Event boundaries and anaphoric reference.
The current study explored the finding that parsing a narrative into separate events impairs anaphor resolution. According to the Event Horizon Model, when a narrative event boundary is encountered, a new event model is created. Information associated with the prior event model is removed from working memory. So long as the event model containing the anaphor referent is currently being processed, this information should still be available when there is no narrative event boundary, even if reading has been disrupted by a working-memory-clearing distractor task. In those cases, readers may reactivate their prior event model, and anaphor resolution would not be affected. Alternatively, comprehension may not be as event oriented as this account suggests. Instead, any disruption of the contents of working memory during comprehension, event related or not, may be sufficient to disrupt anaphor resolution. In this case, reading comprehension would be more strongly guided by other, more basic language processing mechanisms and the event structure of the described events would play a more minor role. In the current experiments, participants were given stories to read in which we included, between the anaphor and its referent, either the presence of a narrative event boundary (Experiment 1) or a narrative event boundary along with a working-memory-clearing distractor task (Experiment 2). The results showed that anaphor resolution was affected by narrative event boundaries but not by a working-memory-clearing distractor task. This is interpreted as being consistent with the Event Horizon Model of event cognition.


Effects of water chemistry on the destabilization and sedimentation of commercial TiO2 nanoparticles: Role of double-layer compression and charge neutralization.
Nanomaterials are considered to be emerging contaminants because their release into the environment could cause a threat to our ecosystem and human health. This study aims to evaluate the effects of pH, ions, and humic acid on the destabilization and sedimentation of commercial stabilized TiO2 nanoparticles (NPs) in aquatic environments. The average hydrodynamic size of TiO2 NPs was determined to be 52 ± 19 nm by dynamic light scattering. The zero point charge (ZPC) of the commercial TiO2 NPs was found to occur at pH 6. The stability of commercial TiO2 NPs is independent of its concentration in the range of 50-200 mg/L. In the absence of NaCl, the commercial TiO2 NPs rapidly settled down near pHzpc when the aggregated nanoparticle size surpassed 1 μm. However, when the commercial TiO2 NPs aggregated with the increase of NaCl concentrations, the large aggregates (>1 μm) were found to remain suspended. For example, even at the critical aggregation concentration of NaCl (100 meq/L), TiO2 NP aggregates suspended for 45 min and then slowly deposited. This implies an increase in the exposure risk of NPs. In the presence of Suwannee river humic acid (SRHA), the commercial TiO2 NPs did not settle down until the SRHA concentration increased to 20 mg/L, and were seen to restabilize at SRHA concentrations of 50 mg/L. The uncommon behaviors of the commercial TiO2 NPs we observed may be attributed to the different destabilization mechanisms caused by different species (i.e., NaCl and SRHA) in water.


The usefulness of first-rank symptoms in the diagnosis of schizophrenia in a Saudi Arabian population.
Ninety-two schizophrenic patients of both sexes admitted to hospital at Taif, Saudi Arabia were examined to discover the incidence of Schneider's first-rand symptoms and their usefulness in diagnosing schizophrenia in this country. Fifty-two patients (56.5 per cent) were found to have these symptoms, most frequently 'made' phenomena and 'somatic passivity'. The role of possible socio-cultural factors and the need for serious studies on transcultural psychiatry are discussed.


The physical properties of an effective lung surfactant.
It is suggested that the phospholipids at the alveolar/air interface exhibit both thermodynamic (equilibrium) and kinetic forces during the course of a respiratory cycle. The alveolae are kept open at full expiration by a residue of nearly pure dipalmitoyl phosphatidylcholine which is condensed and therefore, incompressible at 37 degrees C.


Predictors of multi-domain cognitive decline following DBS for treatment of Parkinson's disease.
Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS). We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD. Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (>70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables. MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages. Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.


Fast activity as a surrogate marker of epileptic network function?
The detection of epileptiform discharges in electroencephalography recordings is a crucial part in diagnosing epilepsy. Thorough electrophysiologic evaluation yields information that allows for tailored surgical therapy in many cases, and thus improves treatment outcome. In recent years, fast activity (>60-80Hz) has been investigated for its diagnostic value in addition to well-known patterns such as epileptic transients. It was shown that these high frequency oscillations are highly specific for epileptic network function and might provide valuable information for localization of epileptic networks and understanding of their mechanisms. In this review, an overview of the electrophysiologic characteristics, putative cellular and network mechanisms in epilepsy is given. Recent studies are reviewed and interpreted in the context of a common hypothetical model.


Capacity building in food composition for Africa.
Capacity building in food and nutrition involves more than formal training and individual development. Such a process is long term and continues, requiring lasting mentorship, coaching and leadership development, including individual commitment to continued self-development. It expands to include the development of knowledge and skills of an individual within his/her organizational or institutional arrangements, and requires buy-in and support from his/her institution or organization, as well as other funding bodies involved in agriculture and health. It needs to be supported by government and be part of the regional and international agenda for agriculture and health. Under the auspices of International Network of Food Data Systems (INFOODS), an African Network of Food Data Systems (AFROFOODS) was established in September 1994, and a number of training courses, educational and scientific publications, posters, presentations and visits were hosted, organized and delivered with the aim to build enthusiasm, long term commitment and capacity in food composition within the AFROFOODS region. Formal training and human resource development were the major focus to take food composition forward in Africa. Significant progress was made in food composition activities, but constraints including lack of organizational and institutional commitment and financial support are straining the pace of progress.


Interneurons from embryonic development to cell-based therapy.
Many neurologic and psychiatric disorders are marked by imbalances between neural excitation and inhibition. In the cerebral cortex, inhibition is mediated largely by GABAergic (γ-aminobutyric acid-secreting) interneurons, a cell type that originates in the embryonic ventral telencephalon and populates the cortex through long-distance tangential migration. Remarkably, when transplanted from embryos or in vitro culture preparations, immature interneurons disperse and integrate into host brain circuits, both in the cerebral cortex and in other regions of the central nervous system. These features make interneuron transplantation a powerful tool for the study of neurodevelopmental processes such as cell specification, cell death, and cortical plasticity. Moreover, interneuron transplantation provides a novel strategy for modifying neural circuits in rodent models of epilepsy, Parkinson's disease, mood disorders, and chronic pain.


Laquinimod ameliorates secondary brain inflammation.
Accumulating evidence suggests that a degenerative processes within the brain can trigger the formation of new, focal inflammatory lesions in Multiple Sclerosis (MS). Here, we used a novel pre-clinical MS animal model to test whether the amelioration of degenerative brain events reduces the secondary recruitment of peripheral immune cells and, in consequence, inflammatory lesion development. Neural degeneration was induced by a 3 weeks cuprizone intoxication period. To mitigate the cuprizone-induced pathology, animals were treated with Laquinimod (25 mg/kg) during the cuprizone-intoxication period. At the beginning of week 6, encephalitogenic T cell development in peripheral lymphoid organs was induced by the immunization with myelin oligodendrocyte glycoprotein 35-55 peptide (i.e., Cup/EAE). Demyelination, axonal injury and reactive gliosis were determined by immunohistochemistry. Positron emission tomography (PET) imaging was performed to analyze glia activation in vivo. Vehicle-treated cuprizone mice displayed extensive callosal demyelination, glia activation and enhanced TSPO-ligand binding. This cuprizone-induced pathology was profoundly ameliorated in mice treated with Laquinimod. In vehicle-treated Cup/EAE mice, the cuprizone-induced pathology triggered massive peripheral immune cell recruitment into the forebrain, evidenced by multifocal perivascular inflammation, glia activation and neuro-axonal injury. While anti myelin oligodendrocyte glycoprotein 35-55 peptide immune responses were comparable in vehicle- and Laquinimod-treated Cup/EAE mice, the cuprizone-triggered immune cell recruitment was ameliorated by the Laquinimod treatment. This study clearly illustrates that amelioration of a primary brain-intrinsic degenerative process secondary halts peripheral immune cell recruitment and, in consequence, inflammatory lesion development. These findings have important consequences for the interpretation of the results of clinical studies.


Repeat-protein folding: new insights into origins of cooperativity, stability, and topology.
Although our understanding of globular protein folding continues to advance, the irregular tertiary structures and high cooperativity of globular proteins complicates energetic dissection. Recently, proteins with regular, repetitive tertiary structures have been identified that sidestep limitations imposed by globular protein architecture. Here we review recent studies of repeat-protein folding. These studies uniquely advance our understanding of both the energetics and kinetics of protein folding. Equilibrium studies provide detailed maps of local stabilities, access to energy landscapes, insights into cooperativity, determination of nearest-neighbor interaction parameters using statistical thermodynamics, relationships between consensus sequences and repeat-protein stability. Kinetic studies provide insight into the influence of short-range topology on folding rates, the degree to which folding proceeds by parallel (versus localized) pathways, and the factors that select among multiple potential pathways. The recent application of force spectroscopy to repeat-protein unfolding is providing a unique route to test and extend many of these findings.


Predicting stream N and P concentrations from loads and catchment characteristics at regional scale: a concentration ratio method.
We used a concentration ratio method to predict yearly and summer averages of stream total nitrogen, nitrate and total phosphorus concentrations at a regional scale. The ratio of the median daily concentration on the flow weighted annual concentration was used. This ratio characterizes the concentration dynamics of a catchment. We took advantage of the commonly used budget type models applied at a regional scale to relate concentrations to loads instead of directly to land uses, as has previously been done. The relationship was modeled with Boosted Regression Trees using catchment and stream characteristics along with loads and flows obtained from the SPARROW budget model. The ratio modeling approach was compared to a direct approach for concentration prediction, and also to a simple method where the mean ratio was used. The modeling performances of the ratio models were overall satisfying (r2 of 49% to 78%), and a better choice than the two other methods tested. This ratio modeling approach is based on a steady state assumption and largely ignores temporal dynamics. As such, this modeling technique does not replace the more physically-based techniques, but allows for hybrid approaches for improved spatial interpolations. This method could be used to predict effectively the impact (at equilibrium) of land use change and management scenarios on water quality at a regional scale.


Laparoscopic cardiomyotomy for achalasia: A single unit study.
Achalasia is a rare incurable neuromuscular disorder of the oesophagus. A number of treatment options are available. We reviewed our results of laparoscopic cardiomyotomy over a 30 month period. 18 patients with manometric features of achalasia underwent surgery between 2004 and 2006. Pre and postoperative weight and dysphagia scores were recorded (maximum score 45=normal, 0=complete dysphagia). Change in the Body Mass Index (BMI) was measured. Other symptoms (heartburn, epigastric pain, regurgitation, odynophagia and sleep disturbance) were scored on a 0-4 scale of increasing severity. At mean follow up of 16.2 months the mean dysphagia score was significantly improved from 7.5 to 33.9 (p<0.005). BMI was significantly increased from 22.3 to 25.8 kg/m(2) (p<0.05). Scores for heartburn, epigastric pain, regurgitation, odynophagia and sleep disturbance were also significantly improved. The average inpatient stay was 3.1 days and average operating time 111 minutes. One mucosal perforation occurred which was repaired intraoperatively. No patients required secondary operative intervention. Laparoscopic cardiomyotomy is a safe, highly effective, minimally invasive treatment for achalasia.


Syphilis in an Italian medieval jewish community: A bioarchaeological and cultural perspective.
We aim to discuss the presence of treponemal infections in three individuals belonging to a large (∼400 individuals) Late Medieval cemetery (14th -16th century) that archaeological and documentary sources place within a Jewish context, and to discuss the role of these diseases in a biocultural perspective. An anthropological and paleopathological study was conducted on skeletal remains of three individuals, though macroscopic and tomographic examination. Cranial lesions in which simultaneous destructive and proliferative processes (caries sicca) are noted. Long bones also present osseous alterations with increased bone density and non-uniform thickening. Skeletal lesions are consistent with treponemal infections (possibly either endemic or acquired syphilis). Historical documentation could help the interpretation of our cases, recording a syphilis outbreak in Bologna in 1496, possibly coeval to the Late Medieval Jewish cemetery. These cases of treponematosis are unique, documenting the presence of the disease within the Jewish Medieval community in Italy, as they frame the effects and consequence of the infection in shaping social and cultural contexts of the medieval Italian and European communities. They offer material evidence to elaborate on the historical documents on the hostility Jewish community suffered. Radiocarbon dating have not been performed directly on skeletal remains of the three pathological individuals. δ13C and δ15N isotope ratios should also be acquired to estimate the marine diet component, to account for possible marine reservoir effect on radiocarbon age calibration.


Assessment for vagus nerve stimulation in patients with difficult-to-treat depression: a model from the Newcastle Regional Affective Disorders Service (RADS).
Vagus nerve stimulation (VNS) has been shown to improve long-term outcomes for some patients with difficult-to-treat depression (DTD). Set out criteria to support the identification of patients for whom VNS is a suitable treatment option. Published clinical evidence, coupled with clinical experience garnered at the Regional Affective Disorders Service (RADS; Newcastle, UK) to inform VNS criteria. Patients with major depressive disorder or bipolar disorder (predominantly depressive) and a history of failed trials of multiple treatment modalities including pharmacotherapy, psychotherapy and/or electroconvulsive therapy (ECT) may be suitable candidates for VNS, if no contraindications are present. In the RADS such patients are offered VNS if they are able to provide informed consent and two specialists agree it is appropriate. VNS provides a valuable treatment option for DTD when used under appropriate circumstances; these assessment criteria facilitate the identification of patients with greatest potential to benefit.


The More the Better, Only in the Longer Term: A Cluster Randomized Controlled Trial to Evaluate a Compound Intervention Among Mainland Chinese Immigrants in Hong Kong.
Barriers to adaptation faced by mainland Chinese immigrants to Hong Kong can be reduced by improving two targets of adaptation: information about negotiating their new environment and psychological well-being. We developed and evaluated a Compound intervention to address these two domains simultaneously and compared its effects to two separate interventions exclusively targeting either information about Hong Kong or psychological well-being. This cluster randomized controlled trial assigned 251 immigrants to an information provision arm (IP, n = 84) targeting knowledge and adaptation difficulties, a psychological well-being enhancement arm (WBE, n = 80) targeting resilience and mental health, or a Compound arm (i.e., IP + WBE, n = 87). The Compound arm showed stronger effects from baseline to postintervention on knowledge than the WBE arm. From postintervention to 6-month follow-up, the Compound arm showed better sustained effects on knowledge and adaptation difficulties than the IP arm and on resilience and mental health than the WBE arm. Additionally, participants in the Compound arm with more baseline depressive symptoms showed greater improvements in adaptation difficulties and general mental health than those with fewer symptoms. The study demonstrated the longer-term effectiveness of the Compound intervention and its greater benefits for immigrants with more depressive symptoms.


Surgical approaches for the gliomas.
Neurosurgical intervention remains the first step in effective glioma management. Mounting evidence suggests that cytoreduction for low- and high-grade gliomas is associated with a survival benefit. Beyond conventional neurosurgical principles, an array of techniques have been refined in recent years to maximize the effect of the neurosurgical oncologist and facilitate the impact of subsequent adjuvant therapy. With intraoperative mapping techniques, aggressive microsurgical resection can be safely pursued even when tumors occupy essential functional pathways. Other adjunct techniques, such as intraoperative magnetic resonance imaging, intraoperative ultrasonography, and fluorescence-guided surgery, can be valuable tools to safely reduce the tumor burden of low- and high-grade gliomas. Taken together, this collection of surgical strategies has pushed glioma extent of resection towards the level of cellular resolution.


Determining oncogenic patterns and cancer predisposition through the transcriptomic profile in Mitchell-Riley syndrome with heterotopic gastric mucosa and duodenal atresia: a case report.
Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell-Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. A constitutive inactivation of RFX6 leads also to gastric heterotopia. Application of RNA-seq in human diseases may help to better understand pathogenic mechanism of diseases and to predict the risk of developing chronic disorders and personalizing their prevention and treatment. We evaluated oncogenic patterns and cancer predisposition using the transcriptomic profile in a case of MRS with neonatal diabetes, duodenal atresia, and extensive intestinal tract gastric heterotopia. We signalled the interactors of RFX6 with other up and downregulated genes, that may be interested in severity of diabetic condition, in multi-organs impairment and cancer predisposition. Furthermore, several dysregulated genes are involved in biological processes that can lead to promote cancer including "Evading apoptosis" (BAD, BBC3, EGF, FGFR2, FLT3LG, HMOX1, HRAS, IFNAR2, IGF1R, IL12RB1, IL13RA1, IL15, IL2RB, IL2RG, IL6R, KEAP1, MGST1, PDGFA, PDGFRB, PIK3R3, RALB, RALGDS, RASSF1, SOS1, TGFA, TXNRD3), "Proliferation" (APC, BRAF, CCND2, CCND3, CCNE2, FGFR2, FLT3LG, FZD1, FZD6, HMOX1, HRAS, IGF1R, KEAP1, LRP6, MAPK3, MGST1, PDGFA, PDGFB, PDGFRB, RB1, SOS1, TGFA, TXNRD3, WNT10B), "Sustained angiogenesis" (BRAF, FGFR2, FLT3LG, HRAS, IGF1R, JAG1, MAPK3, NOTCH2, PDGFA, PDGFB, PDGFRB, SOS1, TGFA, TGFB1), "Genomic instability" (BAD, BBC3) and "Insensitivity to anti-growth signals" (SMAD2, TGFB1). We also inspected the signalings and their related genes in cancer, such as "PI3K signaling", "ERK signaling", "JAK-STAT signaling", "Calcium signaling", "Other RAS signaling", "WNT signaling". In our MRS patient, we signaled the interactors of RFX6 with other up- and downregulated genes that may be related to severe diabetic condition, multi-organ impairment, and cancer predisposition. Notably, many dysregulated genes may lead to triggering carcinogenesis. The possibility of the patient developing cancer degeneration in heterotopic gastric mucosa and/or additional long-term tumoral sequelae is not excluded. Personalized prevention and treatment strategies should be proposed.


Reflex bradycardia occurring in response to diving, nasopharyngeal stimulation and ocular pressure, and its modification by respiration and swallowing.
1. Digital pressure applied to the eyes evokes reflex bradycardia in human subjects and anaesthetized dogs. The bradycardia is most pronounced when breathing stops. 2. In the dog oculo-cardiac reflex bradycardia is mediated by vegal stimulation and by sympathetic withdrawal. 3. Oculo-cardiac reflex bradycardia in the dog is reduced by central neural inspiratory activity and by the excitation of pulmonary afferents by inflation of the lungs. In human subjects it is reduced when inspiratory efforts are made against a closed glottis. 4. Nasopharyngeal stimulation with water evokes reflex bradycardia in the anaesthetized dog. This bradycardia is reduced by central neural inspiratory activity and by the excitation of pulmonary afferents by inflation of the lungs. 5. Bradycardia occurs in normal human subjects during immersion of the face in water ('diving'). This bradycardia is reduced when inspiratory efforts are made against a closed glottis. 6. Swallowing evokes transient tachycardia in human subjects. During diving or the application of ocular pressure, swallowing reduces the reflex bradycardia which these evoke.


Transcriptomic analysis reveals peripheral pathway in 3-phenoxybenzoic acid degradation by Aspergillus oryzae M-4.
As a major intermediate metabolite of synthetic pyrethroids, the occurrence of 3-phenoxybenzoic acid hinders the decomposition of the parent pesticide and poses uncertain risks to environmental ecology and living organisms. Strain Aspergillus oryzae M-4 was previously reported to degrade 3-PBA and several substances were identified as downstream transformation products (TPs). But the mechanism underlying the cleavage of ether bond remains largely unclear. Here, we attempted to address such concern through identifying the peripheral TPs and analyzing transcriptomics, coupled with serial batch degradation experiments. Analysis results of chromatographic/mass spectrometry suggested that 3-PBA underwent twice hydroxylation, to yield mono- and dihydroxylated 3-PBA successively. In parallel, a mutual transformation between 3-PBA and 3-phenoxybenzyl alcohol (3-PBOH) also existed. The proposal of peripheral pathway represents an important advance towards fully understanding the whole 3-PBA metabolism in M-4. A specific altered metabolization was found for the first time, that is, resting cells of M-4 skipped the reduction step and initiate hydroxylation directly, by comparison with growing cells. Transcriptome analysis indicated that 3-PBA induced the up-regulation of genes related to energy investment, oxidative stress response, membrane transport and DNA repair. In-depth functional interpretation of differential expression genes suggested that the generation 3-PBOH and hydroxylated 3-PBA may be due to the participation of flavin-dependent monooxygenases (FMOs) and cytochrome P450 (CYP450), respectively. This study provides new insight to reveal the biodegradation mechanism of 3-PBA by A. oryzae M-4.


Degradation of the fungal cell wall by clostridial strains isolated from soil subjected to biological soil disinfestation and biocontrol of Fusarium wilt disease of spinach.
Biological soil disinfestation (BSD) involves elimination of soil-borne plant pathogens in an environmentally friendly manner. Two anaerobic bacterial strains (H110 and TB8) isolated from BSD-treated soil samples were analyzed for their roles in elimination of pathogenic fungi. The two strains were identified as Clostridium beijerinckii based on 16S rRNA gene sequences and phenotypic properties. The strains fermented various carbohydrates and produced acetate, butyrate, and n-butanol as major products as well as abundant gases (H2 and CO2). For evaluation of the antifungal potential of these strains, cells of a pathogen (spinach wilt disease, Fusarium oxysporum f. sp. spinaciae) were co-inoculated into anaerobic media with each anaerobic strain. After incubation for ~3 weeks at 30 °C, 10-30% of the cells of the pathogen survived when incubated without the anaerobic isolates, whereas the pathogen was eliminated when co-incubated with each anaerobe because of the growth of the anaerobic bacterium. It was found by microscopic examination that mycelial cells of the fungal pathogen were severely degraded during the first 3-7 days of the co-incubation. The two strains utilized major cell wall polysaccharides of ascomycetous fungi-chitosan and ß-1,3-glucan (curdlan and laminarin)-as fermentative substrates added to the medium. Furthermore, both isolates degraded a cell wall preparation isolated from the mycelium of the Fusarium pathogen of spinach wilt disease. We concluded that the two anaerobic strains kill the pathogen of spinach wilt disease by degrading major fungal cell wall components as antifungal activities.


Anti-invasion drugs.
Most of the pharmaceuticals in clinical practice today for treatment of breast and other cancers are cytotoxic or cytostatic inhibitors of tumor growth. While this type of drug has found its place, along with surgery and radiotherapy, in treatment of disease, the breast cancer death rate has not decreased. This appears to be the result of rising incidence, resistance to therapy, and metastasis of the disease. Since distant metastasis (usually indicated by lymph node involvement) of breast cancer is related only indirectly to tumor size, it would appear that a concerted effort should be made to discover drugs which directly interfere with this complex process. Metastasis appears to depend upon tumor cell motility, dedifferentiation, local invasion, and angiogenesis. Significant progress has been recently made in the creation of new animal models of metastasis and in identifying several new drugs which may be suitable for clinical inhibition of this process. This article reviews current findings on anti-invasion/metastasis drugs with a focus on breast cancer.


The integrity of the syllable in developmental apraxia of speech.
Three children with developmental apraxia of speech (DAS) identified the number of syllables in words, judged intrasyllabic sound positions, and constructed syllable shapes within monosyllabic frames. Results suggest that DAS children demonstrate an apparent breakdown in the ability to perceive "syllableness" and to access and compare syllable representations with regard to position and structure. Based on these findings, DAS is viewed as a disorder characterized by an impoverished phonological representation system. On the basis of this article, the reader will be able to (1) describe the deficits in syllabic perception demonstrated by some participants with DAS; (2) examine the utility of metalinguistic tasks in the differential diagnosis of DAS; and (3) evaluate the findings with respect to competing theoretical perspectives on DAS.


The actin nucleation factor JMY is a negative regulator of neuritogenesis.
Junction-mediating and regulatory protein (JMY) is a p53 cofactor that was recently shown to nucleate actin assembly by a hybrid mechanism involving tandem actin monomer binding and Arp2/3 complex activation. However, the regulation and function of JMY remain largely uncharacterized. We examined the activity of JMY in vitro and in cells, its subcellular distribution, and its function in fibroblast and neuronal cell lines. We demonstrated that recombinant full-length JMY and its isolated WASP homology 2 domain, connector, and acidic region (WWWCA) have potent actin-nucleating and Arp2/3-activating abilities in vitro. In contrast, the activity of full-length JMY, but not the isolated WWWCA domain, is suppressed in cells. The WWWCA domain is sufficient to promote actin-based bead motility in cytoplasmic extracts, and this activity depends on its ability to activate the Arp2/3 complex. JMY is expressed at high levels in brain tissue, and in various cell lines JMY is predominantly cytoplasmic, with a minor fraction in the nucleus. Of interest, silencing JMY expression in neuronal cells results in a significant enhancement of the ability of these cells to form neurites, suggesting that JMY functions to suppress neurite formation. This function of JMY requires its actin-nucleating activity. These findings highlight a previously unrecognized function for JMY as a modulator of neuritogenesis.


Portable device for presbyopia correction with optoelectronic lenses driven by pupil response.
A novel portable device has been developed and built to dynamically, and automatically, correct presbyopia by means of a couple of opto-electronics lenses driven by pupil tracking. The system is completely portable providing with a high range of defocus correction up to 10 D. The glasses are controlled and powered by a smartphone. To achieve a truly real-time response, image processing algorithms have been implemented in OpenCL and ran on the GPU of the smartphone. To validate the system, different visual experiments were carried out in presbyopic subjects. Visual acuity was maintained nearly constant for a range of distances from 5 m to 20 cm.


Impact of the ratio of graft kidney volume to recipient body surface area on graft function after live donor kidney transplantation.
Functioning nephron mass is a determinant of the graft function of kidney transplant recipients. The graft kidney volume and its weight have been reported to be surrogates of the nephron mass. To investigate the impact of the ratios of the surrogates to recipient body surface area (BSA) and body weight on the graft function within six months post-transplantation, we measured the graft kidney volume, using computed tomography with 3-dimensional reconstruction before transplantation, and measured the graft kidney weight during surgery. Ninety-four cases of live donor kidney transplants were included in this study. The graft kidney volume/recipient BSA ratio was correlated with the glomerular filtration rate (GFR) of recipients at one and six months post-transplantation (r = 0.416, p < 0.001 and r = 0.381, p < 0.001, respectively). We found a difference in the graft function between recipients with a graft kidney volume/recipient BSA ratio of ≥90.9 mL/m(2) and those with a ratio of <90.9 mL/m(2) (p < 0.001). Multivariate analysis demonstrated that the graft kidney volume/recipient BSA ratio and donor age are independent predictors of recipient GFR at one and six months post-transplantation (p < 0.05). During living donor and recipient matching, both the potential volume of the donated kidney and the body size of recipient should be considered.


MicroRNA-552 promotes hepatocellular carcinoma progression by downregulating WIF1.
MicroRNAs (miRNAs/miRs) are involved in the metastasis of hepatocellular carcinoma (HCC). In the present study, it was demonstrated that miR‑552 was upregulated in HCC tissues. High miR‑552 expression was associated with malignant clinicopathological features and decreased survival rates. The in vitro results indicated that miR‑552 overexpression promoted migration, invasion and epithelial‑mesenchymal transition in Hep3B cells. However, the knockdown of miR‑552 inhibited its oncogenic roles in Huh‑7 cells. Additionally, Wnt inhibitory factor 1 (WIF1) was demonstrated to be a direct target of miR‑552 in Hep3B and Huh‑7 cells. Additional experiments identified that miR‑552 promotes β‑catenin expression by increasing the phosphorylation of GSK3β at Ser9. In conclusion, the results suggested that miR‑552 may promote HCC progression by blocking WIF1‑mediated GSK3β dephosphorylation. miR‑552 may be a biomarker for predicting the outcomes of patients with HCC.


Limitations in detection of 15N incorporation by mass spectrometry in protein-based stable isotope probing (protein-SIP).
The method of protein-based stable isotope probing (protein-SIP) has previously been shown to allow the modeling of carbon fluxes in microbial communities, thus tackling one of the key questions in microbial ecology. The method allows the analysis of stable isotope distribution in peptides, revealing metabolic activities of the species present in an ecosystem. Besides carbon, an application of protein-SIP with nitrogen is of interest for resolving the nitrogen fluxes in microbial communities. Thus, the sensitivity and reliability of a protein-SIP approach employing (15)N was analyzed. For this, cultivations of Pseudomonas fluorescens ATCC 17483 with different ratios of (14)N/(15)N were performed, from 10 % down to 0.1 % (15)N. After incubation leading to complete labeling of biomass, proteins were extracted and separated by one-dimensional gel electrophoresis, followed by tryptic digest and UPLC Orbitrap MS/MS analysis. (15)N relative isotope abundance (RIA) was calculated based on isotopic patterns from identified peptides in mass spectra. Proteomics data have been deposited to ProteomeXchange with identifier PXD000127. The distribution of (15)N RIA values among peptides was analyzed in samples with different (15)N amount, and potential causes for variations within individual samples of either technical or biological origin were investigated. Using a number of 50 peptides, significant differences (p ≤ 0.05) in (15)N incorporation were found between samples of different (15)N RIA down to 0.1 %. The study demonstrates that protein-SIP using (15)N is sufficiently sensitive for quantitative investigation of microbial activity in nitrogen cycling processes.


Occurrence of Hyp3-bradykinin in methanol extracts of the skin of the South African leptodactylid frog Heleophryne purcelli.
Methanol extracts of the skin of the South African amphibians belonging to the genus Heleophryne (H. purcelli purcelli, H. purcelli depressa, H. purcelli orientalis, H. natalensis) contain large amounts (20--500 microgram/g fresh tissue) of Hyp3-bradykinin.


Clinical and cost effectiveness of staff training in Positive Behaviour Support (PBS) for treating challenging behaviour in adults with intellectual disability: a cluster randomised controlled trial.
Many people with intellectual disability present with challenging behaviour which often has serious consequences such as the prescription of long term medication, in-patient admissions and disruption of normal daily activities. Small scale studies of Positive Behaviour Support (PBS) delivered by paid carers suggest that it reduces challenging behaviour and costs of care and improves quality of life. This study aims to investigate whether professionals training in the delivery of PBS as part of routine practice is clinically and cost effective compared to treatment as usual in community intellectual disability services. The study is a multi-centre cluster randomised controlled trial involving community intellectual disability services in England and service users with mild to severe intellectual disability and challenging behaviour. The teams will be randomly allocated into one of two conditions, either training and support to deliver PBS or treatment as usual. We will carry out assessments of challenging behaviour, use of services, quality of life, mental health, and family and paid carer burden at six and 12 months. We will monitor treatment fidelity and we will interview a sample of paid and family carers, service users, staff and managers about what they think of the treatment and how best we can deliver it in routine care. The main outcome is reduction in challenging behaviour at one year after randomisation. We will also carry out a health economic evaluation to examine the costs and consequences of staff training in PBS. The study findings will have significant implications for the delivery of PBS in community based services with the potential for reducing inpatient admissions and out-of-area placements for adults with intellectual disability and challenging behaviour. This trial is registered with Clinical Trials.gov (Ref NCT01680276 ). Clinical Trials Unit: PRIMENT https://www.ucl.ac.uk/priment/ .


Quantitative investigation on the heterogeneity of deformation fields in sandstone pre-existing cracks during damage evolution.
The inherently heterogeneous microstructures of rocks lead to heterogeneity of the deformation distribution within the rock volume. In this study, experiments were conducted on red sandstone specimens with four different pre-existing crack inclinations stressed under uniaxial loading to investigate these features. Acoustic emission and digital image correlation techniques were used to confirm the damage process and obtaining deformation fields, respectively. The results showed that the heterogeneity of the deformation fields in the rock specimens amplifies with increasing stress magnitude, i.e., the displacement field heterogeneity shows two dense bands around the pre-existing crack, and the strain field heterogeneity shows localized regions with a numerical difference (quantified by the normalized standard deviation) and spatial concentration (quantified by the spatial correlation coefficient). The variations in the normalized standard deviation and spatial correlation coefficient were closely related to the damage process. The normalized standard deviation presented four evolution stages: relatively constant low value, steady growth, significant growth, and high rate growth. The spatial correlation coefficient changed from increasing at a relatively constant rate to increasing at a gentle rate and finally increasing rapidly. The evolution rate along with the strain showed two sharp fluctuations. The first could be used as precursor information of the damage. Finally, we confirmed the feasibility of the damage variable obtained from the heterogeneous deformation indicators used to calibrate or form damage evolution laws.


HOX genes in ovarian cancer.
The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development. Here we review a number of recent studies showing that HOX genes are strongly expressed in ovarian cancer, and that in some cases the expression of specific HOX genes is sufficient to confer a particular identity and phenotype upon cancer cells. We also review the recent advances in elucidating the different functions of HOX genes in ovarian cancer. A literature search was performed using the search terms HOX genes (including specific HOX genes), ovarian cancer and oncogenesis. Articles were accessed through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect. Taken together, these studies have shown that HOX genes play a role in the oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA repair and enhanced cell motility. The function of HOX genes in ovarian cancer oncogenesis supports their potential role as prognostic and diagnostic markers, and as therapeutic targets in this disease.


Establishment and application of a survival rate graph model based on biomarkers and imaging indexes after primary hepatocellular carcinoma resection.
Primary liver cancer (PLC) is a highly malignant disease. This study developed an effective and convenient tool to evaluate survival times of patients after hepatectomy, which can provide a reference point for clinical decisions. Clinical and laboratory data of 243 patients with PLC after hepatectomy were collected. Univariate cox regression analysis, Lasso regression analysis and multivariate cox regression analysis were used to determine the best prediction index. Multivariate cox regression analysis was used to construct a survival prediction model. A receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the model. The patients in this model were divided into was divided into high-risk and low-risk groups according to the optimal cut-off value of the ROC curve for different prognostic years. Kaplan-Meier survival analysis and log-rank test were used to analyse the survival differences between the two groups. Tumour size, portal vein thrombosis, distant metastasis, alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were independent risk factors for overall survival (OS) after PLC surgery. The area under the concentration-time curve for 2-, 3- and 4-year survival of patients was 0.710, 0.825 and 0.919, respectively, with a good calibration of the Hosmer-Lemeshow test (p > 0.05) and net benefit. The mortality rates in patients with 2, 3 and 4 years of survival were 70.59%, 67.83% and 66.67% for the high-risk group and 21.84%, 22.50% and 22.67% for the low-risk group, respectively. The mortality rate of the high-risk group was significantly higher than that of the low-risk group (p < 0.05). The OS model of prognosis after PLC surgery constructed in this study can be used to predict the 2-, 3- and 4-year survival prognoses of patients, and patients with different prognosis years can be re-stratified so that they achieve more accurate and personalised assessment, thereby providing a reference point for clinical decision-making.


Critical levels of extracellular glutamate mediating gerbil hippocampal delayed neuronal death during hypothermia: brain microdialysis study.
When the brain temperature was lowered by 2 degrees C from normothermic temperature, a protective effect on postischemic neuronal death was exhibited and levels of extracellular glutamate were attenuated to about half of those at normothermic brain temperature in the gerbil hippocampus. Hypothermia has been reported to confer a protective effect on ischemia-induced delayed neuronal death. The present study was carried out to quantify this protective effect of hypothermia on the degree of alteration in extracellular release of glutamate during ischemia and the final histopathological outcome in the hippocampus. Extracellular glutamate levels were measured by microdialysis. In gerbils whose brain temperature was maintained at normothermia (37 degrees C), glutamate increased during ischemia and the early period of recirculation (by 15-fold), and CA1 neurons were consistently damaged. In animals whose brain temperature was maintained at 35 or 33 degrees C during ischemia, the release of glutamate was significantly attenuated to half or a quarter, respectively, at 37 degrees C. In animals whose brain temperature was maintained at 31 degrees C during ischemia, the release of glutamate was slightly lower than that at 33 degrees C. No CA1 ischemic neuronal damage was seen in 60% of gerbils at 35 degrees C and none was seen in any gerbils at 33 and 31 degrees C. In animals whose brain temperature was maintained at 39 degrees C during ischemia, the release of glutamate was slightly higher than that at 37 degrees C, and a high mortality rate of animals (75%) was observed. Our results reinforce other recent evidence suggesting that one of the mechanisms by which lowering of the brain temperature by only a few degrees during ischemia exerts a protective effect in the hippocampus, involves the reduction of ischemia-induced glutamate release.


A study on associations of single-nucleotide polymorphisms within H19 and HOX transcript antisense RNA (HOTAIR) with genetic susceptibility to rheumatoid arthritis in a Chinese population.
The purpose of our study was to examine whether the H19 rs2839698, rs217727, and HOX transcript antisense RNA (HOTAIR) rs12826786 polymorphisms were associated with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population. A total of 777 participants were enrolled in this study, including 328 RA patients and 449 healthy controls. The H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms were detected by the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. No significant difference in genotype distribution between RA patients and healthy controls was found (P = 0.38 for rs2839698; P = 0.79 for rs217727; P = 0.39 for rs12826786). The difference in allele frequencies between RA patients and controls was also non-significant (rs2839698 T versus C, P = 0.23, odds ratio (OR) = 1.15, 95% confidence interval (CI) = 0.92-1.43; rs217727 C versus T, P = 0.55, OR = 1.07, 95% CI = 0.87-1.32; and rs12826786 T versus C, P = 0.32, OR = 1.14, 95% CI = 0.88-1.47). We have also evaluated the relationships of above-mentioned polymorphisms with risk of RA under dominant model and recessive model, but non-significant evidence was found. No significant evidence was detected for the relationships of H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms with risk of different serotypes of RA. Our results indicated that H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms might not be involved in the genetic background of RA in Chinese.


Prophylactic use of phenoxymethylpenicillin and tinidazole in mandibular third molar surgery, a comparative placebo controlled clinical trial.
A clinical double-blind placebo controlled trial was carried out in 136 patients to test the value of the prophylactic use of phenoxymethylpenicillin and tinidazole in mandibular third molar surgery. The three patient groups were uniform with regard to the background data such as age and weight of the patients and the clinical status of the operated tooth, as well as to the observations made at surgery. No statistically significant differences were found between the study groups in the parameters used for evaluation. The results indicate that neither penicillin nor tinidazole have more effect on postoperative complications following operative extraction of wisdom teeth, than placebo tablets.


Late metachronous cerebral metastasis of pancreatic adenocarcinoma of the tail of the pancreas: a case report.
Pancreatic cancer is one of the leading causes of cancer mortality and one of the most lethal malignant neoplasms worldwide. It is known for its local tumor extension to the liver; other common sites include the lung, distant lymph nodes, and bone. Brain metastases are extremely rare and represent less than 0.6% of all brain metastases. We report the case of a 66-year-old Caucasian female known to have adenocarcinoma of the tail of the pancreas treated with chemotherapy. During follow-up, thoracoabdominal computed tomography scans did not reveal any residual tumor or any metastasis. Moreover, tumor markers were within normal limits. She presented to the emergency department of our institution following an episode of a generalized tonic-clonic seizure 5 years following the initial diagnosis. Brain magnetic resonance imaging revealed an expansive left frontal intraaxial lesion compatible with high-grade glioma. The patient underwent surgical treatment. Histological examination revealed pancreatic metastasis. Thought to be rare, metachronous cerebral pancreatic metastasis should be kept in mind in patients with pancreatic cancer. Early diagnosis and complete surgical resection play a key role in the survival of these patients.


Aetiological variation in the amnesic syndrome: comparisons using the Brown-Peterson task.
This study examined the performance of temporal lobe and Korsakoff amnesic patients on two versions of the Brown-Peterson task. One version involved trials with distractor intervals ranging from three to 60 second. The other investigated the effects of massed versus distributed practice with a constant nine-second retention interval. Korsakoff patients produced significantly poorer performance on both versions of the task. Further analyses indicated that impaired Brown-Peterson performance was correlated with frontal dysfunction but not with the severity of the memory deficit. Previous inconsistencies concerning the performance of amnesic patients on the Brown-Peterson task are considered.


Review of Regional Therapies for Gastric Cancer with Peritoneal Metastases.
Gastric cancer carries a poor prognosis and is a leading cause of cancer-related mortality worldwide. Patients with gastric cancer who develop peritoneal metastases have an even more dismal prognosis, with median survival time measured in months. Since studies have demonstrated that systemic chemotherapy has poor penetration into the peritoneum, multimodal treatment with intraperitoneal chemotherapy has been proposed for the treatment of peritoneal metastases and has become the foundation for newer therapeutic techniques and clinical trials. These include heated intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS), which involves the application of heated chemotherapy into the abdomen with or without tumor debulking surgery; normothermic intraperitoneal chemotherapy (NIPEC), in which non-heated chemotherapy can be delivered into the abdomen via a peritoneal port allowing for repeat dosing; and pressurized intraperitoneal aerosolized chemotherapy (PIPAC), a newer technique of pressurized and aerosolized chemotherapy delivered into the abdomen during laparoscopy. Early results with intraperitoneal chemotherapy have shown promise in increasing disease-free and overall survival in select patients. Additionally, there may be a palliative effect of these regional therapies. In this review, we explore and summarize these different intraperitoneal chemotherapy treatment regimens for gastric cancer with peritoneal metastases.


Self-assembly of alkynylplatinum(II) terpyridine amphiphiles into nanostructures via steric control and metal-metal interactions.
A series of mono- and dinuclear alkynylplatinum(II) terpyridine complexes containing the hydrophilic oligo(para-phenylene ethynylene) with two 3,6,9-trioxadec-1-yloxy chains was designed and synthesized. The mononuclear alkynylplatinum(II) terpyridine complex was found to display a very strong tendency toward the formation of supramolecular structures. Interestingly, additional end-capping with another platinum(II) terpyridine moiety of various steric bulk at the terminal alkyne would lead to the formation of nanotubes or helical ribbons. These desirable nanostructures were found to be governed by the steric bulk on the platinum(II) terpyridine moieties, which modulates the directional metal-metal interactions and controls the formation of nanotubes or helical ribbons. Detailed analysis of temperature-dependent UV-visible absorption spectra of the nanostructured tubular aggregates also provided insights into the assembly mechanism and showed the role of metal-metal interactions in the cooperative supramolecular polymerization of the amphiphilic platinum(II) complexes.


Partnered pharmacist charting on admission in the General Medical and Emergency Short-stay Unit - a cluster-randomised controlled trial in patients with complex medication regimens.
Patients admitted to general medical units and emergency short-stay units are often complex with multiple comorbidities, polypharmacy and at risk for drug-related problems associated with increased morbidity and mortality. The aim of this study was to evaluate the effectiveness of a partnered pharmacist charting model completed at the time of admission to prevent medication errors. We conducted an unblinded cluster randomized controlled trial comparing partnered pharmacist charting to standard medical charting among patients admitted to general medical units and emergency short-stay units with complex medication regimens or polypharmacy. This trial was conducted at an adult major referral hospital in metropolitan Melbourne, Australia, with an annual emergency department attendance of approximately 60 000 patients. The evaluation included patients' medication charts written in the period of 16 March 2015 to 27 July 2015. Patients randomized to the intervention were managed using the partnered pharmacist charting model. The primary outcome variable was a medication error identified by an independent assessor within 24 h of admission, who was not part of the patient's admission process. Of the 473 patients who received standard medical staff charting during the study period, 372 (78·7%) had at least one medication error identified compared to 15 patients (3·7%) on the partnered pharmacist charting arm (P < 0·001). The relative risk of an error with standard medical charting was 21·4 (95% CI: 13·0-35·0) with a number needed to treat (NNT) to prevent one error of 1·3 (95% CI: 1·3-1·4), and the relative risk of a high or extreme risk error with standard medical charting was 150·9 (95% CI: 21·2-1072·9) with a NNT to prevent one high or extreme error of 2·7 (95% CI 2·4-3·1). Partnering between medical staff and pharmacists to jointly chart initial medications on admission significantly reduced inpatient medication errors (including errors of high and extreme risk) among general medical and emergency short-stay patients with complex medication regimens or polypharmacy.


Voices from frontline nurses on care quality and patient safety during COVID-19: An application of the Donabedian model.
The COVID-19 pandemic has adversely impacted quality of care and patient safety. This study aimed to describe registered nurses' (RNs) perceptions on the impact of the COVID-19 pandemic on their ability to adhere to patient safety protocols using Donabedian's Health Care Quality model. In October 2020, a survey was conducted among all actively licensed RNs in New Jersey who provided direct patient care during the first peak of COVID-19. Of 3,027 participants, 68% reported that the number of patients assigned impacted their ability to adhere to protocols. RNs identified a variety of organizational structures impacting adherence, including inadequate staffing, staff qualifications, and inadequate resources. Impacted processes included the inability to adhere to patient safety protocols and conduct comprehensive assessments and surveillance, the need for additional time spent on personal protective equipment and isolation policies, and difficulty maintaining isolation integrity; the need to prioritize and cluster care; and guidelines limiting personnel who could enter the room. Nurses attributed both adverse patient and staff outcomes to inadequate staffing and high patient acuity. These findings highlight the need for health care organizations to support frontline nursing staff in adhering to patient safety and infection prevention and control protocols during times of crises. Infection preventionists have substantial contact with bedside nurses and should leverage their collegial relationships to promote patient safety.


Cross-reactive antibodies against dust mite-derived enolase induce neutrophilic airway inflammation.
Neutrophilic inflammation is a hallmark of some specific asthma phenotypes; its aetiology is not yet fully understood. House dust mite (HDM) is the most common factor in the pathogenesis of airway inflammation. This study aims to elucidate the role of cross-antibodies against HDM-derived factors in the development of neutrophilic inflammation in the airway. Blood samples were collected from asthma patients with chronic neutrophilic asthma for analysis of HDM-specific cross-reactive antibodies. The role of an antibody against HDM-derived enolase (EnoAb) in the impairment of airway epithelial barrier function and induction of airway inflammation was assessed in a cell culture model and an animal model. High similarity (72%) of the enolase gene sequences was identified between HDM and human. Serum EnoAb was detected in patients with chronic neutrophilic asthma. The EnoAb bound to airway epithelial cells to form complexes with enolase, which activated complement, impaired airway epithelial barrier functions and induced neutrophilic inflammation in the airway tissues. HDM-derived enolase can induce specific cross-antibodies in humans, which induce neutrophilic inflammation in the airway.


The single-unit delivery system--a safe alternative to home deliveries.
The need has arisen for the development of a health care/delivery system that can allow for a natural and personalized childbirth experience, within the safe confines of a modern obstetric unit. The single-unit delivery system (SUDS) is designed to achieve this objective by: strict prenatal screening of patients into low- and high-risk categories, utilization of a single room for the entire labor process, and close personalized supervision of women in "normal" labor by trained midwives/monitrixes. Physicians supervise the entire unit and are directly responsible for the management of all high-risk and complicated labors. The SUDS concept has been tried in clinical practice and has been proved to be an effective method of providing safe and satisfying obstetric care without compromising modern obstetric standards.


Erratum: Structure Model Index Does Not Measure Rods and Plates in Trabecular Bone.
[This corrects the article on p. 162 in vol. 6, PMID: 26528241.].


Comprehensive analysis of left ventricular geometry and function by three-dimensional echocardiography in healthy adults.
Recent European Association of Echocardiography and American Society of Echocardiography guidelines on three-dimensional echocardiography state that normal values of left ventricular (LV) parameters for age and body size remain to be established. In 226 consecutive healthy subjects (125 women; age range, 18-76 years), comprehensive three-dimensional echocardiographic analyses of LV parameters were performed, and values were compared with those obtained by conventional echocardiography. Upper reference values (mean+ 2 SDs) for three-dimensional LV end-diastolic and end-systolic volumes were 85 and 34 mL/m(2) in men and 72 and 28 mL/m(2) in women, respectively. Indexing LV volumes to body surface area did not eliminate gender differences. Lower reference values (mean - 2 SDs) for ejection fraction were 54% in men and 57% in women and for stroke volume were 25 and 24 mL/m(2), respectively. Upper reference values for LV mass were 97 g/m(2) in men and 90 g/m(2) in women and for end-diastolic sphericity index were 0.49 and 0.48, respectively. Significant age dependency of LV parameters was identified and reported across age groups. Three-dimensional echocardiographic LV volumes were larger, ejection fraction was similar, and LV stroke volume and mass were significantly smaller in comparison with the corresponding values obtained by conventional echocardiography. The investigators report a comprehensive analysis of LV geometry and function using three-dimensional echocardiography in a relatively large cohort of healthy Caucasian subjects with a wide age range. These may serve to establish age-specific and gender-specific reference ranges, which are crucial for the routine implementation of three-dimensional echocardiography to detect LV remodeling and dysfunction in clinical practice.


Structure-activity relationship of antibacterial chalcones.
The antibacterial activity of 31 chalcones was tested against bacterial strains, Bacillus cereus ATCC 11778, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC 25923. Some of the tested chalcones showed fair to significant activity against Gram-positive bacteria. By comparison of the results obtained, the antibacterial activity can be related to features such as the presence of a C-4 hydroxyl group, a C-4' oxygenated substituent or a C-3' isoprenoid side chain, while the C-2' hydroxyl group might have importance for the stability of the molecule. The inhibitory effect of chalcones on human pathogenic microorganisms can be correlated with the substitution patterns of the aromatics rings.


The X-ray Pump-Probe instrument at the Linac Coherent Light Source.
The X-ray Pump-Probe instrument achieves femtosecond time-resolution with hard X-ray methods using a free-electron laser source. It covers a photon energy range of 4-24 keV. A femtosecond optical laser system is available across a broad spectrum of wavelengths for generating transient states of matter. The instrument is designed to emphasize versatility and the scientific goals encompass ultrafast physical, chemical and biological processes involved in the transformation of matter and transfer of energy at the atomic scale.


Physiological energetics of the intertidal sea anemone Anthopleura elegantissima : III. Biochemical composition of body tissues, substrate-specific absorption, and carbon and nitrogen budgets.
Lipid is the major energy storage molecule, and protein is highly conserved when food availability is low in high- and low-intertidal individuals of Anthopleura elegantissima. Under laboratory conditions zooxanthellae were lost from anemones, and tissue carbohydrate was mobilized to support metabolic demands. Routine catabolic requirements for carbohydrate are probably met by translocated photosynthate. Substrate-specific absorption efficiencies were greater than 95% for protein and lipid, but considerably lower (10 to 60%) for carbohydrate. This pattern of absorption is directly related to very low levels of dietary carbohydrate compared to the other substrates. High-intertidal anemones absorbed more lipid than low-intertidal anemones. Integrated budgets for organic nitrogen, the first reported for any cnidarian, indicate that low-intertidal anemones require larger daily rations than high-intertidal anemones to meet their higher metabolic demands for protein. These results are considered in relation to potential importance of zooxanthellae in nutrient cycling.


Rethinking the Relationship Between Academia and Industry: Qualitative Case Studies of MIT and Stanford.
As knowledge has become more closely tied to economic development, the interrelationship between academia and industry has become stronger. The result has been the emergence of what Slaughter and Leslie call academic capitalism. Inevitably, tensions between academia and industry arise; however, universities such as MIT and Stanford with long traditions of industry interaction have been able to achieve a balance between academic and market values. This paper describes the strategies adopted by MIT and Stanford to achieve this balance. The results indicate that implicit culture is a stronger determinant of balance than are explicit rules. Finally, the author proposes a concept of balance to reconsider the relationship between academia and industry: today's universities, particularly those with strengths in engineering and management, are both symbiotic and interdependent with industry. A reasonable attitude toward the university-industry relationship is that of balance rather than strict separation. Universities can thus establish effective mechanisms to reach a balance between conflicting values.


Neuronal RARβ Signaling Modulates PTEN Activity Directly in Neurons and via Exosome Transfer in Astrocytes to Prevent Glial Scar Formation and Induce Spinal Cord Regeneration.
Failure of axonal regeneration in the central nervous system (CNS) is mainly attributed to a lack of intrinsic neuronal growth programs and an inhibitory environment from a glial scar. Phosphatase and tensin homolog (PTEN) is a major negative regulator of neuronal regeneration and, as such, inhibiting its activity has been considered a therapeutic target for spinal cord (SC) injuries (SCIs). Using a novel model of rat cervical avulsion, we show that treatment with a retinoic acid receptor β (RARβ) agonist results in locomotor and sensory recovery. Axonal regeneration from the severed roots into the SC could be seen by biotinylated dextran amine labeling. Light micrographs of the dorsal root entry zone show the peripheral nervous system (PNS)-CNS transition of regrown axons. RARβ agonist treatment also resulted in the absence of scar formation. Mechanism studies revealed that, in RARβ-agonist-treated neurons, PTEN activity is decreased by cytoplasmic phosphorylation and increased secretion in exosomes. These are taken up by astrocytes, resulting in hampered proliferation and causing them to arrange in a normal-appearing scaffold around the regenerating axons. Attribution of the glial modulation to neuronal PTEN in exosomes was demonstrated by the use of an exosome inhibitor in vivo and PTEN siRNA in vitro assays. The dual effect of RARβ signaling, both neuronal and neuronal-glial, results in axonal regeneration into the SC after dorsal root neurotmesis. Targeting this pathway may open new avenues for the treatment of SCIs. Spinal cord injuries (SCIs) often result in permanent damage in the adult due to the very limited capacity of axonal regeneration. Intrinsic neuronal programs and the formation of a glial scar are the main obstacles. Here, we identify a single target, neuronal retinoic acid receptor β (RARβ), which modulates these two aspects of the postinjury physiological response. Activation of RARβ in the neuron inactivates phosphatase and tensin homolog and induces its transfer into the astrocytes in small vesicles, where it prevents scar formation. This may open new therapeutic avenues for SCIs.


Interleukin 1-like factors can accumulate 5-hydroxytryptamine in the liver of mice and can induce hypoglycaemia.
After the injection into mice of culture medium of P388D1 cells, a murine macrophage cell line, 5-hydroxytryptamine accumulated in the liver and blood glucose declined. The factors capable of inducing these responses were purified by gel filtration and chromatofocusing. With these procedures, the activity to induce the increase in 5-hydroxytryptamine in the liver accompanied the activity to induce hypoglycaemia. Moreover, through the purification, the factors were found in the fraction of interleukin 1, a lymphocyte-activating factor. These results suggest that the factors capable of inducing the increase in 5-hydroxytryptamine and hypoglycaemia are likely to be interleukin 1 molecules or molecules closely related to interleukin 1. The present and previous findings together with those in the literature support the idea that the increase in 5-hydroxytryptamine in the liver might be a cause of hypoglycaemia. These findings may provide new and important information about the roles of macrophages in inflammation or in immune responses.


Vertical, horizontal, and torsional eye movement responses to head roll in the squirrel monkey.
The vestibulo-ocular reflex (VOR) serves to stabilize images on the retina by rotating the eyes in the direction which opposes angular (aVOR) or linear (IVOR) head movement. The aVOR responds to rotations in any plane. Head rotations about the naso-occipital axis (roll) are accompanied by compensatory torsional eye movements, with gains typically less than 0.7. However, geometric considerations suggest that the response should not be restricted to torsion, and that horizontal, vertical, and torsional response components should depend upon eye position relative to the axis of rotation. Since eye position can differ for the two eyes (e.g., during convergence), the response to head roll should be accordingly disconjugate. Further, because the eyes are typically displaced from the axis of rotation, head roll entails a calculable translation of the eyes in space, and compensation for this component of motion is expected to add to the response to angular motion. The translational response component should be modulated by fixation distance. To test these geometric considerations in the aVOR, we investigated the three-dimensional ocular responses of squirrel monkeys to head roll. Torsional aVOR responses were accompanied by vertical components which were modulated by horizontal gaze position, and by horizontal components which were modified by vertical gaze position. The vertical response components were often appropriately disconjugate, and even opposing, yielding responses that appeared "see-saw" in character.(ABSTRACT TRUNCATED AT 250 WORDS)


A New Radiopharmaceutical 225 Ac-DOTA-IBA in the Treatment of a Case of Bone Metastases.
α-Emitter 225 Ac has been considered a candidate for targeted α-therapy. DOTA-IBA is new a precursor targeting bone metastasis. It can be used for radionuclide labeling with 225 Ac. We present a case with refractory bone pain for bone metastasis, who demonstrated an excellent therapy response after 1 cycle of 225 Ac-DOTA-IBA therapy. Moreover, the patient did not have any observable adverse effects.


Comparative acute toxicity of chlorocitrate and fluorocitrate in dogs.
The high-dose effects of chlorocitrate [(-)-threo-chlorocitric acid] were compared in vivo to another halogenated citrate analog, and a well-known inhibitor of the tricarboxylic acid (TCA) cycle, fluorocitrate. The compounds were given iv to two dogs per sex per group, and a control group received an equimolar amount of citric acid. Chlorocitrate (100 mg/kg) showed TCA cycle inhibition as did fluorocitrate (8 mg/kg) in that both caused depletion of ATP and accumulation of citrate in the liver. Chlorocitrate was a significantly weaker inhibitor of citrate metabolism than fluorocitrate as evidenced by a substantially lower accumulation of serum citrate despite a much higher dose. Both halocitrates produced a similar diabetes-like syndrome (hyperglycemia, glycosuria) mediated by a significant hyperglucagonemia and slight hypoinsulinemia. Chlorocitrate was more potent in this effect and a much greater buildup of plasma lactate ensued (18- versus 3.7-fold increase), enough to explain lethality observed in earlier studies. In contrast, fluorocitrate produced a severe life-threatening hypocalcemia (-30%), and hypercalcuria was observed. This effect on calcium distribution was only minimal with chlorocitrate. Both halocitrates had a similar depressive effect on circulation as evidenced by hypothermia, bradycardia, and elongation of the QT-interval. These changes were considered to be the result of lactic acidosis and the ongoing ion imbalance since heart ATP levels were not depleted.


Home range geometry of the desert scorpion Paruroctonus mesaensis.
The home range of the desert scorpion Paruroctonus mesaensis is analyzed using techniques of Ford & Krumme (1979). Possible factors influencing home range geomtry of P. mesaensis include prey distribution, prey abundance and renewal, energy requirements, risk of predation and body size. There are differences in home range size among the three year classes with the youngest year class maintaining a significantly smaller home range. Home ranges of each year class are approximately circular indicating that these scorpions are remarkably symmetric in the directional use of space around their burrow. The majority of surface activity occurs within 1.0 m from the burrow for all ages. These patterns along with equal probabilities of prey capture at all distances from the burrow suggest that scorpions do not deplete prey within their home ranges.


A Rare Case of Adenoid Cystic Carcinoma of the Sphenoid Sinus Presenting with Lateral Rectus Palsy.
A rare case of adenoid cystic carcinoma arising from the sphenoid sinus causing lateral rectus palsy is presented here. Adenoid cystic carcinoma of the paranasal sinuses is an aggressive neoplasm which needs early diagnosis and treatment. Ideal treatment paradigm for paranasal sinus tumors is yet to be established. A combination of surgery and radiotherapy offers a better disease control and survival.


Localization of atrial fibrillation triggers in patients undergoing pulmonary vein isolation: importance of the carina region.
This study sought to identify the origin within the pulmonary vein (PV) of reproducible atrial fibrillation (AF) triggers. Triggers for AF frequently originate from PVs. However, a systematic evaluation of the location of origin within the PV orifice and associated techniques for eliciting triggers has not been performed. Spontaneous triggers and those provoked with isoproterenol (up to 20 microg/min) and/or cardioversion in 45 patients with AF were identified using multipolar catheter recordings. In identifying origin, PVs were divided into 17 equal segments from ipsilateral PVs with "carina zone" (CZ) (7 segments between the PVs) and 10 "noncarina zone" (NCZ) segments. Sixty-three reproducible triggers were noted in 37 of the 45 (82%) patients with 57 from PV and 6 (10%) from non-PV sites. Although triggers were identified from 26 of 34 distinct PV segments, most PV triggers (36, 63%) originated from CZ segments (p < 0.05) from both right (17 triggers) and left (19 triggers) PVs. The CZ triggers were more often spontaneous (11 of 36 in CZ vs. 2 of 21 in NCZ; p < 0.05) or elicited with CV (17 of 36 in CZ vs. 6 of 21 in NCZ; p < 0.05). In contrast, NCZ triggers were more likely to require isoproterenol to be provoked (13 of 21 [62%] vs. 8 of 36 [22%], p < 0.05). Reproducible spontaneous and provoked PV triggers initiating AF can be observed in most patients undergoing AF ablation. These triggers most commonly originate from the carina region of both right and left PVs. Noncarina PV triggers more commonly require provocation with isoproterenol infusion.


Aging of the human eye lens--a morphological point of view.
Age-related cortical lens changes are mainly due to oxidative stress induced membrane disorganization increasing with time to (1) membrane ruptures, (2) local fibre opacification, (3) local opacities and eventually to (4) more advanced segmental and annular opacities and mature cataract. Early occurrence of these cortical opacities is delayed by the presence of several defence systems: (1) radical scavengers, (2) a membrane repair-lysosomal system, (3) a segregation system and (4) the inertness of the deep cortical and nuclear membranes. Posterior subcapsular age-related changes As shown by Spector (1991), oxidative stress also affects the DNA of lenticular epithelial cells leading to single strand breaks. Although these DNA breaks are efficiently repaired by excision repair, longlasting low dose insults, as in the human lens or massive insults as in experimental studies, can lead to incomplete repair and therefore to germinative epithelial cells with aberrant DNA. These will give rise to cohorts of deviating cells with an abnormal developmental programme. That abnormal DNA, e.g. regarding the genes for cytoskeletal proteins, leads to abnormal development of fibres has been shown in studies in transgenic mice (Dunia et al., 1991). Irradiation in animals leading to abnormal development of fibres and finally to posterior subcapsular cataract has been extensively documented (Worgul, 1989). In our studies of donor eye lenses, we have incidentally found lenses with one or two regions with abnormal and abnormally interdigitating lens fibres which would beyond doubt have led to posterior subcapsular cataract. Compared with the other two types of age-related changes, posterior subcapsular changes are rather infrequent (Sasaki et al., 1987, 1989).(ABSTRACT TRUNCATED AT 250 WORDS)


Combination of ovalbumin-coated iron oxide nanoparticles and poly(amidoamine) dendrimer-cisplatin nanocomplex for enhanced anticancer efficacy.
Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR)-based tumor targeted 4.5 generation poly(amidoamine) dendrimer(4.5GDP)-cisplatin (Cis-pt) nanocomplex (NC) (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs were examined via FTIR spectroscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy. The conjugation of Cis-pt with 4.5GDP was confirmed using carbon NMR spectroscopy. The tumor-specific 4.5GDP-Cis-pt NC provided 45%and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed for the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NPs were biocompatible with different cell lines, even at a high concentration (200 µg mL-1). However, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL-1) significantly increased the cytotoxicity against the cancer cells in a dose-dependent manner with the increasing AC-IO-Ova NPs concentrations. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, AC-IO-Ova NPs might assist the efficiency of anticancer cells, inducing an innate immune response via M1 macrophage polarization. We provide a novel synergistic chemoimmunotherapeutic strategy to enhance the anticancer efficacy of cisplatin via a chemotherapeutic agent 4.5GDP-Cis-pt NC and induce proinflammatory cytokines stimulating innate immunity through AC-IO-Ova NPs against tumors.


A cohort study and matched pair analysis evaluating the effects of the COVID-19 pandemic on access to dental care for people with inherited bleeding disorders.
Patients with inherited bleeding disorders (IBDs) can experience challenges in accessing dental care. The COVID-19 pandemic saw the cessation of routine dentistry in England. This study aims to highlight whether access to dental care for patients with IBDs was impacted by the pandemic, and whether the severity of their IBD impacts patients experience of dental care. Patients over the age of 18 with Haemophilia A and B, Von Willibrands (VWD), Bernard-Soulier syndrome (BSS) and Glanzmann's disease were recruited. One hundred and seventy-eight patients were called and invited to complete a questionnaire. Full cohort and matched pair analysis was performed. Seventy participants completed the questionnaire (62 males, mean age 39.9), 26 had a mild IBD and 44 severe. Mild and severe patients were matched on IBD, gender, deprivation index and age. Thirty-one percent of patients tried to seek dental advice during the pandemic. Eighty-one percent of mild patients saw a dentist routinely prior to the pandemic, compared to 58% of severe patients. Doctors were more likely to discuss the importance of dental prevention with patients with severe IBDs (p = .0042). Fewer patients with severe IBDs accessed regular dental care compared to their matched pair counterparts prior to the pandemic. This could indicate that access to care is more difficult for those with severe IBDs. Patients felt that oral health is relevant to their IBD. While doctors were more likely to discuss the importance of preventing dental disease with patients who have severe IBDs, the profession needs to ensure this translates into routine engagement.


Asymmetrical abdominal muscle morphometry is present in injury free adolescent cricket pace bowlers: A prospective observational study.
This study aimed to determine if abdominal muscle thickness, activation and symmetry are associated with prospective in-season injury among adolescent cricket pace bowlers. A quantitative, prospective, observational study design was used. Data was collected at an indoor venue at a secondary school. 28 injury-free, male, adolescent pace bowlers between the ages of 13 and 18 participated. Muscle thickness of the transversus abdominis (TA), internal oblique (IO) and external oblique (EO) muscles were measured at rest and during an abdominal drawing-in maneuver (ADIM) i.e. activation, using ultrasound imaging. Incidence of injury was monitored monthly during the cricket season. Thickness of the non-dominant IO at rest was greater than the dominant side for pace bowlers who remained injury free during the cricket season (p = 0.01, effect size (ES) = 0.65). This was, however not the case for bowlers who sustained injuries (p = 0.47; ES = 0.24). TA percentage change during ADIM (activation) on the dominant side was less in bowlers who sustained non-contact injuries compared to those who remained injury free (p = 0.03; ES = 1.17). Asymmetry in IO thickness may play a protective role against injury, whilst poor TA activation on the dominant side may pose a risk to injury.


Estradiol and levonorgestrel: effects on bleeding pattern when administered in a sequential combined regimen with a new transdermal patch.
A 1-year, randomized, multicenter study was carried out to assess the effects of estradiol/levonorgestrel, delivered transdermally by 7-day patches in a sequential combined regimen, on bleeding pattern and acceptability in postmenopausal women. A total of 468 postmenopausal women were randomized to 15-cm2, 22.5-cm2 or 30-cm2 patches containing 17 beta-estradiol alone (50, 75 or 100 micrograms/24 h, respectively) for 2 weeks followed by 17 beta-estradiol/levonorgestrel (50/10, 75/15 or 100/20 micrograms/24 h) for 2 weeks. The occurrence of cyclic bleeds was dose-dependent, with an increase at higher dosages; the frequency of a cyclic bleed per treatment cycle was 40% in the 50/10 micrograms/24 h patch, 62% in the 75/15 micrograms/24 h patch and 76% in the 100/20 micrograms/24 h patch. The incidence of intermittent bleeding also increased with higher doses, from 22% in the 50/10 group to 35% in the 100/20 group; 20% of women in the 50/10 group did not bleed at all; the corresponding figures for the 75/15 and 100/20 groups were 7% and 0%, respectively. Time of onset of cyclic bleeding was constant in all groups. The mean duration of cyclic bleeding was constant within each group, but increased from 4.4 days in the 50/10 to 6.3 days in the 100/20 group. The regularity and predictability of cyclic bleeding were high in all groups. Recurrence of cyclic bleeds was acceptable for most women (90%). Sequential combined transdermal 17 beta-estradiol/levonorgestrel shows very good cycle control that is well accepted by postmenopausal women.


Spinal cord compression caused by a metastatic lesion from an aortic body tumour.
An aortic body tumour in a 7-year-old wire-haired fox terrier with hind limb ataxia is described. A metastatic lesion in the dorsal arch of the eighth thoracic vertebra caused compression of the spinal cord. Radiographic techniques are discussed that enabled the position and extent of the primary tumour and its metastasis to be defined and allowed a provisional diagnosis of chemodectoma.


An investigation into the taxonomy of "Bacillus aminovorans" and its reclassification to the genus Domibacillus as Domibacillus aminovorans sp. nov.
The species "Bacillus aminovorans" was categorized as species Incertae Sedis meaning taxa with uncertain taxonomic position because of insufficient description of phenotypic properties and lack of understanding of its phylogenetic relationship (Claus and Berkeley [5]). In this study two strains "B. aminovorans" DSM 1314T and DSM 4337 were phenotypically and phylogenomically analyzed. The strains are Gram-staining-positive, spore forming rods and unable to utilize/ferment most of the sugars tested except glucose. The major fatty acids are anteiso-C15:0 and iso-C15:0. The major polar lipids are diphosphatidylglycerol, phosphatidylglycerol and an aminophosphoglycolipid. The cell wall peptidoglycan is of A1γ type with meso-Dpm as the diamino acid. The menaquinone type present is MK-6. The G+C content of the genomic DNA of the type strain is 40.8mol%. These characteristics were found to be in line with description of the genus Domibacillus. Moreover phylogenetic analysis based on 16S rRNA gene sequence retrieved "B. aminovorans" within the genus Domibacillus with D. antri XD 80T as the closest relative. Additionally genome sequencing of the strains and their comparison with whole genome sequences of other Domibacillus spp. confirmed their distinctiveness and separate species status within the genus based on parameters of genome to genome distance calculator (GGDC) and average nucleotide identity (ANI) values. Therefore a novel species Domibacillus aminovorans sp. nov. (DSM 1314T=LMG 16796T) is proposed.


The relationships between early ionic events, the pattern of protein synthesis, and oocyte activation in the surf clam, Spisula solidissima.
The ionic events linked to activation of surf clam (Spisula solidissima) oocytes include a transient increased Ca2+ influx and an acid release. The aim of the present work was to further elucidate the respective roles of these two ionic events and to clarify the possible role of protein kinase C in the sequence of events leading to oocyte activation. K+-enriched seawater, ammonium chloride, and the phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA), a protein kinase C activator, were tested for their ability to promote germinal vesicle breakdown (GVBD), an acid release, increased 45Ca2+ uptake, and a shift in the pattern of protein synthesis. Oocytes activated by addition of K+ ions release an amount of H+ similar to that induced by fertilization, with the same time course, show an increased, verapamil-sensitive, 45Ca2+ uptake that is proportional to the amount of added K+, and undergo a shift in their pattern of protein synthesis, which requires the presence of external Ca2+. Ammonium chloride, at concentrations causing a higher production of acid than that induced by K+ ions or fertilization, does not trigger GVBD nor any increased 45Ca2+ uptake or any detectable shift in the pattern of protein synthesis. Combined additions of ammonium chloride with subthreshold concentrations of K+ ions allow GVBD to occur, thus revealing a synergistic effect of ammonia and K+ ions. TPA slowly induces GVBD, an Na+-dependent acid release, and a shift in the pattern of protein synthesis, in the absence of increased 45Ca2+ uptake. Our results lead us to propose the following sequence of events for the activation of Spisula oocytes: an increased Ca2+ influx contributes to activate protein kinase C which causes a Na+-dependent acid release leading to a rise of pHi. This rise of pHi, although insufficient by itself, may set the pHi in a permissive range for activation to occur through the action of other protein kinase C-sensitive events leading to the production of meiosis-inducing proteins.


Toxic actions of senaetnine, a new pyrrolizidine-type alkaloid, in rats.
Senaetnine is a new type of Senecio alkaloid with a dihydropyrrolizinone structure. A limited amount of the crude alkaloid was available for preliminary toxicity tests in weanling male rats via i.p., oral and i.v. routes. Single i.p. or p.o. doses up to 280 mg/kg were not acutely toxic, and showed no evidence of hepatotoxicity. The compound or its metabolites appeared to be eliminated rapidly via the kidneys. However, senaetnine had a direct irritant action on tissues near to the site of i.p. administration, and caused damage to pulmonary vascular tissue when given i.v. Senaetnine is closely related to, but less reactive than, dehydrosenecionine, a putative short-lived metabolite of the alkaloid senecionine. It possesses mild alkylating reactivity, and the evidence indicates that it can cause moderate tissue injury without the need for metabolic activation. This suggests the need for testing of this and related compounds for chronic toxicity and carcinogenicity.


Selection of an Amino Acid Site with One of the Fastest Cleavage Kinetics by the Endosomal Protease Cathepsin B for Potential Use in Drug Delivery Systems.
On the basis of known published data, six peptide sequences were selected that are potentially capable of being rapidly cleaved by the endosomal protease cathepsin B. For comparison, the cleavage of common linker sequences, polyglycine and polyglycine-serine, by cathepsin B was also studied. Different ends of these peptides were labeled with sulfoCyanine3 and sulfoCyanine5 fluorescent dyes, between which Förster resonant energy transfer (FRET) is possible. The kinetics of cleavage of peptides by cathepsin B was studied on a multimodal plate reader by FRET signal reduction. FKFL and FRRG cleavage sites have been shown to be the most suitable for potential use in various drug delivery systems. These sites are much more efficiently cleaved under slightly acidic conditions of endosomes than at neutral extracellular pH.


Ultra-broadband near-infrared emission CuInS2/ZnS quantum dots with high power efficiency and stability for the theranostic applications of mini light-emitting diodes.
Broadband near-infrared CuInS2/ZnS quantum dots with up to 94.8% quantum yield were synthesized with fast precursor decomposition leading to monomer conversion improvement. In the mini-LED package, the device showed high power efficiency and stability was also demonstrated with a penetration test and vein imaging showing its potential biomedical application in the theranostics field.


Arthroscopically assisted ACL reconstruction. Is a drain necessary?
We report on the results of a prospective randomised controlled trial to evaluate the use of an intra-articular drain following arthroscopically assisted ACL reconstruction using patellar tendon autograft. Forty-nine patients were recruited for the trial and randomised into receiving or not receiving a drain following surgery. An independent observer who was blinded for the use of the drain assessed the knees for swelling, range of movement (ROM) and pain at 2, 4 and 6 weeks postoperatively. Muscle strength was assessed at 12 weeks following surgery using the KIN COM III isometric dynamometer. We found that the knees that were drained following surgery initially had less swelling and a better ROM. However, at 4 weeks this difference had disappeared. At 3 and 6 months, there was no functional difference between the two groups. We recommend that no drain be used following ACL reconstruction as removal of the drain is uncomfortable and carries theoretical and avoidable risks.


RNA-quality control by the exosome.
The exosome complex of 3'-->5' exonucleases is an important component of the RNA-processing machinery in eukaryotes. This complex functions in the accurate processing of nuclear RNA precursors and in the degradation of RNAs in both the nucleus and the cytoplasm. However, it has been unclear how different classes of substrate are distinguished from one another. Recent studies now provide insights into the regulation and structure of the exosome, and they reveal striking similarities between the process of RNA degradation in bacteria and eukaryotes.


A review on health risk assessment of PM in the construction industry - Current situation and future directions.
Particulate matter (PM) is one of the primary pollutants of the environment. The amount of PM discharged from construction projects is considerably high; it generates 70-80% of the overall PM. The composition of PM is complex and may contain various toxic substances that have severe health effects on human health. Existing health risk assessment in the construction industry lacks the efficiency to reduce the risk level of PM exposure. This study systematically reviews literature in this research area to understand the primary reasons which generates PM health risk assessments. The authors reviewed health risk assessment studies in the construction industry to analyze the current situation, and then reviewed health risk assessment studies from four different industries to compare the advancement of research and outcomes in all the five industries. From the study it is understood that the area of research related to ambient air were more developed compared to those in other areas due to their sampling methods and the size of the PM studied. From the findings of the systematic review, it is understood that majority of the risk assessment studies still rely on a two decade-old system and neglect recent research findings pertaining inhalation rate and size of PM. To overcome this, the level of risk involved in various common construction activities needs to be explored using real-time location-based PM monitoring and real-time inhalation monitoring methods. The findings of this review will help researchers gain a better perspective while conducting occupational health risk studies in the construction industry.


Massively parallel sequencing reveals the complex structure of an irradiated human chromosome on a mouse background in the Tc1 model of Down syndrome.
Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome. However, the individual dosage-sensitive genes underlying each phenotype remain largely unknown. To help dissect genotype--phenotype correlations in this complex syndrome, the first fully transchromosomic mouse model, the Tc1 mouse, which carries a copy of human chromosome 21 was produced in 2005. The Tc1 strain is trisomic for the majority of genes that cause phenotypes associated with DS, and this freely available mouse strain has become used widely to study DS, the effects of gene dosage abnormalities, and the effect on the basic biology of cells when a mouse carries a freely segregating human chromosome. Tc1 mice were created by a process that included irradiation microcell-mediated chromosome transfer of Hsa21 into recipient mouse embryonic stem cells. Here, the combination of next generation sequencing, array-CGH and fluorescence in situ hybridization technologies has enabled us to identify unsuspected rearrangements of Hsa21 in this mouse model; revealing one deletion, six duplications and more than 25 de novo structural rearrangements. Our study is not only essential for informing functional studies of the Tc1 mouse but also (1) presents for the first time a detailed sequence analysis of the effects of gamma radiation on an entire human chromosome, which gives some mechanistic insight into the effects of radiation damage on DNA, and (2) overcomes specific technical difficulties of assaying a human chromosome on a mouse background where highly conserved sequences may confound the analysis. Sequence data generated in this study is deposited in the ENA database, Study Accession number: ERP000439.


Mitosis: short-circuiting spindle checkpoint signaling.
The spindle checkpoint forms an intricate signaling circuit to sense unattached kinetochores, to inhibit the anaphase-promoting complex/cyclosome (APC/C), and to delay anaphase onset. Using clever genetic experiments in the budding yeast, Lau and Murray define the endpoint of checkpoint signaling and provide key mechanistic insights into checkpoint inhibition of APC/C.