The risk to import ESBL-producing Enterobacteriaceae and Staphylococcus aureus through chicken meat trade in Gabon.
A main export market for chicken meat from industrialized countries is sub-Saharan Africa. We hypothesized that antibiotic resistant bacteria could be exported to developing countries through chicken meat trade. The objective was to investigate the occurrence and molecular types of ESBL-producing Enterobacteriaceae and Staphylococcus aureus in chicken meat in Gabon and to assess their dissemination among humans. Frozen chicken meat samples imported from industrialized countries to Gabon (n = 151) were screened for ESBL-producing Enterobacteriaceae and S. aureus. Genotypes and resistance genes (SHV, TEM, CTX-M, CMY-2) of isolates from meat were compared with isolates derived from humans. The contamination rate per chicken part (i. e. leg, wing) with ESBL-producing Escherichia coli (ESBL E. coli, no other ESBL-producing Enterobacteriaceae were found) and S. aureus was 23% and 3%, respectively. The beta-lactamase CTX-M 1 was predominant in ESBL E. coli from meat samples but was not found in isolates from cases of human colonization or infection. S. aureus belonging to spa type t002 (multilocus sequence type ST5) were found both in chicken meat and humans. There is a risk to import ESBL E. coli to Gabon but molecular differences between isolates from humans and chicken meat argue against a further dissemination. No MRSA isolate was detected in imported chicken meat.


Anorectal melanoma.
Primary malignant melanoma of the anorectum is a rare and virulent malignancy associated with an extremely poor prognosis in spite of aggressive initial therapy. Fifty-one patients with this disease were treated at Memorial Sloan-Kettering Cancer Center during the last 50 years and only six (12%) survived five years. This report views in detail 36 of the patients treated since 1950. In this group there was a female predominance (21 females, 15 males), and median age was in the 6th decade (range 27-75). Common presenting symptoms were pain, bleeding, mass or "hemorrhoids" of 1-12 months duration. In two-thirds, of the cases, a radical surgical approach was attempted. Other therapy included local excision alone or combined with groin dissection, local excision followed by delayed rectal resection and local tumor destruction by cryosurgery or fulguration. Mean survival was 21.5 months. Three patients had palliative treatment only with radiation therapy. Histopathologic study of 30 lesions showed that two-thirds were bulky or polypoid lesions and two-thirds showed junctional changes. The virulent prognosis of primary anorectal melanoma appears directly related to tumor size and thickness. Although all four of the five-year survivors had radical surgery, the three whose tumors could be measured had superficial lesions. In general, curative efforts by radical surgery were no more effective than local treatment by excision or cryosurgery. One patient, however, did have a thin lesion but also had nodal metastases and survived over five years after radical surgery. Although these data suggest that radical resection may cure patients with lesions thinner than 3 mm, it does not exclude the possibility that local excision might also be curative. For larger lesions that have not been cured by radical surgery, more conservative local approaches by excision or cryotherapy might be the optimum way of achieving local palliation.


Nanostructures of polyelectrolyte gel-surfactant complexes in uniaxially stretched networks.
Nanostructures of poly(acrylate) gel and dodecylpyridinium complexes equlibrated with the NaCl aqueous solution (from 5 to 100mM) and their time evolution after stretching uniaxially were investigated by means of time-resolved small-angle x-ray scattering. The scattering profile revealed the existence of the cubic nanostructure belonging to Pm3n space group in the gel before and long after the stretch. Each of the three intensive peaks was found to be resolved into two, which suggested the existence of two cubic structures with the slightly different lattice spacings. On the other hand, the splits of scattering peaks were not observed for the linear poly(acrylate) and dodecylpyridinium complexes. This indicates that the existence of the cross-linked chain is concerned in the formation of the double structure in the complex system. A series of time-resolved experiments demonstrated that the peaks corresponding to the longer lattice constant disappeared once just after stretching and regenerated to grow up, whereas the peaks corresponding to the shorter lattice constant were continuously observed. The growing rates of the peaks increased with the NaCl concentration. It was also found that a two-dimensional scattering pattern changed from the Debye-Scherrer ring type into the Laue spot type with stretching at the lower NaCl concentrations. This indicates that the single-crystal-like domains align in the stretched network due to the strong electrostatic interaction between the dodecylpyridinium cation and poly(acrylate) anion.


Microarray Я US: a user-friendly graphical interface to Bioconductor tools that enables accurate microarray data analysis and expedites comprehensive functional analysis of microarray results.
Microarray data analysis presents a significant challenge to researchers who are unable to use the powerful Bioconductor and its numerous tools due to their lack of knowledge of R language. Among the few existing software programs that offer a graphic user interface to Bioconductor packages, none have implemented a comprehensive strategy to address the accuracy and reliability issue of microarray data analysis due to the well known probe design problems associated with many widely used microarray chips. There is also a lack of tools that would expedite the functional analysis of microarray results. We present Microarray Я US, an R-based graphical user interface that implements over a dozen popular Bioconductor packages to offer researchers a streamlined workflow for routine differential microarray expression data analysis without the need to learn R language. In order to enable a more accurate analysis and interpretation of microarray data, we incorporated the latest custom probe re-definition and re-annotation for Affymetrix and Illumina chips. A versatile microarray results output utility tool was also implemented for easy and fast generation of input files for over 20 of the most widely used functional analysis software programs. Coupled with a well-designed user interface, Microarray Я US leverages cutting edge Bioconductor packages for researchers with no knowledge in R language. It also enables a more reliable and accurate microarray data analysis and expedites downstream functional analysis of microarray results.


[Monocyte-macrophage activation syndrome].
The activation of macrophage after stimulations (infectious, immunologic, irritative) is the ability of this cell to destroy intracellular bacteria and tumoral cells. Activated macrophage is characterized by morphological, biological and immunological properties and by its phagocytosis ability. The activation of macrophage can explain most of the signs encountered in several diseases: familial hemophagocytic lymphoreticulosis, accelerated phases of some immunodeficiencies but also protection of the organism against infectious diseases, immunological tolerance and antitumoral immunity.


[Resistance of nongroupable streptococci to beta-lactams. Detection by antibiogram and the activity of combinations of penicillin G and gentamicin].
Expression of disk-diffusion method of the activity of penicillin G against 68 strains of ungroupable streptococci susceptible to this drug (MIC less than or equal to 0.12 mg/l), 30 strains with a reduced susceptibility ("s") (0.25 mg/l less than or equal to MIC less than or equal to 1 mg/l), and 16 resistant (R) (MIC greater than or equal to 2 mg/l) has been studied. Generally, the R strains exhibited reduced inhibition zone diameters around the penicillin G disks but were best screened with an oxacillin disk (5 micrograms) as it has been proposed for the pneumococci. The study of the relations between the MICs of penicillin G and zone diameters obtained with oxacillin disks showed that the strains with oxacillin zones of less than 21 mm were R or "s". The strains with oxacillin zones less than 26 mm should be tested for sensitivity to penicillin by measurement of MIC. The resistance was crossed towards amoxicillin, cefotaxime, and at a lower degree imipenem. However, the routine test of amoxicillin and cefotaxime did not allow the detection of the resistance to these drugs. Amoxicillin and cefotaxime might not be tested by disk-diffusion method because of the cross resistance to penicillin G. Combinations of penicillin G with gentamicin resulted in bactericidal effects in 6 h or less for 6 of 7 strains tested.


[The concept of liberty in Jaspers' psychopathology].
The debate on conceptional problems represents a fundamental and inevitable challenge also for contemporary biological psychiatry. Especially questions concerning liberty, loss of liberty and regaining liberty are relevant for daily psychiatric practice. This study attempts to critically and systematically investigate the answers given in the philosophy and psychopathology of Karl Jaspers. Thereby, the key term "Grenzsituation" (border situation) plays a significant role. The interpretation of psychiatric disorder as an exceptional state of existence, possibly converting "Alltagssituationen" (situations of daily life) to "Grenzsituationen", sheds new light on Jaspers' thoughts about the concept of liberty which, thus, turn out to be of crucial relevance for the necessary discussions of ethical principles in the era of molecular psychiatry.


Molecular and biological characteristics of the infectious bronchitis virus TC07-2/GVI-1 lineage isolated in China.
In the present study, a thorough comparison of the infectious bronchitis virus (IBV) TC07-2/GVI-1 linage was conducted by comparing the S1 gene sequences of GVI-1 viruses with those of viruses representing the established genotypes and lineages. IBV GVI-1 strains were found to be closely genetically related to each other, irrespective of where the viruses were isolated, and differed from other known IBV genotypes and lineages; thus, it was confirmed that GVI represents a novel genotype. However, the GVI-1 viruses exhibited variable antigenicity when compared to each other. Further analysis found that strains CO8089L and CO8091L, which were isolated in Colombia in 2003, were closely related to GVI-1 viruses, suggesting that GVI-1 viruses likely originated from Colombia and are prevalent in at least five countries (Colombia, China, the Republic of Korea, Japan, and Vietnam). Analysis of the complete GVI-1 virus genomes suggested that the GVI-1 strains in China may be independently derived from recombination events that occurred between GI-19 strains and CO8089L/CO8091L-like viruses following the introduction of the viruses from Colombia. Similar to the viruses isolated in the Republic of Korea, GVI-1 viruses isolated in China also showed an affinity for the respiratory tract of chickens, which differed from one of the deduced parental viruses, the GI-19 strain. This difference may be due to recombination events that occurred in the genomes of the GVI-1 viruses, resulting in the replacement of the spike gene sequences in an YX10-like strain of GI-19 lineage.


Bone Density Screening in Postmenopausal Women With Early-Stage Breast Cancer Treated With Aromatase Inhibitors.
In postmenopausal women with breast cancer treated with aromatase inhibitors (AIs), most expert panels advise baseline bone mineral density testing with a dual-energy x-ray absorptiometry (DXA) scan repeated every 1 to 2 years. How often this recommendation is followed is unclear. We performed a retrospective analysis of women with stage I to III breast cancer who started AI therapy from January 1, 2008, to December 31, 2010, with follow-up through December 31, 2012, by using the SEER-Medicare database. Selection criteria included AI use for ≥ 6 months and no recent osteoporosis diagnosis or bisphosphonate use. We used multivariable logistic regression to investigate associations between patient characteristics and receipt of a baseline DXA scan. In patients who continued AI treatment, we assessed rates of follow-up scans. In the sample of 2,409 patients (median age, 74 years), 51.0% received a baseline DXA scan. Demographic characteristics associated with the absence of a baseline DXA scan were older age (85 to 94 years v 67 to 69 years; odds ratio [OR], 0.62; 95% CI, 0.42 to 0.92) and black v white race (OR, 0.68; 95% CI, 0.47 to 0.97). Among patients who underwent a baseline DXA scan and continued AI for 3 years, 28.0% had a repeat DXA scan within 2 years and 65.9% within 3 years. In aggregate, of the 1,164 patients who continued with AI treatment for 3 years, only 34.5% had both a baseline and at least one DXA scan during the 3-year follow-up period. The majority of older Medicare beneficiaries with breast cancer treated with AIs do not undergo appropriate bone mineral density evaluation.


Outcomes at a Minimum of 2 Years After Medial Collateral Ligament Reconstruction Using Partial-Thickness Quadriceps Tendon-Bone Autograft.
This study reports outcomes at a minimum of 2 years after a technique using quadriceps tendon-bone autograft for medial collateral ligament reconstruction. This technique effectively restored medial stability in medial collateral ligament-deficient knees. It is particularly valuable when nonirradiated allograft is unavailable or harvesting medial knee restraints (semitendinosus) for medial collateral ligament reconstruction is to be avoided. [Orthopedics. 2017; 40(3):e557-e562.].


Health-related quality of life outcomes from CABARET: a randomized phase 2 trial of carboplatin and bevacizumab in recurrent glioblastoma.
In recurrent glioblastoma, health-related quality of life (HRQL) is a crucial trial endpoint. We examined HRQL outcomes as a secondary endpoint for patients in the CABARET randomized phase 2 trial. 122 patients were randomly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin. We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Brain Cancer Module (QLQ-BN20), together with time to deterioration in HRQL, and the proportion of participants with clinically meaningful improvements in specific disease-related symptoms. At baseline, 117 of 122 randomized patients (96%) attempted questionnaires. Questionnaire participation rates were >90% for patients continuing on treatment, however at the end-of-treatment visit only 72 (64% of eligible participants) returned a form. There were no differences between arms in change scores over the treatment period. Time to ≥10 point deterioration in scores from baseline was also similar between arms. HRQL deterioration occurred largely before progression for the domains tested, but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50% of patients with symptoms at baseline. Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab, with a proportion of patients on both arms experiencing symptomatic benefit. Given the reduced questionnaire completion at end of treatment, time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population. Clinical trials registration number: ACTRN12610000915055.


Morphine and pain: effects on aspartate, GABA and glutamate in four discrete areas of mouse brain.
Experiments were performed to evaluate the effects on the levels of aspartate, GABA and glutamate in the periaqueductal central gray matter, hypothalamus, midbrain reticular formation and cortex of mouse brain following various treatments. The results indicate that only glutamate among the 3 neurohumors is systematically altered relative to the experimental manipulations. Moreover, among the 4 brain areas examined, the data implicate only the periaqueductal central gray matter as a locus of morphine's antinociceptive action. Morphine also appears to produce a drug-specific effect in hypothalamus which, however, is not analgesia-related. There were no significant pain, stress or drug-related effects on the levels of glutamate in either the midbrain reticular formation or the cortex.


Development of microwave imaging reflectometry in large helical device.
Three key devices of the microwave imaging reflectometry (MIR) are under development in large helical device (LHD). The 2-D mixer array is developed by stacking the one-dimensional array of the planar Yagi-Uda antenna. The new type of the bandpass filter bank is modified to match the requirement of the MIR. The low-cost quadrature demodulator is also developed for the phase detection system. By using the low-price commercial wireless devices, the development cost becomes much lower than the expensive waveguide system. These devices enable the development of 2-D/3-D microwave imaging system for the plasma diagnostics and industrial applications.


[Pelvic varicose veins thrombosis in a patient with pulmonary embolism].
We describe hereafter a case of idiopathic varicose veins in a patient with pulmonary embolism. To our knowledge, the condition has not been reported yet in the literature and enhances the usefulness of complementing the workup of pulmonary embolism by pelvic examination.


A study of relapse after MDT in a district in West Bengal, India.
A study was undertaken to estimate the magnitude of the problem of relapse and to identify factors responsible for relapse in leprosy units that were delivering MDT in Purulia District of West Bengal. From records patients were classified as "Relapse" or "Not relapse". "Not relapse" patients were selected by simple random sampling from the Surveillance Register and were matched according to age, sex, and the leprosy control unit. 128 cases ("Relapse") and 128 controls ("Not relapse") were interviewed in the clinic using a pre-tested questionnaire. Details of methods to identify and confirm relapse were circulated to all reporting units for ensuring uniformity and reliability. NGOs covered 42% of the population, while the State Government covered the remaining. The patients had been followed up after completion of treatment for a period of two years in PB leprosy and for five years in MB leprosy. The study revealed that the relapse rate was 1.71/1000 person-years for original PB cases and 0.76/1000 person-years for original MB cases. The study also showed that history of contact with an active leprosy patient and irregular treatment led more PB cases to relapse than control cases. All patients with an initial BI of 3+ relapsed with a BI of 1+ or 2+.


Developmental psychiatry and intellectual disabilities: an American perspective.
The Natalie Cobbing Travelling Fellowship gives the opportunity to medical professionals trained in the Psychiatry of Intellectual Disabilities to gain experience in their field from centres overseas. This article concentrates on specialist work settings and the practice in developmental disabilities in Boston, USA. The authors conclude that such training opportunities not only are important educational milestones but also help in creating a network of professionals who can work together to improve standards of research and clinical practice across different cultural and ethnic divides.


Exercise-induced oxidative stress affects erythrocytes in sedentary rats but not exercise-trained rats.
Oxidant stress is one of the factors proposed to be responsible for damaged erythrocytes observed during and after exercise. The impact of exertional oxidant stress after acute exhaustive treadmill running on erythrocyte damage was investigated in sedentary (Sed) and exercise-trained (ET) rats treated with or without antioxidant vitamins C and E. Exhaustive exercise led to statistically significant increments in the levels of thiobarbituric acid-reactive substance (TBARS) and H2O2-induced TBARS in Sed rats and resulted in functional and structural alterations in erythrocytes (plasma hemoglobin concentrations, methemoglobin levels, and rise in osmotic fragility of erythrocytes with decrease in erythrocyte deformability). Administration of antioxidant vitamin for 1 mo before exhaustive exercises prevented lipid peroxidation (TBARS, H2O2-induced TBARS) in Sed rats without any functional or structural alterations in erythrocytes. Parameters indicating erythrocyte lipid peroxidation and deterioration after exhaustive exercise in rats trained regularly with treadmill running for 1 mo were not different from those in Sed controls. Erythrocyte lipid peroxidation (TBARS) increased in exhausted-ET rats compared with ET controls; however, the plasma hemoglobin, methemoglobin levels, and erythrocyte osmotic fragility and deformability did not differ. Exhaustive exercise-induced lipid peroxidation in ET rats on antioxidant vitamin treatment was prevented, whereas functional and structural parameters of erythrocytes were not different from those of the ET controls. We conclude that exertional oxidant stress contributed to erythrocyte deterioration due to exercise in Sed but not in ET rats.


Evolution of the Histo-Epidemiological Profile of Urological Cancers in Togo
Background: Urological cancers are an important public health issue and pose problems with diagnosis and adequate management in developing countries. Our aim was to determine and report epidemiological and histological features of urological cancers in Togo. Materials and methods: A retrospective descriptive study was conducted of cases of urological cancers observed in the laboratory of pathological anatomy of the CHU Tokoin over the last 4 years (2012-2016). The parameters studied were frequency, age, sex, sites of development and histological type. Results: Epidemiological data were collected for 182 cases, representing 16.4% of all cancers (1108 cases). The annual frequency was 45.5±1.1 cases on average. The male:female sex ratio was 8.6 with a mean age of 60.2 years. Regarding location, in decreasing order of frequency, the tumors were found in the prostate (n=121 cases; 66.5%), bladder (n=28; 15.4%), kidney (n=19; 10.4%), testis (n=10; 5%), penis (n=3; 1.7%) and scrotum (n=1; 0.5%). Histologically, prostate cancers were predominantly adenocarcinomas (n=116 cases; 95.8%) with a Gleason score of 6 (n=46; 39.7%) predominant. Bladder cancers were mainly squamous cell carcinomas (n=11; 39.3%) followed by transitional carcinomas (n=9 cases; 32.1%) and adenocarcinomas (n=7; 25%). Kidney cancers were predominantly nephroblastomas (n=10, 52.6%) in children and clear cell carcinomas (n=8 cases; 42.1%) in adults. Testicular cancers were Burkitt lymphomas in 5 cases. The cases of penis and scrotum cancers were all squamous cell carcinomas. Conclusion: Urological cancers are experiencing an upsurge in frequency in Togo, dominated by prostate cancer, with a high frequency of squamous cell carcinoma of the bladder due to endemic bilharziasis.


Ultrasound for the early diagnosis of tibial fracture healing after static interlocked nailing without reaming: histologic correlation using a canine model.
Ultrasound is thought to be clinically useful in evaluating bone formation through its presumed identification of fracture callus. However, documentation of the actual histology of the tissue identified by ultrasound has been lacking. The purpose of this study was to determine the histologic composition of the hyperechoic tissue "seen" by ultrasound. Unilateral fractures were created in eight canine tibias and then fixed by using locked intramedullary nailing without reaming. The limbs were studied at two, three, four, six, and eight weeks postoperatively with plain radiographs, ultrasound, and ultrasound-directed needle biopsy. The presence of a hyperechoic ultrasound signal was found to have a 100 percent correlation with the presence of hard fracture callus biopsy tissue. In addition, fracture union by ultrasound criteria significantly predated radiographic fracture union (5.6 vs. 7.3 weeks, p = 0.05). These results support and provide a scientific basis for the clinical use of ultrasound to assess tibial fracture healing following static interlocked nailing without reaming.


Histamine(H1) antagonists and airway hyperreactivity in the guinea-pig.
Ketotifen inhibits development of airway hyperreactivity in guinea-pigs exposed to PAF, (+/-)isoprenaline, immune complexes or endotoxin. Ketotifen is not a competitive histamine(H1) antagonist, so that it cannot be concluded that there is mandatory involvement of histamine in the development or expression of these forms of airway hyperreactivity. This conclusion has been reinforced by determining the efficacy of other histamine(H1) antagonists as inhibitors of PAF-induced airway hyperreactivity. When compounds were administered intravenously, at a dosage (1 mg/kg) which fully abolished responses to intravenous histamine, the observed rank order for inhibition of PAF-induced hyperreactivity was: ketotifen greater than cetirizine greater than acrivastine greater than KB-2413 greater than oxatomide greater than azelastine greater than terfenadine = astemizole = clemastine = mepyramine = loratadine = saline. Terfenadine may lack inhibitory activity because of a capacity to induce airway hyperreactivity in the guinea-pig. It can be concluded that inhibition of the development of airway hyperreactivity is not a characteristic of histamine(H1) antagonists.


Habits and self-efficacy moderate the effects of intentions and planning on physical activity.
Behavioural intentions as well as action planning can facilitate the adoption and maintenance of physical activity under certain conditions. The present study examined levels of plan-specific self-efficacy and habit strength as possible conditions that may modify this relationship. As a secondary analysis of a larger randomized trial to improve physical activity, n = 225 recipients of a planning intervention were followed up at five measurement points over one year. Two-level models were fit. Within-person levels, that is, fluctuations of intention and action planning around person means, were modelled to predict self-reported moderate-to-vigorous physical activity. Moreover, between-person, that is, average person, levels of self-efficacy and habit strength were specified as putative moderators of this relationship. The within-person intention-activity relationship was moderated by between-person levels of habit strength, yielding a compensatory effect: higher-than-usual intention predicted physical activity only when average activity habit levels were low. The within-person planning-activity relationship was moderated by between-person levels of self-efficacy, yielding a synergistic effect: higher-than-usual planning combined with high average self-efficacy resulted in highest physical activity levels. Higher-than-usual intention may only be required in the presence of low activity habits. Moreover, high self-efficacy seems to be required to translate higher-than-usual action planning into augmented physical activity because self-efficacious individuals may invest more efforts to enact their plans.


Hemophagocytic lymphohistiocytosis at initiation of kawasaki disease and their differential diagnosis.
The authors report a case of hemophagocytic lymphohistiocytosis that became apparent and was confirmed by a specific Th1/Th2 cytokine pattern at the initiation of Kawasaki disease in an 18-month-old child. His condition deteriorated fast and produced no response to intravenous immunoglobulin and dexamethasone. A standard HLH-2004 regimen was started. But he developed respiratory failure, seizure, and cardiac arrest, and died. This case is unique for developing hemophagocytic lymphohistiocytosis at the initiation of Kawasaki disease, with fatal outcome. This case may indicate a yet unknown mechanism triggers these 2 diseases; a specific Th1/Th2 cytokine pattern helps rapid differential diagnosis between these 2 diseases.


[Computed tomography in the diagnosis and selection of surgical treatment for angiodysplasia].
Fifty-five patients (31 males and 24 females) with various localization of angiodysplasia (the region of the pelvis and pelvic organs, trunk, head and face, and the limbs) were examined. Comparison of angiography and computed tomography of the 55 patients showed that only 8 cases (15%) of arteriovenous angiodysplasia had vascular changes characteristic of angiodysplasia in arteriography. Changes of vessels were not revealed by phlebography, whereas computed tomography yielded a positive result in 54 cases. Thus, computed tomography, even without the use of contrast intensification, is the main method for the diagnosis of venous-cavernous angiomatosis of organs and deeply situated tissues. Computed tomography makes it possible to determine the tactic and volume of operative treatment and to control the efficacy of the applied treatment.


In Vitro Inhibition of NFAT5-Mediated Induction of CCL2 in Hyperosmotic Conditions by Cyclosporine and Dexamethasone on Human HeLa-Modified Conjunctiva-Derived Cells.
To investigate the pro-inflammatory intracellular mechanisms induced by an in vitro model of dry eye disease (DED) on a Hela-modified conjunctiva-derived cells in hyperosmolarity (HO) stress conditions. This study focused on CCL2 induction and explored the implications of the nuclear factor of activated T-cells 5 (NFAT5) as well as mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NFĸB). This work was completed by an analysis of the effects of cyclosporine A (CsA), dexamethasone (Dex) and doxycycline (Dox) on HO-induced CCL2 and NFAT5 induction. A human HeLa-modified conjunctiva-derived cell line was cultured in NaCl-hyperosmolar medium for various exposure times. Cellular viability, CCL2 secretion, NFAT5 and CCL2 gene expression, and intracytoplasmic NFAT5 were assessed using the Cell Titer Blue® assay, enzyme-linked immunosorbent assay (ELISA), RT-qPCR and immunostaining, respectively. In selected experiments, inhibitors of MAPKs or NFκB, therapeutic agents or NFAT5 siRNAs were added before the hyperosmolar stimulations. HO induced CCL2 secretion and expression as well as NFAT5 gene expression and translocation. Adding NFAT5-siRNA before hyperosmolar stimulation led to a complete inhibition of CCL2 induction and to a decrease in cellular viability. p38 MAPK (p38), c-Jun NH2-terminal kinase (JNK) and NFĸB inhibitors, CsA and Dex induced a partial inhibition of HO-induced CCL2, while Dox and extracellular signal-regulated kinase (ERK) inhibitor did not. Dex also induced a partial inhibition of HO-induced NFAT5 gene expression but not CsA or Dox. These in vitro results suggest a potential role of CCL2 in DED and highlight the crucial role of NFAT5 in the pro-inflammatory effect of HO on HeLa-modified conjunctiva-derived cells, a rarely studied cellular type. This inflammatory pathway involving NFAT5 and CCL2 could offer a promising target for developing new therapies to treat DED, warranting further investigations to fully grasp the complete intracellular mechanisms.


Nanoprobe-based affinity mass spectrometry for selected protein profiling in human plasma.
In recent decades, magnetic nanoparticles have emerged as a promising new platform in biomedical applications, particularly bioseparations. We have developed an immunoassay using antibody-conjugated magnetic nanoparticles as an efficient affinity probe to simultaneously preconcentrate and isolate targeted antigens from biological media. We combined this probe with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI MS) to profile proteins in diluted human plasma. The nanoparticles were designed to detect several disease-associated proteins and could be used directly in MALDI MS without an elution step, thereby facilitating multiple antigen screening and the characterization of antigen variants. Plasma antigens bound rapidly (approximately 10 min) to the antibody-conjugated nanoparticles, allowing the assay to be performed within 20 min. With sensitivity of detection in the femtomole range, the nanoscale immunoassay is superior to assays using microscale particles. We applied our method to comparative protein profiling of patients with gastric cancer and healthy individuals and found differential protein expression levels associated with the disease as well as individuals. Given the flexibility of manipulating functional groups on the nanoprobes, their low cost, robustness, and simplicity of the assay, our approach shows promise for targeted proteome profiling in clinical settings.


Conditional-lethal mutations that suppress genetic defects in morphogenesis by altering structural proteins.
An analysis of revertants of missense mutants in phage P22 has shown: (i) New temperature-sensitive (TS) and cold-sensitive (CS) phenotypes are often acquired concomitant with reversion. (ii) In many cases, these new phenotypes are due to second-site mutations (suppressors) that correct the original defect. (iii) Sometimes the suppressor mutation is not in the same gene as the original mutation. (iv) Extragenic suppressors are almost always in genes whose products are known to interact physically with the original gene products. (v) The suppressor mutations typically retain their TS or CS phenotypes when crossed into wild-type genetic backgrounds. (vi) Some TS and CS mutants derived by reversion can themselves be reverted to produce additional mutations. We have shown that genetic reversion of missense mutants can be of value in producing new temperature-sensitive and cold-sensitive mutations affecting related functions. We suggest that our approach can be extended to organisms with large genomes.


A risk assessment framework for assessing metallic nanomaterials of environmental concern: aquatic exposure and behavior.
Nanomaterials are finding application in many different environmentally relevant products and processes due to enhanced catalytic, antimicrobial, and oxidative properties of materials at this scale. As the market share of nano-functionalized products increases, so too does the potential for environmental exposure and contamination. This study presents some exposure ranking methods that consider potential metallic nanomaterial surface water exposure and fate, due to nano-functionalized products, through a number of exposure pathways. These methods take into account the limited and disparate data currently available for metallic nanomaterials and apply variability and uncertainty principles, together with qualitative risk assessment principles, to develop a scientific ranking. Three exposure scenarios with three different nanomaterials were considered to demonstrate these assessment methods: photo-catalytic exterior paint (nano-scale TiO₂), antimicrobial food packaging (nano-scale Ag), and particulate-reducing diesel fuel additives (nano-scale CeO₂). Data and hypotheses from literature relating to metallic nanomaterial aquatic behavior (including the behavior of materials that may relate to nanomaterials in aquatic environments, e.g., metals, pesticides, surfactants) were used together with commercial nanomaterial characteristics and Irish natural aquatic environment characteristics to rank the potential concentrations, transport, and persistence behaviors within subjective categories. These methods, and the applied scenarios, reveal where data critical to estimating exposure and risk are lacking. As research into the behavior of metallic nanomaterials in different environments emerges, the influence of material and environmental characteristics on nanomaterial behavior within these exposure- and risk-ranking methods may be redefined on a quantitative basis.


A "countertransference cure" evoked by enactment.
A psychotherapeutic impasse, the product of projective identification, led to a countertransference enactment that had an immediate, profound, and beneficial effect on the patient that persisted and was explored during the therapy. The change was confirmed in a 20-year follow-up. The theoretical basis for this change is discussed from the point of view of the implications of enactment and using a model of personality change through life experience.


Efficacy and Safety of Clinically Driven Low-Dose Treatment with Direct Oral Anticoagulants in Asians with Atrial Fibrillation: a Systematic Review and Meta-analysis.
Although clinically driven low-dose (CDLD) treatment with direct oral anticoagulants (DOACs) is frequently administered to Asian patients with atrial fibrillation, clinical evidence confirming its efficacy remains insufficient. We evaluated the clinical efficacy and safety of CDLD treatment with DOACs compared to on-label dose treatment in Asian patients with atrial fibrillation and assessed the differences in the baseline characteristics between patients receiving these treatments. We searched the MEDLINE, CENTRAL, EMBASE, Web of Science, and Scopus databases for articles from inception through July 2020. Thirteen studies were included in this meta-analysis. The baseline characteristics of the CDLD group were significantly different from those of the standard dose (STD) and standard low-dose (SLD) groups. The incidences of thromboembolic events (risk ratio [RR] 0.46, 95% confidence interval [CI] 0.29-0.73, p < 0.001) and major bleeding (RR 0.55, 95% CI 0.35-0.87, p = 0.01) in the CDLD group were lower than those in the SLD group; however, they were comparable with those in the STD group. The incidence of a composite endpoint in the CDLD group was not significantly different from that in the STD group but was significantly lower than that in the SLD group (RR 0.50, 95% CI 0.38-0.65, p < 0.001). The clinical outcomes of CDLD treatment showed no difference compared to those of the STD treatment despite the vulnerable baseline characteristics of the CDLD group for thromboembolic and major bleeding events.


Graphene quantums dots combined with endonuclease cleavage and bidentate chelation for highly sensitive electrochemiluminescent DNA biosensing.
A novel strategy for highly sensitive electrochemiluminescence (ECL) detection of DNA was proposed based on site-specific cleavage of BamHI endonuclease combined with the excellent ECL activity of graphene quantum dots (GQDs) and bidentate chelation of the dithiocarbamate DNA (DTC-DNA) probe assembly. The difference between photoluminescence and ECL spectral peaks suggested that a negligible defect existed on the GQDs surface for generation of an ECL signal. The formed DTC-DNA was directly attached to the gold surface by bidentate anchoring (S-Au-S bonds), which conferred a strong affinity between the ligands and the gold surface, increasing the robustness of DNA immobilization on the gold surface. BamHI endonuclease site-specifically recognized and cleaved the duplex symmetrical sequence, which made the double-stranded DNA fragments and GQDs break off from the electrode surface, inducing a decrease of the ECL signal. Using hepatitis C virus-1b genotype complementary DNA (HCV-1b cDNA) as a model, a novel signal-off ECL DNA biosensor was developed based on variation of the ECL intensity before and after digestion of the DNA hybrid. Electrochemical impedance spectroscopy confirmed the successful fabrication of the ECL DNA biosensor. This ECL biosensor for HCV-1b cDNA determination exhibited a linear range from 5 fM to 100 pM with a detection limit of 0.45 fM at a signal-to-noise ratio of 3 and showed satisfactory selectivity and good stability, which validated the feasibility of the designed strategy. The proposed strategy may be conveniently combined with other specific biological recognition events for expansion of the biosensing application, especially in clinical diagnoses.


Obesity and arthritis.
Obesity affects over 20% of the UK's adult population and its prevalence is rising. Obesity can lead to a variety of musculoskeletal problems and is independently associated with locomotor disability and joint pain. Obesity increases the risk of radiographic knee osteoarthritis (OA), but has a lesser effect on disease progression. The association with hip and hand OA is weaker, but implies that excess adipose tissue produces humoral factors, altering articular cartilage metabolism. It has been postulated that the leptin system could be a link between metabolic abnormalities in obesity and increased risk of OA. Although obesity was initially thought to increase the risk of rheumatoid arthritis (RA), further studies showed, that heavier patients with RA have less radiological disease progression and possibly better survival. On the other hand, obesity is strongly associated with hypeuricaemia and gouty arthritis. High body weight correlates independently with metabolic syndrome and may contribute to increased cardiovascular morbidity in patients with gout. Weight reduction should be an important part of treatment for OA and gout. Because obesity at a young age correlates with the development of OA and gout in later life, preventive public health strategies aimed at lowering the incidence of obesity are of most importance.


Usefulness of the MNA in the long-term and acute-care settings within the United States.
The Mini Nutritional Assessment (MNA) is a tool that was developed for use with elders to provide rapid assessment of nutritional risk. Although this screening tool has been validated and frequently used in longterm and acute-care settings in Europe, the MNA has not been used extensively within the United States. The MNA may need to be validated for use within U.S. nursing and acute-care facilities because validity may be affected by the acuity of illness, the use of aggressive nutrition support, which makes the scoring of the MNA difficult, and the age of patients admitted for care (acute care). Additionally, in most long-term care settings, a specific screening tool (Minimum Data Set) is already required to assess resident function including nutritional risk. The MNA may be more useful in an assisted living facility, where nutrition screening and assessment tools are not currently in place, yet maintenance of functional status is important to prevent transfer to a nursing facility.


Immunoglobulin A monoclonal antibodies protect against Sendai virus.
Immunoglobulin A anti-Sendai virus HN protein monoclonal antibodies, generated via a mucosal immunization protocol, were shown to neutralize virus in vitro and, when passively administered to the mouse respiratory tract, to protect against Sendai virus in vivo. Thus, immunoglobulin A antibodies by themselves can protect against respiratory virus infection.


Robust isolation of malignant plasma cells in multiple myeloma.
Molecular characterization of malignant plasma cells is increasingly important for diagnostic and therapeutic stratification in multiple myeloma. However, the malignant plasma cells represent a relatively small subset of bone marrow cells, and need to be enriched prior to analysis. Currently, the cell surface marker CD138 (SDC1) is used for this enrichment, but has an important limitation in that its expression decreases rapidly after sampling. Seeking alternatives to CD138, we performed a computational screen for myeloma plasma cell markers and systematically evaluated 7 candidates. Our results conclusively show that the markers CD319 (SLAMF7/CS1) and CD269 (TNFRSF17/BCMA) are considerably more robust than CD138 and enable isolation of myeloma plasma cells under more diverse conditions, including the samples that have been delayed or frozen. Our results form the basis of improved procedures for characterizing cases of multiple myeloma in clinical practice.


Wireless technology in the ICU: boon or ban?
Wireless communication and data transmission are playing an increasing role in the critical care environment. Early anecdotal reports of electromagnetic interference (EMI) with intensive care unit (ICU) equipment resulted in many institutions banning these devices. An increasing literature database has more clearly defined the risks of EMI. Restrictions to the use of mobile devices are being lifted, and it has been suggested that the benefits of improved communication may outweigh the small risks. However, increased use of cellular phones and ever changing communication technologies require ongoing vigilance by healthcare device manufacturers, hospitals and device users, to prevent potentially hazardous events due to EMI.


Improved odds ratio estimation by post hoc stratification of case-control data.
We propose a logistic regression analysis of unmatched or frequency matched case-control studies with conditional maximum likelihood estimation through post hoc stratification. In this model fewer parameters have to be estimated. With a simulation study we show that parameter estimates have smaller variance and are less biased. Also, the residual confounding effect was quantified. A more refined post hoc stratification reduces computing time, but to the cost of a larger bias and a loss in efficiency. The model was also applied to data of unmatched case-control studies on laryngeal cancer, oesophageal cancer and lung cancer.


[A study on the relationship between Helicobacter pylori and chronic gastritis and peptic ulcer by the case-control method and sequential analysis].
The association between Helicobacter pylori and the chronic gastritis and peptic ulcer was investigated by the case-control method, 1:1 matched study and sequential analysis. The results of three methods showed that the degree of association between Helicobacter pylori and the chronic gastritis and peptic ulcer was significant (chi 2 = 22.70, P < 0.001, OR = 15.63, 95% CI of OR was 5.05, 48.43), especially that between Helicobacter pylori and active chronic gastritis (OR = 20.92). The results indicate that Helicobacter pylori might be an etiological factor for patients with chronic gastritis and peptic ulcer.


Flagellum tapering and midpiece volume in songbird spermatozoa.
In contrast to numerous studies on spermatozoa length, relatively little work focuses on the width of spermatozoa, and particularly the width of the midpiece and flagellum. In flagellated spermatozoa, the flagellum provides forward thrust while energy may be provided via mitochondria in the midpiece and/or through glycolysis along the flagellum itself. Longer flagella may be able to provide greater thrust but may also require stronger structural features and more or larger mitochondria to supply sufficient energy. Here, we use scanning electron microscopy to investigate the ultrastructure of spermatozoa from 55 passerine species in 26 taxonomic families in the Passerides infraorder. Our data confirm the qualitative observation that the flagellum tapers along its length, and we show that longer flagella are wider at the neck. This pattern is similar to mammals, and likely reflects the need for longer cells to be stronger against shearing forces. We further estimate the volume of the mitochondrial helix and show that it correlates well with midpiece length, supporting the use of midpiece length as a proxy for mitochondrial volume, at least in between-species studies where midpiece length is highly variable. These results provide important context for understanding the evolutionary correlations among different sperm cell components and dimensions.


Equilibrium spherically curved two-dimensional Lennard-Jones systems.
To learn about the basic aspects of nanoscale spherical molecular shells during their formation, spherically curved two-dimensional N-particle Lennard-Jones systems are simulated, studying curvature evolution paths at zero temperature. For many N values (N<800) equilibrium configurations are traced as a function of the curvature radius R. Sharp jumps for tiny changes in R between trajectories with major differences in topological structure correspond to avalanche-like transitions. For a typical case, N=25, equilibrium configurations fall on smooth trajectories in state space which can be traced in the E-R plane. The trajectories show up with local energy minima, from which growth in N at steady curvature can develop.


Depressive symptoms in Parkinson's disease are related to decreased left hippocampal volume: correlation with the 15-item shortened version of the Geriatric Depression Scale.
Background The relationship between hippocampal and amygdaloid volumes and depression in patients with Parkinson's disease (PD) is a controversial issue. Purpose To investigate the correlation between the 15-item shortened version of the Geriatric Depression Scale (GDS-15) and gray matter volume in PD. Material and Methods In the present study, 46 participants with PD were scanned with 3 T magnetic resonance imaging (MRI) to obtain three-dimensional (3D) T1-weighted (T1W) images. Neurologists specializing in movement disorders performed clinical evaluations of the participants (e.g. GDS-15, Mini-Mental State Examination, PD duration, age, sex). Statistical Parametric Mapping 8 software was used for image gray matter segmentation and for a correlation analysis between gray matter volume and GDS-15 score. Results The results showed a significant negative correlation between GDS-15 score and left hippocampal volume, and between GDS-15 score and right parahippocampal gyrus volume. No significant positive correlations were found in the whole brain. Conclusion The current results provide new evidence regarding the relationship between depression in PD and hippocampal volume.


The Effect of Drug Loading on Micelle Properties: Solid-State NMR as a Tool to Gain Structural Insight.
The present study highlights the importance of understanding the structural changes of micelles induced by drug loading on their physico-chemical properties. A block copolymer with attached fructose, which interacts with GLUT5 receptor, was used and conjugated with a low and a high amount of platinum drugs. Against expectations, the low-loading micelle, despite having a less defined morphology and larger nanoparticle size according to TEM, displays higher cellular uptake and higher toxicity. This behaviour can only be understood when elucidating additional information on the structure of micelles. Extensive solid-state NMR measurements were therefore employed to reveal that the drug loading affected swelling and mobility of core and shell of the micelle. The results obtained from solid-state NMR spectroscopy could explain all the observations on this system. In summary, solid-state NMR spectroscopy is an excellent tool to understand the effects of drug loading on the behavior of micelles.


Oral administration of glutathione improves memory deficits following transient brain ischemia by reducing brain oxidative stress.
Oxidative stress aggravates brain injury following ischemia. The glutathione (GSH) system plays a pivotal role in combating oxidative stress in various cell types. To determine whether oral GSH administration elicits anti-oxidative effects, we assessed its potential neuroprotective effects in transient bilateral common carotid artery occlusion (BCCAO) mice. In naïve mice, acute oral administration of GSH significantly increased GSH levels by 1h in the cortex and hippocampus. Eleven days after BCCAO, untreated mice showed significantly decreased GSH levels and an inverse elevation of glutathione-disulfide (GSSG) levels in both the cortex and hippocampus. Oral administration of GSH (100 and 500 mg/kg p.o.) for 10 consecutive days after ischemia restored reduced GSH levels and inhibited GSSG elevation. Notably, post-administration of GSH (100 and 500 mg/kg p.o.) significantly prevented neuronal cell death in the hippocampal CA1 region in BCCAO mice, an effect closely correlated with decreased levels of oxidative markers such as 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2-deoxyguanosine (8-OHdG) and nitrotyrosine in that region. Finally, GSH administration for 10 days improved memory deficits observed in BCCAO mice. Taken together, our findings indicate that the anti-oxidative effect of oral GSH administration ameliorates post-ischemia neuronal cell death and, in turn, may improve memory.


A review of world literature finds iron oxides noncarcinogenic.
Iron oxide appeared in the first list of 154 Threshold Limit Values adopted by the American Conference of Governmental Industrial Hygienists at its April 1949 annual meeting. It was set to control dust and fume at the recommended value of 15 mg/M3, at the time, the limit for an inert or "nuisance" dust, and was based on studies of welders made earlier by the U.S. Dept. of Labor and by Drinker and Nelson. By 1964, the TLV was tentatively reduced to 10 mg/M3 after a considerable body of literature had accumulated not only on the health experience of welders, but of other occupations involving iron oxides as well. As a group, these studies indicated that 15 mg/M3 permitted too great accumulations of iron pigmentation in the lung whose chronic retention effects were not known with certainty. Also, an occasional report of cancer of the lungs appeared particularly among British hematite miners, although these findings were immediately questioned on statistical grounds. In seeming confirmation of these early reports of cancer, an alarming number of reports of cancer of the lung and respiratory tract among welders and foundrymen began to appear by 1970, reaching a crescendo by the end of that decade. As past chairman of the TLV Committee, I decided to examine the bases of these findings. This review is the result of this examination.


Diastereomer-differentiating photochemistry of beta-arylbutyrophenones: Yang cyclization versus type II elimination.
The diastereomers of ketones 2 and 3 are shown to exhibit distinct photochemical reactivities due to conformational preferences; while the anti isomers of 2 and 3 undergo efficient Yang cyclization in 75-90% yields with a remarkable diastereoselectivity (> 90%), the syn isomers predominantly undergo Norrish Type II elimination. The differences in the product profiles of the diastereomers are consistent with a mechanistic picture involving the formation of precursor diastereomeric triplet 1,4-biradicals in which the substituents at alpha and beta-positions stabilize the cisoid (cyclization) or transoid (elimination) geometry. The fact that such a diastereomeric relationship does indeed ensue at the triplet-excited-state itself is demonstrated via the nanosecond laser-flash photolysis of model ketones 1. The diastereomeric discrimination in the product profiles observed for ketones 2 and 3 as well as in the triplet lifetimes observed for ketones 1 can both be mechanistically traced back to different conformational preferences of the ground-state diastereomeric ketones and the intermediary 1,4-biradicals. Additionally, it emerges from the present study that the syn and anti diastereomers of ketones 2 and 3 represent two extremes of a broad range of widely examined butyrophenones, which lead to varying degrees of Yang photocyclization depending on the alkyl substitution pattern.


A triple-stain technique for evaluating normal acrosome reactions of human sperm.
A triple-stain technique has been developed to score normal acrosome-reacted human sperm in fixed smears. Live and dead sperm are first differentiated using the vital stain trypan blue. Sperm are then fixed in glutaraldehyde, dried onto slides, and the postacrosomal region and acrosome are differentiated using Bismark brown and Rose Bengal. Slides are examined at 1,000 X with a bright-field microscope and assessed for 1) the percentage of sperm that were alive at the time of fixation and 2) the percentage of sperm that had undergone normal acrosome reactions. Experiments are included that show that trypan blue is a reliable stain for dead sperm and that Rose Bengal stains only sperm having intact acrosomes. This technique may have applications in experimental and clinical studies on sperm capacitation, acrosome reactions, and fertilization in laboratory and domestic animals as well as in man.


Bone mineral density decrements and children diagnosed with cancer.
This integrative literature review is focused on (1) the prevalence of bone mineral density (BMD) decrements in children treated for acute lymphoblastic leukemia (ALL), and when these decrements are observed; (2) the risk factors associated with the development of decreased BMD and resultant complications in children treated for ALL; (3) the role, if any, that corticosteroids play in decreasing BMD in children treated for ALL; (4) interventions that can potentially manage bone loss in people treated for ALL during childhood or adolescence. The results showed that people who have been diagnosed with ALL can have decrements in BMD. The etiology of BMD decrements can be attributed to multiple factors including genetic endowment, lifestyle behaviors, the leukemia disease process, and treatment exposures especially to corticosteroids and cranial radiotherapy. Male gender, age greater than 10 years, and physical inactivity are associated with BMD decrements in ALL survivors. The role of pediatric oncology nurses in the management of bone disease in children with cancer across the illness trajectory is discussed.


A statistical model for functional mapping of quantitative trait loci regulating drug response.
Differential drug response, that is, pharmacodynamics, is most often likely to be a complex trait, controlled by the combined influences of multiple genes and environmental influences. Genetic mapping has proven to be a powerful tool for detecting and identifying specific genes affecting complex traits, that is, quantitative trait loci (QTL), based on polymorphic markers. In this article, we present a novel statistical model for genetic mapping of QTL governing pharmacodynamic processes. In principle, this model is a combination of functional mapping proposed to map function-valued traits and linkage disequilibrium mapping designed to provide high-resolution mapping of QTL by making use of recombination events created at a historic time. We implement a closed-form solution for the Expectation-Maximization algorithm to estimate the population genetic parameters of QTL and the simplex algorithm to estimate the curve parameters describing the pharmacodynamic changes of different QTL genotypes in response to drug dose or concentrations. Extensive simulations are performed to investigate the statistical properties of our model. The implications of our model in pharmacogenetic and pharmacogenomic research are discussed.


Elite formation under occupation: the internal stratification of palestinian elites in the West Bank and Gaza Strip.
This paper examines the internal stratification of Palestinian elites in the West Bank and Gaza Strip under Israeli occupation. Our general aim is to clarify the extent to which social and political subordination to outside rule influences the development of indigenous elites in stateless societies. In contrast to nation-state societies, such elites may be horizontally stratified into a wider range of institutional settings, and vertically stratified by anti-occupation activism alongside the attainment of occupational prestige. In addition, context-specific determinants of their stratification patterns, such as refugee status, regionality, and country in which educational credentials were acquired, should be considered. A secondary content analysis of interviews conducted by the Palestinian Panorama centre with 249 elite members reveals, that the vertical stratification of Palestinian elites along occupational attainment and anti-occupation activism constitutes two quite independent status dimensions. A multinomial logit regression shows that, horizontally, elite groups are embedded in four distinct types of institutional activity, further demonstrating the multi-faceted formation of Palestinian elites. Contextual resources, such as refugee versus non-refugee status, regionality, and the acquiring of Western credentials, have differential effects on the vertical and horizontal stratification of Palestinian elites. The implications of these findings for further research on elite formation in the post-Oslo Palestinian society and in other stateless societies are discussed in conclusion.


Incidental detection of late presenting co-arctation of the aorta on chest x-ray: the importance of rib notching.
A 31-year-old obese male presented to the emergency department with symptoms and signs suggestive of a viral upper respiratory tract illness with a background of low exercise tolerance. Rib notching was identified on plain film chest radiography and subsequent CT of the thorax identified a moderately tight 2-mm juxta-ductal co-arctation of the aorta with multiple enlarged chest wall collaterals. The patient underwent a two-stage percutaneous procedure involving stent insertion and angioplasty up to 16 mm with significant improvement in exercise capacity and a modest reduction in blood pressure.


Structural Neuroimaging Findings in Mild Traumatic Brain Injury.
Common neuroimaging findings in mild traumatic brain injury (mTBI), including sport-related concussion (SRC), are reviewed based on computed tomography and magnetic resonance imaging (MRI). Common abnormalities radiologically identified on the day of injury, typically a computed tomographic scan, are in the form of contusions, small subarachnoid or intraparenchymal hemorrhages as well as subdural and epidural collections, edema, and skull fractures. Common follow-up neuroimaging findings with MRI include white matter hyperintensities, hypointense signal abnormalities that reflect prior hemorrhage, focal encephalomalacia, presence of atrophy and/or dilated Virchow-Robins perivascular space. The MRI findings from a large pediatric mTBI study show low frequency of positive MRI findings at 6 months postinjury. The review concludes with an examination of some of the advanced MRI-based image analysis methods that can be performed in the patient who has sustained an mTBI.


Temperature-Dependent Infrared Refractive Index of Polymers from a Calibrated Attenuated Total Reflection Infrared Measurement.
We demonstrate a straightforward method by which a commonly available reference sample such as water can be used to calibrate an attenuated total internal reflection infrared absorbance measurement in order to account for the polarization of the beam incident on the internal reflecting element, and the spread of angles about the nominal angle of incidence. This enables quantitative comparison of attenuated total reflection-derived absorbance data with spectra calculated from optical constants. We then apply this calibration to the measurement of temperature-dependent absorption spectra of a polydimethylsiloxane sample. We illustrate that the extracted optical constants scale with the temperature-dependent changes in the polymer density better than the raw absorbance values on vibrational resonance.


[Asymptomatic choledocholithiasis associated with diabetic neuropathy. Report of a case].
A case of severe autonomic diabetic neuropathy with abolished visceral pain sensitivity is reported. A patient was admitted who presented jaundice without abdominal pain. Diabetes was diagnosed. The pathogenesis of jaundice was traced to the inflammation of a postoperative stenosis of the choledochus. An episode of gallstone disease had occurred 7 years before. Interestingly, although there were stones located both in the gallbladder and in the distal extremity of the choledochus, no pain was present. Possible relationships between gallstone disease and diabetic autonomic neuropathy are discussed.


Inversion of Ferrimagnetic Magnetization by Ferroelectric Switching via a Novel Magnetoelectric Coupling.
Although several multiferroic materials or heterostructures have been extensively studied, finding strong magnetoelectric couplings for the electric field control of the magnetization remains challenging. Here, a novel interfacial magnetoelectric coupling based on three components (ferroelectric dipole, magnetic moment, and antiferromagnetic order) is analytically formulated. As an extension of carrier-mediated magnetoelectricity, the new coupling is shown to induce an electric-magnetic hysteresis loop. Realizations employing BiFeO_{3} bilayers grown along the [111] axis are proposed. Without involving magnetic phase transitions, the magnetization orientation can be switched by the carrier modulation driven by the field effect, as confirmed using first-principles calculations.


Bioavailability of [2-(14)C]quercetin-4'-glucoside in rats.
[2-(14)C]quercetin-4'-glucoside (4 mg/kg body weight) was fed by gavage to rats housed in metabolic cages, and over an ensuing 72 h period, radiolabeled products in body tissues, plasma, feces, and urine were monitored by high-performance liquid chromatography with online radioactivity and MS2 detection. One and 6 h after ingestion, while in the small intestine, the flavonol glucoside was converted to glucuronide and methylated and sulfated derivatives of quercetin, but only trace amounts of these metabolites were excreted in urine. On entering the cecum and the colon, the flavonol metabolites declined as they were converted to phenolic acids, principally 3-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid, by the colonic microflora. Feces contained mainly 3-hydroxyphenylacetic acid. Urine collected 0-12 and 0-24 h after ingestion contained radiolabeled hippuric acid and 3-hydroxyphenylacetic acid. 14C-Hippuric acid declined markedly in the 24-48 and 48-72 h urine samples, and there was a concomitant increase in labeled benzoic acid. There was minimal accumulation of radioactivity in plasma, despite a 69% recovery of label in urine over the 72 h period, and likewise, very little radioactivity was detected in body tissues out with the gastrointestinal tract. This is reflected in the fact that 72 h after ingestion 96% of the ingested radioactivity was recovered in feces, urine, and the cage washes, which comprise a mixture of urine and feces. The study reveals that as it passes through the gastrointestinal tract, almost all of the of [2-(14)C]quercetin-4'-glucoside is converted to phenolic acids, compounds not monitored in previous flavonol bioavailability studies with model animal systems, some of which have used exceedingly high doses of the aglycone quercetin (500 mg/kg body weight), which is not a normal dietary component.


Novel aneurysm neck reconstruction device: initial experience in an experimental preclinical bifurcation aneurysm model.
Treatment of wide-necked bifurcation aneurysms often poses procedural and long-term outcome challenges. The initial preclinical experience with the Pulsar Vascular Aneurysm Neck Reconstruction Device (PVANRD) in a canine bifurcation model is described. Experimental bifurcation vein pouch aneurysms were surgically created in the carotid arteries of eight dogs. Endovascular coiling of the aneurysms with assistance of the PVANRD was performed in all cases with acute performance compared with Y-stenting. Twelve devices were deployed in the eight cases. Deployment of the devices was straightforward and successfully protected the parent artery and maintained patency of the bifurcation in all cases, despite the use of oversized coils. The PVANRD is a novel bifurcation stent that facilitates treatment of wide-necked bifurcation aneurysms compared with currently available adjunctive devices.


Influence of the a-ring on the redox and nuclease properties of the prodigiosins: importance of the bipyrrole moiety in oxidative DNA cleavage.
Prodigiosin (Prod, 1) is the parent member of a class of polypyrrole natural products that exhibit promising immunosuppressive and cytotoxic activity. They can facilitate copper-promoted oxidative double-strand (ds) DNA cleavage through reductive activation of Cu(II). This is triggered by oxidation of the electron-rich Prod molecule and may provide a basis for the cytotoxicity of the prodigiosins. To gain an understanding of this activity, we prepared several Prod analogues with various A-ring systems to examine their electrochemical properties in acetonitrile (MeCN) as a means to establish a basis for structure-reactivity relationships in copper-promoted nuclease activity. The intact bipyrrole (BP) chromophore is critical for the copper-mediated nuclease properties of the Prods. In fact, simple BP systems are shown to facilitate oxidative single-strand (ss) DNA cleavage. Replacement of the Prod A-pyrrole ring with alternative arenes (phenyl, furan-2-yl, or thiophen-2-yl) inhibits DNA strand scission and raises the half-peak oxidation potential (E(p/2)) of the Prod free base [E(p/2) = 0.44 V vs saturated calomel electrode (SCE) in MeCN] by ca. 200 mV. The same effect was achieved through attachment of an electron-withdrawing group (acetyl) at the 5'-position of the A-pyrrole ring. The structural modifications that inhibit DNA cleavage correlate with known structure-reactivity relationships of Prods against leukemia and melanoma cancer cells. The implications of our findings with regard to the cytotoxicity of the Prods are discussed.


Production of curdlan-type polysaccharide by Alcaligenes faecalis in batch and continuous culture.
The biosynthesis of a thermogelable, extracellular homo-beta-(1 leads to 3)-glucan called "curdlan," has been studied in batch and continuous cultures of Alcaligenes faecalis var. myxogenes. Curdlan production is associated with the poststationary phase of a nitrogen-depleted, aerobic batch culture. Exopolymer is not detected in single-stage, carbon-limited continuous cultures but curdlan can be isolated from the effluent of a nitrogen-limited chemostat operating at a dilution rate (D) of less than 0.1 h-1. A spontaneous variant of strain ATCC 21680 was isolated and found to be compatible with long-term, nitrogen-limited chemostat culture. The specific rate of curdlan production is approximately four times higher in poststationary batch cultures than in single-stage continuous fermentations. The product yield (Yp/S) associated with batch processing (nongrowing cultures) is approximately 0.5 g curdlan/g glucose, with CO2 being the only detectable by-product.


Carbazole-Fluorene Copolymers with Various Substituents at the Carbazole Nitrogen: Structure-Properties Relationship.
Carbazole derivatives, carbazole-containing polymers and iridium complexes are of interest due to many possible applications in photonics, electronics and biology, particularly as active or hole-transporting layers in organic as well as perovskite devices due to their interesting properties. Here, a series of carbazole-fluorene conjugated copolymers with various substituents at the N-carbazole position (2-methoxycarbonylethyl, 2-carboxyethyl, 2-ethylhexyl, and nonan-2,4-dionatoiridium(III)bis(2-phenylpyridine-N,C2')-9-yl) was prepared by Suzuki coupling. Their photophysical, electrochemical and electroluminescence (EL) properties were studied. Effects of molecular weight and substituents attached to carbazole unit on their properties are reported. The carbazole-fluorene copolymers in dilute solutions exhibited intense photoluminescence (PL) emission in the blue spectral region with high PL quantum yields (78-87%) except for the copolymer with the iridium complex (23%). Similar PL spectra were observed in dilute solutions. More pronounced differences were found in thin film PL and EL properties due to excimer/aggregate formation. Light-emitting devices (LEDs) made of copolymers with 2-ethylhexyl as N-carbazole substituent exhibited efficient EL emission with the best performance and the lowest EL onset voltages (3-4 V), while the LEDs made of copolymers with other substituents were not as efficient, but showed anomalous behavior and memory effects in current-voltage characteristics promising also for bio-inspired electronics.


Creating mosaics: the interrelationships of knowledge and context.
This qualitative interpretivist study analyzed the interrelationships between the knowledge gained through continuing nursing education programs and the context of nurses' clinical practice. The content of nursing continuing education programs offered 9-12 months previously was reviewed. Forty semi-structured, tape-recorded interviews were conducted with nurses from hospitals, nursing homes and home care agencies to determine their use of this new knowledge. Findings indicate that nurses used information from continuing education programs to construct a knowledge base and that this process was affected by the structural, human resources, political and symbolic frames of the context in which nurses practice.


Does the choice of acute treatment influence future ulcer relapse?
Despite the fact that the direct effect of drugs used for healing of ulcers does not last longer than hours, or at most a few days, some clinical studies have indicated that the rate of new ulcers after short courses of treatment depends on the drug used for healing. Several studies have now shown that the development of new ulcers in the same, regardless whether active ulcers have been healed with antacids or histamine H2-receptor antagonists. This lack of difference in clinical outcome is very likely true also for sucralfate and omeprazole in comparison with histamine H2-antagonists. A bismuth compound can perhaps prolong the period of clinical remission in a subgroup of patients in whom campylobacter pylori do not recur after finalized ulcer healing treatment. Other factors, i.e. smoking, and not the choice of ulcer healing drug, are of importance to recurrencies of new ulcers.


The Fragment Network: A Chemistry Recommendation Engine Built Using a Graph Database.
The hit validation stage of a fragment-based drug discovery campaign involves probing the SAR around one or more fragment hits. This often requires a search for similar compounds in a corporate collection or from commercial suppliers. The Fragment Network is a graph database that allows a user to efficiently search chemical space around a compound of interest. The result set is chemically intuitive, naturally grouped by substitution pattern and meaningfully sorted according to the number of observations of each transformation in medicinal chemistry databases. This paper describes the algorithms used to construct and search the Fragment Network and provides examples of how it may be used in a drug discovery context.


Interrelation between Systemic Lupus Erythematosus and Thrombotic Thrombocytopenic Purpura.
Features suggestive of thrombotic thrombocytopenic purpura (TTP) are known to occur in patients with systemic lupus erythematosus (SLE). We report a patient who had TTP which resolved with plasma exchange and immunosuppression, but presented three years later with features of SLE. The diagnosis satisfied all the required criteria in both instances. The interrelationship between the two conditions is discussed.


Blunt abdominal trauma: current management.
Management of blunt abdominal trauma has evolved over the last decade and non-operative management (NOM), initially viewed with scepticism, has now become widely used. The aim of this retrospective study was to examine the results of liberal utilisation of NOM of blunt abdominal trauma. For that purpose we examined the charts of 119 patients admitted to our Department of Surgery from January 1998 to July 2006 for blunt abdominal trauma. NOM was opted for in cases of haemodynamic stability. When surgery was mandatory, it consisted in exploratory laparotomy or laparoscopy. Six of the NOM patients (7%) needed surgical exploration during the 24 hours following the trauma. Thus, the success rate for NOM was 93%. Mean length of hospital stay was 12.5 days (range: 2-78); for emergency surgery patients it was 17 days (range: 2-78), and for NOM patients 14.5 days (range: 2-45). In conclusion, NOM may be safely used in cases of blunt abdominal trauma. Haemodynamic instability, suspicion of hollow viscus perforation and multiple transfusions are contraindications to this approach.


[Effect of spinal anesthesia on peripheral hemodynamics].
In eight persons central hemodynamic parameters as well as peripheral circulatory parameters were measured before and during spinal anaesthesia (L3/4; 5 ml Carbostesin mit Adrenalin): heart rate, arterial pressure, central venous pressure, peripheral venous pressure, peripheral blood flow, venous capacity (Cv 70) using a venous pressure of 70 mm Hg (lethysmographic method) as well as intravascular basic volume. Intravascular basic volume and the venous capacity are representing total intravascular volume; changes in this parameter- in correlation to a well defind intravenous pressure - give information on the distensibility of capacitance vessels. During spinal anesthesia an increase in resting blood flow of the calf as well as in total blood volume was noted as a result of a decreasing total peripheral resistance and changes in blood distribution (shunting, nutritive blood supply). Intravascular total blood volume in the calf increased from 9.7 +/- 1.0 ml/100 ml to 10.9 +/- 1.1 ml/100 ml, being caused mainly by changes in basic volume not so much by changes in venous capacity. These results may be interpreted as an increase in distensibility of the low pressure vessels during spinal anesthesia.


Bisphenol A impairs decidualization of human uterine stromal fibroblasts.
This study examined the effect of bisphenol A (BPA) exposure on human uterine stromal fibroblast cells (HuF) undergoing decidualization. HuF cells were isolated and cultured for eight days in the presence of a decidualization-inducing cocktail, while concurrently exposed to physiological and supra-physiologic doses of BPA (1ng/mL, 10ng/mL, 0.5μg/mL, 10μg/mL and 20μg/mL). Decidualization markers, steroid hormone receptors and cell cycle gene expression were detected by qRT-PCR and cellular proliferation was assessed by KI-67 immunofluorescent staining and MTS assay. BPA impaired decidualization at 10μg/mL and 20μg/mL, but not at lower doses. Additionally, BPA at 20μg/mL decreased progesterone receptor and estrogen receptor-alpha compared to controls. The highest dose of BPA also reduced cellular proliferation and cyclin D2 expression compared to controls. These findings demonstrate that BPA disrupts in vitro decidualization of uterine stromal fibroblasts by altering steroid hormone receptor expression at higher concentrations but not at lower physiological doses.


The immunotherapy of patients with ovarian cancer.
Ovarian cancer is a leading cause of cancer mortality. Chemotherapy is effective in reducing tumor burden in a majority of patients, however, only approximately 20% of advanced disease patients will ultimately survive tumor free, and further treatment options are needed. Continuing advances in immunology make immunotherapy a promising area for future research. The design of immunotherapy strategies for ovarian cancer requires an understanding of the immune microenvironment of the peritoneal cavity, which is frequently involved with ovarian cancer metastases and is the site of its most devastating effects. Immunotherapy approaches for ovarian cancer include locoregional and systemic cytokine therapies, prophylactic and therapeutic vaccines, and adoptive immunotherapy strategies. This review will summarize previous clinical trials as well as future directions for research. Further progress in T-cell specific immune responses will require the identification of specific ovarian cancer antigens that are processed and presented on the surface of tumor cells in the context of specific HLA molecules. In addition, a more detailed understanding of functional relations between the peritoneal microenvironment and the metastatic process is required.


"Not Just a Receiver": Understanding Patient Behavior in the Hospital Environment.
Patient engagement leads to better health outcomes and experiences of health care. However, existing patient engagement systems in the hospital environment focus on the passive receipt of information by patients rather than the active contribution of the patient or caregiver as a partner in their care. Through interviews with hospitalized patients and their caregivers, we identify ways that patients and caregivers actively participate in their care. We describe the different roles patients and caregivers assume in interacting with their hospital care team. We then discuss how systems designed to support patient engagement in the hospital setting can promote active participation and help patients achieve better outcomes.


Effects of ginsenosides-Rb1 on exercise-induced oxidative stress in forced swimming mice.
The fleshy root of Panax ginseng C.A. Meyer (ginseng) is one of the most well-known and valued herbs in traditional Chinese medicine. Ginsenosides are considered mainly responsible for the pharmacological activities of ginseng. The purpose of this study was to investigate the effects of ginsenoside-Rb1 (G-Rb1) on swimming exercise-induced oxidative stress in male mice. A total of 48 animals were randomly divided into four groups, with twelve mice in each group. The first, second and third groups were designed as G-Rb1 treatment groups, got 25, 50 and 100 mg/kg bodyweight of G-Rb1, respectively. The fourth group was designed as the control group, got physiologic saline. The mice were intragastrically administered once daily for 4 weeks. The weight-loaded forced swimming test was conducted on the final day of experimentation. Then the exhaustive swimming time, blood lactate, serum creatine kinase (CK), malondialdehyde (MDA) and antioxidant enzymes in liver of mice were measured. The results showed that G-Rb1 could prolong the exhaustive swimming time and improve exercise endurance capacity of mice, as well as accelerate the clearance of blood lactate and decrease serum CK activities. Meanwhile, G-Rb1 could decrease MDA contents and increase superoxide dismutase, catalase, glutathione peroxidase activities in liver of mice. The study suggested that G-Rb1 possessed protective effects on swimming exercise-induced oxidative stress in mice.


Administration of mulberry leaves maintains pancreatic β-cell mass in obese/type 2 diabetes mellitus mouse model.
Type 2 diabetes mellitus is characterized by insulin resistance and pancreatic β-cell dysfunction. A decrease in β-cell mass, which occurs during the progression of Type 2 diabetes mellitus, contributes to impaired insulin secretion. Mulberry leaves contain various nutritional components that exert anti-diabetic and anti-atherogenic effects. The present study analyzed the effects of mulberry leaf intake on pancreatic β-cells to clarify the mechanisms underlying its anti-diabetic function. Mulberry leaves (Morus alba L.) were dried at 180 °C for 8 s in a hot-air mill and fed to obesity/Type 2 diabetes mellitus db/db mouse models at 5% (w/w) as part of a normal diet from 7 to 10, 15, or 20 weeks of age. An intraperitoneal glucose tolerance test was then performed on the mice. To evaluate the β-cell mass, the pancreas was subjected to immunohistological analysis with an anti-insulin antibody. A TUNEL assay and immunohistological analysis with a proliferation marker was also performed. Expression levels of endoplasmic reticulum stress-responsible genes and proliferation markers were assessed by quantitative RT-PCR. Intake of mulberry leaves maintained the β-cell function of db/db mice. Moreover, oral administration of mulberry leaves significantly decreased cell death by reducing endoplasmic reticulum stress in the pancreas. Mulberry leaves significantly increased proliferation of β-cells and the expression of pancreatic duodenal homeobox1 mRNA in the pancreas. Considered together, these results indicate that dietary mulberry leaf administration can maintain insulin levels and pancreatic β-cell mass, at least in part, by suppressing endoplasmic reticulum stress in Type 2 diabetes mellitus mouse models.


Protective effect of forphenicinol, a low molecular weight immunomodifier, against infection with Pseudomonas aeruginosa in mice and its mechanisms.
The oral administration of forphenicinol increased the survival rate of both normal and immunodepressed mice intraperitoneally or intratracheally infected with clinically isolated strains of Pseudomonas aeruginosa. The therapeutic effect of amikacin on intraperitoneal infection with P. aeruginosa was enhanced by combined use with forphenicinol. Forphenicinol did not enhance the bactericidal activity of polymorphonuclear cells (PMN) towards P. aeruginosa in vitro, but enhanced it in vivo. In vitro study indicated that the macrophages taken from mice treated with forphenicinol or the cultured supernatant of these macrophages enhanced the bactericidal activity of PMN. The protective effect of forphenicinol against P. aeruginosa infection was thus suggested to be due to macrophage activation followed by the enhancement of the bactericidal activity of PMN.


New species of Grubeulepis Pettibone, 1969 (Eulepethidae, Annelida) from northern Brazil.
Eulepethidae is one of the least diverse families of scale polychaetes, with only 23 species described thus far. In this study we describe an additional species of Grubeulepis from unconsolidated substrata from Maranhão, tropical Brazil (ca. 2°S). Grubeulepis serrata sp. nov. differs from other species of the family due to the presence of one pair of eyes, 14 pairs of branchiae, posterior lamellae beginning in the 27th segment, with hooked upper notochaetae and serrated outer edge acicular neurochaeta in the 3rd segment. The diagnosis of the genus formerly included species with 10-13 pairs of branchiae, and thus is modified to accommodate the 14 pairs of branchiae from the new species described here. Grubeulepis serrata sp. nov. shares with Grubeulepis mexicana (Berkeley Berkeley 1939) the number of lateral processes of the 12th elytra, the segment of the foliaceous lamellae and the presence of acicular neurochaeta in the 3rd segment, but they differ in the number of branchiae pairs, eyes and the notochaetae shape. Grubeulepis serrata sp. nov. shares with Grubeulepis geayi (Fauvel 1918) the spiny notochaetae with spoon-shaped distal end, but differ in the hooked upper notochaetae, amount of lateral processes, and elytra articulation.


Identification of a polymorphism in the transmembrane domain of the protooncogene c-kit in healthy subjects.
c-Kit is the receptor for stem cell factor (SCF) and is found on hematopoietic stem cells, mast cells, melanocytes, and germ cells. Aggregation of c-Kit by SCF regulates cell proliferation, differentiation, and survival. In the process of examining c-Kit, a polymorphism in the transmembrane domain of the protooncogene c-Kit was identified. This polymorphism consisted of an A-to-C transversion at nucleotide (nt) 1642, and was deduced to substitute leucine for methionine at codon 541. The frequency of the allele with 'C' at nt 1642 was 0.09 in 64 unrelated subjects. Analysis of a two-generation family with the polymorphism suggested that this polymorphism did not result in disease. This is the first report of a polymorphism in the transmembrane domain of c-Kit, and may be of value in understanding and following the function of c-Kit in normal subjects and in those with other abnormalities of c-Kit.


Tracheal laceration from endotracheal intubation in a cat.
Iatrogenic trauma to the upper airway as a result of the clinical use of endotracheal tubes has rarely been reported in domestic animals. This report describes a case of tracheal laceration in a cat after endotracheal intubation for a dental procedure under general anaesthesia. The diagnosis and successful management of the condition are discussed, and other complications of the use of cuffed endotracheal and tracheostomy tubes are considered.


Multiple interaction domains in FtsL, a protein component of the widely conserved bacterial FtsLBQ cell division complex.
A bioinformatic analysis of nearly 400 genomes indicates that the overwhelming majority of bacteria possess homologs of the Escherichia coli proteins FtsL, FtsB, and FtsQ, three proteins essential for cell division in that bacterium. These three bitopic membrane proteins form a subcomplex in vivo, independent of the other cell division proteins. Here we analyze the domains of E. coli FtsL that are involved in the interaction with other cell division proteins and important for the assembly of the divisome. We show that FtsL, as we have found previously with FtsB, packs an enormous amount of information in its sequence for interactions with proteins upstream and downstream in the assembly pathway. Given their size, it is likely that the sole function of the complex of these two proteins is to act as a scaffold for divisome assembly.


BDNF alters ERK/p38 MAPK activity ratios to promote differentiation in growth plate chondrocytes.
The ERK and p38 MAPK pathways are well-known transducers of signals that regulate proliferation and differentiation, but precisely how these pathways control growth plate chondrocyte development is unclear. For example, the ERK pathway has been reported to be required by some investigators but inhibitory to chondrocyte development by others. Moreover, how these two pathways interact to regulate chondrocyte development is even less clear. Using primary bovine growth plate chondrocytes and murine ATDC5 cells, we demonstrate that the ERK and p38 pathways have opposing effects on proliferation but are both absolutely required for differentiation. Two factors that promote chondrocyte differentiation, brain-derived neurotrophic factor (BDNF) and C-type natriuretic peptide, increase p38 activity while decreasing, but not completely inhibiting, ERK activity. The attenuation of ERK activity by BDNF occurs via p38-dependent raf-1 inhibition. The inhibition of raf-1 by p38 is direct, because purified p38 protein inhibits the kinase activity of purified active raf-1 as well as raf-1 immunoprecipitated from chondrocyte lysates. Moreover, IGF-I, which stimulates proliferation, suppresses p38 activation. This work describes a model wherein unopposed IGF-I promotes high ERK/p38 activity ratios favoring proliferation, whereas BDNF signals a transition to differentiation by decreasing the ERK/p38 activity ratio without completely inhibiting ERK, which involves the direct inhibition of raf-1 by p38.


Retrospective analysis of factors affecting the progression of chronic renal failure in adult polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is the commonest congenital cystic renal disease. Factors such as hypertension, urinary tract infection, hematuria, and proteinuria may affect the progression to chronic renal failure in ADPKD patients. Therapeutic interventions, such as the use of angiotensin converting enzyme inhibitors (ACEI) or diet modification, may impact the natural progression of the disease. We aim in this study to review a registry of ADPKD patients in order to compare the slow and fast progressors and identify possible predictors of progression and interventions that slow the progression of this disease. Sheffield Kidney Institute (SKI), one of the largest kidney institutes in Northern Europe, has registered a large number of ADPKD patients since 1981. SKI's computer network contains a wide range of information on these patients. We selected 94 adult polycystic patients from the SKI for retrospective analysis of factors affecting progression to chronic renal failure. Patients who doubled their s. creatinine in < or = 36 months were considered fast progressors (FP), while those who doubled their s. creatinine in > 36 months were regarded as slow progressors (SP). There were 70 patients in the FP group and 24 patients in the SP group. A third group of 137 patients consisted of non-progressors (NP) who had stable s. creatinine levels during the same period. We found that the incidence of hypertension, UTI, macroscopic and microscopic hematuria, and overt proteinuria in the FP group was higher than in the SP and NP groups. Modification of some factors, such as hypertension and UTI, may decrease the rate of the deterioration of renal function.


Depletion-Induced Encapsulation by Dumbbell-Shaped Patchy Colloids Stabilize Microspheres against Aggregation.
In this paper, we demonstrate the stabilization of polystyrene microspheres by encapsulating them with dumbbell-shaped colloids with a sticky and a nonsticky lobe. Upon adding a depletant, an effective short ranged attraction is induced between the microspheres and the smaller, smooth lobes of the dumbbells, making those specifically sticky, whereas the interaction with the larger lobes of the dumbbells is considerably less attractive due to their rough surface, which reduces the overlap volume and leaves them nonsticky. The encapsulation of the microspheres by these rough-smooth patchy dumbbells is investigated using a combination of experiments and computer simulations, both resulting in partial coverage of the template particles. For larger microspheres, the depletion attraction is stronger, resulting in a larger fraction of dumbbells that are attached with both lobes to the surface of microspheres. We thus find a template curvature dependent orientation of the dumbbells. In the Monte Carlo simulations, the introduction of such a small, curvature dependent attraction between the rough lobes of the dumbbells resulted in an increased coverage. However, kinetic constraints imposed by the dumbbell geometry seem to prevent optimal packing of the dumbbells on the template particles under all investigated conditions in experiments and simulations. Despite the incomplete coverage, the encapsulation by dumbbell particles does prevent aggregation of the microspheres, thus acting as a colloid-sized steric stabilizer.


Discriminant score for celiac disease based on immunohistochemical analysis of duodenal biopsies.
Celiac disease (CD) represents a spectrum, which includes cases with minor histological abnormalities (potential CD). The aim of this work is to evaluate the contribution of immunohistochemical analysis of duodenal biopsies to the diagnosis of gluten-related minor enteropathy. Duodenal biopsies from 56 patients with untreated CD and 56 controls were analyzed for CD3 and γδ intraepithelial lymphocyte number, γδ/CD3 ratio, and density of CD25+ lamina propria cells. A discriminant equation was obtained by which 61 more biopsies with normal villous architecture were blindly evaluated. All of the immunohistochemical parameters were significantly different between patients with CD and controls. None of the single parameters showed sufficient specificity for CD. The combination of all of the 4 markers resulted in the following discriminant equation: discriminant score (Dscore) = (CD3 × 0.06) - (γδ × 0.119) + (CD25 × 0.012) + (γδ/CD3 × 0.131) - 4.709. Using this Dscore, patients were correctly classified as celiac or controls in 97.3% of the cases. When this equation was applied to a validation set of 61 patients with normal villous architecture and unknown diagnosis, 92.9% of those with a positive score turned out to be patients with potential CD. A normal score, however, did not exclude this condition. Immunohistochemistry represents a specific tool for the diagnosis of CD, but does lack sensitivity in detecting all of the potential CD cases.


Growth inhibition of Leishmania tropica amastigotes in vitro by rifampicin combined with amphotericin B.
Rifampicin and Amphotericin B (AMB) were studied separately and in combination to determine their effect in vitro on intracellular Leishmania tropica amastigotes. On the fourth day of treatment, rifampicin at 200 micrograms ml-1 or AMB at 0.15 microgram ml-1 reduced the parasites' survival index (PSI) to 10% compared with the untreated control. In combination, there was a significant synergistic effect at several concentrations. The synergistic therapeutic effects were not accompanied by toxicity to the host cells, although each drug alone caused cellular degeneration in the ultrastructure of the parasites with the formation of large autophagic-like vacuoles, while the combination increased the percentage of degenerate cells.


Prevalence and determinants of erectile dysfunction among people with type 2 diabetes in Ilorin, Nigeria.
To determine the prevalence and determinants of Erectile Dysfunction (ED) among men with Type 2 diabetes mellitus. Seventy-seven adult men with Type 2 Diabetes Mellitus were assessed for Erectile Dysfunction using the 'IIEF-5' questionnaire. They were also assessed for the presence of certain clinical factors in other to determine their degree of correlation with ED. The mean age of the study subjects was 56.8(+/-2.4) years. Almost all (96.1%) were married. Forty-four (56.4%) men volunteered a history of Erectile Dysfunction. When assessed with the 'IIEF - 5' questionnaire, the prevalence of any degree of ED was 74% while moderate to severe ED was found in 39(51%) of the patients. The only clinical variables that had statistically significant correlation with ED were the age of the patients (p=0.04) as well as the duration of diabetes (p=0.04). - Erectile Dysfunction is a very common condition among men with Type 2 Diabetes mellitus in Ilorin, Nigeria and should therefore be routinely sought for by the clinicians. The two clinical factors that confer significant risk to development of ED, from this study are non-modifiable. More emphasis should therefore be placed on treatment rather than the prevention of this condition.