Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function.
The mechanisms by which enteropathogenic Escherichia coli (EPEC), an important cause of diarrhea among infants in developing countries, induce symptoms are not defined. EPEC have a type III secretion system required for characteristic attaching and effacing changes that modify the cytoskeleton and apical surface of host cells. Infection of polarized intestinal epithelial cell monolayers by EPEC leads to a loss of transepithelial electrical resistance, which also requires the type III secretion system. We demonstrate here that EspF, a protein that is secreted by EPEC via the type III secretion system, is not required for quantitatively and qualitatively typical attaching and effacing lesion formation in intestinal epithelial cells. However, EspF is required in a dose-dependent fashion for the loss of transepithelial electrical resistance, for increased monolayer permeability, and for redistribution of the tight junction-associated protein occludin. Furthermore, the analysis of EPEC strains expressing EspF-adenylate cyclase fusion proteins indicates that EspF is translocated via the type III secretion system to the cytoplasm of host cells, a result confirmed by immunofluorescence microscopy. These studies suggest a novel role for EspF as an effector protein that disrupts intestinal barrier function without involvement in attaching and effacing lesion formation.


Protein sequence alignment techniques.
The basic algorithms for alignment of two or more protein sequences are explained. Alternative methods for scoring substitutions and gaps (insertions and deletions) are described, as are global and local alignment methods. Multiple alignment techniques are explained, including methods for profile comparison. A summary is given of programs for the alignment and analysis of protein sequences, either from sequence alone, or from three-dimensional structure.


Global assessment of the status of coral reef herbivorous fishes: evidence for fishing effects.
On coral reefs, herbivorous fishes consume benthic primary producers and regulate competition between fleshy algae and reef-building corals. Many of these species are also important fishery targets, yet little is known about their global status. Using a large-scale synthesis of peer-reviewed and unpublished data, we examine variability in abundance and biomass of herbivorous reef fishes and explore evidence for fishing impacts globally and within regions. We show that biomass is more than twice as high in locations not accessible to fisheries relative to fisheries-accessible locations. Although there are large biogeographic differences in total biomass, the effects of fishing are consistent in nearly all regions. We also show that exposure to fishing alters the structure of the herbivore community by disproportionately reducing biomass of large-bodied functional groups (scraper/excavators, browsers, grazer/detritivores), while increasing biomass and abundance of territorial algal-farming damselfishes (Pomacentridae). The browser functional group that consumes macroalgae and can help to prevent coral-macroalgal phase shifts appears to be most susceptible to fishing. This fishing down the herbivore guild probably alters the effectiveness of these fishes in regulating algal abundance on reefs. Finally, data from remote and unfished locations provide important baselines for setting management and conservation targets for this important group of fishes.


Stress and atopic dermatitis.
Atopic dermatitis (AD) is a complex disease traditionally involving interaction of genetic, environmental, and immunologic factors. Recent studies suggest psycho-neuro-immunologic factors and emotional stress are important in its evolution. The observations that internal (bacterial infections) or external (psycho-logic) stressors may induce AD flares is explained by studies showing that stress impairs the skin barrier function and favors a shift in immunity toward a T helper type 2 cell/allergic response. Furthermore, those with AD appear to have an inherited hypothalamic deficiency that impairs normal hypothalamic-pituitary-adrenal axis function. Neuropeptides released in the skin may also mediate neurogenic inflammation, including mast cell degranulation. AD causes significant stress and impaired quality of life in patients and their family members. Psychologic and stress-reduction interventions were recently shown to improve patient well-being, and to significantly improve cutaneous manifestations.


Tobacco addiction.
Tobacco use is associated with 5 million deaths per year worldwide and is regarded as one of the leading causes of premature death. Comprehensive programmes for tobacco control can substantially reduce the frequency of tobacco use. An important component of a comprehensive programme is the provision of treatment for tobacco addiction. Treatment involves targeting several aspects of addiction including the underlying neurobiology and behavioural processes. Furthermore, building an infrastructure in health systems that encourages and helps with cessation, as well as expansion of the accessibility of treatments, is necessary. Although pharmacological and behavioural treatments are effective in improving cessation success, the rate of relapse to smoking remains high, emphasising the strong addictive nature of nicotine. The future of treatment resides in improvement in patient matching to treatment, combination or novel drugs, and viewing nicotine addiction as a chronic disorder that might need long-term treatment.


Mutations which alter the DNA binding properties of the herpes simplex virus type 1 transactivating protein Vmw175 also affect its ability to support virus replication.
The crucial role of herpes simplex virus type 1 immediate early protein Vmw175 (ICP4) in the regulation of all classes of viral genes has been established by extensive analysis of temperature-sensitive, insertion and deletion mutants. It has long been known that Vmw175 binds to selected DNA sequences, and recent studies have shown that it interacts with components of the basal transcription machinery. However, the role of DNA binding in its mechanism of action has been controversial. Despite the presence of Vmw175 recognition sites at numerous locations throughout the viral genome, it has proved difficult to establish that these sites are important for the activation of early and late promoters. In this study we have analysed the ability of a large number of insertion and single point mutant derivatives of Vmw175 to bind to DNA and to support virus replication. Vmw175 mutants which were unable to bind to DNA were also incapacitated in terms of their ability to activate gene expression in transfection assays and to complement the growth of a Vmw175 deletion mutant virus. These results strongly support the hypothesis that interaction with DNA is an essential feature of the mechanism of action of Vmw175.


Organoapatites: materials for artificial bone. II. Hardening reactions and properties.
This article reports on chemical reactions and the properties they generated in artificial bone materials termed "organoapatites." These materials are synthesized using methodology we reported in the previous article of this series. Two different processes were studied here for the transition from organoapatite particles to implants suitable for the restoration of the skeletal system. One process involved the hardening of powder compacts by beams of blue light derived from a lamp or a laser and the other involved pressure-induced interdiffusion of polymers. In both cases, the hardening reaction involved the formation of a polyion complex between two polyelectrolytes. In the photo-induced reaction an anionic electrolyte polymerizes to form the coulombic network and in the pressure-induced one, pressure forms the complex by interdiffusion of two polyions. Model reactions were studied using various polycations. Based on these results the organoapatite selected for the study was that containing dispersed poly(L-lysine) and sodium acrylate as the anionic monomer. The organomineral particles can be pressed at room temperature into objects of great physical integrity and hydrolytic stability relative to anorganic controls. The remarkable fact about these objects is that intimate molecular dispersion of only 2-3% by weight organic material provides integrity to the mineral network in an aqueous medium and also doubles its tensile strength. This integrity is essentially nonexistent in "anorganic" samples prepared by the same methodology used in organoapatite synthesis. The improvement in properties was most effectively produced by molecular bridges formed by photopolymerization. The photopolymerization leads to the "hardening" of pellets prepared by pressing of organoapatite powders. The reaction was found to be more facile in the microstructure of the organomineral, and it is potentially useful in the surgical application of organoapatites as artificial bone.


[Herpes zoster in immunocompetent pregnant women and their perinatal outcome].
A prospective and descriptive study was done in pregnant women diagnosed with herpes zoster, to know the demographic characteristics and clinical manifestations as well as maternal and/or neonatal complications to cause by this viral infection during pregnancy. The study included all pregnant women diagnosed with herpes zoster at the Department of Infectious Diseases of the Instituto Nacional de Perinatologia México, between 1994 and 2002. A total of 17 women were included in the study. All were given clinical and ultrasound follow-up to discard any maternal or fetal complications also at the moment of birth. A review in the newborn was made to establish the demographic, anthropometric and clinical characteristics; also the data collected included mother's age, gestational age at the moment of diagnosis with herpes zoster, anatomical lesion site, treatments administered, ultrasound characteristics, newborn's gestational age, weight, height, Apgar at birth and type of delivery. The most frequent site (58.8%) for herpes zoster lesions on the mother was the intercostal area, followed by the scapular region, the lumbar region and the limbs. None of the patients experienced complications during pregnancy, including post-herpetic pain. Sixteen of the newborns had no complications and one was a stillborn due to 60% of placental separation. These findings suggest a benign evolution of herpes zoster during pregnancy, supporting similar findings in the literature. No complications during pregnancy are suggested, and no phenotypical alterations occurred in the child at the moment of birth.


Body image and body satisfaction differ by race in overweight postpartum mothers.
Body image (BI) and body satisfaction may be important in understanding weight loss behaviors, particularly during the postpartum period. We assessed these constructs among African American and white overweight postpartum women. The sample included 162 women (73 African American and 89 white) in the intervention arm 6 months into the Active Mothers Postpartum (AMP) Study, a nutritional and physical activity weight loss intervention. BIs, self-reported using the Stunkard figure rating scale, were compared assessing mean values by race. Body satisfaction was measured using body discrepancy (BD), calculated as perceived current image minus ideal image (BD<0: desire to be heavier; BD>0: desire to be lighter). BD was assessed by race for: BD(Ideal) (current image minus the ideal image) and BD(Ideal Mother) (current image minus ideal mother image). Compared with white women, African American women were younger and were less likely to report being married, having any college education, or residing in households with annual incomes >$30,000 (all p < 0.01). They also had a higher mean body mass index (BMI) (p = 0.04), although perceived current BI did not differ by race (p = 0.21). African Americans had higher mean ideal (p = 0.07) and ideal mother (p = 0.001) BIs compared with whites. African Americans' mean BDs (adjusting for age, BMI, education, income, marital status, and interaction terms) were significantly lower than those of whites, indicating greater body satisfaction among African Americans (BD(Ideal): 1.7 vs. 2.3, p = 0.005; BD(Ideal Mother): 1.1 vs. 1.8, p = 0.0002). Racial differences exist in postpartum weight, ideal images, and body satisfaction. Healthcare providers should consider tailored messaging that accounts for these racially different perceptions and factors when designing weight loss programs for overweight mothers.


Identifying clinical complexity in patients affected by severe acquired brain injury in neurorehabilitation: a cross sectional survey.
Literature shows that occurrence of comorbidities in people with severe acquired brain injury (sABI) is a common problem in rehabilitation stay. Consequently, patients could require an increase of interventions for diagnosis and treatment of clinical conditions, with a reduction of the rehabilitative take in charge for both clinical and organizational aspects. The first aim was to evaluate the rate of clinical conditions of sABI patients at admission in rehabilitation and the types of rehabilitative interventions performed in the first week; second objective was to explore the impact of clinical conditions on real rehabilitative take in charge. Cross sectional study. Inpatient rehabilitation centers. The study included data from 586 sABI patients. Collected data regarded anamnestic information, functional status assessed by means of Glasgow Outcome Scale, Levels of cognitive functioning, Early Rehabilitation Barthel Index, comorbidities at admission and type of rehabilitative interventions carried out in first week of rehabilitation stay. Spearman correlation coefficients were applied to detect possible correlations between the number of treatments in first week and clinical variables; through a multiple regression analysis the effect of patient's characteristics on rehabilitative take in charge was explored. Data from the sABI patients: mean age 55.1±17.1 years; etiology of sABI was vascular in 315 patients (53.8%), anoxic in 83 (14.2%), neoplastic in 17 (2.9%), infectious in 15 (2.6%), traumatic in 150 (25.6%); 6 subjects (1%) presented a mixed etiology. Need of cardiorespiratory monitoring, pressure sores, infections or presence of multi drug resistant bacteria were the most frequent comorbidities. Passive mobilization, sitting positioning, arousal/awareness stimulation, evaluation and management of dysphagia were the interventions most frequently carried out in the first week. The regression analysis showed that severe neurological and clinical conditions, acute organ failure, cardio-respiratory instability and paroxysmal sympathetic hyperactivity significantly limit access to rehabilitative sessions. In sABI patients clinical comorbidities requiring elevated care assistance are frequent at admission in rehabilitation from acute wards and may interfere with rehabilitative take in charge. The knowledge of clinical complexity of sABI patients may improve their care pathways, promoting early and appropriate transition from acute care to rehabilitation settings.


Segmental and generalized vitiligo: both forms demonstrate inflammatory histopathological features and clinical mosaicism.
Segmental vitiligo (SV) and generalized vitiligo (GV) are perceived to evolve by different mechanisms, the former with unspecified neural mechanisms and the latter by melanocyte specific autoimmune mechanisms. However, the two diverse mechanisms are difficult to reconcile in cases of "mixed vitiligo". To test the possibility of a common pathogenesis, we reviewed clinical and histopathological features of SV and GV. As part of an ongoing histopathological study on vitiligo and vitiligo like lesions, over a 10 year period from 2002 to 2011, biopsies were taken routinely from evolving or recently evolved lesions. 50 cases of SV with quasi-dermatomal distribution and 154 cases of GV were identified and the clinical and histopathological features were compared. Mild clinical inflammation was recorded in 33 of 154 GV cases but, none among 50 SV had such features. In addition to bilateral symmetrical involvement, mirror image lesions with unusual segmentation were observed in nine cases of GV. SV with a few bilateral lesions (4) and GV with quasi-dermatomal lesions (3), i.e., mixed vitiligo, were included in their corresponding groups for analytical purposes. Focal lichenoid inflammation of varying degrees around epidermal/adnexal melanocytes was identified as a common feature in evolving lesions of both SV (78%) and GV (70%). SV and GV demonstrated a similar inflammatory histopathological spectrum. "Segmentation/mosaicism", identified for the first time in GV is another unifying factor. Cutaneous mosaicism harboring fragile melanocyte populations, which are susceptible to external as well as auto-inflammatory mechanisms, is an attractive hypothesis to pursue in the causation of vitiligo.


Reliability of a rating scale used to distinguish direction of eye movement using infrared/video ENG recordings during repositioning maneuvers.
The purpose of this study was to determine the validity of the nystagmus rating scale (NRS) and to assess inter- and intra-rater reliability of audiologists and experts using the scale. Face and content validity was established by eliciting feedback from two neurotologists and one neurologist. A training tape was developed to describe the rating scale and provide practice with patterns of nystagmus in benign paroxysmal positional vertigo (BPPV). Eye movements of 34 patients, ages 33 to 82 years, were videotaped using infrared/video ENG during repositioning maneuvers. Six randomly paired audiologists and six experts viewed the videotape recordings and completed the NRS for each pattern. Cohen's kappa coefficients were calculated to determine inter-rater reliability. The kappa values were 0.31 with 41% agreement for audiologists, and 0.48 with 59% agreement for experts. Intra-rater reliability for a subgroup of audiologists was 0.55 with 64% agreement, and for experts was 0.75 with 81% agreement. In summary, even in this experienced population, additional training in viewing nystagmus patterns is needed to improve reliability among clinicians during diagnosis and treatment.


Transcriptome analysis of miRNA-lncRNA-mRNA interactions in the malignant transformation process of gastric cancer initiation.
Gastric cancer is a common heterogeneous malignancy that is pathologically characterized by the development of chronic atrophic gastritis and dysplasia of the epithelium. The pathogenic mechanisms at the molecular level are completely unclear. In the present study, we first address the expression network and miRNA-lncRNA-mRNA interaction in the malignant transformation process from normal mucosa and atrophic gastritis to a tumor. First, the long non-coding RNA (lncRNA), micro RNA (miRNA) and messenger RNA (mRNA) expression profiles of normal gastric mucosa, atrophic gastritis, gastric cancer and the peri-tumor tissues were analyzed using microarrays. Then, bioinformatic analyses were used to predict the gene targets and analyse their potential roles in tumorigenesis and progression of gastric cancer. Finally, an intersection analysis of microarray data showed that 10 miRNAs and 11 lncRNAs were detected in the malignant transformation process from normal mucosa tissues and atrophic gastritis to tumorigenesis, and many miRNAs and lncRNAs were novel and had important roles. Meanwhile, the significant pathways and biological functions regulated by the deregulated 21 non-coding genes were enriched. In conclusion, our work provides an important theoretical, experimental and clinical foundation for further research on more effective targets for the diagnosis, therapy and prognosis of gastric cancer.


Malignant hemangioendothelioma of metacarpal bones.
Malignant hemangioendothelioma is a tumour of vascular origin with wide distribution in various organs and tissues of the body. However, it is seldom localized primarily in bone. In this report our experience with a case of primary multifocal malignant hemangioendothelioma of the metacarpal bones is reported. Because of the focal pattern of malignancy excisional biopsy failed to give the diagnosis which was not established until the tumour was radically removed.


Microsecond time-scale kinetics of transient biochemical reactions.
To afford mechanistic studies in enzyme kinetics and protein folding in the microsecond time domain we have developed a continuous-flow microsecond time-scale mixing instrument with an unprecedented dead-time of 3.8 ± 0.3 μs. The instrument employs a micro-mixer with a mixing time of 2.7 μs integrated with a 30 mm long flow-cell of 109 μm optical path length constructed from two parallel sheets of silver foil; it produces ultraviolet-visible spectra that are linear in absorbance up to 3.5 with a spectral resolution of 0.4 nm. Each spectrum corresponds to a different reaction time determined by the distance from the mixer outlet, and by the fluid flow rate. The reaction progress is monitored in steps of 0.35 μs for a total duration of ~600 μs. As a proof of principle the instrument was used to study spontaneous protein refolding of pH-denatured cytochrome c. Three folding intermediates were determined: after a novel, extremely rapid initial phase with τ = 4.7 μs, presumably reflecting histidine re-binding to the iron, refolding proceeds with time constants of 83 μs and 345 μs to a coordinatively saturated low-spin iron form in quasi steady state. The time-resolution specifications of our spectrometer for the first time open up the general possibility for comparison of real data and molecular dynamics calculations of biomacromolecules on overlapping time scales.


Using dual-purpose crops in sheep-grazing systems.
The utilisation of dual-purpose crops, especially wheat and canola grown for forage and grain production in sheep-grazing systems, is reviewed. When sown early and grazed in winter before stem elongation, later-maturing wheat and canola crops can be grazed with little impact on grain yield. Recent research has sought to develop crop- and grazing-management strategies for dual-purpose crops. Aspects examined have been grazing effects on crop growth, recovery and yield development along with an understanding of the grazing value of the crop fodder, its implications for animal nutrition and grazing management to maximise live-weight gain. By alleviating the winter 'feed gap', the increase in winter stocking rate afforded by grazing crops allows crop and livestock production to be increased simultaneously on the same farm. Integration of dual-purpose wheat with canola on mixed farms provides further systems advantages related to widened operational windows, weed and disease control and risk management. Dual-purpose crops are an innovation that has potential to assist in addressing the global food-security challenge.


X-irradiation-induced changes of the prelysosomal and lysosomal compartments and proteolysis in HT-29 cells.
As a consequence of external and internal ionizing radiation, lysosome-like bodies have been observed to increase both in size and number in some cell types. We investigated this process by morphological methods (electron microscopy, cationized ferritin uptake, acid phosphatase histochemistry, morphometry) in cultured HT-29 cells. In parallel with these studies, we measured the rate of protein degradation on the basis of 14C-valine release from prelabeled cellular proteins. We found that at 2 and 4 Gy doses of X-irradiation the volume of the vacuolar (probably lysosomal) compartment increased without detectable changes of acid phosphatase activity. A 2 Gy irradiation dose did not change protein degradation rate. However, 4 Gy caused a significant inhibition of 14C-valine release from prelabeled proteins. Our results indicate, that the radiation induced expansion of the lysosomal compartment is not necessarily accompanied by increased lytic activity of HT-29 cells.


Total 25-Hydroxyvitamin D Is an Independent Marker of Left Ventricular Ejection Fraction in Heart Failure with Reduced and Mildly Reduced Ejection Fraction.
Vitamin D emerged as an important prognostic biomarker in heart failure (HF), with currently highly debated therapeutic implications. Several trials on vitamin D supplementation in HF showed improvements in left ventricular (LV) remodeling and function and health-related quality of life (HRQoL), which did not translate into mid- to long-term beneficial effects regarding physical performance and mortality. We addressed total 25-hydroxyvitamin D (25(OH)D), serum albumin, and uric acid (UA) levels, focusing mainly on vitamin D deficiency, as potential markers of LV systolic dysfunction in HF with reduced and mildly reduced ejection fraction (HFrEF, HFmrEF). Seventy patients with LVEF < 50% were comprehensively evaluated using ECG, echocardiography, lung ultrasound (LUS), blood sampling, and the six-minute walk test (6MWT). HRQoL was also assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Statistically significant positive correlations were found between LVEF, 25(OH)D, serum UA, and albumin, respectively (p = 0.008, p = 0.009, and p = 0.001). Serum UA (7.4 ± 2.4 vs. 5.7 ± 2.1, p = 0.005), NT-proBNP levels (1090.4 (675.2-2664.9) vs. 759.0 (260.3-1474.8), p = 0.034), and MLHFQ scores (21.0 (14.0-47.0) vs. 14.5 (4.5-25.5), p = 0.012) were significantly higher, whereas 25(OH)D concentrations (17.6 (15.1-28.2) vs. 22.7 (19.5-33.8), p = 0.010) were lower in subjects with severely reduced LVEF. Also, 25(OH)D was independently associated with LVEF in univariate and multiple regression analysis, maintaining its significance even after adjusting for confounders such as age, NT-proBNP, the presence of chronic coronary syndrome, hypertension, and anemia. According to our current findings, 25(OH)D is closely associated with LVEF, further supporting the need to establish correct vitamin D supplementation schemes and dietary interventions in HF. The changes in LVEF, 25(OH)D, serum UA, and albumin levels in HFrEF and HFmrEF indicate a similar pathophysiological background.


H-Bonded Donor-Acceptor Units Segregated in Coaxial Columnar Assemblies: Toward High Mobility Ambipolar Organic Semiconductors.
A novel approach to ambipolar semiconductors based on hydrogen-bonded complexes between a star-shaped tris(triazolyl)triazine and triphenylene-containing benzoic acids is described. The formation of 1:3 supramolecular complexes was evidenced by different techniques. Mesogenic driving forces played a decisive role in the formation of the hydrogen-bonded complexes in the bulk. All of the complexes formed by nonmesogenic components gave rise to hexagonal columnar (Colh) liquid crystal phases, which are stable at room temperature. In all cases, X-ray diffraction experiments supported by electron density distribution maps confirmed triphenylene/tris(triazolyl)triazine segregation into hexagonal sublattices and lattices, respectively, as well as remarkable intracolumnar order. These highly ordered nanostructures, obtained by the combined supramolecular H-bond/columnar liquid crystal approach, yielded donor/acceptor coaxial organization that is promising for the formation of ambipolar organic semiconductors with high mobilities, as indicated by charge transport measurements.


Safety of the synthetic retinoid fenretinide: long-term results from a controlled clinical trial for the prevention of contralateral breast cancer.
To describe the pattern of occurrence of adverse events commonly arising during treatment with fenretinide, a synthetic retinoid under investigation for cancer prevention. The series includes 2,867 women accrued in a trial aimed at assessing the effect of fenretinide on the prevention of second breast malignancy. Women were randomly assigned to receive no treatment (1,435 patients) or 5-year fenretinide treatment (1,432 patients). In terms of disease recurrence in the breast, the trial showed a possible beneficial effect of the compound in premenopausal women, and an opposite trend in postmenopausal women. End points considered for safety assessment were the occurrence of diminished dark adaptation, dermatologic disorders, gastrointestinal symptoms, disorders of the ocular surface, and abnormal laboratory values. The most common adverse events were diminished dark adaptation (cumulative incidence, 19.0%) and dermatologic disorders (18.6%). Less common events were gastrointestinal symptoms (13.0%) and disorders of the ocular surface (10.9%). In comparison, incidence figures in the control arm were 2.9% for diminished dark adaptation, 2.9% for dermatologic disorders, 5.4% for gastrointestinal symptoms, and 3.2% for disorders of the ocular surface. Symptoms occurring during fenretinide treatment tended to recover with time. No between-group difference was observed for the occurrence of laboratory data abnormalities. Overall, 63 (4.4%) treatment discontinuations were caused by adverse events. Given the number of patients involved in the study and the prolonged intake of the drug, the experience on fenretinide tolerability can be considered sufficiently reassuring to justify further testing of the retinoid.


The clinical severity of hemoglobin S/Black (A γδβ)0 -thalassemia.
Hemoglobin S/Black (A γδβ)0 -thalassemia is a rare sickle cell disease (SCD) variant. On the basis of limited descriptions in the literature, the disease is reported as a mild microcytic anemia with an uncomplicated course. We report the clinical and laboratory data of nine patients whose diagnoses were confirmed by DNA-based techniques. Despite having mild anemia and high fetal hemoglobin level postinfancy, these patients developed many of the classic complications of SCD, including vaso-occlusive crisis, acute chest syndrome, avascular necrosis, and cholelithiasis. On the basis of these findings, we recommend that patients with this rare disorder receive specialized hematology care according to SCD guidelines.


Genome-wide identification of CCO gene family in cucumber (Cucumis sativus) and its comparative analysis with A. thaliana.
Carotenoid cleavage oxygenase (CCO) is an enzyme capable of converting carotenoids into volatile, aromatic compounds and it plays an important role in the production of two significant plant hormones, i.e., abscisic acid (ABA) and strigolactone (SL). The cucumber plant genome has not been mined for genomewide identification of the CCO gene family. In the present study, we conducted a comprehensive genome-wide analysis to identify and thoroughly examine the CCO gene family within the genomic sequence of Cucumis sativus L. A Total of 10 CCO genes were identified and mostly localized in the cytoplasm and chloroplast. The CCO gene is divided into seven subfamilies i.e. 3 NCED, 3 CCD, and 1 CCD-like (CCDL) subfamily according to phylogenetic analysis. Cis-regulatory elements (CREs) analysis revealed the elements associated with growth and development as well as reactions to phytohormonal, biotic, and abiotic stress conditions. CCOs were involved in a variety of physiological and metabolic processes, according to Gene Ontology annotation. Additionally, 10 CCO genes were regulated by 84 miRNA. The CsCCO genes had substantial purifying selection acting upon them, according to the synteny block. In addition, RNAseq analysis indicated that CsCCO genes were expressed in response to phloem transportation and treatment of chitosan oligosaccharides. CsCCD7 and CsNCED2 showed the highest gene expression in response to the exogenous application of chitosan oligosaccharides to improve cold stress in cucumbers. We also found that these genes CsCCD4a and CsCCDL-a showed the highest expression in different plant organs with respect to phloem content. The cucumber CCO gene family was the subject of the first genome-wide report in this study, which may help us better understand cucumber CCO proteins and lay the groundwork for the gene family's future cloning and functional investigations.


Autoimmunity in primary immune deficiency: taking lessons from our patients.
The elucidation of the genes leading to selected immune defects has accelerated our understanding of the molecular basis of tolerance in autoimmunity disorders. Mutations in genes of the immune system are known to lead to a catalogue of functional deficits, including loss of activation-induced Fas-mediated apoptosis, an inability to remove self-reactive T and/or B cells and insufficient numbers or functions of regulatory T cells. In most cases, microbial antigen stimulation occurs simultaneously, leading to further inflammatory responses. In each case, probing the molecular pathways involved in these primary immune defects has led to a better understanding of autoimmune diseases in general. While subjects with X-linked agammaglobulinaemia are almost devoid of autoimmune diseases, B cells which are present, but dysfunctional in other defects, lead to a significant incidence of autoimmune disease. Autoimmunity is also particularly common in the antibody deficiency states. Although organ-based autoimmunity also occurs, for unclear reasons the main conditions are immune thrombocytopenia purpura and autoimmune haemolytic anaemia. The common variable immune deficiency subjects most afflicted by these cytopenias are those with specific peripheral blood memory B cell phenotypes. B cells of these subjects have a retained autoimmune potential, lack of somatic hypermutation, profound loss of proliferative potential, accelerated apoptosis and loss of normal Toll-like receptor signalling. Treatment with high-dose immunoglobulin and/or steroids can be helpful, while rituximab provides benefits in the treatment of refractory cytopenias with apparently little risk, even with repeated use, due to ongoing immune globulin therapy.


[Use of immunological and molecular biological methods to diagnose cerebral toxoplasmosis in HIV infection].
Cerebral toxoplasmosis is one of the leading causes of neurologic diseases with high mortality rates in patients with HIV infection. Invasion was difficult to diagnose for a number of objective reasons. The objective of the investigation was to determine the clinical sensitivity of different laboratory techniques as both a single study and their various combinations to verify the diagnosis of cerebral toxoplasmosis in HIV-infected patients. Blood and cerebrospinal fluid were tested in 51 patients with Stage 4B HIV infection (AIDS) with the verified diagnosis of cerebral toxoplasmosis. Separate determination of specific antibodies of IgG, IgM, IgA and toxoplasma DNA in the blood and cerebrospinal fluid was shown to have an insufficient clinical sensitivity (37.3-68.6%). The benefits of various combinations of immunological and molecular biological assays enhancing the diagnostic efficiency up to 76.5-96.1% are demonstrated.


Pineal gland lipid characterization in the seven-week-old cockerel (Gallus domesticus).
The composition of pineal gland lipid was characterized in young cockerels. The total pineal lipid was 159.7 microgram, which was equivalent to 3.0 and 14.1% of fresh and dry tissue weight, respectively. The major phospholipids were phosphatidyl choline (63.1%), phosphatidyl ethanolamine (16.1%), and sphingomyelin (14.7%). Palmitic, stearic, oleic, and arachidonic acids composed 27.9%, 19.4%, 15.8%, and 13.7% of the phospholipid fatty acid fraction, respectively. Free fatty acids (38.4%), cholesterol (17.6%), and cholesterol ester (17.2%) comprised the major fraction of neutral lipids, while the predominant neutral lipid fatty acids were palmitic (26.0%) and oleic (23.8%). The percentage of wet tissue weight that is lipid in the pineal is considerably less when compared to brain cortex or retina. When chickens are compared to several mammalian species, there is little difference in percent lipid per milligram pineal tissue, but definite differences exist in the percentage of various lipid classes.


Free radicals generation by the inflammatory cells.
One of the most impressive property of the leucocytes is that of changing the oxidative metabolism during various functions. When challenged with phagocytosable particles or with membrane perturbing agents such as chemotactic factors, detergents, lectins and other ligands, granulocytes and mononuclear phagocytes undergo a dramatic increase of oxygen consumption which is associated with the production of superoxide anion (O-2), of hydrogen peroxide (H2O2) and of hydroxyl radical (OH.). These events are referred to as "respiratory burst' . Most of the functions of the inflammatory cells (killing of micro-organisms, tissue damage, amplification of the inflammatory process) are linked to the production, to the fate and to the chemical reactivity of these highly reactive compounds. The authors examine the following aspects: (i) the mechanism responsible for the respiratory burst; (ii) the conditions present in the inflammatory site that induces the metabolic activation of leucocytes; (iii) the variability of the respiratory burst in different types of leucocytes; (iv) the fate, the interrelationships and the reactivity of the intermediate products of oxygen reduction; (v) the relationships between the inflammatory process and the production of free radicals by the inflammatory cells.


Natural Products as a Foundation for Drug Discovery.
Many natural products have been used as drugs for the treatment of diverse indications. Although most U.S. pharmaceutical companies have reduced or eliminated their in-house natural-product research over the years, new approaches for compound screening and chemical synthesis are resurrecting interest in exploring the therapeutic value of natural products. The aim of this commentary is to review emerging strategies and techniques that have made natural products a viable strategic choice for inclusion in drug discovery programs. Published 2019. U.S. Government.


[Conceptual basics of paralytic lagophthalmos correction].
The article discusses complications of paralytic lagophthalmos, such as exposure keratopathy, keratitis, corneal lysis, as well as other exposure-related problems and abnormalities of eyelid position. Thorough analysis of surgical methods of eyelids malposition correction, besides conservative protective measures for the cornea, has been performed. The primary treatment goal in facial nerve paralysis is the prevention of severe corneal complications. The most effective methods of static correction of paralytic lagophthalmos, once of narrowing of palpebral fissure by means of circular suture, and different techniques of ectropion correction are discussed. Application results on an upper eyelid implant are presented. Indications for suture and permanent tarsorrhaphy in patients with facial paralysis are also observed.


[Effect of combined vitamin D and E deficiencies on calcium metabolism and bone tissue of the rat].
In experiments on young rats a study was made of the influence of combined vitamin D and E deficiency on biochemical signs of rickets. It was shown that in intact animals vitamin E deficiency induced moderate hypocalcemia, a tendency to decreased Ca active transport in the small intestine and mineral saturation of the bone tissue, as well as a significantly increased Ca content in the skeletal muscles and heart. The concentration of 25-oxyvitamin D (25-OVD) in the blood serum of these animals was not changed. Combined vitamin D and E deficiency intensified disorders typical for rickets; sometimes synergy of such a negative effect was recorded. A delay in the recovery of Ca metabolism parameters, bone tissue condition and 25-OVD circulating concentration persisted, when the animals with vitamin D and E deficiency were injected cholecalciferol during 6 days. The data obtained have evidenced a possible role of vitamin E deficiency in the rickets development, that is, probably, mediated, to a certain extent, by its influence on metabolism and (or) biochemical function of vitamin D.


Cohort profile: the Funen Diabetes Database-a population-based cohort of patients with diabetes in Denmark.
Detailed population-based data are essential to understanding the epidemiology of diabetes and its clinical course. This article describes the Funen Diabetes Database (FDDB). The purpose of the FDDB was to serve as a shared electronic medical record system for healthcare professionals treating patients with diabetes. The cohort can also be used for research. The FDDB covers a geographical area of almost 500 000 Danish inhabitants. It currently includes 3691 patients with type 1 diabetes, 19 085 patients with type 2 diabetes, 292 patients with other types of diabetes and 5992 patients with an unknown type of diabetes. Patients have been continuously enrolled from general practitioners and endocrinology departments in the Funen area in Denmark since 2003. Patients undergo a clinical work-up at their first diabetes contact and during follow-up visits. The information collected includes type of diabetes contact, blood pressure, height, weight, lifestyle factors (smoking, exercise), laboratory records (eg, haemoglobin A1c and cholesterol levels), results from foot examinations (eg, pulse, cutaneous sensitivity and ankle brachial index), results from eye examinations (eg, degree of retinopathy assessed by retinal photo and eye examination), glucose-lowering drugs and diabetic complications. The FDDB cohort was followed for a total of 212 234 person-years up to 2016. A cross-sectional study described the prevalence of diabetic retinopathy and its associated risk factors. The clinical outcomes of patients with type 1 diabetes, type 2 diabetes and latent autoimmune diabetes in adults have been assessed. Linkage to population-based medical registries with complete follow-up has enabled the collection of extensive continuous data on general practice contacts, diagnoses and procedures from hospital contacts, medication use and mortality. The FDDB serves as a strong data resource that will be used in future studies of diabetes epidemiology with focus on occurrence, risk factors, treatment, complications and prognosis.


[Influence of intravenous steroid administration on kidney function].
The acute renal response to 1,0 g Prednisolon i.v. in kidney transplant recipients and normal controls was investigated. The results indicate an acute suppression of glomerular filtration rate (CIN, CCR) and effective plasma flow (CPAH). The reabsorption of sodium in the proximal tubule was shown to be impaired as a direct effect of the steroid infusion, as well as there was an increase in the filtered fraction of potassium. The creatinine clearance under treatment of high doses of steroids does not reflect the actual changes in glomerular filtration rate


Comparison of the paper-based and electronic versions of the Dermatology Life Quality Index: evidence of equivalence.
The use of patient-reported outcome measures in electronic format has been increasing. However, these formats are usually not validated or compared with the original paper-based formats, so there is no evidence that they are completed in the same way. To compare the conventional paper version with a web-based application (iPad® ) version of the Dermatology Life Quality Index (DLQI) to assess equivalence of scores. The study employed a randomized crossover design using a within-subjects comparison of the two formats of the questionnaire. International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines were followed. Participants aged over 18 years with any confirmed skin condition were recruited from a teaching hospital dermatology outpatient clinic. Expected intraclass correlation coefficient (ICC) was 0·9 (α = 0·05). A total of 104 patients were recruited, median age 53·5 years (interquartile range 37·3-67·8; 43% male). The ICC showed high concordance between the total DLQI scores from paper and iPad versions (ICC 0·98; 95% confidence interval 0·97-0·99). Patients took a median of 78 s to complete the electronic version and 73 s for paper (P = 0·008): 76% preferred the electronic version and perceived completion to take a shorter time. There is high concordance and thus equivalence between the iPad and paper versions of the DLQI, with an ICC of 0·98, and a clear patient preference for the iPad version.


Effects of space flight on endocrine system function in experimental animals.
The effects exposing rats to space flights of various lengths in a series of COSMOS satellites are reported based on an evaluation of plasma hormone levels and several enzyme activities in the tissues. The results after space flights are compared with those obtained from rats exposed to acute or repeated stress. Space flight induced selective morphological responses in the corticotrophs and gonadotrophs of the pituitary. Plasma levels of ACTH did not change, but plasma growth hormone and TSH levels decreased after longer space flights (>14 days), while prolactin in the plasma increased after short flights (5-7 days). Plasma corticosterone was higher after all flights. Catecholamine levels in plasma increased only after long space flights. These changes in plasma hormone levels affected the activities of enzymes involved in the amino acid metabolism of the liver and lipolysis in the adipose tissues. Norepinephrine level and catecholamine synthesizing enzyme activity in the hypothalamus did not change in flight rats. The norepinephrine content, however, decreased in several nuclei selected from the hypothalamus of flight rats. Increases in plasma insulin and glucose were noted in rats after space flight. Glucagone values in plasma remained unchanged. Comparing these results from flight rats against rats exposed to acute or repeated stress indicate that long stays in microgravity do not represent intensive stressogenic stimulus of the adrenocortical and sympathetic adrenomedullar systems, and hormone alterations observed after space flight may be due primarily to acute stressor activity resulting from a return to Earth's gravity (gravitational stress).


[High-dose chemotherapy with four drugs and peripheral blood progenitor cell autologous transplantation in disseminated breast cancer].
To evaluate the therapeutic efficacy (in terms of overall survival [OS] and progression-free survival [PFS]) of a high-dose chemotherapy protocol including four drugs and peripheral stem cell rescue (PSCR) plus posttransplant G-CSF (filgrastim) in disseminated breast cancer patients. Fifty-three metastatic breast cancer patients were treated with a four-drug program of high-dose chemotherapy including cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), carboplatin (800-1,600 mg/m2) and mitoxantrone (20-60 mg/m2) with autologous peripheral blood progenitor cell support followed by filgrastim. Most cases (92%) had previously received conventional induction chemotherapy with anthracycline-containing combinations. After a median follow-up of 27 months (range 12-43 months) from transplant, the median survival of the overall group was 25 months, with an OS projected at 43 months of 31%. Patients in complete remission after induction chemotherapy or status NED (no evidence of disease: surgical resection of metastases) presented the best outcome, with a projected PFS of 50% at 43 months. Patients intensified without complete response had a poor outcome. The most important extramedullary toxicity was mucositis. Four patients (7.5%) died as a consequence of treatment (2 with sepsis-associated ARDS, one with venooclussive disease of the liver, one with congestive cardiac failure). The outcome of metastatic breast cancer patients in complete remission after induction chemotherapy or NED status seems to be good with our high-dose chemotherapy including four drug and PSCR. On the other hand, patients intensified without complete response presented a bad outcome and do not seem candidates for future trials with this therapeutic approach.


Automatic Reaction Pathway Search via Combined Molecular Dynamics and Coordinate Driving Method.
We proposed and implemented a combined molecular dynamics and coordinate driving (MD/CD) method for automatically searching multistep reaction pathways of chemical reactions. In this approach, the molecular dynamic (MD) method at the molecular mechanics (MM) or semiempirical quantum mechanical (QM) level is employed to explore the conformational space of the minimum structures, and the modified coordinate driving (CD) method is used to build reaction pathways for representative conformers. The MD/CD method is first applied to two model reactions (the Claisen rearrangement and the intermolecular aldol reaction). By comparing the obtained results with those of the existing methods, we found that the MD/CD method has a comparable performance in searching low-energy reaction pathways. Then, the MD/CD method is further applied to investigate two reactions: the electrocyclic reaction of benzocyclobutene-7-carboxaldehyde and the intramolecular Diels-Alder reaction of ketothioester with 11 effectively rotatable single bonds. For the first reaction, our results can correctly account for its torquoselectivity. For the second one, our method predicts eight reaction channels, leading to eight different stereo- and regioselective products. The MD/CD method is expected to become an efficient and cost-effective theoretical tool for automatically searching low-energy reaction pathways for relatively complex chemical reactions.


Autologous Chondrocyte Implantation in Osteoarthritic Surroundings: TNFα and Its Inhibition by Adalimumab in a Knee-Specific Bioreactor.
Autologous chondrocyte implantation (ACI) fails in up to 20% of cases. Advanced intra-articular degeneration paired with an inflammatory environment may be closely related to implantation failure. Certain cytokines have been identified to play a major role during early osteoarthritis. To investigate the effects of tumor necrosis factor α (TNFα) and its potential inhibition by adalimumab on cartilage regeneration in an in vitro model of ACI. Controlled laboratory study. Bovine articular chondrocytes were cultivated and transferred at passage 3 to fibrin-polyurethane scaffolds. Constructs were loaded by compression (10%-20% scaffold height) and shear (±25°) in a fully characterized multiaxial load (L) bioreactor to simulate clinical ACI or were subjected to free swelling (FS) conditions for a duration of 2 weeks. TNFα (20 ng/mL), adalimumab (10 µg/mL), or both were added to the medium. To assess the outcome, DNA, GAG (glycosaminoglycan), and total collagen were quantified, and gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein, proteoglycan 4), catabolic (matrix metalloproteinases [MMP] 3 and 13), dedifferentiation (collagen 1), and hypertrophy (collagen 10) markers and proinflammatory cytokines (TNFα, IL-1β) was analyzed. Histological evaluation was performed with safranin O/fast green, toluidine blue, and immunohistochemistry of collagen 1 and 2. Apoptosis was analyzed by immunolabeling of anti-active caspase 3. For statistical evaluation, nonparametric tests were chosen with a significance level of P < .05. A general downregulation of anabolic and upregulation of catabolic markers was detected in the TNFα groups. Collagen 2 was suppressed by TNFα (FS, P = .029; L, P = .006), while MMP 3 was significantly upregulated (FS, P = .035; L, P = .001). Dynamic loading induced a chondrogenic response, which could not fully antagonize the effect of the cytokine. Adalimumab antagonized all effects of TNFα. The histological and immunohistochemical assessments demonstrated less matrix formation in the cytokine-only groups. TNFα induced apoptosis, and this effect was increased by loading. TNFα does negatively affect chondrogenesis under simulated ACI conditions. Both dynamic load and, more potentially, adalimumab showed the capability of antagonizing the negative effects. Catabolic cytokine suppression (ie, TNFα inhibition) combined with compression and shear load may best meet the conditions for chondrogenesis in an osteoarthritic environment.


Metabolic response of pelvic and para-aortic lymph nodes during radiotherapy for carcinoma of the uterine cervix: using positron emission tomography/computed tomography.
We evaluated the metabolic response of lymph nodes (LNs) using consecutive F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) and correlated the metabolic response with the volumetric response measured by consecutive CT. Twenty-two patients with cervical cancer that had positive LNs underwent preradiotherapy (pre-RT) and inter-RT PET/CT. The metabolic response of the LNs was assessed quantitatively and semiquantitatively by measurement of the maximal standardized uptake value. All patients underwent inter-RT CT simulation after 45 Gy to the whole pelvis and inter-RT PET/CT scans after median 63 Gy to the gross LNs. A total of 48 pelvic and para-aortic LNs were found on the pre-RT PET/CT. The mean maximal standardized uptake value of nodal disease decreased from the pre-RT of 5.2 (SD, 3.1; range, 1.8-15.6) to the inter-RT of 1.1 (SD, 2.1; range, 0-11.1). Classifying the metabolic response of all 48 nodal lesions on the inter-RT PET/CT, 38 had a complete metabolic response. The initial volume of LNs had no correlation with the metabolic response (r = 0.194, P = 0.186). The metabolic response between the pre-RT PET/CT and inter-RT PET/CT was significantly associated with the volume response between the pre-RT CT and inter-RT CT (r = 0.314, P < 0.05). However, 18 (38%) LNs showed discrepancy between metabolic response and residual LN volume. Six (27%) patients had modified RT during treatment based on inter-RT PET/CT. We suggest that the PET/CT can be a useful tool for the evaluation of the interim response of the LNs and aid in selecting patients that need further treatment. The results showed a significant correlation between the metabolic and volumetric responses during RT, although the anatomical changes of LNs would not always represent the metabolic status.


Real-world treatment patterns of gout patients treated with colchicine or other common treatments for gout in acute care settings: a retrospective chart review study.
To describe real-world treatment patterns of patients receiving colchicine or other treatments during a gout-related emergency room or acute care facility (ER/ACF) visit. An online physician-administered questionnaire was used to collect chart data on 500 patients with a gout-related ER/ACF visit after 16 October 2009; 250 patients receiving colchicine (Colchicine Cohort) and 250 receiving NSAIDs, systemic corticosteroids, narcotics, allopurinol, febuxostat, pegloticase, probenecid, or sulfinpyrazone (Other Cohort). Patient characteristics and treatment received/prescribed during the ER/ACF visit (Period 1 [P1]), at discharge (P2), and at the first follow-up visit (P3) are reported. A total of 45 rheumatologists and 63 primary care physicians participated in the study. Patient mean age was 51 years and 74.8% were male. The most common treatments in the Other Cohort were NSAIDs (59.6%), systemic corticosteroids (45.2%), and narcotics (33.6%). The 500 patients contributed 307 distinct treatment patterns from P1 to P3. Of the 20.6% patients not prescribed a treatment in P2, 60.2% were restarted on a treatment in P3. Of the 78.6% treated patients in P2, 27.0% had a treatment adjustment (dose increase, treatment add-on, or initiation of a different gout-related treatment - not with a urate lowering therapy only) in P3; for 72.6% of these patients, physicians justified the treatment adjustment by inadequacy of the treatment for maintenance therapy, insufficient dosage, or inadequate response. In the Colchicine Cohort, 60.8% of patients were prescribed colchicine consistently from P1 to P3, while 26.8% and 17.7% of patients in the Other Cohort were prescribed consistently NSAIDs and systemic corticosteroids from P1 to P3, respectively. Specific nature of the acute gout-related symptoms or potential attack/flare during the ER/ACF visit was not recorded. Real-world clinical practice reveals a substantial number of distinct treatment patterns and frequent treatment adjustments by treating physicians for patients with a gout-related ER/ACF visit.


Ocean deoxygenation in a warming world.
Ocean warming and increased stratification of the upper ocean caused by global climate change will likely lead to declines in dissolved O2 in the ocean interior (ocean deoxygenation) with implications for ocean productivity, nutrient cycling, carbon cycling, and marine habitat. Ocean models predict declines of 1 to 7% in the global ocean O2 inventory over the next century, with declines continuing for a thousand years or more into the future. An important consequence may be an expansion in the area and volume of so-called oxygen minimum zones, where O2 levels are too low to support many macrofauna and profound changes in biogeochemical cycling occur. Significant deoxygenation has occurred over the past 50 years in the North Pacific and tropical oceans, suggesting larger changes are looming. The potential for larger O2 declines in the future suggests the need for an improved observing system for tracking ocean 02 changes.


Can Clinician-Stabilization with Hand-Held Dynamometry Yield a Reliable Measure of Knee Flexion Torque?
Assessment of knee flexion torque is a relevant clinical measure following various injuries and surgeries to determine progress in rehabilitation and inform decision making. A variety of methods using hand-held dynamometry have been shown to be reliable in obtaining this measure, and typically require a means of external fixation or stabilization. Clinically efficient methods of reliable clinician-stabilization are sparse in the literature. Determine inter and intra-rater reliability of two clinically efficient methods of assessing isometric knee flexion torque using hand-held dynamometry with clinician-stabilization. The hypothesis was that each method would yield good to excellent reliability. Cross-Sectional Study. Twenty healthy individuals were assessed by two clinicians on two separate days. During each session, knee flexion torque was assessed with hand-held dynamometry with two methods: 1) in the seated position with the hip and knee flexed to 90 degrees while the clinician stabilized the dynamometer between the participant's leg and table and 2) in prone with the hip at 0 degrees and knee at 90 degrees while the clinician assumed a stride stance with elbows locked in extension to stabilize the dynamometer on the participant's leg. Inter and intra-rater reliability were determined for each method. ICC values were 0.88-0.94 and 0.77-0.90 for inter and intra-rater reliability respectively with the seated method. The prone method yielded ICC values of 0.84-0.96 and 0.89-0.94 for inter and intra-rater reliability respectively. MDC values ranged from 30-62% with the seated method and 21-40% with the prone method. Inter and intra-rater reliability were good to excellent for assessing knee flexion torque with hand-held dynamometry using both the seated and prone methods with clinically efficient clinician-stabilization approaches. The prone method may be more sensitive to detecting change over time due to lower MDC values. 2b.


Epizootic of balantidiasis in lowland gorillas.
Acute enteritis characterized by watery diarrhea and lethargy occurred in 4 lowland gorillas (Gorilla gorilla gorilla) during a 5-week period at the Los Angeles Zoo. Numerous trophozoites of Balantidium coli were seen in fresh feces from each gorilla. Potentially pathogenic bacteria were isolated from 1 fecal sample. Results of fecal flotation examinations were negative for eggs of metazoan parasites. The gorillas were treated with antibiotics and metronidazole or paromomycin, or both. The most severely affected gorilla had blood and mucus in its feces, became dehydrated, and required hospitalization for supportive fluid therapy. This gorilla as well as the other gorillas recovered rapidly with treatment. Balantidium coli was not seen in fecal samples after the gorillas' recovery.


Complete amino acid sequence of the catalytic chain of human complement subcomponent C1-r.
The amino acid sequence of human C1-r b chain hs been determined, from sequence analysis performed on fragments obtained by CNBr cleavage, dilute acid hydrolysis, tryptic cleavage of the succinylated protein, and subcleavages by staphylococcal protease. The polypeptide chain contains 242 amino acids (Mr 27 096), and the sequence shows strong homology with other mammalian serine proteases. The histidine, aspartic acid, and serine residues of the active site (His-57, Asp-102, and Ser-195 in bovine chymotrypsinogen) are located at positions 39, 94, and 191, respectively. The chain which lacks the "histidine-loop" disulfide bridge, contains five half-cystine residues, of which four (positions 157-176 and 187-217) are homologous to residues involved in disulfide bonds generally conserved in serine proteases, whereas the half-cystine residue at position 114 is likely to be involved in the single disulfide bridge connecting the catalytic b chain to the n-terminal a chain. Two carbohydrate moieties are attached to the polypeptide chain, both via asparagine residues at positions 51 and 118.


Independent expression of Rep and RepA and their roles in regulating bean yellow dwarf virus replication.
Bean yellow dwarf virus (BeYDV) is a mastrevirus specific for dicotyledenous hosts. It contains four ORFs encoding a movement protein, a coat protein, and two Rep gene products, Rep and RepA, which are encoded by two overlapping ORFs. In this study, the roles of Rep and RepA in regulating replication of the BeYDV-based replicon were investigated by uncoupling them and placing Rep and RepA each under constitutive promoter control. Constitutive expression of both Rep and RepA supported replication and enhanced gene expression. When a reporter plasmid containing the Rep gene in the context of its native promoter was supplemented with additional Rep protein, replication was enhanced but the increase in gene expression was found to be more modest. Furthermore, expression of constitutively expressed RepA alone was found to reduce replication of this reporter construct as well as delay BeYDV replication in general. The effect of a RepA mutant with an altered retinoblastoma-related-protein binding motif on the efficiency of BeYDV replication was also examined. This mutant was found to severely diminish replication efficiency. Finally, the relationship of BeYDV coat protein to virus replication and reporter gene expression was investigated. Addition of coat protein increased accumulation of single-stranded DNA and had a detrimental effect on reporter gene expression.


Enhancing Anticipatory and Compensatory Postural Responses to Improve Balance in Individuals with TBI.
Traumatic Brain Injury (TBI) is one of the leading causes of sensorimotor deficits in adults and often results in balance impairments. Two types of postural mechanisms are employed to achieve balance during perturbations: Anticipatory Postural Adjustments (APA) and Compensatory Postural Adjustments (CPA). People with TBI have reduced APA/CPA responses due to sensory-motor deficits from the injury. The objective of this feasibility study was to evaluate a Perturbation-based Balance Training program with visual cues (PBTvc) to target both APA/CPA responses to improve balance. The evaluation included biomechanical (reactive balance during random perturbation) and functional (Berg Balance Scale, Timed Up and Go and Falls Efficacy Scale) metrics. Preliminary data is presented for two participants with chronic TBI who received 16 sessions of PBTvc. The results show an improved range of trunk oscillation and time to stability during random perturbation tasks with corresponding improvements in Berg Balance Scale, Timed Up & Go, and Falls Efficacy Scale. The results suggest that PBTvc has the potential to improve APA/CPA mechanisms for functional recovery.Clinical Relevance- Preliminary data provides initial evidence for PBTvc as a therapeutic intervention for balance rehabilitation in adults with TBI.


Ductal carcinoma in situ: what the pathologist needs to know and why.
Ductal carcinoma in situ is a proliferation of malignant epithelial cells confined to the ductolobular system of the breast. It is considered a pre-cursor lesion for invasive breast cancer and when identified patients are treated with some combination of surgery, +/- radiation therapy, and +/adjuvant tamoxifen. However, no good biomarkers exist that can predict with accuracy those cases of DCIS destined to progress to invasive disease or once treated those patients that are likely to suffer a recurrence; thus, in the era of screening mammography it seems likely that many patients with DCIS are overtreated. This paper details the parameters that should be included in a pathology report for a case of DClS with some explanations as to their importance for good clinical decision making.


[Jadassohn linear nevus sebaceous. Report of a case].
Report of a case of linear nevus sebaceous of Jadassohn with the classical syndrome: 1) the facial linear nevus; 2) focal convulsions and 3) mental retardation. Skin biopsy didn't show proliferation of the sebaceous glands showing to be an early case. Computerized tomography showed slight cortico-subcortical atrophies, in contrast with the intensity of the mental retardation and focal crisis. Convulsions were controlled by several drug associations.


Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry.
The French Acromegaly Registry records data of acromegalic patients' since 1992 in French, Belgian (Liège), and Swiss (Lausanne) centers. We studied the prevalence of diabetes in this population looking for risk factors. Patients from one of the centers (Reims) were then analyzed more thoroughly. This study has been conducted on all the patients recorded from 1999 until 2004 (519 patients). Evolution of cohorts' was reassessed in 2009. Of the different variables recorded in the registry: age, sex, body mass index (BMI), duration of acromegaly, GH, IGF1 and prolactin levels, pituitary tumor size, hormonal deficiencies, presence, duration and treatment of diabetes, hypertension, and rheumatological disease were analyzed. The prevalence of diabetes in the registry was 22.3%. Diabetic patients were older and had a higher BMI. Compared with the data of the French Social Security, acromegalic patients showed a more precocious apparition of diabetes and prevalence was higher in each age group. Compared with non-diabetic acromegalic subjects, diabetic patients had a more prolonged evolution of acromegaly before diagnosis. The levels of GH and IGF1 were not significantly different between the two groups. Only hypertension was significantly more frequent in diabetic patients. In our population, the prevalence of diabetes was estimated to be 22.3%. The GH and IGF1 levels did not appear as predictive factors for the presence of diabetes. On the contrary, age, BMI, and hypertension were significant risk factors as in the general population of type 2 diabetics.


Compression of dynamic tactile information in the human hand.
A key problem in the study of the senses is to describe how sense organs extract perceptual information from the physics of the environment. We previously observed that dynamic touch elicits mechanical waves that propagate throughout the hand. Here, we show that these waves produce an efficient encoding of tactile information. The computation of an optimal encoding of thousands of naturally occurring tactile stimuli yielded a compact lexicon of primitive wave patterns that sparsely represented the entire dataset, enabling touch interactions to be classified with an accuracy exceeding 95%. The primitive tactile patterns reflected the interplay of hand anatomy with wave physics. Notably, similar patterns emerged when we applied efficient encoding criteria to spiking data from populations of simulated tactile afferents. This finding suggests that the biomechanics of the hand enables efficient perceptual processing by effecting a preneuronal compression of tactile information.


A Pineal Parenchymal Tumor of Intermediate Differentiation in an Octogenarian Contains a Rare KBTBD4 Insertion.
Pineal parenchymal tumors are rare central nervous system tumors that pose diagnostic challenges for surgical pathologists. Due to their paucity, their clinicopathologic features are still being defined. We report an 86-year-old woman with a remote history of breast lobular carcinoma who presented with a 2-month neurologic history that included gait instability, blurry vision, and headaches. Magnetic resonance imaging revealed a lobular, heterogeneously enhancing pineal region mass compressing the aqueduct of Sylvius. A biopsy performed concomitant with endoscopic third ventriculostomy consisted of small sheets of cells with eosinophilic to clear cytoplasm, multipolar processes, and ovoid nuclei with stippled chromatin. Whole exome sequencing revealed a small in-frame insertion (duplication) in exon 4 of KBTBD4 (c.931_939dup, p.P311_R313dup/ p.R313_M314insPRR), which has very recently been reported in 2 pineal parenchymal tumors of intermediate differentiation (PPTID). Additionally, variants of uncertain significance in CEBPA (c.863G > C, p.R288P) and MYC (c.655T > C, p.S219P) were identified. Although PPTID is considered a disease of young adulthood, review of 2 institutional cohorts of patients with pineal region tumors revealed that 25% of individuals with PPTID were over 65 years of age. In conclusion, PPTID should be considered in the differential diagnosis of pineal region tumors in older adults.


Dental Treatment of a Child with Pallister-Killian Syndrome.
The Pallister-Killian syndrome (PKS) is an extremely rare genetic disorder with an incidence estimated around 1/25000. PKS is a multiple congenital anomaly deficit syndrome caused by mosaic tissue limited tetrasomy for chromosome 12p. The presented report is the first confirmed case with PKS in Turkey. This report focuses on the orofacial clinical manifestations of an 6-year-old boy with PKS who was referred to the Department of Paediatric Dentistry clinic, Gazi University. It has been learned that the PKS was diagnosed 1 year after birth. Due to intellectual disability, it was decided to make the dental treatments under moderate sedation. Although significant tongue thrust and anterior open bite were determined, any oral appliances could not be applied because of the 2 epilepsy seizures in the last 2 years. The aim was to treat decayed teeth and set good oral hygiene in the patient's mouth. Still, there is a probability for epilepsy seizures. If epileptic seizures stop permanently, we can apply an oral appliance to block tongue thrust. The patient is now under control. In cases of systemic and oral findings such as PKS, conducting medical and dental approaches together will increase the life quality of patients.


Identification of a subdomain of CENP-B that is necessary and sufficient for localization to the human centromere.
We have combined in vivo and in vitro approaches to investigate the function of CENP-B, a major protein of human centromeric heterochromatin. Expression of epitope-tagged deletion derivatives of CENP-B in HeLa cells revealed that a single domain less than 158 residues from the amino terminus of the protein is sufficient to localize CENP-B to centromeres. Centromere localization was abolished if as few as 28 amino acids were removed from the amino terminus of CENP-B. The centromere localization signal of CENP-B can function in an autonomous fashion, relocating a fused bacterial enzyme to centromeres. The centromere localization domain of CENP-B specifically binds in vitro to a subset of alpha-satellite DNA monomers. These results suggest that the primary mechanism for localization of CENP-B to centromeres involves the recognition of a DNA sequence found at centromeres. Analysis of the distribution of this sequence in alpha-satellite DNA suggests that CENP-B binding may have profound effects on chromatin structure at centromeres.


Antibiotics and pancreatitis.
Despite improvements in the general supportive care of patients with acute pancreatitis, the morbidity of infectious complications remains high and bacterial infections account for most deaths. The role of antibiotics in reducing infectious morbidity and mortality has been debated for decades because of a lack of supportive clinical data. Research completed over the past decade has helped to define the microbiology, establish the risk factors, and improve the understanding of the pathogenesis of infectious complications in patients with acute pancreatitis. Patients with acute necrotizing pancreatitis are at the greatest risk of developing an infection with enteric gram-negative or gram-positive bacteria translocated from the bowel lumen into the necrotic pancreatic tissue. The most effective antimicrobial agents are the fluoroquinolones, imipenem-cilastatin, and metronidazole, which achieve adequate penetration into pancreatic juice and necrotic tissue and inhibit the growth of enteric bacteria. Animal and human studies support the use of antibiotics for the prevention of infectious morbidity and mortality in severe acute pancreatitis. Recent clinical trials have assessed the role of both systemic antibiotic prophylaxis and selective bowel decontamination with nonabsorbable oral antimicrobials in high-risk patients with acute necrotizing pancreatitis. This article provides an overview of our current knowledge of pancreatic infections and a critical analysis of studies on the role of antibiotics in this disease.


Transcription factor-dependent regulation of CBP and P/CAF histone acetyltransferase activity.
CREB-binding protein (CBP) and CBP-associated factor (P/CAF) are coactivators possessing an intrinsic histone acetyltransferase (HAT) activity. They are positioned at promoter regions via association with sequence-specific DNA-binding factors and stimulate transcription in a gene-specific manner. The current view suggests that coactivator function depends mainly on the strength and specificity of transcription factor-coactivator interactions. Here we show that two dominant-negative mutants of hepatocyte nuclear factor-1alpha (HNF-1alpha), P447L and P519L, occurring in maturity onset diabetes of the young (MODY3) patients, exhibit paradoxically stronger interactions than the wild-type protein with either CBP or P/CAF. However, CBP and P/CAF recruited by these mutants lack HAT activity. In contrast, wild-type HNF-1alpha and other transcription factors, such as Sp1 or HNF-4, stimulated the HAT activity of CBP. The results suggest a more dynamic role for DNA-binding proteins in the transcription process than was considered previously. They are not only required for the recruitment of coactivators to the promoter but they may also modulate their enzymatic activity.


Bioengineering of physiologically functional intrinsically innervated human internal anal sphincter constructs.
Muscle replacement for patients suffering from extensive tissue loss or dysfunction is a major objective of regenerative medicine. To achieve functional status, bioengineered muscle replacement constructs require innervation. Here we describe a method to bioengineer functionally innervated gut smooth muscle constructs using neuronal progenitor cells and smooth muscle cells isolated and cultured from intestinal tissues of adult human donors. These constructs expressed markers for contractile smooth muscle, glial cells, and mature neuronal populations. The constructs responded appropriately to physiologically relevant neurotransmitters, and neural network integration was demonstrated by responses to electrical field stimulation. The ability of enteric neuroprogenitor cells to differentiate into neuronal populations provides enormous potential for functional innervation of a variety of bioengineered muscle constructs in addition to gut. Functionally innervated muscle constructs offer a regenerative medicine-based therapeutic approach for neuromuscular replacement after trauma or degenerative disorders.


Major Adverse Cardiovascular Events and Prognosis in Patients With Coronary Slow Flow.
This study aimed to investigate its clinical implications, risk factors, prognosis, and overall long-term outcomes. Demographic profiles, various clinical characteristics, and clinical outcomes were compared between 614 patients with coronary slow flow (CSF) and 428 patients with normal coronary artery. The incidence of CSF was found to be 2.65%. Significant differences were observed between patients with CSF and control subjects in terms of sex, chest tightness, hyperlipidemia, smoking history, alcohol consumption, age, height, weight, body mass index, diastolic blood pressure, heart rate, and body surface area (P < 0.05). CSF (hazard ratio: 1.531; 95% confidence interval: 1.064-2.202; p = 0.022) proved to be independent prognostic predictors of major adverse cardiovascular events (MACEs). Kaplan-Meier survival evaluations for MACEs presented a worser outcome for patients with CSF. Patients with CSF are at high risk for cardiovascular events and experience generally poor clinical outcomes.


Effect of cold indoor environment on physical performance of older women living in the community.
the effects of cold on older persons' body and mind are not well documented, but with an increased number of older people with decreasing physical performance, these possible effects need to be understood. to investigate the effect of cold indoor environment on physical performance of older women. cross-sectional experimental study with two test conditions. movement laboratory in a climate chamber. eighty-eight community-dwelling, cognitively unimpaired older women (mean age 78 years). participants were exposed to moderately cold (15°C) and warm/normal (25°C) temperature in a climate chamber in random order with an interval of 1 week. The assessment protocol included leg extensor power (Nottingham Power Rig), sit-to-stand performance velocity (linear encoder), gait speed, walk-ratio (i.e. step length/cadence on an instrumented walk way), maximal quadriceps and hand grip strength. physical performance was lower in 15°C room temperature compared with 25°C room temperature for leg extensor power (P < 0.0001), sit-to-stand performance velocity (P < 0.0001), gait speed (P < 0.0001), walk-ratio (P = 0.016) and maximal quadriceps strength (P = 0.015), but not for hand grip strength. in healthy older women a moderately cold indoor environment decreased important physical performance measures necessary for independent living.


Sulfated glycosaminoglycan-based block copolymer: preparation of biocompatible chondroitin sulfate-b-poly(lactic acid) micelles.
Despite a growing interest in amphiphilic polysaccharide-based diblock copolymers as functional polymeric drug delivery nanosystems, biologically relevant sulfated glycosaminoglycan systems were not yet investigated. Here, we report the synthesis and the self-assembly properties in water of chondroitin sulfate-b-poly(lactic acid) (CS-b-PLA(n)). The CS-b-PLA(n) were synthesized using click-grafting onto method implying reducing-end alkynation of low-molecular weight depolymerized CS (M(w) = 5000 g·mol(-1)) and azide-terminated functionalization of PLAn (M(w) = 6500 g·mol(-1) (n = 46) and M(w) = 1700 g·mol(-1) (n = 20)). The diblock copolymer self-assembled in water giving rise to spherical micelles that were characterized in solution using dynamic/static light scattering and at dry state by TEM technique. In vitro assays on healthy cells showed that at high concentrations, up to 10 μg·mL(-1), CS-b-PLA(n) were noncytotoxic. Those preliminary studies are promising in the perspective to use them as biocompatible nanovehicles for anticancer drug delivery.


Circumstantial evidence for phytoalexin involvement in the resistance of peanuts to Aspergillus flavus.
Three stilbene phytoalexins, elicited by slicing and incubating imbibed peanut kernels under aerobic conditions, inhibited spore germination and hyphal extension of Aspergillus flavus with ED50 values in the range 4.9-12.8 micrograms ml-1. Phytoalexin yield was dependent on cultivar, conditions and duration of incubation after slicing, and crop history. The yield of phytoalexin from ten cultivars studied, after slicing and incubating at 25 degrees C for 24 h, ranged from 28 to 935 micrograms per g fresh weight and was negatively correlated with dry kernel colonization by A. flavus [r = -0.868 when plotted as 1n (phytoalexin concn) against 1n (percentage peanut colonization)]. When the incubation period was extended to 96 h there was no such correlation. Reduced phytoalexin yields were obtained when sliced kernels of one cultivar studied were incubated in water or at 37 degrees C, and no phytoalexin was obtained when the slices were incubated under nitrogen gas or frozen before aerobic incubation. Drought stress during pod development in four cultivars studied reduced phytoalexin yields of sliced kernels incubated at 25 degrees C for 24 h by 17-65% compared with non-stressed controls.


Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies.
In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16-213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.


Femoral/axillary volume flow ratio as a new index for the assessment of iliac atherosclerosis.
To measure the arterial volume flow (VF) with duplex scan, calculate femoral/axillary VF ratio, and discuss its applicability as a new index for the hemodynamic significance of an aorto-iliac occlusive lesion. Several measures of VF were obtained consecutively with duplex scan in both common femoral and axillary arteries of healthy volunteers with no signs of atherosclerosis and patients with documented evidence of occlusive aorto-iliac disease with segmental pressure measurement. Then the patient group was sent to complimentary evaluation for a second confirmatory examination. There were a total of 635 measures of VF performed in 10 healthy volunteers and 8 patients with severe iliac stenoses or occlusion, 2 of then with bilateral disease. When comparing normal participants and patients with severe iliac stenoses or occlusion, there was statistical significant difference between these 2 groups (P < .01 Mann-Whitney). Similar result was found when comparing patient with diseased limbs with their own contralateral normal side (P < .05 Wilcoxon). And measuring the VF only during the systolic phase was a much more sensitive parameter for differentiating the normal from the diseased. Besides that a good correlation between proximal thigh pressure index and femoral/axillary systolic flow ratio was found in the patient group (P < .01 Spearman correlation). The femoral/axillary VF ratio is useful in assessing the hemodynamic significance of aorto-iliac disease, and the systolic femoral-axillary ratio may also be useful as a follow-up tool.


[Physicochemical study of the state of protein and lipid phases in synaptosome membranes following irradiation with fast electrons].
No activation of lipid peroxidation and structural rearrangements were noted in the lipid phase of synaptosome membranes after exposure of animals to electrons of 300 Gy/min at doses inducing cerebral lesions. At the same time, in isolated synaptosome membranes, radiation induced defined changes manifested by a decrease in tryptophan fluorescence.


A new rRNA processing mutant of Saccharomyces cerevisiae.
We have identified from a collection of temperature sensitive yeast mutants strains which fail to process rRNA normally. Characterization of one such mutant is reported here. This strain accumulates increased amounts of the 35S primary transcript, '24S' molecules extending from the transcription start site to the 5.8S region, and two classes of 5.8S rRNA with 5' extensions of 7 and 149 bases, respectively. We show that this pleiotropic change in the rRNA processing pattern is due to a single mutation. Possible models for the function of the mutated gene are discussed.


Combined cremaster muscle and inner thigh skin composite flap: a novel experimental flap model in the rat.
Unlike the composite musculocutaneous flap models, the combined composite muscle-skin flap model allows evaluating muscle and skin viability independently, because it has an independent blood supply to the muscle and skin component. However, to our knowledge, only two combined muscle-skin flaps have been reported to date. During our cremaster dissection in our laboratory, we perceived a new vessel as a terminal continuation of the pudic-epigastric artery (PEA) on which the cremaster muscle flap is raised. Therefore, we designed this study to determine whether the scrotal and inner thigh skin can be harvested with the cremaster muscle as a combined cremaster muscle-skin composite flap. Thirty male Sprague-Dawley rats were used in this experiment. In five rats, ink study selective to the PEA marked a skin territory. In 15 rats, cremaster muscle and 4 x 3 cm ipsilateral scrotal and medial thigh skin flap was raised on the PEA. Fluorescein study after 4 hours showed fluorescein stain in the skin island. On postoperative day 7, both muscle and skin components of the flaps were viable. Microangiographic study after the flap elevation revealed the vascularity of all components of the flap and clearly identified the branch to the skin island. To the best of our knowledge, this is the first report describing the combined flap model including the cremaster muscle. Our flap seems to have an important advantage over the other combined muscle-skin flap models in terms of the cremaster muscle being suitable for the intravital microscopy. Additionally, the two components of the flap have separate nutrient vessels with adequate length, which gives the flap flexibility in the placement of the skin component in a location distant from the muscle component. The flap may be also be raised as a skin flap without the cremaster muscle. It can be used for different applications, including microcirculatory, pharmacological, physiological, biochemical, and immunological studies as well as for transplantation studies.


Complexity within the plasma cell compartment of mice deficient in both E- and P-selectin: implications for plasma cell differentiation.
Antibody-secreting plasma cells represent the critical end-stage effector cells of the humoral immune response. Here, we show that several distinct plasma cell subsets are concurrently present in the lymph nodes, spleen, and bone marrow of mice deficient in both E- and P-selectin. One of these subsets was a B220-negative immunoglobulin g (IgG) plasma cell population expressing low to negative surface levels of syndecan-1. Examination of the chemotactic responsiveness of IgG plasma cell subsets revealed that migration toward stromal cell-derived factor 1/CXC ligand 12 (SDF-1/CXCL12) was primarily limited to the B220-lo subset regardless of tissue source. Although B220-negative plasma cells did not migrate efficiently in response to CXCL12 or to other chemokines for which receptor mRNA was expressed, these cells expressed substantial surface CXC chemokine receptor-4 (CXCR4), and CXCL12 stimulation rapidly induced extracellular signal regulated kinase 1 (ERK1)/ERK2 phosphorylation, demonstrating that CXCR4 retained signaling capacity. Therefore, B220-negative plasma cells exhibit a selective uncoupling of chemokine receptor expression and signaling from migration. Taken together, our findings document the presence of significant heterogeneity within the plasma cell compartment, which suggests a complex step-wise scheme of plasma cell differentiation in which the degree of differentiation and tissue location can influence the chemotactic responsiveness of IgG plasma cells.


Poor survival in t(8;21) (q22;q22)-associated acute myeloid leukaemia with leukocytosis.
Twenty-nine consecutive cases with a t(8;21)(q22;q22) in the bone marrow (BM) karyotype were retrospectively studied concerning clinical, morphological and cytogenetic data. All had been diagnosed as acute myeloid leukaemia (AML), 27 FAB subtype M2 and two M1, comprising 5% of all cytogenetically analysed AML during 18 yr. Auer rods were the most consistent t(8;21)-associated morphological finding and were demonstrated in 92% of the reviewed BM specimens, whereas BM eosinophilia was seen in only 24%. The median age was 53 yr, and 30% of the patients were > 60 yr old. Twenty-four patients had received induction chemotherapy; 22 of these (91%) entered a complete remission (CR). The median survival time in treated patients was 18 months. Leukocytosis at diagnosis (> or = 20 x 10(9)/1) was significantly (p = 0.01) associated with shorter survival time. All four children are still in first CR after 9-80 months. Seven cases (25%) developed granulocytic sarcomas, discovered either at diagnosis (n = 4) or at first relapse (n = 3). Secondary chromosome abnormalities were found in 62% of the cases, most often loss of a sex chromosome. The presence of such secondary aberrations did not correlate with any morphological or clinical characteristics, including survival. This first Scandinavian study of AML with t(8;21) corroborates the previous findings that these AMLs are characterized by distinct morphological features, a high frequency of CR and a striking tendency to develop extramedullary leukaemic manifestations. Leukocytosis at diagnosis indicates a less favourable prognosis.


Microencapsulation of anthocyanin-rich black soybean coat extract by spray drying using maltodextrin, gum Arabic and skimmed milk powder.
Black soybean coat is insufficiently valorised food production waste rich in anthocyanins. The goal of the study was to examine physicochemical properties of spray dried extract of black soybean coat in regard to carrier materials: maltodextrin, gum Arabic, and skimmed milk powder. Maltodextrin and gum Arabic-based microparticles were spherical and non-porous while skimmed milk powder-based were irregularly shaped. Low water activity of microparticles (0.31-0.33), good powders characteristics, high solubility (80.3-94.3%) and encapsulation yields (63.7-77.0%) were determined. All microparticles exhibited significant antioxidant capacity (243-386 μmolTE/g), good colour stability after three months of storage and antimicrobial activity. High content of total anthocyanins, with cyanidin-3-glucoside as predominant, were achieved. In vitro release of anthocyanins from microparticles was sustained, particularly from gum Arabic-based. These findings suggest that proposed simple eco-friendly extraction and microencapsulation procedures could serve as valuable tools for valorisation and conversion of black soybean coat into highly functional and stable food colourant.


[Chronic tonsillitis in the students of a humanitarian higher school: incidence, diagnostics, and therapeutic strategies].
The objective of the present work was to study peculiar features of the nosological structure of chronic ENT pathology in the applicants and students of a higher education institution and perform a thorough analysis of the prevalence of various forms of chronic pharyngeal diseases. The study was based at the Polyclinic of Moscow State Institute of International Relations, Russian Ministry of Foreign Affairs, and lasted from 1998 to 2011. A total of 42 829 subjects aged between 15-30 years were examined including 32 186 applicants undergoing physical qualification by the medical evaluation board and 10 643 students subjected to routine annual medical examination. The latter group was characterized by the high prevalence of chronic ENT diseases predominated by pharyngeal pathology (39.6-59.8%). Chronic pharyngeal pathology was prevailed by chronic tonsillitis (32.7-50.6%) followed in the descending order by chronic pharyngitis (16.9-25.2%), papillomas affecting the soft palate, palatine arches and tonsils (0.8-1.5%), and adenoid vegetations (0.05-0.4%). It is concluded that regular medical check-up and treatment provide an effective tool for the prevention of CT progression and the development of its complications in the young subjects. 93.81% of the students were removed from dispensary observation due to improvement of health conditions or recovery. It is concluded that the surgical treatment of CT (bilateral tonsillectomy) should be more extensively applied in the absence of the desired effect of its conservative therapy.


A new method to evaluate human-robot system performance.
One of the key issues in space exploration is that of deciding what space tasks are best done with humans, with robots, or a suitable combination of each. In general, human and robot skills are complementary. Humans provide as yet unmatched capabilities to perceive, think, and act when faced with anomalies and unforeseen events, but there can be huge potential risks to human safety in getting these benefits. Robots provide complementary skills in being able to work in extremely risky environments, but their ability to perceive, think, and act by themselves is currently not error-free, although these capabilities are continually improving with the emergence of new technologies. Substantial past experience validates these generally qualitative notions. However, there is a need for more rigorously systematic evaluation of human and robot roles, in order to optimize the design and performance of human-robot system architectures using well-defined performance evaluation metrics. This article summarizes a new analytical method to conduct such quantitative evaluations. While the article focuses on evaluating human-robot systems, the method is generally applicable to a much broader class of systems whose performance needs to be evaluated.


Effects of attenuation correction and reconstruction method on PET activation studies.
The outcome of Statistical Parametric Mapping (SPM) analyses of PET activation studies depends among others, on the quality of reconstructed data. In general, filtered back-projection (FBP) is used for reconstruction in PET activation studies. There is, however, increasing interest in iterative reconstruction algorithms such as ordered subset expectation maximization (OSEM) algorithms. The aim of the present study was to investigate the effects of reconstruction techniques and attenuation correction (AC) on the detection of activation foci following statistical analysis with SPM. First, a replicate study was performed to assess the effects of the reconstruction method on pixel variance. Second, a phantom study was performed to evaluate the influence of both locations of an activated area and applied reconstruction method on SPM outcome. A volumetric method was used to compute the number of false positive voxels for all reconstructions. In addition, average t values within activation foci and for false positive voxels were calculated. For the assessment of the effects of reconstruction on clinical data, a group of 11 patients was studied. For all reconstructions SPM maps were created and compared. Both the clinical and the phantom data showed that use of iterative reconstruction methods reduced false positive results, while showing similar SPM results within activated areas as FBP. Reconstruction of data without attenuation correction reduced noise for FBP only, but did not affect the quality of SPM results for OSEM. It is concluded that OSEM is a good alternative for FBP reconstructions providing SPM results with less noise.