Functional bracing of ACL injuries: current state and future directions.
Functional braces are commonly prescribed to treat anterior cruciate ligament (ACL) injury. The results of the existing literature on functional brace use are mixed. The purpose of this study was to evaluate the history and current state of functional ACL bracing and to identify design criteria that could improve upon current bracing technologies. A literature search was performed through the PubMed MEDLINE database in April 2013 for the keywords "anterior cruciate ligament" and "brace". Articles published between January 1, 1980, and April 4, 2013, were retrieved and reviewed. Current functional braces used to treat ACL injury were identified. The function of the native ACL was carefully studied to identify design requirements that could improve upon current bracing technologies. Biomechanical evaluations of functional brace effects at time zero have been mixed. Functional brace use reportedly does not improve long-term patient outcomes following ACL reconstruction, but has been shown to reduce subsequent injury rates while skiing in both ACL-deficient and reconstructed skiers. In situ force in the ACL varies with flexion angle and activity. Currently, no brace has been designed and validated to replicate the force-flexion behavior of the native ACL. Biomechanical and clinical evidence suggests current functional bracing technologies do not sufficiently restore normal biomechanics to the ACL-deficient knee, protect the reconstructed ACL, and improve long-term patient outcomes. Further research into a functional brace designed to apply forces to the knee joint similar in magnitude to the native ACL should be pursued. III.


Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9.
Toll-like receptors (TLRs) activate the innate immune system in response to pathogens. Here we show that TLR9 proteolytic cleavage is a prerequisite for TLR9 signaling. Inhibition of lysosomal proteolysis rendered TLR9 inactive. The carboxy-terminal fragment of TLR9 thus generated included a portion of the TLR9 ectodomain, as well as the transmembrane and cytoplasmic domains. This cleavage fragment bound to the TLR9 ligand CpG DNA and, when expressed in Tlr9(-/-) dendritic cells, restored CpG DNA-induced cytokine production. Although cathepsin L generated the requisite TLR9 cleavage products in a cell-free in vitro system, several proteases influenced TLR9 cleavage in intact cells. Lysosomal proteolysis thus contributes to innate immunity by facilitating specific cleavage of TLR9.


Cardiac Biomarkers in Advanced Heart Failure: How Can They Impact Our Pre-transplant or Pre-LVAD Decision-making.
Decision-making in advanced heart failure (HF) is a complex process that involves careful consideration of competing tradeoffs of risks and benefits in regard to heart transplantation (HT) or left ventricular assist device (LVAD) placement. The purpose of this review is to discuss how biomarkers may affect decision-making for HT or LVAD implantation. N-Terminal probrain natriuretic peptide, soluble suppression of tumorigenicity-2, galectin-3, copeptin, and troponin T levels are associated with HF survival and can help identify the appropriate timing for advanced HF therapies. Patients at risk of right ventricular failure after LVAD implantation can be identified with preimplant biomarkers of extracellular matrix turnover, neurohormonal activation, and inflammation. There is limited data on the adoption of biomarker measurement for decision-making in the allocation of advanced HF therapies. Nonetheless, biomarkers can improve risk stratification and prognostication thereby optimizing patient selection for HT and LVAD implantation.


Diagnostic significance of immunological assay of pancreatic elastases in acute pancreatitis.
Pancreatic elastases have been assumed to be implicated in the pathogenesis of the vascular injury in acute hemorrhagic pancreatitis. We reported the purification and some properties of human pancreatic elastases. In the present study, the value of the determination of serum pancreatic elastases was investigated. 39 patients with acute hemorrhagic and acute edematous pancreatitis were studied. Serum elastase 1(E-1) and elastase 2(E-2) were measured by radioimmunoassay recently developed in our laboratory. The molecular form of exogenous and endogenous elastases in serum was studied by gel filtration on Sephadex G-200. The mean and standard deviation of serum pancreatic E-1 and E-2 were 1.49 +/- 0.49 ng/ml and 292 +/- 82 ng/ml, respectively. In acute pancreatitis, both E-1 and E-2 had markedly raised serum concentrations. However, no significant difference was observed between acute hemorrhagic and acute edematous pancreatitis. Endogenous immunoreactive E-1 and E-2 were present in serum in complex form with alpha 1-antitrypsin. In contrast, exogenous elastases were bound to alpha 1-antitrypsin and alpha 2-macroglobulin.


Quality of life improves in patients with chronic heart failure and Cheyne-Stokes respiration treated with adaptive servo-ventilation in a nurse-led heart failure clinic.
The aim of this study was to investigate if quality of life improved in chronic heart failure patients with Cheyne-Stokes respiration treated with adaptive servo-ventilation in nurse-led heart failure clinic. Cheyne-Stokes respiration is associated with decreased quality of life in patients with chronic heart failure. Adaptive servo-ventilation is introduced to treat this sleep-disordered breathing. Randomised, controlled design. Fifty-one patients (ranging from 53-84 years), New York Heart Association III-IV and/or left ventricular ejection fraction ≤40% and Cheyne-Stokes respiration were randomised to an intervention group who received adaptive servo-ventilation or a control group. Minnesota Living with Heart Failure Questionnaire was used to assess quality of life at randomisation and after three months. Both groups were followed in the nurse-led heart failure clinic. Adaptive servo ventilation improved quality of life-scores both in a per protocol analysis and in an intention to treat analysis. Twenty-one patients dropped out of the study, nine in the control and 12 in the intervention group. Use of adaptive servo-ventilation improved quality of life in chronic heart failure patients with Cheyne-Stokes respiration. However, the drop-out rate was high. Chronic heart failure patients come regularly to the nurse-led heart failure clinic. The heart failure nurses' competency has to include knowledge of equipment to provide support and continuity of care to the patients.


A mathematical model for the decay of short-term memory with age.
A mathematical neural net model based on our previous studies (Anninos et al, 1970; Anninos, 1972) is proposed here to show that the short-term memory of events decays with man age. In particular, in this work we try to explain why recent memories die out with age before the establishment of permanent memory. As it was shown we lose some connections due to the loss of a large number of neurons with age, and in our model this corresponds to a smaller hysteresis loop which, according to our assumption, represents the short-term memory of an event. Thus we showed that if we decrease the number of connections even further the hysteresis loop will vanish to a single curve which, according to Katchalsky & Oplatka (1969), corresponds to a memory-less system.


Metabolic profiling of valproic acid in patients using negative-ion chemical ionization gas chromatography-mass spectrometry.
A negative-ion chemical ionization gas chromatographic-mass spectrometric method for the determination of valproic acid (VPA) and fourteen of its metabolites in a single chromatographic run is reported. The assay features the use of four internal standards and is applicable to the analysis of small serum and urine volumes. A combination of pentafluorobenzyl and trimethylsilyl derivatization resulted in the [M - 181]- ion as the base peak for all the metabolites measured. When these ions were monitored sensitivities in the low picogram levels were achieved. The VPA metabolite profile was determined in pediatric patients on VPA monotherapy and on combined VPA therapy with either carbamazepine or clobazam. The recently characterized diene metabolite, (E,E)-2,3'-diene-VPA, was found to be a major serum metabolite of VPA. In the patient groups taking VPA in combination with carbamazepine, the induction of omega and omega-1 pathways of VPA metabolism was apparent, while the levels of the beta-oxidation products were significantly decreased.


Hydrodynamic chronoamperometry for probing kinetics of anaerobic microbial metabolism--case study of Faecalibacterium prausnitzii.
Monitoring in vitro the metabolic activity of microorganisms aids bioprocesses and enables better understanding of microbial metabolism. Redox mediators can be used for this purpose via different electrochemical techniques that are either complex or only provide non-continuous data. Hydrodynamic chronoamperometry using a rotating disc electrode (RDE) can alleviate these issues but was seldom used and is poorly characterized. The kinetics of Faecalibacterium prausnitzii A2-165, a beneficial gut microbe, were determined using a RDE with riboflavin as redox probe. This butyrate producer anaerobically ferments glucose and reduces riboflavin whose continuous monitoring on a RDE provided highly accurate kinetic measurements of its metabolism, even at low cell densities. The metabolic reaction rate increased linearly over a broad range of cell concentrations (9 × 10(4) to 5 × 10(7) cells.mL(-1)). Apparent Michaelis-Menten kinetics was observed with respect to riboflavin (KM = 6 μM; kcat = 5.3 × 10(5) s(-1), at 37 °C) and glucose (KM = 6 μM; kcat = 2.4 × 10(5) s(-1)). The short temporal resolution allows continuous monitoring of fast cellular events such as kinetics inhibition with butyrate. Furthermore, we detected for the first time riboflavin reduction by another potential probiotic, Butyricicoccus pullicaecorum. The ability of the RDE for fast, accurate, simple and continuous measurements makes it an ad hoc tool for assessing bioprocesses at high resolution.


Sex Differences in Poststroke Cognitive Impairment: A Multicenter Study in 2343 Patients With Acute Ischemic Stroke.
Poststroke cognitive impairment (PSCI) occurs in about half of stroke survivors. Cumulative evidence indicates that functional outcomes of stroke are worse in women than men. Yet it is unknown whether the occurrence and characteristics of PSCI differ between men and women. Individual patient data from 9 cohorts of patients with ischemic stroke were harmonized and pooled through the Meta-VCI-Map consortium (n=2343, 38% women). We included patients with visible symptomatic infarcts on computed tomography/magnetic resonance imaging and cognitive assessment within 15 months after stroke. PSCI was defined as impairment in ≥1 cognitive domains on neuropsychological assessment. Logistic regression analyses were performed to compare men to women, adjusted for study cohort, to obtain odds ratios for PSCI and individual cognitive domains. We also explored sensitivity and specificity of cognitive screening tools for detecting PSCI, according to sex (Mini-Mental State Examination, 4 cohorts, n=1814; Montreal Cognitive Assessment, 3 cohorts, n=278). PSCI was found in 51% of both women and men. Men had a lower risk of impairment of attention and executive functioning (men: odds ratio, 0.76 [95% CI, 0.61-0.96]), and language (men: odds ratio, 0.67 [95% CI, 0.45-0.85]), but a higher risk of verbal memory impairment (men: odds ratio, 1.43 [95% CI, 1.17-1.75]). The sensitivity of Mini-Mental State Examination (<25) for PSCI was higher for women (0.53) than for men (0.27; P=0.02), with a lower specificity for women (0.80) than men (0.96; P=0.01). Sensitivity and specificity of Montreal Cognitive Assessment (<26.) for PSCI was comparable between women and men (0.91 versus 0.86; P=0.62 and 0.29 versus 0.28; P=0.86, respectively). Sex was not associated with PSCI occurrence but affected domains differed between men and women. The latter may explain why sensitivity of the Mini-Mental State Examination for detecting PSCI was higher in women with a lower specificity compared with men. These sex differences need to be considered when screening for and diagnosing PSCI in clinical practice.


Polyradiculopathy post-concomitant chemoradiation for carcinoma of the uterine cervix treated with pelvic and para-aortic fields.
It is becoming more common to include the para-aortic lymph nodes in the radiation fields of patients treated with concomitant weekly cisplatin for node-positive squamous cell carcinoma of the cervix. We report on two patients who developed unexpected subacute neurological toxicity with lower extremity paresis and paresthesis, beginning 1 and 4 months post-treatment. We believe this to be a rare side effect of chemoradiation. As the dose delivered to the spinal nerve roots was less than 37 Gy in 25 fractions, we believe that the extended fields and concomitant cisplatin had a synergistic effect on the nerves.


Open-tubular capillary electrochromatography/electrospray ionization-mass spectrometry using polymeric surfactant as a stationary phase coating.
We describe the use of the polymeric surfactant poly(sodium undecylenic sulfate) (poly-SUS) as a stationary phase coating in open-tubular capillary electrochromatography (OT-CEC) coupled with electrospray ionization-mass spectrometry (ESI-MS) for the analysis of beta-blocker and benzodiazepine analytes. The production of a polymeric surfactant coating on the capillary inner wall involves (i) adsorption of the cationic polymer poly(diallyldimethylammonium chloride) (PDADMAC) to the inner surface of capillary, and (ii) adsorption of the negatively charged poly-SUS onto the cationic polymer layer via strong physical interaction of the two polymer layers. As compared with micellar electrokinetic chromatography (MEKC) coupled with ESI-MS, the main advantage of this proposed method is minimization of introduction of the monomeric or polymeric surfactant into the mass spectrometer, thus avoiding the interference of the nonvolatile micelle in ESI-MS. The effects of buffer pH and applied voltage on the separation of the analytes are also discussed. Under optimum conditions, four of the five beta-blockers and four benzodiazepines are separated.


p44/42MAPK and p90RSK modulate thermal stressed physiology response in Apostichopus japonicus.
Reversible protein phosphorylation (RPP) plays a key role in signal transduction, enzyme activity and metabolic maintenance in response to extreme changes in the environment. In this study, we identified 55 phosphorylated proteins in Apostichopus japonicus coelomocytes by iTRAQ analysis, and sixteen proteins displayed differently expressed profiles between thermal stressed and control groups. Mitogen-activated protein kinase (MAPK) signaling cascade was further characterized by Western blot. Spatial expression analysis revealed that phospho-p44/42MAPK levels were mainly detected in coelomocytes and muscle, and no signal in intestine and respiratory trees, although the protein were constitutively expressed in all examined tissues. Time-course expression analysis shown that the amount of phospho-p44/42MAPK decreased by 57-60% in coelomocytes and 29-40% in muscle in acute exposure stage of 20°C and 25°C, respectively. In higher temperature remaining stage, phospho-p44/42MAPK was both induced with 1.7-fold increase at 20°C and 5.2-fold at 25°C at the first 12h in coelomocytes, which was consistent with the change of p44/42MAPK. Similarly, 2.5-fold and 2.7-fold increases were detected in muscle at corresponding exposure temperature. In contrast, the p44/42MAPK in muscle showed depressed expression profiles. As time progressed, phospho-p44/42MAPK levels were all decreased significantly both in coelomocytes and in muscles. A reduction in phosphorylation levels was detected at 84h in 20°C exposed coelomocytes with 0.42-fold decrease, and at 36h in 25°C challenged muscle by 0.80-fold decrease. Correlated expression profiles between phospho-p90RSK and phospho-p44/42MAPK suggest that p44/42MAPK may be involved in temperature-induced metabolic suppression through targeting p90RSK in A. japonicus.


Assessment of systemic and pulmonary arterial remodelling in women with systemic sclerosis.
Systemic sclerosis (SSc) leads to pulmonary circulation dysfunctionand there are some indications of systemic circulation impairment. We evaluated the influence of SSc on the elastic properties of large systemic arterial walls and potential correlations between systemic and pulmonary circulation involvement. We examined 75 consecutive women (mean age 53.13±10.1 years) with confirmed SSc [mean disease duration (DD) 7.1±9.1 years] and 21 age-matched female volunteers (mean age 52.6±8.3 years, ns). Pulse wave velocity (PWV) and transthoracic echocardiography were performed. SSc patients were divided into two groups according to the median of DD: ≤3 years (39 patients) and >3 years (36 patients). Patients with DD>3 years had higher PWV than those with DD≤3 years and controls (log PWV: 2.23±0.23 vs. 2.13±0.16 and vs. 2.11±0.16 m/s; p=0.028 and 0.029, respectively). In addition, echocardiographic indices showed impaired right ventricular (RV) function in the patients with DD>3 years. Also in these SSc patients, PWV correlated with clinical and echocardiographic parameters of pulmonary circulation: age (r=0.64, p<0.0001), acceleration time of pulmonary ejection (AcT; r=-0.38, p=0.021), and tricuspid regurgitation peak gradient (TRPG; r=0.34, p=0.04). Multiple linear regression analysis showed that PWV was independently associated with DD (β=0.22, p==0.02), AcT (β=-0.215, p=0.03), and age (β=0.44, p<0.001). In patients with SSc lasting more than 3 years, the disease is characterized by increased stiffness of the large systemic arteries. Longer duration of SSc leads simultaneously to the increased stiffness of the large systemic arteries and to the progressive impairment of RV function and its coupling to the pulmonary arterial bed.


Homoeologue expression insights into the basis of growth heterosis at the intersection of ploidy and hybridity in Cyprinidae.
Hybridization and polyploidization are considered important driving forces that form new epigenetic regulations. To study the changing patterns of expression accompanying hybridization and polyploidization, we used RNA-seq and qRT-PCR to investigate global expression and homoeologue expression in diploid and tetraploid hybrids of Carassius auratus red var. (♀) (R) and Cyprinus carpio (♂) (C). By comparing the relative expression levels between the hybrids and their parents, we defined the expression level dominance (ELD) and homoeologue expression bias (HEB) in liver tissue. The results showed that polyploidization contributed to the conversion of homoeologue ELD. In addition, hybridization had more effect on the change in HEB than polyploidization, while polyploidization had more effect on the change of global gene expression than hybridization. Meanwhile, similar expression patterns were found in growth-related genes. The results suggested that hybridization and polyploidization result in differential degrees of maternal HEB in three tissues (liver, muscle and ovary) tested. The results of this study will increase our understanding of the underlying regulation mechanism of rapid growth in diploid hybrids and allotetraploids. The differential degrees of global expression and homoeologue expression contribute to growth heterosis in newly formed hybrids, ensuring the on-going success of allotetraploid speciation.


Figure tracking by flies is supported by parallel visual streams.
Visual figures may be distinguished based on elementary motion or higher-order non-Fourier features, and flies track both. The canonical elementary motion detector, a compact computation for Fourier motion direction and amplitude, can also encode higher-order signals provided elaborate preprocessing. However, the way in which a fly tracks a moving figure containing both elementary and higher-order signals has not been investigated. Using a novel white noise approach, we demonstrate that (1) the composite response to an object containing both elementary motion (EM) and uncorrelated higher-order figure motion (FM) reflects the linear superposition of each component; (2) the EM-driven component is velocity-dependent, whereas the FM component is driven by retinal position; (3) retinotopic variation in EM and FM responses are different from one another; (4) the FM subsystem superimposes saccadic turns upon smooth pursuit; and (5) the two systems in combination are necessary and sufficient to predict the full range of figure tracking behaviors, including those that generate no EM cues at all. This analysis requires an extension of the model that fly motion vision is based on simple elementary motion detectors and provides a novel method to characterize the subsystems responsible for the pursuit of visual figures.


A model of intrinsic sphincteric deficiency in the rat: electrocauterization.
Intrinsic sphincteric deficiency (ISD) denotes a malfunction of the distal urethral sphincter. Our objective was to produce a durable model of ISD in the rat. Surrounding tissues lateral to the mid-urethra were cauterized to produce sphincteric injury in 24 adult female Sprague-Dawley rats. The rats were divided into four groups of six rats each and followed for 2, 4, 6, and 16 weeks. Sphincteric function was studied by using the vertical tilt table/intravesical pressure clamp model to measure leak point pressures (LPPs). Muscle and nerve damage were assessed with hematoxylin and eosin (H&E) and anti-protein gene product (PGP) 9.5 staining, respectively. As a control, 12 rats underwent a sham operation and subsequent LPP testing at 2, 4, 6, and 16 weeks. The mean LPPs of the rats 2, 4, 6, and 16 weeks after cauterization were 18.7 +/- 0.8 cm H2O, 27.6 +/- 1.6 cm H2O, 24.3 +/- 1.7 cm H2O, and 19.1 +/- 2.2 cm H2O, respectively. The mean LPPs of the rats 2, 4, 6, and 16 weeks after the sham operation were 49.8 +/- 1.3 cm H2O, 51.2 +/- 1.5 cm H2O, 51.6 +/- 2.0 cm H2O, and 49.7 +/- 0.6 cm H2O, respectively. When compared to time-matched control groups, the decreased LPPs in each cauterized group were significantly lower (P < 0.001). Histological analysis showed muscle damage and fewer nerves in all cauterized groups. Cauterization of tissues lateral to the mid-urethra decreased LPP without affecting bladder function. This electrocauterization model produced low LPPs that, after 2 weeks, were maintained for up to 16 weeks. Histology suggests that damage to striated muscle and nerves might have contributed to the change in LPP in this model for ISD.


miR-155-1 as a positive factor for novel duck reovirus replication by regulating SOCS5-mediated interferons.
Diseases caused by novel duck reovirus (NDRV) have brought considerable economic losses to the poultry industry. MicroRNAs (miRNAs) have an impact on virus replication and antiviral immunity. However, the miRNA profile upon NDRV infection in duck embryo fibroblasts (DEFs) remains to be discovered. In this study, small RNA (sRNA) sequencing was performed to decipher the cellular miRNA response to NDRV infection. Based on 26 differentially expressed miRNAs (19 upregulated and 7 downregulated miRNAs) obtained from sequencing data and their target genes predicted by software, GO and KEGG analyses were performed to elucidate the functions of miRNAs in NDRV invasion, replication, and virus spread. "FoxO signaling pathway", "autophagy", and "Toll-like receptor signaling pathway" might participate in NDRV replication as revealed by KEGG enrichment analysis. The miR-155-1 sequence was found to be identical to rno-miR-155-5p and was sharply increased with the progression of NDRV infection. Moreover, NDRV-induced miR-155-1 could act as a positive factor for virus replication in DEFs, which inhibited type I interferon (IFN-I) production. Luciferase assay confirmed that miR-155-1 disturbed the abundance of suppressor of cytokine signaling (SOCS) 5 by targeting 3'-UTR. SOCS5, which is linked to increased IRF7 expression, restricts IFN expression and promotes NDRV replication in DEFs. Therefore, this study proposed that miR-155-1 was used by NDRV to restrict SOCS5 expression, attenuating the production of IFN-I and creating a favorable environment for virus replication.


Assessing the effects of common topical exposures on skin bacteria associated with atopic dermatitis.
While patients and families struggling with atopic dermatitis (AD) have documented concerns for a contributory role of skin care products in AD pathology, nearly all the skin microbiome studies to date have asked participants to avoid topical products (such as soaps or select medications) for the preceding days to weeks prior to sample collection. Thus, given the established role of the microbiome in AD, the interactions between topical exposures, dysbiosis and AD remains underrepresented in the academic literature. To address this knowledge gap, we expanded our previous evaluations to test the toxicological effects of a broader range of common chemicals, AD treatment lotions, creams and ointments using both health- and AD-associated strains of Roseomonas mucosa and Staphylococcus spp. Use of in vitro culture techniques and mouse models were deployed to identify chemicals with dysbiotic or pre-biotic potential. A proof-of-concept study was subsequently performed in healthy volunteers to assess global microbiome shifts after exposure to select chemicals using dermatologic patch testing. Numerous chemicals possessed antibiotic properties, including many not marketed as anti-microbials. Through targeted combination of potentially beneficial chemicals, we identified combinations which promoted the growth of health-associated isolates over disease-associated strains in bacterial culture and enhanced microbe-specific outcomes in an established mouse model of AD; the most promising of which was the combination of citral and colophonium (often sold as lemon myrtle oil and pine tar). Additional studies would likely further optimize the combination of ingredients use. Similar results were seen in the proof-of-concept human studies. Our results could offer a systematic, multiplex approach to identify which products carry dysbiotic potential and thus may guide formulation of new topicals to benefit patients with AD.


Synthesis and identification of new sacubitril derivatives as lead compounds for antibacterial, antifungal and antitubercular (TB) activities against dormant tuberculosis.
We identified twenty-two new sacubitril derivatives (5a-v) as lead compounds for various biologically active targets. These compounds were synthesized by reacting an intermediate compound (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-(amino)-2-methylpentanoic acid ethyl ester hydrochloride with respective carboxylic acid (RCOOH). The molecular structures of all the newly synthesized compounds were determined by 1H and 13C NMR, ESI mass spectrometry, FTIR spectroscopy, and CHN analysis. Moreover, compound 5n was characterized by a single-crystal X-ray diffraction (SXRD) study to confirm the structure obtained from spectral data. All these compounds were screened for various biological functions such as antifungal, antibacterial, and anti-TB activities. Among these twenty-two compounds (5a-v), some exhibited good to moderate anti-bacterial properties. Similarly, some compounds showed moderate anti-TB and antifungal activities. In addition, the anti-TB activity of compound 5q was estimated against M. tuberculosis in a nutrient starvation model (NSM). Similarly, toxicity was examined against RAW 264.7 cells. These biological activity studies were also correlated with molecular docking studies.


Bruxism, temporomandibular dysfunction and cervical impairments in females - Results from an observational study.
Bruxism is highly prevalent and defined as abnormal habitual mouth activity including clenching of the teeth and increased jaw muscle activity. The association between bruxism and temporomandibular dysfunction (TMD) is debated, in particular the association between cervical spine impairments, bruxism, and TMD. Hence the purpose of this study was to identify the relationship between bruxism, TMD, and cervical spine impairments. This observational study categorized 55 female volunteers suitable for evaluation to a bruxism (n = 33) or non-bruxism group (n = 22) based on comprehensive screening using questionnaires and visual observation of the mouth by 2 independent dentists. Following this, both groups were evaluated for TMD, severity and location of head/neck pain, neck disability index (NDI), cervical spine impairments, and tissue mechanosensitivity. Regression analysis was used to evaluate the relationship between bruxism, TMD severity, and cervical impairments. Coefficients of pain and bruxism were significantly associated with NDI scores (0.43, p < 0.001; 3.24, p = 0.01) with large and medium sized effects. As a consequence, both severity of TMD and bruxism status are independently associated with cervical impairments. Having TMD is an independent predictor for head/neck pain and cervical impairments. Pain associated with movement tests and tissue mechanosensitivity was found to be an important factor in bruxism. Clinicians need to be aware that signs of cervical movement impairment are not likely to be associated with bruxism, rather they should focus on improving orofacial function and tissue mechanosensitivity.


Nitric oxide increases biofilm formation in Saccharomyces cerevisiae by activating the transcriptional factor Mac1p and thereby regulating the transmembrane protein Ctr1.
Biofilms with immobilized cells encased in extracellular polymeric substance are beneficial for industrial fermentation. Their formation is regulated by various factors, including nitric oxide (NO), which is recognized as a quorum-sensing and signal molecule. The mechanisms by which NO regulates bacterial biofilms have been studied extensively and deeply, but were rarely studied in fungi. In this study, we observed the effects of low concentrations of NO on biofilm formation in Saccharomyces cerevisiae. Transcriptional and proteomic analyses were applied to study the mechanism of this regulation. Adding low concentrations of NO donors (SNP and NOC-18) enhanced biofilm formation of S. cerevisiae in immobilized carriers and plastics. Transcriptional and proteomic analyses revealed that expression levels of genes regulated by the transcription factor Mac1p was upregulated in biofilm cells under NO treatment. MAC1 promoted yeast biofilm formation which was independent of flocculation gene FLO11. Increased copper and iron contents, both of which were controlled by Mac1p in the NO-treated and MAC1-overexpressing cells, were not responsible for the increased biofilm formation. CTR1, one out of six genes regulated by MAC1, plays an important role in biofilm formation. Moreover, MAC1 and CTR1 contributed to the cells' resistance to ethanol by enhanced biofilm formation. These findings suggest that a mechanism for NO-mediated biofilm formation, which involves the regulation of CTR1 expression levels by activating its transcription factor Mac1p, leads to enhanced biofilm formation. The role of CTR1 protein in yeast biofilm formation may be due to the hydrophobic residues in its N-terminal extracellular domain, and further research is needed. This work offers a possible explanation for yeast biofilm formation regulated by NO and provides approaches controlling biofilm formation in industrial immobilized fermentation by manipulating expression of genes involved in biofilm formation.


"Health Is on the Back Burner:" Multilevel Barriers and Facilitators to Primary Care Among People Who Inject Drugs.
The estimated 2.2 million people who inject drugs (PWID) in the USA experience significant gaps in preventive healthcare and a high burden of infectious, psychiatric, and other chronic diseases. Many PWID rely on emergency medical services, which are costly and not designed to deliver preventive services, manage chronic conditions, or address social needs. The objective of this study was to explore barriers and facilitators to primary care utilization from the perspectives of PWID in New England, a region highly affected by the overdose crisis. Participants completed semi-structured qualitative interviews exploring substance use and healthcare utilization patterns. We recruited 78 PWID through community-based organizations (e.g., syringe service programs) in 16 urban and non-urban communities throughout Massachusetts and Rhode Island. Thematic analysis identified barriers and facilitators to primary care utilization at the individual, interpersonal, and systemic levels. Among 78 PWID, 48 described recent primary care experiences; 33 had positive experiences and 15 described negative experiences involving discrimination or mistrust. Individual-level barriers to primary care utilization included perceived lack of need and competing priorities (e.g., avoiding opioid withdrawal, securing shelter beds). Interpersonal-level barriers included stigma and perceived low quality of care for PWID. Systemic-level barriers included difficulty navigating healthcare systems, inadequate transportation, long wait times, and frequent provider turnover. Participants with positive primary care experiences explained how appointment reminders, flexible hours, addiction medicine-trained providers, case management services, and transportation support facilitated primary care utilization and satisfaction. Findings regarding the multilevel barriers and facilitators to accessing primary care among PWID identify potential targets for programmatic interventions to improve primary care utilization in this population. Based on these findings, we make recommendations for improving the engagement of PWID in primary care as a means to advance individual and public health outcomes.


Masked Hypertension in Healthy Children and Adolescents: Who Should Be Screened?
The goal is to review masked hypertension (MH) as a relatively new phenomenon when patients have normal office BP but elevated out-of-office BP. Firstly, it was described in children in 2004. It has received increased attention in the past decade. The prevalence of MH in different pediatric populations differs widely between 0 and 60% based on the population studied, definition of MH, or method of out-of-office BP measurement. The highest prevalence of MH has been demonstrated in children with chronic kidney disease (CKD), obesity, diabetes, and after heart transplantation. In healthy children but with risk factors for hypertension such as prematurity, overweight/obesity, diabetes, chronic kidney disease, or positive family history of hypertension, the prevalence of MH is 9%. In healthy children without risk factors for hypertension, the prevalence of MH is very low ranging 0-3%. In healthy children, only patients with the following clinical conditions should be screened for MH: high-normal/elevated office BP, positive family history of hypertension, and those referred for suspected hypertension who have normal office BP in the secondary/tertiary center.


Hovk 1 and the Middle and Upper Paleolithic of Armenia: a preliminary framework.
The territory of present day Armenia is a geographic contact zone between the Near East and the northern Caucasus. Armenian Middle and Upper Paleolithic records are both few and patchy as a result of the historical paucity of systematic archaeological research in the country. Consequently, it is currently difficult to correlate the Armenian Middle and Upper Paleolithic records with those from other neighboring regions. We present new archaeological and chronometric data (luminescence, U-Th, and 14C) from our ongoing research at Hovk 1 Cave in northeast Armenia. We discuss in particular two activity phases in Hovk 1 Cave for which we have outline chronometric data: (1) an early Middle Paleolithic occupational phase, dated by optically stimulated luminescence (OSL) to 104+/-9.8 ka BP(OSL); and (2) a Paleolithic occupational phase characterized by microlithic flakes dated by AMS 14C to 39,109+/-1,324 calibrated years BP(Hulu). The two phases are separated by a hiatus in hominin occupation corresponding to MIS 4 and an episode in early MIS 3. These chronometric data, taken together with the preliminary paleoenvironmental reconstruction of the Hovk 1 Cave and environment, suggest that these activity phases represent short-lived and seasonal use of the cave presumably by small groups of hunters during episodes of mild climate. Neither tool manufacture nor butchery appears to have taken place within the cave, and consequently, the archaeological record included, for the most part, finished tools and blanks. We address the chronology and techno-typological aspects of Hovk 1 lithics in relation to: (1) the Paleolithic records of Armenia, and (2) the broader interregional context of early Middle Paleolithic hominin occupation and the Middle-Upper Paleolithic transition in the Caucasus.


p53 represses the transcription of snRNA genes by preventing the formation of little elongation complex.
The regulation of transcription by RNA polymerase II (Pol II) is important for a variety of cellular functions. ELL/EAF-containing little elongation complex (LEC) was found to be required for transcription of Pol II-dependent small nuclear RNA (snRNA) genes. It was shown that the tumor suppressor p53 interacts with ELL and inhibits transcription elongation activity of ELL. Here, we show that p53 inhibits interaction between ELL/EAF and ICE1 in LEC and thereby p53 represses transcription of Pol II-dependent snRNA genes through inhibiting LEC function. Furthermore, induction of p53 expression by ultraviolet (UV) irradiation decreases the occupancy of ICE1 at Pol II-dependent snRNA genes. Consistent with the results, knockdown of p53 increased both the expression of snRNA genes and the occupancy of Pol II and components of LEC at snRNA genes. Our results indicate that p53 interferes with the interaction between ELL/EAF and ICE1 and represses transcription of snRNA genes by Pol II.


The Effect of Decongestion on Intrarenal Venous Flow Patterns in Patients With Acute Heart Failure.
Discontinuous intrarenal venous flow patterns, as assessed by renal Doppler ultrasound examination, are associated with changes in hemodynamics such as volume expansion and poorer diuretic response in patients with heart failure (HF). We aimed to study intrarenal venous and arterial flow patterns after decongestive treatment in patients with acute HF. Fifteen patients with acute HF were enrolled. Intrarenal venous and arterial flow patterns were assessed at baseline, 1 hour after administration of loop diuretics, at day 2 and day 3. Among patients hospitalized for acute HF, 13 (87%) had a discontinuous venous flow pattern at admission. After decongestive treatment, a significant improvement of the venous impedance index (P = .021) and venous discontinuity index (P = .004) was observed at day 3 compared with baseline. There was no effect on the intrarenal arterial flow patterns. In patients who exhibit discontinuous renal venous flow patterns hospitalized for decongestive treatment owing to acute HF led to a normalization of intrarenal venous flow to a continuous pattern.


Heterogeneity in the definition of delirium in ICUs and association with the intervention effect in randomized controlled trials: a meta-epidemiological study.
To evaluate the heterogeneity in the definition of delirium in randomized controlled trials (RCTs) included in meta-analyses of delirium in intensive care units (ICUs) and to explore whether intervention effect depends on the definition used. We searched PubMed for meta-analyses including RCTs evaluating prevention or treatment strategies of delirium in ICU. The definition of delirium was collected from RCTs and classified as validated (DSM criteria, CAM-ICU, ICDSC, NEECHAM, DRS-R98) or non-validated (non-validated scales, set of symptoms, physician appreciation or not reported). We conducted a meta-epidemiological analysis to compare intervention effects between trials using or not a validated definition by a two-step method as primary analysis and a multilevel model as secondary analysis. A ratio of odds ratios (ROR) < 1 indicated larger intervention effects in trials using a non-validated definition. Of 149 RCTs (41 meta-analyses), 109 (73.1%) used a validated definition and 40 (26.8%) did not (including 31 [20.8%] not reporting the definition). The primary analysis of 7 meta-analyses (30 RCTs) found no significant difference in intervention effects between trials using a validated definition and the others (ROR = 0.54, 95% CI 0.27-1.08), whereas the secondary multilevel analysis including 12 meta-analyses (67 RCTs) found significantly larger effects for trials using a non-validated versus a validated definition (ROR = 0.36, 95% CI 0.21-0.62). The definition of delirium was heterogeneous across RCTs, with one-fifth not reporting how they evaluated delirium. We did not find a significant association with intervention effect in the primary analysis. The secondary analysis including more studies revealed significantly larger intervention effects in trials using a non-validated versus a validated definition.


Evaluation of antioxidant and antibacterial effects of lactobacilli metabolites- preconditioned bone marrow mesenchymal stem cells in skin lesions amelioration.
Mesenchymal stem cells (MSCs) therapeutically intensify wound-healing. Meanwhile, probiotics are capable to inhibit pathogenic bacteria by secreting antimicrobial and antioxidant agents. They ameliorate more the wounds, by MSCs' synergistic effect. This way, MSCs exposed to probiotics metabolites (the extracts of Lactobacillus plantarum and Lactobacillus casei), become more viable, and the optimum doses of probiotics metabolites were determined by Trypan blue and MTT assays. Then, preconditioned MSCs (pre-MSCs) faced again the oxidative stress (100 µM H2O2), and their survival rate was assessed by MTT assay. Conditioned medium (CM) prepared from pre-MSCs and the expression rate of antioxidant proteins evaluated by Real-time PCR. The antimicrobial activity of the samples was evaluated using the MIC method. Then mice wound models were treated with the mixture of a basal ointment and each CM of pre-MSCs. The proliferation and viability of MSCs improved by the probiotic's metabolites preconditioning (P ≤ 0.05). pre-MSCs exhibited significant up-regulated in antioxidant genes expression (P ≤ 0.001). Also, probiotics metabolites presented a significant free radical scavenging effect (P ≤ 0.001). CMs of pre-MSCs showed considerably increased antibacterial activity (P ≤ 0.05). Experimental groups compared with the controls revealed that wound contraction was more rapid in groups that received CMs of LP-MSCs, LC-MSCs, MSCs, and then finally mixed probiotics metabolites, respectively. These results provide a novel insight into the probiotics extract effect on the improvement of MSCs' potential for wound healing procedures.


Research and Education Needs for Complex Generics.
Complex generics are generic versions of drug products that generally have complex active ingredients, complex formulations, complex routes of delivery, complex dosage forms, are complex drug-device combination products, or have other characteristics that can make it complex to demonstrate bioequivalence or to develop as generics. These complex products (i.e. complex generics) are an important element of the United States (U.S.) Food and Drug Administration's (FDA's) Generic Drug User Fee Amendments (GDUFA) II Commitment Letter. The Center for Research on Complex Generics (CRCG) was formed by a grant from the FDA to address challenges associated with the development of complex generics. To understand these challenges, the CRCG conducted a "Survey of Scientific Challenges in the Development of Complex Generics". The three main areas of questioning were directed toward which (types of) complex products, which methods of analysis to support a demonstration of bioequivalence, and which educational topics the CRCG should prioritize. The survey was open to the public on a website maintained by the CRCG. Regarding complex products, the top three selections were complex injectables, formulations, and nanomaterials; drug-device combination products; and inhalation and nasal products. Regarding methods of analysis, the top three selections were locally-acting physiologically-based pharmacokinetic modeling; oral absorption models and bioequivalence; and data analytics and machine learning. Regarding educational topics, the top three selections were complex injectables, formulations, and nanomaterials; drug-device combination products; and data analytics, including quantitative methods and modeling & simulation. These survey results will help prioritize the CRCG's initial research and educational initiatives.


Rapid conversion of newly-synthesized orotate to uridine-5-monophosphate by rat liver cytosolic enzymes.
It had been noted previously that the activity of mitochondrial dihydroorotate dehydrogenase was lower in crude tissue preparations containing cytosol than in isolated mitochondria. Closer examination reveals that the apparent lower enzyme activity is due to rapid conversion of newly-synthesized orotate to uridine-5-monophosphate by the cytosolic enzymes, orotate phosphoribosyltransferase and orotidylate decarboxylase.


[Article on SEIMC Procedure No.42: Environmental microbiological monitoring].
The inanimate hospital environment is rarely implicated in infection transmission, except among vulnerable patients. Some authors argue against the use of environmental surveillance cultures because the tests can be expensive and time consuming, and because they should not be used instead of quality control and good practices in disinfection and maintenance procedures. Routine environmental sampling is not usually advised, except in situations where sampling is directed by epidemiologic principles, and results can be applied to adopt infection control measures. The incidence of health-care associated infections can be minimised by appropriate maintenance of medical equipment such as endoscope cleaning and disinfection, adherence to water-quality standards for haemodialysis, and to ventilation standards for specialised care environments such as isolation units, or operating rooms. This paper reviews the current knowledge on surveillance cultures in these settings in order to prevent iatrogenic infections in operating and isolation rooms, haemodialysis and endoscope reprocessing units, and cultures related to nosocomial infection outbreaks.


Preschool center quality and school readiness: quality effects and variation by demographic and child characteristics.
This article examines associations between observed quality in preschool center classrooms for approximately 6,250 three- to five-year-olds and their school readiness skills at kindergarten entry. Secondary analyses were conducted using data from four large-scale studies to estimate the effects of preschool center quality and interactions between quality and demographic characteristics and child entry skills and behaviors. Findings were summarized across studies using meta-analytic methods. Results indicate small, but statistically significant associations for preschool center quality main effects on language and mathematics outcomes with little evidence of moderation by demographic characteristics or child entry skills and behaviors. Preschool center quality was not reliably related to socioemotional outcomes. The authors discuss possible explanations for the small effect sizes and lack of differential effects.


Partnering to lead change: nurses' role in the redesign of health care.
Health care has a long-held perception of perioperative nurses as providers who advocate for patients and who carry out physician orders. According to the Institute of Medicine's 2010 report on the future of nursing, not only must that view evolve, but nurses also must play a leading role, in partnership with physicians and other health care colleagues, if health care reform is to succeed. Several factors will prepare nurses for this new role of partnering to advance health, including advancing their formal education, developing leadership as a core competency, acquiring leadership skills, and being active in new models of leadership (ie, mentorship, volunteering, advocacy).


An automated method for segmentation and quantification of blood vessels in histology images.
Alzheimer's disease (AD) is a chronic neuro-degenerative disease that adversely affect many people on a global scale. Despite different diagnostic and therapeutic treatment, there is no cure for AD. The brain is one of the most complex organ and researchers are still trying to understand so as to find a cure. To complement the efforts of clinical researchers engaged in research in alzheimer's disease, accurate segmentation and quantification of blood vessels in brain images is required. For robust segmentation of blood vessels even in the presence of colour variation, we introduce a fully automated morphological tool that can extract and quantify vessels from haematoxylin and diaminobenzidine stained histology brain image. The method, exploits saturation channel of stained image slides, ISODATA threshold method is applied to obtain a binary image. This helps in eliminating background and remaining with only blood vessels. A one-stage procedure that includes eliminating small artefacts is performed on the binary mask. The intensity of the image is transformed. Joining is performed to deal with fragmentation of intact blood vessels on the images, and artefactual appearance of the blood vessel structures. The artefactual fragments based on measured incoherence with neighbouring tissue are removed. The vessels are then labelled to facilitate quantification. Morphometric measurements are used during the vessel quantification assess both vessels with lumen and vessels without lumen. We have quantified the diameter of blood vessels. The image processing technique is developed in close collaboration with neuroscientist experts to help clinician. We have evaluated our proposed approach qualitatively. The method was validated against their manual quantification results. Qualitative results show that the method can indeed segment the blood vessels in the presence of colour variations and artefacts. The quantitative method produces fairly better results.


Serous Cystadenomas Follow a Benign and Asymptomatic Course and Do Not Present a Significant Size Change During Follow-Up.
Serous cystadenoma is a benign pancreatic cystic neoplasm. Conservative management is favored. We studied the clinical characteristics and course of serous cystadenoma in patients undergoing surgery or conservative management only at an academic referral center. Patients presenting with serous cystadenoma in the years 2000-2013 were selected. Hospital records were evaluated for patient and serous cystadenoma characteristics. A total of 22 patients with serous cystadenoma were identified. Mean age at diagnosis was 63 years and 82% were women. Diagnosis was incidental in 59%, and 18% presented with unspecific abdominal pain, 14% unexplained weight loss, 4.5% gastrointestinal obstructive symptoms, and 4.5% cholangitis. Location was pancreas body 36%, head 32%, tail 23%, and uncinate 9%. Mean serous cystadenoma diameter at diagnosis was 37 ± 23 mm. After diagnosis five patients underwent surgery. Initial size was similar between surgical and follow-up groups (p = 0.9). Four cases were lost to follow-up; 13 continued conservative management with a mean follow-up time of 54 ± 27 months. The initial and last serous cystadenoma size in the follow-up group remained similar (p = 0.9). Six cases presented significant tumor growth during follow-up (p > 0.05). All patients remained asymptomatic throughout follow-up. No malignancy or serous cystadenoma-related death occurred. Size change of serous cystadenoma was minimal and patients remained asymptomatic during follow-up. Surgery should be limited to symptomatic and selected cases.


Psychological stress and cortisol during pregnancy: An ecological momentary assessment (EMA)-Based within- and between-person analysis.
Although the linkage between psychological stress and cortisol is believed to mediate the association of stress with health outcomes, several studies have been unable to demonstrate this association. We suggest this inability may be a consequence of limitations in the measurement approach and/or reliance on analytic strategies that focus on associations across, rather than within individuals. The link between psychological stress and cortisol is of particular interest in the context of pregnancy and fetal development. Using an ecological momentary assessment (EMA) design, we examined the association between psychological stress and cortisol at the between- and the within-person level. 152 participants completed a 4-day long EMA protocol serially in early, mid and late pregnancy to provide momentary stress appraisals (average of 150 measures/subject) and saliva samples (average of 55 samples/subject) for quantification of cortisol. The association between stress and cortisol was estimated using linear mixed models. After accounting for the effects of key determinants of variation in cortisol, momentary stress was significantly and positively associated with cortisol at the within-person level (B = .030, p = .031), but not at the between-person level. No association was evident for traditional retrospective measures of stress with cortisol at either the between- or the within-person level. Our study highlights the value of EMA methods and linear mixed-modeling approaches in linking maternal psychological and physiological states across pregnancy. These findings may have important implications for the development of personalized risk identification and "just-in-time" intervention strategies to optimize maternal and child health.


Studies on the enzymatic hydrolysis of polyglutamyl folates by chicken liver folyl poly-gamma-glutamyl carboxypeptidase. I. Intracellular localization, purification and partial characterization of the enzyme.
Intracellular distribution, purification and properties of a folyl poly-gamma-glutamyl carboxypeptidase (peptidyl-L-glutamate hydrolase, EC 188.8.131.52) from chicken liver have been investigated. The post-nuclear particulate and cell supernatant fractions showed activity. The particulate enzyme exhibited characteristics suggestive of its lysosomal origin; on solubilization, however, it cannot be distinguished from the cell cytosol activity. The bulk enzyme was purified about 80-fold to apparent homogeneity by 50--90% ammonium sulfate fractional precipitation, dialysis and chromatography on a 'mixed column' of Sephadex G-100 superimposed on CM-Sephadex C-50. The purified enzyme behaved homogeneously on Sephadex G-100 chromatography, sucrose density gradient centrifugation analyses and polyacrylamide gel electrophoresis. However, polyacrylamide gel electrophoresis in the presence of mercaptoethanol dissociated the native enzyme into two separable isoenzymic components. The enzyme exhibits two pH optima (4.1 and 5.2) and a temperature optimum of 35--40 degrees C. The reaction is linear for 20 min. The enzyme sequentially cleaves the terminal gamma-glutamyl residues of polyglutamylfolates, finally releasing a monoglutamyl end-product. An apparent Km value of 0.83 - 10(-6) M and a V of 1.50 mmol/min were determined for N5-methyltetrahydropteroyltetraglutamate with 0.20 mg enzyme protein/ml reaction. The enzyme is substantially stimulated in the presence of mercaptoethanol, Na+, Mn2+ and low concentrations of denaturing agents (urea). Citrate potently inhibits and phosphate inactivates the enzyme.


Can mutation and selection explain virulence in human P. falciparum infections?
Parasites incur periodic mutations which must ultimately be eliminated to maintain their genetic integrity. It is hypothesised that these mutations are eliminated not by the conventional mechanisms of competition between parasites in different hosts but primarily by competition between parasites within the same infection. This process is enhanced by the production of a large number of parasites within individual infections, and this may significantly contribute to parasitic virulence. Several features of the most virulent human malaria parasite Plasmodium falciparum can usefully be re-interpreted in this light and lend support to this interpretation. More generally, it constitutes a novel explanation for the evolution of virulence in a wider range of microparasites.


Genetic analysis of tumorigenesis. XXXI: Retention of short arm of chromosome 3 in suppressed CHEF cell hybrids containing c-Ha-ras (EJ) gene.
Hybrids between nontransformed Chinese hamster embryo fibroblast (CHEF) cells and their c-Ha-ras (EJ) -transformed derivatives are suppressed for tumor-forming ability when tested at early passage. Hybrid subclones with suppressed (fibroblastic) or transformed appearance have now been selected by multiple recloning. Morphology, but not serum or anchorage requirement, was a sensitive indicator of suppression: Subclones with normal morphology were nontumorigenic, subclones with transformed morphology were highly tumorigenic, and intermediate subclones (7-70% normal colonies) formed tumors with a frequency of 17-50%. Suppressed lines retained the short arm of chromosome 3, but transformed and tumor-derived lines had lost this region (greater than or equal to 1 copy). Transformed and tumor-derived cells exhibited additional chromosome changes, including the loss of at least one copy of chromosomes 7 and/or 8. These findings suggest that a tumor suppressor gene lies on the short arm of chromosome 3, consistent with prior studies from this laboratory. Other suppressor genes may be located on chromosomes 7 and 8.


Modeling residential coastal flood vulnerability using finished-floor elevations and socio-economic characteristics.
Densely populated coastal regions are vulnerable to threats associated with climate change and variability, especially storms. In the United States, millions of people are repeatedly at risk of flooding and because this number will only continue to grow, the identification of the intersection of social vulnerability and physical risk to flood inundation is essential for both coastal planning and adaptation purposes. Although a key tool to identify vulnerable populations, most vulnerability models are built at the county or coarser scales, thereby hindering the effectiveness of mitigation and adaptation planning at community scales, which are more socially and physically diverse than what county-scale analyses can reveal. We present an integrated social and physical model of vulnerability at the block-group level of geography using census data to measure social variability based population and housing data and physical exposure based on the intersection of finished floor elevation of all buildings in coastal North Carolina, USA with flood hazards maps. We identify, in a spatially-explicit manner and at multiple levels of governance, areas of high social vulnerability and their intersection with areas of high physical exposure to inundation. We found that in the 28 coastal counties of North Carolina, 45.3% of the structures within the 100-year floodplain were structurally exposed to potential damage from inundation. Supporting our hypothesized patterns of vulnerability to inundation, a significant clustering of highly vulnerable block-groups were located in Albemarle and Eastern Carolina coastal regions, yet high vulnerability outliers were also located at significant distance away from the highly physically-exposed coastline. Our findings suggest that the high-resolution block-group level analysis identified multiple levels of vulnerability to inundation at the sub-county scale and provide essential information for effective hazard mitigation within scales ranging from the community to transboundary governing bodies.


Host Ant Change of a Socially Parasitic Butterfly (Phengaris alcon) through Host Nest Take-Over.
The socially parasitic Alcon blue butterfly (Phengaris alcon) starts its larval stage by feeding on the seeds of gentians, after which it completes development in the nests of suitable Myrmica ant species. The host plant and host ant species can differ at the population level within a region, and local adaptation is common, but some host switches are observed. It has been suggested that one mechanism of change is through the re-adoption of caterpillars by different ant species, either through occupation of abandoned nests or take-over of established nests by competitively superior colonies. To test this question in the lab we introduced relatively strong colonies (50 workers) of alien Myrmica species to the arenas of weaker colonies (two caterpillars with six workers), and to orphaned caterpillars (two caterpillars without ants). We used caterpillars from a xerophylic population of P. alcon, and both local hosts, M. sabuleti and M. scabrinodis, testing the possibility of host switch between these two host ant species during larval development. Most of the caterpillars were successfully readopted by alien ants, and survived well. Our results suggest higher ecological plasticity in host ant usage of this butterfly than generally thought.


Coronary angiography in the elderly with acute myocardial infarction.
Despite the high mortality rate in elderly patients with acute myocardial infarction (AMI), the value of coronary angiography (CA) in the elderly has been questioned due to a less favorable outcome. The aim of the study was to determine the prognostic significance of CA on mortality of elderly patients AMI in "real world" practice. The study cohort comprised 1009 elderly (age > or = 75 years) patients with AMI who were derived from three prospective national surveys between 1996 and 2000 in all 25 CCUs operating in Israel. Baseline characteristics, hospital course, management and outcome of 274 (27%) elderly patients who underwent CA during the index hospitalization were compared with 735 (73%) counterpart patients who did not. Patients who underwent CA were on average 2.2 years younger, and were more often with hyperlipidemia (p<0.0001 for each) and with a history of previous percutaneous coronary intervention (p<0.03) than the control group. They had a more favorable clinical presentation: a higher systolic blood pressure (p<0.04), a better Killip class (p<0.03) and an increased frequency of non-Q wave MI (p<0.03). They developed more often recurrent MI (p=0.002) and re-ischemia (p<0.0001). Variables associated with CA use during the index hospitalization were re-infarction, re-ischemia, the year of the index AMI and the availability of an on-site a catheterization laboratory in the hospital, while a higher age and fibrinolytic therapy decreased the likelihood of CA use. Of the patients who underwent CA, 67% underwent coronary revascularization (either PCI and/or CABG). Crude and adjusted mortality rates at 1 year were significantly lower in patients who underwent CA, as compared to counterparts who did not: 21% vs. 37.3%, respectively (p<0.0001), hazard ratio=0.52 (95% confidence interval 0.38-0.71). The benefit of CA was noted in a wide range of subgroups analyzed. In "real world" practice, elderly patients with AMI who undergo CA during hospitalization have a better prognosis at 1 year. Age alone should not be a deterrent to performing CA in elderly patients with AMI. Further large randomized trials are needed to confirm that an invasive approach is beneficial in high-risk elderly patients with AMI. To determine the prognostic significance of coronary angiography (CA) during the course of acute myocardial infarction (AMI) in "real world" practice on mortality of elderly patients, 1009 such patients were studied. Re-infarction, re-ischemia, the year of the index AMI and the availability of an on-site a Cath. Lab. were variables which increased the likelihood of undergoing CA, while a higher age and fibrinolytic therapy decreased this likelihood. The crude and covariate adjusted mortality rates at 1 year were significantly lower in patients who underwent CA in comparison to counterparts who did not: 21% vs. 37.3%, respectively (p<0.0001), hazard ratio 0.52 (95% confidence interval 0.38-0.71). The benefit of CA was noted across a wide range of subgroups analyzed.


Xantphos Doped POPs-PPh3 as Heterogeneous Ligand for Cobalt-Catalyzed Highly Regio- and Stereoselective Hydrosilylation of Alkynes.
A Co(acac)2 /POL-Xantphos@10PPh3 -catalyzed hydrosilylation of unsymmetrical internal alkynes with Ph2 SiH2 has been developed for the synthesis of highly selective syn-α-vinylsilane products. Furthermore, terminal alkynes were also used and gave the products with excellent regioselectivity and a wide functional group tolerance. Because this porous organic polymer combines the selectivity and activity merits of Xantphos with the stability advantage derived from the high concentration of PPh3 , the Co(acac)2 /POL-Xantphos@10PPh3 can be recycled multiple times without loss of activity and selectivity. This heterogeneous catalyst is expected to find promising applications in industrial synthesis.


The use of weasels for natural control of mouse and vole populations in a coastal coniferous forest.
If the natural enemy component of biological control is functional in small mammals, then the introduciton of weasels should effectively reduce populations of deer mice and Oregon voles. Seven weasels introduced to an area of forest habitat in coastal British Columbia did not appreciably lower the abundance of mice or voles. However, these natural predators may have contributed to the localized extinction of the vole population on the experimental area. Weasels were generally more abundant in the late summer and early fall and preferred clearcut (logged) successional habitats compared with forested areas. The results of this study are discussed with respect to the futility of poison baiting and related techniques of removing rodent pest populations from forest and agricultural land developments.


Cyantraniliprole impairs reproductive parameters by inducing oxidative stress in adult female wistar rats.
Cyantraniliprole is a synthetic insecticide used to control pests of up to 23 different types of crops. It is able to modulate ryanodine-like calcium channels, which are widely found in the organism of insects and mammals. The objective of this research was to verify the possible reproductive effects of adult female Wistar rats exposure to cyantraniliprole. Animals (67 days old) were exposed to the chemical at doses of 10 or 150 mg/kg/day, orally, for 28 consecutive days (control animals received only the vehicle). Vaginal secretions were collected during the exposure period to assess the regularity of the estrous cycle; the liver, kidneys, pituitary gland, adrenal gland, uterus, and ovaries were collected and weighed; reproductive organs were assessed for histopathological evaluation and for biochemical markers of oxidative stress and progesterone plasma level was measured. Both doses caused negative changes in the morphology and redox system of the uterus and ovaries. Animals exposed to 10 mg/kg also exhibited higher level of plasma progesterone, elevated levels of lipid peroxidation in reproductive organs, increased superoxide dismutase activity in the uterus and glutathione peroxidase activity on the ovary, while the 150 mg/kg group exhibited an increment in estrous cycle length and diminished uterine glandular epithelium. Based on these results, we conclude that cyantraniliprole may have acted as an endocrine disruptor, and its effects are mediated by oxidative stress.


Cholesterol enrichment of rabbit platelets enhances the Ca(2+) entry pathway induced by platelet-derived secondary feedback agonists.
Hypersensitivity of platelets due to increased platelet cholesterol levels has been reported in hypercholesterolemia. However, the signaling pathways linking increased platelet reactivity and cholesterol contents are not fully understood. This study aims to determine the direct effect of cholesterol enrichment of platelets on the pathways including Ca(2+) mobilization and secondary feedback agonists such as adenosine diphosphate (ADP) and thromboxane A2 (TXA2). In vitro cholesterol enrichment of rabbit platelets was performed by incubation with cholesterol complexed with methyl-β-cyclodextrin. Ca(2+) mobilization was monitored using platelets loaded with fura-PE3/AM, a fluorescent calcium indicator. Released ATP and TXB2 from platelets were measured by a luciferin-luciferase ATP assay system and a TXB2 ELISA Kit, respectively. Cholesterol enrichment of rabbit platelets significantly enhanced Ca(2+) mobilization induced by thrombin, accompanying an augmented Ca(2+) entry. The augmentation of Ca(2+) entry by cholesterol enrichment was significantly suppressed by treatment with inhibitors for secondary feedback agonists. In cholesterol-enriched platelets, the amount of released ATP or TXB2 induced by thrombin was not significantly altered in comparison with control platelets, whereas an increase in [Ca(2+)]i induced by ADP or U46619, a TXA2 mimetic, was significantly enhanced. These results suggest that cholesterol enrichment of rabbit platelets results in enhanced Ca(2+) mobilization via ADP/TXA2-dependent augmentation of the Ca(2+) entry pathway. The results reveal a novel mechanism by which platelet hypersensitivity is regulated by cholesterol contents.


A genetic linkage study of familial breast-ovarian cancer.
Linkage analysis was conducted in 17 families identified by the familial occurrence of breast and ovarian cancer using a series of 17 serologic and biochemical markers. Lod scores suggestive of linkage of breast/ovarian cancer susceptibility to the RH blood group locus on chromosome 1p were obtained. When the presence of fibrocystic disease of the breast in a first-degree relative of an affected family member was added as an indicator of susceptibility, the evidence for linkage increased. No evidence of linkage to GPT or ABO, both previously suggested to be linked to breast cancer susceptibility, was seen in this study.


Mechanism of canagliflozin-induced vasodilation in resistance mesenteric arteries and the regulation of systemic blood pressure.
Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, is reported to produce beneficial cardiovascular effects including a reduction in arterial contractility, and blood pressure. However, whether canagliflozin could directly relax resistance mesenteric arteries, underlying molecular mechanism and its role in regulating systemic blood pressure remain unclear. Here, we investigated the mechanism of regulation of small mesenteric artery contractility and its relevance for blood pressure regulation. Our pressure myography data showed that canagliflozin application rapidly produces a concentration-dependent vasodilation in mesenteric arteries. Such vasodilation was inhibited by concurrent inhibition of smooth muscle cell voltage-gated K+ channels KV1.5 (by 1 μM DPO-1), KV2.1 (by 100 nM guangxitoxin), and KV7 (by 10 μM linopirdine) but not by the inhibition of small-, intermediate-, and large-conductance Ca2+-activated K+ channels (SKCa by 1 μM apamin, IKCa 10 μM TRAM-34, and BKCa by 10 μM paxilline, respectively), ATP-sensitive (KATP) channels (by 10 μM glibenclamide), or SERCA pump (by 0.1 μM thapsigargin). Inhibition of SGLTs (by 1 μM phlorizin or the inhibition of endothelial signaling did not alter canagliflozin-evoked vasodilation. Consistently, acute canagliflozin treatment (4 mg/kg body weight) lowered systemic blood pressure in vivo. Overall, our data suggests that canagliflozin stimulates KV1.5, KV2.1, and KV7 channels, leading to vasodilation and a reduction of systemic blood pressure.


Lymphadenitis in children is caused by Mycobacterium avium hominissuis and not related to 'bird tuberculosis'.
Mycobacterium avium is the most commonly encountered mycobacterium species among non-Mycobacterium tuberculosis complex (nontuberculous mycobacteria) isolates worldwide and frequently causes lymphadenitis in children. During a multi-centre study in The Netherlands that was performed to determine the optimal treatment for mycobacterial lymphadenitis, concern was expressed in the media about the possible role of birds as sources of these M. avium infections, referred to as 'bird tuberculosis.' To examine the involvement of birds in mycobacterial lymphadenitis, 34 M. avium isolates from lymphadenitis cases were subjected to IS1245 restriction fragment length polymorphism (RFLP) typing. This genotyping method enables the distinction of the subspecies M. avium subsp. hominissuis and the 'bird-type' M. avium spp. avium. Highly variable RFLP patterns were found among the lymphadenitis M. avium isolates, and all belonged to the M. avium hominissuis subspecies. A relation to pet birds in the etiology of mycobacterial lymphadenitis could not be established, and the source of the infections may be environmental.


Correlation of haemophagocytosis with clinical criteria of haemophagocytic lymphohistiocytosis and recommendations for bone marrow reporting.
Haemophagocytic lymphohistiocytosis (HLH) is a rare condition resulting from a dysregulated inflammatory response. Currently there are no guidelines on the reporting of haemophagocytosis on bone marrow biopsy (BM) and lack of evidence on correlation between haemophagocytosis with the clinical diagnostic criteria for HLH. We aimed to assess if the amount of haemophagocytosis identified in the BM correlates with HLH-2004 criteria. Secondary aims were to evaluate inter-observer variability in reporting haemophagocytosis, and to formulate recommendations for screening in bone marrow specimens. A retrospective review of bone marrow biopsies from adult patients under investigation for HLH was undertaken independently by two haematopathologists who were blinded to the original biopsy report. The average number of actively haemophagocytic cells in each slide were quantified. Cases with discordance pertaining to the degree of haemophagocytosis were reviewed by both assessors to reach a consensus. Sixty-two specimens from 59 patients were available for assessment. An underlying haematological condition was identified in 34 cases (58%). There was a significant association between the amount of haemophagocytosis identified on the aspirate samples and the number of HLH-2004 criteria met (p<0.0001). In patients where haemophagocytosis was present (n=31), there was a correlation between the amount of haemophagocytosis and ferritin (p=0.041). Based on our review, we have made recommendations for the reporting of BM haemophagocytosis. Our findings indicate that the amount of haemophagocytosis present on BM samples correlates with the number of HLH-2004 criteria. We found marked interobserver variability which we anticipate can be rectified with our recommendations for reporting.


Effects of silver nanoparticles on the fluidity of bilayer in phospholipid liposome.
This paper describes the formation and characterization of liposome entrapping the silver nanoparticles in bilayer. Silver nanoparticles were entrapped in the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposome, named as silver-loaded liposome. Specifically, above the gel to liquid-crystalline phase transition temperature of this lipid (i.e., 41 degrees C), it was observed that membrane fluidities of silver-loaded liposomes were increased, and fluorescence anisotropy values were reduced from 0.114 to 0.097. This might be due to the structural modifications and interactions between DPPC molecules and silver nanoparticles within the bilayer. It was also confirmed that silver nanoparticles were entrapped in hydrophobic region of lipid bilayer with transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) measurements.


Characterization of the human blood coagulation factor X promoter.
Blood coagulation Factor X is a serine protease required for both the intrinsic and extrinsic pathways of coagulation. The gene for Factor X spans 27 kilobases and is located on chromosome 13, in close proximity to the gene encoding Factor VII. Expression of Factor X is restricted to the liver. We have characterized the human Factor X promoter by mapping the start sites of transcription and carrying out a functional analysis of the promoter. The first 279 base pairs (bp) of 5'-flanking sequence upstream from the first AUG are sufficient to confer maximal promoter activity in HepG2 cells. Protein-binding sites within the 279-bp fragment are defined using gel mobility shift assays. Mutagenesis of two specific sequences within the 279-bp fragment (CCAAT at -120 to -116, and ACTTTG at -56 to -51), results in loss of ability to bind proteins from a HepG2 nuclear extract, and profound reduction in promoter activity of the 279-bp fragment. We conclude that these two protein-binding sites are critical for the activity of the Factor X promoter.


[DNA synthesis in connective tissue elements of regenerating skin under the influence of thyrocalcitonin and hypoxia].
The influence of TCT on the proliferation activity of the connective tissue elements of the regenerating skin in normal and lowered partial oxygen tension was studied by means of H3-thymidin autoradiography. Continuous saturation of the organism with exogenous TCT is characterized by an increase in the count of cells during the S-period of mitotic cycle, the DNA synthesis intensification, and a considerable decrease in the number of silver grains over the nuclei in the course of the 24-hour observation period; this can testify to the acceleration of the cell passage of mitotic cycle stages in normal and low partial oxygen tension in hypoxia.


WITHDRAWN: The modified impact factor; a letter to the editor.
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The effect of somite manipulation on the development of motoneuron projection patterns in the embryonic chick hindlimb.
Although the formation of motoneuron projections to individual muscles in the embryonic chick hindlimb has been shown to involve the specific recognition of environmental cues, the source of these cues and their mode of acquisition are not known. I show in the accompanying paper (C. Lance-Jones, 1988, Dev. Biol. 126, 394-407) that there is a correlation between the segmental level of origin of motoneurons and the somitic level of origin of the muscle cells of their targets in the chick hindlimb. These data are compatible with the hypothesis that the developmental basis for specific recognition is a positional one. Motoneurons and myogenic cells may be uniquely labeled in accord with their axial level of origin early in development and subsequently matched on the basis of these labels. To test this hypothesis, I have assessed motoneuron projection patterns in the embryonic chick hindlimb after somitic tissue manipulations. In one series of embryos, somitic mesoderm at levels 26-29 or 27-29 was reversed about the anteroposterior axis prior to myogenic cell migration and axon outgrowth. Since previous studies have shown that cells migrate from the somites in accord with their position and that somites 26-29 populate anterior thigh musculature, this operation will have reversed the somitic level of origin of anterior thigh muscles. Retrograde HRP labeling of projections to anterior thigh muscles at stage (st) 30 and st 35-38 showed that motoneuron projections were largely normal. This finding suggests that limb muscle cells or their source, the somites, do not contain the cues responsible for specific recognition prior to myogenic cell migration and axon outgrowth. To confirm that specific guidance cues were still intact after somitic mesoderm reversal, I also assessed motoneuron projections in embryos where somitic tissue plus adjacent spinal cord segments at levels 26-29 were reversed in a similar manner. Analyses of the distribution of retrogradely labeled motoneurons in reversed cord segments at st 35-36 indicated that motoneuron projections were reversed. This finding suggests that motoneurons have altered their course to project to correct targets despite the altered somitic origin of their targets and, thus, that specific guidance cues were intact. I conclude that if cues governing target or pathway choice are encoded positionally then they must be associated with other embryonic tissues such as the connective tissues or that guidance cues are acquired by myogenic cells after the onset of migration and motoneuron specification.


Pancreatic heterotopia in mesentery.
The pancreatic heterotopia of fortuitous operational discovery remains rare because of the medical imagery progress. We report a mesenteric localisation of aberrant pancreas identified during the assumption of responsibility of an abdominal emergency. A 26-year-old man was allowed with the urgencies for an acute obstruction of the small bowel. Surgical exploration revealed a distal support an ileo-parietal adherence near to an inflammatory hearth of appendicular origin. We noted, in addition to the mesentery of the first jejunal loop, a bilobate mass of glandular-like tissue with a pancreatic aspect. The adjacent jejunal handles were macroscopically healthy. The Pathological examination of the mass confirmed the existence of a mixed glandular exocrine and endocrine origin of pancreatic tissue, type I of the Heinrich's classification. This rare topographic entity of fortuitous discovery underlines the need for a meticulous surgical exploration of the abdominal cavity particularly in urgency when a summarized radiological assessment does not permit a complete morphological study.


Association of RanGAP to nuclear pore complex component, RanBP2/Nup358, is required for pupal development in Drosophila.
Ran's GTPase-activating protein (RanGAP) is tethered to the nuclear envelope (NE) in multicellular organisms. We investigated the consequences of RanGAP localization in human tissue culture cells and Drosophila. In tissue culture cells, disruption of RanGAP1 NE localization surprisingly has neither obvious impacts on viability nor nucleocytoplasmic transport of a model substrate. In Drosophila, we identified a region within nucleoporin dmRanBP2 required for direct tethering of dmRanGAP to the NE. A dmRanBP2 mutant lacking this region shows no apparent growth defects during larval stages but arrests at the early pupal stage. A direct fusion of dmRanGAP to the dmRanBP2 mutant rescues this arrest, indicating that dmRanGAP recruitment to dmRanBP2 per se is necessary for the pupal ecdysis sequence. Our results indicate that while the NE localization of RanGAP is widely conserved in multicellular organisms, the targeting mechanisms are not. Further, we find a requirement for this localization during pupal development.


Construction of magnetic NiO/C nanosheets derived from coordination polymers for extraordinary adsorption of dyes.
Herein, a facial stratagem for the large-scale synthesis of NiO/C nanosheets used as magnetic adsorbents is proposed by using nanoscale coordination polymers (nanoCPs) as precursors. The NiO nanoparticles (NPs) scattered on the NiO/C nanosheets have an untrasmall size (~3 nm) as well as uniform dispersion, since the Ni2+ ions are preassembled into the nanoCPs precursors by coordination bonds and transformed to NiO NPs in situ under the restriction of carbon layers. Thanks to the small size and spatially uniform distribution of NiO NPs, fully exposed carbon matrix containing part of graphene structures, and the high specific surface area of the special nanosheet structure, the magnetic NiO/C nanosheets have an a great breakthrough in the adsorption performance toward Congo Red (CR) among many reported NiO-based materials. The maximum adsorption capacity for CR is up to 2000 mg/g, and the adsorption kinetics and thermodynamics are also systematically studied. Moreover, the NiO/C nanosheets can be separated from water and reused simply by an external magnetic field. The NiO/C nanosheets with low cost and extraordinary adsorption ability have great potential in water pollution treatment area.


After-effects of transcranial alternating current stimulation on evoked delta and theta power.
Phase synchronization is suggested to be among the mechanisms that can explain the effects of transcranial alternating current stimulation (tACS). However, little is known about the effects of tACS on event-related oscillatory activity. Therefore the objective was to investigate frequency-related effects of frontal tACS on event-related oscillatory power. In a double blind randomized controlled cross-over design, twenty-four participants received 12min of delta (2.5Hz), theta tACS (5Hz) and sham tACS at an intensity of 1mA peak-to-peak. Event-related delta- and theta-related oscillatory activity was recorded to reward- and punishment-related feedback signals. Delta tACS decreased feedback-related oscillatory power in the 1.5 and 3.5Hz frequency range. This effect was driven by power changes below the tACS frequency stimulation. Exogenous field potentials can attenuate event-related oscillatory activity in a rhythm slightly below the stimulation frequency. Our findings suggest an interaction between tACS and event-related rhythmic activity that extends beyond phase synchronization. These findings add novel insights into the mechanisms of tACS after-effects.


Association of infantile convulsions with paroxysmal dyskinesias (ICCA syndrome): confirmation of linkage to human chromosome 16p12-q12 in a Chinese family.
We have studied one family of Chinese origin, in which benign infantile convulsions and paroxysmal choreoathetosis (of the dystonic form) were co-inherited as a single autosomal dominant trait. This association is specific to ICCA syndrome, which we have recently described in four French families. Some patients in the new family also exhibit recurrence of epileptic seizures at a much later age, making the ICCA syndrome in this family atypical. DNA samples isolated from this family of 22 members (9 affected) have been tested with genetic markers at chromosome 16p12-q12, in which region the ICCA syndrome has previously been linked. Confirmation of linkage to this pericentromeric region of human chromosome 16 has been obtained and no critical meiotic recombination event has been detected in the ICCA region. This result suggests that, in contrast to marked clinical heterogeneity, the association of infantile convulsions with paroxysmal dyskinetic movements could be genetically homogeneous.


Accidental intraneural injection into the musculocutaneous nerve visualized with ultrasound.
Ultrasound has become a widely used tool within the practice of regional anesthesia, offering real-time visualization of the nerves, needle, and local anesthetic during performance of a block. A successful ultrasound-guided axillary block was performed on a healthy adult male undergoing wrist surgery. Postoperative review of the ultrasound video recording of the block suggested that an intraneural injection had occurred during the procedure. The patient had an effective block and suffered no adverse neurological effects. Recording and reviewing ultrasound images of a regional block can be important for documentation and educational purposes.


Microbiota populations and short-chain fatty acids production in cecum of immunosuppressed broilers consuming diets containing γ-irradiated Astragalus polysaccharides.
This study was designed to evaluate the effects of γ-irradiated Astragalus polysaccharides (IAPS) on growth performance, cecal microbiota populations, and concentrations of cecal short-chain fatty acids of immunosuppressed broilers. A total of 144 one-day-old broiler chicks were randomly assigned into 3 groups: nontreated group (control), cyclophosphamide (CPM)-treated groups fed either a basal diet or the diets containing 900 mg/kg IAPS, respectively. On day 16, 18, and 20, broilers in the control group were intramuscularly injected with 0.5 mL sterilized saline (0.75%, wt/vol), and those in the CPM and IAPS groups were intramuscularly injected with 0.5 mL CPM (40 mg/kg of BW). The trial lasted 21 d. Compared with the control group, CPM treatment decreased the broiler average daily gain (ADG) and feed intake (P < 0.05) but did not affect the overall microbial diversity and compositions, as well as the concentrations of cecal acetate, propionate, and butyrate in cecum of broilers (P > 0.05). Dietary IAPS supplementation increased broiler ADG, Shannon index, and decreased Simpson index (P < 0.05). Specifically, broilers fed diets containing IAPS showed lower abundances of Faecalibacterium, Bacteroides, and Butyricicoccus and higher proportions of Ruminococcaceae UCG-014, Negativibacillus, Shuttleworthia, Sellimonas, and Mollicutes RF39_norank, respectively (P < 0.05). The IAPS treatment also increased butyrate concentration (P < 0.05) and tended to elevate acetate concentration (P = 0.052) in cecal digesta. The results indicated that IAPS are effective in increasing the cecal beneficial bacteria and short-chain fatty acids production, contributing to improvement in the growth performance of immunosuppressive broilers. These findings may expand our knowledge about the function of modified Astragalus polysaccharides in broiler chickens.


Antenatal corticosteroids for fetal lung maturation in threatened preterm delivery: indications and administration.
Antenatal maternal administration of corticosteroids has been shown to reduce morbidity and mortality rates in preterm delivery. Threatened spontaneous or medically indicated preterm delivery for maternal or fetal indications between 24 and 34 weeks of gestation with unknown fetal lung maturity status are indications for antenatal corticosteroid administration. Recent studies have challenged current practice of antenatal glucocorticoid use. The goal of this expert letter is to provide recommendations based for the clinical use of antenatal glucocorticoids based on the current evidence from published studies. The published literature (PubMed search), as well as the recommendations of other national societies, has been searched and taken into consideration for these recommendations. The standard regimen of antenatal corticosteroids involves a single course of 2 × 12 mg betamethasone administered intramuscularly within 24 h. The administration of corticosteroids usually is performed between 24 and 34 weeks gestation. However, under particular circumstances it may be beneficial even at 23 weeks and at 35-36 weeks of gestation. The evidence to date is clearly against the routine administration of multiple antenatal steroid courses. In special clinical situations, a second course of betamethasone ("rescue course") may be justifiable. Tocolysis during administration of steroids is not routinely indicated in the absence of contractions, cervical shortening or rupture of membranes.


Carpal tunnel syndrome and work.
Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome, and it frequently presents in working-aged adults. Its mild form causes 'nuisance' symptoms including dysaesthesia and nocturnal waking. At its most severe, CTS can significantly impair motor function and weaken pinch grip. This review discusses the anatomy of the carpal tunnel and the clinical presentation of the syndrome as well as the classification and diagnosis of the condition. CTS has a profile of well-established risk factors including individual factors and predisposing co-morbidities, which are briefly discussed. There is a growing body of evidence for an association between CTS and various occupational factors, which is also explored. Management of CTS, conservative and surgical, is described. Finally, the issue of safe return to work post carpal tunnel release surgery and the lack of evidence-based guidelines are discussed.


Body Diffusion-weighted MR Imaging in Oncology: Imaging at 3 T.
Advances in hardware and software enable high-quality body diffusion-weighted images to be acquired for oncologic assessment. 3.0 T affords improved signal/noise for higher spatial resolution and smaller field-of-view diffusion-weighted imaging (DWI). DWI at 3.0 T can be applied as at 1.5 T to improve tumor detection, disease characterization, and the assessment of treatment response. DWI at 3.0 T can be acquired on a hybrid PET-MR imaging system, to allow functional MR information to be combined with molecular imaging.


A redox switch regulates the assembly and anti-CRISPR activity of AcrIIC1.
Anti-CRISPRs (Acrs) are natural inhibitors of bacteria's CRISPR-Cas systems, and have been developed as a safeguard to reduce the off-target effects of CRISPR gene-editing technology. Acrs can directly bind to CRISPR-Cas complexes and inhibit their activities. However, whether this process is under regulation in diverse eukaryotic cellular environments is poorly understood. In this work, we report the discovery of a redox switch for NmeAcrIIC1, which regulates NmeAcrIIC1's monomer-dimer interconversion and inhibitory activity on Cas9. Further structural studies reveal that a pair of conserved cysteines mediates the formation of inactive NmeAcrIIC1 dimer and directs the redox cycle. The redox switch also applies to the other two AcrIIC1 orthologs. Moreover, by replacing the redox-sensitive cysteines, we generated a robust AcrIIC1 variant that maintains potent inhibitory activity under various redox conditions. Our results reveal a redox-dependent regulation mechanism of Acr, and shed light on the design of superior Acr for CRISPR-Cas systems.


Startle response is dishabituated during a reaction time task.
Recent experiments pairing a startling stimulus with a simple reaction time (RT) task have shown that when participants are startled, a prepared movement may be triggered earlier in comparison to voluntary initiation (Carlsen et al. 2003, in press; Siegmund et al. 2001; Valls-Solé et al. 1999). The use of this paradigm in experiments may provide new insights into processes that control rapid voluntary actions. However, because the startle response habituates with repeated exposure to the startling stimulus, its use in experiments may be limited. Previously Brown et al. (1991) and later Siegmund et al. (2001) noted that individuals habituate to a startling stimulus at different rates depending on the required activity level of the participant in the task. The present experiment was designed to determine the rate at which participants habituate to a startle during the completion of a RT task. Participants completed 100 trials in which an active wrist extension to a target was performed as fast as possible following an auditory tone. An unexpected 124 dB auditory startle stimulus accompanied the imperative stimulus in 20 of these trials. For the duration of the experiment, startle response electromyographic (EMG) activity continued to be produced in the sternocleidomastoid muscle (SCM) indicating that habituation was not complete after 20 startle trials. Furthermore RT in the startle condition was significantly shorter than control RT. However, findings indicate that when a measurable EMG burst in the SCM was present, RT was significantly shorter than when no SCM burst was present.


Disparities in Breast Cancer Screening Uptake for Women With Mental Illness in the United Kingdom.
Although there is evidence of disparities in breast cancer screening for women with mental illness in the U.S., there is a dearth of studies examining this association in the United Kingdom, where health care is provided free at the point of access. This population-based study examines the influence of mental illness, as assessed by the uptake of psychotropic medications, on breast screening uptake in the United Kingdom. A cohort of 57,328 women identified from 2011 Census records within the Northern Ireland Longitudinal Study was followed through a single 3-year screening cycle (2011-2014) of the National Health Service Breast Screening Programme. Mental illness was identified by a receipt of psychotropic medication in the 3 months preceding screening invite. Individual- and household-level attributes were derived from Census records. Data were analyzed in 2019. More than a third of women received ≥1 prescription for psychotropic medication in the 3 months preceding screening invite. The odds of attendance in these individuals were reduced by 15% (OR=0.85, 95% CI=0.81, 0.88). Attendance was particularly low for women prescribed antipsychotics (OR=0.63, 95% CI=0.56, 0.70), anxiolytics (OR=0.61, 95% CI=0.57, 0.66), and hypnotics (OR=0.68, 95% CI=0.63, 0.72). These findings confirm the existence of significant disparities in breast screening uptake for women with mental illness. Targeted interventions are warranted to prevent avoidable breast cancer deaths in these individuals, especially given the increasing prevalence of mental illness.


[Expression of Fas, FasL, and NF-kappa B in the process of osteoclast-like cell apoptosis effected by sodium fluoride].
To detect the changes in the expression of apoptosis signals: Fas, FasL and NF-kappa B in the process of osteoclast-like cell (OLC) apoptosis effected by sodium fluoride. After co-culture of osteoclast-like cells with 0, 5, 10 and 15 mg/L sodium fluoride, Fas, FasL and NF-kappa B antibody expressions were detected by immune-histochemistry. The expression of Fas and FasL increased with the concentration of the sodium fluoride, however the expression of NF-kappa B decreased with the concentration of sodium fluoride. In the process of OLC apoptosis induced by sodium fluoride, the expression of Fas and FasL increased, and that of NF-kappa B decreased with the concentration of sodium fluoride respectively, and the changes of the expression present a dose-dependent pattern.