Assessment of automated genotyping protocols as tools for surveillance of HIV-1 genetic diversity.
The routine use of drug resistance testing provides an abundant source of HIV-1 sequence data. However, it is not clear how reliable standard genotyping of these sequences is for describing HIV-1 genetic variation and for detecting novel genetic variants and epidemiological trends. To compare assignment of HIV-1 resistance test sequences to reference strains across commonly used genotyping protocols. Subtype assignments were compared across three standard genotyping protocols for 10 537 resistance test sequences, representing approximately one-fifth of all reported infections in the United Kingdom. Sequences that were inconsistently genotyped across methods, or that were unassigned by at least one method, were examined for evidence of recombination using sliding-window-based approaches. Although agreement across methods was high for subtypes B, C and H, it was generally much lower (< 50%) for other subtypes. Disagreement between methods typically involved closely related, but epidemiologically distinct, groups or involved a significant proportion ( approximately 12%) of divergent sequences in which analysis revealed widespread evidence of recombination and a remarkable diversity of unusual recombinant forms. With frequent long-distance transfer of viral strains and widespread recombination between them, genetic and epidemiological relationships within HIV-1 are becoming increasingly complex. Current methods of subtype assignment vary in their ability to identify novel genetic variants and to distinguish epidemiologically distinct strains. Capturing meaningful epidemiological information from resistance test data will require a critical understanding of the methodologies used in order to appreciate the possible sources of error and misclassification.


Deciphering signalling network in broad spectrum Near Isogenic Lines of rice resistant to Magnaporthe oryzae.
Disease resistance (R) genes like Pi9, Pita, Pi21, Pi54 are playing important role for broad spectrum blast resistance in rice. Development of near isogenic lines (NILs) using these type of broad spectrum genes and understanding their signalling networks is essential to cope up with highly evolving Magnaporthe oryzae strains for longer duration. Here, transcriptional-level changes were studied in three near-isogenic lines (PB1 + Pi1, PB1 + Pi9 and PB1 + Pi54) of rice resistant to blast infection, to find the loci that are unique to resistant lines developed in the background of Pusa Basmati 1 (PB1). The pathway analysis of loci, unique to resistant NILs compared to susceptible control revealed that plant secondary metabolite synthesis was the common mechanism among all NILs to counter against M. oryzae infection. Comparative transcriptome analysis helped to find out common clusters of co-expressed significant differentially expressed loci (SDEL) in both PB1 + Pi9 and PB1 + Pi54 NILs. SDELs from these clusters were involved in the synthesis and degradation of starch; synthesis and elongation of fatty acids; hydrolysis of phospholipids; synthesis of phenylpropanoid; and metabolism of ethylene and jasmonic acid. Through detailed analysis of loci specific to each resistant NIL, we identified a network of signalling pathways mediated by each blast resistance gene. The study also offers insights into transcriptomic dynamics, points to a set of important candidate genes that serve as module to regulate the changes in resistant NILs. We suggest that pyramiding of the blast resistance gene Pi9 with Pi54 will lead to maximum broad spectrum resistance to M. oryzae.


Immunohistochemical markers in the differentiation of thymic and pulmonary neoplasms.
The histopathological features of some thymic neoplasms overlap with those of pulmonary squamous and large-cell undifferentiated carcinomas, and identification of the primary site may be difficult on routine staining. We have assessed a panel of antibodies that may help to distinguish between neoplasms from these two sites. Antibodies identifying cytokeratin 7 (CK7), CD5, CD10, CD1a and thyroid transcription factor-1 (TTF-1) were applied to a series of 20 thymic neoplasms (thymic carcinomas, atypical thymomas and thymomas), 10 primary squamous cell carcinomas of the lung and 10 large-cell undifferentiated carcinomas of the lung. Staining for TTF-1 was positive in 3/10 large-cell undifferentiated carcinomas, but negative in all other tumours. CD5 showed strong membranous staining in 3/6 thymic carcinomas and 1/14 thymomas, but only focal staining in 1/20 pulmonary carcinomas. CD1a was consistently positive in thymic lymphocytes in both typical and atypical thymomas, but only focally in 1/6 thymic carcinomas. CD1a stained dendritic cells in 7/20 pulmonary carcinomas, but did not stain lymphocytes. Staining for CK7 and CD10 did not aid in differentiating between a pulmonary or thymic origin of the tumour. Staining for TTF-1, CD5 and CD1a have potential use in distinguishing between pulmonary and thymic neoplasms.


The 55K protein on the 5' termini of adenovirus type 2 DNA is unrelated to virus-coded candidate transformation proteins (E1-53K, E1-40K-50K) and DNA-binding proteins (E2-42K/47K/73K).
A polypeptide of 55,000 daltons (55K) is linked, probably covalently, to the K' termini of adenovirus type 2 DNA. The 55K polypeptide is synthesized during early stages of infection (T. Yamashita, M. Arens, and M. Green, J. Virol. 30: 497-507, 1979) and thus may function in viral DNA replication, gene regulation, or cell transformation. Several virus-coded early polypeptides have been identified that could correspond to the terminal 55K, including the E1-40K-50K and E1-53K candidate transformation polypeptides and the E2-42K/47K/73K single-stranded DNA-binding polypeptide. We show here that two-dimensional tryptic [35S]methionine-peptide maps of the terminal 55K differ completely from [35S]methionine-peptide maps of four related E1-40K-50K polypeptides, the E1-53K, and the related E2-42K, E2-47K, and E2-73K polypeptides. We conclude that the terminal 55K polypeptide does not correspond to any of the known virus-coded early polypeptides.


The effect of oral contraceptives on vitamin B12 metabolism.
Serum vitamin vitamin B12 levels were determined in 199 women who were on a regimen of oral contraceptives of either the combination or sequential type and in a control group of 196 women. The group using oral contraceptive agents (OCA) had significantly lower serum levels of vitamin B12 vitamin as compared to those of the control group. A total of 19 women using OCAs had serum vitamin B12 levels that were lower than normal values. However, the Schilling test and urinary methylmalonate excretion in this group were normal. The OCA group had a significantly lower total serum vitamin B12 binding capacity, a lower total transcobalamin I level, and a higher transcobalamin III level. Our study suggests that the fall of serum vitamin B12 in OCA users is due to the changes in vitamin B12 binders of serum and does not represent vitamin B12 deficiency. Therefore, according to our data, there is no justification for vitamin B12 supplementation in users of oral contraceptives.


Sclerosing peritonitis.
An unusual case of widespread peritoneal fibrosis of unknown cause ("sclerosing peritonitis") is described. The patient presented with ascites and bowel obstruction and was found to have numerous fibrous plaques involving primarily the serosa of the small bowel. The plaques were composed of bland spindle cells, ultrastructurally characterized as myofibroblasts, set within a collagenous stroma. Progressive involvement led to the patient's death 17 months after onset of symptoms. A literature review shows similar cases reported with a variety of names and a number of associated clinical conditions, none of which was present in this patient. The pathologic features seen in this case suggest that sclerosing peritonitis represents a nonspecific reaction of the peritoneal surface to a variety of insults and is characterized by florid reactive hyperplasia of submesothelial mesenchymal cells.


The role of ADAM33 in the pathogenesis of asthma.
While asthma is a disorder of the conducting airways characterised by Th2-directed inflammation, a second set of mechanisms is being increasingly recognised as fundamental to disease chronicity and severity, for which the term "remodelling" has been used. The cellular and mediator responses underpinning airway remodelling involve aberrant communication between the airway epithelium and underlying mesenchyme, involving the generation of growth factors that lead to proliferation of fibroblasts and smooth muscle and the deposition of matrix proteins to cause airway wall thickening linked to bronchial hyperresponsiveness and fixed airflow obstruction. The identification of ADAM33 on chromosome 20p13 from positional cloning as a novel candidate gene involved in the pathogenesis of these structural and functional changes has opened the way to further insight into these processes that contribute to corticosteroid refractoriness. The preferential expression of ADAM33 in mesenchymal cells and its multiple molecular actions provide ample opportunity for incriminating this molecule in chronic asthma. Its association with progressive asthma and in predicting reduced lung function in young children suggest that ADAM33 has an important role in the natural history and possibly the origins of asthma, a disease unique to humans.


Planning on Autopilot? Associative Contributions to Proactive Control.
Proactive cognitive control is thought to rely on the active maintenance of goals or contextual information in working memory. It is often measured using the AX-CPT, in which antecedent cues (A/B) are used to proactively prepare a response to a subsequently-presented probe (X/Y). Although control in this task purportedly requires active maintenance of information in working memory, it also provides conditions in which learning the contingencies between relevant events could influence performance via associative learning. We tested this hypothesis using a dot-pattern expectancy version of the AX-CPT whereby a set of new rules (test phase) for responding changed the control operations required for some previously trained cues, while keeping the operations the same for others, allowing us to measure associative interference. We also tested the relationship between associative interference and working memory capacity (operation span; Experiments 1-3) and tested the effect of applying working memory load during the initial acquisition period (Experiment 2) and during the test phase (Experiment 3). We found robust evidence of interference after the rule change based on previously learnt contingencies, suggesting that learnt contingencies come to influence proactive planning, even when they are task-irrelevant. This associative effect had no relationship with working memory capacity or load, based on a load manipulation commonly used in executive control tasks. The findings suggest that proactive control does not always require active maintenance of current goals and environmental cues in working memory. Instead, proactive control may run on autopilot if the individual can rely upon stable relationships in the environment to trigger planning and preparation. SIGNIFICANCE: Navigating daily life requires us to anticipate future events and plan our thoughts and actions accordingly to achieve our goals. This forward planning, or proactive control, is thought to be a resource-intensive and metabolically costly process that recruits higher-order cognitive functions, such as working memory, where relevant thoughts and actions have to be maintained online. The current study challenged this notion by finding that proactive control can be incrementally relegated to simpler processes based on one's learning of stable relationships in the environment, thereby reducing the need to actively maintain information online. Individuals can come to rely on underlying contingencies in stimuli associated with proactive control, even when it is detrimental to their goals.


Efficacy of liposomal bupivacaine in pediatric patients undergoing spine surgery.
Liposomal bupivacaine may be an option for reducing opioid utilization in pediatric scoliosis surgery. The use of liposomal bupivacaine in this patient population has not been previously described. Patients who underwent posterior spinal fusion surgery at our institution from 2011-2016 were identified. We performed a retrospective matched cohort study, matching patients who received intraoperative liposomal bupivacaine by age, gender, and extent of surgery to patients who did not. The primary endpoint was the use of morphine equivalents in the first 72 hours after surgery. Data collection included demographic and surgical data, pain medication utilization, and pain scores. Area under the curve (AUC) for pain scores was calculated. Descriptive statistical methods and univariable analysis were used to compare patients who received liposomal bupivacaine to patients who did not. One hundred and forty-one patients met study criteria; 47 patients who received liposomal bupivacaine were matched to 94 control patients who did not receive liposomal bupivacaine. No significant differences were noted in the patient population with the patients requiring a median of 11 segments (range 10-13 segments) fused. Patients received a mean of 56.6 ± 37.4 mg/kg of intravenous acetaminophen, a mean of 3.4 ± 2.1 mg/kg of intravenous ketorolac, and 1.9 ± 0.93 mg/kg of morphine equivalents in the first 72 hours after surgery. On univariable analysis, no differences were noted in intravenous acetaminophen use, pain score AUC, intravenous ketorolac use, or morphine equivalents (2.0 ± 98 vs 1.8 ± 0.82) in patients who did not receive liposomal bupivacaine as compared to those patient who did received liposomal bupivacaine. Liposomal bupivacaine was not associated with reductions in postoperative opioid use in pediatric spinal surgery.


Breast feeding, birth interval and polygyny in Nigeria.
Polygyny has routinely been claimed to facilitate rules and taboos relating to postpartum sexual abstinence. However, in Nigeria polygyny cannot wholly explain length of postpartum taboo following child birth on the ground that competition among cowives to out do one another in child-bearing results in a tendency of higher fertility and hence shorter postpartum taboo in polygynous households than that in monogamous families. Economic factors have been adduced as reasons explaining the recent tendency for mothers in polygynous families to have longer postpartum abstinence than their counterparts in monogamous households. Specifically, for young mothers aged 15-34, bearing children in quick succession is no longer attractive as in essentially traditional cultures where husband's commitment to caring for children is taken for granted. Hence, the tendency for women in polygynous households to adhere more strictly to rules and taboos relating to postpartum abstinence could be associated to the changing roles of women as they affect their responsibility with respect to the maintenance and training of their children rather than to the institution of polygyny per se.


TLR-5 ligand conjugated with Per a 10 and T cell peptides potentiates Treg/Th1 response through PI3K/mTOR axis.
Novel strategies are needed to enhance efficacy of immunotherapy for allergic diseases. The present study evaluates role of conjugating flagellin with allergen, Per a 10 and its T cell epitopes in DC mediated polarization. Fusion proteins (FPer a 10, FPT1, FPT2 and FPT3) were sub-cloned, expressed and purified to homogeneity. FlaA fused proteins showed TLR-5 binding in TLR5+HEK293 cells as observed by enhanced NF-κB dual luciferase assay and IL-8 secretion in culture supernatant. Fusion proteins upregulate co-stimulatory molecules CD80, CD83 and CD86 on BMDCs and enhanced IL-6, IL-β, IL-12p70 and IL-10 secretion. Inhibition studies suggest fusion proteins mediate IL-10 secretion via activation of PI3K/mTOR/NF-κB pathway. FPT1 and FPT3 deviate Th2 cytokine milieu towards Th1/Treg by upregulating the expression of IFN-γ, IL-12p70, IL-10 and TGF-β in BMDCs co-culture with allergen specific T cells. Flow cytometric examination of BMDC:T cell co-culture revealed CD4+ T cell differentiation towards Th1/Treg by FPT1 and FPT3. Thus, our results indicate that flagellin fused with T cell peptides are efficient immunomodulators and may possess potential for allergy therapeutics.


Photoplethysmograph quality estimation through multichannel filtering.
Information about the quality of a recorded physiological waveform can be valuable for the detection of critical medical conditions. This work presents a new point-by-point signal quality index (SQI) based on adaptive multichannel prediction which does not rely on ad-hoc morphological feature extraction from the target waveform. An application of the SQI to photoplethysmograph waveforms showed that the SQI is monotonically related to SNR (simulated by adding white noise) and subjective human quality assessment of 1,313 waveform epochs. A receiver-operating-characteristic (ROC) curve analysis, with the human "bad" quality label as negative and the human "good" quality label as positive, yielded an area under the ROC curve of 0.863. For photoplethysmograph waveforms, a SQI greater than 0.8 seems in general to be indicative of good signal quality.


[Catheter ablation of persistent and long-standing persistent atrial fibrillation. Strategies and results].
Catheter ablation for paroxysmal atrial fibrillation is a meanwhile established therapy option, which is most frequently performed using radiofrequency ablation. Mid-term success rate of 70 % are achievable with a single ablation procedure. However, the mechanistics of persistent atrial fibrillation are less well understood and catheter ablation is a far more challenging procedure. Different ablation approaches are being performed to treat persistent atrial fibrillation ranging from sole pulmonary vein isolation to additional ablation of fractionated electrograms aiming for termination of atrial fibrillation. Thus far, it has not been investigated which strategy is most successful in treating persistent atrial fibrillation. After extended ablation of atrial fibrillation, occurrence of organized atrial arrhythmias is not uncommon and can be successfully ablated. These consecutive arrhythmias can be considered as a next step towards stable sinus rhythm after repeat ablation. Improvement of mapping methods as well as a better understanding of mechanisms of atrial fibrillation may increase success rate of catheter ablation of persistent atrial fibrillation and may also help to improve success rate of these complex procedures.


Immobilization of trivalent actinides by sorption onto quartz and incorporation into siliceous bulk: investigations by TRLFS.
The adsorption of Cm(III) on quartz is studied by time resolved laser fluorescence spectroscopy (TRLFS) in the pH range from 3.75 to 9.45. The raw spectra are deconvoluted into three single components. The first one has a peak maximum at 593.8 nm and can be attributed to the Cm(III) aquo ion with an emission lifetime of 68+/-3 micros. The second one corresponds to an adsorbed species and has a peak maximum at 601.4 nm and an emission lifetime of 123+/-10 micros. The peak maximum of the third component is shifted to higher wavelength (603.6 nm) while the lifetime remains constant. Additionally, the adsorption of Am(III) on quartz is investigated in batch experiments. Based on the spectroscopic data a sorption mechanism is suggested. In addition, the obtained Am uptake data and the Cm-TRLFS data are modeled simultaneously using a single site Basic Stern model in combination with the charge distribution concept of Pauling. The finally suggested model consists of two bidentate surface complexes where the second one is the product of hydrolysis of the first sorption species. In a separate set of experiments the influence of silicic acid at different concentrations on the Cm(III) speciation in a quartz system is investigated by TRLFS. In suspension silicic acid at low concentration (3.5x10(-4) mol/L) has no influence on the Cm(III) speciation. At high concentration (3.5x10(-2) mol/L) the Cm(III) speciation is definitely influenced. The results at higher concentration indicate the formation of Cm(III)/silicic acid complexes and the incorporation of Cm(III) into siliceous bulk. This is confirmed by measurements at a quartz single crystal surface. Moreover, these measurements indicate the formation of quartz/Cm(III)/silicic acid ternary complexes at the mineral surface.


The prevalence of cysticerci of Taenia saginata in cattle reared on sewage-irrigated pasture.
The hearts, masseter muscles, tongues and laryngeal muscles from 200 cattle aged 10 to 11 months, and 100 cattle aged 20 to 21 months, which had been reared on sewage-irrigated pastures at the Melbourne and Metropolitan Board of Works Farm, Werribee, Victoria, were examined for infection with cysticerci of Taenia saginata by slicing in the laboratory and the result obtained were compared with those recorded during normal meat inspection procedures at the abattoir. Of the 10 to 11-month-old cattle 51-5% were found to be infected and 8% of the total animals harboured viable cysticerci. Of the 20 to 21-month-old animals 33% were infected, and, even at this age, 8% of the animals still carried viable cysticerci. On-line meat inspection at the abattoir detected significantly fewer infections than did laboratory slicing.


Influence of Yanyankang Powder on Th1/Th2 in rats with experimental autoimmune uveitis.
To study the influence of Yanyankang powder on Th1/Th2 in rats with experimental autoimmune uveitis (EAU). The EAU models were induced in Lewis rats by immunization with interphotoreceptor retinoid binding protein (IRBP) 1177-1191 in complete Freund's adjuvant. The rats were randomly divided into 3 groups: a model control group, a Yanyankang group, and a prednisone group, 9 rats in each group. The model control group was intervened with saline solution by gavage. The Yanyankang group was intervened with Yanyankang powder 4 g/(kg day) by gavage. The prednisone group were intervened with prednisone acetate tablets 5 mg/(kg d) by gavage. All groups were intervened after immunization once every 2 days for 18 days and monitored by slit-lamp biomicroscopy daily until day 18. The levels of gamma interferon (INF-γ) and interleukin-10 (IL-10) in the supernatants of T cells were determined by enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) technology was used for measuring Th1 and Th2 related cytokine mRNA expressions. Slighter intraocular inflammation was found in the Yanyankang group and the prednisone group than the control group. The levels of the IFN-γ and IL-10 in the supernatants of the spleen lymph node cells were 382.33±6.30, 155.87±4.46 μg/L in the Yanyankang group and 270.93±7.76, 265.32±11.88 μg/L in the prednisone group. Both had significant differences compared with the control group (941.53±8.59, 20.67±4.65 μg/L; =0.01). The PCR results showed the same tendency. Yanyankang powder showed favorable effects in the rats with EAU by influencing the function of Th1 and Th2 cells.


Synthesis, Cytotoxicity, and Mechanistic Investigation of Platinum(IV) Anticancer Complexes Conjugated with Poly(ADP-ribose) Polymerase Inhibitors.
Many clinical trials using combinations of platinum drugs and PARP-1 inhibitors (PARPi) have been carried out, with the hope that such combinations will lead to enhanced therapeutic outcomes against tumors. Herein, we obtained seven potential PARPi with structural diversity and then conjugated them with cisplatin-based platinum(IV) complexes. Both the synthesized PARPi ligands and PARPi-Pt conjugates [PARPi-Pt(IV)] show inhibitory effects against PARP-1's catalytic activity. The PARPi-Pt(IV) conjugates are cytotoxic in a panel of human cancer cell lines, and the leading ones display the ability to overcome cisplatin resistance. A mechanistic investigation reveals that the representative PARPi-Pt(IV) conjugates efficiently enter cells, bind to genomic DNA, disturb cell cycle distribution, and induce apoptotic cell death in both cisplatin-sensitive and -resistant cells. Our study provides a strategy to improve the cytotoxicity of platinum(IV)-based anticancer complexes and overcome cisplatin resistance by using a small-molecule anticancer complex that simultaneously damages DNA and inhibits PARP.


Carotid endarterectomy, siphon stenosis, collateral hemispheric pressure, and perioperative cerebral infarction.
To determine whether moderate stenosis (50% to 80%) of the intracranial segment of the internal carotid artery increases the risk of cerebral infarction after carotid endarterectomy, the arteriograms, ocular pneumoplethysmograms, internal carotid back pressure, and clinical outcome after 169 operations were reviewed. Siphon stenoses less than 50% were not included because of their doubtful anatomic and hemodynamic significance. No patients with stenosis greater than 80% underwent operation. Moderate siphon stenosis affected 37 vessels, 24 (14.2%) ipsilateral and 13 (7.6%) contralateral to the side of operation. Eight patients had bilateral siphon stenosis. Three patients had stroke after operation; none of these cases had siphon stenosis. Moderate siphon stenosis did not increase the risk of perioperative cerebral infarction. Stroke only occurred in those patients in whom there was arteriographic or functional evidence that the affected hemisphere was isolated from effective collateral vessels.


A double absorption-phase model adequately describes mycophenolic acid plasma profiles in de novo renal transplant recipients given oral mycophenolate mofetil.
Mycophenolic acid (MPA) shows complex plasma concentration-time profiles, particularly in the immediate (first month) post-transplantation phase for which no relevant pharmacokinetic model has been proposed thus far. The aim of this study was to develop a model to accurately describe the time profile of plasma MPA concentrations after oral administration of mycophenolate mofetil in adult kidney transplant patients, in any post-transplantation period. Full interdose pharmacokinetic profiles were collected in 45 adult renal transplant patients who were orally administered mycophenolate mofetil and ciclosporin; 25 patients were de novo transplant patients for whom individual pharmacokinetics were assessed at three post-transplantation periods (days 3, 7 and 30) and 20 patients were stable transplant patients (>3 months post-transplantation). MPA was determined in plasma by liquid chromatography-mass spectrometry. Models combining a single- or double-input (described as single or double gamma distributions) with one- or two-compartments were developed using in-house software and fitted to the individual profiles by nonlinear regression. Visual inspection of the pharmacokinetic profiles showed highly variable absorption profiles and secondary peaks of various intensity. The pharmacokinetic models including a double gamma distribution best fitted these various profiles in the immediate post-transplantation period (mean bias and precision of -0.92% and 20.19%; -1.5% and 18.02%, on day 7 and day 30, respectively), while in the stable post-grafting phase (beyond 3 months), the single- and double-absorption models performed similarly (mean bias and precision of -3.37% and 17.64%; -3.12% and 18.44%, on day 7 and day 30, respectively). The proposed pharmacokinetic models adequately describe the concentration-time profiles of MPA in renal transplant patients and could be helpful in the development of tools for MPA monitoring.


Effects of supplemented multicomponent mycotoxin detoxifying agent in laying hens fed aflatoxin B1 and T2-toxin contaminated feeds.
The present study was conducted to determine the ability of multicomponent mycotoxin detoxifying agent (MMDA) in feed to prevent the gastrointestinal absorption of aflatoxin B1 (AFB1) and T2-toxin supplemented via spiked maize. For comparisons, hens were fed with uncontaminated basal diet without or with addition of MMDA at 2 g/kg feed. The trial consisted of 105 laying hens (Lohmann Brown) without obvious signs of disease allocated to 7 treatment groups in 35 pens. Responses were demonstrated on laying performance and health status throughout the 42 d experimental period. The results of laying performance indicated significantly decreased egg mass with increasing mycotoxin (AFB1 and T2-toxin) levels up to the maximum tolerated dosage, however simultaneous presence of MMDA laying performance was slightly modified linearly to increasing application. Dose-dependent pathological changes in liver and kidneys and their relative weights, changes in blood parameters and reduced eggshell weights were observed in the hens fed AFB1 and T2-toxin. The pathological changes in the hens fed with diets containing AFB1 and T2-toxin without MMDA were significantly higher as compared with the control group, but eggshell stability was not affected. The contents of AFB1, T2-toxin and their metabolites in liver and kidney tissues were significantly decreased in the hens supplemented with MMDA at 2 and 3 g/kg in feed. MMDA supplementation significantly reduced the deposition of AFB1, T2-toxin and their metabolites in liver and kidneys at the maximum tolerated dosage (2 and 3 g/kg) indicating specific binding to AFB1 and T2-toxin in the digestive tract as compared to the corresponding diets without MMDA. Exposure of AFB1 and T2-toxin indicated significantly decreased egg mass with increasing mycotoxin levels up to the maximum tolerated dosage because of the significantly reduced egg production. Therefore, in this study, MMDA could reduce negative effects of feeding AFB1 and T-2 to laying hens.


Quality of life assessment in patients with heart failure: validity of the German version of the generic EQ-5D-5L™.
Chronic heart failure patients typically suffer from tremendous strain and are managed mainly in primary care. New care concepts adapted to the severity of heart failure are a challenge and need to consider health-related quality of life aspects. This is the first psychometric validation of the German EQ-5D-5L™ as a generic instrument for assessing health-related quality of life (HRQOL) in a primary care heart failure patient sample. Confirmatory factor analysis (CFA) was performed on the baseline EQ-5D-5L™ data from the RECODE-HF study (responses to all items from n = 3225 of 3778 patients). Basic CFA models for HRQOL were calculated based on the EQ-5D-5L™ items using the maximum likelihood (ML) and the asymptotic distribution-free method. In an extended CFA, physical activity and depression were added. The basic CFA ML model was verified for the reduced number of cases of the extended CFA model (n = 3064). In analyses of variance the association of the EQ-5D-5L™ visual analogue scale (VAS) and both the German and the British EQ-5D-5L™ crosswalk index with the SF-36 measure of general health were examined. The discriminant validity was analysed using Pearson's chi-squared tests applying the New York Heart Association classification, for the VAS and indices analyses of variance were calculated. In the basic CFA models the root mean square error of approximation was 0.095 with the ML method, and 0.081 with the asymptotic distribution-free method (Comparative Fit Index > 0.90 for both). Physical activity and depression were confirmed as influential factors in the extended model. The VAS and indices were strongly associated with the SF-36 measure of general health (partial eta-squared 0.525/0.454/0.481; all p < 0.001; n = 3155/3210/3210, respectively), also for physical activity and depression when included together (partial eta-squared 0.050, 0.200/0.047, 0.213/0.051 and 0.270; all p < 0.001; n = 3015/n = 3064/n = 3064, respectively). The discriminant validity analyses showed p-values < 0.001 and small to moderate effect sizes for all EQ-5D-5L™ items. Analyses of variance demonstrated moderate effect sizes for the VAS and indices (0.067/0.087/0.084; all p < 0.001; n = 3110/3171/3171). The German EQ-5D-5L™ is a suitable method for assessing HRQOL in heart failure patients.


The critical role of IL-6 in the pathogenesis of Takayasu arteritis.
To investigate T cell subsets and immune cytokine profiles in untreated Takayasu arteritis (TAK) patients and the underlying immunopathological mechanism. We enrolled 50 untreated TAK patients and 40 age-matched controls (20 healthy controls, 20 untreated SLE patients). Enzyme-linked immunosorbent assays (ELISAs) were used to define cytokine profiles in all patients, and flow cytometry was performed for 9 TAK patients and 12 healthy controls. Hematoxylin and eosin (Handamp;E) staining and immunohistochemistry (IHC) were performed in aortic tissues of 9 TAK and 9 atherosclerosis patients; clinical data were also collected. Circulating CD4(+) T cells were more frequent in TAK patients (p<0.05). Frequencies of Th1, Th2, and Th17 cells were higher, whereas Treg cells were reduced in TAK. Significantly higher levels of IL-6 and lower levels of IFN-γ, IL-4, and IL-17 were detected in TAK patients (p<0.05). By H & E staining, thickened vascular walls with proliferation of collagen fibre were observed in most patients. Inflammatory sites with infiltrating macrophages, lymphocytes, and neutrophils were located in adventitia. IHC revealed T cells (mainly CD4(+) T cells) in vascular lesions. Additionally, IL-6 was positive throughout the vascular wall in most specimens, whereas IFN-γ, IL-12, and IL-17 were detected in inflammatory sites of active patients. IL-6 levels were positively related to ESR, CRP, and Kerr scores (p<0.05). Significantly increased levels of IL-6 were detected in peripheral blood and aortic tissues of untreated patients. IL-6 might be a sensitive biomarker to assess disease activity and could be critical in the immunopathogenesis of TAK.


Localization of angiotensin II receptors along the anteroventral third ventricle area of the rat brain.
Autoradiographic techniques were utilized to localize and to quantify angiotensin II (ANG) binding sites in rat forebrain. Specific, localized ANG binding sites were demonstrated in midline sagittal sections, corresponding to the entire anteroventral third ventricle (AV3V) area, including the nucleus preopticus medianus and the subependymal area of the anterior third ventricle from the nucleus preopticus medianus to the organon vasculosum laminae terminalis. A continuous band of ANG receptors extended dorsally from the nucleus preopticus medianus along the subependymal area of the third ventricle to the organon subfornicalis. Scatchard analysis performed with consecutive sections from single animals revealed a single class of high-affinity ANG receptors in both the organon subfornicalis and the organon vasculosum laminae terminalis. In addition, ANG receptors were localized in areas anatomically and physiologically related to the AV3V area, including the nuclei paraventricularis and periventricularis and the eminentia mediana. These results support the idea that ANG may act as both a hormone and a neurotransmitter in the central regulation of fluid balance and cardiovascular function, and suggest that the circumventricular organs are the most likely sites for an interaction between the peripheral and central ANG systems.


Early pregnancy angiogenic markers and spontaneous abortion: an Odense Child Cohort study.
Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. We investigated the association between maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week <22 (median 83 days of gestation, interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum <22+0 gestational weeks, and the prevalence was 3.52% (59 cases). The time-dependent effect of maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor on subsequent late first-trimester or second-trimester spontaneous abortion (n = 59) was evaluated using a Cox proportional hazards regression model, adjusting for body mass index, parity, season of blood sampling, and age. Furthermore, receiver operating characteristics were employed to identify predictive values and optimal cut-off values. In the adjusted Cox regression analysis, increasing continuous concentrations of both soluble Fms-like kinase 1 and placental growth factor were significantly associated with a decreased hazard ratio for spontaneous abortion: soluble Fms-like kinase 1, 0.996 (95% confidence interval, 0.995-0.997), and placental growth factor, 0.89 (95% confidence interval, 0.86-0.93). When analyzed by receiver operating characteristic cut-offs, women with soluble Fms-like kinase 1 <742 pg/mL had an odds ratio for spontaneous abortion of 12.1 (95% confidence interval, 6.64-22.2), positive predictive value of 11.70%, negative predictive value of 98.90%, positive likelihood ratio of 3.64 (3.07-4.32), and negative likelihood ratio of 0.30 (0.19-0.48). For placental growth factor <19.7 pg/mL, odds ratio was 13.2 (7.09-24.4), positive predictive value was 11.80%, negative predictive value was 99.0%, positive likelihood ratio was 3.68 (3.12-4.34), and negative likelihood ratio was 0.28 (0.17-0.45). In the sensitivity analysis of 54 spontaneous abortions matched 1:4 to controls on gestational age at blood sampling, the highest area under the curve was seen for soluble Fms-like kinase 1 in prediction of first-trimester spontaneous abortion, 0.898 (0.834-0.962), and at the optimum cut-off of 725 pg/mL, negative predictive value was 51.4%, positive predictive value was 94.6%, positive likelihood ratio was 4.04 (2.57-6.35), and negative likelihood ratio was 0.22 (0.09-0.54). A strong, novel prospective association was identified between lower concentrations of soluble Fms-like kinase 1 and placental growth factor measured in early pregnancy and spontaneous abortion. A soluble Fms-like kinase 1 cut-off <742 pg/mL in maternal serum was optimal to stratify women at high vs low risk of spontaneous abortion. The cause and effect of angiogenic factor alterations in spontaneous abortions remain to be elucidated.


Cognitive Impairment in Alzheimer's and Metabolic Diseases: A Catecholaminergic Hypothesis.
Catecholaminergic transmission plays an essential role in both physiological and pathological cognitive functions. Plastic changes subserving learning and memory processes are highly dependent on catecholaminergic activity, altering their function and impacting cognition. This review assesses changes in the dopaminergic and norepinephrine systems as part of the mechanisms underlying cognitive impairment in Alzheimer's disease as associated with metabolic dysfunctions such as type 2 diabetes, metabolic syndrome, and neuroinflammation and peripheral inflammation. Understanding the role of catecholaminergic systems in these conditions is relevant for identifying etiological factors that could advance diagnostic and therapeutic approaches for ameliorating cognitive alterations, disease onset, and progression.


Meal-stimulated C-peptide and insulin antibodies in type I diabetic subjects and their nondiabetic siblings characterized by HLA-DR antigens.
We studied serum C-peptide (CP) response 90 min after a breakfast meal and insulin antibody titers in 171 type I diabetic (IDDM) patients and 272 of their nondiabetic siblings from 169 unrelated families. HLA typing was performed in all participants. In IDDM patients, there was a decline in CP response with increased duration of disease. CP responses of greater than or equal to 1.8 ng/ml were seen significantly less often in patients who were less than 10 yr old at the time of diagnosis of IDDM than in patients who were greater than 10 yr old at the time of diagnosis (8% versus 21%, P less than 0.05). More patients with HLA-DR4 had a CP response greater than or equal to 1.8 ng/ml than did patients who lacked this antigen whether duration of IDDM was less than 10 yr (30% versus 18%, P greater than 0.05) or greater than or equal to 10 yr (15% versus 0%, P less than 0.05). Mean C-peptide was also higher in HLA-DR4-positive patients compared with HLA-DR4-negative patients both when duration of disease was less than 10 yr (1.7 +/- 1.9 versus 1.4 +/- 1.0, P less than 0.01) and greater than or equal to 10 yr (1.2 +/- 1.5 versus 1.0 +/- 0.4, P less than 0.0001). Insulin antibody binding was slightly higher in patients with HLA-DR4 compared with patients lacking this antigen (5.96 +/- 7.20 versus 4.89 +/- 4.74, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Contemporary Views of Research Participant Willingness to Participate and Share Digital Data in Biomedical Research.
Using social media to recruit participants is a common and cost-effective practice. Willingness to participate (WTP) in biomedical research is a function of trust in the scientific team, which is closely tied to the source of funding and institutional connections. To determine whether WTP and willingness to share social media data are associated with the type of research team and online recruitment platform. This mixed-methods longitudinal survey and qualitative study was conducted over 2 points (T1 and T2) using Amazon's Mechanical Turk (MTurk) platform. Participants were US adults aged 18 years or older who use at least 1 social media platform. Recruitment was stratified to match race/ethnicity proportions of the 2010 US Census. The volunteer sample consisted of 914 participants at T1, and 655 participants completed the follow-up survey 5 months later (T2). Outcomes were (1) past experience with online research and sharing social media data for research; (2) WTP in research advertised online; (3) WTP in a study sponsored by a pharmaceutical company, a university, or a federal agency; and (4) willingness to share social media data. Opinions were solicited regarding the European Union's General Data Protection Regulation statute, which came into effect between T1 and T2. Of 914 participants completing the first survey (T1), 604 (66.1%) were aged 18 to 39 years and 494 (54.0%) were female. Of these, 655 participants (71.7%) responded at T2. While 680 participants (74.4%) indicated WTP in biomedical research, only 454 (49.3%) were willing to share their social media data. Participants were significantly less likely to participate in federally sponsored (odds ratio [OR], 0.58; 95% CI, 0.51-0.64; P < .001) or pharmaceutical company (OR, 0.59; 95% CI, 0.53-0.66; P < .001) research than university-led studies. They were also less likely to share their social medial data for federal (OR, 0.65; 95% CI, 0.58-0.72; P < .001) or pharmaceutical company (OR, 0.50; 95% CI, 0.44-0.56; P < .001) research compared with academic studies. Willingness to participate in pharmaceutical company-led research decreased 11.89% from T1 to T2 (OR for T2, 0.62; 95% CI, 0.54-0.77; P < .001). Reasons for WTP were interest in furthering science, financial incentives, trust in the organization, and data security. While 63.0% of respondents reported seeing new privacy policy emails related to the General Data Protection Regulation law, only 27.1% indicated this positively influenced their WTP. Thematic analysis of responses indicated that WTP may improve with stronger data security measures. This study suggests that researchers may see reduced online research participation and data sharing, particularly for research conducted outside academia.


A clinical approach to autoantibody testing in systemic autoimmune rheumatic disorders.
Musculoskeletal (MSK) disorders constitute one of the most common clinical presentations to clinical care givers. Within this category of illnesses, systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SjS) and rheumatoid arthritis (RA) are included in the differential diagnosis. A hallmark of SARD is the production of autoantibodies, which are routinely requested as a guide to diagnosis and clinical decision making. The field of serological tests, including the detection of autoantibodies, is complex and often leads to confusion and misunderstanding. When used appropriately, autoantibodies can be a valuable adjunct to the diagnosis, and occasionally therapy and prognosis, of SARD. The role of autoantibody testing and a 'practical' approach to using these tests is the focus of this paper.


End-to-end learning for compound activity prediction based on binding pocket information.
Recently, machine learning-based ligand activity prediction methods have been greatly improved. However, if known active compounds of a target protein are unavailable, the machine learning-based method cannot be applied. In such cases, docking simulation is generally applied because it only requires a tertiary structure of the target protein. However, the conformation search and the evaluation of binding energy of docking simulation are computationally heavy and thus docking simulation needs huge computational resources. Thus, if we can apply a machine learning-based activity prediction method for a novel target protein, such methods would be highly useful. Recently, Tsubaki et al. proposed an end-to-end learning method to predict the activity of compounds for novel target proteins. However, the prediction accuracy of the method was still insufficient because it only used amino acid sequence information of a protein as the input. In this research, we proposed an end-to-end learning-based compound activity prediction using structure information of a binding pocket of a target protein. The proposed method learns the important features by end-to-end learning using a graph neural network both for a compound structure and a protein binding pocket structure. As a result of the evaluation experiments, the proposed method has shown higher accuracy than an existing method using amino acid sequence information. The proposed method achieved equivalent accuracy to docking simulation using AutoDock Vina with much shorter computing time. This indicated that a machine learning-based approach would be promising even for novel target proteins in activity prediction.


Obesity and the polycystic ovary syndrome.
Polycystic ovarian syndrome (PCOS) is extremely common among reproductive-aged women, but often goes undiagnosed. PCOS is associated with the metabolic syndrome and carries a greatly increased risk of impaired glucose tolerance and type 2 diabetes mellitus, and cardiovascular risks. Treatment of PCOS may provide relief of cosmetic problems and depression by improving patient self-esteem. In addition, because of its association with the metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease, its recognition and treatment can potentially be life saving. This article reviews the impact, pathophysiology, and associated risks of obesity and the metabolic syndrome in PCOS.


Possible association of HTLV-I infection and dementia.
We report a Swedish patient with progressive dementia possibly associated with human T cell-lymphotropic virus type I (HTLV-I) infection. The clinical investigation revealed no typical sings of other neurological disorders. The patient was probably infected in East-Asia 35 years before onset of the disease. High titers of specific HTLV-I antibodies were detectable with solid-phase peptide ELISA in serum (1:1.600) and cerebrospinal fluid (CSF) (1:20), and the CSF/serum anti-HTLV-I antibody ratio indicated intrathecal HTLV-I antibody synthesis. Western blot for HTLV-I and polymerase chain reaction with primers selected for the HTLV-I pol gene were positive in both peripheral blood and cerebrospinal fluid. HTLV-I antigen was also demonstrated after in vitro co-cultivation of mononuclear cells from peripheral blood. Thus, our findings indicate that HTLV-I infection also may be associated with dementia. In addition, this case report calls attention upon HTLV-I as a possible etiologic agent to neurological diseases in countries previously spared from the infection.


Low dose intraarterial cis-platinum/radiotherapy after local tumour preradiation.
The simultaneous use of intraarterial Cis-Platinum and Radiotherapy (CP/RT) was found to be a very effective and relatively little burdened treatment for a palliative treatment concept. This affects life quality as well as the remission--and survival times. The fast and continual remission with low CP/RT concentrations, even in extreme palliative cases, is surprising. CP/RT treatment shows additive and synergistic effects which are not explainable by the single effects of the cis-platinum dose used (60 mg/1.73 m2 in our case) or the total irradiation dose (e.g., 5 Gy TD) or the fractionation (e.g., 5 X 1 Gy), especially since the doses of each which were used are by themselves without therapeutic relevance. Only the combination of the modalities with a low dose two-day preradiation program induced the described effects.


Mitochondrial electron transport chain complex dysfunction in the colonic mucosa in ulcerative colitis.
Ulcerative colitis (UC) is characterized by an energy deficiency state of the colonic epithelium. This study evaluated mitochondrial electron transport chain (ETC) complex activity in normal and disease mucosa in patients with UC. Alterations in ETC complexes were also investigated in experimental colitis in mice. Biopsies were obtained from macroscopically normal and diseased colonic mucosa of 43 patients with UC and 35 controls undergoing screening colonoscopy and ETC complex activity was assayed biochemically. ETC complex activities were also assayed in colonic epithelial cells isolated from Swiss albino mice with dextran sodium sulfate (DSS)-induced colitis at various stages of induction of colitis. Mucosal nitrite levels and protein carbonyl content were determined. The activity of Complex II was significantly decreased in colonic biopsies from UC patients compared with controls, while activities of other mitochondrial complex were normal. Complex II activity was equally decreased in diseased and normal mucosa in UC; the degree of reduction did not correlate with clinical, endoscopic, or histological grading of disease activity. In DSS-fed mice, a reduction in activity of Complex IV and Complex II was observed. Activity of other complex was not affected. Administration of aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, attenuated all parameters of colitis as well as the reductions in Complex IV and Complex II activity. Reduction in Complex II activity appears to be a specific change in UC, present in quiescent and active disease. Mitochondrial complex dysfunction occurs in DSS colitis in mice and appears to be mediated by nitric oxide.


Predictors of evidence-based practice competency among Tunisian nursing students.
Evidence-based practice (EBP) is an important competency of undergraduate nursing students which should be cultivated before graduation by increasing future healthcare providers' knowledge, skills and attitudes towards EBP. This study aimed to describe nursing students' competencies (attitudes, knowledge, skills) in Evidence-based practice (EBP) and to determine factors predicting EBP competency. A descriptive cross-sectional study was conducted at the Higher School of Health Sciences and Techniques of Sousse (Tunisia) among 365 nursing students. Data were collected using the validated Evidence Based Practice Competencies Questionnaire (EBP-COQ). Multiple linear regression was performed to determine factors predicting EBP competencies. The overall score of EBP-COQ questionnaire was 3.26 ± 0.53 out of 5. The attitude, skills and knowledge subscales received 4.04 ± 0.41; 3.05 ± 0.77 and 2.70 ± 0.74 as mean scores respectively. Multiple linear regression analysis (table 4) revealed that significant related factors were academic level (β = 0.271, p = 0.001), English-language reading skills (β = 0.435, p < 0.001), facing staff resistance in implementing a new evidence-based procedure (β = - 0.081, p = 0.035) difficulties in obtaining full-text papers (β = - 0.127, p < 0.001) and training in methodology (β = 0.232, p < 0.001) and also in statistics (β = 0.205, p < 0.001). These results help to understand students' attitudes, knowledge and skills in EBP and can be therefore a starting point to develop effective strategies for EBP curricula.


Late Quaternary loss of genetic diversity in muskox (Ovibos).
The modern wildherd of the tundra muskox (Ovibos moschatus) is native only to the New World (northern North America and Greenland), and its genetic diversity is notably low. However, like several other megafaunal mammals, muskoxen enjoyed a holarctic distribution during the late Pleistocene. To investigate whether collapse in range and loss of diversity might be correlated, we collected mitochondrial sequence data (hypervariable region and cytochrome b) from muskox fossil material recovered from localities in northeastern Asia and the Arctic Archipelago of northern North America, dating from late Pleistocene to late Holocene, and compared our results to existing databases for modern muskoxen. Two classes of haplotypes were detected in the fossil material. "Surviving haplotypes" (SHs), closely similar or identical to haplotypes found in modern muskoxen and ranging in age from approximately 22,000 to approximately 160 yrbp, were found in all New World samples as well as some samples from northeastern Asia. "Extinct haplotypes" (EHs), dating between approximately 44,000 and ~18,000 yrbp, were found only in material from the Taimyr Peninsula and New Siberian Islands in northeastern Asia. EHs were not found in the Holocene muskoxen specimens available for this study, nor have they been found in other studies of extant muskox populations. We provisionally interpret this evidence as showing that genetic variability was reduced in muskoxen after the Last Glacial Maximum but before the mid-Holocene, or roughly within the interval 18,000-4,000 yrbp. Narrowing this gap further will require the recovery of more fossils and additional genetic information from this interval.


[Atrial fibrillation in the ICU. Distinct entity--special treatment?].
Atrial fibrillation (AF) is the single most frequent arrhythmia in the intensive care unit, occurring among 44-61 % of all patients with arrhythmias in the intensive care unit. The success rate of electrical cardioversion (DC-CV) early after surgery is as low as 10-35 % in postoperative AF but 6 weeks after discharge 90 % are in sinus rhythm (SR). Several guidelines recommend rate control in these patients and rate control with β-blockers and calcium channel blockers is not inferior with respect to outcome, 6 min walk test, and quality of life. DC-CV is recommended in unstable and heart failure patients. The term resistant AF is suggested for that distinct situation of AF not amenable to cardioversion solely in the acute phase of critical illness.


Exploration of Isoxazole-Carboxylic Acid Methyl Ester Based 2-Substituted Quinoline Derivatives as Promising Antitubercular Agents.
In pursuit of potent anti-TB agents active against drug resistant tuberculosis (DR-TB), herein we report synthesis and bio-evaluation of a new series of isoxazole-carboxylic acid methyl ester based 2-substituted quinoline derivatives. Preliminary evaluation indicated selectivity towards Mtb H37Rv, with no inhibition of non-tubercular mycobacterial (NTM) & bacterial pathogen panel. Out of 36 synthesized compounds, majority exhibited substantial inhibition of Mtb H37Rv (MIC 0.5-8 μg/mL). Cell viability test against Vero cells revealed no significant cytotoxicity. Further, screening against drug resistant strains (DR-Mtb) found hit compound displaying promising potency (MIC 1-4 μg/mL). Structure optimization of the hit led to the identification of lead compound demonstrating potent inhibition of both drug-susceptible Mtb (MIC 0.12 μg/mL) and drug-resistant Mtb (MIC 0.25-0.5 μg/mL) along with a high selectivity index (SI) >80. Taken together, with appreciable selectivity and potent activity, these chemotypes show prospect to be turned into a potential anti-TB candidate.


Scoring HLA class I mismatches by HistoCheck does not predict clinical outcome in unrelated hematopoietic stem cell transplantation.
Currently, there is no well-accepted rating system for reliably predicting which HLA-mismatched (MM) unrelated donor should be selected for a patient without an HLA allele-matched donor. We evaluated the ability of an MM ranking system, HistoCheck, to predict the risk associated with HLA class I disparity in a population of 744 single allele or antigen HLA-A, -B, or -C MM myeloablative unrelated donor hematopoietic stem cell transplantation recipients with acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome, facilitated through the National Marrow Donor Program between 1988 and 2003. Multivariate models were used to adjust for other significant clinical risk factors. HLA MMs were scored using the HistoCheck Web-based tool, and the patients were divided into 4 quartiles: dissimilarity score (DSS) 1.04-2.84 (allele MM), DSS >2.84-13.75 (allele and antigen MM), DSS >13.75-19.39 (antigen MM), and DSS >19.39-36.62 (antigen MM). Using the lowest scoring quartile as the reference, the DSS groups were evaluated for associations with relapse, treatment-related mortality, acute and chronic graft-versus-host disease, leukemia-free survival, and overall survival in the entire cohort and also in subset analyses by disease and disease stage. No significant associations were found between DSS and any outcomes in the overall cohort using the quartile categories or treating DSS as a continuous variable. Higher DSS scores were associated with decreased engraftment in early-stage disease (P = .0003), but not in other disease stages. In summary, DSS does not correlate with transplantation outcomes, and the HistoCheck scoring system does not provide an effective technique for ranking HLA class I MM. The dataset used in this study is available to evaluate new algorithms proposed for donor selection.


Diagnosis and treatment of common metabolic spinal disorders in the geriatric population.
Bone is constantly resorbed and remodeled throughout life. After approximately age 30, there is a net loss of bone mass. This places the geriatric population at an increased risk of pathologic bone disorders that can lead to fractures and deformity. In this paper, we review bone metabolism and remodeling and introduce the proper diagnostic techniques. The most common pathologic spinal disorders are introduced, with emphasis on presentation and treatment options. To prevent excessive bone loss, patients should be educated on proper nutrition (calcium and vitamin D requirements) and lifestyle (avoiding alcohol and cigarette smoking). Sex hormone and drug therapies are available to reduce bone loss. New bisphosphonates such as alendronate sodium (Fosamax) have been effective in increasing bone mass. Early diagnosis and proper treatment of pathologic bone disorders can reduce the incidence of fracture and allow the patient a more productive and comfortable life.


Children's Participation in Ceremonial Life in Bali: Extending LOPI to Other Parts of the World.
This chapter extends a model of how children in Indigenous communities of the Americas Learn by Observing and Pitching In (LOPI; Rogoff, 2014) to another region of the world, by examining which aspects of the model can be applied to the ways in which Balinese children learn with their peers and adults. We describe clear parallels in the role of observation and communication, the social organization of endeavors, and children's motivation to participate as they learn the music of gamelan (the traditional orchestra) that is used in religious ceremonies.


Auto-anti-A1 antibody in a patient with metastatic adenocarcinoma.
An autoantibody was found on the red cells of a patient who had never been transfused previously, but was ill with metastatic adenocarcinoma. The patient's blood group was A1. In addition, the patient's serum and the eluate from the patient's red cells agglutinated A1 but not A2, B, and O red cells. This auto-A1 antibody was reactive at a wide thermal range and was inactivated by dithiothreitol, suggesting the presence of an IgM immunoglobulin. Moreover, the antibody was not associated with a hemolytic anemia.


Protein kinase C as mediator of arachidonic acid-induced decrease of neuronal M current.
The M current, IM, of NG108-15 neuroblastoma x glioma hybrid cells, a non-inactivating K+ current, is decreased by arachidonic acid (5-25 microM), often after an initial transitory increase. To test the possibility that the decrease is caused by activation of protein kinase C (PKC) we used the PKC 19-31 peptide, which is an effective inhibitor of PKC. With 1 microM peptide in the pipette solution the normally observed strong reduction of IM by 1 microM phorbol 12,13-dibutyrate (PDB) was almost totally prevented, indicating that PKC is completely inhibited; also the voltage dependence of the M conductance, gM(V), was shifted to more negative membrane potentials. In the presence of 1 microM peptide the effect of 25 microM arachidonic acid on IM was significantly reduced, suggesting that the effect, or at least a large part of it, is mediated by PKC.


[Effects of digital information display time on human and machines monitoring performance].
To provide an index for function allocation of information monitoring between human and machine by studying the effect of digital information display time on human or machine monitoring performance. Two computers were used. One computer, ten numbers with two decided digits were displayed randomly for three times. The display time varied from 200 ms to 5000 ms with different intervals. The other's monitor was simulated by a camera recorder and image identifying arithmetics was designed. Subjects watched the CRT and press the computer keys related with the figure on the CRT. In every experiment, the correct rate of human press or machine identification was recorded. The subjects' correct rate varied sharply when display time was 1500 ms. When display time was shorter then 1500 ms, subjects' correct rate decreased accordingly and may approach 0. From 1500 ms to 4500 ms, the subjects' correct rate was close to 100.0%. But when the display time was 5000 ms, the subjects' correct rate decreased slightly to 97.67%. From 50 ms to 5000 ms, the machine's correct rate varied little at different display times. The digital display time has very great effect on human monitoring performance. But it has little effect on machine performance.


Orbital pseudotumor in a child: diagnostic implications and treatment strategies.
Orbital pseudotumor is a benign, idiopathic, non-infectious and non-neoplastic clinical syndrome characterized by the presence of an inflammatory mass at orbital level with no identifiable cause. The disease is rarely observed in the pediatric population. This article describes a relapsing bilateral orbital pseudotumor in a young girl. The diagnostic implications and treatment strategies are discussed.


Simple geometry in complex organisms.
Many cultures throughout history have used the regularities of numbers and patterns as a means of describing their environment. The ancient Greeks believed that just five archetypal forms--the 'platonic solids'--were part of natural law, and could describe everything in the universe because they were pure and perfect. The formation of simple geometric shapes through the interactions of physical forces, and their development into more complex biological structures, supports a re-appreciation of these pre-Darwinian laws. The self-assembly of molecular components at the nano-scale, and their organization into the tensegrities of complex organisms is explored here. Hierarchies of structure link the nano and micro realms with the whole organism, and have implications for manual therapies.


Method of reconstruction or preservation of external auditory canal.
A brief summary of methods for reconstruction of the external auditory meatus for whatever reason, which have been recommended and used by a number of authors, is presented. Recurrence of the atretic problem occurs in a great percentage of individuals necessitating further attempts with an even greater failure rate. In 13 ases with this problem, including congenital agenesis and/or atresia of the external auditory canal, exostectomies, and postsurgical stenosis, I have fund that surgery with concomitant use of Merocel wicks has given a "cure rate" of better than 90%. The first patient in this group has been followed for approximately two years.


[The gene mutation analysis of a Wiskott-Aldrich syndrome family with normal mean platelet volume].
To investigate the history of a Wiskott- Aldrich syndrome (WAS) family with normal mean platelet volume (MPV), analyse the WASP gene mutation of to better understand its clinical characteristics. A four- generation WAS family histories of 22 members were investigated. Peripheral blood samples were collected from propositus and his mother to analyse all exon mutations of WASP gene using sanger sequencing. The MPV of both propositus and his elder brother were normal. The patient's clinical score was 5, antibodies to PM-Scl, PCNA and PO were positive with very high level of ASO, the patient co- suffered from autoimmune disease, anemia, abnormal renal function, fungal infection and scleritis. A homozygous mutation (C>T) was found at 173 bp of exon 2, corresponding to amino acids Pro (P) 58 abnormally changed to Leu (L). His mother was the carrier of the mutation. Of 112 blood diseases- related genes, mutation frequencies of CBL, CREBBP, DNM2 and ADAMTS13 were higher than normals. This was the first report the phenotype 173C>T mutation of WASP without eczema, but with normal MPV and autoimmune disease in Chinese, WAS should be recognized earlier and diagnosed correctly by genomic methods.


Molecular characterization of a novel translocation t(5;14)(q21;q32) in a patient with congenital abnormalities.
Chromosomal translocations are frequently found to be associated with various malignant disorders as well as congenital abnormalities. We report the characterization of a novel reciprocal translocation t(5;14)(q21;q32) in a patient with congenital abnormalities manifested by severe mental retardation, athetotic tetraplegia, microcephaly, peculiar facies (upward slanting of palpebral fissures), clinodactyly of the fifth fingers, and overlapping toes. Using a JHGP24 lymphoblast cell line derived from this patient, metaphase fluorescence in situ hybridization with bacterial artificial chromosome and cosmid probes and subsequent molecular analysis mapped the translocation breakpoint to the nucleotide level. Sequence analysis of the breakpoint junctions revealed the presence of a homologous sequence, GTGGC, along with a single nucleotide substitution and an insertion in der(14), and a single nucleotide deletion in the der(5) chromosome. We also attempted to identify and characterize the transcripts near the breakpoint by 5' and 3' rapid amplification of cDNA ends. Although we found several transcripts near the breakpoint of chromosome 14, the lack of significant ORFs within these transcripts suggests they are likely to be non-coding RNAs. These transcripts may have an important role in the neurogenesis or differentiation.


[The transcutaneous method of monitoring partial pressure of O2 and CO2 during laser surgery of the trachea and bronchi].
Anesthesia during Nd-YAG laser resection of the airways necessitates continuous O2 and CO2 monitoring. Although only partial, monitoring may be performed using a transcutaneous method utilising Clark's electrode to measure O2 and Stowe-Severinghaus' electrode to assess CO2 on the skin surface. The paper evaluates the advantages and limits of this form of monitoring during anesthesia in 85 patients undergoing laser resection of the airways. In conclusion, in spite of the fact that it is currently impossible to build up a complete picture of blood gas status from a single transcutaneous finding, the use of the transcutaneous method increases the level of safety of the operation as a whole.


Procedures of measurement of the body mass in children by community health agents in Macaé, Rio de Janeiro, Brazil, 2010-2011.
to describe the measurement process of the body mass in children under seven years old, assisted by community health agents in primary health care units of the Family Health Strategy, in Macaé-RJ, Brazil. a descriptive study with community health agents who measured the body mass of children, from August 2010 to August 2011. ¾ (n=65) of the community health agents from Macaé Primary Health Care were observed in 196 measurements; in 66.8% of measurements, the professionals used domestic scales (p<0.001); 65.3% of the scales were put on uneven floor; the procedure 'undress the child' was followed in 18.4% of cases; of those, 72.2% were performed properly (p<0.001). failures in the technical procedures of measurement were detected, pointing to the need to expand the reflection and discussion on the impact of the measurements, which help determine the nutritional diagnose of children.


The effects of matrix stiffness and RhoA on the phenotypic plasticity of smooth muscle cells in a 3-D biosynthetic hydrogel system.
Studies using 2-D cultures have shown that the mechanical properties of the extracellular matrix (ECM) influence cell migration, spreading, proliferation, and differentiation; however, cellular mechanosensing in 3-D remains under-explored. To investigate this topic, a unique biomaterial system based on poly(ethylene glycol)-conjugated fibrinogen was adapted to study phenotypic plasticity in smooth muscle cells (SMCs) as a function of ECM mechanics in 3-D. Tuning the compressive modulus between 448 and 5804 Pa modestly regulated SMC cytoskeletal assembly in 3-D, with spread cells in stiff matrices having a slightly higher degree of F-actin bundling after prolonged culture. However, vinculin expression in all 3-D conditions was qualitatively low and was not assembled into the classic focal adhesions typically seen in 2-D cultures. Given the evidence that RhoA-mediated cytoskeletal contractility represents a critical node in mechanosensing, we molecularly upregulated contractility by inducing SMCs to express constitutively active RhoA. In these cells, F-actin bundling and total vinculin expression increased, and focal adhesion-like structures began to emerge, consistent with RhoA's mechanism of action in cells cultured on 2-D substrates. Furthermore, SMC proliferation in 3-D did not depend significantly on matrix stiffness, and was reduced by constitutive activation of RhoA irrespective of ECM mechanical properties. Conversely, the expression of contractile markers globally increased with constitutive RhoA activation and depended on 3-D matrix stiffness only in cells with heightened RhoA activity. Combined, these data suggest that the synergistic effects of ECM mechanics and RhoA activity on SMC phenotype in 3-D are distinct from those in 2-D, and highlight the importance of studying the mechanical role of cell-matrix interactions in tunable 3-D environments.


[The effect of alimentary hypercholesterolemia on the level of lipids and essential fatty acids in rabbit enterohepatic circulation].
Patterns of lipid metabolism were estimated in biological fluids and tissues involved in enterohepatic circulation of bile lipid complexes in female rabbits with alimentary hypercholesterolemia. Cholesterol gallstones were not found in gallbladder of rabbits with alimentary hypercholesterolemia. A number of reasons was responsible for the phenomenon, including specific ratio of four lipid components, which contributed to maintaining bile cholesterol in soluble form: concentration of bile acids was unaltered simultaneously with high contents of cholesterol and a decrease in phospholipids level, while content of free fatty acids was increased and the content of arachidonic acid was elevated in majority of lipid fractions.


[A case of multiple chemodectoma: clinical and electron microscopical studies].
We observed electronmicroscopically and clinically a case of multiple chemodectoma, which has occurred from glomus caroticum sinistra and glomus jugularis sinistra of a 18 year old boy. The diagnosis was especially made by an angiography of the left common carotid artery and by a retrograde venography of the left internal jugular vein. Electronmicroscopically two kinds of tumor cells in this chemodectoma were identified. These cytoplasmas showed cored neurosecretory granules measured 125 to 250 A in diameter markedly increasing in number. Moreover in the island of the tumor cells of the carotid body tumor we happened to observe the nerve ending.


Individual, Community, and Health Facility Predictors of Postnatal Care Utilization in Rural Tanzania: A Multilevel Analysis.
Postnatal care (PNC) is an underused service in the continuum of care for mothers and infants in sub-Saharan Africa. There is little evidence on health facility characteristics that influence PNC utilization. Understanding PNC use in the context of individual, community, and health facility characteristics may help in the development of programs for increased use. We analyzed data from 4,353 women with recent births in Kigoma Region, Tanzania, and their use of PNC (defined as at least 1 checkup in a health facility in the region within 42 days of delivery). We used a mixed-effects multilevel logistic regression analysis to explain PNC use while accounting for household, individual, and community characteristics from a regionwide population-based reproductive health survey and for distance to and adequacy of proximal health facilities from a health facility assessment. PNC utilization rate was low (15.9%). Women had significantly greater odds of PNC if they had a high level of decision-making autonomy (adjusted odds ratio [aOR]: 1.56; 95% confidence interval [CI]=1.11, 2.17); had a companion at birth (aOR: 1.57; 95% CI=1.19, 2.07); had cesarean delivery (aOR: 2.27; 95% CI=1.47, 3.48); resided in Kasulu district (aOR: 3.28; 95% CI=1.94, 5.52); or resided in a community that had at least 1 adequate health facility within 5 km (aOR: 2.15; 95% CI=1.06, 3.88). Women's decision-making autonomy and presence of companionship at birth, as well as proximity to a health facility with adequate infrastructure, equipment, and workforce, were associated with increased PNC use. More efforts toward advocating for the health benefits of PNC using multiple channels and increasing quality of care in health facilities, including companionship at birth, can increase utilization rates.


New and emerging biomarkers in cardiovascular disease.
Cardiovascular disease (CVD) is the most common cause of death and disability worldwide. Therefore, great importance has been placed on the discovery of novel risk factors and metabolic pathways relevant in the prevention and management of CVD. Such research is ongoing and may continue to lead to better risk stratification of individuals and/or the development of new intervention targets and treatment options. This review highlights emerging biomarkers related to lipid metabolism, glycemia, inflammation, and cardiac damage, some of which show promising associations with CVD risk and provide further understanding of the underlying pathophysiology. However, their measurement methodology and assays will require validation and standardization, and it will take time to accumulate evidence of their role in CVD in various population settings in order to fully assess their clinical utility. Several of the novel biomarkers represent intriguing, potentially game-changing targets for therapy.


Combined hemodynamic echocardiographic Doppler evaluation of prostaglandin E1 effects in patients with severe dilated cardiomyopathy undergoing evaluation for heart transplantation.
Prostaglandin E1 has been used in patients undergoing evaluation for heart transplantation. Because of high lung metabolism, the drug has been used to test pulmonary vasoreactivity, although a systemic effect is also present. The purpose of this study is a more thorough assessment of the drug. Prostaglandin E1 was infused with progressive steps in 14 patients in New York Heart Association class III to IV with severe dilated cardiomyopathy. The patients were studied through a combined hemodynamic and Doppler echocardiographic evaluation. With prostaglandin E1, mean aortic and pulmonary arterial pressure decreased by 7% (p < 0.01) and 24% (p < 0.001), respectively with a 23% (p < 0.001) increase in stroke volume index. Systemic vascular resistance decreased by 22% (p < 0.001), and pulmonary vascular resistance decreased by 33% (p < 0.001), with a 15% decrease in the pulmonary/systemic vascular resistance ratio. Heart rate was unaffected. Minimum and end-diastolic left ventricular pressure decreased by 35% (p < 0.001) and 21% (p < 0.001), respectively. The logarithmic time constant of left ventricular isovolumetric relaxation and maximum rate of isovolumic pressure decline were not modified. Early and late left ventricle diastolic filling were not significantly modified if considered separately, but there was a 27% (p < 0.01) decrease in the early/late filling ratio, suggesting a redistribution of diastolic filling to later in diastole. The 34% (p < 0.01) decrease in right atrial pressure suggests a reduction in intrapericardial pressure which mirrors the significant change in the early/late ratio toward a less restrictive filling pattern. It is possible that the end-stage ventricles of these patients respond to the reduction in pulmonary and systemic resistances secondary to prostaglandin E1 infusion by increasing stroke volume, with a redistribution of diastolic filling to later in diastole.


Integrated population pharmacokinetics of etanercept in healthy subjects and in patients with rheumatoid arthritis and ankylosing spondylitis.
Etanercept pharmacokinetics in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriasis were assessed separately with distinct models using population pharmacokinetics methods of limited precision. The different model structures and associated significant covariates identified by these earlier methods made it difficult to compare etanercept pharmacokinetics among disease groups. This integrated analysis aimed to establish a framework to evaluate previously established population pharmacokinetic models of etanercept, and to identify consistent and important demographic and disease factors that affected etanercept pharmacokinetics in a diverse population of healthy subjects and patients with RA and AS. In this integrated analysis, cumulative rich and sparse etanercept concentration data from 53 healthy volunteers, 212 patients with RA, and 346 patients with AS were examined and compared using nonlinear mixed effect methodology implemented the in NONMEM VI software package. A more precise estimation method (FOCEi) was employed and compared with the first-order method in population pharmacokinetics model building and evaluation. The integrated analysis found that an optimal population pharmacokinetics model with a 2-compartment structure adequately characterized etanercept pharmacokinetics in all subject groups. Health status or disease type did not significantly affect etanercept pharmacokinetics. In adult patients with RA and AS, age and body weight do not significantly affect etanercept pharmacokinetics.


Choroidal thickness and intraocular pressure after 25-gauge and 23-gauge vitrectomy for idiopathic epiretinal membrane.
To determine the relationship between the subfoveal choroidal thickness (SCT) and intraocular pressure (IOP) following 25-gauge (25G) and 23-gauge (23G) vitrectomy for idiopathic epiretinal membrane (ERM). Retrospective, consecutive, interventional case series. Sixty-two patients undergoing 25G vitrectomy and 56 patients undergoing 23G vitrectomy for ERM participated. SCT was measured using enhanced depth imaging optical coherence tomography and IOP were measured both at baseline and postoperatively. In both groups, the IOPs on day one and one week after surgery were significantly lower than at baseline (P < 0.001 for both). The rates of changes of IOP were significantly greater in 23G compared to 25G on day one (P = 0.026). In 23G the SCTs on day one and one week after surgery were significantly thicker (P < 0.001) than baseline. The rates of changes in SCT between baseline and day one negatively correlated with those of IOP in 23G (r = -0.559, P < 0.001) but no correlation was observed with 25G (r = -0.129, P = 0.316). Choroidal thickness increases soon after 23G vitrectomy for ERM which is probably due to the transient hypotony, however, early SCT change does not appear in 25G vitrectomy. Twenty-five-gauge vitrectomy may have an advantage in minimizing postoperative choroidal changes.


The levator syndrome and its treatment with high-voltage electrogalvanic stimulation.
Electrogalvanic stimulation by means of a specially designed rectal probe is a simple, safe, and effective modality of treatment for patients with levator spasm. It probably acts by overstimulating and overcontracting the levator muscles and thereby fatiguing them. Results were excellent in 69 percent of the patients, good in 21 percent, and poor in only 10 percent. We recommend electrogalvanic stimulation as the primary treatment of levator spasm in which a neurologic cause cannot be documented.


Salvage therapy of intraprostatic failure after radical external-beam radiotherapy for prostate cancer: a review.
Radical external-beam radiotherapy (EBRT) is a standard treatment for prostate cancer (PC) patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. Treatment strategies after PC relapse are strongly influenced by the effective site of the tumor recurrence, and thus the instrumental evaluation with different imaging techniques becomes crucial. In cases of demonstrated intraprostatic failure, several systemic (androgen deprivation therapy) or local (salvage prostatectomy, cryotherapy, high-intensity focused ultrasound, brachytherapy, stereotactic EBRT) treatment options could be proposed and are currently delivered by clinicians with a variety of results. In this review we analyze the correct definition of intraprostatic relapse after radiotherapy, focusing on the recent developments in imaging to detect intraprostatic recurrence. Furthermore, all available salvage treatment options after a radiation therapy local failure are presented and thoroughly discussed.


Community psychology in Thailand.
In a developing country such as Thailand, where many pressing problems must be dealt with promptly, quick solutions, though often short-lived, are usually preferred over long-term preventive measures. This paper attempts to describe the Thai community psychology movement and its struggles to overcome momentous obstacles, along with innovations that serve as a foundation for future work.


The arthroscopic treatment of unicompartmental gonarthrosis: a five-year follow-up study of abrasion arthroplasty plus arthroscopic debridement and arthroscopic debridement alone.
A retrospective review with a mean follow-up time of 60 months was performed on 126 patients who had treatment of unicompartmental gonarthrosis with either abrasion arthroplasty plus arthroscopic debridement or arthroscopic debridement alone. Fifty-nine patients had abrasion arthroplasty and arthroscopic debridement, and 67 patients had arthroscopic debridement alone. All patient had stage II Ahlbäck changes roentgenographically, as well as Outerbridge stage IV changes arthroscopically in the involved compartment. All the knees were evaluated postoperatively at a minimum of 60 months, utilizing The Hospital For Special Surgery Knee Scoring System. In the group treated with abrasion arthroplasty, 51% had good to excellent results, 16% had fair results, and 33% had poor results. The conditions of ten of the patients who had poor results actually became worse subsequent to their abrasion arthroplasty. In the group that had arthroscopic debridement, 66% had good to excellent results, 13% had fair results, and 21% had poor results. The conditions of 12 of the patients who had poor results actually became worse subsequent to the arthroscopic debridement.


The effects of experience and attrition for novice high-school science and mathematics teachers.
Because of the current high proportion of novice high-school teachers, many students' mastery of science and mathematics depends on the effectiveness of early-career teachers. In this study, which used value-added models to analyze high-school teachers' effectiveness in raising test scores on 1.05 million end-of-course exams, we found that the effectiveness of high-school science and mathematics teachers increased substantially with experience but exhibited diminishing rates of return by their fourth year; that teachers of algebra 1, algebra 2, biology, and physical science who continued to teach for at least 5 years were more effective as novice teachers than those who left the profession earlier; and that novice teachers of physics, chemistry, physical science, geometry, and biology exhibited steeper growth in effectiveness than did novice non-science, technology, engineering, and mathematics teachers.


Precordial pain induced by the isolated cardiac hydatid cyst in interventricular septum: a case report.
Human hydatid disease occurs after infection with Echinococcus granulosus, mainly involves liver and lung, while hydatid involves heart is infrequent. A great majority of hydatid diseases could be asymptomatic, and incidentally found through examination. Here, we reported a woman who suffered an isolated cardiac hydatid cyst located at the interventricular septum. A 48-year-old woman presented intermittent chest pain was admitted to the hospital. Imaging examination revealed a cyst located at the interventricular septum near the right ventricular apex. Considering medical history, radiological findings and serological results, cardiac hydatid disease was suspected. The cyst was successfully removed, while pathological biopsy confirmed the diagnosis of infection of Echinococcus granulosus. Postoperative course was uneventful, the patient was discharged from hospital without complications. For symptomatic cardiac hydatid cyst, surgical resection is necessary to avoid progression of disease. During surgical procedure, appropriate methods to reduce the potential risk of hydatid cyst metastasis are essential. Besides surgery, combined with regular drug therapy is an effective strategy to prevent reappearance.


Phenotypic and genotypic detection of β-lactamases in Acinetobacter spp. isolates recovered from Lebanese patients over a 1-year period.
The aim of this study was to determine the prevalence of β-lactamases in Acinetobacter spp. recovered from Lebanese patients over a 1-year period using phenotypic and molecular methods. A total of 100 non-duplicate consecutive Acinetobacter spp. isolates were collected from various clinical specimens. Antimicrobial susceptibility testing was performed by the disk diffusion method. Susceptibility to colistin, imipenem and meropenem was determined by broth microdilution. The β-lactamase inhibitors phenylboronic acid, cloxacillin and ethylene diamine tetra-acetic acid (EDTA) were used for presumptive detection of KPC-type β-lactamase, AmpC β-lactamase and metallo-β-lactamase (MBL), respectively. Simplex PCR was conducted for molecular detection of β-lactamases. Trilocus PCR typing was performed to determine the clonality of the isolates. Among the 100 Acinetobacter spp. isolates, 78% were resistant to imipenem and 84% to meropenem. Only one isolate was resistant to colistin by the microdilution method. Phenotypically, 23% of the isolates were presumptively diagnosed as producing extended-spectrum β-lactamase (ESBL), 15% as producing KPC and 4% MBL, whilst 5% were diagnosed as overproducing AmpC β-lactamase. The blaOXA-51-like gene was detected in 99% of isolates, blaADC in 93%, blaOXA-23-like in 77% and blaOXA-24/40-like in 3%. Trilocus PCR identified 86% (82/95) of the Acinetobacter baumannii isolates as international clone II (IC II). A high rate of carbapenem resistance, with a predominance of OXA-23-like and IC II, was shown in this study. Moreover, the inhibitor-based method was shown not to be accurate for the prediction of carbapenemases in A. baumannii.


On the role of self-excitation in the development of topographic order in the visual system of the frog.
A two-level model is presented for explaining the development of the topographically ordered retinotectal connections of the visual system of the frog. The columnar structure of the tectum were taken into account explicitly. Simulations suggest that the self-excitatory intracolumnar connections play an important role in the formation of the topography. In the case of self-excitation the system is able to recognize the topology of the visual field by the continuity of the object's movement.


The expression of calpain-1 and androgen receptor in breast cancer and their correlation with clinicopathological characteristics: An immunohistochemical retrospective study.
Breast cancer is a heterogeneous disease with different biological outcome and ability to acquire resistance to therapy. The calpain family of proteases and androgen receptor (AR) are implicated in breast cancer pathogenesis and progression and are potential targets for novel treatment regimens. The aim of this study was to investigate the expression of calpain-1 and AR in breast cancer and to correlate their expression with clinicopathological variables and prognosis of patients. In this study we enrolled 219 breast cancer patients with long term follow-up information available. Immunohistochemical methods on a tissue microarray were used to investigate expression of calpain-1 and AR in tumor cells. The expression of calpain-1 and AR both differed significantly between the tumor subtypes of patients (p = 0.002 and p = 0.042 respectively). High calpain-1 expression was associated with patient's age over 50 years (p = 0.005) and positive ER status (p = 0.009), but not with other clinicopathological variables. Women with AR negative breast cancers were more likely to be older (p = 0.016), to have bigger tumors (p = 0.032), higher stage of the disease (p = 0.026), presence of exulceration (p = 0.017), negative ER status (p = 0.007) and higher Ki-67 proliferative index (p = 0.027). Calpain-1 expression was not associated with breast cancer specific overall survival in the total cohort of patients, however low calpain-1 expression was associated with adverse survival (p = 0.018) in triple negative subgroup of patients. Low calpain-1 expression was also associated with significantly shorter 5-year disease-free survival in total cohort of patients (p = 0.03). AR status was not associated with overall and disease-free survival of patients. This study has demonstrated that the expression of calpain-1 and androgen receptors are associated with important clinicopathological variables. The expression of calpain-1 was associated with improved disease-free survival of all analyzed patients and with improved overall survival of triple negative breast cancer patients.


Selective breeding for sensitivity to DFP: generalization of effects beyond criterion variables.
The degree of generalization to the effects of DFP, an organophosphate anticholinesterase, was studied in two lines of Sprague-Dawley derived rats selectively bred for varying sensitivities to DFP. In the S13, S14, S15, and S16 generations the Flinders S-line of rats were still more sensitive to the effects of DFP on the criterion variables upon which selection was based: core body temperature, body weight and a simple operant response for water reward. The flinders S-line were also more sensitive to the effects of DFP on locomotor activity, FR5 responding for a water reward, and analgesia, indicating some degree of generalization. However, diarrhea, a symptom of peripheral effects of DFP, occurred at a similar incidence in the two lines, although males of both lines had higher incidences than the females. Neither of the two lines was affected by DFP for variables in which aversive (i.e. shock) motivation was used: The number of discriminative escape responses and the escape times were similar. These findings indicate that while the effects of DFP do generalize beyond the criterion variables upon which selection was based, the generalization is relatively specific. The data are consistent with the hypothesis that the changes in sensitivity have arisen because of changes in the functioning of a central cholinergic system(s).


Intrafamilial phenotypic variability in autosomal recessive DOCK6-related Adams-Oliver syndrome.
Adams-Oliver syndrome (AOS) is diagnosed in presence of aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). The autosomal recessive (AR) DOCK6-related form of AOS is most often associated with a severe phenotype including also central nervous system and ocular abnormalities. We report a sister and brother with different expression of the phenotype. Both were compound heterozygous pathogenic variants in the DOCK6 gene, including a heterozygous c.5939+2T > C intronic variant that was maternally inherited, and a heterozygous deletion of exons 10 to 21 that was paternally inherited. The sister had microcephaly, periventricular calcifications, minor retinal vasculopathy, and mild impaired neurodevelopment, but only very subtle limb abnormalities and no ACC. Her brother showed a classical DOCK6-related AOS phenotype, including a severe bilateral peripheral ischemic retinopathy. From a review of 22 molecularly confirmed cases with DOCK6-related AOS with ophthalmic examination, we found that 16 of them had retinal vascular pathology (72.7%), confirming as the major ocular anomaly. Documented intrafamilial variability in our family and the evidence revised from previous reports, confirm that AR DOCK6-related AOS expressivity can produce a "milder" phenotype without ACC or TTLD, which could be underdiagnosed in simplex cases because it is difficult to recognize out of a familial context. Therefore, in order to know its real magnitude is required the future inclusion of DOCK6 gene in NGS panels directed to the study of simplex cases of patients with microcephaly, periventricular calcifications, retinal vasculopathy, and/or cardiovascular defects.


Bloodstream infection by Rhodococcus corynebacterioides in a pediatric patient diagnosed with high-risk retinoblastoma.
Rhodococcus is a pathogen that is known to cause infections in animals and humans, mainly in cases of immunocompromised patients. A case of a pediatric cancer patient suffering from a bloodstream infection caused by Rhodococcus corynebacterioides was described in this work. Gram positive rods were isolated from blood cultures. The target bacterium was identified using a combination of biochemical tests, the MALDI-TOF mass spectrometry technique, and the analysis of the 16S rRNA sequence. Moreover, an antimicrobial susceptibility test was performed using the E-test. The isolated bacterium was identified as R. corynebacterioides. The 3-year-old patient was successfully treated with vancomycin and meropenem. This is the first published report of R. corynebacterioides in a pediatric patient diagnosed with retinoblastoma that developed a bloodstream infection. R. corynebacterioides should be considered among the opportunistic infectious agents affecting pediatric cancer patients.


Impact of composition on the dynamics of autocatalytic sets.
Autocatalytic sets are sets of entities that mutually catalyse each other's production through chemical reactions from a basic food source. Recently, the reflexively autocatalytic and food generated theory has introduced a formal definition of autocatalytic sets which has provided promising results in the context of the origin of life. However, the link between the structure of autocatalytic sets and the possibility of different long-term behaviours is still unclear. In this work, we study how different interactions among autocatalytic sets affect the emergent dynamics. To this aim, we develop a model in which interactions are presented through composition operations among networks, and the dynamics of the networks is reproduced via stochastic simulations. We find that the dynamical emergence of the autocatalytic sets depends on the adopted composition operations. In particular, operations involving entities that are sources for autocatalytic sets can promote the formation of different autocatalytic subsets, opening the door to various long-term behaviours.


Interface properties of ionic liquids containing metal ions: features and potentialities.
Interfaces and surfaces are the regions where important events happen: catalysis, molecular recognition, charge transfer, polymerization, and many other critical processes take place at the boundary between one medium and another. In this article we discuss the interface (liquid/air) properties of ionic liquids (ILs) containing dissolved metal ions with the aim to show the possibility to use metal salts to transform ILs and their surfaces into engineered liquid supports to apply in material sciences, separation procedures or to use as optical devices.


Diagnosing functional complete denture fractures.
Many factors can contribute to the fracture of complete dentures. This article has identified some of these factors and presented some methods that can greatly reduce or eliminate functional complete denture base fractures when used with a thorough diagnosis and treatment plan.