Characterization of patients that can continue conservative treatment for adenomyosis.
Historically, hysterectomy has been the radical treatment for adenomyosis. Although, some patients may not want to have their uterus removed, patients often have to no choice but to request hysterectomy during conservative treatment. The factors necessitating these hysterectomies remain unknown. The purpose of this study was to determine which patients can continue conservative treatment for adenomyosis. We selected women diagnosed with adenomyosis and provided with conservative treatment at the Kindai University Hospital and Osaka Red Cross Hospital in Osaka Japan from 2008 to 2017. Age at diagnosis, parity, uterine size, subtype of adenomyosis, type of conservative treatment, and timing of hysterectomy for cases with difficulty continuing conservative treatment were examined retrospectively. A total of 885 patients were diagnosed with adenomyosis, and 124 started conservative treatment. Conservative treatment was continued in 96 patients (77.4%) and hysterectomy was required in 28 patients (22.6%). The cumulative hysterectomy rate was 32.4%, and all women had hysterectomy within 63 months. In the classification tree, 82% (23/28) of women aged 46 years or younger were able to continue conservative treatment when parity was zero or one. In those with parity two and over, 95% (20/21) of those aged 39 years and older had hysterectomy. Patients who continue conservative treatment for approximately 5 years are more likely to have successful preservation of the uterus. Multiparity and higher age at diagnosis are factors that contribute to hysterectomy after conservative treatment. Parity and age at diagnosis may be stratifying factors in future clinical trials of hormone therapy.


Syntheses of 4,6'-epoxymorphinan derivatives and their pharmacologies.
A modification of the message site in the skeleton of naltrexone was carried out to improve the potency and selectivity of the compound for an opioid receptor subtype. In the course of conversion, we synthesized 7-membered ring ether derivatives, which had an inserted OCH(2) group between 4- and 6-positions of morphinan skeleton. One of the 7-membered ring ether derivatives possessed more potent antagonistic activity than naltrexone for the mu opioid receptor. Another compound possessing 17-methyl group derived from noroxycodone may be a mu opioid receptor partial agonist and showed analgesic activity. We are currently examining the subtype selectivity of these compounds.


The effect of food on the pharmacokinetics of oral ivermectin.
Ivermectin is an older anthelminthic agent that is being studied more intensely given its potential for mass drug administration against scabies, malaria and other neglected tropical diseases. Its pharmacokinetics (PK) remain poorly characterized. Furthermore, the majority of PK trials are performed under fasted-state dosing conditions, and the effect of food is therefore not well known. To better plan and design field trials with ivermectin, a model that can account for both conditions would be valuable. To develop a PK model and characterize the food effect with single oral doses of ivermectin. We performed a population-based PK analysis of data pooled from two previous trials of a single dose of 12 mg ivermectin, one with dosing after a high-fat breakfast (n=12) and one with fasted-state dosing (n=3). The final model described concentration-time profiles after fed and fasted dosing accurately, and estimated the food effect associated with relative bioavailability to 1.18 (95% CI 1.10-1.67). In this analysis, the effect of a high-fat breakfast compared with a fasted-state administration of a single oral dose of 12 mg ivermectin was minimal.


Chirped Brillouin dynamic gratings for storing and compressing light.
We demonstrate theoretically that chirped dynamic gratings can be created in optical fibers through stimulated Brillouin scattering with frequency-chirped "signal" and "write" pulses. When the grating is interrogated with a third pulse of the opposite chirp, a compressed signal pulse is retrieved. This provides a method to regenerate stored pulses and enhance signal levels for communications applications.


Effect of Yoga Based Cardiac Rehabilitation on Blood Pressure Variability and Baroreflex Sensitivity: RCT in Patients Post MI.
To assess the effects of 12 weeks Yoga based Cardiac Rehabilitation program on Blood Pressure Variability and Baroreflex Sensitivity in Eighty patients post myocardial infarction. Randomized controlled trial with two parallel groups. A tertiary care institution in India. The Yoga group received 13 hospital-based structured yoga sessions in adjunct to the standard care. Control Group participants received enhanced standard care involving three brief educational sessions on importance of diet and physical activity. Beat to beat arterial pressure variability and baroreflex sensitivity was determined non-invasively. Baseline measurement was done at 3 weeks post Myocardial Infarction. The measurements were repeated at 13th week and at 26th week post MI. There was no significant difference between the groups in time domain indices of SBP variability. At 26th week post MI, after normalization the Low Frequency power increased in the yoga group as compared to the decrease in the standard care group (p = 0.02). Though the High Frequency power increased in both the groups, the magnitude of increase was higher in the standard care group (p = 0.005). However, the total power increased significantly in yoga group with a concurrent decrease in standard care group (p = < 0.001). The SBP All BRS was significantly different between the groups with an increase in the yoga group and a decline in standard care group (p = 0.003) at 13th week. A short-term Yoga based cardiac rehabilitation has additive effects in improving baroreflex sensitivity and dampening blood pressure variability post myocardial infarction in patients under optimal medication.The main trial is registered in Clinical Trials Registry-India (CTRI) (Ref. No: CTRI/2012/02/002408). In addition, CTRI has also been registered for the sub-study. (Ref. No: CTRI/2017/09/009925).


Effect of five-membered heteroaromatic linkers to the performance of phenothiazine-based dye-sensitized solar cells.
Phenothiazine derivatives with various conjugated linkers (furan, thiophene, and 3,4-ethylenedioxythiophene) were synthesized and used in dye-sensitized solar cells to study the effect of conjugated linkers on device performance. Among them, one with furan as a conjugated linker showed a solar energy-to-electricity conversion efficiency (η) of 6.58%, an improvement of over 24% compared with the T2-1 reference cells' 5.29% under AM 1.5 G irradiation.


Identification and analysis of collagen alpha 1(XXI), a novel member of the FACIT collagen family.
The FACIT collagens bind to the surface of collagen fibrils linking them with other matrix molecules. Bioinformatics analysis of cDNA clone DKFZp564B052 showed that it resembled the FACIT collagens and was therefore designated collagen alpha 1(XXI). Phylogenetic analyses of the N-terminal NC3 domains of alpha 1(XXI) and other FACIT collagens showed that (i) alpha 1(XXI) clustered with the FACIT collagens; (ii) collagen alpha 1(XXI) arose before the divergence of alpha 1(XII), alpha 1(XIV) and alpha 1(XX); (iii) collagen alpha 1(XIV) derived from the C-terminal region of the NC3 domain of a collagen alpha 1(XII)-like molecule; and (iv) collagen alpha 1(XX) derived from a collagen alpha 1(XIV)-like molecule. This study provides a framework for the evolution of the FACIT collagens which will be of value in linking NC3 domains with their functions.


A simple surgical treatment for bovine digital dermatitis-associated white line lesions and sole ulcers.
Non-healing white line disease (nhWLD) and sole ulcers (nhSU) are seen increasingly in herds endemically affected with bovine digital dermatitis (BDD). In 35 cows with 42 nhWLD or nhSU lesions, the healing process was monitored for up to 28 or 38 days following extensive debridement of loose horn and infected corium under regional anaesthesia, and topical application of tetracycline spray with bandaging. By 28 days, 27/42 (64%) nhWLD and nhSU were completely covered by a new horn layer and this increased to 30/42 (71%) that had healed by 38 days. Lesion sizes on day 0 correlated with clinical healing within the study period. In view of this satisfying therapeutic result, the terms nhWLD and nhSU are proposed for BDD-associated white line disease (BDD-WLD) and BDD-associated sole ulcers (BDD-SU), respectively.


White paper on pancreatic ductal adenocarcinoma from society of abdominal radiology's disease-focused panel for pancreatic ductal adenocarcinoma: Part I, AJCC staging system, NCCN guidelines, and borderline resectable disease.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal malignancy with a poor 5-year survival rate. Accurate staging of PDAC is an important initial step in the development of a stage-specific treatment plan. Different staging systems/consensus statements convened by different societies and academic practices are currently used. The most recent version of the American Joint Committee on Cancer (AJCC) tumor/node/metastases (TNM) staging system for PDAC has shifted its focus from guiding management to assessing prognosis. In order to preoperatively define the resectability of PDAC and to guide management, additional classification systems have been developed. The National Comprehensive Cancer Network (NCCN) guidelines, one of the most commonly used systems, provide recommendations on the management and the determination of resectability for PDAC. The NCCN divides PDAC into three categories of resectability based on tumor-vessel relationship: 'resectable,' 'borderline resectable,' and 'unresectable'. Among these, the borderline disease category is of special interest given its evolution over time and the resulting variations in the definition and the associated recommendations for management between different societies. It is important to be familiar with the evolving criteria, and treatment and follow-up recommendations for PDAC. In this article, the most current AJCC staging (8th edition), NCCN guidelines (version 2.2019-April 9, 2019), and challenges and controversies in borderline resectable PDAC are reviewed.


Prevalence of osteoporosis in middle Anatolian population using calcaneal ultrasonography method.
There are a few studies on the prevalence of osteoporosis in Turkey. Most of such studies have been performed using classical diagnostic methods. Quantitative calcaneal ultrasonography is a contemporary procedure used in the diagnosis of osteoporosis. The aim of this study is to determine the prevalence of the osteoporosis and risk factors in middle Anatolian population aged more than 40, using quantitative calcaneal ultrasonography. The present study was carried out in rural and urban areas of primary health care units. Evaluation of skeletal status was based on calcaneal quantitative ultrasound measurement, carried out by the Sahara Clinical Bone Sonometer (Hologic Waltham, MA, USA). There were 1437 individuals, 866 were females (60.3%) and 571 were males (39.7%), aged in between 40 and 89 years. Standardized prevalence rates using Segi's population were found to be 14.0% in total, 17.1% in female and 9.2% in male. Osteoporosis prevalence increased with increasing ages. The highest prevalence value was determined in the individuals older than 70 years of age. Osteoporosis was more common among women compared to men. Osteoporosis prevalence increased in consistent with a decrease in the amount of milk, yoghurt and cheese consumption. Based on current study, it is concluded that osteoporosis is an important health problem. Requiring health education about life styles (activity and nutrition) to avoid and even control osteoporosis.


Combing genomic DNA for structural and functional studies.
Molecular combing is a process whereby single DNA molecules bind by their extremities to a silanised surface and are then uniformly stretched and aligned by a receding air/water interface (1). This method, with a high resolution ranging from a few kilobases to megabases, has many applications in the field of molecular cytogenetics, allowing structural and functional analysis at the genome level. Here we describe protocols for preparing DNA for combing and for the use of fluorescent hybridisation (FH) applied to combed DNA to conduct physical mapping or genomic structural analysis. We also present the methodology for visualising and studying DNA replication using combed DNA.


Changes in thumb tapping rates and central motor conduction times are associated in persons with multiple sclerosis.
In persons with multiple sclerosis, nerve conductivity can be reduced. The assessment is generally performed via motor evoked potentials (MEP). So far, a strongly associated motor performance surrogate for changes in the extracted central motor conduction time (CMCT) is missing. CMCT and performance in the nine-hole peg test and maximum thumb tapping frequencies over 10 s of 12 persons with multiple sclerosis were measured prior to and after training over 5 consecutive days. Each training consisted of 10,000 thumb taps at maximum effort with the dominant upper limb. The dominant upper limb improved in maximum tapping frequency over 10 s (d = 0.79) and 10,000 taps (d = 1.04), the nine-hole peg test (d = 0.60), and CMCT (d = 0.52). The nondominant upper limb only improved in the nine-hole peg test (d = 0.38). Models of multiple linear regression predicted 0.78 (model 1, tapping performance as factors) and 0.87 (model 2, patient baseline characteristics as factors) of the variance in CMCT changes. Changes in CMCT were well predictable, although the assessment of those surrogates is either not economic (model 1) or rather describing a potential of change (model 2). However, we were able to show moderate changes in CMCT within 5 days.


Quality control in treating patients with patent foramen ovale: 7-year-experience of the Heart and Brain team of the Careggi University Hospital.
The right comprehension of ischemic stroke pathogenesis guarantees the best prevention therapy. The term "patent foramen ovale (PFO) related stroke" has been proposed for those events where PFO is supposed to be pathogenetic, but their definition is challenging. A multidisciplinary evaluation in a "Heart & Brain" team (HBteam) including stroke neurologists and interventional cardiologists was therefore highly recommended in the recent guidelines of secondary stroke prevention. We aimed at describing the organization of the HBteam of Careggi-University-Hospital of Florence (Italy), and the results of the first seven years of activity. In 2016 Interventional Cardiologists and Stroke Neurologists set up an outpatient clinic for the joined evaluation of patients with PFO and other cardio/neurological conditions. A specific diagnostic-therapeutic hospital plan was produced for PFO patients. Patient empowerment was guaranteed by a hospital explicative webpage, a booklet regarding risks/benefits of PFO closure and a 3D heartmodel to simulate the intervention. Data were collected in a dedicated registry. We evaluated 594 patients for PFO, 40 for left atrial appendage closure and 38 for other conditions. In 20% of PFO-patients, HBteam diagnosis was discordant from that of referring physicians, 14% were stroke misdiagnoses. We advised against closure in 53% of patients. At follow-up 94% of closed patients had no/minimum residual shunt; 3 patients had a cerebral ischemic event. A dedicated HBteam represents a unique opportunity to share decisions with patients after a thorough empowerment process. The joining of cardioneurological skills allows a better classification of PFO-patients, reducing futile interventions.


The complete mitochondrial genome of Strongylus equinus (Chromadorea: Strongylidae): Comparison with other closely related species and phylogenetic analyses.
The roundworms of genus Strongylus are the common parasitic nematodes in the large intestine of equine, causing significant economic losses to the livestock industries. In spite of its importance, the genetic data and epidemiology of this parasite are not entirely understood. In the present study, the complete S. equinus mitochondrial (mt) genome was determined. The length of S. equinus mt genome DNA sequence is 14,545 bp, containing 36 genes, of which 12 code for protein, 22 for transfer RNA, and two for ribosomal RNA, but lacks atp8 gene. All 36 genes are encoded in the same direction which is consistent with all other Chromadorea nematode mtDNAs published to date. Phylogenetic analysis based on concatenated amino acid sequence data of all 12 protein-coding genes showed that there were two large branches in the Strongyloidea nematodes, and S. equinus is genetically closer to S. vulgaris than to Cylicocyclus insignis in Strongylidae. This new mt genome provides a source of genetic markers for the molecular phylogeny and population genetics of equine strongyles.


Computerized ultrasonic tissue characterization of ocular tumors.
Mathematical evaluation techniques to derive the calibrated power spectrum of reflected ultrasonic echoes from ocular tumors can be used with a clinical computer system to objectively classify malignant melanoma and metastatic carcinoma of the eye. Sets of spectral data provide a reproducible standard for classification that closely approximates the Callender system used in histologic classification. We used spectral data with a computer data library to separate spindle B malignant melanomas (20 tests in 17 patients) from mixed-epithelioid melanomas (17 tests in 13 patients) and to identify metastatic carcinoma (20 tests in 17 patients) with approximately 98% reliability. Tissue structures can be acoustically stained in B-mode images to define the specific anatomic and structural properties that provide the acoustic differentiation. These data are obtained under in vivo conditions and allow a noninvasive classification of tumors in a way not previously possible, aiding in the definitive diagnosis of ocular tumors, as well as in the planning and monitoring of treatment.


Compatibility of ropivacaine with morphine, sufentanil, fentanyl, or clonidine.
Ropivacaine hydrochloride (HCl) ('Naropin') is a long-acting local anaesthetic agent, administered epidurally to patients undergoing various surgical procedures. A combination of local anaesthetic and opioid is often administered for the management of severe pain to ensure that a minimal dose of each is used. Ropivacaine might be used in combination with an alpha2-adrenergic agonist for the management of visceral pain. Stability data have shown that ropivacaine is compatible with the systemic narcotic opioid analgesics morphine sulphate, sufentanil citrate and fentanyl citrate for 14 days in a Polybag (AstraZeneca-AB, Sweden), but no data have been obtained for the longer-term compatibility of ropivacaine with these opioids or with the alpha2-adrenergic agonist clonidine HCl. This study used the Mark II Polybag (AstraZeneca-AB, Sweden) to test the physical and chemical compatibility of these products for up to 30 days. Ropivacaine HCl solution for epidural infusion, 2 mg/mL, in 200 mL Mark II Polybag and commercially available additives in glass ampoules or vials were used as starting material. Appropriate admixtures were made and their appearance, pH, and drug concentrations were monitored on days 0, 7, 14, and 30. The appearance of the admixtures was examined with the aid of a stereomicroscope (Olympus, no. 220186, New York, USA) at 10x magnification. Drug concentration and enantiomeric purity were determined using high-performance liquid chromatographic analysis. All combinations at all doses stayed within the compatibility criteria (if no visible signs of physical changes in the admixture appeared throughout the 30 days of storage, and if pH and drug concentrations in each admixture did not vary by more than 10% between day 0 and days 7, 14, or 30 in storage). In addition, there were no important differences in the enantiomeric purity of ropivacaine with each combination. The study demonstrated that ropivacaine was suitable for use in combination with the opioids morphine sulphate, sufentanil citrate, and fentanyl citrate, or with the alpha2-adrenergic agonist clonidine HCl, for up to 30 days of storage before the management of severe or visceral pain. From a microbiological point of view, combinations not prepared under aseptic conditions should be used immediately. 'Naropin' is a trade mark of the AstraZeneca group of companies.


Air quality impact assessment for the Eurasia Tunnel in Istanbul, Turkey.
The Eurasia Tunnel, a 5.4-km tunnel connecting the Asian and European sides of Istanbul, Turkey, was opened for operation in December 2016. This paper describes the air quality modeling that was conducted during the design phase of the structure, to evaluate the impact of the tunnel traffic on ambient air quality in the vicinity of the tunnel. The ventilation of the tunnel consists of longitudinal forced ventilation with vertical extraction through two stacks located near the Asian and European portals of the tunnel. The analysis was conducted using the AERMOD computer program for three pollutants CO, NO2, and PM10. Model results show that pollutants will rapidly disperse once released from the stack and will not affect air quality in the vicinity of the tunnel. The most critical parameters which controlled the ventilation system design were found to be NO2 and PM10. Maximum concentrations are not expected to violate the pertinent Turkish and EU air quality standards. Overall, this analysis shows that the ventilation system is efficient for the dispersion of the pollutants.


Cell lineage analysis of neural induction: origins of cells forming the induced nervous system.
Horseradish peroxidase (HRP) was used as an intracellular lineage tracer in two experiments designed to reveal the sites of origin of cells that formed the duplicate embryo which developed in relation to an organizer grafted in the ventral marginal zone (VMZ) of Xenopus laevis embryos. In the first experiment a dorsal blastoporal lip fully labeled with HRP was grafted in the VMZ of an unlabeled embryo at the beginning of gastrulation. This resulted in development of a second embryo in which labeled cells, of graft origin, formed the notochord, and parts of the somites, endoderm, and neural tube. The second experiment was designed to show the sites of origin of the host's cells that formed parts of the induced embryo. HRP was injected into individual blastomeres in a series of Xenopus embryos at the 32-cell stage and each embryo received an unlabeled organizer graft in the VMZ at the beginning of gastrulation. In these embryos the lineages that contributed to the host's primary neural tube did not contribute any cells to the induced neural tube. All the cells in the induced neural tube which originated from the host were descendants of ventral blastomeres that did not contribute to the neural tube normally. This shows that the second neural tube is formed as a result of the action of the organizer on cells in its immediate vicinity which would not normally have entered neural pathways of differentiation.


The structural diversity of CACTA transposons in genomes of Chenopodium (Amaranthaceae, Caryophyllales) species: specific traits and comparison with the similar elements of angiosperms.
CACTA transposable elements (TEs) comprise one of the most abundant superfamilies of Class 2 (cut-and-paste) transposons. Over recent decades, CACTA elements were widely identified in species from the plant, fungi, and animal kingdoms, but sufficiently studied in the genomes of only a few model species although non-model genomes can bring additional and valuable information. It primarily concerned the genomes of species belonging to clades in the base of large taxonomic groups whose genomes, to a certain extent, can preserve relict and/or possesses specific traits. Thus, we sought to investigate the genomes of Chenopodium (Amaranthaceae, Caryophyllales) species to unravel the structural variability of CACTA elements. Caryophyllales is a separate branch of Angiosperms and until recently the diversity of CACTA elements in this clade was unknown. Application of the short-read genome assembly algorithm followed by analysis of detected complete CACTA elements allowed for the determination of their structural diversity in the genomes of 22 Chenopodium album aggregate species. This approach yielded knowledge regarding: (i) the coexistence of two CACTA transposons subtypes in single genome; (ii) gaining of additional protein conserved domains within the coding sequence; (iii) the presence of captured gene fragments, including key genes for flower development; and (iv)) identification of captured satDNA arrays. Wide comparative database analysis revealed that identified events are scattered through Angiosperms in different proportions. Our study demonstrated that while preserving the basic element structure a wide range of coding and non-coding additions to CACTA transposons occur in the genomes of C. album aggregate species. Ability to relocate additions inside genome in combination with the proposed novel functional features of structural-different CACTA elements can impact evolutionary trajectory of the host genome.


An effective strategy for improving the specific activity and saccharification efficiency of cellulase by pre-incubation with phenolic acids.
This short communication analyzed the effects of lignin-derived phenolic acid compounds on cellulase. Vanillic acid, syringic acid, ferulic acid, and isovanillic acid improved cellulase specific activity and saccharification efficiency. In the enzymatic hydrolysis process, the promotion effect of phenolic acid was concentration-dependent. The effect of low concentration of phenolic acids (less than 5 mM) was negligible. After pre-incubating 1 g cellulase with 5 mmol phenolic acid, FPase-specific activity, CMCase-specific activity, and pNPGase-specific activity increased by 57.06%, 136.79%, and 110.61%, respectively. After digestion with pre-incubated cellulase, the saccharification efficiency of phosphoric acid-swollen cellulose increased by 45.13%. Pre-incubation with phenolic acid improved the saccharification efficiency of cellulase. It might be helpful to enhance the comprehensive utilization capacity of lignin-derived compounds.


Characterizing distribution of steroidal alkaloids in Fritillaria spp. and related compound formulas by liquid chromatography-mass spectrometry combined with hierarchial cluster analysis.
Bulbus Fritillariae (BF), referred to the bulbs of several Fritillaria species (Liliaceae), is a commonly used antitussive and expectorant herb in traditional Chinese medicine (TCM). Due to the complexity of BF botanical origin in the herbal markets, it is urgently needed to develop a reliable method for species identification. Previous studies based on morphological and histological as well as molecular biological techniques have respective limitations. For the purpose of finding a possible discriminant method among Fritillaria species, 27 steroidal alkaloids in 17 Fritillaria species and 12 BF-containing compound formulas were identified and characterized by a high-performance liquid chromatography with mass spectrometry (HPLC-MS) method. The estimated relative composition of steroidal alkaloids was used to carry out a chemotaxonomical study on Fritillaria species by means of hierarchial cluster analysis. In addition, the characteristic occurring patterns of the examined bases were compared in an effort to distinguish the botanical origin of BF-containing compound formulas. The results demonstrated that the qualitative and quantitative differences in steroidal alkaloids were useful not only for chemotaxonomy in some medicinal Fritillaria species but also for species identification in compound formulas. The described method has important implications in quality control of BF-containing TCM preparations, allowing for the prevention of BF confusion, and also revealing the possible presence of adulteration.


Impaired categorical perception of synthetic speech sounds in schizophrenia.
Simple speech sounds such as /ba/ and /da/ differ in the frequency composition of their underlying formants. Normal volunteers asked to identify intermediate phonemes along the /ba/ to /da/ continuum abruptly switch from perceiving "ba" to perceiving "da". The present study investigates precision of phonemic processing in schizophrenia. Categorical perception of speech sounds was evaluated in 15 schizophrenic and 14 control subjects, using a forced-choice phonemic discrimination paradigm. Patients and controls were equally able to recognize endpoint forms of both phonemes, but differed significantly in their perception of intermediate forms near the center of the continuum. Patients also showed a significantly shallower response curve, suggesting an impairment in boundary definition. Despite their impairment in categorical perception, schizophrenic subjects showed normal adaptation of response when test stimuli were preceded by a series of /ba/ or /da/ stimuli from the endpoints of the continuum. The present results suggest that precision of phonemic processing is impaired in schizophrenia. This categorical perception deficit may represent upward generalization of impaired memory-dependent acoustic processing. Deficits in the precision of cortical processing may contribute significantly to cognitive dysfunction in schizophrenia.


Varying time delay Smith predictor process controller.
One of the perceived weaknesses of the classical Smith predictor is that the time delay is fixed. For systems with a varying time delay, underestimating or overestimating the time delay significantly degrades control quality. This paper presents theoretical and practical results of applying the Smith predictor with a varying time delay when the nature of the application allows the time delay to be practically computed in real time.


Using disulfide bond engineering to study conformational changes in the beta'260-309 coiled-coil region of Escherichia coli RNA polymerase during sigma(70) binding.
RNA polymerase of Escherichia coli is the sole enzyme responsible for mRNA synthesis in the cell. Upon binding of a sigma factor, the holoenzyme can direct transcription from specific promoter sequences. We have previously defined a region of the beta' subunit (beta'260-309, amino acids 260 to 309) which adopts a coiled-coil conformation shown to interact with sigma(70) both in vitro and in vivo. However, it was not known if the coiled-coil conformation was maintained upon binding to sigma(70). In this work, we engineered a disulfide bond within beta'240-309 that locks the beta' coiled-coil region in the coiled-coil conformation, and we show that this "locked" peptide is able to bind to sigma(70). We also show that the locked coiled-coil is capable of inducing a conformational change within sigma(70) that allows recognition of the -10 nontemplate strand of DNA. This suggests that the coiled-coil does not adopt a new conformation upon binding sigma(70) or upon recognition of the -10 nontemplate strand of DNA.


[Prognostic factors for metastatic renal cell carcinoma treated with second-line targeted therapies].
To assess the prognostic value of clinical and biological features in patients treated with second-line targeted therapies (TT) for a metastatic renal cell carcinoma (mRCC). A retrospective study was performed including 60 patients treated with second-line TT from 2006 to 2013. Clinical and biological features were collected, including TT-induced toxicities, Heng and MSKCC prognostic scores, and renal function. Overall survival (OS) and progression-free survival (PFS) were assessed using univariate and multivariate analysis. The median age was 61 years [39-81]. MSKCC and Heng scores were significantly prognostic for OS and PFS (P<0.05). Hypo-albuminemia, anemia and brain metastasis were associated with poorer OS and PFS (P<0.05). Severe induced toxicities had a prognostic impact with higher OS (26 months vs 10 months, P=0.003) and PFS (5 months vs 4 months, P=0.047). Renal function impairment at the initiation of the second line was also associated with higher survival (OS=24 months vs 9 months, P=0.035 and PFS=7 months vs 4 months, P=0.043). On multivariate analysis, induced toxicity was found as an independent factor of good prognosis for OS (HR=0.36; P=0.01). Our results suggested that renal function impairment and TT-induced toxicities in the second line of treatment for mRCC have a potential prognostic interest as it had previously been reported for the first line of TT. 5.


[Internal carotid artery dissection in a patient with recent respiratory infection: case report of a possible link].
The pathogenesis of spontaneous cervical artery dissection remains unknown. Infection-mediated damage of the arterial wall may be an important triggering mechanism. We describe a 21 year-old man with respiratory infection (bronchial pneumonia) which was diagnosed and treated with antibiotic few days prior to the right internal carotid artery dissection. The patient presented ischemic retinal and cerebral strokes. Based on literature review, we discuss the possibility of a causal link between infection and arterial dissection.


Mechanistic bases for adverse vaccine reactions and vaccine failures.
Mild local and systemic reactions to vaccines are to be expected as a natural consequence of vigorously stimulating the immune system. Dramatic adverse reactions to vaccines are occasionally due to mistakes during the production or handling of vaccines. More often, they are due to not following label instructions, particularly the restriction to only use vaccines in healthy animals. It is important to publish well-documented instances of adverse vaccine reactions so that producers and users of vaccines can all learn from the experience and avoid similar problems. Vaccine failure to protect from disease is usually due to problems with either client education or compliance with good animal management practices. It is important for clients to understand the proper timing and method of vaccine administration, what to realistically expect for vaccine efficacy, and the importance of minimizing immunosuppressive factors and exposure to high doses of infectious agents in vaccinated animals. Veterinary vaccines have produced dramatic benefits in terms of animal health, human health, and efficiency of food production. Advances in research and the accumulating experience with vaccines are leading to safer and more effective vaccines. Proper usage of vaccines and adherence to good management practices will continue to be essential to achieve maximal vaccine safety and efficacy.


The Role of Core Needle Biopsy and Its Impact on Surgical Management in Patients with Medullary Thyroid Cancer: Clinical Experience at 3 Medical Institutions.
Medullary thyroid carcinoma is an uncommon malignancy that is challenging to diagnose. Our aim was to present our experience using core needle biopsy for the diagnosis of medullary thyroid carcinoma compared with fine-needle aspiration. Between January 2000 and March 2012, 202 thyroid nodules in 191 patients were diagnosed as medullary thyroid cancer by using sonography-guided fine-needle aspiration, core needle biopsy, or surgery. One hundred eighty-three thyroid nodules in 172 patients were included on the basis of the final diagnosis. We evaluated the sensitivity and positive predictive value of fine-needle aspiration and core needle biopsy for the diagnosis of medullary thyroid cancer. We compared the rate of a delayed diagnosis, a diagnostic surgery, and surgery with an incorrect diagnosis for fine-needle aspiration and core needle biopsy and investigated the factors related to the fine-needle aspiration misdiagnosis of medullary thyroid cancer. Fine-needle aspiration showed 43.8% sensitivity and 85.1% positive predictive value for the diagnosis of medullary thyroid cancer; 25.7% (44/171) of patients had a delayed diagnosis, while 18.7% (32/171) underwent an operation for accurate diagnosis, and 20.5% (35/171) underwent an operation with an incorrect diagnosis. Core needle biopsy achieved 100% sensitivity and positive predictive value without a delay in diagnosis (0/22), the need for a diagnostic operation (0/22), or an operation for an incorrect diagnosis (0/22). A calcitonin level of <100 pg/mL was the only significant factor for predicting the fine-needle aspiration misdiagnosis of medullary thyroid cancer (P = .034). Core needle biopsy showed a superior sensitivity and positive predictive value to fine-needle aspiration and could optimize the surgical management in patients with medullary thyroid cancer. Because the ability of fine-needle aspiration to diagnose medullary thyroid cancer significantly decreases in patients with serum calcitonin levels of <100 pg/mL, core needle biopsy could be indicated for these patients to optimize their surgical management.


Phospholipid molecular species distribution of Porphyromonas asaccharolytica ATCC 25260T: effects of temperature, culture age and pH.
The aim of this study was to determine the extent to which phospholipid molecular species profiles are affected by different environmental factors in Porphyromonas asaccharolytica ATCC 25260T. Phospholipids were analysed by Fast Atom Bombardment Mass Spectrometry (FAB-MS) in negative-ion mode. Under standard growth conditions (37 degrees C, pH 7.0, 48 h), the most intense high mass anions were m/z 653 and 662. The latter is consistent with the expected presence of PE (30:0). The only changes in profiles were quantitative. These were compared using the Pearson Coefficient of Linear Correlation. The r-values for initial pH comparisons ranged from 0.82 (pH 7.0 vs pH 6.0) to 1.00 (pH 5.0 vs pH 8.0), for incubation period, from 0.86 (48 vs 72 h) to 0.97 (96 vs 168 h), and for temperature, from 0.57 (40 vs 37 degrees C) to 0.96 (37 vs 36 degrees C). Differences were also seen when plates were incubated in anaerobe jars as opposed to an anaerobic work station (r = 0.75). It is concluded that it is essential to standardize growth parameters, and to use an anaerobe jar or an anaerobe work station, but not both.


The efficacy of EC-IC anastomoses: evaluation by directional c-w Doppler sonography.
We report the results obtained by means of directional c-w Doppler sonography on 33 patients with superficial temporal-to-middle cerebral artery anastomoses. The efficiency of the anastomosis was evaluated by the modified Pourcelot indices (relative end-diastolic flow velocities) of the preauricular superficial temporal artery and of the bypass-supplying branch at the edge of the burr-hole. The influence of intermittent compression of the bypass-supplying branch on the modified Pourcelot index of the ipsilateral common carotid was used as a further criterion in the sonographic evaluation. All efficient anastomoses, defined by a modified Pourcelot index of at least 0.20 at the edge of the burr-hole, exhibited a reduction of the relative end-diastolic flow velocity of 0.08 on the average in the common carotid during compression. In the 18 cases with unilateral occlusion of the internal carotid, bypass surgery was predominantly efficacious in those patients who showed a reduction in the sum of the modified Pourcelot indices of the remaining brain-supplying arteries of at least two standard deviations with respect to the mean of age-matched controls. The subgroups of patent and absent collaterals through the ophthalmic artery did not show any difference with respect to the percentage of efficient anastomoses. In all 4 patients with bilateral internal carotid artery occlusion, bypass surgery was effective, while 50% of the patients with intracranial carotid artery disease exhibited an insufficient anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)


[<< Reverse >> latissimus dorsi musculocutaneous flap: anatomic study of the secondary pedicles].
The latissimus dorsi flap based on the secondary segmental vessels, wich is termed << reverse >> or << distally based >> latissimus dorsi flap, has been used to repair major thoraco-lumbar defects, to close myelomeningoceles and to reconstruct congenital diaphragmatic absences. The arc of flap rotation is markedly restricted because the blood supply is segmental. It is the most important factor that limits the flap mobility and so restricts its use. The authors report an anatomic study of these secondary pedicles in order to improve the flap dissection and to extend the arc of flap rotation. The precise location of the secondary pedicles of the flap was determined by 24 anatomic dissections. The latissimus dorsi has 3, 4 or 5 secondary pedicles respectively in 50%, 25% and 25% of cases in the study. These pedicles take origin from the dorsal branches of the posterior intercostal arteries of the 7th, 8th, 9th, 10th and 11th intercostal spaces. The number of secondary pedicles is not constant. The entire flap can be safely based on 2 secondary pedicles when the latissimus dorsi muscle has 3 secondary pedicles. When this muscle has 4 or 5 secondary pedicles, the entire flap should be at least based on 3 secondary pedicles, particularly if the skin island is very far from the origin of these vessels.


The impact of Covid-19 pandemic on services for children and adolescents with ADHD: results from a survey of paediatricians in the United Kingdom.
The Covid-19 pandemic has led to huge disruptions and multi-domain healthcare crisis, with additional impact on children and young people (CYP) affected by Attention Deficit and Hyperactivity Disorder (ADHD). We conducted an online survey and obtained responses from 62 Paediatricians who provide ADHD services for CYP about their experience of Service disruption and adaptations during the first Covid-19 lockdown in the United Kingdom between March and June 2020. The responses were both quantitative and qualitative. The Paediatricians reported huge service disruptions such that almost half ceased the assessment of new patients with ADHD, and only 5% were able to offer physical monitoring for most patients. However, all respondents had adopted telemedicine, which allowed them to maintain high levels of non-physical service provision for existing patients. The Paediatricians used risk stratification strategies to determine which patients were more likely to benefit from the limited available face to face appointments for physical monitoring. The Paediatricians demonstrated clinical pragmatism to meet the needs of their patients such as starting medication without physical exam especially if the patient's behaviour was so challenging that it was presenting a crisis at home, and setting aside monthly limits for stimulant medications. Some respondents reported helpful cross-service collaborations to support CYP with ADHD and their families. The Covid-19 pandemic has had adverse effect on many CYP with ADHD and caused huge disruption to the ADHD services that support them. As the pandemic continues to cause disruptions to ADHD services, the service adaptations emerging from the literature including some of those identified in this study could be useful to support more stable and sustainable ADHD services, both during and after the pandemic.


Melatonin prevents secondary intra-abdominal hypertension in rats possibly through inhibition of the p38 MAPK pathway.
Exogenous administration of melatonin has been demonstrated to down-regulate inflammatory responses and attenuate organ damage in various models. However, the salutary effect of melatonin against secondary intra-abdominal hypertension (IAH) remains unclear. This study sought to test the influence of melatonin on secondary IAH in a pathophysiological rat model and the underlying mechanisms involved. Before resuscitation, male rats underwent a combination of induced portal hypertension, applying an abdominal restraint device, and hemorrhaging to mean arterial pressure (MAP) of 40mmHg for 2h. After blood reinfusion, the rats were treated with lactated Ringer solution (LR) (30mL/h), melatonin (50mg/kg) +LR, and SB-203580 (10μmol/kg)+LR. LR was continuously infused for 6h. MAP, the inferior vena cava pressure and urine output were monitored. Histopathological examination, immunofluorescence of tight junction proteins, and transmission electron microscopy were administered. Intestinal permeability, myeloperoxidase activity, malondialdehyde, glutathione peroxidase, and levels of TNF-a, IL-2, and IL-6, were assessed. The expression of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, translocation of nuclear factor kappa B subunit, signal transducers and activators of transcription and tight junction proteins were detected by Western blot. We found that melatonin inhibited the inflammatory responses, decreased expression of p38 MAPK, attenuated intestinal injury, and prevented secondary IAH. Moreover, administration of SB203580 abolished the increase in p38 MAPK and also attenuated intestinal injury. These data indicate that melatonin exerts a protective effect in intestine in secondary IAH primarily by attenuating the inflammatory responses which are in part attributable to p38 MAPK inhibition.


Laparoscopic medial oophoropexy prior to radiation therapy in an adolescent with Hodgkin's disease.
Advances in radiation therapy have led to long term survival in young patients with Hodgkin's disease. Oophoropexy may reduce ovarian damage and preserve hormonal production and future fertility. When ovarian ligaments are shortened, incising the serosa parallel to the infundibulopelvic ligaments at laparoscopy permits the completion of a medial oophoropexy. An adolescent female underwent a laparoscopic medial oophoropexy prior to radiation therapy for Stage IIIB Hodgkin's disease. Due to shortened ovarian ligaments the ovaries could not be placed behind the uterus without excessive tension. The infundibulopelvic ligaments were sharply dissected off of the lateral pelvic sidewalls eliminating tension on the ligaments and allowing completion of the medial oophoropexy. Twenty-two months after completion of her radiation therapy the patient was normally menstruating and conceived spontaneously. Laparoscopic dissection of the infundibulopelvic ligaments allowed for a medial oophoropexy to be performed in an adolescent patient and was associated with return of ovarian function after radiation therapy.


Fourier transform infrared and mass spectrometry analyses of a site-directed mutant of D1-Asp170 as a ligand to the water-oxidizing Mn4CaO5 cluster in photosystem II.
The Mn4CaO5 cluster, the catalytic center of water oxidation in photosystem II (PSII), is coordinated by six carboxylate and one imidazole ligands. The roles of these ligands in the water oxidation mechanism remain largely unknown. In this study, we constructed a D1-D170H mutant, in which the Asp ligand bridging Mn and Ca ions was replaced with His, in the cyanobacterium Synechocystis sp. PCC 6803, and analyzed isolated PSII core complexes using Fourier transform infrared (FTIR) difference spectroscopy and mass spectrometry (MS). The S2-minus-S1 FTIR difference spectrum of the PSII complexes of the D1-D170H mutant showed features virtually identical to those of the wild-type PSII. MS analysis further showed that ~70% of D1 proteins from the PSII complexes of D1-D170H possessed the wild-type amino acid sequence, although only the mutated sequence was detected in genomic DNA in the same batch of cells for PSII preparations. In contrast, a D1-S169A mutant as a control showed a modified FTIR spectrum and only a mutated D1 protein. It is thus concluded that the FTIR spectrum of the D1-D170H mutant actually reflects that of wild-type PSII, whereas the Mn4CaO5 cluster is not formed in PSII with D1-D170H mutation. Although the mechanism of production of the wild-type D1 protein in the D1-D170H mutant is unknown at present, a caution is necessary in the analysis of site-directed mutants of crucial residues in the D1 protein, and mutation has to be confirmed not only at the DNA level but also at the amino acid level.


Effect of fish oil supplementation on aortic compliance in rats: role of the endothelium.
Arterial compliance improves with dietary fish oils in patients with high cardiovascular risk. Since fish oils alter prostaglandin metabolism and the L-arginine-nitric oxide pathway, and since compliance may be modified by vasoactive substances, the effect of the endothelium and some of its derivatives on aortic complaince were examined. Rats were randomly allocated to four groups, the first of which fed only the regular chow. The remaining three groups were fed the chow supplemented by daily gavage with either coconut, fish or safflower oil for 8 weeks. The thoracic aorta was removed and six 2 mm rings obtained. Rings were paired and one from each pair treated with either N(W)-nitro-L-arginine, indomethacin or de-endothelialized. A diameter-tension curve was initiated from wire touch position using incremental increases in wire distance until no further response observed. The data was transformed to a diameter-pressure relationship and fitted with a linear equation, the slope of which related directly to compliance. De-endothelialization (slopes: control vs de-endothelialized: 9.05+/-0.15 vs 8.31+/-0.24; P< 0.05) and indomethacin (slopes: control vs indomethacin: 9.11+/-0.15 vs 7.76+/-0.37; P< 0.05) significantly decreased arterial compliance as did dietary fish oils (slopes: control vs n-3: 9.16+/-0.11 vs 7.84+/-0.39; P< 0.05). No further effect was seen with indomethacin in the fish oil treated group. It is concluded that the endothelium and in particular, endothelium derived prostanoids, contribute to vessel compliance. We also conclude that fish oils have a similar action to indomethacin, leading to the increase in aortic stiffness observed.


PKA-mediated eNOS phosphorylation in the protection of ischemic preconditioning against no-reflow.
To investigate whether ischemic preconditioning (IP) can reduce myocardial no-reflow by activating endothelial (e-) nitric oxide synthase (NOS) via the protein kinase A (PKA) pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were assigned into sham, ischemia-reperfusion (IR), IR+IP, IR+IP+L-NNA (an eNOS inhibitor, 10mg·kg(-1)), IR+IP+H-89 (a PKA inhibitor, 1.0μg·kg(-1)·min(-1)), IR+L-NNA, and IR+H-89 groups. IP pretreatment improved cardiac function and coronary blood flow, decreased the activities of creatine kinase by 36.6% after 90 min of ischemia and by 32.8% after 3 h of reperfusion (P<0.05), reduced the no-reflow areas from 49.9% to 11.0% (P<0.01), and attenuated the infarct size from 78.2% to 35.4% (P<0.01). IP stimulated myocardial PKA activities and the expression of PKA and Ser(133) phosphorylated (p-) cAMP response element-binding protein (CREB) in the reflow and no-reflow myocardium, and enhanced the activities of constitutive NOS and the phosphorylation of eNOS at Ser(1179) and Ser(635) in the no-reflow myocardium. IP suppressed the expression of tumor necrosis factor-α and P-selectin, and attenuated cardiomyocytes apoptosis by regulating the expression of Bcl-2 and caspase-3 in the reflow and no-reflow myocardium. The eNOS inhibitor L-NNA completely canceled these beneficial effects of IP without any influence on PKA activity, whereas the PKA inhibitor H-89 partially blocked the IP cardioprotective effects and eNOS phosphorylation at the same time. IP attenuates myocardial no-reflow and infarction after ischemia and reperfusion by activating the phosphorylation of eNOS at Ser(1179) and Ser(635) in a partly PKA-dependent manner.


Bilobalide abates inflammation, insulin resistance and secretion of angiogenic factors induced by hypoxia in 3T3-L1 adipocytes by controlling NF-κB and JNK activation.
Obesity leads to inflammation and insulin resistance in adipose tissue. Hypoxia, observed in obese adipose tissue is suggested as a major cause of inflammation and insulin resistance in obesity. However, the role of hypoxia in adipose tissue during obesity and insulin resistance was not well established. Here we mainly explored the crosstalk between hypoxia induced inflammation, and insulin resistance and also secretion of angiogenic factors in 3T3-L1 adipocytes and possible reversal with bilobalide. Hypoxia for 24h significantly (P≤0.05) increased the secretion of MCP-1 (4.59 fold), leptin (2.96 fold) and reduced adiponectin secretion (2.93 fold). In addition, the mRNA level of resistin (6.8 fold) and TLR4 receptors (8.8 fold) was upregulated in hypoxic adipocytes. The release of inflammatory cytokines and expression of TLR4 receptors led to activation of JNK and NF-κB signalling. We further investigated the effects of JNK and NF-κB activation on insulin signalling receptors. The present study showed increased (P≤0.05) serine 307 phosphorylation of IRS-1 (1.9 fold) and decreased expression of IRS-2 (0.53 fold) in hypoxic group showing hypoxia induced impairment in insulin signalling. Hypoxia significantly (P≤0.05) increased basal glucose uptake (3.3 fold) as well as GLUT-1 expression in adipocytes indicating GLUT-1 mediated glucose uptake. Hypoxia for 24h significantly increased (P≤0.05) the expression of angiogenic factors. Bilobalide protected adipocytes from hypoxia induced inflammation and insulin resistance mainly by reducing inflammatory adipokine secretion, improving adiponectin secretion, reducing NF-κB/JNK activation, and inhibiting serine phosphorylation of IRS-1 receptors of insulin signalling pathway.


Allozyme variability in the Italian wolf (Canis lupus) population.
Multilocus protein electrophoresis was used to estimate genetic variability in a sample of 38 Italian wolves (Canis lupus). Percentage of polymorphic loci was p = 10.0 per cent (four polymorphic loci out of 40 examined), and average observed heterozygosity was Ho = 0.028. Genotypes were in Hardy-Weinberg equilibrium. Electrophoretic analysis does not indicate a significant reduction of genetic variability at nuclear gene loci following at least one century of isolation from other European populations and demographic fluctuations suggested by recent range contraction and expansion. These findings are compared with published allozyme and mitochondrial DNA data for dogs, Canadian wolves, and introgressed wolf x coyote populations from Minnesota and Isle Royale (U.S.A.).


Merkel cell tumor of the hand: report of two cases.
Merkel cell carcinoma is a rare cutaneous neuroendocrine neoplasm. Often located on the head and neck, reports of Merkel cell carcinoma in the hand are extremely limited. In this article, we review 2 cases of Merkel cell carcinoma of a digit treated with ray resection and sentinel lymph node dissection with greater than 5 years of follow-up.


Enzyme-assisted immune detection of plant virus proteins electroblotted onto nitrocellulose paper.
A technique for the detection of plant virus coat proteins in plant sap is described. The method entails the electroblotting of sodium dodecyl sulphate-polyacrylamide gel electrophoresis-fractionated plant extracts onto nitrocellulose paper, probing the paper with virus-specific rabbit antisera, and indirect detection of virus proteins with horseradish peroxidase-conjugated goat anti-rabbit globulins. The sensitivity and specificity of the technique were tested using brome mosaic and barley stripe mosaic viruses. As little as 1 ng per track of virus protein was detectable, either as pure virus or when mixed with plant sap. Distant serological relationships were detected amongst tobamoviruses, and amongst the bromoviruses, with single antisera. The uses of the technique in probing capsid configuration in a presumed aphid picornavirus, and in routine diagnostic practice, are described.


Towards the implementation of breastfeeding-related health services in community pharmacies: Pharmacists' perspectives.
The scope of community pharmacy practice has expanded over the years. Pharmacists are now involved in the provision of a range of professional services. Pharmacists have regular contact with breastfeeding women, and are perceived as easily accessible, trusted health advisors. There is limited information on factors needed to be considered when implementing breastfeeding-related services in pharmacies to meet the needs of this population group. This study aimed to explore community pharmacists' perspectives on the implementation of breastfeeding-related services, the factors to consider and the required implementation strategies in community pharmacies. The study involved semi-structured interviews with 30 community pharmacists practising in Western Australian. Interviews were audio-recorded and transcribed verbatim to facilitate analysis. NVivo® Version 10.0 was used to aid organisation of qualitative data and thematic analysis. Responses to closed-ended questions were summarised using the descriptive approach. Participants' perceptions about their role in providing breastfeeding-related services in community pharmacies were generally favourable. Participants reported receiving regular enquiries from the public about the use of various medicines during breastfeeding, in particular non-prescription medicines. Most of their knowledge regarding the use of medicines in breastfeeding and breastfeeding in general was a culmination of day-to-day work experience, self-directed continuing professional development, personal or close-contact breastfeeding experience, and university training. Multifaceted efforts including public and professional education, research and development, and government initiatives were identified as essential to facilitate quality use of medicines in breastfeeding, and to increase pharmacists' support of breastfeeding women. Based on the needs and demand, appropriate training and continuing development is warranted so that pharmacists are well-equipped with knowledge regarding the use of medicines in breastfeeding, and breastfeeding in general. There appear to be opportunities for pharmacists to expand their professional services and contribute towards improved care and support of breastfeeding women at primary care level.


Acid phosphatase and adenosine triphosphatase activities in the cell wall of baker's yeast.
In order to establish whether a specific adenosine triphosphatase is present in yeast cell wall, hydrolysis rates for p-nitrophenylphosphate (acid phosphatase activity) and for ATP (ATPase activity) were compared under various conditions. Rate determinations were made with both, intact cells and with preparations containing secreted enzymes from protoplasts. Acid phosphatase and ATPase activities had the same pH profile and were susceptible in the same way to the repression by orthophosphate and to the inhibition by 2-deoxyglucose. The Lineweaver-Burk plot shows biphasic kinetic behaviour for the hydrolysis of either p-nitrophenylphosphate or ATP. This suggests the existence of two enzymes with different affinities for the substrates, or one enzyme with at least two active sites. The two activities differ in thermostability and only one activity could be completely abolished by heat treatment. The thermostable enzyme activity had K-m values of 0.475 mM for p-nitrophenylphosphate, and 0.040 mM for ATP. ATP behaved as a partially competitive inhibitor of p-nitrophenylphosphate hydrolysis. Substrate competition studies showed that only a non-specific acid phosphatase is responsible for the hydrolysis of ATP.


Changes in detrusor contractility after incontinence surgery.
To study the effects of incontinence surgery on detrusor contractility, a group of 24 women who preoperatively voided without a detrusor contraction during voiding urethrocystometry were re-evaluated for detrusor contractility three months after surgery for stress urinary incontinence. Twelve women regained detrusor contractility during voiding and were able to resume spontaneous voiding after incontinence surgery. The remaining 12 patients, representing true detrusor atony, continued to void without a detrusor contraction, and the majority (10/12) needed prolonged postoperative bladder drainage prior to resumption of spontaneous voiding. Presence of reduced flow rates and absence of detrusor contraction during preoperative voiding indicated true detrusor hypotonicity. Two thirds of the patients voiding with normal flow rates but without a detrusor contraction during preoperative voiding regained detrusor contraction after incontinence surgery (p less than 0.05).


Subliminal perception and its cognates: theory, indeterminacy, and time.
Unconscious processes, by whatever name they may be known (e.g., "subliminal," "implicit"), are invariably operationalized by the dissociation paradigm, any situation involving the dissociation between two indicators (or sets of indicators), one of availability (epsilon) and the other, of accessibility (alpha), such that, epsilon>alpha. Subliminal perception has been traditionally defined by a special case of the dissociation paradigm in which availability exceeds accessibility when accessibility is null (epsilon>alpha/alpha=0). Construct validity issues bedevil all dissociation paradigms since it is not clear what might constitute appropriate indicators that, moreover, are pure and exhaustive. Semantic and theoretic drifts in the recent literature--e.g., the confusion of different versions of the dissociation paradigm, the equation of conscious-unconscious with direct-indirect tests, and the foisting of the criterion of qualitative differences--have tended to undermine emerging theoretic parsimony. On the other hand, a crucial factor has been left out of theory development: time. Both epsilon and alpha can rise and fall over time, often asynchronously, and so dissociations may wax and wane and, even, reverse over time. Some laboratory evidence suggests that accessibility measures (e.g., d'), as they approach chance, may actually dip below chance (subchance perception). If so, d'=0 (the chance-limen or objective threshold), could be an averaging artifact of positive and negative d's. Conscious accessibility is not either-or but more or less, and variable over time.


Novel scoring tool of hypoxemic respiratory failure and pulmonary hypertension for defining severity of persistent pulmonary hypertension of newborn.
To obtain preliminary validity data for a hypoxemic respiratory failure/pulmonary hypertension (HRF/PH) score for classifying persistent pulmonary hypertension of the newborn (PPHN). Retrospective chart review of 100 consecutive neonates admitted to a Children's hospital from 2016-2021 with PPHN, gestational age ≥34 weeks, and echocardiograms in the first week. We assessed the correlation between HRF/PH score and short-term outcomes using linear and logistic regressions. HRF/PH scores ranged 2-12 (mean 8.5), and were classified mild (0-5), moderate (6-10), and severe (11-15), with 6%, 77% and 17% infants in respective categories. HRF/PH score category correlated with invasive ventilation, nitric oxide, high frequency ventilation, vasoactive infusions, extracorporeal life support and death. HRF/PH score category did not correlate with duration of support or length of stay. The HRF/PH score offers a promising representation of disease severity for PPHN. The tool requires further validation in prospective studies and evaluation for long-term outcomes.


Role of phorbol ester receptors in the 12-0-tetradecanoyl-phorbol-13-acetate (TPA)-induced down-regulation of colony-stimulating factor (CSF-1) binding to murine peritoneal exudate macrophages.
Treatment of murine peritoneal exudate macrophages (PEM) by tumor-promoting phorbol esters (TPA) results in a rapid loss of binding activity to radioactive-labeled colony-stimulating factor ([125I]-CSF-1) on the cell surface. The inhibitory effect of TPA on PEM is transient; treated cells recover full [125I]-CSF-1 binding activity in less than 6 hr at 37 degrees C either in the presence or after the removal of added TPA. The role of phorbol ester receptors in the induction of [125I]-CSF-1 binding inhibition was studied. The biologically active ligand [3H]-phorbol 12,13-dibutyrate ([3H]-PDBu) bound specifically to cultured murine PEM. At 0 degree C, stable and equilibrium binding occurred after 2-3 hr. Scatchard analysis revealed linear plots with a dissociation constant and receptor number per cell of 20.9 nM and 3.9 X 10(5)/cell, respectively. Treatment of PEM with biologically active phorbol esters at 37 degrees C rapidly inhibited the binding activity of [3H]-PDBu on cell surface (down-regulation) and rendered these cells refractory to the TPA-induced [125I]-CSF-1 binding inhibition by the subsequent TPA treatment. The inhibition of phorbol ester binding activity on TPA-treated PEM is caused by a reduction in the total number of available phorbol ester receptors rather than by a decrease in receptor affinity as judged by Scatchard analysis. The disappearance of [3H]-PDBu binding activity is reversible and transient. However, unlike CSF-1 receptors the restoration of phorbol ester receptors on TPA-treated PEM is a very slow process; a prolonged incubation of up to 72 hr after the removal of TPA was required for PEM to regain fully its [3H]-PDBu binding activity. Furthermore, the degree of TPA-induced CSF-1-receptor down-regulation is closely associated with the number of available phorbol ester receptors present on PEM at the time of treatment. Thus, the refractoriness to TPA diminished as the phorbol ester receptors on PEM recovered. A 72-hr incubation time at 37 degrees C was needed for PEM to lose their refractoriness and again become fully sensitive to TPA-induced CSF-1-receptor down-regulation. This study provides evidence that the loss of CSF-1-receptors induced by TPA treatment requires the presence of phorbol ester receptors and proceeds presumably via a co-internalization of both CSF-1 and phorbol ester receptors; the refractoriness to TPA is thereby induced by a transient loss of available phorbol ester receptors.


Effects of plasticizers and surfactants on the film forming properties of hydroxypropyl methylcellulose for the coating of diclofenac sodium tablets.
Hydroxy propyl methyl cellulose (HPMC) 5cPs, an aqueous soluble polymer was employed for coating diclofenac sodium (DFS) tablets 25 mg for protecting the integrity of the drug yet rendering the drug to release at a faster rate on contact with the gastric environment. Proper optimization for the aqueous based film coating formulation was undertaken primarily employing plasticizers like polyethylene glycol (PEG) 400 and propylene glycol (PG). The defect free selected formulations were further subjected for studying the effects of surfactants like sodium lauryl sulphate (SLS) and Tween-80 along with the plasticizers. The quality of the aqueous film coats or the plasticizer efficiency in case of PEG-400 is in the order 1.5 > 0.5 > 1.0% and for PG 1 > 4 > 3% which can be stated on the basis of less incidence of major coat defects like chipping, cracking, orange peel, roughness, blistering, blooming, picking. The quality of aqueous film coat or the surfactant efficiency in case of SLS + PEG-400 is in the order 0.3 < 0.5 < 0.1% and SLS + PG is in the order 0.5 < 0.1 < 0.3%. In case of Tween-80 + PEG-400 the order is 0.3 < 0.5 < 0.1% and Tween-80 + PG is in the order 0.3 < 0.1 < 0.5%. Elegant film formation can be stated from fewer incidences of coat defects. The obtained coated tablets eventually satisfied all the normal physical parameters like thickness, weights, and weight gain, drug content, crushing strength, percent friability, disintegration time, dissolution profile and possible drug-polymer interactions. ANOVA was undertaken followed by Dunnet multiple comparison for the dissolution profile considering uncoated as the standard. The difference was considered significant at p ⩽ 0.01.


A neonatal rat model of pulmonary vein stenosis.
Pulmonary vein stenosis (PVS), one of the most challenging clinical problems in congenital heart disease, leads to secondary pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy. Due to the lack of a rodent model, the mechanisms underlying PVS and its associated secondary effects are largely unknown, and treatments are minimally successful. This study developed a neonatal rat PVS model with the aim of increasing our understanding of the mechanisms and developing possible treatments for PVS. PVS was created at postnatal day 1 (P1) by banding pulmonary veins that receive blood from the right anterior and mid lobes. The condition was confirmed using echocardiography, computed tomography (CT), gross anatomic examination, hematoxylin and eosin (H&E) staining, fibrosis staining, and immunofluorescence. Lung and RV remodeling under the condition of PVS were evaluated using H&E staining, fibrosis staining, and immunofluorescence. At P21, echocardiography revealed a change in wave form and a decrease in pulmonary artery acceleration time-indicators of PAH-at the transpulmonary valve site in the PVS group. CT at P21 showed a decrease in pulmonary vein diameter in the PVS group. At P30 in the PVS group, gross anatomic examination showed pulmonary congestion, H&E staining showed wall thickening and lumen narrowing in the upstream pulmonary veins, and immunofluorescence showed an increase in the smooth muscle layers in the upstream pulmonary veins. In addition, at P30 in the PVS group, lung remodeling was evidenced by hyperemia, thickening of pulmonary small vessel walls and smooth muscle layers, and reduction of the number of alveoli. RV remodeling was evidenced by an increase in RV free wall thickness. A neonatal rat model of PVS was successfully established, showing secondary lung and RV remodeling. This model may serve as a useful platform for understanding the mechanisms and treatments for PVS.


Combined experimental and theoretical study of o-xylene elimination on Fe-Mn oxides catalysts.
The development of low-cost and easily accessible catalysts to realize the practical applications of catalytic combustion of volatile organic compounds remains a challenge. In this work, a series of Fe-Mn oxides catalysts were prepared via a facile redox-precipitation route for the elimination of o-xylene. Among the synthesized catalysts, Fe3Mn1-RP exhibited excellent activity for o-xylene elimination with a T50 and T90 of 223 °C and 236 °C, respectively (o-xylene concentration = 500 ppm, WHSV = 36,000 mL g-1 h-1). Characterization results demonstrated that superior catalytic activity could be achieved from large specific surface area, good reducibility and high proportion of Mn4+. Besides, high Fe contents proved beneficial in generating additional oxygen vacancies, thereby improving the performance of the catalyst. The stable crystal structures and surface electron density distributions of the catalysts, and adsorption sites of o-xylene on the catalyst surface, were also determined through density functional theory (DFT) calculations to provide an in-depth mechanism on how the o-xylene oxidation occurred. Moreover, analysis of the energy barrier during the oxidation process proved that the ring-opening reaction on the surface of Fe3Mn1-RP with an activation energy as low as 2.46 eV would more likely occur via oxygen vacancies.


Identification and potential role of PSD-95 in Schwann cells.
Postsynaptic density-95 (PSD-95) is one of neuronal nitric oxide synthase (nNOS)-anchoring proteins and plays an important role in specifying the sites of reaction of nitric oxide (NO) in the nervous system. The present study aims to investigate the presence of PSD-95 in rat Schwann cells (SCs) and the association of PSD-95 and nNOS with serum-induced SCs proliferation. The expression of both molecules downregulated significantly after 48 h of serum deprivation, and increased gradually to the peak at 12 h, ultimately returned to the control level at 48 h after serum stimulation. The association of PSD-95 with nNOS was observed in Ki67 and BrdU-positive SCs. The selective nNOS inhibitor arrested the cell cycle progress and decreased the proliferating cell nuclear antigen (PCNA) levels. These findings suggested that PSD-95 and nNOS may collectively participate in the proliferation of SCs, providing further evidence for the role of NO during peripheral nerve regeneration.


Factors restricting maximal preservation of neuronal glycogen after perfusion fixation with dimethyl sulfoxide and iodoacetic acid in Bouin's solution. Histochemical observations in the brain of the Netherlands dwarf rabbit.
Thirty seconds after an initial intracardial epinephrine injection, deeply anesthetized animals are perfused consecutively with saline, Bouin's and 100% ethanol solutions, each containing 1% or 5% DMSO (Me2SO) and 0.01 M iodoacetic acid. In the Netherlands dwarf rabbit and the guinea pig, a maximal preservation of dimedone PAS-stainable, saliva-digestible glycogen is achieved, without signs of polarization of glycogen, in many neuronal and neuroglial cells occupying either brain stem nuclei or occasionally narrow perivascular zones. Tentatively, these results are ascribed to a combined effect of (a) the alleged capacity of DMSO to accelerate fixation and to suppress activation of adenylate cyclase and (b) the rapid action of Bouin's solution so that the glycogen particles become instantaneously enclosed in situ in a skeleton of coagulated proteinaceous elements. The paradoxical over-all reduction in preservation of neuronal and astrocytic glycogen may be associated either with a demonstrable loss of the fixative into the peripheral vasculature, because of contrary actions of DMSO and epinephrine, or with a transvascular passage of epinephrine resulting in neuronal glycogenolysis where the blood-brain barrier is absent or affected by DMSO. Other defects are the occurrence of myriad pericapillary foci of inadequate tissue preservation, rare petechial hemorrhages, post mortem fat emboli, and ubiquitous Buscaino plaques. Despite these adverse results preventing utilization of this technique in systematic histochemical investigations on neuronal glycogen, remarkable qualitative characteristics such as the neurons' capacity to store glycogen throughout their perikarya have been revealed.


Diet quality of cancer survivors and noncancer individuals: Results from a national survey.
Patterns of poor nutritional intake may exacerbate the elevated morbidity experienced by cancer survivors. It remains unclear whether cancer survivors adhere to existing dietary guidelines and whether survivors' diets differ from those of individuals without cancer over the long term. The authors evaluated dietary intake and quality in 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010 compared with dietary intake and quality in 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity. Dietary intake was assessed using 24-hour dietary recalls. The 2010 Healthy Eating Index (HEI-2010) was used to evaluate diet quality. The mean ± standard deviation HEI-2010 total score was 47.2 ± 0.5 in the cancer survivors and 48.3 ± 0.4 in the noncancer group (P = .03). Compared with the noncancer group, cancer survivors had a significantly lower score for empty calories (13.6 vs 14.4; P = .001), which corresponded to worse adherence to dietary intake of calories from solid fats, alcohol, and added sugars. Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group (15.0 vs 15.9 g per day; P = .02). In relation to recommended intake, survivors' mean dietary intake of vitamin D, vitamin E, potassium, fiber, and calcium was 31%, 47%, 55%, 60%, and 73%, respectively; whereas their mean dietary intake of saturated fat and sodium was 112% and 133%, respectively, of the recommended intake. Cancer survivors had poor adherence to the US Department of Agriculture 2010 Dietary Guidelines for Americans, and their intake patterns were worse than those in the general population for empty calories and fiber.


Hepatic myelopathy with spastic paraparesis.
Progressive myelopathy is a rare neurological complication of chronic liver disease with portal hypertension and there is no special diagnostic tool for hepatic myelopathy. Neuropathological studies of the patients with hepatic myelopathy have demonstrated demyelination of the lateral corticospinal tracts with various degree of axonal loss. Transcranial magnetic stimulation (TMS) is widely utilized as an indicator of changes in excitability and conductivity of the motor pathways. TMS studies are also used for the diagnosis of hereditary spastic paraparesis in the literature. In this study, we described two patients who presented with spastic paraparesis; TMS studies suggested that they had myelopathy and diagnosed as hepatic myelopathy when all the other possible diagnoses were ruled out.


The concept of a 'case' in psychiatric population surveys.
A series of in-patients, a series of out-patients and a series of women from a general population sample, all aged under 65, and all living in the same area of south-east London, were examined using the ninth edition of the Present State Examination (PSE). An 'index of definition' (ID), based on number, type and severity of PSE symptoms, was constructed in order to define a threshold point above which sufficient information was available to allow classification into one of the functional psychoses or neuroses. The index specified 8 levels of definition of disorder; the threshold point for a 'case' lying between levels 4 and 5. The identification of 'cases' by this means in the general population series was highly concordant with global clinical judgement. When the 3 series were compared, the in-patient series contained the most definite cases, the outpatient series was intermediate, and the general population series was characterized mainly by below-threshold conditions. Disorders above the threshold point were classified using the CATEGO program. The clinical severity of the depressive disorders and anxiety states identified in this way in the 3 series was compared on the basis of symptom and syndrome profiles and PSE scores. As expected, the inpatients had the most severe, and the general population 'cases' the least severe disorders. It is suggested that the PSE-ID-CATEGO techniques can be used to help standardize certain aspects of case-finding and case-description in both referred and non-referred populations and thereby make the results of surveys more comparable.


A systematic review with pooled analysis of clinical presentation and immunodiagnostic testing in mucous membrane pemphigoid: association of anti-laminin-332 IgG with oropharyngeal involvement and the usefulness of ELISA.
Mucous membrane pemphigoid (MMP) is characterized by subepithelial blistering due to IgG autoantibodies targeting various components of the dermal-epidermal basement membrane zone. Immunodiagnostics play an important role in making a precise diagnosis. Measures of test sensitivity and specificity, however, typically come from studies in diseases such as bullous pemphigoid, where the exact antigenic site may not be the same. Additionally, the association of clinical phenotype and autoantibody profiles has been an area of debate. We evaluated the sensitivity and specificity of ELISA in MMP for the known target antigens BP180 and laminin-332, as well as characterized the frequency of IgG antibodies against each laminin-332 subdomain. Lastly, we analysed whether IgG auto-antibody profiles were associated with clinical phenotype. We performed a systematic review of Medline/PubMed to compile MMP patient demographics, clinical manifestations and immunodiagnostic results. ELISA sensitivities and specificities for autoantigens were calculated in patients with positive immunoblot or immunoprecipitationstudies. IgG reactivity for each laminin-332 subunit was recorded. Associations between positive immunological tests and clinical presentation were evaluated using chi-squared test tests or Fisher's exact test when appropriate. For patients with a positive immunoblot or immunoprecipitation to NC16a, ELISA using both the NC16a and C-terminal portion of BP180 demonstrated a sensitivity and specificity of 73% and 93%. However, for individuals with IgG against the C-terminal domain of BP180, the sensitivity and specificity was 43% and 56%, respectively. LN-332 ELISA demonstrated 75% sensitivity, but only for patients with IgG reactivity against the α3 subunit. In patients with laminin-332 MMP, 86.4% demonstrated IgG against the α3 subunit. IgG autoantibodies against laminin-332 are significantly associated with pharyngo-laryngeal (P < 0.0001) and oro-pharyngo-laryngeal (P = 0.006) involvement. Immunodiagnostics play a major role in diagnosing MMP, though limited sensitivity may necessitate several forms of testing for confirmation.


"Vacuum-assisted staining": a simple and efficient method for screening in Drosophila.
The constantly growing number of genetic tools rapidly increases possibilities for various screens in different model organisms and calls for new methods facilitating screen performance. In particular, screening procedures involving fixation and staining of samples are difficult to perform at a genome-wide scale. The time-consuming task to generate these samples makes such screens less attractive. Here, we describe the use of multi-well filter plates for high throughput labellings of different Drosophila organs and zebrafish embryos. Our inexpensive vacuum-assisted staining protocol minimises the risk of sample loss, reduces the amount of staining reagents and drastically decreases labour and repetitive work. The simple handling of the system and the commercial availability of its components makes this method easily applicable to every laboratory.


Renal osteodystrophy: some new questions on an old disorder.
The two major lesions of renal osteodystrophy are osteitis fibrosa cystica (OFC) and osteomalacia (OM). OFC is the characteristic bone lesion of uremic hyperparathyroidism. Although renal failure causes predictable parathyroid hyperplasia, the precise pathogenetic mechanism is still not defined. The "hyperphosphatemia-hypocalcemia-parathyroid hormone (PTH) hypersecretion" sequence of events is no longer an adequate model for the pathogenesis of uremic hyperparathyroidism. Other abnormalities associated with uremia include reduced 1,25-dihydroxyvitamin D (1,25D) synthesis, changes in intracellular phosphorus content or transcellular phosphate fluxes, or alteration in PTH metabolism, eg, change in set-point for PTH secretion. Each abnormality interacts with others and contributes to PTH hypersecretion, but none can completely account for the development and persistence of hyperparathyroidism in renal failure. The possibility that uremia may directly cause parathyroid hyperplasia remains open. It is also possible that factor(s) that initiate hyperparathyroidism may turn out to be quite different from that which sustains the hyperparathyroid state. Although both vitamin D-deficient and vitamin D-resistant OM may develop in patients with renal failure, the majority of uremic OM seen currently is "vitamin D-refractory." Although now there is persuasive evidence implicating aluminum (Al) accumulation as the major pathogenetic cause for the mineralization defect seen in this disorder, additional disturbances may play important contributory roles. Such factors would include extraskeletal effects of Al, differences in host-susceptibility to this element, the localization of Al within bone, uremia per se, and the participation of other metals and toxins. Finally, possible interactions between hyperparathyroidism and OM of uremia are speculated on.


Nucleo-cytoplasmic ratio in ageing skeletal muscle.
In order to investigate possible changes in the nucleo-cytoplasmic ratio of the muscle fibres during ageing, samples of quadriceps femoris from 15 normal individuals whose age ranged from 17 to 82 years were studied (autopsy material). The mean lesser diameter and the number and size of the muscle fibre nuclei were calculated using a planimetric technique. It was found that nucleo-cytoplasmic ratio increased significantly after the age of 60 years. This was due to a decrease in the mean fibre size whilst the number and the size of myonuclei remained unchanged. The resemblance of this finding to denervation atrophy changes is noted.


Do current outcomes justify more liberal use of revascularization for vasculogenic claudication? A single center experience of 1,000 consecutively treated limbs.
The purpose of this study was to reconsider current recommended treatment guidelines for vasculogenic claudication by examining the contemporary results of surgical intervention. We performed a retrospective review of 1,000 consecutive limbs in 669 patients treated for medically refractory vasculogenic claudication and prospectively followed. Outcomes measured included procedural complication rates, reconstruction patency, limb salvage, maintenance of ambulatory status, maintenance of independent living status, survival, symptom resolution, and symptom recurrence. Of the 1,000 limbs treated, endovascular therapy was used in 64.3% and open surgery in 35.7% of patients; aortoiliac occlusive disease was treated in 70.1% and infrainguinal disease in 29.9% of patients. The overall 30-day periprocedural complication rate was 7.5%, with no notable difference in complication rates when comparing types of treatment or levels of disease. Overall reconstruction primary patency rates were 87.7% and 70.8%; secondary patencies were 97.8% and 93.9%; limb salvage, 100% and 98.8%; and survivals, 95.4% and 76.9%, at 1 and 5 years, respectively. More than 96% of patients maintained independence and ambulatory ability at 5 years. Overall symptom resolution occurred in 78.8%, and symptom recurrence occurred in 18.1% of limbs treated, with slightly higher resolution and recurrence noted in patients treated with endovascular therapy. Contemporary treatment of vasculogenic claudication is safe, effective, and predominantly endovascular. These data support a more liberal use of revascularization for patients with claudication and suggest that current nonoperative treatment guidelines may be based more on surgical dogma than on achievable outcomes.


Tumors of the brain in the Sudan.
One hundred twenty-three cases of tumors of the brain encountered in patients admitted over a 10-year period (1971-1981) at the Neurosurgical Section, Shaab Teaching Hospital, Khartoum, Sudan are presented. Special emphasis is directed at the high incidence (45.5%) of meningiomas. Clinical and pathological findings are reported.


Kirchhoff rod-based three-dimensional dynamical model and real-time simulation for medical-magnetic guidewires.
Magnetic guidewire, fabricated from hard-magnetic soft composites, has recently emerged as an appropriate candidate for magnetic actuation systems to perform intravascular surgical navigation, owing to its elastic, magnetically steerable properties and good interphase with biological tissues. A suitable and efficient mathematical model for the magnetic guidewire is essential in the system to execute remote manipulation and active control. This paper presents a real-time Kirchhoff rod-based dynamical modeling approach, the magneto-elastic rod model, to simulate magnetic guidewire, which provides accurate simulations for two- and three-dimensional dynamic deflections induced by external magnetic fields and obtains deformed guidewire shapes in quasi-static status. The proposed model is capable of describing the intrinsic principles of elastic body actuation by torques generated from the hard-magnetic soft matrix. The effectiveness of the developed model is validated, and the real-time simulation application is conducted via the semi-implicit numerical integration method. It has been shown that the presented dynamical model captures large nonlinear deformations and transient responses of the magnetic guidewire in an imitated human blood environment, which could offer robust support for the construction of a simulated magnetically driven surgical system.


Symbiotic relationship between Prevotella denticola and Streptococcus mutans enhances virulence of plaque biofilms.
This study aimed to explore that whether interactions between Prevotella denticola and Streptococcus mutans could promote the establishment of hypervirulent biofilms on teeth surface and eventually influence the occurrence and development of caries. Based on single-species biofilms of either P. denticola or S. mutans, and dual-species biofilms of both bacteria, we compared the virulence properties associated with cariogenicity in vitro, including carbohydrate metabolism and acid productivity, synthesis of extracellular polysaccharides, biomass and architecture of biofilms, level of enamel demineralization and expression of virulence genes associated with carbohydrate metabolism and adhesion in S. mutans. The data demonstrated that, compared to single-species of above two taxa, dual-species produced lactate by metabolizing carbohydrates at a higher level during the observation period. Moreover, dual-species biofilms accrued more biomass and exhibited more dense microcolonies and abundant extracellular matrix. And it's noticeable that the level of enamel demineralization in dual-species biofilms was more augmented than that of single-species. In addition, the presence of P. denticola induced the expression of virulence genes gtfs and gbpB in S. mutans. Symbiotic relationship between P. denticola and S. mutans enhances caries-associated virulence of plaque biofilms, which might provide new strategies for effective prevention and treatment of caries.


Adrenal solitary fibrous tumor: A case report.
Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm, originally described in the pleural cavity. It may also occur in extrapleural organs like adrenal gland. We present a case of a fifty two-year old Arab man who has been admitted in urology department for right lumbar pain. A suspect malignant adrenal mass has been detected. He underwent right adrenalectomy and histologically it was SFT. The follow-up three years after surgery is unremarkable. The prognosis of SFT after surgery is unpredictable. A long term follow-up is mandatory to detect local recurrence or distant metastasis.


Benchmarking State-of-the-Art Approaches for Norovirus Genome Assembly in Metagenome Sample.
A recently published article in BMCGenomics by Fuentes-Trillo et al. contains a comparison of assembly approaches of several noroviral samples via different tools and preprocessing strategies. It turned out that the study used outdated versions of tools as well as tools that were not designed for the viral assembly task. In order to improve the suboptimal assemblies, authors suggested different sophisticated preprocessing strategies that seem to make only minor contributions to the results. We have reproduced the analysis using state-of-the-art tools designed for viral assembly, and we demonstrate that tools from the SPAdes toolkit (rnaviralSPAdes and coronaSPAdes) allow one to assemble the samples from the original study into a single contig without any additional preprocessing.


Endoscopic removal of a gastric pharmacobezoar induced by clomipramine, lorazepam, and domperidone overdose: a case report.
Gastric pharmacobezoars are a rare entity that can induce mechanical gastric outlet obstructions and sometimes prolong toxic pharmacological effects. Certain medications, such as sustained-release forms, contain cellulose derivatives that may contribute to the adhesion between pills and lead to the creation of an aggregate resulting in a pharmacobezoar. Case reports are rare, and official guidelines are needed to help medical teams choose proper treatment options. Our patient was a 40-year-old Caucasian woman with borderline personality disorder and active suicidal thoughts who was found unconscious after a massive drug consumption of slow-release clomipramine, lorazepam, and domperidone. On her arrival in the emergency room, endotracheal intubation was preformed to protect her airway, and a chest x-ray revealed multiple coffee grain-sized opaque masses in the stomach. She was treated with activated charcoal followed by two endoscopic gastric decontaminations 12 h apart in order to extract a massive gastric pharmacobezoar by manual removal of the tablets. This case demonstrates that in the case of a massive drug consumption, a pharmacobezoar should be suspected, particularly when cellulose-coated pills are ingested. Severe poisoning due to delayed drug release from the gastric aggregate is a potential complication. Detection by x-ray is crucial, and treatment is centered on removal of the aggregate. The technique of decontamination varies among experts, and no formal recommendations exist to date. It seems reasonable that endoscopic evaluation should be performed in order to determine the appropriate technique of decontamination. Care should be patient-oriented and take into account the clinical presentation and any organ failure, and it should not be determined solely by the suspected medication ingested. Thus, serum levels are not sufficient to guide management of tricyclic antidepressant intoxication.


Children come first? A brief history of children's mental health services.
This article provides a brief history on the evolution of child mental health services. From 1961 when modern day mental health programming began with the Joint Commission on Mental Health and Illness to key developments in children's mental health services and prevention in modern day.


Understanding Signatures of Emergent Magnetism in Topological Insulator/Ferrite Bilayers.
Magnetic insulator-topological insulator heterostructures have been studied in search of chiral edge states via proximity induced magnetism in the topological insulator, but these states have been elusive. We identified MgAl_{0.5}Fe_{1.5}O_{4}/Bi_{2}Se_{3} bilayers for a possible magnetic proximity effect. Electrical transport and polarized neutron reflectometry suggest a proximity effect, but structural data indicate a disordered interface as the origin of the magnetic response. Our results provide a strategy via correlation of microstructure with magnetic data to confirm a magnetic proximity effect.


Fast precipitation of uniform CaCO3 nanospheres and their transformation to hollow hydroxyapatite nanospheres.
Shape-controlled synthesis of calcium carbonate with specific polymorphs can be achieved by the assistance of organic additives. In this study, highly uniform nanosized calcium carbonate spheres were synthesized by a fast precipitation method in the presence of a simple polymer, poly(styrene sulfonate) (PSS). The polymorph of the synthesized calcium carbonate products changes from pure calcite in PSS-free reactions to vaterite in PSS-containing (1-50 g/L) reactions. The effect of PSS on the formation of vaterite can be attributed to the two aspects: decrease of driving force by reducing the interfacial energy, and phase stabilization effect caused by the adsorbed PSS. A higher PSS concentration (50 g/L) results in highly uniform vaterite nanospheres of 400-500 nm in diameter. Furthermore, PSS is found more effective to induce the formation of vaterite in the Ca(2+)-rich reaction condition (Ca(2+):CO(3)(2-)=5:1) than in the CO(3)(2-)-rich conditions (Ca(2+):CO(3)(2-)=1:5). It has also been found that different mixing mode of the calcium and carbonate precursor solutions has a significant influence on the size distribution of the products. Finally, with a controlled anion-exchange method, the as-prepared vaterite nanospheres can be easily transformed to hollow hydroxyapatite spheres, which exhibit great potential to be used as the drug carriers due to their considerably high surface area and biocompatibility.


Insulin suppresses intake without inducing illness in sham feeding rats.
Insulin's effects on consumption were investigated in rats feeding with open gastric cannulas. Insulin produced small but statistically reliable decreases in sham intake. Intake was reduced during the one-hour sham feeding interval by 11 to 18%, however, the second, third and fourth 15-min intervals were reduced by 20 to 33%. An initial increase (first 15 min of sham feeding) following insulin injection offset somewhat insulin's suppressive effects on sham intake. All reductions were obtained by comparing sham intake following 0.1 to 0.75 U insulin per rat to intake following saline. When insulin or saline injections were paired with alternatively flavored sweetened condensed milk during sham feeding, subjects preferred the insulin-paired flavor in a subsequent two-bottle test. After just 6 complete pairings, insulin-paired, flavored milk was preferred at a ratio of almost six to one. The results indicate the effectiveness of insulin in inhibiting intake in a situation in which the actions of other potential satiety mechanisms are minimized. Additionally, insulin accomplishes this without inducing a flavor aversion for the milk sham consumed.