ZD7288 reduces the enhancement of neurotransmitter release at motor terminals by serotonin but this drug has no effect on basal neurotransmitter release, implying that the channel does not contribute to firing under basal conditions. Here, we show that genetic disruption of the sole HCN gene (Ih) reduces the amplitude of the evoked response at the neuromuscular junction (NMJ) of third instar larvae by decreasing the number of released vesicles. The anatomy of the (NMJ) is not notably affected by disruption of the Ih gene. We propose that the presynaptic HCN channel is active under basal conditions and promotes neurotransmission at larval motor terminals. Finally, we demonstrate that Ih partial loss-of-function mutant adult flies have impaired locomotion, and, thus, we hypothesize that the presynaptic HCN channel at the (NMJ) may contribute to coordinated movement.


Successful treatment of intractable gastrointestinal tract graft-vs-host disease with oral beclomethasone dipropionate in pediatric and young adult patients: Case reports.
The gastrointestinal (GI) tract is a common target organ of graft-vs-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT) patients, and GI tract GVHD is often resistant to standard treatments such as corticosteroids. Moreover, longterm use of systemic corticosteroids sometimes induces adverse events such as infection. Beclomethasone dipropionate (BDP) is a potent, topically active corticosteroid, which is metabolized to an active derivative in the intestinal mucosa. Oral BDP therapy is reportedly effective against GI tract GVHD in adult HSCT patients, but its efficacy and safety in pediatric patients remain undefined. Here, we report three pediatric and young adult cases who were treated with oral BDP. Three (6-, 7-, and 18-year-old) patients developed stage 2 to 4 lower GI tract GVHD, which was resistant to standard immunosuppressive therapies. Lower GI tract GVHD in these patients was histopathologically proven by endoscopic biopsy. Oral administration of enteric-coated capsules of BDP (3-8 mg/day) was started for the treatment of lower GI tract GVHD. With the introduction of oral BDP therapy, their GI tract symptoms promptly resolved (abdominal pain, within 3-7 days; diarrhea, within 2-3 weeks). Subsequently, systemic immunosuppressive agents such as corticosteroids and mycophenolate mofetil were successfully tapered off. During oral BDP therapy, although cytomegalovirus antigenemia and Acinetobacter Iwoffii sepsis developed in 2 cases, both were curable with conventional treatments. In a young adult case, concomitant BK virus-associated hemorrhagic cystitis resolved after oral BDP was introduced and systemic immunosuppressive agents were reduced. Transient growth restriction was observed in a pediatric case who was treated with oral BDP for approximately 300days. Our experiences suggest that oral BDP therapy is an effective approach for GI tract GVHD that is resistant to standard immunosuppressive therapies. Of clinical importance, our case suggests the possibility that oral BDP therapy may improve the immunosuppressive condition in GI tract GVHD patients by contributing to the reduction of systemic immunosuppressive medications as a result of prompt improvement of GI tract GVHD symptoms.


SEROLOGICAL DIAGNOSIS OF BAYLISASCARIS PROCYONIS IN PRIMATES USING A HUMAN ELISA TEST.
The usefulness of a human enzyme-linked immunosorbent assay (ELISA) for serological diagnosis of Baylisascaris procyonis larva migrans was assessed in nonhuman primates (NHP). The test was originally developed as an assay performed on human samples at Purdue University. Six participating zoos submitted 258 NHP serum samples, spanning these major phylogenetic groups: 1) great apes (n = 84), 2) lesser apes (n = 17), 3) Old World monkeys (n = 84), 4) New World monkeys (n = 20), and 5) prosimians (n = 53). Sera were tested in duplicate using a microtiter-well ELISA with B. procyonis larval excretory-secretory proteins as antigen, and serum from an experimentally infected baboon (Papio anubis) served as positive control. The ELISA clearly identified seropositive animals in all zoos. With putative cutoffs of optical density (OD) measured at 405 nm (OD405) of <0.150 = negative, 0.150-0.250 = indeterminate, and >0.250 = positive, 149 of 258 (57.8%) were clearly negative (mean OD 0.046), and 78 of 258 (30.2%) were clearly positive (mean OD 0.657, range 0.253-1.773), the rest being indeterminate. Of these, 15 were high positive with OD 1.095-1.773 (mean 1.314). Positive animals were seen from all zoos; 76 (97.4%) were great apes, lesser apes, or Old World monkeys. The four highest ODs were in a siamang (Symphalangus syndactylus), lion-tailed macaque (Macaca silenus), Sumatran orangutan (Pongo abelii), and western lowland gorilla (Gorilla gorilla gorilla), all from different zoos. Prosimians had a mean OD of 0.039 and New World monkeys 0.021, indicating that human reagents either did not work for these groups or few infected animals were represented. These results indicate that the human ELISA for B. procyonis works well for at least higher phylogeny NHP and that serologic evidence of infection is surprisingly common, correlating with what is known for exposure to this parasite in zoos.


[Opportunities of delayed densitometry of "late (fixed) contrast" as a test for tumors in residual mediastinal lesion in primary mediastinal lymphosarcoma after polychemotherapy].
To clarify the potential of delayed densitometry of late (fixed) contrast in differentiation between tumor and fibrosis in residual mediastinal lesion (RML). Computed tomography (computed tomograph of the third generation COMATOM CR-3 made in Germany, SIEMENS) has examined 12 patients with mediastinal lymphosarcomas after polychemotherapy. All of them had a RML 3 to 6 cm in diameter. CT has detected 8 cases of the tumor and 4 cases of fibrosis. The criteria of the tumor were the following: increased RML density shortly after the contrast medium introduction and 30 min after urographine introduction (p < 0.01); RML density 30 min after introduction of contrast medium was higher than above the aorta (p < 0.01). Fibrosis in RML was stated if RML density before, at the high of concentration and after introduction of the contrast medium was the same (p > 0.01); aortic density was significantly higher of RML density at the height of the contrast (p < 0.01). The above method differentiates the tumor with fibrosis in RML with maximal probability. This facilitates further choice of therapeutic policy in secondary resistant form of primary mediastinal lymphosarcoma.


Nanopore long-read next-generation sequencing for detection of mitochondrial DNA large-scale deletions.
Primary mitochondrial diseases are progressive genetic disorders affecting multiple organs and characterized by mitochondrial dysfunction. These disorders can be caused by mutations in nuclear genes coding proteins with mitochondrial localization or by genetic defects in the mitochondrial genome (mtDNA). The latter include point pathogenic variants and large-scale deletions/rearrangements. MtDNA molecules with the wild type or a variant sequence can exist together in a single cell, a condition known as mtDNA heteroplasmy. MtDNA single point mutations are typically detected by means of Next-Generation Sequencing (NGS) based on short reads which, however, are limited for the identification of structural mtDNA alterations. Recently, new NGS technologies based on long reads have been released, allowing to obtain sequences of several kilobases in length; this approach is suitable for detection of structural alterations affecting the mitochondrial genome. In the present work we illustrate the optimization of two sequencing protocols based on long-read Oxford Nanopore Technology to detect mtDNA structural alterations. This approach presents strong advantages in the analysis of mtDNA compared to both short-read NGS and traditional techniques, potentially becoming the method of choice for genetic studies on mtDNA.


Multisite prospective investigation of psychological outcomes following cataract surgery in Vietnam.
Cataract surgery is a low-cost and effective intervention. There is increasing evidence to suggest that cataract surgery is associated with improvements in mobility, overall functioning and reductions in psychological distress. Within low-income and middle-income countries, cataract surgery has also been documented to lead to reductions in psychological distress; however, differences in economic activity and engagement in paid and domestic work in these countries may moderate such reductions. We aimed to examine the psychological outcomes following cataract surgery among a diverse Vietnamese sample. We report findings from the VISIONARY study, a 12-month multisite prospective study of cataract surgery outcomes conducted in Vietnam (N=462). Generalised estimating equations (GEEs) were used to identify the variables which were associated with reduced psychological distress. A high proportion of participants (56.6%) reported psychological distress before surgery and severity of psychological distress had decreased by 12 months following surgery (95% CI (4.13 to 4.95)). There were regional differences in the extent of improvement in psychological distress and change in paid and unpaid work. The extent of improvement in visual acuity, male gender, and increase in paid and unpaid work hours were significant predictors of reductions in psychological distress. Cataract surgery appears to result in the greatest reductions in psychological distress in communities where work engagement is highest. The VISIONARY study was funded by a grant provided by the Fred Hollows Foundation, Australia. During the course of this work, BME was in receipt of an Ian Potter Foundation Fellowship and a National Health and Medical Research Council (NHMRC) fellowship (1072148), SJ received an NHMRC Senior Research Fellowship, MLH was in receipt of a National Heart Foundation Future Leader Fellowship 100034.


Correlation of HBV DNA levels in serum and liver of chronic hepatitis B patients with cirrhosis.
We sought to evaluate whether serum HBV DNA levels correlates with the liver free HBV DNA levels in chronic hepatitis B. Thirty-three consecutive chronic hepatitis B patients with cirrhosis were included in this study. Twenty cases had detectable serum HBV DNA (> 1.8 pg/ml). All had detectable free liver HBV DNA. There was a strong correlation between the serum and liver HBV DNA levels (P = 0.0018, r = 0.717). Thirteen cases had undetectable serum HBV DNA. Among them, six cases still had detectable liver free HBV DNA. Eight cases were HBeAg-positive. Among them, seven cases were positive for both serum and liver HBV DNA, and one case was negative for both serum and liver HBV DNA. Twenty-five cases were HBeAg-negative and anti-HBe-positive. Among them, 13 cases were positive for serum HBV DNA, and 19 cases were positive for liver HBV DNA. No significant difference was noted for positivity of serum HBV DNA or liver free HBV DNA between HBeAg-positive and HBeAg-negative groups. The level of serum HBV DNA(491 +/- 772 pg/ml versus 203 +/- 447 pg/ml, p = 0.07) and liver free HBV DNA (33 +/- 81 pg/microg versus 6 +/- 15 pg/microg, p = 0.13) was also not statistically different. In conclusion, serum HBV DNA levels is strongly correlated with liver HBV DNA levels in chronic hepatitis B with cirrhosis. Liver free HBV DNA can still be detected in about half of the cirrhotic patients with undetectable serum HBV DNA. Serum HBeAg is not a good predictor of serum or liver HBV DNA levels in cirrhotic patients.


Micro-pulverized extraction pretreatment for highly sensitive analysis of 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol in hair by liquid chromatography/tandem mass spectrometry.
A primary metabolite of Δ(9) -tetrahydrocannabinol, 11-nor-9-carboxytetrahydrocannabinol (THC-COOH), serves as an effective indicator for cannabis intake. According to the recommendations of the Society of Hair Testing, at least 0.2 pg/mg of THC-COOH (cut-off level) must be present in a hair sample to constitute a positive result in a drug test. Typically, hair is digested with an alkaline solution and is subjected to gas chromatography/tandem mass spectrometry (GC/MS/MS) with negative ion chemical ionization (NICI). It is difficult to quantify THC-COOH at the cut-off level using liquid chromatography/tandem mass spectrometry (LC/MS/MS) without acquisition of second-generation product ions in triple quadrupole-ion trap mass spectrometers, because large amounts of matrix components in the low-mass range produced by digestion interfere with the THC-COOH peak. Using the typical pretreatment method (alkaline dissolution) and micro-pulverized extraction (MPE) with a stainless bullet, we compared the quantification of THC-COOH using GC/MS/MS and LC/MS/MS. MPE reduced the amount of matrix components in the low-mass range and enabled the quantification of THC-COOH at 0.2 pg/mg using a conventional triple quadrupole liquid chromatograph coupled to a mass spectrometer. On the other hand, the MPE pretreatment was unsuitable for GC/MS/MS, probably due to matrix components in the high-mass range. The proper combination of pretreatments and instrumental analyses was shown to be important for detecting trace amounts of THC-COOH in hair. In MPE, samples can be prepared rapidly, and LC/MS/MS is readily available, unlike GC/MS/MS with NICI. The combination of MPE and LC/MS/MS might therefore be used in the initial screening for THC-COOH in hair prior to confirmatory analysis using GC/MS/MS with NICI.


Reduction of KCC2 expression and GABAA receptor-mediated excitation after in vivo axonal injury.
After axotomy, application of muscimol, a GABA(A) receptor agonist, induced an increase in intracellular Ca(2+) ([Ca(2+)](i)) in dorsal motor neurons of the vagus (DMV neurons). Elevation of [Ca(2+)](i) by muscimol was blocked by bicuculline, tetrodotoxin, and Ni(2+). In axotomized DMV neurons measured with gramicidin perforated-patch recordings, reversal potentials of the GABA(A) receptor-mediated response, presumably equal to the equilibrium potential of Cl(-), were more depolarized than that in intact neurons. Thus, GABA(A) receptor-mediated excitation is suggested to be attributable to Cl(-) efflux out of the cell because of increased intracellular Cl(-) concentration ([Cl(-)](i)) in axotomized neurons. Regulation of [Cl(-)](i) in both control and injured neurons was disturbed by furosemide and bumetanide and by manipulating cation balance across the membrane, suggesting that functional alteration of furosemide-sensitive cation-Cl(-) cotransporters is responsible for the increase of [Cl(-)](i) after axotomy. In situ hybridization revealed that neuron-specific K(+)-Cl(-) cotransporter (KCC2) mRNA was significantly reduced in the DMV after axotomy compared with that in control neurons. Similar expression of Na(+), K(+)-Cl(-) cotransporter mRNA was observed between axotomized and control DMV neurons. Thus, axotomy led to disruption of [Cl(-)](i) regulation attributable to a decrease of KCC2 expression, elevation of intracellular Cl(-), and an excitatory response to GABA. A switch of GABA action from inhibitory to excitatory might be a mechanism contributing to excitotoxicity in injured neurons.