Development and characterization of mucoadhesive-thermoresponsive gels for the treatment of oral mucosa diseases.
The mucositis is an inflammatory, erosive and ulcerative process of the oral mucosa. It is usually caused by radiation, chemotherapy, infections, diabetes, smoking and it is characterized by severe pain and difficulty eating and can have a very serious impact on quality of life. A suitable treatment must ensure pain control and mechanical protection to promote mucosal healing. The purpose of this work was to study an in-situ gelling formulation to be sprayed onto the damaged oral mucosa by self-administration. The formulation must be able to quickly form a film when applied in the oral cavity. many batches were prepared mixing a thermosensitive polymer (poloxamer PF127 or P123) with mucoadhesive polymers polyvinylpyrrolidone (PVP), sodium carboxymethyl cellulose (NaCMC), Carbopol 971P, chitosan (CS). By an experimental design three suitable formulations were identified and loaded with the model drug benzydamine hydrochloride. The hydrogel based on 25.50% PF127, 0.20% PVP and 0.35% CS maintained its original properties (gelling, rheological and mucoadhesive) after loading and showing a sustained drug release. the selected hydrogel showed to be suitable for the treatment of mucositis, able to reduce the number of daily administration and to protect the damaged mucosa from mechanical and chemical solicitations.


Substance P induced hydrolysis of inositol phospholipids in guinea-pig ileum and rat hypothalamus.
The recent development of a sensitive assay procedure for monitoring the hydrolysis of inositol phospholipids allowed the detection of substance P-induced lipid hydrolysis in tissue slices of rat hypothalamus and guinea-pig ileum longitudinal smooth muscle. The EC50 values observed for substance P were similar on both tissues and corresponded well with the value previously reported for the rat parotid. Furthermore, the structure-activity profile for this response on all three tissues was similar and closely resembled that for ileum contraction. We therefore suggest that these three functionally distinct tissues possess the same subtype of substance P receptor coupled to inositol phospholipid hydrolysis, and that this receptor has the characteristics of the previously reported SP-P subtype.


Body composition in hypopituitary dwarfs before and during human growth hormone therapy.
The clinical characteristics and body composition of eight hypopituitary dwarfs (10.2-21.6 yr) were analyzed before and after 6 and 12 mo of growth hormone therapy. 2 IU 3 times/wk. Before treatment, growth rate was 1.8 +/- 0.7 cm/yr, height age was 2.0-12.8 yr less, and bone age 2.0-11.1 yr less than chronologic age. Total body water (TBW), lean body mass (LBM), extracellular water (ECW), and intracellular water (ICW) were below normal for chronologic age, but normal for height. Muscle mass (MM) was below normal for age and height. During HGH therapy, growth rate was 7.1 +/- 1.6 cm/yr in the first 6 mo and 7.8 +/- 1.4 cm/yr during the next 6 mo; the ratio of change in height age to change in chronologic age was greater than or equal to 1.0 in all patients and the ratio of change in bone age to change in height age was 1.2 in one patient and less than or equal to 1.0 in the others. TBW, LBM, ECW, and ICW increased according to height increments; however, MM increased at a faster rate than expected from the height gains. Also, a relative or absolute loss of total body fat was recorded during the first 6 mo of therapy. It is suggested (1) that among the body composition parameters studied, muscle mass is the tissue most closely reflecting the lack of HGH and also its therapeutic benefits and (2) evaluation of body composition in hypopituitary dwarfs in response to HGH therapy shows striking changes not reflected by the determination of stature or weight alone.


In vitro controlled release of antigen in dendritic cells using pH-sensitive liposome-polymeric hybrid nanoparticles.
A hybrid nanoparticle (NP) consisting of a pH sensitive lipid shell and a poly(lactic-co-glycolic) acid (PLGA) core was constructed. This hybrid NP has a mean size of 120.1 ± 8.8 nm and positively charged surface (zeta potential of 14.2 ± 1.4 mV). The lipid shell of the hybrid NP was quickly disintegrated in buffer with a pH of 5.5, which resembles the acidic environment of endosomes in dendritic cell (DC). Less than 20% of the antigen enclosed in pH-sensitive hybrid NP was released into human serum at physiological pH within 24 h, but more than 40% of the enclosed antigen was released within 8 h after pH was adjusted to 5.5. Fast uptake of the pH sensitive hybrid NP by DC was also observed. It was found that pH sensitive hybrid NP displayed faster degradation and antigen release compared to regular hybrid NPs after uptake by DC.


Phylogenetic studies of two rubredoxins from sulfate reducing bacteria.
The sequences of two rubredoxins isolated from the sulfate reducing bacteria: Desulfovibrio vulgaris and Desulfovibrio gigas have been elucidated. They have similar sequences but many more differences occur than would be expected from two bacteria of the same genus. Of the 52 sites, only 37 are occupied by identical residues. The primary structures are compared with those of the anaerobic bacteria rubredoxins of Clostridium pasteurianum, Micrococcus aerogenes, Pseudomonas oleovorans and Peptostreptococcus elsdenii: only 12 identities are found, mostly in the two clusters that contain two iron-bound cysteines each. A phylogenetic tree based on the primary structures is presented and possible relations with plant and bacterial ferredoxins are discussed. A secondary and tertiary structure stereochemically compatible with the sequence data, is proposed.


Distribution and risk assessment of trace metals in riverine surface sediments in gold mining area.
Recognizing the pollution characteristics and potential risks of trace metals in sediments are important to protect water ecosystem safety. In the present study, a systematic investigation was performed to assess the pollution and risk level of trace metals in river sediments located in the greatest gold production base in China. The geo-accumulation index was used to assess the contamination degree. The sediment quality guidelines and potential ecological risk index were employed to complete an ecological risk assessment. A non-carcinogenic health risk assessment was also carried out to evaluate potential adverse health risks. Correlations and principal component analyses were applied to check relationships among trace metals and ascertain potential pollution sources. The results suggested that the sediments in the river were most polluted by As, Cd, and Hg followed by Cu, Pb, and Zn. The assessment of potential human health risk revealed that there was no significant non-carcinogenic risk to the inhabitants. Gold mining and smelting activities and the long-term excessive application of fertilizers and agrochemicals were identified as the main anthropogenic releases. This study contributed an understanding that possible sources, contamination degree, and ecological risk level of trace metals in riverine surface sediments in a gold mining area.


Study of Pansalt® or Laminaria Ochroleuca seaweed powder as potential NaCl replacers in dry-cured foal "cecina".
This study aimed to evaluate the effect of the total or partial replacement of NaCl by a commercial low-salt mixture Pansalt® (T1) or Kombu (L. ochroleuca) seaweed powder (T2), respectively, on the quality properties of dry-cured foal "cecina". Salt reformulation unaffected fat percentages, decreased (P < 0.001) moisture and ash contents, while protein amounts increased (P < 0.001) in the T2 batch. Considering the physicochemical variables, any significant differences were observed among batches, except for a*, water activity, and springiness values. T1 and T2 samples presented a significant (P < 0.001) sodium decrease of 39% and 48%, respectively, as well as, potassium and magnesium increase (P < 0.001). In addition, the seaweed improved (P < 0.001) calcium, iron, phosphorus, and zinc contents. All batches showed similar lipid profiles and the nutritional indices were in line with the health recommendations. NaCl replacement increased the proteolysis, causing the increment (P < 0.001) of the free amino acids total contents, especially in T2 samples. Changes were also detected in the aromatic profile of our samples, where lipid-derived compounds predominated in the CON batches, while substances originating from carbohydrate fermentation and amino acid breakdown were prevalent in reformulated samples, particularly in T2. In addition, the salting treatments did not affect the sensory profile, except for saltiness (T2). Hence, data indicated that the employ of these potential NaCl alternatives, in particular T2 formulation, represents a favorable approach to achieving equine "cecinas" with an enhanced mineral and healthier profile, without altering most of the sensorial properties.


Beyond integration: modeling every pixel to obtain better structure factors from stills.
Most crystallographic data processing methods use pixel integration. In serial femtosecond crystallography (SFX), the intricate interaction between the reciprocal lattice point and the Ewald sphere is integrated out by averaging symmetrically equivalent observations recorded across a large number (104-106) of exposures. Although sufficient for generating biological insights, this approach converges slowly, and using it to accurately measure anomalous differences has proved difficult. This report presents a novel approach for increasing the accuracy of structure factors obtained from SFX data. A physical model describing all observed pixels is defined to a degree of complexity such that it can decouple the various contributions to the pixel intensities. Model dependencies include lattice orientation, unit-cell dimensions, mosaic structure, incident photon spectra and structure factor amplitudes. Maximum likelihood estimation is used to optimize all model parameters. The application of prior knowledge that structure factor amplitudes are positive quantities is included in the form of a reparameterization. The method is tested using a synthesized SFX dataset of ytterbium(III) lysozyme, where each X-ray laser pulse energy is centered at 9034 eV. This energy is 100 eV above the Yb3+ L-III absorption edge, so the anomalous difference signal is stable at 10 electrons despite the inherent energy jitter of each femtosecond X-ray laser pulse. This work demonstrates that this approach allows the determination of anomalous structure factors with very high accuracy while requiring an order-of-magnitude fewer shots than conventional integration-based methods would require to achieve similar results.


Development and psychometric validation of an educational support assessment scale for novice home healthcare nurses.
Educational support quality is an essential factor in determining the education of novice home healthcare nurses. This study developed a scale to assess the educational support provided by home healthcare agencies among novice home healthcare nurses. Hypothetical components were derived from a literature review, including experiential learning theory. Expert panels evaluated the initial scale items, and the scale was tested with 3000 agencies from April to June 2022. A total of 627 valid responses were analyzed. Exploratory factor analysis produced a four-subscale structure consisting of 34 items that supported the hypothesized components. Cronbach's alphas ranged 0.889 to 0.961, and the intraclass correlation coefficients ranged 0.703 to 0.905 in the test-retest survey. The educational support assessment scale developed for novice home healthcare nurses is valid and reliable. Managers in home healthcare agencies should apply the results of assessments using the scale to improve their human resource development.


Expression of invariant chain and pro-cathepsin L in Alzheimer's brain.
Inflammatory and immune systems are involved in the pathogenesis of Alzheimer's disease (AD), but those systems in the human brain have not been well identified. Cathepsin L might play a predominant role in the degradation of the invariant chain (Ii), which plays a critical role in antigen presentation to block the antigen-binding site of the major histocompatibility complex class II. We examined the expression of Ii and pro-cathepsin L (pCPL) in AD and normal brains by using immunohistochemistry. Ii expresses only in resting or mildly activated microglia, whereas pCPL strongly expresses in fully activated microglia but not in resting or mildly activated microglia in AD. Normal brain tissues have rarely been stained for Ii or pCPL. These results suggest that the activation of microglia leads to expression of a complex of Ii and human leukocyte antigen class II at first, and that further activation, which is followed by cluster formation and enlargement of microglia frequently seen in the AD brain, might cause pCPL expression to degrade Ii. Our study confirmed that microglia plays a central role in the immune system of the brain, and that an activation of microglia is involved in the pathogenesis of AD.


Patient-Reported Impact of Axial Spondyloarthritis on Working Life: Results From the European Map of Axial Spondyloarthritis Survey.
To evaluate work-related issues (WRIs) and their determinants in patients with axial spondyloarthritis (SpA) across Europe. The European Map of Axial Spondyloarthritis is a cross-sectional online survey (2017-2018) of unselected patients with self-reported axial SpA from 13 European countries. Participants were classified as active or inactive members of the labor force according to the International Labor Organization standards. Those employed reported WRIs due to axial SpA in the past 12 months. Sociodemographic characteristics and patient-reported outcomes were compared between patients with and without WRIs. Stepwise regression analysis was conducted to identify independent determinants of WRIs. The sample comprised 2,846 patients with axial SpA, 1,653 were active members of the labor force, 1,450 were employed, and of those employed, 67.7% reported at least 1 WRI. The most frequently reported WRIs were taking sick leave (56.3%), difficulty fulfilling working hours (44.6%), and missing work for doctor's appointments (34.6%). Of the total sample, 74.1% declared that they had faced or would face difficulties finding a job due to axial SpA. Patients with WRIs were more often female, were less likely to be married or in a relationship, and had a higher educational level, poorer patient-reported outcomes, and a greater prevalence of anxiety and depression. Multivariable regression showed that WRIs were associated with a higher Bath Ankylosing Spondylitis Disease Activity Index score (odds ratio [OR] 1.30 [95% confidence interval (95% CI) 1.16-1.45]) and the 12-item General Health Questionnaire score (OR 1.15 [95% CI 1.09-1.22]), and were negatively associated with inflammatory bowel disease (OR 0.58 [95% CI 0.36-0.91]). Approximately two-thirds of employed patients experienced WRIs due to axial SpA. Association between disease activity and psychological distress with WRIs suggests the need to ensure that axial SpA patients receive the required support to cope with their working life.


Antibiotic Resistance Profile and Distribution of Oxacillinase Genes Among Clinical Isolates of Acinetobacter baumannii in Shiraz Teaching Hospitals, 2012 - 2013.
The emergence of multidrug-resistant Acinetobacter baumannii complicates the therapy of the related infections. Hospital isolates of A. baumannii are usually multidrug-resistant. The problem is compounded by increasing resistance to broad-spectrum antibiotics including carbapenems. The aim of this study was to determine antimicrobial susceptibility patterns and distribution of bla OXA -type carbapenemases genes among A. baumannii isolates from hospitalized patients in Shiraz, Southwest Iran. Two hundred A. baumannii isolates were recovered from different clinical specimens in four Shiraz teaching hospitals. Isolates were detected as A. baumannii by Microgen kit and PCR with specific primers of bla OXA-51-like gene. Antimicrobial susceptibility testing was determined by disk diffusion method for all the isolates. Multiplex PCR assays were performed for detection of bla OXA-23-like , bla OXA-24-like and bla OXA-58-like genes. All the isolates were susceptible to colistin and polymyxin B. Moreover, all of them were resistant to piperacillin, piperacillin-tazobactam, ampicillin, ceftazidime, cefoxitin and aztreonam. Eighty (40%) isolates had positive results for bla OXA-23-like , 14 (7%) for bla OXA-24-like and 1 (0.5%) isolate for bla OXA-58-like . The co-existence of studied genes was detected for bla OXA-23-like plus bla OXA-24-like in nine (4.5%) isolates. The prevalence of carbapenem resistant A. baumannii isolates in Shiraz hospitals is high. The bla OXA-23-like gene was the most frequent carbapenemase identified among resistant A. baumannii isolated in Shiraz hospitals. The increasing incidence of A. baumannii is a serious concern, therefore control of this pathogen and taking preventive measures are emphasized.


Tracheocarotid fistula secondary to laryngeal carcinoma presenting as massive hemoptysis.
Tracheovascular fistulas are not traditionally included in the differential diagnosis of massive hemoptysis. We report the first such case due to a tracheocarotid fistula produced by occult subglottic laryngeal cancer. Also described is the unusual role the cuffed endotracheal tube played in obscuring the diagnosis and palliating the hemorrhage.


Targeted Metabolomic Analysis of the Eye Tissue of Triple Transgenic Alzheimer's Disease Mice at an Early Pathological Stage.
Alzheimer's disease (AD) is a severe neurodegenerative disease in older people. Despite some consensus on pathogenesis of AD established by previous researches, further elucidation is still required for better understanding. This study analyzed the eye tissues of 2- and 6-month-old triple transgenic AD (3 × Tg-AD) male mice and age-sex-matched wild-type (WT) mice using a targeted metabolomics approach. Compared with WT mice, 20 and 44 differential metabolites were identified in 2- and 6-month-old AD mice, respectively. They were associated with purine metabolism, pantothenate and CoA biosynthesis, pyruvate metabolism, lysine degradation, glycolysis/gluconeogenesis, and pyrimidine metabolism pathways. Among them, 8 metabolites presented differences in both the two groups, and 5 of them showed constant trend of change. The results indicated that the eye tissues of 3 × Tg-AD mice underwent changes in the early stages of the disease, with changes in metabolites observed at 2 months of age and more pronounced at 6 months of age, which is consistent with our previous studies on hippocampal targeted metabolomics in 3 × Tg-AD mice. Therefore, a joint analysis of data from this study and previous hippocampal study was performed, and the differential metabolites and their associated mechanisms were similar in eye and hippocampal tissues, but with tissue specificity.


[Effects of HIV status and other variables on the outcome of tuberculosis treatment in Spain].
To analyze the effect of human immunodeficiency virus (HIV) status and other variables on the outcome of tuberculosis treatment in Spain. Multicenter retrospective cohort study in 6 autonomous communities of Spain (from May 1996 to April 1997). Data on treatment outcome were collected for new cases of tuberculosis in accordance with European guidelines. Follow up of patients continued for 3 months after scheduled end of treatment. Of the 4899 patients included, 3417 (69.7%) had a satisfactory outcome, 438 (8.9%) died before or during treatment, and 1044 (21.4%) had a potentially unsatisfactory outcome. On stratification by HIV status, satisfactory outcome, mortality, and potentially unsatisfactory outcome were reported for 43.4%, 21.5%, and 35.1%, respectively, of HIV-positive patients; 71%, 6.2%, and 22.8%, respectively, of HIV-negative patients; and 74.3%, 7.5%, and 18.2%, respectively, of patients with no HIV status available. HIV modified the effect of several variables on the outcome of treatment, and so separate logistic regression models for each HIV category were constructed. Among HIV-positive patients, mortality increased in patients with neoplastic disease and in users of drugs by nonintravenous routes of administration, whereas potentially unsatisfactory outcomes increased in intravenous drug users and in women. In Spain, the outcome of tuberculosis treatment is much worse in HIV-positive patients. Drug use and presence of neoplastic disease substantially affect mortality.


Noninvasive LV pressure estimation using subharmonic emissions from microbubbles.
To develop a new noninvasive approach to quantify left ventricular (LV) pressures using subharmonic emissions from microbubbles, an ultrasound scanner was used in pulse inversion grayscale mode; unprocessed radiofrequency data were obtained with pulsed wave Doppler from the aorta and/or LV during Sonazoid infusion. Subharmonic data (in dB) were extracted and processed. Calibration factor (mm Hg/dB) from the aortic pressure was used to estimate LV pressures. Errors ranged from 0.19 to 2.50 mm Hg when estimating pressures using the aortic calibration factor, and were higher (0.64 to 8.98 mm Hg) using a mean aortic calibration factor. Subharmonic emissions from ultrasound contrast agents have the potential to noninvasively monitor LV pressures.


Triphenyltin exposition induces spermatic parameter alters of Calomys laucha species.
The present study aims to evaluate the influence of triphenyltin (TPT) exposure on reproductive physiology on Calomys laucha species, since this species inhabits regions susceptible to exposure to this contaminant. Animals exposed to the highest dose (10.0 mg/kg) presented signs of severe intoxication in only 7 days of exposure, demonstrating a higher sensitivity of this species to triphenyltin. The 10.0 mg TPT/kg dose was analyzed separately for short-term exposure and results suggest that exposure to this dose was severely detrimental to sperm activity. Among the main results obtained in the evaluation of sperm kinetics, a reduction in total motility was observed from the 0.5 mg TPT/kg group, accentuated according to the increase in the doses of TPT. In progressive motility, there was a decrease from the dose of 0.5 mg TPT/kg and maintained the plateau until the dose of 5.0 mg TPT/kg. It was also observed an increase in the distances and velocities average path, rectilinear and curvilinear in doses of 2.5 and 5.0 mg/kg. From the flow cytometry, evaluation a decrease in mitochondrial functionality was observed as the dose increased. Increased membrane fluidity was also observed from the 5.0 mg TPT/kg dose and the acrosome reaction presented higher values at doses of 0.5 and 5.0 mg TPT/kg. We can conclude that TPT causes impairment of the sperm activity, reducing it in individuals exposed in the adult phase.


Kinetics of voltage-induced conductance increases in the outer mitochondrial membrane.
The kinetics of the increase in conductance in the outer mitochondrial membrane induced by patch-clamping at various negative potentials (pipette inside negative) are reported. The changes are biphasic, a rapid increase is followed by a slowly developing larger change. The results can be predicted by a model in which an initial activation of channels is followed by their assembly into highly conducting channels. The model suggests that five to seven activated subunits form each high-conductance channel.


Carnitine and acetylcarnitine in red blood cells.
Carnitine and acetylcarnitine were found to be present in human erythrocytes. Their presence was not as a factor of leucocyte contamination. Carnitine is present within the erythrocyte at a level comparable to that of the plasma, whilst acetylcarnitine is more concentrated within the cell. Red blood cell carnitine and acetylcarnitine do not freely exchange with plasma but intra-erythrocyte acetylcarnitine has a significant relationship to the plasma levels.


Crystal structure of the [2Fe-2S] protein I (Shethna protein I) from Azotobacter vinelandii.
Azotobacter vinelandii is a model diazotroph and is the source of most nitrogenase material for structural and biochemical work. Azotobacter can grow in above-atmospheric levels of oxygen, despite the sensitivity of nitrogenase activity to oxygen. Azotobacter has many iron-sulfur proteins in its genome, which were identified as far back as the 1960s and probably play roles in the complex redox chemistry that Azotobacter must maintain when fixing nitrogen. Here, the 2.1 Å resolution crystal structure of the [2Fe-2S] protein I (Shethna protein I) from A. vinelandii is presented, revealing a homodimer with the [2Fe-2S] cluster coordinated by the surrounding conserved cysteine residues. It is similar to the structure of the thioredoxin-like [2Fe-2S] protein from Aquifex aeolicus, including the positions of the [2Fe-2S] clusters and conserved cysteine residues. The structure of Shethna protein I will provide information for understanding its function in relation to nitrogen fixation and its evolutionary relationships to other ferredoxins.


The role of robotic gait training and tDCS in Friedrich ataxia rehabilitation: A case report.
Friedrich ataxia (FA) is the most common inherited neurodegenerative cerebellar ataxic syndrome. In patients with FA, physiotherapy is highly recommended to improve motor function outcome. Cerebellar transcranial direct current stimulation (tDCS) has been demonstrated to be effective in improving symptoms by modulating cerebellar excitability. Recently, robotic rehabilitation with Lokomat-Pro has been used to treat motor impairment in ataxic syndromes by "modulating" cortical plasticity and cerebello-motor connectivity. A 29-year-old Italian male with FA, come to our Institute to undergo intensive rehabilitation training. He presented a moderate-to-severe spastic tetraparesis, brisk deep tendon reflexes, moderate dysarthria, occasional difficulty in speaking, and mild delay in swallowing. He was able to stand for at least 10 seconds in the natural position with constant support, and thus he used a wheelchair. Tetraparesis in a young patient with FA. The effects of a stand-alone robotic gait training with Lokomat-Pro preceded by cerebellar anodal tDCS (a-tDCS) versus Lokomat-Pro preceded by cathodal-tDCS (c-tDCS) are compared. The coupled approach (i.e., tDCS and Lokomat) demonstrated better improvement in functional motor outcomes on the Scale for the Assessment and Rating of Ataxia (SARA). Although only a single case is described, we found that the combined neuromodulation-neurorobotic approach could become a promising tool in the rehabilitation of cerebellar ataxias, possibly by shaping cerebello-cerebral plasticity and connectivity.


Xl019, a novel JAK inhibitor, suppressed osteoclasts differentiation induced by RANKL through MAPK signaling pathway.
Inbonemetabolism,osteoclastsare the only cellscapableofresorbingbone. Hyperactivity of osteoclasts may lead to osteolytic disease like osteoporosis and arthritis. Although there are several drugs for the treatment of osteolytic diseases, they have limitations and a variety of side effects. An inhibitor of Janus kinase (JAK), XL019, has shown promising results in the treatment of myelofibrosis and other cancers. But whether it can functionally impact osteoclast activity has not been proven. In this study, the effects of XL019 on osteoclastogenesis and the mechanism pathway were investigated in vitro. It was found that XL019 could impair osteoclasts formation, interfere with bone resorption ability and downregulate the osteoclast-specific genes and proteins expression. Furthermore, Western blot and molecular docking studies demonstrated that XL019 inhibited RANKL-induced osteoclastogenesis by suppressing MAPK signaling. A molecular docking analysis explained how XL019 binds to MAPK pathway factors. In addition, titanium particles induced calvarial osteolysis in mice further confirming its beneficial effect on bone homeostasis in vivo. In conclusion, this study demonstrates that Osteoclastactivity canbeeffectivelyinhibitedby XL019viaMAPK signalingpathway,making it a promising alternative pharmacologicaltreatmentfor bone metabolicdisorders.


Glomerular aging in females is a multi-stage reversible process mediated by phenotypic changes in progenitors.
The glomeruli of postmenopausal C57BL6 mice, and age-matched males, show progressive hypertrophy and glomerulosclerosis. We asked whether this was a multistage process, was due to alterations in glomerular progenitors, and was reversible in female mice. Using cross bone marrow transplants (BMT) between young and old females, we found that BMT delivered a phenotype that was donor age-specific. The fact that lesions in young recipients were more severe if the donors were in late rather than early menopause suggested that new progenitor phenotypes had appeared. Postmenopausal recipients of BMT from young donors had reduced glomerular hypertrophy and sclerosis, implying that the aging lesions in females were reversible and that progenitors, rather than the local environment, determined the glomerular profile. The altered phenotype included increased extracellular matrix synthesis and decreased matrix metalloproteinase-2 levels as well as cell hypertrophy. The mechanism of the cellular hypertrophy was due to uncoupling of hypertrophy from proliferation, resulting from elevated p27 levels. Thus, glomerular hypertrophy and sclerosis in aging females is a multistage process, is reversible, and may be determined by the phenotype of bone marrow-derived progenitor cells.


Acquired idiopathic sideroblastic anemia: a new chromosomal abnormality.
We describe two patients with acquired idiopathic sideroblastic anemia and a terminal deletion of chromosome No. 11. In spite of the marked chromosomal abnormality neither patient has developed acute leukemia.


Antidepressant-induced increase in GluA2 expression does not translate in changes of AMPA receptor-mediated synaptic transmission at CA3/CA1 synapses in rats.
Chronic treatment with serotonin selective reuptake inhibitors or tryciclic antidepressant drugs in rodents has been shown to increase the expression of GluA1 and/or GluA2 AMPA receptor (AMPAR) subunits in several brain areas, including the hippocampus. These changes in AMPAR composition have been suggested to result in increased glutamatergic neurotransmission and possibly underlie enhanced hippocampal synaptic plasticity through the increased availability of calcium-permeable AMPARs, specifically at CA3/CA1 synapses. However, the possibility that chronic treatment with antidepressants actually results in strengthened glutamatergic neurotransmission in CA1 has poorly been investigated. Here, we studied whether chronic treatment with the multimodal antidepressant drug trazodone mimicked the effect of paroxetine on the expression of AMPAR subunits in male wistar rat hippocampus and whether these drugs produced a parallel facilitation of field excitatory postsynaptic potentials (fEPSP) responses evoked by activation of CA3/CA1 synapses in dorsal hippocampal slices. In addition, we investigated whether the quality of glutamatergic AMPARs involved in basal neurotransmission was changed by altered subunit expression, e.g. leading to appearance of calcium-permeable AMPARs. We found a significant increase in GluA2 subunit expression following treatment with trazodone or paroxetine for twenty-one days, but not after seven-days treatment. In contrast, we did not find any significant changes in fEPSP responses supporting either a facilitation of glutamatergic neurotransmission in basal conditions or the appearance of functional calcium-permeable AMPARs at CA3/CA1 pyramidal neuron synapses. Thus, neurochemically-detected increases in the expression of AMPAR subunits cannot directly be extrapolated in increased number of functioning receptors and/or facilitated basal neurotransmission.


Nuclear cardiac troponin and tropomyosin are expressed early in cardiac differentiation of rat mesenchymal stem cells.
Nuclear actin - which is immunologically distinct from cytoplasmic actin - has been documented in a number of differentiated cell types, and cardiac isoforms of troponin I (cTnI) and troponin T (cTnT) have been detected in association with nuclei of adult human cardiac myocytes. It is not known whether these and related proteins are present in undifferentiated stem cells, or when they appear in cardiomyogenic cells following differentiation. We first tested the hypothesis that nuclear actin and cardiac isoforms of troponin C (cTnC) and tropomyosin (cTm) are present along with cTnI and cTnT in nuclei of isolated, neonatal rat cardiomyocytes in culture. We also tested the hypothesis that of these five proteins, only actin is present in nuclei of multipotent, bone marrow-derived mesenchymal stem cells (BM-MSCs) from adult rats in culture, but that cTnC, cTnI, cTnT and cTm appear early and uniquely following cardiomyogenic differentiation. Here we show that nuclear actin is present within nuclei of both ventricular cardiomyocytes and undifferentiated, multipotent BM-MSCs. We furthermore show that cTnC, cTnI, cTnT and cTm are not only present in myofilaments of ventricular cardiomyocytes in culture but are also within their nuclei; significantly, these four proteins appear between days 3 and 5 in both myofilaments and nuclei of BM-MSCs treated to differentiate into cardiomyogenic cells. These observations indicate that cardiac troponin and tropomyosin could have important cellular function(s) beyond Ca(2+)-regulation of contraction. While the roles of nuclear-associated actin, troponin subunits and tropomyosin in cardiomyocytes are not known, we anticipate that the BM-MSC culture system described here will be useful for elucidating their function(s), which likely involve cardiac-specific, Ca(2+)-dependent signaling in the nucleus.


A psychometrically derived impulsive trait related to a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in a Japanese nonclinical population: assessment by the Barratt impulsiveness scale (BIS).
Although a number of studies have shown that human impulsive traits are associated with indices of central serotonin function, few researchers have investigated the relationship between a polymorphism in the serotonin transporter gene-linked region (5-HTTLPR) and a psychometrically derived impulsive trait. We determined the 5-HTTLPR polymorphism in 123 employed Japanese male adults using the polymerase chain reaction. The distribution of allelic frequency was determined and also investigated the relationship of the 5-HTTLPR polymorphism to a impulsive trait as measured by the Barratt Impulsiveness Scale, 11th version (BIS-11). The distribution of allelic frequency was found to be almost identical to that previously reported in Japanese (the frequency for the long (L)/L, L/short (S), and S/S genotypes was: 3, 28, and 68%, respectively). In a comparison between the genotype groups, the S/S genotype group significantly higher scored for the total BIS-11 and the subscale attentional impulsiveness than the L/S + L/L genotype group. These findings suggest that individuals with a homozygous S-allele may be more impulsive than those with the other genotype.


[Determination of umbilical cord blood Ig and its correlation with prenatal infections (author's transl)].
IgG, IgM and IgA were measured in 120 funicular blood samples. At the same time, these determinations were assayed in the mothers. In the serum samples of the newborn, IgA and IgM were found to have levels over 20 mg/100 ml. Antibodies against rubella virus, cytomegalus virus, Listeria monocytogenes and Toxoplasma gondii were measured in order to investigate a possible intrauterine infection. All Ig determinations were performed through the radial immunodiffusion method.


The Influence of Age on Complications After Correction of Congenital Breast Deformities: A National Analysis of the Pediatric and Adult NSQIP Data Sets.
Timing of surgical intervention is controversial among patients seeking correction of congenital breast deformities. This study aimed to assess the influence of age on 30-day complications and unplanned healthcare utilization after reconstruction of congenital breast deformities. Female patients undergoing breast reconstruction for congenital breast deformities and Poland syndrome were identified on the basis of International Classification of Diseases (ICD) codes in the 2012 to 2021 pediatric and adult National Surgical Quality Improvement Project (NSQIP) data sets. Complications based on age at correction were compared, and multivariate logistic regression was used to identify predictors of overall and wound healing complications. Among 528 patients meeting inclusion criteria, mean (SD) age at surgical correction was 30.2 (13.3) years. Patients most commonly underwent implant placement (50.5%), mastopexy (26.3%), or tissue expander placement (11.6%). Across the cohort, overall incidence of postoperative complications was 4.4%, most commonly superficial surgical site infection (1.0%), reoperation (1.1%), or readmission (1.0%). After multivariate adjustment, increasing age at time of correction was associated with higher incidence of wound complications [odds ratio (OR) 1.001; 95% confidence interval (CI) 1.0003-1.002; P = .009], in addition to BMI (OR 1.002; 95% CI 1.0007-1.004; P = .006) and tobacco use (OR 1.06; 95% CI 1.02-1.11; P = .003). Breast reconstruction for congenital breast deformities may be safely undertaken at a young age with a low associated risk of postoperative complications. Large, multi-institutional studies are needed to assess the influence of surgical timing on psychosocial outcomes in this population.


Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis.
Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v. antibiotic therapy) vs. an abbreviated (2-day i.v. antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP). We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement. Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v. every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v. every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days). No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups. The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs. 95%, respectively) were similar in both groups. Patients who received early oral therapy had shorter hospital stays (7.3 vs. 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs. $5002, P < 0.05). It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy. Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome.


Magnesium represses trichothecene biosynthesis and modulates Tri5, Tri6, and Tri12 genes expression in Fusarium graminearum.
Growth and production of type-B trichothecenes mycotoxins by the Fusarium graminearum strain CBS 185.32 were compared in GYEP medium supplemented with Mg(2+) at different concentrations (0-4 mM). Mg(2+) led to a strong decrease in toxin accumulation without affecting the mycelial growth, suggesting a specific Mg(2+) effect on fungal secondary metabolism. Expression of Tri5, Tri6, and Tri12 genes was followed throughout the time courses of type-B trichothecenes (TCTB) yield in standard and 2 mM Mg(2+)-supplemented GYEP media. Mg(2+) addition significantly decreased Tri5, Tri6, and Tri12 expression. The inhibition of toxin production by Mg(2+ )was shown to be highly correlated with inhibition of Tri5 transcription and, to a lesser extend, of Tri6 and Tri12. This is the first report of a transcriptional control of TCTB production by Mg(2+).


Raman spectroscopy and order in biological systems.
The Raman spectra in the low 5-200 cm-1 frequency region of metabolically active E. coli cells have been analyzed to determine whether they are indicators of a possible in vivo underlying order by applying standard concepts derived from the Raman spectroscopy of crystalline systems with varying degrees of order. The analysis suggests that in-vivo space-time ordered structures involving amino acids associated with DNA exist since the low frequency lines of metabolically active cells can be assigned to lines seen in the spectra of crystals of given amino acids known to associate with DNA early in the lifetime of a cell.


Resonating holes vs molecular spin-orbit coupled states in group-5 lacunar spinels.
The valence electronic structure of magnetic centers is one of the factors that determines the characteristics of a magnet. This may refer to orbital degeneracy, as for jeff = 1/2 Kitaev magnets, or near-degeneracy, e.g., involving the third and fourth shells in cuprate superconductors. Here we explore the inner structure of magnetic moments in group-5 lacunar spinels, fascinating materials featuring multisite magnetic units in the form of tetrahedral tetramers. Our quantum chemical analysis reveals a very colorful landscape, much richer than the single-electron, single-configuration description applied so far to all group-5 GaM4X8 chalcogenides, and clarifies the basic multiorbital correlations on M4 tetrahedral clusters: while for V strong correlations yield a wave-function that can be well described in terms of four V4+V3+V3+V3+ resonant valence structures, for Nb and Ta a picture of dressed molecular-orbital jeff = 3/2 entities is more appropriate. These internal degrees of freedom likely shape vibronic couplings, phase transitions, and the magneto-electric properties in each of these systems.


Slow orthograde axonal transport of radiolabelled protein in sciatic motoneurones of rats with short-term experimental diabetes: effects of treatment with an aldose reductase inhibitor or myo-inositol.
This study examined the effect of streptozotocin diabetes of 5 weeks duration on the profile of slow orthogradely transported radiolabelled protein in rat sciatic motoneurones. The diabetic rats showed a retardation of the tail of the slow-component profile. This selective retardation was unaffected by treatment with an aldose reductase inhibitor, although this treatment reduced the accumulation of sorbitol and prevented the depletion of myo-inositol in the sciatic nerves of the treated diabetic rats. Other groups, treated with myo-inositol, had normal or elevated sciatic nerve myo-inositol levels in the presence of accumulated sorbitol. The axonal transport profiles from both control and diabetic myoinositol-treated groups gave normal tail velocities but an altered shape such that retardation of the tail of the profile may have been present in both. The study concludes that rats with 5 weeks streptozotocin diabetes show retardation of the velocity of the most slowly transported proteins in sciatic motoneurones, and that this defect is not linked to the polyol pathway.


Record linkage for routinely collected health data in an African health information exchange.
The Patient Master Index (PMI) plays an important role in management of patient information and epidemiological research, and the availability of unique patient identifiers improves the accuracy when linking patient records across disparate datasets. In our environment, however, a unique identifier is seldom present in all datasets containing patient information. Quasi identifiers are used to attempt to link patient records but sometimes present higher risk of over-linking. Data quality and completeness thus affect the ability to make correct linkages. This paper describes the record linkage system that is currently implemented at the Provincial Health Data Centre (PHDC) in the Western Cape, South Africa, and assesses its output to date. We apply a stepwise deterministic record linkage approach to link patient data that are routinely collected from health information systems in the Western Cape province of South Africa. Variables used in the linkage process include South African National Identity number (RSA ID), date of birth, year of birth, month of birth, day of birth, residential address and contact information. Descriptive analyses are used to estimate the level and extent of duplication in the provincial PMI. The percentage of duplicates in the provincial PMI lies between 10% and 20%. Duplicates mainly arise from spelling errors, and surname and first names carry most of the errors, with the first names and surname being different for the same individual in approximately 22% of duplicates. The RSA ID is the variable mostly affected by poor completeness with less than 30% of the records having an RSA ID.The current linkage algorithm requires refinement as it makes use of algorithms that have been developed and validated on anglicised names which might not work well for local names. Linkage is also affected by data quality-related issues that are associated with the routine nature of the data which often make it difficult to validate and enforce integrity at the point of data capture.


Resting energy expenditure in vasospastic subjects and its potential relevance in glaucoma.
Peripheral vasospastic syndrome is frequently encountered in normal tension glaucoma patients. We tested the hypothesis as to whether peripheral vascular spastic tendency is due to an attempt to preserve body heat in subjects with reduced resting energy expenditure. Twenty healthy non-smoking female individuals were enrolled into the study. Subjects were classified as having vasospasm (10 subjects) if they related a clear history of frequent cold hands, and as normal subjects (10 subjects) if they denied such a history. Sample size calculation was based on a power of 80 % to find a difference of 20 %. Resting energy expenditure (REE) was assessed by indirect calorimetry and corrected for fat-free mass (FFM), which was assessed by bioelectric impedance analysis. REE was 1198 +/- 155 kilocalories (kcal) in vasospastics and 1169 +/- 122 in controls (Mann-Whitney U-test: p = 0.62). FFM was 39.6 +/- 3.3 kg in vasospastics and 41.1 +/- 2.3 kg in controls (Mann-Whitney U-test: p = 0.16). REE adjusted for FFM was 30.2 +/- 2.5 kcal/kg in vasospastics and 28.4 +/- 2.3 kcal/kg in controls (Mann-Whitney U-test: p = 0.08). Peripheral vasospastic syndrome seems not to be a secondary response to insufficient resting energy expenditure. The results of the present study rather indicate an opposite tendency which deserves further investigation.


The development and validation of the clinicians' awareness towards cognitive errors (CATChES) in clinical decision making questionnaire tool.
Despite their importance on diagnostic accuracy, there is a paucity of literature on questionnaire tools to assess clinicians' awareness toward cognitive errors. A validation study was conducted to develop a questionnaire tool to evaluate the Clinician's Awareness Towards Cognitive Errors (CATChES) in clinical decision making. This questionnaire is divided into two parts. Part A is to evaluate the clinicians' awareness towards cognitive errors in clinical decision making while Part B is to evaluate their perception towards specific cognitive errors. Content validation for both parts was first determined followed by construct validation for Part A. Construct validation for Part B was not determined as the responses were set in a dichotomous format. For content validation, all items in both Part A and Part B were rated as "excellent" in terms of their relevance in clinical settings. For construct validation using exploratory factor analysis (EFA) for Part A, a two-factor model with total variance extraction of 60% was determined. Two items were deleted. Then, the EFA was repeated showing that all factor loadings are above the cut-off value of >0.5. The Cronbach's alpha for both factors are above 0.6. The CATChES questionnaire tool is a valid questionnaire tool aimed to evaluate the awareness among clinicians toward cognitive errors in clinical decision making.


Successful resection of colonic metastasis of lung cancer after colonic stent placement: A case report and review of the literature.
Lung cancer is the leading cause of cancer deaths worldwide. Although lung cancer can metastasize to various organs such as the liver, lymph nodes, adrenal gland, bone, and brain, metastases to the digestive organs, especially the colon, are rare. An 83-year-old man diagnosed with lung cancer received radiation and chemoimmunotherapy, resulting in a complete clinical response. One year after the initial lung cancer diagnosis, the patient presented with obstructive ileus caused by a tumor in the descending colon. An elective left hemicolectomy was successfully performed after the endoscopic placement of a self-expandable metallic stent (SEMS). Pathologically, the tumor of the descending colon was diagnosed as lung cancer metastasis. The postoperative course was uneventful, and the patient is in good condition 13 mo after surgery, with no signs of recurrence. The previous 23 cases of surgical resection of colonic metastasis from lung cancer were reviewed using PubMed to characterize their clinicopathological features and outcomes. SEMS is useful for obstructive colonic metastasis as a bridge to surgery to avoid emergency operations.


BCL2 inhibitor ABT-199 and BCL2L1 inhibitor WEHI-539 coordinately promote NOXA-mediated degradation of MCL1 in human leukemia cells.
Human leukemia U937 cells that were continuously treated with hydroquinone (HQ) were transformed into U937/HQ cells with increased MCL1 and BCL2L1 expression. Compared with their parental cells, U937/HQ cells were less sensitive to ABT-263 (BCL2/BCL2L1 inhibitor)/ABT-199 (BCL2 inhibitor) cytotoxicity. The combination of WEHI-539 (BCL2L1 inhibitor) with either ABT-199 or ABT-263 showed synergistic cytotoxicity to U937 and U937/HQ cells. Therefore, we further investigated the cytotoxic mechanism induced by the combination of WEHI-539 and ABT-199. The combined treatment of WEHI-539 and ABT-199 induced NOX4/ROS/p38 MAPK axis-mediated autophagy, which in turn accelerated β-TrCP mRNA turnover. Downregulation of β-TrCP increased Sp1 expression, thereby promoting Sp1-mediated NOXA transcription, which in turn induced NOXA-dependent MCL1 degradation. Enforced expression of MCL1 alleviated the cytotoxicity of WEHI-539 plus ABT-199 to induce the loss of mitochondrial membrane potential and cell viability. WEHI-539 alone induced Sp1/NOXA axis-mediated MCL1 downregulation, while ABT-199 significantly decreased the dose of WEHI-539 by approximately 350- and 50-fold to induce MCL1 suppression in parental and HQ-selected cells, respectively. Furthermore, WEHI-539 sensitized ABT-199-resistant U937 cells to ABT-199 cytotoxicity by inducing NOXA-mediated degradation of MCL1. Collectively, the data in this study indicate that ABT-199 and WEHI-539 cooperatively induce NOXA-dependent MCL1 degradation, and the inhibition of MCL1 mainly explains their combined cytotoxicity in parental, HQ-selected, and ABT-199-resistant U937 cells.


Distinct mental trainings differentially affect altruistically motivated, norm motivated, and self-reported prosocial behaviour.
Global challenges such as climate change or the refugee crises emphasize the necessity of altruism and cooperation. In a large-scale 9-month intervention study, we investigated the malleability of prosociality by three distinct mental trainings cultivating attention, socio-affective, or socio-cognitive skills. We assessed numerous established measures of prosociality that capture three core facets: Altruistically motivated behaviours, norm motivated behaviours, and self-reported prosociality. Results of multiple time point confirmatory factor analyses support the validity and temporal stability of this model. Furthermore, linear mixed effects models reveal differential effects of mental trainings on the subcomponents of prosociality: Only training care and compassion effectively boosted altruistically motivated behaviour. No effects were revealed for norm-based behaviour. Self-reported prosociality increased with all training modules; this increase was, however, unrelated to changes in task-based measures of altruistic behaviour. These findings corroborate our motivation-based framework of prosociality, challenge economic views of fixed preferences by showing that socio-affective training boosts altruism, and inform policy makers and society about how to increase global cooperation.


The role of the guanine nucleotide exchange factor Tiam1 in cellular migration, invasion, adhesion and tumor progression.
While advances in molecular genetics have provided new insights into molecular alterations that lead to the development of many tumors, including breast carcinoma, the genetic and epigenetic alterations that result in metastatic spread of the disease, from which afflicted patients ultimately succumb, are much more poorly understood. Important biologic processes in the development of metastasis include increased migration and invasion of tumor cells. While the regulation of these processes is complex, they are controlled in part by small G proteins of the Rho family, including Rho, Rac, and Cdc42, that are involved in cytoskeletal organization. These proteins, active when bound to GTP, are, in turn, regulated by guanine nucleotide exchange factors (GNEFs) and guanine nucleotide activating proteins. The GNEF Tiam1 catalyzes nucleotide exchange for Rac in vivo, and Rac, Cdc42 and Rho in vitro. Tiam1 was identified first in 1994 by in vitro selection for invasiveness in T-lymphoma cells. Accordingly, Tiam1 has been shown to increase invasion in T-lymphoma cells, as well as to increase cellular migration in fibroblasts, and to promote motility in some neuronal cells. In contrast, Tiam1 has been demonstrated to increase cellular adhesion in some epithelial cell populations. Thus, Tiam1 has multiple roles in regulating cellular functions, likely dependent on the cell type, the substratum, transformation status of the cells, and the activation state of small G proteins in a given cell. Increasing evidence has focused on Tiam1's regulation, as well as Tiam1's role in cancer progression and metastasis. Recent results from other laboratories and ours have demonstrated that increased Tiam1 expression correlates with grade of breast cancer in humans and metastatic potential of human breast carcinoma cell lines in nude mice. This review will discuss Tiam1's cellular functions and methods of regulation, and will highlight Tiam1's contribution to cancer progression and metastasis.


Nitroglycosylated meso-arylporphyrins as photoinhibitors of gram positive bacteria.
Novel porphyrins bearing nitro groups and glucosyl moieties were synthesized. The antibacterial activity of these compounds on Escherichia coli and Staphylococcus aureus is described. Results reveal that their photocytotoxicity is markedly dependent on the nature, the number and the linking position of the glycosyl moieties and nitro groups controlling their amphiphilic characters.


Cardiovascular responsiveness to arginine vasopressin in water-loaded and sodium-depleted pregnant and non-pregnant sheep.
1. In conscious ewes pregnancy was associated with a significantly increased heart rate and cardiac output, while mean arterial pressure (MAP) and stroke volume were unchanged. 2. The present study examines the effect of arginine vasopressin (AVP) infused at 0.3, 1, 3.0, and 10 micrograms/h, into water-loaded and sodium-depleted ewes, either non-pregnant or during the last third of gestation. 3. In the water-loaded state, MAP rose significantly at the lowest rate of infusion in both pregnant and non-pregnant ewes. Bradycardia occurred first at 0.3 micrograms/h in the pregnant ewes but not until 3.0 micrograms/h in the non-pregnant animals. 4. In sodium deficiency there was no increase in MAP at any rate of infusion in either group. Bradycardia occurred in both groups at 1 microgram/h. 5. This study shows that the pressor effects of AVP are unchanged by pregnancy. However, pregnant ewes are more sensitive to AVP-induced bradycardia when the ewes are water-loaded.


Hip resurfacing for small-sized osteonecrosis: 73 cases at a median 8years' follow-up.
Total hip resurfacing arthroplasty (THRA) is an alternative to conventional total hip replacement (THR) in young patients with osteonecrosis of the femoral head. Series have been small, without criteria regarding extent of necrosis, thus vitiating results. We therefore conducted a retrospective assessment of THRA for small necrosis, to determine (1) implant survival, (2) functional scores, and (3) systemic chromium, cobalt and titanium ion concentrations. The study hypothesis was that the revision rate is low, meeting the National Institute for Health and Care Excellence (NICE) criterion of<0.5% revision per year. A single-center single-surgeon retrospective study included 62 patients, for 73 RTHAs, with a mean age of 45.6years (range: 23-68years) presenting Ficat stage 3 or 4 osteonecrosis of the femoral head with<330° total Kerboul angle (frontal+lateral angles) on simple preoperative X-ray. Study data comprised implant survival and preoperative and last follow-up functional scores (Postel-Merle-d'Aubigné, Oxford-12, Harris, and Devane) and titanium, chromium and cobalt blood concentrations. Necrosis size was assessed on preoperative Kerboul angle. At a median 8years' follow-up (IQR: 5.9-9.3years), implant survival was 98.6% (95% CI: 97.22-99.98%). Only 1 implant was exchanged, for femoral loosening. Three other patients underwent revision surgery: 2 cases of lavage for infection, and 1 muscle hernia repair. Postel-Merle-d'Aubigné, Oxford-12 and Harris functional scores and Devane activity scores were significantly improved at follow-up, by a median +5 (IQR: 5 to 7), -26 (IQR: -29 to -23), +55 (IQR: 49 to 61) and +1 (IQR: 1 to 2), respectively (all p<0.001). Ion concentrations at last follow-up for titanium, chromium and cobalt were respectively 4.0μg/L (range: 3.6-4.1), 1.1μg/L (range: 0.8-1.9) and 1.1μg/L (range: 0.6-1.8). THRA is a useful option in the long-term for young patients with osteonecrosis with Kerboul angle<330°. IV, retrospective study.


Retrovesical soft-tissue metastasis of malignant thymoma: case report.
Malignant thymomas are usually confined to the mediastinum at the time of diagnosis and follow-up. Distant metastasis is distinctly rare. This is the first clinical case report of a thoracic malignant thymoma with distant soft-tissue metastasis that involves the retrovesical area to include the seminal vesicle.


Prevalence, Risk Factors, and Outcomes of Adult Interstitial Lung Abnormalities: A Systematic Review and Meta-Analysis.
Rationale: Incidental parenchymal abnormalities detected on chest computed tomography scans are termed interstitial lung abnormalities (ILAs). ILAs may represent early interstitial lung disease (ILD) and are associated with an increased risk of progressive fibrosis and mortality. The prevalence of ILAs is unknown, with heterogeneity across study populations. Objectives: Estimate the pooled prevalence of ILAs in lung cancer screening, general population-based, and at-risk familial cohorts using meta-analysis; identify variables associated with ILA risk; and characterize ILA-associated mortality. Methods: The study protocol was registered on PROSPERO (CRD42022373203), and Meta-analyses of Observational Studies in Epidemiology recommendations were followed. Relevant studies were searched on Embase and Medline. Study titles were screened and abstracts reviewed for full-text eligibility. Random effect models were used to pool prevalence estimates for specified subgroups and ILA-associated mortality risk. Risk of ILAs was estimated based on age, sex, and FVC. Quality assessment was conducted using an adapted Assessment Tool for Prevalence Studies. Measurements and Main Results: The search identified 9,536 studies, with 22 included, comprising 88,325 participants. The pooled ILA prevalence was 7% (95% confidence interval [CI], 0.01-0.13) in lung cancer screening, 7% (95% CI, 0.04-0.10) in general population, and 26% (95% CI, 0.20-0.32) in familial cohorts. Pooled mortality risk was increased in those with ILAs (odds ratio, 3.56; 95% CI, 2.19-5.81). Older age, male sex, and lower FVC% were associated with greater odds of ILA. Conclusions: Populations undergoing imaging for non-ILD indications demonstrate high ILA prevalence. Standardized reporting and follow-up of ILAs is needed, including defining those at greatest risk of progression to ILD.


The global burden of child burn injuries in light of country level economic development and income inequality.
Child burn mortality differs widely between regions and is closely related to material deprivation, but reports on their global distribution are few. Investigating their country level distribution in light of economic level and income inequality will help assess the potential for macro-level improvements. We extracted data for child burn mortality from the Global Burden of Disease study 2013 and combined data into 1-14 years to calculate rates at country, region and income levels. We also compiled potential lives saved. Then we examined the relationship between country level gross domestic product per capita from the World Bank and income inequality (Gini Index) from the Standardized World Income Inequality Database and child burn mortality using Spearman coefficient correlations. Worldwide, the burden of child burn deaths is 2.5 per 100,000 across 103 countries with the largest burden in Sub-Saharan Africa (4.5 per 100,000). Thirty-four thousand lives could be saved yearly if all countries in the world had the same rates as the best performing group of high-income countries; the majority in low-income countries. There was a negative graded association between economic level and child burns for all countries aggregated and at regional level, but no consistent pattern existed for income inequality at regional level. The burden of child burn mortality varies by region and income level with prevention efforts needed most urgently in middle-income countries and Sub-Saharan Africa. Investment in safe living conditions and access to medical care are paramount to achieving further reductions in the global burden of preventable child burn deaths.


Swahili translation and validation of the Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) in adolescents and adults taking part in the girls' education challenge fund project in Tanzania.
The Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) is validated for measuring mental wellbeing in populations aged 11 + and has been translated into 30 + languages. The aims of this study were a) to translate and validate WEMWBS for use in Swahili-speaking populations to facilitate measurement and understanding of wellbeing, evaluation of policy and practice, and enable international comparisons; and b) to examine sociodemographic characteristics associated with higher and lower mental wellbeing in participants in the Girls' Education Challenge (GEC) project in Tanzania. A short questionnaire including WEMWBS and similar scales for comparison, socio-demographic information, and self-reported health was translated into Swahili using gold standard methodology. This questionnaire was used to collect data from secondary school students, learner guides, teacher mentors and teachers taking part in the GEC project in Tanzania. Focus groups were used to assess acceptability and comprehensibility of WEMWBS and conceptual understanding of mental wellbeing. These were audio-taped, transcribed and analysed thematically. Internal consistency of WEMWBS, correlation with comparator scales and confirmatory factor analysis were completed as quantitative validation. Finally, multivariable logistic regression was used to explore associations between individual characteristics and 'high' and 'low' mental wellbeing, defined as the highest and lowest quartile of WEMWBS scores. 3052 students and 574 adults were recruited into the study. Participants reported that WEMWBS was understandable and relevant to their lives. Both WEMWBS and its short form met quantitative standards of reliability and validity, were correlated with comparator scales and met the criteria to determine a single factor structure. For students in the GEC supported government schools: mental wellbeing was higher in students in the final two 'forms' of school compared with the first two. In addition: being male, urban residence, the absence of markers of social marginality and better self-reported health were all significantly associated with better mental wellbeing. For adults, urban residence and better self-reported health were associated with better mental wellbeing. The Swahili translation of WEMWBS is available for use. Further work to explore how to intervene to increase mental wellbeing in vulnerable GEC participants is needed.


Visual acuity in esotropic cats following occlusion of the non-deviating eye.
The present study examined the possibility that strabismic amblyopia may be explained in terms of binocular competition. This was done by measuring visual acuity in strabismic kittens whose deviating eye was placed at an advantage over the other. Four groups of kittens were studied: Normal/Normal (N/N); Lid-sutured/Normal (LS/N); Strabismic/Normal (S/N); Strabismic/Lid-sutured (S/LS). In conditions 2-4 kittens underwent lateral rectus section and/or unilateral lid suture around the time of natural eye opening. Visual acuity measurements were made using the jumping stand technique and the following results were obtained: all S/N kittens showed an acuity deficit in the strabismic eye; each S/LS kitten had a better acuity in the deviating eye than any S/N kitten; the acuity of the LS/S kittens was slightly below that of the N/N kittens or the normal eye of the LS/N kittens. These data suggest that binocular competition can account for essentially all of the strabismic amblyopia observed in kittens.


Prognostic implication of cyclin E expression and its relationship with cyclin D1 and p27Kip1 expression on tissue microarrays of node negative breast cancer.
Altered expression of cell-cycle regulators is prevalent in clinical breast cancer. This study was performed to analyze the impact of cyclin E expression to the outcome of breast cancer together with cyclin D1 and p27Kip1. The correlation between cyclin D1/E and p27Kip1 expression was analyzed in tissue arrays of 175 node-negative breast cancers treated by the same chemotherapy composed of fluorouracil, cyclophosphamide, and methotrexate. Data from the immunohistochemical assays of three molecules were correlated and were analyzed with clinical outcome of the patients. Cyclin E expression was observed in 48 (27.4%) of 175 breast carcinomas. Cyclin E expression was significantly increased in young age patients and poorly differentiate tumors. Expression of cyclin E was significantly increased in cyclin D1 expressing tumors (P = 0.034). p27Kip1 expression was preserved above the 50% level in 87 tumors (49.7%) and was inversely correlated with cyclin E expression (P = 0.042). Ki67 labeling index was significantly increased in cyclin E-expressing tumors (P = 0.033) and was inversely related with p27Kip1 expression. In multivariate survival analysis, cyclin E expression was significant for the prediction of poor survival of the patients. Cyclin E expression was associated with poor prognosis and intimately correlated with the expression of cyclin D1 and p27Kip1. Integration of TMA technology allowed a high-throughput analysis for correlating molecular in situ findings with clinico-pathologic information.


Operative management of chronic pancreatitis: A review.
Pain secondary to chronic pancreatitis is a difficult clinical problem to manage. Many patients are treated medically or undergo endoscopic therapy and surgical intervention is often reserved for those who have failed to gain adequate pain relief from a more conservative approach. There have been a number of advances in the operative management of chronic pancreatitis over the last few decades and current therapies include drainage procedures (pancreaticojejunostomy, etc.), resection (pancreticoduodenectomy, etc.) and combined drainage/resection procedures (Frey procedure, etc.). Additionally, many centers currently perform total pancreatectomy with islet autotransplantation, in addition to minimally invasive options that are intended to tailor therapy to individual patients. Operative management of chronic pancreatitis often improves quality of life, and is associated with low rates of morbidity and mortality. The decision as to which procedure is optimal for each patient should be based on a combination of pathologic changes, prior interventions, and individual surgeon and center experience.


Interaction potentials, structural ordering and effective charges in dispersions of charged colloidal particles.
As colloidal dispersions of charged particles exhibit a wide variety of commercial, technological and scientific applications, a considerable theoretical effort has been devoted to finding an effective interaction potential from primitive models. The forces derived from this potential should justify the spatial ordering experimentally observed under certain conditions. This paper reviews the advances in these theoretical studies as well as some experiments (based on the mentioned order) that try to corroborate them. Special attention has been paid to the Derjaguin-Landau-Verwey-Overbeek (DLVO) potential. Nowadays, many of these theoretical investigations suggest that it could be applied if some of its parameters are renormalized. Nevertheless, to achieve a renormalization procedure in a strict way (from a primitive model) is a difficult task as a result of the size and charge asymmetries between small ions and macroions. Thus, several procedures for computing renormalized charges in a simple way have been developed. However, the notion of effective charge has also been widely used (as a adjustable parameter) in order to justify results found for several kinds of colloids (like solid particle dispersions or micellar systems) by means of quite different experimental techniques. Renormalization (as well as ion condensation) approaches, experiments and the controversial relationship between theoretical and phenomenological effective charges are also reviewed in this work.


Prevalence of underweight and wasting in Iranian children aged below 5 years: a systematic review and meta-analysis.
Wasting and underweight are the 2 main indicators of children's undernutrition. We aimed to estimate the prevalence of undernutrition at the national level in Iran. We performed a search for original articles published in international and Iranian databases including MEDLINE, Web of Science, Google Scholar, Scopus, CINHAL (Cumulative Index to Nursing and Allied Health Literature), Scientific Information Database, Irandoc, Iranmedex, and Magiran during January 1989-August 2017. Seven keywords, in English and Persian, including malnutrition, protein energy malnutrition, growth disorders, underweight wasting, weight loss, children below 5 years old, and children, were used to search the databases. Finally, 17 articles were included in the meta-analysis, based on which the prevalence of underweight and wasting in Iranian children were estimated to be 11% and 5%, respectively. The prevalence rates of underweight among children in the central, western, southern, and northern parts of Iran and at the national level were 24%, 5%, 20%, 17%, and 6%, respectively. The prevalence rates of wasting in the central, western, southern, and northern parts of Iran and at the national level were 9%, 4%, 11%, 5%, and 4%, respectively. Although the prevalence of underweight and wasting in Iran was low, some parts of the country showed high prevalence. The main reason behind this difference in the prevalence of malnutrition may be due to the level of development in different regions.


Inclusion bodies containing adenovirus-like particles in the intestine of a psittacine bird affected by inclusion body hepatitis.
This paper reports a case of inclusion body hepatitis with intranuclear inclusion bodies in the liver and the intestine of a Yellow-naped Amazon parrot (Amazona ochrocephala). Structurally, basophilic intranuclear inclusion bodies were found in hepatic cells and enterocytes. Ultrastructurally, icosahedral adenovirus-like particles, 60-75 nm in diameter, were found in the same cells.


Hexavalent and trivalent chromium in leather: What should be done?
Trivalent chromium compounds are used for leather tanning, and chromium may be released during use of leather goods. In certain instances, small amounts of hexavalent chromium can be formed and released. Both trivalent and hexavalent chromium can elicit allergic skin reaction in chromium sensitised subjects, the latter being significantly more potent. Induction of sensitisation only occurs after exposure to hexavalent chromium. A minority of subjects are sensitised to chromium, and in a fraction of these subjects allergic skin reaction have been described after wearing leather shoes or, less frequently, other leather goods. The evidence that in all these cases the reaction is related to hexavalent chromium is not always strong. The content of hexavalent chromium in leather is regulated in European Union, but rate of release rather than content is relevant for allergic skin reaction. The role of trivalent chromium appear much less relevant if at all. Modern tanning procedure do not pose significant risk due to either hexavalent or trivalent chromium. Dismissing bad quality and worn-off leather goods is relevant in reducing or eliminating the skin reaction. It should also be pointed out that shoe components or substances other than chromium in leather may cause allergic/irritative skin reactions.


Meso-Rex bypass versus portosystemic shunt for the management of extrahepatic portal vein obstruction in children: systematic review and meta-analysis.
Extrahepatic portal vein obstruction (EHPVO) is a major cause of non-cirrhotic portal hypertension in children. Surgical procedures for EHPVO include portosystemic shunts (PSS) and meso-Rex bypass (MRB). We conducted a systematic review and meta-analysis to compare the effectiveness of MRB versus PSS in EHPVO patients. A systematic literature search was performed using four databases. Articles reporting EHPVO and comparing patients who received MRB and PSS were included in the analysis. We retrieved 851 papers, of which five observational studies met the inclusion criteria. There was no difference in shunt complications, mortality, or gastrointestinal bleeding after surgery between MRB and PSS in the meta-analysis. MRB had increased shunt complications compared with PSS in the non-comparative studies. MRB had a potential advantage over PSS in long-term prognosis in one comparative study. Overall, the quality of the evidence was low. Based on available data, our meta-analysis indicates that MRB does not increase shunt complications, mortality, or gastrointestinal bleeding after surgery. The present study did not reveal superiority for either MRB or PSS. The paucity of well conducted trials in this area justifies future multicenter studies and studies that examine long-term outcomes.


Polysaccharides from Lyophyllum decastes reduce obesity by altering gut microbiota and increasing energy expenditure.
Polysaccharides are known to confer protection against obesity via modulation of gut microbiota. To expand our knowledge of mushroom-derived prebiotics, we investigated the structural characteristics and anti-obesity effects of Lyophyllum decastes polysaccharides. Two heteroglycans were purified and characterized. The isolated polysaccharides effectively reduced obesity and the related disorders in the diet-induced obese (DIO) mice. An altered gut microbiota with enrichments of Bacteroides intestinalis and Lactobacillus johnsonii and an increase of secondary bile acids were detected in the polysaccharide-treated mice. Supplementation of B. intestinalis and L. johnsonii prevented the obesity and hyperlipidemia in DIO mice, demonstrating their causal linkage to the efficacy of polysaccharides. An enhancement of energy expenditure in the brown adipose tissues due to up-regulation of the secondary bile acids-activated TGR5 pathway was deduced to be one of the mechanisms underlying the effect of polysaccharides. These results confirmed Lyophyllum decastes-derived polysaccharides as new prebiotics for preventing and treating obesity.


Exploratory Genome-Wide Association Analysis to Identify Pharmacogenetic Determinants of Response to R-CHOP in Diffuse Large B-Cell Lymphoma.
R-CHOP standard chemotherapy is successful in about 60% of diffuse large B-cell lymphoma (DLBCL) patients. Unresponsive patients have a poor prognosis, and predictive biomarkers of response to R-CHOP are lacking. We conducted the first prospective GWAS study aimed at exploring constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 216 any-stage chemonaïve DLBCL patients candidate to R-CHOP were enrolled. The median age of the 185 eligible patients was 59.2 years, 49.7% were women and 45.4% were stage I-II patients. According to the Revised International Prognostic Index (R-IPI), 14.1%, 56.8% and 29.2% were in the very good, good and poor prognosis groups, respectively. Of the patients, 85.9% produced a complete response. Highly significant associations (i.e., p < 5 × 10-8) were found between progression-free survival (PFS) and six SNPs (i.e., rs116665727, rs1607795, rs75614943, rs77241831, rs117500207, rs78466241). Additionally, five SNPs (i.e., rs74832512, rs117500207, rs35789195, rs11721010, rs12356569) were highly associated with overall survival (OS). Wild-type patients showed a prolonged PFS or OS compared with patients carrying deleterious alleles (p < 0.001). No association with the adequate significant threshold was observed between SNPs and the objective response or toxicity. In the future, these SNPs, alone or in combination, after a proper validation in an independent cohort, could contribute to improving the prediction of R-CHOP response.


Participation of propionate in cholesterol biosynthesis by rat liver.
Incorporation of (214C) propionate into cholesterol was demonstrated using rat liver slices and homogenates. The incorporation of (214C) propionate was greater than that of (214C) acetate. Using the same liver homogenate preparation (214C) succinate and (214C) pyruvate were incorporated into cholesterol to a lesser extent than (214C) acetate and (214C) propionate. Addition of unlabeled acetate failed to dilute the incorporation of (214C) propionate. Incorporation of the 2 and 3 carbon atoms pf propionate were equal; little incorporation of the 1 carbon atom was demonstrable. These results indicate that propionate is an excellent source of 2 carbon units for isoprenoid biosynthesis; the intermediary pathway does not involve a common acetate pool nor can these results be satisfactorily explained by citric acid intermediary metabolism.


Identification of phenolic compounds in Equisetum giganteum by LC-ESI-MS/MS and a new approach to total flavonoid quantification.
Equisetum giganteum L., commonly called "giant horsetail", is an endemic species of Latin America. Its aerial parts have been widely used in ethnomedicine as a diuretic and in herbal medicine and food supplements as a raw material. The phenolic composition of E. giganteum stems was studied by liquid chromatography coupled to diode array detection (LC-DAD) and liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS), which identified caffeic acid derivatives, flavonoids and styrylpyrones. The most abundant glycosilated flavonoids in this sample were kaempferol derivatives. Other rare phenolic components, namely, quercetin-3-O-(caffeoyl)-glucoside and 3-hydroxyhispidin-3,4'-di-O-glucoside, were reported for first time in the Equisetum genus. An LC-UV method for the simultaneous quantification of flavonoid aglycones in E. giganteum obtained after hydrolysis was developed and validated. The method exhibited excellent linearity for all analytes, with regression coefficients above 0.998, LOD ≥ 0.043μg mL(-1), LOQ ≥ 0.158 μg mL(-1) and recovery rates of 96.89-103.33% and 98.22-102.49% for quercetin and kaempferol, respectively. The relative standard deviation for the intra- and inter-day precision was ≤ 3.75%. The hydrolysis process was optimized by central composite rotational design and response surface analysis. The second-order response models for the aglycones contents were as follows: quercetin (μg g(-1))=24.8102+55.2823 × HCl+0.776997 × Time-7.23852 × HCl(2)-7.46528E-04 × Time(2)-0.229167 × HCl × Time; kaempferol (μg g(-1))=-9.66755+974.822 × HCl+11.8059 × Time-130.612 × HCl(2)-0.0125694×Time(2) -3.22917 × HCl × Time, with estimated optimal conditions of 1.18 M HCl and 205 min of hydrolysis. The results obtained with these new methods were compared to those from a spectrophotometric assay used to determine the total flavonoids in the Equisetum arvense monograph (Horsetail, British Pharmacopoeia 2011). For all four species analyzed (E. giganteum, E. arvense, E. hyemale and E. bogotense), the calculated aglycone content was higher using the optimized hydrolysis conditions. Additionally, the LC method was more appropriate and specific for quantitative analysis.


Analysis of neutrophil membrane traffic during phagocytosis.
In this chapter, we describe methods to study membrane traffic during phagosome formation and maturation. Although it is convenient to define events as occurring either before (i.e., during formation) or after (during maturation) the creation of a sealed phagosome, it might not be correct to assume that this is reflected by a sudden change in the membrane traffic events involved. Nevertheless, formation events are studied by approaches different from those of maturation events. Before closure of a phagosome, methods relying on immunochemistry and fluorescent markers are employed. Once phagosomes have formed, these can be isolated and additional methods can be used for their characterization. Here, we describe (1) methods to study membrane traffic during phagosome formation and (2) magnetic purification of bacteria-containing phagosomes for maturation studies.


An automatic system to identify heart disease risk factors in clinical texts over time.
Despite recent progress in prediction and prevention, heart disease remains a leading cause of death. One preliminary step in heart disease prediction and prevention is risk factor identification. Many studies have been proposed to identify risk factors associated with heart disease; however, none have attempted to identify all risk factors. In 2014, the National Center of Informatics for Integrating Biology and Beside (i2b2) issued a clinical natural language processing (NLP) challenge that involved a track (track 2) for identifying heart disease risk factors in clinical texts over time. This track aimed to identify medically relevant information related to heart disease risk and track the progression over sets of longitudinal patient medical records. Identification of tags and attributes associated with disease presence and progression, risk factors, and medications in patient medical history were required. Our participation led to development of a hybrid pipeline system based on both machine learning-based and rule-based approaches. Evaluation using the challenge corpus revealed that our system achieved an F1-score of 92.68%, making it the top-ranked system (without additional annotations) of the 2014 i2b2 clinical NLP challenge.


Reservoir characteristics of Mainz pouch studied in animal model. Osmolality of filling solution and effect of oxybutynin.
In a canine model of the Mainz pouch, intracavitary pressure and compliance were measured during instillation of isosmotic and hyperosmotic (900 mmol/kg water) solutions of saline. Wall properties of small- and large-bowel segments of the pouch were assessed individually by sonomicrometry. Intraluminal pressures increased more steeply during filling with hyperosmotic solution, resulting in reduced distensibility of small- and large-bowel segments. Additionally, instillation of the hyperosmotic solution resulted in increased amplitudes and frequency of intracavitary pressure waves. The results indicate that this was the result of a combination of intensified bowel contractions and an increased mural tension. Topical application of oxybutynin abolished these effects. These findings are reviewed in light of the nocturnal increase in urine osmolality, its correlation with nocturnal incontinence in patients with enterocystoplasty, and possible treatment choices.


[Jean-Louis-Paul Denucé (1824-1889): A forgotten pioneer of plastic surgery].
The authors propose to define as main characterization of plastic reconstructive surgery the conceptual thinking that leads to a rational choice of an operative treatment. Conceptual thinking in plastic surgery started halfway the nineteenth century with the first schematic representations of the operative procedures available at that time, in which Von Ammon and Baumgarten, Szymanowski and Denucé played a prominent role. These four authors and their works are presented with special attention for the less known of them, Jean-Paul Denucé, surgeon in Bordeaux.


Eimeria necatrix: induced proteolytic sensitivity of infected chick crypt cells.
While devising a protocol for the isolation of chick crypt cells infected with Eimeria necatrix, it was observed that infected cells were readily lysed by 0.25% trypsin. Time-course studies at 17 C with 5.5 x 10(5) cells at 96 hr postinfection revealed that 0.001% trypsin effectively lysed greater than 90% of infected cells within 10 min. Uninfected crypt cells were not lysed under these conditions. To determine the site of action of trypsin, the plasma membrane proteins from trypsin-treated and untreated infected cells were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. While the major proteins were unaffected by the trypsin treatment, some minor changes were noted: (1) three components (congruent to 60, congruent to 52, and congruent to 20 KDa) were trypsin sensitive and (2) a new band (congruent to 42 KDa) appeared in the membrane of trypsin-treated infected cells. Previously, it was found that the plasma membrane of infected cells, in contrast to uninfected cells, accumulated gel-phase lipid (J. E. Thompson, M. A. Fernando, and J. Pasternak, Biochimica et Biophysica Acta 555, 472-487, 1979). Here, it was examined whether trypsin would perturb the physical state of the plasma membrane of infected cells. Both X-ray diffraction patterns and transition temperature studies revealed no difference between membranes from untreated and trypsin-treated infected cells. Thus, "trypsin sensitivity" may be a secondary phenomenon that is due primarily to the cellular leakiness that accompanies the accumulation of gel-phase lipid in the plasma membrane of infected cells. The uptake of trypsin may stimulate the release of catabolic enzymes that, consequently, lyse an infected cell.


A disposable chitosan-modified carbon fiber electrode for dengue virus envelope protein detection.
A chitosan-modified carbon fiber electrode (CFE) for dengue virus envelope protein (DENV) was developed. Antibodies against DENV were covalently immobilized on the chitosan (CHIT) matrix after activation with sodium periodate. Cyclic voltammetries and scanning electron microscopies analysis were performed to monitor steps involved in the CFE surface modification. Amperometric response of the competitive immunoassays was generated by hydrogen peroxide reaction with the peroxidase conjugated to DENV and 2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) as mediator. The immunosensor showed a lower limit of detection for DENV (0.94 ng mL(-1)) than previously described and a linear range from 1.0 to 175 ng mL(-1), in concentration levels clinically relevant for dengue virus diagnosis. The intra- and inter-assay were respectively 5.8% and 3.6%. The unique and simple design of this immunoassay format provides an economical alternative for the manufacture of other sensitive sensors.


Comparison of speech parameters and olfaction using different tracheotomy speaking valves.
The objective of this work was to obtain a controlled subjective and objective in vivo clinical comparison of the Passy-Muir, Shiley, and Ball speaking valves. Ten patients free of laryngeal pathology but dependent on tracheotomy for respiration were tested with each of the speaking valves. Olfaction was assessed for each patient using the University of Pennsylvania Smell Identification Test (UPSIT). Acoustic and perceptual analyses included subjective assessments, noninstrumental objective assessments (including maximum phonation time, and S:Z ratio), and instrumental objective assessments (including fundamental frequency:maximum phonation range, vocal intensity, perturbation, naturalness, and turbulence). Oxygen saturation was assessed by pulse oximetry. There was a highly significant statistical difference in olfaction and speech naturalness, in favor of the Ball valve (The Airway Company, Forest Hill, MD). The Ball valve's speech parameters were generally better than with the Passy-Muir and Shiley valves, including maximum phonation, S:Z ratio, jitter, noise, and turbulence, although the differences were not statistically significant. There were no differences among the valves in oxygen saturation levels. This study illustrates that olfaction and certain speech parameters, most noticeably speech naturalness, are significantly improved with the Ball valve as compared to the Passy-Muir and Shiley valves.


[Obesity and symptoms of depression and anxiety in pre- and postmenopausal women: a comparison of different obesity indicators].
This study examines differences in the rates of depression and anxiety symptoms in overweight vs. normal weight women before and after the menopause. In a population sample of 1 416 participants of the KORA-Survey F3 2004-2005 (age 35-74 years), body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR) und waist-to-height-ratio (WHtR) were measured via physical examination. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. Compared with normal weight, obesity was associated with depression in premenopausal women. This held for elevated BMI-, WC- and WHtR-scores (OR=3.7, 4.2, and 2.8), underlining the relevance of both general and abdominal obesity. Menopausal status may be a moderator for the association of obesity and depression, which - given the interaction between these 2 risk factors - may be of preventive importance in regard to the development of cardiovascular outcomes such as coronary heart disease.


Isolation of Chemoresistant Cell Subpopulations.
Chemoresistance is a major challenge for cancer therapy and drives tumor relapse. The emergence, within the treated tumor mass, of specific cancer cell subpopulations endowed with high tolerance to the microenvironment stress induced by therapy is being growingly recognized as a mechanism of tumor progression. To obtain detailed information with regard to the pathways underlying survival, expansion, and microenvironmental cross talk of such chemoresistant cell subpopulations may be instrumental for cancer chemoprevention. Additionally, the obtained cell subpopulations may be used for direct screening of cancer chemopreventive compounds, in appropriate experimental settings. Here we report detailed experimental procedures that we and others have setup in order to obtain cell cultures enriched for chemoresistant cells from both malignant pleural mesothelioma specimens and primary cell cultures. We provide indications for the purification and characterization of those chemoresistant cell populations and to generally validate the obtained enriched cell populations for their chemoresistance.


Uniparental disomy: can SNP array data be used for diagnosis?
Purpose:Single-nucleotide polymorphism microarray analysis identifies copy-number variants and blocks of homozygosity, suggestive of consanguinity or uniparental disomy. The purpose of this study was to validate chromosomal microarray analysis for the identification of uniparental disomy in a clinical laboratory.Methods:In phase I of this retrospective study, nine cases with uniparental disomy for chromosomes 7 (n = 1), 14 (n = 1), and 15 (n = 7), identified by conventional polymorphic microsatellite marker analysis were analyzed on the Affymetrix 6.0 single-nucleotide polymorphism array. In phase II, four cases of uniparental disomy 15 showing heterozygosity for all microsatellite markers were analyzed using the same array.Results:Chromosomal microarray analysis detected blocks of homozygosity in eight of the nine cases in phase I. Phase II analysis of molecularly defined heterodisomy failed to detect blocks of homozygosity in three of the four cases. The four cases in which microarray did not detect blocks of homozygosity all involved chromosome 15.Conclusion:A failure to recombine may predispose to nondisjunction and, therefore, to uniparental disomy. Four cases of heterodisomy 15 were not detected by array, suggesting a lack of recombination. Therefore, a normal chromosomal microarray result for chromosome 15 does not exclude the possibility of uniparental disomy. This observation may apply to other chromosomes; however, further study is needed.Genet Med advance online publication 26 April 2012.


An exploration of the value of specialist neurosurgical nurses.
The differences in the knowledge and skills of 75 nurses working in a variety of practice settings were examined using a case study vignette of a neurosurgical patient developed by researchers. The case study tested nursing care throughout a patient's hospital experience, including admission, presurgery, postsurgery and discharge preparation. The findings showed that nurses who had specialised in neurosurgery scored markedly higher, in all aspects of practice knowledge, than expert nurses in other specialties and general nurses. Patients undergoing neurosurgery are safer if they have nurses who are experienced, skilled and knowledgeable to care for them.


Immunotherapy of brain tumors.
In the process of malignant transformation, astrocytoma cells display a number of surface antigens not expressed by their normal adult counterparts and which have been identified by monoclonal antibodies and characterized biochemically. These include tumor associated antigens (TAA) such as oncofetal antigens of neuroectodermal origin or oncogene products such as epitopes in the extracellular domain of the epidermal growth factor receptor, as well as major histocompatibility antigens (MHC) of class I and class II. Glioma cells also secrete lymphokines like IL-1 and IL-6. The concomitant expression of TAA and MHC together with the disruption of the blood brain barrier may elicit a humoral or cell mediated immune response from the tumor bearing host as demonstrated by the functional analysis of tumor infiltrating lymphocytes. However this response is extremely weak and obviously inefficient because the tumor cells secrete factors which can inhibit or completely abrogate the immune attack by cytotoxic T cells. Among these factors, TGF-beta 2 and PGE2 are of particular interest since they may explain the generally depressed cellular immune response observed in patients with malignant gliomas. To be efficient any form of immunotherapy will require abatement of these suppressive activities in addition to stimulation of the effector functions.


Salutary actions of thromboxane synthetase inhibition during global myocardial ischemia.
Isolated cat hearts were perfused with blood-free Krebs-Henseleit solution for 165 min. Ischemia was induced by reducing perfusion to 0.02 ml/min/g wet heart weight for 2 h followed by reperfusion at controls flows for 30 min. Hearts perfused with the thromboxane synthetase inhibitor OKY-1581 at concentrations of 5 X 10(-6) M were spared from the increases in circulating thromboxane B2 occurring in untreated ischemic hearts. After reperfusion, cardiac contractile force increased to a higher level in OKY-1581 treated hearts. This was associated with a lower coronary vascular resistance than in untreated ischemic hearts. OKY-1581 treated ischemic hearts exhibited lower perfusate and higher myocardial creatine kinase (CK) activity than untreated ischemic hearts, indicative of preservation of cellular integrity. Also, OKY-1581 treated ischemic hearts showed improved lysosomal stability as evidenced by a lower tissue percent free cathepsin D activity than untreated ischemic hearts. These results are consistent with a significant role of thromboxanes in the propagation of myocardial cellular damage during ischemia.