Quantification of amoA gene abundance and their amoA mRNA levels in activated sludge by real-time PCR.
The transcription level of amoA mRNA encoding a subunit of ammonia monooxygenase (AMO) in ammonia-oxidizing bacteria (AOB) was quantified by reverse transcription-polymerase chain reaction (RT-PCR) methods in combination with real-time PCR technology. The effects of ammonia concentration and dissolved oxygen (DO) on the transcription levels of amoA mRNA and 16S rRNA in AOB were evaluated in batch experiments with nitrifying sludge taken from a lab-scale reactor treating artificial wastewater. A batch incubation without ammonia resulted in a rapid decrease, within four hours, in the transcription level of amoA mRNA to as low as 1/10 of that at the beginning of the experiment, while the 16S rRNA level in AOB was almost constant. After subsequent incubation with 3 mM ammonia for eight hours, a small increase in the transcription level of amoA mRNA occurred, but ammonia oxidation proceeded in the interim. Copy numbers of amoA mRNA showed an almost fixed value for over eight hours in the absence of dissolved oxygen.


Satisfaction with rehabilitation in relation to self-perceived quality of life and function among patients with stroke - a 12 month follow-up.
Stroke causes complex disability and function, and perceived quality of life has been shown to correlate with satisfaction with care as well as with life in general among stroke patients. The aim of this study was to study the relation of satisfaction with how rehabilitation was provided with self-perceived quality of life, self-perceived function and rehabilitation received, 12 months after the incidence. The subjects were assessed 12 months after the onset of stroke. The Barthel index was used to measure function, and the EuroQol-5D to measure quality of life. To measure satisfaction with how rehabilitation was provided, a questionnaire from the Swedish Stroke Register was used. Two hundred and eighty-three patients participated in the follow-up, 137 women and 146 men, aged between 42 and 95 years (mean age 75.2, SD 11.8). For the majority of patients rehabilitation was initiated at in-hospital care (directly after onset). One hundred and sixty-eight patients considered that rehabilitation was well provided for. Sixty-six regarded that the rehabilitation was only partly provided for and 35 that it was not provided for at all. High value on Barthel Index was associated with satisfaction with how rehabilitation was provided for (OR 2.81). Also, rehabilitation on three or more levels was negatively associated with satisfaction with rehabilitation provision (OR 0.24) and so was being male (OR 0.49). In this study, patients with higher values on Barthel Index were more satisfied with how rehabilitation was provided for. However, male patients and patients who received rehabilitation on three or more levels of care were less satisfied. Given the assumption that patients with more severe dysfunction after stroke are being rehabilitated on more levels, this might imply that it is not the amount of rehabilitation that gives satisfaction but the patients self-perceived function after rehabilitation.


[Peritonitis of appendicular origin].
The results of treatment in 2437 patients with peritonitis of the appendicular origin are analysed. The causes of development of this complication, therapeutic aspects and also most frequent tactical and technical errors, made while operating patients with peritonitis, and their influence on issues of the lesion are discussed.


A multicentre phase I and pharmacokinetic study of BN80915 (diflomotecan) administered daily as a 20-min intravenous infusion for 5 days every 3 weeks to patients with advanced solid tumours.
BN80915 (diflomotecan) is an E-ring modified camptothecin analogue, which possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors. This phase I study was carried out using a daily times five administration schedule (dx5) repeated three weekly. The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) for phase II studies. Secondary objectives were to determine the safety and pharmacokinetic (PK) profile, and to make a preliminary assessment of antitumour activity. Diflomotecan was administered intravenously on days 1-5 every 3 weeks. Patients were treated in cohorts of three to six per dose level and the dose of diflomotecan was escalated according to modified Fibonacci schedule. Plasma concentrations of diflomotecan and its metabolite BN80942 were quantified. Thirty patients were assessable for toxicity. Dose levels explored were 0.05, 0.1, 0.125 and 0.15 mg/m(2)/day. The 0.15-mg/m(2) dose level was determined to be the MTD. Toxicity was acceptable at the 0.125-mg/m(2)/day dose level. PK analysis showed the principal parameters were neither time nor dose dependent. There was a wide interpatient variability in PK at all dose levels. One patient with colorectal cancer, previously treated with irinotecan, had a partial response. A further eight patients had disease stabilisation. The MTD and RD of diflomotecan administered according to a dx5 repeated three weekly are 0.15 and 0.125 mg/m(2)/day, respectively. In general, treatment was well tolerated; the principal toxicity was reversible myelosuppression. An objective response was seen in a patient previously treated with irinotecan.


Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox.
Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.


Expression in Escherichia coli, purification and characterization of two mammalian thioesterases involved in fatty acid synthesis.
Thioesterase I, a constituent domain of the multifunctional fatty acid synthase, and thioesterase II, an independent monofunctional protein, catalyse the chain-terminating reaction in fatty acid synthesis de novo at long and medium chain lengths respectively. The enzymes have been cloned and expressed in Escherichia coli under the control of the temperature-sensitive lambda repressor. The recombinant proteins are full-length catalytically competent thioesterases with specificities indistinguishable from those of the natural enzymes.


Absorbable Versus Non-Absorbable Sutures in Open Rhinoplasty: Analysis of Columellar Scarring.
Open rhinoplasty involving columellar incision has gained popularity since the 1930s. Many surgical incision techniques have been employed to obtain better results in terms of postoperative scarring. This study evaluated and compared the results of absorbable and non-absorbable sutures used in open technique rhinoplasty, assessed scar properties regardless of the techniques used, from the perspectives of patients and surgeons. This study evaluated and compared the results of absorbable and nonabsorbable sutures used in open technique rhinoplasty from the perspectives of patients and surgeons. Study population included 70 patients who underwent primary open rhinoplasty between 2013 and 2018. Rhinoplasty Operations were performed in 2 different centers by a total of 2 rhinoplasty surgeons. Both surgeons used suture materials, which can be used for columellar closure, regardless of patients' skin characteristics. Columellar scars were assessed at an outpatient clinic at least 6 months postoperatively. Patients who could not come to the clinic were excluded from the study. Columellar Scars were assessed using the Turkish Patient Observer Scar Assessment Questionnaire. Patients were also asked to complete a Scar Assessment Analysis Questionnaire at the outpatient clinic, and were photographed from the front, basal, and right and left oblique sides. Three surgeons, who were not part of the research team but routinely performed rhinoplasty, completed the Observer Scar Assessment Questionnaire by examining patients in person at the clinic as well as their photographs. Observer Scar Assessment Questionnaire results; for the Vicryl group, surgeons ranked pigmentation of the scar as the best criterion (3.34 ± 0.97) and irregularity of the scar as the worst (3.82 ± 1.01). For the Prolene group, surgeons ranked irregularity as the best criterion (3.30 ± 0.97) and stiffness as the worst (3.54 ± 0.94). Although there was no statistically significant result between the two groups in the criteria, the mean scores of the Prolene group were less than the Vicryl group. (3.36 ± 0.46, 3.50 ± 0.65 respectively).Scar Assessment Analysis Questionnaire Results; patients in both the Vicryl and Prolene groups ranked pain as the least important factor (mean 2.9 ± 1.11 and 3.33 ± 1.35, respectively). The Prolene group scored lower than the Vcryl group in terms of overall scarring (3.49 ± 0.72, 3.66 ± 1.37, respectively, P > 0,05). Absorbable sutures are a convenient alternative to nonabsorbable sutures. Evidence obtained from multiple time series with or without the intervention, such as case studies. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.


Nucleotide-dependent structural fluctuations and regulation of microtubule-binding affinity of KIF1A.
Molecular motors such as kinesin regulate affinity to a rail protein during the ATP hydrolysis cycle. The regulation mechanism, however, is yet to be determined. To understand this mechanism, we investigated the structural fluctuations of the motor head of the single-headed kinesin called KIF1A in different nucleotide states using molecular dynamics simulations of a Gō-like model. We found that the helix α4 at the microtubule (MT) binding site intermittently exhibits a large structural fluctuation when MT is absent. Frequency of this fluctuation changes systematically according to the nucleotide states and correlates strongly with the experimentally observed binding affinity to MT. We also showed that thermal fluctuation enhances the correlation and the interaction with the nucleotide suppresses the fluctuation of the helix α4. These results suggest that KIF1A regulates affinity to MT by changing the flexibility of the helix α4 during the ATP hydrolysis process: the binding site becomes more flexible in the strong binding state than in the weak binding state.


Selective formation of Sed5p-containing SNARE complexes is mediated by combinatorial binding interactions.
Sed5p is the only syntaxin family member required for protein transport through the yeast Golgi and it is known to bind up to nine other soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins in vivo. We describe in vitro binding experiments in which we identify ternary and quaternary Sed5p-containing SNARE complexes. The formation of SNARE complexes among these endoplasmic reticulum- and Golgi-localized proteins requires Sed5p and is syntaxin-selective. In addition, Sed5p-containing SNARE complexes form selectively and this selectivity is mediated by Sed5p-containing intermediates that discriminate among subsequent binding partners. Although many of these SNAREs have overlapping distributions in vivo, the SNAREs that form complexes with Sed5p in vitro reflect their functionally distinct locales. Although SNARE-SNARE interactions are promiscuous and a single SNARE protein is often found in more than one complex, both the biochemical as well as genetic analyses reported here suggest that this is not a result of nonselective direct substitution of one SNARE for another. Rather our data are consistent with the existence of multiple (perhaps parallel) trafficking pathways where Sed5p-containing SNARE complexes play overlapping and/or distinct functional roles.


Antimicrobial peptides from Bombyx mori: a splendid immune defense response in silkworms.
Bombyx mori L., a primary producer of silk, is the main tool in the sericulture industry and provides the means of livelihood to a large number of people. Silk cocoon crop losses due to bacterial infection pose a major threat to the sericulture industry. Bombyx mori L., a silkworm of the mulberry type, has a sophisticated inherent innate immune mechanism to combat such invasive pathogens. Among all the components in this defense system, antimicrobial peptides (AMPs) are notable due to their specificity towards the invading pathogens without harming the normal host cells. Bombyx mori L. so far has had AMPs identified that belong to six different families, namely cecropin, defensin, moricin, gloverin, attacin and lebocin, which are produced by the Toll and immune deficiency (IMD) pathways. Their diverse modes of action depend on microbial pathogens and are still under investigation. This review examines the recent progress in understanding the immune defense mechanism of Bombyx mori based on AMPs.


The effect of apolipoprotein E (ApoE) genotype on biomarkers of amyloidogenesis, tau pathology and neurodegeneration in Alzheimer's disease.
The presence of the ɛ4 allele in apolipoprotein E (ApoE) represents the most important genetic risk factor for late onset sporadic Alzheimer's disease (AD), together with age and mid-life hypercholesterolemia. ApoE4 is the most important lipid transporter between cells in the CNS and it was found that ApoE4 is involved in Amyloid β (Aβ) formation, fibrilisation, accumulation, in the aggregation and hyperphosphorylation of tau and in the metabolism of brain cholesterol and in neurodegeneration. Low cerebrospinal fluid (CSF) Aβ1-42 is a marker of Aβ plaque load in the brain. High CSF t-tau and p-tau concentrations reflect axonal and neuronal damage and injury, which correlates with a neurofibrillary tangle stage and load, also reflecting the intensity of the disease process. Magnetic resonance imaging (MRI) brain atrophy is a biomarker of neurodegeneration and is the result of loss of neurons, synapses and dendritic arborization. ApoE genotype interacts with the AD biomarkers: ɛ4 carriers were found to present with lower concentrations of Aβ1-42, higher tau and p-tau, higher tau/Aβ ratio and a higher degree of brain atrophy at any disease stage, changing the test performances and the ability to distinguish between the different cognitive condition. The presence of the ɛ4 allele was also found to increase the power to predict further cognitive decline. Even if the presence of ApoE4 is not a deterministic factor for AD, it seems to shift the progression of the disease towards a younger age and faster progression. It is also likely that the ɛ4 allele increases the intensity of the pathological process in several ways. In the study of cognitive impaired patients and in their follow-up, biomarkers should be interpreted in consideration of the ApoE genotype in order to better predict the progression of the disease.


Masitinib reverses doxorubicin resistance in canine lymphoid cells by inhibiting the function of P-glycoprotein.
Overexpression of ABC-transporters including Pgp, MRP1, and BCRP has been associated with multidrug resistance (MDR) in both human and canine oncology. Therapeutic interventions to reverse MDR are limited, but include multidrug protocols and the temporary concomitant use of inhibitors of ABC-transporters. Recently, the use of tyrosine kinase inhibitors has been proposed to overcome MDR in human oncology. One of the tyrosine kinase inhibitors, masitinib, is licensed for veterinary use in the treatment of canine mast cell tumors. Therefore, this study aimed to assess the potential of masitinib to revert MDR in canine malignant lymphoma using an in vitro model with canine lymphoid cell lines. Masitinib had a mild antiproliferative effect on lymphoid cells, inhibited Pgp function at concentrations equal to or exceeding 1 μm and was able to reverse doxorubicin resistance. The current findings provide the rationale for a combined use of masitinib with doxorubicin in the treatment of dogs with doxorubicin-resistant malignant lymphoma but await confirmation in clinical trials.


Muslim prayer movements as an alternative therapy in the treatment of erectile dysfunction: a preliminary study.
[Purpose] Our objective was to assess the effect of salat and mimicking salat movements and postures on subjects with erectile dysfunction. [Methods] Ten volunteers were recruited in this study. Subjects who were Muslims (Group I) were asked to perform their daily salat and a new intervention of an additional 12 movement cycles of salat for three sessions a week. Non-Muslim subjects (Group II) were taught to mimic salat movements, and were asked to perform a total of 12 movement cycles without reading the recitation for three sessions a week. An International Index for Erectile Function 5 (IIEF-5) questionnaire was given to the subjects before and after the intervention of performing salat or mimicking salat movements and postures. A nocturnal electrobioimpedance volume assessment (NEVA) device was used to measure the nocturnal penile tumescence (NPT) parameters over two consecutive nights. A nonparametric test was conducted to find the significant NPT parameters. [Results] The results showed that all measured parameters improved significantly, with the largest change observed in the maximum percent volumetric change over the baseline (from 138 to 222%). [Conclusion] This preliminary study suggests that the alternative approach of salat and mimicking salat movements and postures, may have beneficial effects for ED patients.


The relationship between erythropoietin pretreatment with blood-brain barrier and lipid peroxidation after ischemia/reperfusion in rats.
Blood-brain barrier (BBB) leakage plays a role in the pathogenesis of many pathological states of the brain including ischemia and some neurodegenerative disorders. In recent years, erythropoietin (EPO) has been shown to exert neuroprotection in many pathological conditions including ischemia in the brain. This study aimed to investigate the effects of EPO on BBB integrity, infarct size and lipid peroxidation following global brain ischemia/reperfusion in rats. Wistar male rats were divided into four groups (each group n=8); Group I; control group (sham-operated), Group II; ischemia/reperfusion group, Group III; EPO treated group (24 h before decapitation--000 U/kg r-Hu EPO i.p.), Group IV; EPO+ ischemia/reperfusion group (24 h before ischemia/reperfusion--3000 U/kg r-Hu EPO i.p.). Global brain ischemia was produced by the combination of bilateral common carotid arteries occlusion and hemorrhagic hypotension. Macroscopical and spectrophotometrical measurement of Evans Blue (EB) leakage was observed for BBB integrity. Infarct size was calculated based on 2,3,5-triphenyltetrazolium chloride (TTC) staining. Lipid peroxidation in the brain tissue was determined as the concentration of thiobarbituric acid-reactive substances (TBARS) for each group. Ischemic insult caused bilateral and regional BBB breakdown (hippocampus, cortex, corpus striatum, midbrain, brain stem and thalamus). EPO pretreatment reduced BBB disruption, infarct size and lipid peroxide levels in brain tissue with 20 min ischemia and 20 min reperfusion. These results suggest that EPO plays an important role in protecting against brain ischemia/reperfusion through inhibiting lipid peroxidation and decreasing BBB disruption.


Combined therapy with vaginal progesterone, Arabin cervical pessary and cervical cerclage to prevent preterm delivery in high-risk women.
Preterm birth is the leading cause of perinatal morbidity and mortality. Vaginal progesterone cervical cerclage and Arabin cervical pessary are considered as preventive treatments in women at risk for preterm birth. However, there is less evidence as to which of these interventions is the preferred management. The current study aims was to compare the outcome of pregnancy in women with a short cervical length managed with 4 different treatment protocols: therapy with vaginal progesterone, cervical cerclage and an Arabin cervical pessary (group A), Arabin cervical pessary and vaginal progesterone (group B), cervical cerclage and vaginal progesterone (group C), or vaginal progesterone alone (group D). A retrospective cohort study of singleton pregnancies managed in three tertiary medical centers between September 2011 and December 2017. In the study period, 286 pregnant women underwent vaginal ultrasonography between 15 and 29 weeks gestation. They all had a short cervical length (≤25 mm). Of these, 18 (6.3%), 120 (41.9%), 38 (13.3%) and 110 (38.5%) patients received treatment classifying them into groups A, B, C, and D, respectively. A significantly higher rate of patients in group A had either a history of cervical incompetence (44.4 versus 9.2 versus 7.9 and 0.9%, respectively, p = .0001) or a cervical procedure (61.1 versus 37.5 versus 28.9 and 27.3%, respectively, p = .027) compared to patients in group B, C, and D. Despite having a shorter cervical length at recruitment in group A (median (range); 14.5 (0-25) versus 15 (0-25) versus 15.5 (0-25) and 19 (2-25) mm, respectively, p = .002) the rate of spontaneous preterm delivery <37-week gestation was similar across groups (44.4 versus 32.5 versus 36.8 versus 32.7%, respectively, p = .665). A combined rescue therapy involving vaginal progesterone, cervical cerclage, and Arabin cervical pessary emerges as a promising management strategy in pregnant women who have a short cervical length and a high background risk for preterm delivery. This combination may prolong their pregnancy and safely bring them near term. Additional studies are needed to confirm these preliminary findings.


Chiral phosphoric acid-catalyzed desymmetrizative glycosylation of 2-deoxystreptamine and its application to aminoglycoside synthesis.
This work describes chiral phosphoric acid (CPA)-catalyzed desymmetrizative glycosylation of meso-diol derived from 2-deoxystreptamine. The chirality of CPA dictates the outcome of the glycosylation reactions, and the use of enantiomeric CPAs results in either C4-glycosylated (67 : 33 d.r.) or C6-glycosylated (86 : 14 d.r.) 2-deoxystreptamines. These glycosylated products can be converted to aminoglycosides, and the application of this strategy to the synthesis of protected iso-neamine and iso-kanamycin B with inverted connection at the C4 and C6 positions is described.


The egyptian clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.
The landscape of chronic liver disease in Egypt has drastically changed over the past few decades. The prevalence of metabolic-associated fatty liver disease (MAFLD) has risen to alarming levels. Despite the magnitude of the problem, no regional guidelines have been developed to tackle this disease. This document provides the clinical practice guidelines of the key Egyptian opinion leaders on MAFLD screening, diagnosis, and management, and covers various aspects in the management of MAFLD. The document considers our local situations and the burden of clinical management for the healthcare sector and is proposed for daily clinical practical use. Particular reference to special groups was done whenever necessary.


Spanish Menopause Society position statement: use of tibolone in postmenopausal women.
Tibolone is a drug with complex tissue-specific action that exhibits a combination of estrogenic, progestogenic, and slight androgenic activity. Its variable profile explains its clinical effects, depending on the target tissue where it is metabolized, its metabolites' affinity for and potency in hormone receptors, and probable enzymatic activity modulation.In recent reviews and clinical trials, the effectiveness of tibolone in alleviating different hot flush menopause symptoms, mainly in mood and sexuality disorders, has been noted. In Spain, tibolone is the most prescribed hormonal treatment, and one of the most common complaints among postmenopausal women is change in sexual drive. For such reason, a panel of experts from the Spanish Menopause Society met to develop usage recommendations based on the best evidence available.


Multi-level adaptive segmentation of multi-parameter MR brain images.
MR brain image segmentation into several tissue classes is of significant interest to visualize and quantify individual anatomical structures. Traditionally, the segmentation is performed manually in a clinical environment that is operator dependent and may be difficult to reproduce. Though several algorithms have been investigated in the literature for computerized automatic segmentation of MR brain images, they are usually targeted to classify image into a limited number of classes such as white matter, gray matter, cerebrospinal fluid and specific lesions. We present a novel model-based method for the automatic segmentation and classification of multi-parameter MR brain images into a larger number of tissue classes of interest. Our model employs 15 brain tissue classes instead of the commonly used set of four classes, which were of clinical interest to neuroradiologists for following-up with patients suffering from cerebrovascular deficiency (CVD) and/or stroke. The model approximates the spatial distribution of tissue classes by a Gauss Markov random field and uses the maximum likelihood method to estimate the class probabilities and transitional probabilities for each pixel of the image. Multi-parameter MR brain images with T(1), T(2), proton density, Gd+T(1), and perfusion imaging were used in segmentation and classification. In the development of the segmentation model, true class-membership of measured parameters was determined from manual segmentation of a set of normal and pathologic brain images by a team of neuroradiologists. The manual segmentation was performed using a human-computer interface specifically designed for pixel-by-pixel segmentation of brain images. The registration of corresponding images from different brains was accomplished using an elastic transformation. The presented segmentation method uses the multi-parameter model in adaptive segmentation of brain images on a pixel-by-pixel basis. The method was evaluated on a set of multi-parameter MR brain images of a twelve-year old patient 48h after suffering a stroke. The results of classification as compared to the manual segmentation of the same data show the efficacy and accuracy of the presented methods as well as its capability to create and learn new tissue classes.


[The antiphospholipid syndrome. The neurological complications and the therapeutic possibilities].
For several months a 23-year-old woman had been suffering from increasingly frequent attacks of bilateral amaurosis fugax. They affected only individual segments of a monocular visual field and finally occurred several times daily. Physical and cardiological examinations as well as echocardiography were within normal limits. Laboratory tests revealed a slight increase in erythrocyte sedimentation rate and high titres of serum antibodies against phospholipids. Fundoscopy did not show any vascular changes. Because vasculitis--possibly as an expression of systemic lupus erythematodes--was suspected, high-dosage treatment with steroids was commenced, but failed to influence the visual disorder. While steroid dosage was gradually decreased, administration of acetylsalicylic acid (for three months 100 mg daily, then three times daily 100 mg) brought about complete disappearance of the visual signs. Their cause was probably a reversible platelet aggregation induced by antiphospholipid antibodies which, because of the physiological characteristics of the terminal retinal vascular bed brought about the isolated sign of recurrent amaurosis fugax.


A genome-wide association study identifies a region strongly associated with symmetrical onychomadesis on chromosome 12 in dogs.
Symmetrical onychomadesis causes periodic loss of claws in otherwise healthy dogs. Genome-wide association analysis in 225 Gordon Setters identified a single region associated with symmetrical onychomadesis on chromosome 12 (spanning about 3.3 mb). A meta-analysis including also English Setters indicated that this genomic region predisposes for symmetrical onychomadesis in English Setters as well. The associated region spans most of the major histocompatibility complex and nearly 1 Mb downstream. Like many other autoimmune diseases, associations of symmetrical onychomadesis with DLA class II alleles have been reported. In this study, no associated markers were revealed within any of the DLA-DRB1, -DQA1 or -DQB1 genes, and the odds for symmetrical onychomadesis in the Gordon Setters were much higher, carrying significant single nucleotide polymorphisms compared to the odds of any of the recorded DLA-DRB1/DQA1/DQB1 haplotypes. We noticed that some of the associated DLA haplotypes were different between the English Setters and the Gordon Setters. Interestingly, associated SNP chip markers showed a more consistent pattern of allelic variants related to cases or controls regardless of breed. In conclusion, the associated genetic markers identified in this study hold the potential to aid in selection of breeding animals to reduce the frequency of symmetrical onychomadesis in the dog.


To eat, or NOt to eat: S-nitrosylation signaling in autophagy.
Autophagy is the main catabolic cellular process through which cells adapt their needs (e.g., growth and proliferation) to environmental availability of nutrients (e.g., amino acid and glucose) and growth factors. The rapid activation of the autophagy response essentially depends on protein post-translational modifications (PTMs), which act as molecular switches triggering signaling cascades. Deregulation of autophagy contributes to pathological conditions, such as cancer and neurodegeneration. Therefore, understanding how PTMs affect the occurrence of autophagy is of the highest importance for clinical applications. Besides phosphorylation and ubiquitylation, which represent the best known examples of PTMs, redox-based modifications are also emerging as contributing to the regulation of intracellular signaling. Of note, S-nitrosylation of cysteine residues is a redox PTM and is the principal mechanism of nitric oxide-based signaling. Results emerging in recent years suggest that NO has a role in modulating autophagy. However, the function of S-nitrosylation in autophagy regulation remains still unveiled. By this review, we describe the upstream events regulating autophagy activation focusing on recently published evidence implying a S-nitrosylation-dependent regulation.


Leucocyte depletion in cardiopulmonary bypass: a comparison of four strategies.
Leucocytes have been shown to play a fundamental role in the pathophysiology of inflammation. This prospective, randomized, controlled study was designed to identify the most advantageous leucocyte depletion technique in terms of reduction in systemic inflammatory response syndrome and myocardial ischaemia reperfusion injury associated with cardiopulmonary bypass (CPB). Forty consecutive patients undergoing elective coronary artery bypass graft (CABG) surgery were randomly allocated to one of four groups. The four groups consisted of a control group, a systemic leucocyte depletion (SLD) group, a cardioplegic leucocyte depletion (CLD) group and a total leucocyte depletion (TLD) group. There were 10 patients in each group. Lactoferrin (marker of neutrophil activation) and troponin-I (marker of myocardial ischaemia reperfusion injury) were measured at six time points: post induction, 5 min on CPB, 5 min before releasing the aortic crossclamp, 15 min after releasing the clamp and 1 and 24 hours after the discontinuation of CPB. Plasma lactoferrin levels increased rapidly in every group after the commencement of CPB, subsequently reached a peak after releasing the aortic crossclamp and gradually declined after the discontinuation of CPB. The lowest lactoferrin concentration was observed in the TLD (range 2.15-141.9 ng/mL) and CLD groups (7.469-114.6 ng/mL). Regarding myocardial injury, plasma cardiac troponin-I levels did not differ significantly between groups; but troponin-I concentrations rose dramatically after releasing the aortic crossclamp in all groups. Nevertheless, the CLD group had the lowest troponin-I level (1.37-5.55 ng/mL). In conclusion, it is believed that myocardial ischaemia is probably a major contributor to the inflammatory response. Although there is no clear statistical significance shown in this pilot study, the data tend to support the cardioplegic leucocyte depletion strategy as the optimal method for attenuating neutrophil activation and myocardial ischaemia reperfusion injury.


Colonic carcinoma presenting as an appendiceal abscess in a young woman.
A 38-year-old woman with stage T4N0M0 adenocarcinoma of the cecum presented with what seemed to be an appendiceal abscess. She had a 10-month history of intermittent abdominal pain in the right lower quadrant. Initial laparotomy revealed an abscess in that quadrant. The abscess was drained. A mass in the cecum, associated with dense fibrous tissue and abscess formation, was found on subsequent surgical exploration. Pathological examination revealed a well-differentiated mucinous adenocarcinoma of the cecum with transmural invasion. The lesion had replaced most of the vermiform appendix and was associated with a periappendiceal abscess. Colonic carcinoma masquerading as acute appendicitis or an appendiceal abscess is a well-recognized entity in the elderly but may be overlooked in younger patients because malignant disease is not suspected.


Desiccating stress decreases apical corneal epithelial cell size--modulation by the metalloproteinase inhibitor doxycycline.
We investigated the effects of desiccating stress on murine corneal apical epithelial cell area and desquamation by using 4 defined parameters and evaluated the effects of the metalloproteinase inhibitor doxycycline on this process. C57BL/6 mice were subjected to experimental dry eye (EDE) for 5 days without or with topical therapy with doxycycline 0.025% or 0.0025% or vehicle 4 times a day. C57BL/6 mice that were not exposed to desiccating stress served as controls. Whole mount corneas from each group were immunostained for occludin and visualized by laser scanning confocal microscopy. The images were analyzed in a masked fashion, and mean individual cell area, apical cell density, average cell number loss, and average percent loss were recorded. EDE caused a significant decrease in apical corneal cell area (1073 +/- 135.9 microm2), an increase in apical cell density (895.8 +/- 115.4 cells per mm2) and a greater percent of epithelial loss (21.29% +/- 13.40%) than controls (1341 +/- 95.28 microm2, 714.4 +/- 55.60 cells per mm2, 2.897% +/- 3.452%, P < 0.001 for all, respectively). Treatment with 0.025% doxycycline preserved cell area (1337 +/- 144.6 microm2) and the apical cell density (721.0 +/- 91.62 cells per mm2) and decreased percentage loss (5.117% +/- 6.757%) compared with the vehicle control group (1154 +/- 88.10 microm2, 830.2 +/- 49.76 cells per mm2, 22.14 +/- 9.616%, P < 0.001 for all, respectively). Desiccating stress decreases apical corneal epithelial cell area, increases apical cell density, and promotes epithelial cell loss. Treatment with the metalloproteinase inhibitor doxycycline during desiccating stress preserves cell area and apical cell density and prevents EDE-induced corneal epithelial cell loss. These findings suggest that metalloproteinases mediate apical corneal epithelial loss during desiccating stress.


Effectiveness of aromatherapy with inhaled lavender essential oil and breathing exercises on ECT-related anxiety in depressed patients.
Background and aims Electroconvulsive therapy (ECT) is considered a safe, effective, and significant treatment in patients suffering from a major depressive disorder. Anxiety caused by this invasive treatment may impose several side effects on patients. The purpose of this study was to evaluate the effectiveness of aromatherapy with inhaled lavender essential oil and breathing exercises on ECT-related anxiety in depressed patients. Methods In this randomized controlled clinical trial, 90 depressed patients were selected and divided into three groups: aromatherapy, breathing exercise, and routine care using a random allocation method. Before undergoing ECT, the aromatherapy group was exposed to the inhaled lavender essential oil (n = 30), the breathing exercise group performed the breathing exercises (n = 30), and the routine care group received routine care (n = 30). Before (20 min) and after the intervention (30 min later), patients' anxiety was assessed using Beck Anxiety Inventory. Results After the intervention, the results revealed that anxiety score changes were statistically significant among the three groups (p < 0.001). In addition, it was found that the patients' mean anxiety scores significantly decreased in the aromatherapy and breathing exercise groups compared to with the pre-intervention scores (p < 0.001). Conclusion Aromatherapy with inhaled lavender essential oil and breathing exercises can be considered by clinical nurses as simple, applicable, and effective interventions to reduce ECT-related anxiety in depressed patients.


Dysfunction of peripheral blood granulocyte oxidative metabolism in children with recurrent upper respiratory tract infections.
Granulocytes play a key role in the defence against bacterial infections. Their dysfunction may both predispose to and result from infections. The oxidative metabolism of peripheral blood granulocytes was studied in 50 children aged from 1 to 10 years, with recurrent upper respiratory tract infections and/or tonsillar hypertrophy. Four groups of patients were recruited: 15 healthy controls, seven patients with idiopathic tonsillar hypertrophy, 12 patients with upper respiratory tract infections and 16 patients with upper respiratory tract infections with concurrent tonsillar hypertrophy. The ability of granulocytes to produce reactive oxygen species was assessed by nFMLP-induced chemiluminescence. Both increased and depressed granulocyte activity was observed in all studied groups, with the exception of controls. Altered granulocyte function was observed in 30% of patients in the idiopathic tonsillar hypertrophy group. In children with recurrent infections abnormal chemiluminescence results were found in from 75% to nearly 90% of patients. This preliminary study demonstrates the possible relationship between recurrent upper respiratory tract infections, tonsillar hypertrophy and impaired peripheral blood granulocyte chemiluminescence.


Origin of slow and fast oscillations of Ca2+ in mouse pancreatic islets.
1. Pancreatic islets exposed to 11 mM glucose exhibited complex variations of cytoplasmic Ca2+ concentration ([Ca2+]i) with slow (0.3-0.9 min-1) or fast (2-7 min-1) oscillations or with a mixed pattern. 2. Using digital imaging and confocal microscopy we demonstrated that the mixed pattern with slow and superimposed fast oscillations was due to separate cell populations with the respective responses. 3. In islets with mixed [Ca2+]i oscillations, exposure to the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (DTBHQ) resulted in a selective disappearance of the fast pattern and amplification of the slow pattern. 4. In addition, the protein kinase A inhibitor RP-cyclic adenosine 3',5'-monophosphorothioate sodium salt transformed the mixed [Ca2+]i oscillations into slow oscillations with larger amplitude. 5. Islets exhibiting only slow oscillations reacted to low concentrations of glucagon with induction of the fast or the mixed pattern. In this case the fast oscillations were also counteracted by DTBHQ. 6. The spontaneously occurring fast oscillations seemed to require the presence of cAMP-elevating glucagon, since they were more common in large islets and suppressed during culture. 7. Image analysis revealed [Ca2+]i spikes occurring irregularly in time and space within an islet. These spikes were preferentially observed together with fast [Ca2+]i oscillations, and they became more common after exposure to glucagon. 8. Both the slow and fast oscillations of [Ca2+]i in pancreatic islets rely on periodic entry of Ca2+. However, the fast oscillations also depend in some way on paracrine factors promoting mobilization of Ca2+ from intracellular stores. It is proposed that such a mobilization in different cells within a tightly coupled islet syncytium generates spikes which co-ordinate the regular bursts of action potentials underlying the fast oscillations.


Human immunodeficiency virus type 1 envelope glycoprotein is modified by O-linked oligosaccharides.
The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein has been shown to be extensively modified by N-linked glycosylation; however, the presence of O-linked carbohydrates on the glycoprotein has not been firmly established. We have found that enzymatic deglycosylation of the HIV-1 envelope glycoprotein with neuraminidase and O-glycosidase results in a decrease in the apparent molecular weight of the envelope glycoprotein. This result was observed in both vaccinia virus recombinant-derived envelope glycoproteins and glycoproteins derived from the IIIB, SG3, and HXB2, strains of HIV-1. The decrease in molecular weight was also observed when the envelope glycoprotein had been deglycosylated with N-glycanase F after treatment with neuraminidase and O-glycosidase, indicating that the decrease in apparent molecular weight was not attributable to the removal of N-linked carbohydrate. Treatment with neuraminidase, O-glycosidase, and N-glycanase F was found to be necessary to remove all radiolabel from [3H]glucosamine-labelled envelope glycoprotein, a result seen for both recombinant and HIV-1-derived envelope glycoprotein. [3H]glucosamine-labelled carbohydrates liberated by O-glycosidase treatment were separated by paper chromatography and were found to be of a size consistent with O-linked oligosaccharides. We, therefore, conclude that the HIV-1 envelope glycoprotein is modified by the addition of O-linked carbohydrates.


Clinical, immunological, molecular and therapeutic findings in monogenic immune dysregulation diseases: Middle East and North Africa registry.
Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD.


Current strategies in the discovery of small-molecule biomarkers for Alzheimer's disease.
With the number of patients suffering from Alzheimer's disease rapidly increasing, there is a major requirement for an accurate biomarker capable of diagnosing the disease early. Much of the research is focused on protein and genetic approaches; however, small molecules may provide viable marker molecules. Examples that support this approach include known abnormalities in lipid metabolism, glucose utilization and oxidative stress, which have been demonstrated in patients suffering from the disease. Therefore, by-products of this irregular metabolism may provide accurate biomarkers. In this review we present the current approaches previously published in the literature used to investigate potential small-molecule and metabolite markers, and report their findings. A wide range of techniques are discussed, including separation approaches (LC, GC and CE), magnetic resonance technologies (NMR and magnetic resonance spectroscopy), and immunoassays.


Structural Analysis and Spatiotemporal Expression of Atxn1 Genes in Zebrafish Embryos and Larvae.
Zebrafish have come into focus to model cerebellar diseases such as spinocerebellar ataxias (SCAs), which is caused by an expansion of translated CAG repeats in several unrelated genes. In spinocerebellar ataxia type 1 (SCA1), gain-of-function in the mutant ATXN1 contributes to SCA1's neuropathy. Human ATXN1 and its paralog ATXN1L are chromatin-binding factors, act as transcriptional repressors, and have similar expression patterns. However, little is known about atxn1 genes in zebrafish. Recently, two family members, atxn1a and atxn1b, were identified as duplicate orthologs of ATXN1, as was atxn1l, the ortholog of ATXN1L. In this study, we analyzed the phylogenetic relationship of the atxn1 family members in zebrafish, compared their genetic structures, and verified the predicted transcripts by both RT-PCR and whole-mount in situ hybridization. All three genes, atxn1a, atxn1b, and atxn1l, show overlapping, but also distinct, expression domains during embryonic and larval development. While atxn1a and atxn1l display similar spatiotemporal embryonic expression, atxn1b expression is initiated during the onset of brain development and is predominantly expressed in the cerebellum throughout zebrafish development. These results provide new insights into atxn1 genes and their expression patterns in zebrafish during embryonic and late-larval development and may contribute importantly to future experiments in disease modeling of SCAs.


Gene ytkD of Bacillus subtilis encodes an atypical nucleoside triphosphatase member of the Nudix hydrolase superfamily.
Gene ytkD of Bacillus subtilis, a member of the Nudix hydrolase superfamily, has been cloned and expressed in Escherichia coli. The purified protein has been characterized as a nucleoside triphosphatase active on all of the canonical ribo- and deoxyribonucleoside triphosphates. Whereas all other nucleoside triphosphatase members of the superfamily release inorganic pyrophosphate and the cognate nucleoside monophosphate, YtkD hydrolyses nucleoside triphosphates in a stepwise fashion through the diphosphate to the monophosphate, releasing two molecules of inorganic orthophosphate. Contrary to a previous report, our enzymological and genetic studies indicate that ytkD is not an orthologue of E. coli mutT.


Dopamine D3 receptor ligands modulate the acquisition of morphine-conditioned place preference.
The dopamine D3 receptor has been shown to mediate conditioned effects of psychostimulants such as cocaine. The present work was aimed at determining whether drugs acting at D3 receptors alter acquisition of conditioned effects of opiates. We have used the conditioned place preference (CPP) in mice, which permits the measurement of approach behaviour to environmental stimuli previously paired with drug effects. To assess the interaction of morphine and D3 receptor ligands during acquisition of CPP, we have used a particular procedure, in which the animals were given the choice between compartments associated with either morphine alone or the combination of morphine with the tested agent. D3 receptor agonists (7-OH-DPAT, quinelorane, BP 897) did not induce, alone, a significant CPP but, all of them, at the doses tested, and notably BP 897, a highly selective partial agonist, significantly enhanced acquisition of morphine-induced CPP when administered together with morphine at each conditioning session. PNU-99194A, a D3 receptor-preferring antagonist, induced a CPP itself at the dose of 10 mg/kg but not at 5 or 15 mg/kg and impaired significantly at 10 and 15 mg/kg the morphine-induced CPP. In contrast, BP 897 did not alter morphine-induced analgesia, an unconditioned effect of this drug. These results suggest the stimulation of D3 receptors has no rewarding effect per se, but may synergize upon opiate-induced dopamine release with stimulation of other dopamine receptor subtypes to enhance approach behaviour to morphine-associated environment.


Procedure for Over-all Lens Evaluation Using OTF Data.
A method is described for making use of large amounts of photoelectric test data, recorded in the form of OTF curves and filed in computer-accessible form, to evaluate image quality over the field in an arbitrary image plane or to locate an optimum image plane by computer processing of the recorded data. Merit parameters such as the OTF, the predicted photographic resolution, the Strehl criterion, and others, are obtained as over-the-field averages, with arbitrary weighting of information from different parts of the field, and also may be reported from individual field points, in various ways. The method has been tested on a wide-angle aerial photographic objective, and example results for this lens are given. Assessment of the possible utility of such a procedure is based on discussion of the practical feasibility of acquiring large amounts of test data by automated instruments, on the computer requirements and processor time needed, and examples of the variety of evaluation tasks that may be performed, with relative ease once the imagery has been mapped throughout the image space. It is concluded that the method does offer possibilities for practical use and may be a desirable way to utilize directly OTF-type test information, in mass, to facilitate decision making in respect to design, fabrication quality, or individual performance of an actual prototype or production lens.


A case of dental hamartoma associated with unerupted primary canine in maxillary region.
Odontomas are usually one of the most common odontogenic tumors of the jaw and are perhaps more accurately defined as a hamartoma than a true neoplasm. It is asymptomatic, nonaggressive, slow growing, and benign nature. They are considered to be the malformations of the dental tissue and can sometimes interfere with the eruption of the associated tooth leading to its impaction or delayed eruption. Complex odontomas in primary teeth are rare and unusually diagnosed before the second decade of life. This article aims to present the case of a child with complex odontoma and its effective treatment planning. The results indicate that early diagnosis and proper treatment planning can ensure a better prognosis and can prevent later craniofacial complications and other developmental problems.


'The dots just don't join up': Understanding the support needs of families of children on the autism spectrum.
Much research has documented the elevated levels of stress experienced by families of autistic children. Yet remarkably little research has examined the types of support that these families perceive to be beneficial to their lives. This study, co-produced by researchers and school-based professionals, sought to establish these families' support needs from their own perspectives. In total, 139 parents of autistic children with additional intellectual disabilities and limited spoken communication, all attending an inner-city London school, participated in an initial survey examining parental wellbeing, self-efficacy and the extent to which they felt supported. Semi-structured interviews were conducted with a subgroup of parents ( n = 17), some of whom reported in the survey that they felt unsupported, in order to gain their in-depth perspectives. The results from both the survey and the interviews suggested that existing support (particularly from formal support services) was not meeting parents' needs, which ultimately made them feel isolated and alienated. Parents who were interviewed called for service provision that adopted a relational, family-centred approach - one that understands the specific needs of the whole family, builds a close working relationship with them and ensures that they are supported at times when the parents and families feel they need it most.


A connected cytoskeleton network generates axonal tension in embryonic Drosophila.
Axons of neurons are contractile, i.e., they actively maintain a rest tension. However, the spatial origin of this contractility along the axon and the role of the cytoskeleton in generating tension and sustaining rigidity are unknown. Here, using a microfluidic platform, we exposed a small segment of the axons of embryonic Drosophila motor neurons to specific cytoskeletal disruption drugs. We observed that a local actomyosin disruption led to a total loss in axonal tension, with the stiffness of the axon remaining unchanged. A local disruption of microtubules led to a local reduction in bending stiffness, while tension remained unchanged. These observations demonstrated that contractile forces are generated and transferred along the entire length of the axon in a serial fashion. Thus, a local force disruption results in a collapse of tension of the entire axon. This mechanism potentially provides a pathway for rapid tension regulation to facilitate physiological processes that are influenced by axonal tension.


Ultrastructural identification of monocyte-derived foam cells in fatty streak lesions.
In a previous publication (1) we demonstrated that atherosclerotic lesion development in the aorta of hypercholesterolemic pigs was preceded by intimal penetration by blood-borne mononuclear cells, and that medial smooth muscle cells were not involved in the development of fatty streak lesions in this model. The current study shows that lesions in the aortic arch do not progress beyond the fatty streak stage up to 30 wk on a hypercholesterolemic diet, and that mononuclear cell involvement continues during this period. Mononuclear cells adherent to the endothelium, or in the intima of lesion areas were identified as monocytes by the presence of peroxidase-positive granules (peroxisomes) in their cytoplasm. As well, "modified" intimal monocytes which contained a few lipid droplets and which were phagocytic, also sometimes contained peroxisomes. The results suggest that monocytes which invade the intima before or during lesion development undergo transformation into macrophage foam cells in fatty streak lesions. The absence of medial cell involvement indicates that monocytes are the major foam cell precursor in these lesions.


Sexuality and old age.
Sexuality in older people is a multifaceted field of study. Ageing may offer opportunities for and restrictions on sexuality. Ageing individuals may have increased time for and may wish to explore their sexuality, for example, by considering a same-sex relationship, after a long-term partner dies. However, they may also lack a partner or autonomy. They may develop or have increased symptoms from chronic diseases. Consequent medication may affect their sexual functioning. Their attitudes to sex often change and their capacity for sexual activity may diminish unless they seek help. However, they may lack the confidence to do so and the health professionals consulted may be disinclined or ill-equipped to assist them. They may have concerns regarding how their sexuality or their sexual orientation would be perceived should they require residential care or start to lose their memory. We consider the recent work relating to this broad range of influences on sexuality in old age and conclude that, whilst the challenge for researchers is to accurately clarify the impact of individual factors on sexuality and identify helpful potential interventions, increased academic and educational focus on this area is enhancing the prospects for a sexually enjoyable old age.


Analysis of Pena Shokeir phenotype.
At this point in time, we recognize that "Pena Shokeir" is not a diagnosis or a specific syndrome but rather a description of a phenotype produced by fetal akinesia or decreased in utero movement. In its "full blown" form, it is characterized by polyhydramnios, intrauterine growth retardation, pulmonary hypoplasia, craniofacial and limb anomalies, congenital contractures, short umbilical cord, and lethality. From the cases thus far reported, we would anticipate that the phenotype is present in a very heterogeneous group of disorders--heterogeneous both with regard to the specific anomalies present and with regard to the causes (which must include many environmental agents and multiple genetic forms). One challenge for the future is to better describe and delineate specific entities. In the meantime, we would do well to use the terms "Pena Shokeir phenotype" or "fetal akinesia/hypokinesia sequence," which do not imply a single entity. There are many practical aspects of recognizing this phenotype. The presence of any one of the cardinal signs of the fetal akinesia/hypokinesia sequence should alert the physician to look for the other associated anomalies, since specific treatment may be indicated, and catch-up or compensatory growth may occur, if given a chance. The ability to provide prenatal diagnosis and perhaps prenatal treatment in the future may allow us to alter dramatically the natural history of some cases. In others, we need to establish when treatment is possible and when it gives no benefit. Perhaps the most important insight gained from the study of the fetal akinesia sequence is the reaffirmation of the concept that function is an integral part of normal development. Specific structures do not develop in isolation but are part of a carefully timed and integrated system. The "use" of a structure in utero is necessary for its continuing and normal development. The old adage "use it or lose it" seems to apply just as appropriately to prenatal normal development as it does in the crusty adult world of politics, business, and academia.


Temperature Shift Between Vineyards Modulates Berry Phenology and Primary Metabolism in a Varietal Collection of Wine Grapevine.
Global climate change and the expected increase in temperature are altering the relationship between geography and grapevine (V. vinifera) varietal performance, and the implications of which are yet to be fully understood. We investigated berry phenology and biochemistry of 30 cultivars, 20 red and 10 white, across three seasons (2017-2019) in response to a consistent average temperature difference of 1.5°C during the growing season between two experimental sites. The experiments were conducted at Ramat Negev (RN) and Ramon (MR) vineyards, located in the Negev desert, Israel. A significant interaction between vineyard location, season, and variety affected phenology and berry indices. The warmer RN site was generally associated with an advanced phenological course for the white cultivars, which reached harvest up to 2 weeks earlier than at the MR site. The white cultivars also showed stronger correlation between non-consecutive phenological stages than did the red ones. In contrast, harvest time of red cultivars considerably varied according to seasons and sites. Warmer conditions extended fruit developmental phases, causing berry shriveling and cluster collapse in a few cultivars such as Pinot Noir, Ruby Cabernet, and Tempranillo. Analyses of organic acid content suggested differences between red and white cultivars in the content of malate, tartrate, and citrate in response to the temperature difference between sites. However, generally, cultivars at lower temperatures exhibited lower concentrations of pulp organic acids at véraison, but acid degradation until harvest was reduced, compared to the significant pace of acid decline at the warmer site. Sugars showed the greatest differences between sites in both white and red berries at véraison, but differences were seasonal dependent. At harvest, cultivars of both groups exhibited significant variation in hexose/sucrose ratio, and the averages of which varied from 1.6 to 2.9. Hexose/sucrose ratio was significantly higher among the red cultivars at the warmer RN, while this tendency was very slight among white cultivars. White cultivars seem to harbor a considerable degree of resilience due to a combination of earlier and shorter ripening phase, which avoids most of the summer heat. Taken together, our study demonstrates that the extensive genetic capacity of V. vinifera bears significant potential and plasticity to withstand the temperature increase associated with climate change.


Alterations at the cross-bridge level are associated with a paradoxical gain of muscle function in vivo in a mouse model of nemaline myopathy.
Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosin slow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8-9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occurring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo.


Multifunctional quaternized carbon dots with enhanced biofilm penetration and eradication efficiencies.
Biofilm formation can lead to the treatment failure of persistent bacterial infections. Although a variety of antibacterial agents have been developed, the restricted drug penetration and the embedded bacteria's potentiated recalcitrance to these agents synergistically lead to the unsatisfactory anti-biofilm effect. Herein, we report the applications of metal-free quaternized carbon dots (CDs) in imaging and eliminating bacterial biofilms. The CDs prepared by the solvothermal treatment of dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (abbreviated as Si-QAC) and glycerol possess ultrasmall size (ca. 3.3 ± 0.4 nm) and strong positively charged (zeta potential: ca. +33.1 ± 2.5 mV) surfaces with long alkyl chain-linked quaternary ammonium groups. The small size of the CDs endows them with the penetration ability into the interior of Gram-negative and Gram-positive bacterial biofilms, which enables excellent fluorescence imaging of the biofilms. Due to the different surfaces of the two types of bacteria, the positively charged CDs selectively interact with the more negatively charged Gram-positive bacteria via electrostatic and hydrophobic interactions, which inactivates the Gram-positive bacteria and ultimately eradicates the Gram-positive bacterial biofilms. In addition, we synthesize a new type of quaternized CDs without long alkyl chains (termed TTPAC CDs), and validate that the long alkyl chains potentiate the hydrophobic adhesion between CDs and Gram-positive bacteria. Meanwhile, the crystal violet staining results reveal that the cationic CDs inhibit the formation of Gram-positive bacterial biofilms. Collectively, our work highlights the feasibility of using cationic and ultrasmall metal-free CDs to eliminate and inhibit Gram-positive bacterial biofilms, which represents a highly effective strategy to cope with refractory biofilm-associated infections.


[Neuronal reactions of the accessory olfactory bulb in the frog, Rana temporaria, to chemical stimulation of the vomeronasal organ].
Studies have been made on the reactions of 34 neurones from the accessory olfactory bulb of the frog Rana temporaria to stimulation of the receptors in the vomeronasal organ by amino acids (L-alanine, L-aspartic acid, L-valine, L-glytamic acid, glycine, L-proline, L-serine), carboxylic acids (acetic, glutaric, isovaleric, propionic and succinic acids) at a concentration 10(-4) M, as well as by "rinsing" the frog's skin. The general pattern of the background and evoked activities in the neurones of the accessory and main olfactory bulbs is similar. Neurones of the accessory bulb exhibited selective responses to all the amino acids at a concentration 10(-4) M, in which they are effective for stimulation the olfactory receptors of bony fishes. This finding indicates the adequate nature of the stimulation used for receptors of the vomeronasal organ, as well as underlies functional similarity of these receptors in the frog with the olfactory receptors of fishes.


Survival in experimental Candida albicans infections depends on inoculum growth conditions as well as animal host.
Evidence is presented that the growth medium used to prepare a Candida albicans challenge inoculum is a significant factor determining the ability of a fungus strain to gain an initial invasive hold immediately after injection into an animal host, and thus determining gross strain lethality. Three C. albicans strains, one known to be attenuated in virulence, were grown in two broth media and injected intravenously at different doses into female NMRI mice and male albino guinea pigs. For each fungus strain and challenge dose, survival was longer from inocula grown in a diluted, buffered peptone-based broth than from inocula grown in Sabouraud glucose broth. When animals were challenged intravenously with yeast doses adjusted to give the same mean survival time regardless of strain or growth medium, the progression of fungus tissue burdens (c. f.u. g(-1)) in kidneys, lungs, liver, spleen and brain samples was broadly similar for all three C. albicans strains but differed between the two animal hosts. The morphological form of C. albicans recovered from infected tissues differed at the level of both the fungus strain and the host tissue. Use of survival-standardized inocula provides a means of distinguishing differences in progression of experimental disseminated Candida infections that are related to the infecting strain from those related to the animal host.


Establishing guidelines for executing and reporting Internet intervention research.
The field of Internet interventions is growing rapidly. New programs are continually being developed to facilitate health and mental health promotion, disease and emotional distress prevention, risk factor management, treatment, and relapse prevention. However, a clear definition of Internet interventions, guidelines for research, and evidence of effectiveness have been slower to follow. This article focuses on the quality standardization of research on Internet-delivered psychological and behavioural interventions. Although the science underpinning Internet interventions is just starting to be established, across research studies there are often conceptual and methodological difficulties. The authors argue that this situation is due to the lack of universally accepted operational guidelines and evaluation methods. Following a critical appraisal of existing codes of conduct and guidelines for Internet-assisted psychological and health interventions, the authors developed a framework of guidelines for Internet intervention research utilizing aspects of facet theory (Guttman & Greenbaum, 1998). The framework of facets, elements, and guidelines of best practice in reporting Internet intervention research was then sent to several leading researchers in the field for their comment and input, so that a consensus framework could be agreed on. The authors outline 12 key facets to be considered when evaluating and reporting Internet intervention studies. Each facet consists of a range of recommended elements, designed as the minimum features for reporting Internet intervention studies. The authors propose that this framework be utilized when designing and reporting Internet intervention research, so results across studies can be replicated, extended, compared, and contrasted with greater ease and clarity.


Effect of axial groove and resin luting cements on the retention of complete cast metal crowns.
The design of the tooth preparation and the cementing medium are important consid-erations in the retention of crowns and fixed partial dentures. The purpose of this invitro study was to determine the effect of axial groove on the retention of complete cast metal crowns using two resin luting cements. Forty freshly extracted intact human molar teeth were prepared in their long axis to receive complete cast metal crowns. The specimens were randomly divided into two groups (one control and one study group). An axial groove of uniform size and shape was made on the prepared teeth under the study group. Axial surface area of prepared teeth specimens was measured. Complete cast metal crowns were fabricated for each specimen. Specimens of each group were divided into subgroups of 10 samples and were cemented with two resin luting cements, RelyX Unicem® and Calibra®, re-spectively. The cemented crowns were loaded in tension using a Universal Instron testing machine. The maximal tensile strength was recorded. Data were compared using the Mann-Whitney U test (α=0.05). NO SIGNIFICANT DIFFERENCES IN THE TENSILE STRESS VALUES WERE NOTED BETWEEN THE CONTROL (MEAN: 5.76±0.392 MPa) and study (mean: 5.93±0.751 MPa) groups cemented with RelyX Unicem. No significant differences in the tensile stress values were noted between the control (mean: 4.92±0.641 MPa) and study (mean: 5.15 ±0.478 MPa) groups cemented with Calibra. However, significant dif-ference in the tensile stress values was found between the two resin cements in the control and study groups. Axial groove placed in tooth preparations for resin bonded complete cast metal crowns had no statistically significant effect on retention. The use of (RelyX Unicem®) yielded greater retention values when compared to Calibra®.


A comparative study of phenoloxidase activity in diseased and bleached colonies of the coral Acropora millepora.
In scleractinian (hard) corals, immune responses involving phenoloxidase (PO) activity are known to play a role in coral wound healing, but there have been no studies investigating their roles in mitigating either disease or bleaching in an Indo-Pacific coral. PO activity induces the release of reactive oxygen species leading to a cytotoxic cellular environment, which enhances resistance against pathogens, but is also likely to compound oxidative stress induced during bleaching. Antioxidants such as melanin, whose synthesis is activated by PO activity, and peroxidase are potentially important for mitigating the effects of oxidative stress. Therefore, PO activity was investigated in healthy and diseased colonies of Acropora millepora. PO activity levels were compared among tissues bordering white syndrome lesions (WS) and at two locations (mid and outer) at increasing distances from lesions. Equivalent locations were sampled for PO activity on visibly healthy colonies. Additionally, PO and peroxidase activity were compared between severely bleached and healthy colonies of A. millepora. Overall, PO activity of diseased colonies was significantly lower than that of healthy colonies, but with relatively higher activity at the WS lesion border. Severely bleached colonies had significantly lower PO activity than healthy colonies, and peroxidase was also lower, but not significantly. Lower PO activity in unhealthy colonies supports earlier suggestions that lower immune activity leads to increased susceptibility to disease and bleaching. Additionally, low enzyme activity levels may indicate a depletion of colony resources. Increased PO activity at lesion borders in diseased colonies confirms the relative up-regulation of a key coral immune defense in response to WS in A. millepora.


Activator-induced spread of poly(ADP-ribose) polymerase promotes nucleosome loss at Hsp70.
Eukaryotic cells possess many transcriptionally regulated mechanisms to alleviate the nucleosome barrier. Dramatic changes to the chromatin structure of Drosophila melanogaster Hsp70 gene loci are dependent on the transcriptional activator, heat shock factor (HSF), and poly(ADP-ribose) polymerase (PARP). Here, we find that PARP is associated with the 5' end of Hsp70, and its enzymatic activity is rapidly induced by heat shock. This activation causes PARP to redistribute throughout Hsp70 loci and Poly(ADP-ribose) to concurrently accumulate in the wake of PARP's spread. HSF is necessary for both the activation of PARP's enzymatic activity and its redistribution. Upon heat shock, HSF triggers these PARP activities mechanistically by directing Tip60 acetylation of histone H2A lysine 5 at the 5' end of Hsp70, where inactive PARP resides before heat shock. This acetylation is critical for the activation and spread of PARP as well as for the rapid nucleosome loss over the Hsp70 loci.


MRI in unexplained mononeuropathy.
Four young patients with severe unexplained progressive mononeuropathy are described. None had a history of known trauma to the affected limb. In addition to the standard neurologic examination and electrophysiologic studies (nerve conduction studies and electromyography), all underwent neuroimaging of the involved extremity. In three patients, magnetic resonance imaging revealed intrinsic abnormalities of the appropriate nerve. The pattern or absence of magnetic resonance imaging changes directly influenced decisions about surgical exploration of the nerve in all four patients. With the advent of more sophisticated technology, magnetic resonance neurography has become a potent diagnostic tool in the evaluation of disorders of peripheral nerve and muscle.


Increased susceptibility to gingival colonization by specific HACEK microbes in children with congenital heart disease.
It is well established that infective endocarditis (IE) involving the HACEK (Hemophilus, Actinobacillus, Cardiobacter, Eikenella, Kingella) group of microbes occurs in patients with congenital heart defects (CHD) and in those with prosthetic grafts. Dental caries and gingival disease have been presumed to be the focus of microbial shedding. The purpose of this study was to determine if children with CHD had a more severe gingival inflammatory condition and harbored the HACEK group of microbes to a greater extent than normal children. Two groups of 12 age and sex matched children were selected for this study. The experimental group consisted of twelve children with CHD, 1-1/2 to 8 years of age. The control group consisted of 12 healthy children 2 to 8 years of age. Each child had a gingival index score recorded as described by Massler. Subgingival cultures were obtained. Gingival samples were cultured for HACEK microbes and total Streptococcus (spp) using standard techniques. Fisher's exact test was performed with significance defined at P < 0.05. Children with CHD had more severe gingival inflammatory index than the control group (P < 0.05). 8/12 CHD patient had Actinobacillus actinomycetemcomitans (A.a.) as compared with 2/12 controls (P < 0.05). Furthermore, all cyanotic CHD patients (4/4) had A.a. whereas, only 2/12 controls did (P < 0.05). 4/12 CHD patients harbored Eikenella corrodens (E.c.) compared to 1/12 controls (N.S.). There was no significant difference in colonization with E.c. or A.a. between cyanotic and acyanotic patients. No significant difference in total Streptococcus (spp) was found between the two groups. This study suggests that children with CHD have a more severe gingival inflammatory index and are colonized with specific HACEK microbes more so than normal children.


Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy.
Cisplatin is commonly used in ovarian cancer treatment by inducing apoptosis in cancer cells as a result of lethal DNA damage. However, the intrinsic and acquired resistance to cisplatin in cancer cells remains a big challenge for improving overall survival. The cyto-protective functions of autophagy in cancer cells have been suggested as a potential mechanism for chemoresistance. Here, we reported MIR152 as a new autophagy-regulating miRNA that plays a role in cisplatin-resistance. We showed that MIR152 expression was dramatically downregulated in the cisplatin-resistant cell lines A2780/CP70, SKOV3/DDP compared with their respective parental cells, and in ovarian cancer tissues associated with cisplatin-resistance. Overexpression of MIR152 sensitized cisplatin-resistant ovarian cancer cells by reducing cisplatin-induced autophagy, enhancing cisplatin-induced apoptosis and inhibition of cell proliferation. A mouse subcutaneous xenograft tumor model using A2780/CP70 cells with overexpressing MIR152 was established and displayed decreased tumor growth in response to cisplatin. We also identified that ATG14 is a functional target of MIR152 in regulating autophagy inhibition. Furthermore, we found that EGR1 (early growth response 1) regulated the MIR152 gene at the transcriptional level. Ectopic expression of EGR1 enhanced efficacy of chemotherapy in A2780/CP70 cells. More importantly, these findings were relevant to clinical cases. Both EGR1 and MIR152 expression levels were significantly lower in ovarian cancer tissues with high levels of ERCC1 (excision repair cross-complementation group 1), a marker for cisplatin-resistance. Collectively, these data provide insights into novel mechanisms for acquired cisplatin-resistance. Activation of EGR1 and MIR152 may be a useful therapeutic strategy to overcome cisplatin-resistance by preventing cyto-protective autophagy in ovarian cancer.


Chronic lead exposure effects in the cynomolgus monkey (Macaca fascicularis) testis.
Although reproductive consequences of high circulating blood lead levels (> or = 60 micrograms/dL) have been reported, potential adverse effects of chronic lead exposure in males that result in low to moderate blood lead levels (10-25 and 26-60 micrograms/dL, respectively) are unknown. Effects of chronic lead exposure to testis ultrastructure were determined in the cynomolgus monkey after oral administration of lead acetate (1500 micrograms/kg BW/day) in a vehicle in the following groups: from birth to 10 years (lifetime), postnatal day 300 to 10 years (postinfancy), and postnatal day 0-400 (infancy); monkeys in the control group received only the vehicle (95% glycerol and 5% distilled water). At age 10 years, circulating lead concentrations in lifetime and postinfancy-dosed monkeys were approximately 35 micrograms/dL, and in control and infancy animals the concentrations were < 1.0 microgram/dL. Sertoli and spermatogenic cells of dosed monkeys from the infancy and lifetime groups revealed injuries. Chronic exposure to lead that results in moderate blood lead concentrations induced persistent ultrastructural alterations in the cynomolgus monkey testis. Results of this study on the primate, following extrapolation to humans, could influence further refining of the impact of environmental lead contamination concentrations vis-à-vis the health of children, adults, and aged human beings.


Molecular weight distribution of soluble fiber fractions and short chain fatty acids in ileal digesta of growing pigs.
The effect of dietary fiber source on molecular weight (MW) distribution of soluble fiber fractions and short chain fatty acids (SCFA) in ileal digesta of 7 post valve T-cecum (PVTC) cannulated growing pigs was studied. Pigs were fed semisynthetic diets with sugar beet (Beta vulgaris) pulp (SBP) or chicory (Cichorium intybus) forage (CFO) as fiber sources of which the soluble nonstarch polysaccharide (NSP) fraction originated mainly from pectin. Three MW intervals were selected-large MW (MWL): 10,000,000 to 1,000,000 g/mol, medium MW (MWM): 1,000,000 to 200,000 g/mol, and small MW (MWS): 200,000 to 10,000 g/mol-and the relative distribution (% of total) of molecules in each interval was calculated. The MWM fraction was higher (P < 0.05) in ileal digesta of pigs fed diet SBP and the MWS fraction was higher (P < 0.05) in ileal digesta of pigs fed diet CFO. The mole/100 mole of propionic acid (HPr) was higher (P < 0.010) in pigs fed diet SBP whereas pigs fed diet CFO had higher (P < 0.010) mole/100 mole of acetic acid (HAc). The proportion of the MWL and MWM fractions in ileal digesta were negatively correlated to HAc (r = -0.52, P = 0.05, and r = -0.62, P = 0.02, respectively). The proportion of MWM in ileal digesta was positively correlated to HPr (r = 0.83; P = 0.001) whereas MWS and HPr were negatively correlated (r = -0.76; P = 0.002). In conclusion, the bacterial degradation of the soluble NSP fraction is selective and MW distribution may explain differences in SCFA production.


Identification of the TyrOH•+ Radical Cation in the Flavoenzyme TrmFO.
Tyrosine (TyrOH) and tryptophan radicals play important roles as intermediates in biochemical charge-transfer reactions. Tryptophanyl radicals have been observed both in their protonated cation form and in their unprotonated neutral form, but to date, tyrosyl radicals have only been observed in their unprotonated form. With a genetically modified form of the flavoenzyme TrmFO as a suitable model system and using ultrafast fluorescence and absorption spectroscopy, we characterize its protonated precursor TyrOH•+, and we show this species to have a distinct visible absorption band and a transition moment that we suggest to lie close to the phenol symmetry axis. TyrOH•+ is formed in ∼1 ps by electron transfer to excited flavin and decays in ∼3 ps by charge recombination. These findings imply that TyrOH oxidation does not necessarily induce its concerted deprotonation. Our results will allow disentangling of photoproduct states in flavoproteins in often-encountered complex situations and more generally are important for understanding redox chains relying on tyrosyl intermediates.


Mirfentanil: pharmacological profile of a novel fentanyl derivative with opioid and nonopioid effects.
Mirfentanil [N-(2-pyrazinyl)-N-(1-phenethyl-4-piperidinyl)-2-furamide] was studied for its binding affinity in isolated neuronal membranes, and for its effects in vivo. In binding to opioid receptors in monkey brain membranes, mirfentanil was much more selective for mu sites (7.99 nM) than for either kappa (1428 nM) or delta (480 nM) sites as measured by displacement of [3H]DAMGO. [3H]U-69.593 or [3H]DPDPE, respectively. In morphine-treated pigeons discriminating among naltrexone, saline and morphine, mirfentanil failed to substitute for either training drug; in morphine-abstinent pigeons, mirfentanil reversed responding on the naltrexone key (i.e., reversed withdrawal). In morphine-treated monkeys discriminating between saline and naltrexone, mirfentanil substituted completely for naltrexone, and this effect was attenuated by an acute injection of morphine; mirfentanil also attenuated the withdrawal-reversing effects of alfentanil in morphine-abstinent monkeys. Administered i.v., mirfentanil maintained rates of self-administration responding only slightly below rates maintained by alfentanil, and this effect of mirfentanil was antagonized by quadazocine. Small doses of mirfentanil (0.032-0.32 mg/kg) antagonized the analgesic effects of alfentanil; larger doses of mirfentanil both antagonized the analgesic effects of alfentanil and produced analgesic effects when administered alone. The analgesic effects of mirfentanil were not attenuated by large doses of opioid antagonists. Mirfentanil had modest respiratory depressant effects that were not altered by quadazocine; however, mirfentanil antagonized the respiratory depressant effects of large doses of alfentanil. Both in vivo and in vitro, mirfentanil appears to have selectivity for opioid mu receptors. Moreover, at doses larger than those which exert opioid effects, mirfentanil has nonopioid analgesic effects.(ABSTRACT TRUNCATED AT 250 WORDS)


Poor nutrition on the menu: children's meals at America's top chain restaurants.
We evaluated the nutritional quality of children's meals at chain restaurants, because children obtain about a third of their daily calories from away-from-home foods and studies show that restaurant foods are often higher in calories and lower in nutritional value than foods prepared at home. We assessed the nutritional quality of children's meals at the 50 largest U.S. restaurant chains by visiting each chain's web site or calling the company. Eighteen of the chains did not have children's meals and 10 did not provide adequate nutrition information to be included in the study. The nutritional quality of each meal combination was evaluated against a set of nutrition standards based on key nutrition recommendations in the Dietary Guidelines for Americans. Of the 22 restaurants that had children's menus and available nutrition information, 99% of 1662 children's meal combinations were of poor nutritional quality. Restaurants should support healthier choices for children by reformulating existing menu items and adding new healthier items, posting calories on menus, and setting nutrition standards for marketing to children.


Phenotypes and genetic architecture of focal primary torsion dystonia.
The focal primary torsion dystonias (FPTDs) form a group of clinical heterogeneous syndromes and can be considered a genetic complex disease; it is thought to be primed by genetic variants with variable impact and triggered by non-genetic factors. Thorough clinical description of FPTDs cohorts is sparse but essential for further progress in genetic research. To establish suggested relations between age at onset (AaO), site and family history in a large focal dystonias cohort and gain more insight into familial clustering for genetic research. A prospective cohort study between March 2008 and March 2011, including 676 FPTD patients attending the botulinum toxin outpatient clinics of six Dutch movement disorder centres. Of all of the FPTD patients, 25% had a familial predisposition; in 2.4% a Mendelian inheritance pattern was noted. With a stronger family history, a significantly lower AaO was seen in all focal dystonias. In both the sporadic and familial focal dystonia groups, AaO had an effect on the distribution of dystonia, with a caudal to cranial tendency. In all focal dystonia forms, women were more frequently affected, except for writer's cramp. Careful clinical characterisation will allow the formation of phenotype subgroups. We suggest that genetic research into FPTDs will benefit from this approach and discuss genetic research strategies to decipher the complex background of focal dystonias.


Accuracy of computed tomography perfusion in detecting delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage: a meta-analysis.
In recent years, significant literature shows that computed tomography perfusion (CTP) can provide sufficient information on cerebral hemodynamics and effectively indicate delayed cerebral ischemia (DCI) before the development of infarction. We aimed at performing a meta-analysis to provide a more full and accurate evaluation of CTP and CTP parameters in detecting DCI in patients with aneurysmal subarachnoid hemorrhage. We searched the PubMed, MedLine, Embase and Cochrane databases for analysis published from February 2005 to February 2013. We extracted CTP parameters, including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), interhemispheric ratios for CBV and CBF and interhemispheric differences for MTT and TTP. Pooled estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the summary receiver-operating characteristic curve were determined. Four research studies are met the inclusion criteria for the analysis. The pooled sensitivity, specificity, PLR, NLR and DOR of CTP for detecting the DCI were 82%, 82%, 4.56, 0.22 and 20.96, respectively. Through the evaluation of absolute CTP parameters, CBF and MTT showed diagnostic value for DCI, but CBF and TTP did not. Moreover, CBF ratio, MTT difference and TTP difference showed more diagnostic value than CBV ratio in DCI detection by the assessment of relative CTP parameters. As a non-invasive and short time consuming screening method, CTP own a high diagnostic value for the detection of DCI after aneurysm rupture.


Fracture Mechanism of Nanocomposite of Metal and Graphene with Defect Pores.
Molecular dynamics simulations were performed to investigate the fracture mechanism and mechanical response of Ni/Graphene nanocomposites under nanoindentation. The effects of size and location of defect pores were explored by examining the pore structure transition, microstructure transition, variation of HCP atomic fraction and dislocation density with indentation depth, load-displacement relationship, and stress distribution. It was found that when the long edges of the pore are located along the longer dimension, the pores are fractured by indentation forces from the short edges. The closer the pore is to the indent, the smaller loading force is required for the pores to reach its fracture limit. For the long edges located along the transverse direction, the maximum indentation depth increases with the distance of the pore away from the indenter. The density of HCP atoms and dislocations in the composite gradually increases with the indentation depth. To understand the physical mechanism of the fracture behavior, we also evaluated the stress distribution in graphene at the fracture point.


Human papillomavirus-type distribution in women with and without cervical neoplasia in north India.
Our objective was to determine the human papillomavirus (HPV)-type prevalence in cervical samples in women with and without cervical neoplasia in an opportunistic hospital-based cancer-screening program. A cross-sectional study of 524 women presenting from January 2003 through June 2005 with symptoms of persistent vaginal discharge, intermenstrual bleeding, and postcoital bleeding or detected to have an unhealthy cervix underwent HPV genotyping by consensus polymerase chain reaction and reverse line-blot hybridization assay, conventional Pap smear, and colposcopy, with directed biopsy from all lesions detected. The prevalence rates of HPV infection among women with normal, low-grade cervical neoplasia (CIN 1) and high-grade CIN (>CIN2) were found to be 7.6%, 42.3%, and 87.5%, respectively. Seventeen high-risk and 6 low-risk HPV types were identified by the reverse line-blot assay. Multiple infections were seen in 20% of women. In normal women, the 6 commonest types were HPV-16, HPV-89, HPV-39, HPV-52, HPV-62, and HPV-18, whereas in high-grade disease, these were all high-risk types HPV-16, HPV-18, HPV-33, HPV-39, HPV-35, and HPV-56. HPV-16 was the commonest type in all groups, seen in 49.4% cases overall and in 74.3% of high-grade squamous intraepithelial lesion. It was followed by HPV-18 (7.4%) and HPV-33 and HPV-39 (4.9% each). HPV-89 was the commonest low-risk type (9.9%). HPV-16/18 were associated with 34.3% of normal, 45.4% of low-grade and 65.7% of high-grade lesions. A wide spectrum of HPV types is seen in north Indian women, with the majority being HPV-16 in all grades of histology. A vaccine against HPV-16 and HPV-18 could prevent two thirds of cases of high-grade cervical neoplasia.


Learned states of preparatory attentional control.
Individuals regularly experience fluctuations in the ability to perform cognitive operations. Although previous research has focused on predicting cognitive flexibility from persistent individual traits, as well as from spontaneous fluctuations in neural activity, the role of learning in shaping preparatory attentional control remains poorly understood. Across 3 experiments, we manipulated the statistical regularities of an attentional orienting paradigm to examine whether individuals modulated attentional flexibility, the readiness to perform a spatial shift of attention, across learned contexts. We found evidence of learning-based modulations in preparatory attentional control settings when the probability of shifting the focus of attention differed based on temporally or color-defined contexts. Furthermore, in the case of color-defined contexts, these modulations in preparatory control persisted even after a change in the underlying statistical properties. Our results indicate that dynamic adjustments in preparatory attentional control are sensitive to the underlying statistical regularities of an environment. This finding has implications for understanding disordered patterns of attentional control and how these patterns might be modified with training.


Structural characterization of VapB46 antitoxin from Mycobacterium tuberculosis: insights into VapB46-DNA binding.
The ability to form persister cells by Mycobacterium tuberculosis (Mtb) is a prime cause for the emergence of drug-resistant strains. A large number of toxin-antitoxin systems in the Mtb genome are postulated to promote bacterial persistence. The largest family of toxin-antitoxin systems encoded in the genome of Mtb is VapBC, with 47 VapBC toxin-antitoxin systems regulated by VapB antitoxins. In this study, we characterized the structure of VapB46 antitoxin and determined its interaction with its cognate DNA sequence. Using electrophoretic mobility shift assay and DNase I footprinting we showed that VapB46 binds to two sites in the upstream promoter-operator region. Using nuclear magnetic resonance (NMR)-based structural studies we found that VapB46 has a well-folded dimeric N-terminal domain, which contains a Phd/YefM motif and is involved in DNA binding. The remaining C-terminal residues are disordered but promote higher order oligomerization of VapB46. We propose a DNA-binding model in which tetrameric VapB46 binds to the two sites in its promoter-operator region, with each site bound by its dimeric N-terminal domain.


Essential role of STAT3 in the control of the acute-phase response as revealed by inducible gene inactivation [correction of activation] in the liver.
We generated mice carrying a STAT3 allele amenable to Cre-mediated deletion and intercrossed them with Mx-Cre transgenic mice, in which the expression of Cre recombinase can be induced by type I interferon. Interferon-induced deletion of STAT3 occurred very efficiently (more than 90%) in the liver and slightly less efficiently (about 70%) in the bone marrow. Analysis of the induction of liver acute-phase genes in response to bacterial lipopolysaccharide unequivocally identifies STAT3 as a fundamental mediator of their induction. The different degrees of defectiveness displayed by the various genes allowed us to differentiate them into three separate groups according to their degree of dependence on STAT3. Induction was totally defective for group I genes, defective at 24 h but almost normal at earlier time points for group II genes, and only slightly defective for group III genes. This division was in good agreement with the known structures of the respective promoters. We also found that the overall induction of the transcription factors C/EBP beta and -delta was only minimally defective in the absence of STAT3. Finally, even though corticosterone levels and action were found to be normal in the conditional-mutant mice, production of both proinflammatory and antiinflammatory cytokines was increased and prolonged, probably as a result of STAT3 deletion in macrophages.


The effect of C-terminal amidation on the efficacy and selectivity of antimicrobial and anticancer peptides.
Cationic defence peptides show high therapeutic potential as antimicrobial and anticancer agents. Some of these peptides carry a C-terminal amide moiety which has been shown to be required for antimicrobial activity. However, whether this is a general requirement or whether C-terminal amidation is required for the anticancer activity of defence peptides is unclear. In response, this study analyses the toxicity of a series of C-terminally amidated defence peptides and their non-amidated isoforms to normal fibroblast cells, a variety of tumour cells and bacterial cells. The toxicities of these peptides to microbial and cancer cells were generally <200 microM. Peptides were either unaffected by C-terminal amidation or showed up to 10-fold decreases or increases in efficacy. However, these peptides all showed toxicity to normal fibroblast cells with levels (generally <150 microM) that were comparable to those of their antimicrobial and anticancer activities. In contrast to previous claims which have been based on analysis of single amidation events, the results of this study clearly show that the C-terminal amidation of defence peptides has a variable effect on their antimicrobial and anticancer efficacy and no clear effect on their selectivity for these cell types.