Efficacy and safety of CARTIGROW® in patients with articular cartilage defects of the knee joint: a four year prospective studys.
Research shows autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage lesions. In this study, we assessed mid-term efficacy and safety of gel-based ACI or autologous adult live cultured chondrocytes (CARTIGROW®) implantation in patients with cartilage defects of the knee joint. In this prospective, open-label study, patients (19-38 years) with focal, international cartilage repair society grade III or IV articular cartilage defects of the knee joint were enroled at four centres across India from April 2015 to September 2015. Punch biopsy was conducted to harvest cartilage, from which chondrocytes were isolated and cultured, and the characterised chondrocytes were implanted into the cartilage defect. Key efficacy outcomes were assessed by quantitative changes in international knee documentation committee (IKDC), visual analogue scale (VAS) scores, and qualitative changes in magnetic resonance imaging at six months and four years from baseline. Of the14 patients enroled in the study, all patients completed the six month follow-up and 11 completed the four year follow-up. The IKDC score improved significantly from 32.84 ± 9.25 at baseline to 67.49 ± 13.03 at six months (mean difference [MD] 34.66 ± 13.00, p < 0.0001) and to 60.18 ± 10.33 at four years (MD 28.21 ± 15.14, p = 0.0001). The VAS score reduced from 72.00 ± 14.40 at baseline to 16.64 ± 17.03 at six months (MD 55.36 ± 24.50, p < 0.0001) and further to 12.72 ± 9.05 at four years (MD 62.09 ± 10.66, p < 0.0001). All patients showed improvement on MRI of the knee joint. No adverse events were reported. Autologous adult live cultured chondrocytes (CARTIGROW®) implantation showed good mid-term efficacy in patients with cartilage defects of the knee joint with no side-effects.


Femoral mononeuropathy caused by a malignant sarcoma: two case reports.
A 9-year old miniature poodle and a 6-year old American Staffordshire terrier were evaluated for slowly progressive lameness and atrophy of the left pelvic limb. Neurological examinations of both animals were consistent with femoral nerve lesions. In both cases, neoplastic masses were identified within the left psoas muscle, invading the left femoral nerve or, in one case, its nerve roots. Ultrasound-guided fine needle aspirate and histopathological examination of the masses revealed that these were malignant sarcomas. Femoral mononeuropathies are very rare in dogs, and most descriptions of femoral nerve lesions are caused by traumatic injuries. Descriptions of neoplastic processes affecting the femoral nerve are limited to peripheral nerve sheath tumours (PNST). These cases provide the first descriptions of malignant neoplasms other than PNSTs that infiltrate the femoral nerve or its nerve roots and cause unilateral femoral mononeuropathy and lameness of obscure origin.


Atypical salmonellosis: two cases of sacroiliitis.
Two young adult males presented with fever, severe pain, redness, swelling over the left sacroiliac joint and inability to walk and squat. A differential diagnosis of tuberculous sacroiliitis was considered. On blood culture isolation of S. Typhi in both of them was suggestive of sacroiliitis of salmonella etiology. They recovered completely following specific antibiotic therapy, aspirin and bed rest. At recovery both showed extremely high Widal titres.


Characterization of a murine gene encoding a developmentally regulated cytoplasmic dual-specificity mitogen-activated protein kinase phosphatase.
Mitogen-activated protein kinases (MAPKs) play a vital role in cellular growth control, but far less is known about these signalling pathways in the context of embryonic development. Duration and magnitude of MAPK activation are crucial factors in cell fate decisions, and reflect a balance between the activities of upstream activators and specific MAPK phosphatases (MKPs). Here, we report the isolation and characterization of the murine Pyst3 gene, which encodes a cytosolic dual-specificity MKP. This enzyme selectively interacts with, and is catalytically activated by, the 'classical' extracellular signal-regulated kinases (ERKs) 1 and 2 and, to a lesser extent, the stress-activated MAPK p38alpha. These properties define the ability of this enzyme to dephosphorylate and inactivate ERK1/2 and p38alpha, but not JNK (c-Jun N-terminal kinase) in vivo. When expressed in mammalian cells, the Pyst3 protein is predominantly cytoplasmic. Furthermore, leptomycin B causes a complete redistribution of the protein to the nucleus, implicating a CRM (chromosomal region maintenance)1/exportin 1-dependent nuclear export signal in determining the subcellular localization of this enzyme. Finally, whole-mount in situ hybridization studies in mouse embryos reveal that the Pyst3 gene is expressed specifically in the placenta, developing liver and in migratory muscle cells. Our results suggest that this enzyme may have a critical role in regulating the activity of MAPK signalling during early development and organogenesis.


Chromosome diversity of the genus Aotus from Colombia.
Description of six Colombian karyomorphs is completed through an extensive cytogenetic characterization of 35 Aotus (owl monkeys) specimens. The description of a new karyomorph for Colombian Aotus by chromosome on Q, G, R, and C, sequential banding is included. Pairs of karyomorphs 2 and 3 and 6 and 9 with 2n of 54, and 50, respectively, as well as karyomorphs 7 and 8 with 46 and 58 chromosomes were strongly suspected to represent different species on the grounds of large karyotypic differences. A proposal for a chromosome nomenclature of Aotus karyomorphs that aims to clarify Aotus taxonomy is presented which achieves a precise correspondence of different banding patterns, based on Q, G, R, and C sequential banding and chromosome measurements. Although our contribution is not a universal nomenclature system, unique criteria for chromosome denomination within Aotus karyomorphs are established. Previous systems of chromosome nomenclature have not successfully addressed the nomenclature of chromosomes of the same karyotype.


Membrane-associated glucocorticoid activity is necessary for modulation of long-term memory via chromatin modification.
Glucocorticoid hormones enhance the consolidation of long-term memory of emotionally arousing training experiences. This memory enhancement requires activation of the cAMP-dependent kinase pathway and the subsequent phosphorylation of cAMP response-element binding (CREB) protein. Here, we demonstrate that glucocorticoids enhance the consolidation of hippocampus-dependent and hippocampus-independent aspects of object recognition memory via chromatin modification. More specifically, systemic corticosterone increases histone acetylation, a form of chromatin modification, in both the hippocampus and insular cortex following training on an object recognition task. This led us to examine whether increasing histone acetylation via histone deacetylase (HDAC) inhibition enhances memory in a manner similar to corticosterone. We found a double dissociation between posttraining HDAC inhibitor infusion into the insular cortex and hippocampus on the enhancement of object recognition and object location memory, respectively. In determining the molecular pathway upstream of glucocorticoids' effects on chromatin modification, we found that activation of membrane-associated glucocorticoid receptors (GRs) and the subsequent interaction between phospho-CREB and CREB-binding protein (CBP) appear to be necessary for glucocorticoids to enhance memory consolidation via chromatin modification. In contrast, mineralocorticoid receptors (MRs) do not appear to be involved. The findings also indicate that glucocorticoid activity has differential influences on hippocampus-dependent and hippocampus-independent components of memory for objects.


Impact of dietary counselling on nutrient intake during pregnancy: a prospective cohort study.
The aim of this study was to assess the impact of dietary counselling combined with the provision of food products on food and nutrient intake in pregnant women. We carried out a prospective cohort study of healthy and atopic pregnant women (n 209), who were randomized into dietary intervention and control groups. The intervention group received dietary counselling and food products to modify the fat composition of their diet to meet current recommendations. Three-day food records were collected during each trimester of pregnancy. Women in the intervention group consumed more vegetables, fruits, soft margarines and vegetable oils and less butter than those in the control group during the course of pregnancy (P<0.05). The main distinction between the groups in nutrient intake over the pregnancy was attributable to a higher energy intake (% energy) of PUFA by 0.5%energy (95% CI 0.1, 0.8) and to a lower intake of SFA by 0.8 % energy (95% CI -1.4, -0.4) in the intervention group. Dietary intake of vitamin E was 1.4 mg (95% CI 0.6, 2.2), folate 20.9 microg (95% CI 0.8, 41.0) and ascorbic acid 19.8 mg (95 % CI 3.5, 36.0) higher in the intervention group compared to the controls, while no differences in other nutrients were detected. Dietary counselling combined with the provision of food products during pregnancy is of importance in modifying food and nutrient intake, with potential health benefits.


Comparison of surgical stress responses during spinal and general anesthesia in curettage surgery.
Response to the surgical stress is an involuntary response to metabolic, autonomic as well as hormonal changes that leads to heart rate and blood pressure fluctuations. This study aimed to investigate the effect of general versus spinal anesthesia on blood sugar level and hemodynamic changes in patients undergoing curettage surgery. In this randomized clinical trial, 50 patients who were candidate for elective curettage surgery were divided into two groups of general (n = 25) and spinal (n = 25) anesthesia. In both groups, blood glucose level was evaluated 10 minutes before, 20 and 60 minutes after initiation of anesthesia. Also, heart rate and mean arterial blood pressure were evaluated at 10 minutes before, 10, 20, 30, 40, 50 and 60 minutes after intiation of anesthesia. There was not significantly difference between blood glucose level of both groups during 10 minutes before, 20 and 60 minutes after the intiation of anesthesia. Heart rate changes in the general and spinal groups compared to the baseline level were decreased up to maximum12.5% and 14.5%, respectively. The mean arterial pressure changes in the general and spinal groups compared to the baseline level were decreased up to maximum 5.4% and 8%, respectively. Blood glucose and hemodynamic changes caused by surgical stress were not significantly different between two groups.


Longitudinal study of Campylobacter jejuni bacteriophages and their hosts from broiler chickens.
A longitudinal study of bacteriophages and their hosts was carried out at a broiler house that had been identified as having a population of Campylobacter-specific bacteriophages. Cloacal and excreta samples were collected from three successive broiler flocks reared in the same barn. Campylobacter jejuni was isolated from each flock, whereas bacteriophages could be isolated from flocks 1 and 2 but were not isolated from flock 3. The bacteriophages isolated from flocks 1 and 2 were closely related to each other in terms of host range, morphology, genome size, and genetic content. All Campylobacter isolates from flock 1 were genotypically indistinguishable by pulsed-field gel electrophoresis (PFGE). PFGE and multilocus sequence typing indicated that this C. jejuni type was maintained from flock 1 to flock 2 but was largely superseded by three genetically distinct C. jejuni types insensitive to the resident bacteriophages. All isolates from the third batch of birds were insensitive to bacteriophages and genotypically distinct. These results are significant because this is the first study of an environmental population of C. jejuni bacteriophages and their influence on the Campylobacter populations of broiler house chickens. The role of developing bacteriophage resistance was investigated as this is a possible obstacle to the use of bacteriophage therapy to reduce the numbers of campylobacters in chickens. In this broiler house succession was largely due to incursion of new genotypes rather than to de novo development of resistance.


Social class differences in women's fat and fibre consumption: a cross-national study.
This study focuses on social class variation in the intake of fat and fibre in Maastricht, Liège and Aachen, based on food frequency questionnaires of 849 women from nuclear families with schoolgoing children. In Maastricht and Liège higher-middle class women consumed less fat than working class women, while in Aachen no class difference was apparent. The intake of fibre was highest among the higher-middle class women, although this tendency was not significant in Aachen. Analysis of food groups that contribute to the intake of fat and fibre revealed that not all food groups showed this pattern. Higher-middle class women consumed less bread, less potatoes and more cheese than working class women. Moreover, they chose more often high-fat cheese and fats. Yet, working class women consumed more meat, milk and fats, and less grain, fruit and vegetables. In general, social class variations in fat and fibre intake were uniform across the cities, although in Aachen class differences were small or absent. In conclusion, these results suggest that the diet of higher-middle class women is more in accordance with the dietary recommendations regarding fat and fibre than the diet of working class women.


Association between the Rs3087243 polymorphism and risk for diabetes: a meta-analysis.
The aim of this study was to evaluate the association between the rs3087243 polymorphism of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene and the risk of type 1 diabetes mellitus (T1D). A comprehensive meta-analysis of case-control studies was conducted to determine the association between the rs3087243 polymorphism (CT60A/G) and T1D and assess the joint evidence for the abovementioned association, influence of individual studies, and evidence for publication bias. We searched PubMed, Medline, Embase, Cochrane Library, and reference lists of relevant studies up to February 2012 and contacted the authors of these studies via email. For the case-control studies, 1) the rs3087243 polymorphism was significantly associated with T1D [allele (fixed: odds ratio and 95% confidence interval (CI) = 1.249 (1.194-1.307), P < 0.001; random: odds ratio and 95%CI = 1.601 (1.103-2.325), P = 0.013)] [genotype (GG versus GA+AA: odds ratio and 95%CI = 1.249 (1.164-1.341), P < 0.001)], 2) there was no evidence to show that this association was accounted for in any study, and 3) there was no evidence for publication bias. In conclusion, the rs3087243 polymorphism was significantly associated with T1D.


Synthesis of (+)-Greek Tobacco Lactone via a Diastereoablative Epoxidation and a Selenium-Catalyzed Oxidative Cyclization.
An asymmetric synthesis of the C11-homoterpenoid (+)-Greek tobacco lactone is developed starting from readily available (R)-linalool. The synthesis is comprised of four operations and features a diastereoablative epoxidation and an oxidative tetrahydropyran formation using vanadium-, palladium-, and selenium-catalyzed cyclizations.


The effectiveness of behavioral intervention for reduction of nausea and vomiting in children and adolescents receiving chemotherapy.
Fifty-one children 6-17 years of age rated the severity of nausea, vomiting, and the extent to which chemotherapy bothered them during each course of chemotherapy. Sixteen patients had no symptoms and the doses administered to 16 others were not constant so that matched courses could not be assessed. After baseline measurement of two matched courses, the remaining 19 patients were randomized to receive hypnosis or supportive counseling during two more matched courses. An additional course with no intervention was assessed in half of the patients. No significant reduction of symptoms was demonstrated prior to intervention. However, intervention with both hypnosis and supportive counseling was associated with significant reductions in nausea, vomiting, and the extent to which these symptoms bothered patients (all p less than 0.001). Also, after termination of intervention, symptom ratings remained significantly lower than baseline. The data indicate that chemotherapy-related nausea and emesis in children can be reduced with behavioral intervention and that reductions are maintained after intervention has been discontinued.


Role of MAPK Signaling Pathways in Regulating the Hydrophobin Cryparin in the Chestnut Blight Fungus Cryphonectria parasitica.
We assessed the regulation of cryparin, a class II hydrophobin, using three representative mitogen-activated protein kinase (MAPK) pathways in Cryphonectria parasitica. Mutation of the CpSlt2 gene, an ortholog of yeast SLT2 in the cell wall integrity (CWI) pathway, resulted in a dramatic decrease in cryparin production. Similarly, a mutant of the CpBck1 gene, a MAP kinase kinase kinase gene in the CWI pathway, showed decreased cryparin production. Additionally, mutation of the cpmk1 gene, an ortholog of yeast HOG1, showed decreased cryparin production. However, mutation of the cpmk2 gene, an ortholog of yeast Kss1/Fus3, showed increased cryparin production. The easy-wet phenotype and accumulation of the cryparin transcript in corresponding mutants were consistent with the cryparin production results. In silico analysis of the promoter region of the cryparin gene revealed the presence of binding motifs related to downstream transcription factors of CWI, HOG1, and pheromone responsive pathways including MADS-box- and Ste12-binding domains. Real-time reverse transcriptase PCR analyses indicated that both CpRlm1, an ortholog of yeast RLM1 in the CWI pathway, and cpst12, an ortholog of yeast STE12 in the mating pathway, showed significantly reduced transcription levels in the mutant strains showing lower cryparin production in C. prasitica. However, the transcription of CpMcm1, an ortholog of yeast MCM1, did not correlate with that of the mutant strains showing downregulation of cryparin. These results indicate that three representative MAPK pathways played a role in regulating cryparin production. However, regulation varied depending on the MAPK pathways: the CWI and HOG1 pathways were stimulatory, whereas the pheromone-responsive MAPK was repressive.


Synthesis and in Vitro Cytotoxicity Evaluation of Jadomycins.
Jadomycins, which are benzo[b]phenanthridine-type alkaloids isolated from Streptomyces venezuelae ISP5230, exhibit cytotoxic activity against multidrug-resistant breast cancer cells. We have previously achieved the total synthesis of jadomycins using the direct arylation of juglone as a key step. In this study, we achieved the total synthesis of jadomycin T and jadomycin aglycons using L-threonine and 1-amino-2-propanol as nitrogen sources. Additionally, we evaluated the cytotoxic activity of eight compounds, including glycosides, jadomycin T, and their corresponding aglycons, in eight types of tumor cells. The evaluated jadomycins tended to exhibit stronger cytotoxic activity as aglycons than as glycosides. Although the presence of a 1,3-oxazolidine ring derived from an amino acid was not essential, the presence of the 1,3-oxazolidine ring showed strong activity when the ring had a carboxyl group. Furthermore, compared to the non-natural isomer at a different position on the phenolic hydroxyl group, the naturally occurring phenanthroviridin aglycon exhibited stronger cytotoxic activity. In addition, this study suggests that jadomycins may become lead compounds for the treatment of brain tumors; however, further studies on their ability to penetrate the blood-brain barrier are required.


Modeling the development of cognitive reserve in children: A residual index approach.
To model cognitive reserve (CR) longitudinally in a neurodiverse pediatric sample using a residual index approach, and to test the criterion and construct validity of this index. Participants were N = 115 children aged 9.5-13 years at baseline (MAge = 10.48 years, SDAge = 0.61), and n = 43 (37.4%) met criteria for ADHD. The CR index represented variance in Matrix Reasoning scores from the WASI that was unexplained by MRI-based brain variables (bilateral hippocampal volumes, total gray matter volumes, and total white matter hypointensity volumes) or demographics (age and sex). At baseline, the CR index predicted math computation ability (estimate = 0.50, SE = 0.07, p < .001), and word reading ability (estimate = 0.26, SE = 0.10, p = .012). Longitudinally, change in CR over time was not associated with change in math computation ability (estimate = -0.02, SE = 0.03, p < .513), but did predict change in word reading ability (estimate = 0.10, SE = 0.03, p < .001). Change in CR was also found to moderate the relationship between change in word reading ability and white matter hypointensity volume (estimate = 0.10, SE = 0.05, p = .045). Evidence for the criterion validity of this CR index is encouraging, but somewhat mixed, while construct validity was evidenced through interaction between CR, brain, and word reading ability. Future research would benefit from optimization of the CR index through careful selection of brain variables for a pediatric sample.


Genetics of thoracic aortic aneurysm: at the crossroad of transforming growth factor-β signaling and vascular smooth muscle cell contractility.
Aortic aneurysm, including both abdominal aortic aneurysm and thoracic aortic aneurysm, is the cause of death of 1% to 2% of the Western population. This review focuses only on thoracic aortic aneurysms and dissections. During the past decade, the genetic contribution to the pathogenesis of thoracic aortic aneurysms and dissections has revealed perturbed extracellular matrix signaling cascade interactions and deficient intracellular components of the smooth muscle contractile apparatus as the key mechanisms. Based on the study of different Marfan mouse models and the discovery of several novel thoracic aortic aneurysm genes, the involvement of the transforming growth factor-β signaling pathway has opened unexpected new avenues. Overall, these discoveries have 3 important consequences. First, the pathogenesis of thoracic aortic aneurysms and dissections is better understood, although some controversy still exists. Second, the management strategies for the medical and surgical treatment of thoracic aortic aneurysms and dissections are becoming increasingly gene-tailored. Third, the pathogenetic insights have delivered new treatment options that are currently being investigated in large clinical trials.


A 1% Colloidal Oatmeal Cream Alone is Effective in Reducing Symptoms of Mild to Moderate Atopic Dermatitis: Results from Two Clinical Studies.

BACKGROUND: The epidermal barrier in patients with atopic dermatitis (AD) is deficient in ceramides and cathelicidins. Such epidermal defects may be a trigger for AD, thereby encouraging research toward development of skin-barrier-targeted preventive strategies.

METHODS: Two single-center, single-arm clinical trials were conducted (study 1, age greater than equal to 8 years and study 2, greater than equal to 10 years) in patients with mild to moderate AD to evaluate the effects of an over-the-counter 1% colloidal oatmeal cream administered for 14 days. Study 1 assessed the Eczema Area and Severity Index (EASI) and Investigator's Global Atopic Dermatitis Assessment (IGADA) on day 3, and itch severity using a Visual Analogue Scale (VAS) immediately after application as primary efficacy endpoints. In study 2, the primary efficacy endpoint was change from baseline in patients' assessment of itch. Both studies assessed safety through adverse event (AE) recording.

RESULTS: Study 1: 29 patients were enrolled (mean age [range], 27.07 [8 -67]). Comparing to baseline, EASI, IGADA, and itch were improved after the application, and improvements were maintained until day 14. Improvements of greater than/equal to 20% over baseline were noted in 53.6% and 25.0% patients at day 3 for EASI and IGADA scores, respectively, and in 37.9% patients for itch score immediately after the product application. On day 14, these percentages were 82.8%, 62.1%, and 85.7%, respectively.

STUDY 2: 30 patients were enrolled (mean age [range], 32.9 [10-80]). Itch severity and EASI score were significantly improved after product application and improvements were maintained until day 14. Transepidermal water loss values were significantly reduced and skin hydration was significantly increased at all assessment time points. No adverse events (AEs) were reported in study 2 and 2 AEs were reported by 1 patient in study 1.

CONCLUSIONS: The colloidal oatmeal cream was well tolerated and clinically effective in patients with mild to moderate AD.

J Drugs Dermatol. 2017;16(7):671-676.
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Estimating a Logistic Discrimination Functions When One of the Training Samples Is Subject to Misclassification: A Maximum Likelihood Approach.
The problem of discrimination and classification is central to much of epidemiology. Here we consider the estimation of a logistic regression/discrimination function from training samples, when one of the training samples is subject to misclassification or mislabeling, e.g. diseased individuals are incorrectly classified/labeled as healthy controls. We show that this leads to zero-inflated binomial model with a defective logistic regression or discrimination function, whose parameters can be estimated using standard statistical methods such as maximum likelihood. These parameters can be used to estimate the probability of true group membership among those, possibly erroneously, classified as controls. Two examples are analyzed and discussed. A simulation study explores properties of the maximum likelihood parameter estimates and the estimates of the number of mislabeled observations.


Refinement of the theory for extracting cell dielectric properties from dielectrophoresis and electrorotation experiments.
A modified theory is proposed for extracting cell dielectric properties from the peak frequency measurement of electrorotation (ER) and the crossover frequency measurement of dielectrophoresis (DEP). Current theory in the literature is based on the low frequency (DC) approximations for the equivalent cell permittivity and conductivity, which are valid when the measurements are performed in a medium with conductivity less than 1 mS/m. The present theory extracts the cell properties through optimizing an expression for the medium conductivity in terms of the peak ER, or DEP crossover, frequency according to its definition using full expressions of equivalent cell permittivity and conductivity. Various levels of approximation of the theory are proposed and discussed through a scaling analysis. The present theory can extract both membrane and interior properties from the low and the high peak ER, or DEP crossover, frequencies for any medium conductivity provided the peak ER, or DEP crossover, frequency exists. It can be reduced to the linear theory for the low peak ER and DEP crossover frequencies in the literature when the medium conductivity is less than 10 mS/m. However, we can determine the membrane capacitance and conductance via the slope and intercept, respectively, of the straight line fitting of the ER peak and DEP frequency against medium conductivity data according to the linear theory only when the intercept dominates the experimental uncertainty, which occurs when the medium conductivity is less than 1 mS/m in practice.


Modulation and treatment of patient-ventilator dyssynchrony.
The coupling between ventilator delivered inspiratory flow and patient's demands both in terms of timing and drive is a challenging task that has become largely feasible in recent years. This review addresses the new advances to modulate and treat patient-ventilator dyssynchrony. Patient-ventilator dyssynchrony is a common phenomenon with conventional modes of mechanical ventilation which influence the duration of mechanical ventilation. Inspection of pressure, volume and flow waveforms represents a valuable tool for the physician to recognize and take the appropriate action to improve patient-ventilator synchrony. New developments have been introduced aiming to improve patient ventilator synchrony by modulating the triggering function and the variables that control the flow delivery and the cycling off. Patient-ventilator dyssynchrony may affect patients' outcome. New modes of assisted mechanical ventilation have been introduced and represent a major step forward in modulating patient-ventilator dyssynchrony.


Current problems concerning parasitology and mycology with regard to diseases of the skin and its appendages.
Current issues concerning Parasitology and Mycology with regard to diseases of the skin and its appendages are presented. Aspects of diagnostics, clinical picture and therapy of skin and nail mycoses, as well as difficulties in the diagnosis and treatment of both native parasitoses (toxoplasmosis) and imported human tropical parasitoses (malaria, filariosis) have been emphasised. The clinical importance of environmental mould fungi in nosocomial infections and fungal meningitis, as well as selected properties of fungi isolated from patients with head and neck neoplasms treated by radiotherapy are discussed. Other mycological topics include the characteristics of newly-synthesized thiosemicarbazides and thiadiazoles as potential drugs against toxoplasmosis and their biological activity against Toxoplasma gondii tachyzoites, selected molecular mechanisms of resistance to azoles, Candida albicans strains and a new tool (barcoding DNA) for describing the biodiversity of potential allergenic molds. The importance of environmental factors in pathogenesis of mycoses and parasitoses is noted. The characteristics of pathogenic fungi isolated from natural ponds in Bialystok and potentially pathogenic yeast-like fungi isolated from children's recreation areas in Lodz are presented. The ongoing problem of anthropozoonoses is considered, as are the roles of stray cats and dogs in contaminating soil with the developing forms of intestinal parasites. The characteristics of the human microbiome, including population composition, activity and their importance in normal human physiology, are presented, as are the major goals of the Human Microbiome Project initiated by National Institutes of Health (NIH).


In vivo association between positive coronary artery remodelling and coronary plaque characteristics assessed by intravascular optical coherence tomography.
Positive coronary arterial remodelling has been shown to be associated with unstable coronary syndromes and ex vivo histological characteristics of plaque vulnerability such as a large lipid core and high macrophage content. The aim of this study is to evaluate the in vivo association between coronary artery remodelling and underlying plaque characteristics identified by optical coherence tomography (OCT). OCT is a unique imaging modality capable of characterizing these important morphological features of vulnerable plaque. OCT and intravascular ultrasound imaging was performed at corresponding sites in patients undergoing catheterization. OCT plaque characteristics for lipid content, fibrous cap thickness, and macrophage density were derived using previously validated criteria. Thin-cap fibroatheroma (TCFA) was defined as lipid-rich plaque (two or more quadrants) with fibrous cap thickness <65 microm. Remodelling index (RI) was calculated as the ratio of the lesion to the reference external elastic membrane area. A total of 54 lesions from 48 patients were imaged. Positive remodelling compared with absent or negative remodelling was more commonly associated with lipid-rich plaque (100 vs. 60 vs. 47.4%, P = 0.01), a thin fibrous cap (median 40.2 vs. 51.6 vs. 87 microm, P = 0.003) and the presence of TCFA (80 vs. 38.5 vs. 5.6%, P < 0.001). Fibrous cap macrophage density was also higher in plaques with positive remodelling showing a positive linear correlation with the RI (r = 0.60, P < 0.001). Coronary plaques with positive remodelling exhibit characteristic features of vulnerable plaque. This may explain the link between positive remodelling and unstable clinical presentations.


Second to fourth digit ratio is a predictor of sporting ability in elite Indian male kabaddi players.
To determine the 2D:4D ratio in elite Indian male kabaddi players and compare them with non-athletes. Our study was undertaken to find out a possible relation between digit ratio and sporting ability of male kabaddi players. This study also gives an insight into the possible ethnic differences between Indian sports personnel and other populations. Both right and left hands of 33 male kabaddi players attending training camp at the Bangalore regional centre of Sports Authority of India were scanned. Lengths of second and fourth digits were measured and their ratio calculated. Age, weight, height and body mass index matched subjects (25 males) who did not participate in any sports formed the control group. A highly significant difference was found in 2D:4D ratios of both the hands with Kabaddi players having a lower ratio compared to their controls. There was no statistically significant difference in 2D:4D (Δ r-l) between Kabaddi players and controls. Kabaddi is an intermediate sport not requiring a high level of endurance but at the same time requires masculine traits because of combating nature of the game. 2D:4D ratios can be used as reliable additional criteria when screening for prospective players to be inducted into the team.


MiR-21 is required for anti-tumor immune response in mice: an implication for its bi-directional roles.
Here we show that miR-21, a microRNA known for its oncogenic activity, is also essential for mediating immune responses against tumor. Knockout of miR-21 in mice slowed the proliferation of both CD4+ and CD8+ cells, reduced their cytokine production and accelerated the grafted tumor growth. Further investigations indicated that miR-21 could activate CD4+ and CD8+ T cells via the PTEN/Akt pathway in response to stimulations. Taken together, these data suggest the key functions of miR-21 in mediating anti-tumor immune response and thereby uncover a bi-directional role of this traditionally known 'oncomiR' in tumorigenesis. Our study may provide new insights for the design of cancer therapies targeting microRNAs, with an emphasis on the dynamic and possibly unexpected role of these molecules.


Correlation between the ability of tumor cells to incorporate specific fatty acids and their sensitivity to killing by a specific antibody plus guinea pig complement.
Line-1 diethylnitrosamine-induced guinea pig tumor cells can be rendered sensitive to killing by rabbit anti-Forssman IgM antibody plus guinea pig complement (GPC) or antitumor antibody plus GPC following prolonged incubation (17 hr ) of the cells with one of several metabolic inhibitors. Compared to control cells, these cells have been shown to be inhibited in their ability to incorporate fatty acids into complex cellular lipids, which suggested that lipid synthesis is of fundamental importance for the ability of the tumor cells to resist humoral immune killing. In this study, drug-treated cells that were rendered sensitive to killing by anti-Forssman antibody plus GPC, but not antitumor antibody plus GPC, were inhibited in their incorporation of saturated (palmitic or stearic acid), but not an unsaturated, fatty acid (linoleic acid). These data suggested that the fatty acid composition of specific lipids may also be important for the resistance of these tumor cells to killing by antibody and complement.


Impact of Wheat Arabinoxylan with Defined Substitution Patterns on the Heat-Induced Polymerization Behavior of Gluten.
To further depict the interaction mechanism of wheat arabinoxylan (AX) and gluten proteins upon thermal processing, AX was enzymatically tailored with defined substitution patterns and the impact on the heat-induced polymerization behavior of gluten was comparatively studied. The results showed that tailormade AX promoted the formation of glutenin-glutenin and glutenin-gliadin macrocrosslinks upon heating, with the optimal effect detected for AX depleted of Araf of disubstituted Xylp. The tailormade AX, especially AX depleted of monosubstituted Xylp, facilitated the polymerization ability of α-gliadin into glutenin compared with untailored AX. The unfolding process of gluten was partially impeded by AX upon heating, while the tailormade AX promoted the unfolding process. AX could bury Trp and Tyr upon polymerization of glutenin and gliadin and induced the change of the disulfide bridge conformation to a less-stable state, while the effect was alleviated with tailormade AX. The enhanced polymerization with tailormade AX strengthened the gluten network and induced more heterogeneously distributed large protein aggregates.


Local lung ventilation in critically ill patients using nonradioactive xenon-enhanced transmission computed tomography.
Nonradioactive xenon is sufficiently radiodense to increase the density of gas-containing lung as seen in a computed tomography (CT) scan. Subtraction of a baseline CT scan from the xenon-enhanced CT scan can accentuate gas space differences by subtracting fixed tissue densities. The baseline scan and the scan obtained during wash-in of xenon (before equilibration) allow circulation of local ventilation. The xenon CT scan, thus, provides more precise information about distribution of ventilation than planar radiogas techniques. The technical aspects of application to a critically ill patient and the mathematical basis of the technique are presented.


Proximate causes of aggressive fighting in middle school children.
In study 1, 8- and 11-year-old girls and boys (N = 110) were interviewed individually and asked about why children in general, and themselves in particular, fight with fellow pupils in the playground. A substantial proportion of children (51 per cent) reported having had at least one aggressive fight during the previous year. The most common reasons for children resorting to fighting were retaliations to teasing, retaliations to unprovoked assaults, disagreements over aspects of the game that was being played, because another child was disliked, and to settle dominance disputes. In study 2, a direct observational methodology was employed to examine how often children of these ages engage in aggressive fighting, how long fights last, and their proximate causes. Among the younger pupils, a large proportion of fights (43.3 per cent) had no obvious immediate cause to an adult observer, but others were caused when a playful assault received an aggressive retaliation (15.4 per cent), and by disputes over space in the playground (13.5 per cent). Among the 11-year-old pupils, a smaller percentage of fights (14.8 per cent) had no obvious immediate cause. The two most common causes of fighting at this age were aggressive retaliations to teasing (25.9 per cent) and aggressive retaliations to accidental injury/hurt (18.5 per cent). In study 3, in situ interviews were combined with direct playground observations in order to reveal participants' views (or onlookers' views if participants were not available to be interviewed) about the causes of fights. Again, the most common causes of fighting were disputes over some aspect of the game being played (33.3 per cent), aggressive retaliations to teasing (25.0 per cent), disagreements over possession of toys/equipment (14.6 per cent), and aggressive retaliations to accidental injury/hurt (14.6 per cent). Age and sex differences are reported in some measures across all three studies. The results are discussed in terms of their implications for interventions aimed at improving children's experiences of life on the school playground.


Histological and histochemical study on the ependyma of Bradypus tridactylus.
Histological and histochemical aspects of the whole encephalic ventricular system of eight specimens of Bradypus tridactylus were studied. After anesthesia and perfusion, the encephalons were obtained by craniotomy. Transverse serial sections of the encephalon, stained according to Azan (Heidenhain's method) or Kluver-Barrera for nerve cells and myelinated nerve fibers; silver impregnation was carried out according to Cajal-De Castro's or Palmgren's methods. The following histochemical reactions were used: PAS (McManus), metachromasia, acid phosphatase (Gomori), Brachet's and Gomori's trichromic reaction (modified by Bargmann for neurosecretion). Histologically, different characteristics of the ependymal cells in different areas were observed, which would be related to functional peculiarities of each area of the encephalic ventricles. The ependymal cells showed discrete apical basophilia due to the presence of RNA which disappears after treatment with crystalline ribonuclease. The PAS reaction indicated the presence of a small quantity of PAS-positive substances in the apical zone of the ependymal cells and the subependymal tissue. These substances disappeared after the salivary amylase test, indicating the presence of glycogen. The acid phosphatase reaction was negative.


Serotoninergic mechanisms of the effects of neurotensin on passive avoidance behavior in rats.
The aim of the present work was to identify the features of the actions of neurotensin on administration into the substantia nigra or dorsal cervical nucleus on the reproduction of passive avoidance reactions in rats. The results showed that the action of neurotensin administered into the substantia nigra was accompanied by sharp reductions in passive avoidance reactions, while administration into the dorsal cervical nucleus, conversely, led to increases in these reactions and slowing of their extinction. The effects of microinjections of the serotonin 5-HT(1A) receptor agonist 8-hydroxydipropylaminotetraline (8-OH-DPAT) into these brain structures were analogous to the effects of neurotensin. The different behavioral effects of administration of neurotensin corresponded to identifiable changes in the levels of serotonin and its metabolite 5-hydroxyindoleacetic acid in the caudate nuclei of the brain. These data led to the conclusion that the effects of neurotensin on passive avoidance behavior are associated with the regulation of the emotional state of the animals via actions on the functions of brain serotoninergic structures.


Improved procedures for the conjugation of oligosaccharides to protein by reductive amination.
The rate of coupling of oligosaccharides having aldose end groups to protein by reductive amination was significantly increased by changing the temperature and pH of the reaction, and even more significantly by the addition of borate ions. Under optimized conditions half of the lysine residues of bovine serum albumin could be derivatized by lactose in 7 h and their complete derivatization was achieved in approximately 24 h. All attempts to carry out similar reductive amination procedures using oligosaccharides having ketose (D-fructose, 3-deoxy-D-manno-octulosonic acid (KDO), and sialic acid) failed owing to the slowness of the reaction. Model studies on the coupling of D-fructose and KDO to glycine indicate that any coupling procedure based on reductive amination of ketose residues would of necessity require the prior introduction of a small functionalized spacer molecule.


Isolation and analysis of moenomycin and its biosynthetic intermediates from Streptomyces ghanaensis (ATCC 14672) wildtype and selected mutants.
Streptomyces ghanaensis (ATCC 14672) produces the phosphoglycolipid antibiotic moenomycin consisting of several components. A solid phase extraction procedure was developed which allowed a rapid isolation of both moenomycin and its biosynthetic intermediates from culture filtrates. Semi-preparative high performance liquid chromatography followed by high performance liquid chromatography-mass spectrometry provided structural data on the different moenomycin components. In order to obtain initial information on the biosynthetic pathway, moenomycin non-producing mutants were isolated. They were shown to release intermediates with shorter lipid chains suggesting that the lipid chain synthesis probably takes place at a later stage of the moenomycin biosynthesis. Based on the biological activity and the analytical data, we assume that a modification and in particular a shorter lipid portion drastically influences the inhibitory activity of this antibiotic.


Autoimmune pancreatitis associated with immune-mediated inflammation of the papilla of Vater: report on two cases.
Autoimmune pancreatitis (AIP) is defined histologically by periductal and interacinar lymphocytic infiltration. Immunohistochemically, the majority of these lymphocytes are identified as T cells. Epithelial HLA-DR antigen expression was also described as a marker of autoimmunity in this type of chronic pancreatitis. We report 2 cases, a 56-year-old man and a 29-year-old woman, with AIP associated with immune-mediated inflammation of the main duodenal papilla (MDP). Serologically, antinuclear antibody positivity was detected in the male patient. The female patient, treated medically for ulcerative proctitis, had no serological evidence of autoimmune disease. Macroscopic papillitis was present only in the male patient, and endoscopic biopsy samples were taken from this swollen MDP. Since we could not exclude malignancy, a pancreatic head resection was performed in both patients. The histologic and immunohistochemical studies of the resected specimens showed periductal T-lymphocytic infiltration in the pancreatic and papillary tissues. Furthermore, HLA-DR-antigen expression was also demonstrated in epithelial cells of the pancreas and MDP. The immunohistological features of endoscopic biopsy samples from the swollen MDP were identical as in the surgically resected specimens. Immune-mediated inflammation of the MDP may be associated with AIP.


Effects of fructose from apple and honey on serum uric acid in young Chinese: Randomized crossover trials.
Overconsumption of drinks containing fructose increases the risk for hyperuricemia and gout. Comparative analysis evaluating the indicators of serum uric acid (SUA) load caused by natural food-derived fructose and pure fructose in sweeteners is lacking. We aimed to uncover the effect of fructose from apple and honey and pure fructose powder on the SUA concentration of healthy young Chinese individuals. Two randomized crossover trials were performed. The participants were randomly assigned to consume apple or honey (test food) or pure fructose powder (reference food); one week later, the groups' dietary intervention was switched. Blood samples were collected at 0, 30, 60, and 120 min after meal to measure the SUA and blood glucose concentrations. At 30 and 60 min, the SUA concentration in participants consuming apple or honey was lower than in those consuming fructose powder. At 120 min, the SUA concentration of participants consuming apple returned to baseline. The areas under the curve (AUC) within 2 h (2h- AUCs) of SUA exhibited the trend of fructose >honey >apple. The 2h-AUC ratio between test food and reference food was determined using the uric acid index to assess the efficiency of food-derived fructose in increasing the SUA concentration. The uric acid index of honey was higher than that of apple. Men had higher postprandial SUA concentration than women. Food-derived fructose caused a lighter load on uric acid metabolism than pure fructose. Uric acid index can be useful for distinguishing fructose-containing foods.


Mitogen-inducible gene-6 expression correlates with survival and is an independent predictor of recurrence in BRAF(V600E) positive papillary thyroid cancers.
Mitogen-inducible gene-6 (Mig-6) is an immediate early response gene that negatively regulates signaling. EGFR overexpression and activating mutations in MAPK signaling effectors are common events in papillary thyroid cancer (PTC). The purpose of this study was to determine if Mig-6 expression is associated with EGFR expression or surgical outcomes in PTC. We determined Mig-6 transcript levels from a microarray in 19 patients with PTC who underwent thyroidectomy. We established a maximally selected cutoff to discriminate Kaplan-Meier survival estimates. For cross-validation, we performed quantitative RT-PCR on resected well-differentiated PTC from an additional 106 patients. Mig-6 and EGFR mRNA levels correlated directly (P < .0001). Mig-6 expression above the cutoff of 1.10 (2;-dCt[Mig6-GUS]) was associated with greater survival (P = .008). When this cutoff was applied in the cross-validation, high Mig-6 expression was associated with longer survival (P = .03) and disease-free survival (P = .07). Furthermore, high Mig-6 expression was independently predictive of greater disease-free survival in BRAF(V600E)-positive PTC. High Mig-6 expression in PTC is associated with favorable outcomes. Mig-6 is a novel tumor suppressor that may be a candidate for targeted cancer therapeutics in patients with PTC refractory to conventional therapy.


[The lung protection strategy under the support of extracorporeal membrane oxygenation in patients suffering from influenza A H1N1].
To study the effect of extracorporeal membrane oxygenation (ECMO) in patients suffering from severe pneumonia complicating influenza A H1N1 by putting lungs in rest to protect the latter. Five patients with severe pneumonia following influenza A H1N1 were treated with ECMO and different modes of mechanical ventilation at the same time. Two patients died, both of them received synchronized intermittent mandatory ventilation (SIMV) and bi-level positive airway pressure (BiPAP) modes, with airway pressure release ventilation (APRV) to control lung expansion with expansion pressure 40 cm H(2)O (1 cm H(2)O=0.098 kPa). In 3 survivors, the strategy of lung rest was performed by giving an optimized positive end expiratory pressure (PEEP) with an optimal compliance by gradually elevation of PEEP, and high-level pressure (Phigh) at 20 cm H(2)O by application of BiPAP mode. One patient died due to lung damage and repeated spontaneous pneumothorax and sepsis; 1 patient died due to multiple organ dysfunction syndrome. Three patients recovered after following the strategy of lung rest. When ECMO is used for severe pneumonia complicating influenza A H1N1, prognosis can be obviously improved, with decrease in the occurrence of lung damage through the protection strategy of lung rest.


Screening for idiopathic REM sleep behavior disorder: usefulness of actigraphy.
To evaluate the utility of multimodal low-cost approaches including actigraphy, a wrist-worn device monitoring rest/activity cycles, in identifying patients with idiopathic REM sleep behavior disorder (iRBD). Seventy patients diagnosed with sleep disorders causing different motor manifestations during sleep (iRBD, sleep apnea, restless legs syndrome) and 20 subjects without any relevant motor manifestation during sleep, underwent video-polysomnography (vPSG) and 2 week actigraphy, completed six validated RBD screening questionnaires, and sleep apps use was assessed. Actigraphy was analyzed automatically, and visually by seven blinded sleep medicine experts who rated as "no," "possible," and "probable" RBD. Quantitative actigraphy analysis distinguished patients from controls, but not between patients with different types of motor activity during sleep. Visual actigraphy rating by blinded experts in sleep medicine using pattern recognition identified vPSG confirmed iRBD with 85%-95% sensitivity, 79%-91% specificity, 81%-91% accuracy, 57.7% ± 11.3% positive predictive value, 95.1% ± 3.3% negative predictive value, 6.8 ± 2.2 positive likelihood ratio, 0.14 ± 0.05 negative likelihood ratio and 0.874-0.933 area under the ROC curve (AUC). AUC of the best performing questionnaire was 0.868. Few patients used sleep apps; therefore, their potential utility in the evaluated patients' groups is limited. Visual analysis of actigraphy using pattern recognition can identify subjects with iRBD, and is able to distinguish iRBD from other motor activities during sleep, even when patients are not aware of the disease in contrast to questionnaires. Therefore, actigraphy can be a reliable screening instrument for RBD potentially useful in the general population.


Evaluating the clinical effectiveness of 90Y-SMT 487 in patients with neuroendocrine tumors.
Because of the presence of cell membrane somatostatin receptors (SSTRs), many neuroendocrine tumors will bind analogs of somatostatin. (90)Y-Dodecanetetraacetic acid-Phe1-Tyr3-octreotide (SMT 487) is an SSTR radiopharmaceutical currently under investigation as a therapeutic option for neuroendocrine tumors. Although there are a variety of methods for evaluating response to a given cancer therapy, an important indicator of success is the impact on the clinical status of the patient. The purpose of this work was to develop a semiquantitative method and assess the clinical effectiveness of (90)Y-SMT 487 therapy in patients with neuroendocrine tumors. A scoring system was developed to evaluate clinical response that included the following parameters: weight, health status score (determined by the patient), Karnofsky score, and tumor-related symptoms. We applied this scoring system to 21 patients who had completed 3 cycles of therapy with (90)Y-SMT 487. Fourteen of the 21 showed a favorable clinical response, whereas 5 were clinically stable after treatment and 2 showed evidence of clinical progression. There was also a significant reduction in the amount of octreotide being used after completion of (90)Y-SMT 487 therapy in the 20 patients who were on this medication. Using this scoring method, (90)Y-SMT 487 appears effective in improving the clinical status of patients with (111)In-pentetreotide-positive neuroendocrine tumors.


[Advances in biomarkers of ARDS].
Acute respiratory distress syndrome (ARDS) is a common diseases in critical ill patients, which is an acute-onset hypoxic condition with radiographic bilateral lung infiltration. And it can be divided into two phases in pathophysiology: an acute exudative phase combining diffuse alveolar damage and lung edema followed by a later fibro proliferative phase. The early prediction and risk assessment of patients with ARDS is still very poor in the clinical. In recent years, researchers gradually focus their research on exploration of biomarkers of ARDS. The article mainly aims to sum up the development of biomarkers exploration.


Huge Bilateral Paramesonephric Cysts in a 25 year old Nulliparous woman.
Paraovarian cysts are uncommon adnexal masses which are usually asymptomatic. We describe a case of bilateral huge paramesonephric cysts in a nulliparous woman. A 25-year-old lady presented with abdominal distension for one year duration. Examination and imaging revealed large abdominopelvic cystic masses with no solid areas or septations. Intraoperatively there were huge bilateral paraovarian cysts which were excised. Histopathology revealed low cuboidal to ciliated columnar epithelium with no evidence of ovarian parenchyma suggestive of paramesonephric cyst. Paraovarian cyst should be included in the differential diagnosis of a cystic mass visualised on ultrasound.


Essential role of endogenously synthesized tylosin for induction of ermSF in Streptomyces fradiae.
We compared ermSF induction in wild-type Streptomyces fradiae NRRL B-2702 and that in GS-14, a tylA mutant which cannot synthesize tylosin. Our findings suggest that (i) endogenously synthesized tylosin plays an obligatory role in ermSF induction and (ii) tylosin, or a biosynthetic intermediate beyond tylactone, has an "autocrine" function that induces ErmSF synthesis, thereby enabling S. fradiae to resist higher levels of tylosin.


Hierarchical Design of Tissue Regenerative Constructs.
The worldwide shortage of organs fosters significant advancements in regenerative therapies. Tissue engineering and regeneration aim to supply or repair organs or tissues by combining material scaffolds, biochemical signals, and cells. The greatest challenge entails the creation of a suitable implantable or injectable 3D macroenvironment and microenvironment to allow for ex vivo or in vivo cell-induced tissue formation. This review gives an overview of the essential components of tissue regenerating scaffolds, ranging from the molecular to the macroscopic scale in a hierarchical manner. Further, this review elaborates about recent pivotal technologies, such as photopatterning, electrospinning, 3D bioprinting, or the assembly of micrometer-scale building blocks, which enable the incorporation of local heterogeneities, similar to most native extracellular matrices. These methods are applied to mimic a vast number of different tissues, including cartilage, bone, nerves, muscle, heart, and blood vessels. Despite the tremendous progress that has been made in the last decade, it remains a hurdle to build biomaterial constructs in vitro or in vivo with a native-like structure and architecture, including spatiotemporal control of biofunctional domains and mechanical properties. New chemistries and assembly methods in water will be crucial to develop therapies that are clinically translatable and can evolve into organized and functional tissues.


Preservation of kidneys for transplantation. Assessment of ischemic damage by renal autoperfusion.
Autoperfusion of canine kidneys was investigated as an alternative method to determinate the ischmic organ damage following various preservation procedures. As a compromise between implantation of the donor kidney and normotherimic isolated perfusion, autoperfusion is shown to offer some advantages in the study of the pathophysiology of the ischemic damaged kidney. Within 3 hours of autoperfusion, we obtained detailed information about the immediate regenerative ability of the glomerular, tubular, and vascular functions following various sorts of ischemic trauma.


Pairing of propellers: dimerization of octahedral ruthenium(II) and osmium(II) complexes of eilatin via pi-pi stacking featuring heterochiral recognition.
Five octahedral eilatin complexes of the type [M(L-L)(2)(eilatin)](2+) (M = Ru, Os; L-L = bipyridyl-type ligands) were synthesized, and their dimerization via pi-pi stacking was studied by crystallography and (1)H NMR techniques. The X-ray structures of these racemic complexes were solved and revealed that the eilatin complexes are organized as discrete dimers in which the eilatin residues of each complex are stacked in centrosymmetric packing. Chemical shift dependence on concentration in the (1)H NMR spectra support fast dimer-monomer equilibrium, and the structures of the dimers in acetonitrile solution are proposed to be analogous to their solid-state structures. Dimerization constants in acetonitrile were measured for the five racemic eilatin complexes that exhibit different structural parameters, as well as for the two enantiomeric forms of one of these complexes. They were found to be independent of the metal (Ru vs Os), strongly dependent on the steric effects introduced by the L-L ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, and 2,2'-biquinoline), and dependent on the optical purity of the complexes. A clear preference for heterochiral over homochiral dimer formation was demonstrated. This is the first report of chiral recognition in solution, exhibited by simple chemical systems held solely by pi-stacking interactions.


Mandibular Block Graft for Localised Ridge Augmentation Followed by Delayed Implant Placement: A Case Report.
The presence of adequate ridge width is an important prerequisite for implant placement. Reconstruction of the alveolar ridge can be done through various bone augmentation procedures. Autogenous bone grafts are being used for ridge augmentation for a long time and are still considered the gold standard for jaw reconstruction. Intraoral autogenous bone grafts from sites such as mandibular symphysis and ramus offer various advantages over the extraoral sites. This case report describes the use of an autogenous block graft from mandibular symphysis for a ridge augmentation procedure in the maxillary anterior region followed by delayed implant placement. Six months postoperative clinical and radiographic examination revealed significant increase width of the ridge and appropriate implant placement with satisfactory esthetic and functional results.


Characterization of cross-section correction to charge exchange recombination spectroscopy rotation measurements using co- and counter-neutral-beam views.
Measurements of rotation using charge exchange recombination spectroscopy can be affected by the energy dependence of the charge exchange cross section. On DIII-D, the associated correction to the rotation can exceed 100 kms at high temperatures. In reactor-relevant low rotation conditions, the correction can be several times larger than the actual plasma rotation and therefore must be carefully validated. New chords have been added to the DIII-D CER diagnostic to view the counter-neutral-beam line. The addition of these views allows determination of the toroidal rotation without depending on detailed atomic physics calculations, while also allowing experimental characterization of the atomic physics. A database of rotation comparisons from the two views shows that the calculated cross-section correction can adequately describe the measurements, although there is a tendency for "overcorrection." In cases where accuracy better than about 15% is desired, relying on calculation of the cross-section correction may be insufficient.


Interactions between glioma and pregnancy: insight from a 52-case multicenter series.
OBJECTIVE The goal of this study was to provide insight into the influence of gliomas on gestational outcomes, the impact of pregnancy on gliomas, and the identification of patients at risk. METHODS In this multiinstitutional retrospective study, the authors identified 52 pregnancies in 50 women diagnosed with a glioma. RESULTS For gliomas known prior to pregnancy (n = 24), we found the following: 1) An increase in the quantified imaging growth rates occurred during pregnancy in 87% of cases. 2) Clinical deterioration occurred in 38% of cases, with seizures alone resolving after delivery in 57.2% of cases. 3) Oncological treatments were immediately performed after delivery in 25% of cases. For gliomas diagnosed during pregnancy (n = 28), we demonstrated the following: 1) The tumor was discovered during the second and third trimesters in 29% and 54% of cases, respectively, with seizures being the presenting symptom in 68% of cases. 2) The quantified imaging growth rates did not significantly decrease after delivery and before oncological treatment. 3) Clinical deterioration resolved after delivery in 21.4% of cases. 4) Oncological treatments were immediately performed after delivery in 70% of cases. Gliomas with a high grade of malignancy, negative immunoexpression of alpha-internexin, or positive immunoexpression for p53 were more likely to be associated with tumor progression during pregnancy. Deliveries were all uneventful (cesarean section in 54.5% of cases and vaginal delivery in 45.5%), and the infants were developmentally normal. CONCLUSIONS When a woman harboring a glioma envisions a pregnancy, or when a glioma is discovered in a pregnant patient, the authors suggest informing her and her partner that pregnancy may impact the evolution of the glioma clinically and radiologically. They strongly advise a multidisciplinary approach to management. ■ CLASSIFICATION OF EVIDENCE Type of question: association; study design: case series; evidence: Class IV.


[Study on polysaccharide content and monosaccharide composition of Polyporus umbellatus from different production areas].
In order to provide scientific basics for exploitation and sufficient application of Polyporus umbellatus resources and study the monosaccharide composition of P. umbellatus polysaccharides,the anthrone-sulfuric acid method was applied to compare polysaccharide content of P. umbellatus from 17 producing areas. The monosaccharides were derived by 1-phenyl-3-methyl-5-pyrazolone( PMP) and the derivatives were identified by UPLC-MS/MS and the content of each monosaccharide component was determined simultaneously. The results demonstrated that there was a certain difference in total polysaccharide content of P. umbellatus from different regions,and the content of total P. umbellatus polysaccharide from Shaanxi province and Sichuan province( 1. 15% and 1. 90%) was relatively higher than that of others areas. Polysaccharides from P. umbellatus was mainly composed of eight monosaccharides,including glucose,glucuronic acid,galactose,ribose,xylose,arabinose,mannose and fucose. The contents of glucose( 17. 65 mg·g-1) was higher than others. The ribose was the lowest( 0. 13 mg·g-1). In addition,fructose,rhamnose and galacturonic acid were also detected in some samples. Furthermore,the results of cluster analysis( CA) and principal component analysis( PCA) indicated that totally 17 batches of P. umbellatus polysaccharide could be classified into three clusters,samples collected from Wuchang in Heilongjiang province were clustered into one group separately. The study can provide a basis for rational utilization of P. umbellatus resources,and also implies the sequence of monosaccharide linking and pharmacological activity of P. umbellatus polysaccharides.


Effects of glucose on the production of recombinant protein C in mammalian cell culture.
Effects of glucose on a cultured Chinese hamster ovary cell line producing recombinant human protein C were investigated. After the recombinant cells reached confluency, they were maintained in the medium containing 10% serum and different levels of glucose in either batch or daily-exchange mode. High concentrations of glucose to the cultures yielded higher cell densities. Daily exchanges of media produced higher cell densities than the corresponding batch culture. Total protein C production per cell decreased with time in batch culture, in accordance with the declined glucose metabolism. Supplementation of the media with high levels of glucose diminished both the expression and gamma-carboxylation activities of the recombinant cells. Production of protein C persisted in daily-exchange culture, resulting in a constant production rate of protein C. In this case again, glucose reduced the specific productivity of recombinant protein C. An apparent glucose inhibition constant was determined to be 0.11 mg/mL by Dixon plots. The ability to gamma-carboxylate recombinant protein C was also impaired at the highest level of glucose. From these results, a strategy to maximize recombinant protein C productivity is discussed.


Accelerated PET water activation acquisition with signal separation methodology.
Positron emission tomography (PET) water activation studies can be considerably accelerated when the time between the successive water bolus injections is reduced. However, when considering shorter interinjection times, as short as 5 min, there will be a contaminating residual PET signal in brain tissues attributed to the previous injections. In this paper a signal separation methodology is proposed to allow shorter (<10 min) interinjection times. The contaminating signal in the frames of interest is estimated by extrapolating the decaying tail of the previous signal. The method requires the dynamic PET recording of the decaying signals between two injections in order to extrapolate the tail, which can be done post-reconstruction using a weighted least squares method. Several extrapolation functions are investigated, including a quadratic function, a decaying exponential, and a biologically inspired function. The biologically inspired function is based on the one-tissue compartmental model for [(15)O]H2O and makes use of a generating function estimated from the total trues coincidence rate. To evaluate the proposed method and extrapolation functions, one- and two-dimensional simulation studies were performed, using interinjection times as low as 5 min. The resulting corrected images are compared to the conventionally obtained images with an interinjection time of 10 min, which allows the previous signal to almost completely vanish. Among all considered extrapolation functions the biologically inspired function was found to give the best results. The bias introduced when considering shorter interinjection times (<10 min) could be almost completely removed by subtracting the extrapolated remaining activity from the total measured signal of interest. Compared to the standard method of using longer interinjection times the resulting images have a slightly increased variance. Nonetheless the observed increases are small compared to the total variance and the resulting activation maps were visually very similar. The simulation results show that the proposed method can significantly reduce the total scan time (e.g., when considering 12 bolus injections, the total scan time can be reduced from 2 to 1 h). Extensive and very realistic simulations were used in this work, paving the way for future in vivo validation of the method.


Influence of diverse chemical modifications on the ADME characteristics and toxicology of antisense oligonucleotides.
Therapeutic gene silencing is a huge promise for the treatment of a variety of diseases. The translation of this widely used scientific technique toward clinical application has been hindered by insufficient ADME properties of antisense and siRNA oligonucleotides. Despite reasonable therapeutic response after local administration, reaching adequate concentrations at the site of action after systemic application is still a major hurdle and this has resulted in poor efficiency in preclinical and clinical situations. This review focuses on the influence on the ADME parameters of chemical modifications already tested in clinical trials, such as phosphorothioates (PSs), 2'-modified agents, including locked nucleic acids (LNA) and phosphorodiamidate morpholino oligomers (PMO). The dominating PS backbone modification, while conferring adequate nuclease resistance and improving biodistribution, has been shown to be involved in unspecific protein binding and off-target effects on apoptosis pathways. PS-free antisense agents such as PMO generally show poorer pharmacokinetic characteristics. In terms of pharmacokinetics and cell membrane permeation, there is currently no efficient alternative to PS, although doubts about long-term toxicity of this class still remain. Consequently, improved structural modifications or galenic formulations are deemed necessary to create entities with higher efficiency and lower toxicity.


A preliminary analysis of interactive effects between common classroom contingencies and methylphenidate.
To assess the drug-behavior interaction effects with an 8-year-old boy wih attention deficit hyperactivity disorder, common classroom antecedent (e.g., seating arrangement) and consequent (e.g., peer prompts) stimuli were alternated within a school day while drug conditions (methylphenidate vs. placebo) were alternated across days. The results suggested that peer attention maintained disruptive behavior when methylphenidate was absent but not when it was present.


Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats.
Recent studies have reported the preventive effects of probiotics on obesity. Among commensal bacteria, bifidobacteria is one of the most numerous probiotics in the mammalian gut and are a type of lactic acid bacteria. The aim of this study was to assess the antiobesity and lipid-lowering effects of Bifidobacterium spp. isolated from healthy Korean on high fat diet-induced obese rats. Thirty-six male Sprague-Dawley rats were divided into three groups as follows: (1) SD group, fed standard diet; (2) HFD group, fed high fat diet; and (3) HFD-LAB group, fed high fat diet supplemented with LAB supplement (B. pseudocatenulatum SPM 1204, B. longum SPM 1205, and B. longum SPM 1207; 108 ~ 109 CFU). After 7 weeks, the body, organ, and fat weights, food intake, blood serum levels, fecal LAB counts, and harmful enzyme activities were measured. Administration of LAB reduced body and fat weights, blood serum levels (TC, HDL-C, LDL-C, triglyceride, glucose, leptin, AST, ALT, and lipase levels), and harmful enzyme activities (β-glucosidase, β-glucuronidase, and tryptophanase), and significantly increased fecal LAB counts. These data suggest that Bifidobacterium spp. used in this study may have beneficial antiobesity effects.


[Copy number of ribosomal operons in prokaryotes and its effect on phylogenic analyses].
Different aspects of the presence of multiple copies of ribosomal operons in prokaryotic genomes are reviewed. Structure of prokaryotic ribosomal operons is briefly described. The available data are summarized regarding the copy number of ribosomal genes in various prokaryotic genomes, the degree of polymorphism of their individual copies, physiological and evolutionary aspects of the presence of the multiple copies of ribosomal genes. The review also considers the influence of the presence of multiple copies of ribosomal genes on the results of identification of prokaryotic isolates and of the studies of prokaryotic diversity in environmental samples based on phylogenetic analysis of 16S rRNA gene sequences.


Serum biomarkers in periprosthetic joint infections.
The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI. We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis). Our review helped to identify factors that can influence serum biomarkers' level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis.Cite this article:Bone Joint Res 2018;7:85-93.


Oxidative modification to cysteine sulfonic acid of Cys111 in human copper-zinc superoxide dismutase.
Copper-zinc superoxide dismutase (SOD1) plays a protective role against oxidative stress. On the other hand, recent studies suggest that SOD1 itself is a major target of oxidative damage and has its own pathogenicity in various neurodegenerative diseases, including familial amyotrophic lateral sclerosis. Only human and great ape SOD1s among mammals have the highly reactive free cysteine residue, Cys(111), at the surface of the SOD1 molecule. The purpose of this study was to investigate the role of Cys(111) in the oxidative damage of the SOD1 protein, by comparing the oxidative susceptibility of recombinant human SOD1 modified with 2-mercaptoethanol at Cys(111) (2-ME-SOD1) to wild-type SOD1. Wild-type SOD1 was more sensitive to oxidation by hydrogen peroxide-generating fragments, oligomers, and charge isomers compared with 2-ME-SOD1. Moreover, wild-type SOD1, but not 2-ME-SOD1, generated an upper shifted band in reducing SDS-PAGE even by air oxidation. Using mass spectrometry and limited proteolysis, this upper band was identified as an oxidized subunit of SOD1; the sulfhydryl group (Cys-SH) of Cys(111) was selectively oxidized to cysteine sulfinic acid (Cys-SO(2)H) and to cysteine sulfonic acid (Cys-SO(3)H). The antibody raised against a synthesized peptide containing Cys(111)-SO(3)H reacted with only the Cys(111)-peroxidized SOD1 by Western blot analysis and labeled Lewy body-like hyaline inclusions and vacuole rims in the spinal cord of human SOD1-mutated amyotrophic lateral sclerosis mice by immunohistochemical analysis. These results suggest that Cys(111) is a primary target for oxidative modification and plays an important role in oxidative damage to human SOD1, including familial amyotrophic lateral sclerosis mutants.


Pushing the Limits of EEG: Estimation of Large-Scale Functional Brain Networks and Their Dynamics Validated by Simultaneous fMRI.
Functional magnetic resonance imaging (fMRI) is the technique of choice for detecting large-scale functional brain networks and to investigate their dynamics. Because fMRI measures brain activity indirectly, electroencephalography (EEG) has been recently considered a feasible tool for detecting such networks, particularly the resting-state networks (RSNs). However, a truly unbiased validation of such claims is still missing, which can only be accomplished by using simultaneously acquired EEG and fMRI data, due to the spontaneous nature of the activity underlying the RSNs. Additionally, EEG is still poorly explored for the purpose of mapping task-specific networks, and no studies so far have been focused on investigating networks' dynamic functional connectivity (dFC) with EEG. Here, we started by validating RSNs derived from the continuous reconstruction of EEG sources by directly comparing them with those derived from simultaneous fMRI data of 10 healthy participants, and obtaining an average overlap (quantified by the Dice coefficient) of 0.4. We also showed the ability of EEG to map the facial expressions processing network (FEPN), highlighting regions near the posterior superior temporal sulcus, where the FEPN is anchored. Then, we measured the dFC using EEG for the first time in this context, estimated dFC brain states using dictionary learning, and compared such states with those obtained from the fMRI. We found a statistically significant match between fMRI and EEG dFC states, and determined the existence of two matched dFC states which contribution over time was associated with the brain activity at the FEPN, showing that the dynamics of FEPN can be captured by both fMRI and EEG. Our results push the limits of EEG toward being used as a brain imaging tool, while supporting the growing literature on EEG correlates of (dynamic) functional connectivity measured with fMRI, and providing novel insights into the coupling mechanisms underlying the two imaging techniques.


Primary angiosarcoma of the chest wall: CT and MR findings.
A surgically confirmed primary angiosarcoma of the chest wall is described. CT showed a right chest wall mass projecting into the thoracic cavity from the right axilla. The tumor was a high density, inhomogeneous-density mass. Invasion to the rib was noted, and calcified foci were demonstrated. A homogenous high-density mass ventral to the chest wall mass was shown. Contrast-enhanced CT did not demonstrate any enhancement. MRI demonstrated a large heterogeneous mass on both T1-weighted images (T1WI) and T2-weighted images (T2WI). Contrast-enhanced axial T1-weighted MR images did not show any enhancement of the mass, but the homogenous mass ventral to the chest wall mass was shown. MRI demonstrated certain characteristic findings of angiosarcoma of the chest wall. Intratumoral hemorrhage with juxtaposed hematoma and aggressive invasion to the surrounding tissue suggest angiosarcoma.


Does the environment constrain avian sound localization?
A bird needs to keep track not only of social interactions of conspecifics but also of their changing locations in space by determining their directions and distances. Current knowledge of accuracy in the computation of sound source location by birds is still insufficient, partly because physiological mechanisms of few species are studied in well defined laboratory settings, while field studies are performed in a variety of species and complex environments. Velocity gradients and reverberating surfaces may conceivably induce inaccuracy in sound source location (mainly elevation) by distorting the directional cues. However, most birds possess an inherently directional pressure difference receiver, which enhances the directional cues (mainly azimuth), and a computational mechanism in their auditory pathways to suppress echoes of redirected sound.


Calcium - Magnesium imbalance implicated in benign prostatic hyperplasia and restoration by a phytotherapeutic drug - Croton membranaceus Müll.Arg.
Calcium (Ca)- magnesium (Mg) imbalance is implicated in prostate cancer. Ca/Mg ratio increases or decreases with proliferation or apoptosis, respectively. The study examined whether this Ca/Mg imbalance exists in BPH patients and the effect of a phytotherapeutic drug on the Ca/Mg ratio. Thirty (30) BPH patients who used the ethanolic root extract of Croton membranaceus (60 mg/day) for 3 months were examined for serum Ca, Mg, phosphate, parathyroid hormone (PTH), vitamin D, prostate specific antigen (PSA) levels and renal function tests (RFT) before (BT) and after treatment (AT) alongside thirty (30) controls. Twenty (20) trace element including Mg and Ca were determined in the drug by neutron activation analysis (NAA). RFT, PTH and vitamin D for BT, AT and controls (C) were normal. Mean PSA was 1.0 ± 0.64 (C), 27.9 ± 19.0 (BT) and 16.2 ± 11.8 ng/mL (AT) (p = 0.002). Mg, Ca/Mg ratio BT, AT and control were significantly different (p = 0.0001, respectively). After treatment, Mg and Ca/Mg ratio were not different from controls. The prevalence of Ca/Mg imbalance was 80% (BT), 13.3% (AT) and 3.3% (control group). Ca/Mg ratio imbalance is associated with BPH. This has previously not been demonstrated. The imbalance was significantly corrected after treatment with the phytotherapeutic drug.


Spontaneous regression of neovascularization at the disc in diabetic retinopathy.
Neovascularization at the disc (NVD) is the most serious complication in diabetic retinopathy, and leads to vitreous hemorrhage and tractional retinal detachment. We report two cases of spontaneous regression of NVD in proliferative diabetic retinopathy. Two men (31 and 46 years old) with diabetes had NVD in both eyes. They were treated with panretinal photocoagulation on the left eye first, but their right eyes went untreated, because they did not revisit our clinic for several months. Fortunately, on revisit, their neovascularization had disappeared a few months later in both eyes, including their untreated right eyes. We could not find any specific causes for the spontaneous regression of the new vessels.


Hyaluronectin in normal human skin and in basal cell carcinoma.
The localization of hyaluronectin has been studied in normal skin and in basal cell carcinoma. In fetal skin it is abundant in the dermis but absent from the epidermis, and in adult skin it is totally absent except in the hair sheaths and bulbs. In basal cell carcinoma it is abundant only in the stroma reaction. The presence of this protein in mesenchymatous tissues seems to be linked to zones of physiological or neoplastic proliferation.


Chemical Variability of Hexane Extracts from Five Subspecies of Calendula suffruticosa from Spain.
The chemical profile of the hexane extracts of the subspecies carbonellii, greuteri, marginata, trialata, and vejerensis of Calendula suffruticosa growing in Spain, herein described for the first time, were studied to access their value as a chemo taxonomical tool and search for potentially useful compounds. The subsp. greuteri and carbonellii showed higher extract yields. Terpenoids were the most abundant chemical class in subsp. carbonellii, greuteri, trialata, and vejerensis, while alkanes were the most abundant in subsp. marginata. Differences in chemical constituents were identified among the subspecies of C. suffruticosa analysed, which the PCA can prove. The subsp. trialata and greuteri showed more significant phytochemical similarity, which might indicate genetic proximity between these two subspecies. C. suffruticosa subsp. marginata presented the fewest number of compounds and in the smallest quantities, and C. suffruticosa subsp. vejerensis presented the largest number, however, both showed no alcohols. Furthermore, some of the compounds found in significant amounts are known for their pharmacological and nutraceutical properties, denoting potential use.


Escherichia coli: great diversity around a common core.
Escherichia coli outbreak in Germany, which resulted in more than 4,000 cases, including 908 cases of hemolytic-uremic syndrome (HUS) and at least 50 deaths, highlighted the genome plasticity of E. coli and the potential for new virulent strains to emerge. The analysis of 170 E. coli genome sequences for the presence of nine previously identified protective extraintestinal pathogenic E. coli antigens suggested the feasibility of a combination vaccine as a universal intervention against all pathogenic E. coli strains. This article reports on the feasibility of a combination vaccine as a universal intervention against all pathogenic Escherichia coli strains.


Nurses' attitudes towards aggressive behaviour, following attendance at 'The Prevention and Management of Aggressive Behaviour Programme'.
The issue of aggression and violence is current in society. Recent reports indicate that this is not just an issue for society at large, but also for its organizations and institutions. The health care industry is not exception in this regard. Nursing, among other disciplines, has focused an increasing amount of attention on this problem for its members. This is evidenced by the increasing amount of literature on the topic. One feature of this writing is the study of programmes designed to train professionals in techniques to prevent and manage aggression and violence. To date, little attention has been paid to the evaluation of such programmes. In these times of economic difficulty, this position cannot be supported. This paper describes the study of one such educational programme. In this case the evaluation focused on the study of attitude change in participants following attendance at 'The Prevention and Management of Aggressive Behaviour Programme'. Although the indications are that the programme had a positive effect on attitudes, the author concludes that further study is required to illuminate the statistical significance of this positivity.


Treating the diabetic ulcer: practical approach and general concepts.
Neuropathic foot disease is commonly seen in clinical practice and is related primarily to the high and increasing prevalence of diabetes mellitus in the western world. The treatment of diabetic ulcer can be divided into three stages: evaluation, healing, prevention. Based on the evaluation, foot ulceration in diabetic patients can be categorized as non-infected and infected. Non-infected and non-ischemic ulcers heal when the area is off-loaded, constituting the cornerstone of treatment. Off-loading is combined with wound care. Surgical curative procedures are performed when conservative means fail and include internal off-loading, i.e., correction of the foot deformity and wound closure procedures. Off-loading is also important for infected ulcers but controlling the infection is essential. The infection is controlled by antibiotics, pus drainage, debridement of necrotic tissues including surgical debridement, and partial foot amputations. Diabetic ulcer is an expression of a complex systemic disease and requires treatment by multidisciplinary means, combining medical and paramedical personnel. The orthopedic surgeon plays a major role since a prominent part of the treatment involves foot surgery.


Fructose Intolerance: Cause or Cure of Chronic Functional Constipation.
Functional constipation is a common occurrence in the pediatric population. The link between fructose ingestion and constipation is obscure due to a lack of published data. In this article, we discuss the relationship of fructose tolerance and the development of constipation via a literature review and our single-center experience. A literature review of constipation and fructose ingestion was performed using PubMed. A retrospective chart review from the pediatric gastroenterology clinic, January 2012 to December 2015, was completed, with attention to the relationship of fructose intolerance and its clinical presentations. There were 367 patients who underwent the fructose breath hydrogen test (FBHT), out of which 208 patients had fructose intolerance. Clinical presentations included chronic abdominal pain, chronic diarrhea, chronic constipation, emesis, and nausea. Statistical significance was reached for chronic constipation, emesis, and nausea, being less likely to be found in FBHT-positive patients. Thus, fructose intolerance may help resolve symptoms in patients with chronic functional constipation.


Immunocytochemical studies on the central nervous system of the earthworm, Lumbricus terrestris.
There are numerous aldehyde fuchsin (AF)-positive, neurosecretory cells of medium size (A cells) and a small number of large, AF-negative neurons (B cells) in the cortical layer of the cerebral ganglion. In the subesophageal ganglion, symmetrical groups of AF-positive cells lie ventrally. The peroxidase--antiperoxidase (PAP) method was used for the immunocytochemical study of substance P and ACTH in these ganglia. In addition, the presence of L-enkephalin and alpha endorphin could be confirmed. Using rabbit antibodies to substance P we found small immunoreactive neurons among negative A and B cells in the cerebral ganglion. The processes of these immunoreactive cells could be traced to the subcortical synaptic neuropil. With antibodies to ACTH, activity was visible in perikarya similar in size to A neurons. A part of the nerve terminals of the synaptic zone, some of the B neurons and further several nerve cells of the subesophageal ganglion reacted positively. Successive demonstration of substance P and ACTH on the same section showed that the two materials occurred in different cell types. Using antiopsin antibody in an indirect immunocytochemical test we observed strong reaction in numerous medium-sized perikarya and in nerve fibres of the synaptic zone of the cerebral ganglion, further in some neurons of the subesophageal and abdominal ganglia. In contrast to this result, the photoreceptor cells of the prostomium and cerebral ganglion were negative. Presumably, substance P is present in a perikaryon type hitherto unrecognized while ACTH and antiopsin reactions seem to be located first of all in A cells.


Evaluation of Methicillin-Resistant Staphylococcus aureus Carriage in the Elderly in Portugal Using Selective Enrichment Followed by Quantitative Real-Time PCR.
The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals in Portugal is worrisome and among the highest in Europe. Surprisingly, MRSA prevalence in the community was described as very low (<2%) based on studies that used classical culture-based methods (CCBM). We investigated whether the apparent limited spread of MRSA in the community in Portugal might result from low sensitivity of CCBM. Nasopharyngeal- and oropharyngeal-paired samples obtained from senior adults living in nursing (n = 299) or family homes (n = 300) previously characterized by CCBM were reanalyzed. Samples were inoculated in a semi-selective enrichment medium, and those showing visible growth were evaluated by qPCR targeting nuc, mecA, and mecC genes (SSE+qPCR). By SSE+qPCR, 34 of the 1,198 (2.8%) samples were MRSA positive compared with 21 (1.8%) by CCBM. SSE+qPCR improved non-significantly detection of MRSA carriers from 5.4% to 8.0% (p = 0.12) in the nursing home collection, and from 0.3% to 1.7% (p = 0.13) in the family home collection. MRSA isolates belonged to three HA-MRSA clones widely disseminated in Portuguese hospitals. In conclusion, use of semi-selective medium combined with qPCR did not change the overall scenario previously described. In Portugal, MRSA circulation in the community among senior adults is low.


A novel arterial pouch model of saccular aneurysm by concomitant elastase and collagenase digestion.
An ideal aneurysm model of cerebral aneurysm is of great importance for studying the pathogenesis of the lesion and testing new techniques for diagnosis and treatment. Several models have been created in rabbits and are now widely used in experimental studies; however, every model has certain intrinsic limitations. Here we report the development of a novel saccular aneurysm model in rabbits using an arterial pouch that is subject to in vitro pre-digestion with combined elastase and collagenase. A segment of right common carotid artery (CCA) was dissected out and treated with elastase (60 U/ml, 20 min) followed by type I collagenase (1 mg/ml, 15 min) in vitro. The graft was anastomosed to an arterial arch built with the left CCA and the remaining right CCA, while the other end of the graft was ligated. The dimension and tissue structure of the pouch were analysed immediately, 2 or 8 weeks after operation. Ten terminal aneurysms were produced. The gross morphology of the aneurysm resembles the human cerebral terminal aneurysms. We have observed the following pathological changes: (1) growth of the aneurysm (mean diameter increased from (2.0+/-0.1) to (3.2+/-0.3) mm at 2 weeks, P<0.001, n=7-10); (2) thinning of the aneurysmal wall (the mean wall thickness decreased to 44% at 2 weeks), which was accompanied by significant losses of elastic fibres, collagen and the cellular component; and (3) spontaneous rupture (3 out of 9, one aneurysm ruptured 24 h after operation with the other two at 2 and 4 weeks respectively). This rabbit arterial pouch model mimics human cerebral aneurysms in relation to morphology and histology. In particular, this model exhibited an increased tendency of spontaneous rupture.


Effects of AGTR1 A1166C gene polymorphism in patients with heart failure treated with candesartan.
The benefits of angiotensin II receptor blockers (ARBs) in patients with heart failure who are treated with standard pharmacotherapy, including an angiotensin-converting enzyme (ACE) inhibitor, were demonstrated in 2 large randomized trials. It is currently impossible to determine which patient will benefit from the addition of an ARB. To explore the impact of selected candidate genes on the hemodynamic, neurohormonal, and antiinflammatory effects of candesartan in patients with heart failure who are already being treated with an ACE inhibitor. We investigated the impact of 10 candidate genetic polymorphisms on the effects of candesartan in patients with heart failure who are treated with an ACE inhibitor. We evaluated their impact on acute (2 wk) and long-term (24 wk) changes in blood pressure and N-terminal proB-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) during treatment with candesartan. Thirty-one patients were included. Homozygotes of the AGTR1 A1166 allele (n = 13) had a greater decrease in systolic (-9.1 +/- 4.7 vs 1.1 +/- 3.3 mm Hg; p = 0.04 by analysis of variance [ANOVA], adjusting for dose) and diastolic blood pressure (-5.1 +/- 1.5 vs 1.9 +/- 1.9 mm Hg; p = 0.005 by ANOVA, adjusting for dose) compared with C1166 allele carriers (n = 18) following 2 weeks of treatment. After 6 months of treatment, C1166 carriers experienced a greater decrease in NT-proBNP (-151.4 [-207; -19.8] ng/L vs 147.3 [-61.3; 882.9] ng/L; p = 0.03) and hsCRP (-0.8 [-2.2; -0.03] mg/L) vs 0.2 [-1.8; 5.3] mg/L; p = 0.09) compared with patients carrying the AA1166 genotype. No other significant association was found. The results of this proof-of concept study provide the first evidence that the AGTR1 A1166C polymorphism could influence the response to candesartan in patients with heart failure who are receiving ACE inhibitors. Validation of these exploratory findings in larger populations is required before use of the AGTR1 A1166C genotype can be incorporated into clinical practice.


Segmental cable evaluation of somatic transients in hippocampal neurons (CA1, CA3, and dentate).
This study describes a detailed cable model of neuronal structure, which can predict the effects of discrete transient inputs. Neurons in in vitro hippocampal slices (CA1 and CA3 pyramidal cells and dentate granule neurons; n = 4 each) were physiologically characterized and stained with horseradish peroxidase (HRP). The HRP morphology was approximated with numerous small segments. The cable model included both these segments and spatially dispersed dendritic spines. The transient response function at the soma of the segmental model was numerically derived, and charging responses to simulated current inputs were computed. These simulations were compared with the physiological charging responses from the somatic penetrations, using an analysis of the charging time constants (tau i) and intercepts. The time constant ratio (tau 0/tau 1) did not significantly differ between the observed and simulated responses. A second index of comparison was the equivalent cylinder electrotonic length (L), which was derived using only the tau i values and their intercepts. The L values also did not differ significantly between the observed and simulated transients and averaged 0.91 length constant. Thus, using criteria based only on analysis of charging responses, the segmental cable model recreated accurately the observed transients at the soma. The equivalent cylinder model (with a lumped soma) could also adequately simulate the observed somatic transients, using the same criteria. However, the hippocampal neurons (particularly the pyramidal cells) did not appear to satisfy the equivalent cylinder assumption anatomically. Thus, the analysis of somatic charging transients alone may not be sufficient to discriminate between the two models of hippocampal neurons. Anatomical evidence indicates that, particularly for discrete dendritic inputs, the detailed segmental model may be more appropriate than the equivalent cylinder model.